Subgroup (Number of studies)		Summary DOR (95% CI)

Study design	Case-control (24)	134.4 (65.2 – 213.1)

	Cross-sectional (60)	171.1 (106.7 – 274.2)

Blinding	Single or double blinded (29)	90.2 (46.2 – 176.2)

	Unblinded or NR (55)	221.2 (137.7 – 355.2)

DNA extraction method	Chemical (55)	153.7 (90.1 – 262.4)

	Physical (29)	171.7 (96.2 – 306.6)

Amplification method	PCR/multiplex (68)	139.3 (89.2 – 217.7)

	Nested PCR (16)	266.6 (140.8 – 504.6)

Target s	IS6110 (54)	236.1 (152.9 – 36

Subgroup (Number of studies)		Summary DOR (95% CI)

equence		4.6)

	Other target (30)	77.4 (38.2 – 156.9)

Detection method	Probe (49)	130.6 (78.4 – 217.6)

	Gel-UV (35)	215.4 (115.1 – 403.2)

Sputum smear status	Pos/Both/NR (78)	161.5 (107.5 – 242.6)

	Negative (6)	128.6 (33.4 – 495.1)


Region	Value added of export spillover (100 million yuan)a	Proportion of export spilloverb (%)

1997	2002	2007	1997	2002	2007

Eastern provinces

Beijing	127	237	1211	27	34	38


Nanoparticle (NP)	Size of NP (nm)	Ligand/receptor	Drug/agent	Method to trace NP/drug/agent	Ref.

Polymer	70	Protein/TfR	siRNA	PCR	[236]

Liposome	ns	Ab/TfR	p53	p53 via PCR	[271]

Nanoparticle (NP)	Size of NP (nm)	Ligand/receptor	Drug/agent	Method to trace NP/drug/agent	Ref.

	7	Protein/	siRN	PCR	[23

Polymer	0	TfR	A		6]

Liposome	ns	Ab/TfR	p53	p53 via PCR	[271]


No of patients	61

No of CTCs	1262

Age

Median (range)	62 (23–82)

	N (%)

Menopausal status

Pre	17 (27.9)

Post	41 (67.2)

UN	3 (4.9)

ER

Positive	38 (62.3)

Negative	20 (32.8)

UN	3 (4.9)

PR

Positive	30 (49.2)

Negative	28 (45.9)

UN	3 (4.9)

HER 2

Positive	14 (22.9)

Negative	44 (72.1)

UN	3 (4.9)

Triple negative	11 (18.0)

Histology grade

1	1 (1.6)

2	16 (26.2)

3	26 (42.6)

UN	18 (29.5)

No of CTCs/patients

Median (range)	2- 162

2-4	21 (34.4)

≥5	40 (65.6)


V. albo-atrum	V. longisporum	V. dahliae	V. tricorpus

234	Bob-7	2341	2933

CBS-8	Vd-1	330	2901 A

CBS-7	43-3	G12-1	CBS-12

2934	Vd-11	Vd-7	1901

		G12-2

V. albo-atrum	V. longisporum

234	Bob-7

CBS-8	Vd-1

CBS-7	43-3

2934	Vd-11


Essential public health operation	Climate change and foodborne pathogens example

1: Food and foodborne disease surveillance	Enhanced cross country surveillance through the establishment of the European Centre for Disease Prevention and Control. This is tasked with collecting, examining and disseminating surveillance data on over 50 infectious diseases from EU and European Economic Area

2: Monitoring and response to food and health hazards and emergencies	Bodies such as INFOSAN, through which the WHO, enable countries to rapidly share information during food safety emergencies to limit the spread of food hazards

3: Health protection including food safety and others	Regulations including EU General Food Law which specifies the general principles that food producers and retailers should adhere to in order to provide safe food. It also ensures the traceability of food and outlines measures detailing how unsafe food should be withdrawn or recalled

4: Health promotion including action to address social determinants and health inequity	Health promotion campaigns to inform, educate and empower people about health issues that may be associated with climate change

5: Food and foodborne disease prevention, including early detection of illness	Enhance use of rapid diagnostic techniques, such as real-time PCR for rapid and hence early detection of foodborne pathogens

6: Assuring governance for health and wellbeing	Organisations such as the Med-Vet-Net Association for Zoonoses Research which promote cross national and multidisciplinary approaches bringing together veterinary, medical and food scientists

7: Assuring a sufficient and competent public health workforce	Support by organisations such as the WHO and ECDC for materials and activities which increase awareness and build capacity within countries to understand and prevent the negative impacts of climate change on health

8: Assuring sustainable organisational structures and financing	Long-term and sustainable funding for measures to prevent climate-sensitive foodborne diseases

9: Advocacy communication and social mobilisation for health	The European Strategy for the control of non-communicable diseases which highlights the importance of patient empowerment and patient’s rights

10: Advancing public health research to inform policy and practice	UK funding for a series of Health Protection Research Units (HPRUs); partnerships between academics and public health practitioners. The Environmental Change and Health HPRU is tasked with the joint development of knowledge, foresight and tools to mitigate against and adapt to environmental change


Parental Dietary Pattern	Children’s Dietary Pattern

Sweet & Fat 	Ref. Cereals	Animal Products

N	OR	95%CI	N	OR	95%CI	N	OR	95%CI

Maternal dietary pattern (N = 1607)

Different & soft drink not available (reference)	742	1.00		1017	1.00		767	1.00

Different & soft drink is available	138	1.97	1.20; 3.25	294	0.46	0.25; 0.84	256	0.95	0.65; 1.38

Identical & soft drink not available	521	2.04	1.49; 2.80	246	2.48	1.43; 4.27	496	2.16	1.59; 2.92

Identical & soft drink is available	206	2.78	1.80; 4.28	50	1.67	0.66; 4.22	88	1.42	0.82; 2.47

Paternal dietary pattern (N = 763)

Different & soft drink not available (reference)	465	1.00		407	1.00		360	1.00

Different & soft drink is available	92	1.55	0.90; 2.68	122	0.43	0.18; 1.04	80	0.83	0.45; 1.52

Identical & soft drink not available	151	2.48	1.58; 3.87	209	2.05	1.22; 3.45	256	2.48	1.62; 3.79

Identical & soft drink is available	55	4.26	2.16; 8.41	25	1.97	0.61; 6.39	67	1.80	0.96; 3.36

Parental Dietary Pattern	Children’s Dietary Pattern

Sweet & Fat	Ref. Cereals	Animal Products

N	OR	95%CI	N	OR	95%CI	N	OR	95%CI

attern (N = 1607)

Different & soft drink not available (reference)	742	1.00		1017	1.00		767	1.00

Different & soft drink is available	138	1.97	1.20; 3.25	294	0.46	0.25; 0.84	256	0.95	0.65; 1.38

Identical & soft drink not available	521	2.04	1.49; 2.80	246	2.48	1.43; 4.27	496	2.16	1.59; 2.92

Identical & soft drink is available	206	2.78	1.80; 4.28	50	1.67	0.66; 4.22	88	1.42	0.82; 2.47

Paternal dietary pattern (N = 763)

Different & soft drink not available (reference)	465	1.00		407	1.00		360	1.00

Different & soft drink is available	92	1.55	0.90; 2.68	122	0.43	0.18; 1.04	80	0.83	0.45; 1.52

Identical & soft drink not available	151	2.48	1.58; 3.87	209	2.05	1.22; 3.45	256	2.48	1.62; 3.79

Identical & soft drink is available	55	4.26	2.16; 8.41	25	1.97	0.61; 6.39	67	1.80	0.96; 3.36


Variables	Quintiles of household income per capita (mean values)	Brazil

1st	2nd	3rd	4th	5th

Area (%)

 Rural	31.1	18.5	14.6	9.0	4.7	15.6

 Urban	68.9	81.5	85.4	91.0	95.3	84.4

Region (%)

 North and Northeast	61.4	40.2	28.3	19.0	15.8	33.0

 Mid-South	38.6	59.8	71.7	81.0	84.2	67.1

Number of dwellers in households	4.5	3.7	3.0	2.8	2.5	3.3

Proportion of children under 2 years of age in family unit (%)	6.4	4.0	2.5	1.9	1.4	3.2

Proportion of children 2–9 years of age in family unit (%)	17.2	11.2	6.9	5.6	3.7	8.9

Proportion of adolescents (10–19 years) in family unit (%)	23.0	18.1	12.3	9.7	7.5	14.1

Proportion of elderly (65 years or older) in family unit (%)	2.6	7.1	16.8	15.9	15.7	11.6

Proportion of women in family unit (%)	50.7	51.3	51.6	52.7	52.6	51.8

Monthly household income per capita (US$)	97.22	213.22	353.00	591.38	1968.82	644.70

Proportion of monthly household income per capita dedicated to monthly medicine expenses per capita (out-of-pocket expenditure) (%)	5.1	3.6	3.3	2.9	2.0	3.4

Variables	Quintiles of household income per capita (mean values)	Brazil

1st	2nd	3rd	4th	5th

Proportion of women in family unit (%)	50.7	51.3	51.6	52.7	52.6	51.8

Monthly household income per capita (US$)	97.22	213.22	353.00	591.38	1968.82	644.70

Proportion of monthly household income per capita dedicated to monthly medicine expenses per capita (out-of-pocket expenditure) (%)	5.1	3.6	3.3	2.9	2.0	3.4


Additional inclusion criteria

Pain intensity of 20 mm or more by VAS in the previous 48 hours when walking on a flat surface;At least grade II to III on the Kellgren-Lawrence scale by an X-ray taken within 6 months;	And reluctant to continue on previous drug but willing to change drug treatment.

Exclusion criteria

Patients presenting with any of the following will be excluded from the study.

Grade I or Grade IV severity of the index knee based on the Kellgren and Lawrence radiographic criteria as applicable;Use of intra-articular injections or arthroscopy of the index knee within 3 months prior to screening;Evidence of crystalline-induced synovitis in the index knee;History, physical examination, or radiographic results suggestive of acute inflammatory arthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis, gout, pseudogout, fibromyalgia, systemic lupus erythematosus, or other types of inflammatory arthritis of the index knee;Pain in either knee of neurologic origin;	Signs of clinically important active inflammation in the index knee joint including redness, warmth, and/or a large, bulging effusion with the loss of normal contour at the screening and/or baseline visits;History of acute inflammatory arthritis or pseudogout of the study joint;Cancer/metastatic disease;Systemic or intra-articular corticosteroid use within 60 days of the Screening visit;Known sensitivity to any of the ingredients listed in the treatments under investigation;Significant medical and skin conditions which, in the opinion of the investigator, will interfere with study participation and patch adherence;Replacement of the knee joint.


Pathway name	No. genes*	ES	NES	FDRq value

PHONG_TNF_RESPONSE_VIA_P38_COMPLETE	13	0.583	1.743	0.580

DELYS_THYROID_CANCER_DN	11	0.612	1.748	0.599

CORRE_MULTIPLE_MYELOMA_DN	3	0.897	1.733	0.603

SHEPARD_BMYB_MORPHOLINO_UP	10	0.609	1.712	0.617

LI_INDUCED_T_TO_NATURAL_KILLER_UP	17	0.537	1.724	0.617

WILCOX_PRESPONSE_TO_ROGESTERONE_UP	6	0.705	1.700	0.621

WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN	13	0.562	1.674	0.632

KEGG_RENIN_ANGIOTENSIN_SYSTEM	3	0.932	1.761	0.632

OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_DN	11	0.605	1.751	0.633

REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION	16	0.535	1.685	0.644

Pathway name	No. genes*	ES	NES	FDRq value

WILCOX_PRESPONSE_TO_ROGESTERONE_UP	6	0.705	1.700	0.621

WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN	13	0.562	1.674	0.632

KEGG_RENIN_ANGIOTENSIN_SYSTEM	3	0.932	1.761	0.632

OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_DN	11	0.605	1.751	0.633

REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION	16	0.535	1.685	0.644


N = 7	Mean	SD

Age [yrs]	71.3	8.3

Height [cm]	171	5.6

Weight [kg]	70.85	10.1

BMI [kg/m2]	25.1	4.5

MOCA [0-30]	21.4	1.4

Age of disease onset [yrs]	61.0	2.6

Duration of disease [yrs]	10.3	5.7

Hoehn and Yahr	2.5	0.5


	Harar HDSS	Kersa HDSS

TFR	1.9	5.3

GFR	64	166.8

CBR	20.3	37.2


Reference value	day 1	day 2	day 5	day 8	day 11	day 15	day 21	day 28


	IMRT	3DRT

Mean maximum	Mean average	Mean maximum	Mean average

Tongue cancer

Lower teeth

Anterior	56.9	42.8	36.4	32.5

Pre-molars	51.5	43.6	56.9	49.5

Molars	50.8	42.3	64.7	59.1

Upper teeth

Anterior	41.0	26.4	23.7	19.0


	Number of subjects	Mean	Standard deviation	Median	Minimum	Maximum

Age (years)	98	36.00	8.44	37.00	18.00	50.00


Scoring used in the study

The patient has resumed work-related and other activities with slight or no symptoms.	3: Excellent

The patient has resumed work-related and other activities but occasionally feels pain in the back or lower limbs after strenuous work.	2: Good

The patient has reduced work-related and other activities because of residual pain in the back or lower limbs.	1: Fair

The patient cannot work or carry out activities of daily living and is considered to be disabled.	0: Poor

Scoring used in the study

The patient has resumed work-related and other activities with slight or no symptoms.	3: Excellent

The patient has resumed work-related and other activities but occasionally feels pain in the back or lower limbs after strenuous work.	2: Good

The patient has reduced work-related and other activities because of residual pain in the back or lower limbs.	1: Fair

The patient cannot work or ca	0: Poor

Scoring used in the study

rry out activities of daily living and is considered to be disabled.


Exocyclic M1dG and 8-oxodG Adducts

	N	M1dG ± SE	p-Value	8-oxodG ± SE	p-Value

Adduct background in presence or absence of AMF exposures

Control cells

Nonexposed to AMF

Incubation times

24 h a	10	0.4 ± 0.1		3.2 ± 0.2

48 a	10	0.4 ± 0.1		3.1 ± 0.2

Exposed to AMF (20 min)

Incubation times

24 h a	10	0.5 ± 0.1		3.2 ± 0.2

48 a	10	0.5 ± 0.1		3.3 ± 0.3

Exposed to AMF (40 min)

Incubation times

24 h a	10	0.5 ± 0.1		3.4 ± 0.2

48 a	10	0.5 ± 0.1		3.9 ± 0.3

Adduct levels of treated cells in presence or absence of AMF exposures

NP treated cells

Nonexposed to AMF

Incubation times

24 h a	10	0.7 ± 0.1	<0.05 b	16.7 ± 1.7	<0.05 b

48 a	10	0.8 ± 0.1	<0.05 b	21.2 ± 1.9	<0.05 b

Exposed to AMF (20 min)

Incubation times

24 h a	10	4.6 ± 0.5	<0.05 b	40.3 ± 3.3	<0.05 b

48 a	10	6.9 ± 0.6	<0.05 b	69.3 ± 1.4	<0.05 b

Exposed to AMF (40 min)

Incubation times

24 h a	10	6.4 ± 1.4	<0.05 b	36.5 ± 4.0	<0.05 b

48 a	10	15.9 ± 6.7	<0.05 b	79.3 ± 1.1	<0.05 b

Exocyclic M1dG and 8-oxodG Adducts

	N	M1dG ± SE

Adduct background in presence or absence of AMF exposures

Control cells

Nonexposed to AMF

Incubation times

24 h a	10	0.4 ± 0.1

48 a	10	0.4 ± 0.1

Exposed to AMF (20 min)

Incubation times

24 h a	10	0.5 ± 0.1

48 a	10	0.5 ± 0.1

Exposed to AMF (40 min)

Incubation times

24 h a	10	0.5 ± 0.1

48 a	10	0.5 ± 0.1

Adduct levels of treated cells in presence or absence of AMF exposures

NP treated cells

Nonexposed to AMF

Incubation times

24 h a	10	0.7 ± 0.1

48 a	10	0.8 ± 0.1

Exposed to AMF (20 min)

Incubation times

24 h a	10	4.6 ± 0.5

48 a	10	6.9 ± 0.6

Exposed to AMF (40 min)

Incubation times

24 h a	10	6.4 ± 1.4

48 a	10	15.9 ± 6.7

Exocyclic M1dG and 8-oxodG Adducts

p-Value	8-oxodG ± SE	p-Value

Adduct background in presence or absence of AMF exposures

	3.2 ± 0.2

	3.1 ± 0.2

	3.2 ± 0.2

	3.3 ± 0.3

	3.4 ± 0.2

	3.9 ± 0.3

Adduct levels of treated cells in presence or absence of AMF exposures

<0.05 b	16.7 ± 1.7	<0.05 b

<0.05 b	21.2 ± 1.9	<0.05 b

<0.05 b	40.3 ± 3.3	<0.05 b

<0.05 b	69.3 ± 1.4	<0.05 b

<0.05 b	36.5 ± 4.0	<0.05 b

<0.05 b	79.3 ± 1.1	<0.05 b


Time (days)	Treatment	Calcium (mg/dl)

21	Control	9.468 ± 0.275

Osteoinduced	13.496 ± 0.892**

Time (days)	Treatment	Calcium (mg/dl)

21	Osteoinduced	13.496 ± 0.892**


 	Pre-injury	5-months post-injury	12-months post-injury	NZ general population survey

Total	2842	1470	2262	1250

Age:

18-24	14.4%	13.1%	12.1%	7.0%

25-34	20.8%	19.5%	19.5%	13.3%

35-44	22.5%	23.5%	22.5%	20.4%

45-54	24.5%	26.5%	26.3%	20.2%

55-64	17.8%	17.4%	19.6%	16.4%

65+	–	–	–	21.0%

Not reported	–	–	–	1.8%

Sex:

Male	61.4%	60.8%	58.9%	42.7%

Female	38.6%	39.2%	41.1%	56.0%

Not reported	–	–	–	1.3%

Recovery Status:	 	n = 1248	n = 1937

Recovered	 	23.0%	36.4%

Not recovered	 	77.0%	63.6%

Injury Type:

Intracranial	3.7%	3.7%	3.8%

Head/neck superficial	3.6%	3.2%	3.6%

Spine dislocation, sprain, or strain	16.1%	15.3%	15.9%

Upper extremity fracture	17.7%	20.5%	17.6%

Upper extremity dislocation, sprain, or strain	14.3%	15.1%	13.7%

Upper extremity open wound	6.0%	6.1%	5.8%

Upper extremity superficial	5.0%	4.8%	4.9%

Lower extremity fracture	17.2%	18.0%	18.1%

Lower extremity dislocation, sprain, or strain	24.6%	21.9%	25.2%

Lower extremity open wound	4.0%	3.9%	3.9%

Lower extremity superficial	6.6%	6.3%	6.5%

Other injury region/nature	17.1%	19.3%	17.4%

UnadjustedEQ-5D social tariff	0.94	0.75	0.78	0.82

Total

Age:

18-24

25-34

35-44

45-54

55-64

65+

Not reported

Sex:

Male

Female

Not reported

Recovery Status:

Recovered

Not recovered

Injury Type:

Intracranial

Head/neck superficial

Spine dislocation, sprain, or strain

Upper extremity fracture

Upper extremity dislocation, sprain, or strain

Upper extremity open wound

Upper extremity superficial

Lower extremity fracture

Lower extremity dislocation, sprain, or strain

Lower extremity open wound

Lower extremity superficial

Other injury region/nature

UnadjustedEQ-5D social tariff


Classifier	Accuracy (%)	Sensitivity (%)	Specificity (%)	Strength (%)	ROCAUC

BindN-RF	80.00	73.08	80.63	76.86	0.8495


The Tested Compounds 	Side Effects of Rats Treated with Artesunate and Artemisinin, Respectively

The Loss of Body Weight	Vomiting	Diarrhea

Artesunate	−	−	−

Artemisinin	−	−	−

The Tested Compounds	Side Effects of Rats Treated with Artesunate and Artemisinin, Respectively

The Loss of Body Weight	Vomiting	Diarrhea

Artemisinin	−	−	−


Characteristics	Frequencies (n=271)	Percentage (%)

Household Members Ever Suffer Jigger Infestation:

Yes	239	88.2

Households reported with jiggers infested persons:

Yes	64	23.6

Number of household members infested

1 Member	40	14.8

2 Members	19	7.0

3 Members	4	1.5

5 Members	1	0.3

Number of households with jiggers infested persons seen during the study:

Yes	51	18.8

Number of infested household members

1Person	32	11.8

2 Persons	15	5.5

3 Persons	4	1.5

Characteristics	Frequencies (n=271)	Percentage (%)

Yes	51	18.8

Number of infested household members

1Person	32	11.8

2 Persons	15	5.5

3 Persons	4	1.5


Severity of retinopathy	Retinal findings in severe malaria (indirect ophthalmoscopy; n = 139)

Any retinopathy	Hemorrhages	Papilloedema*	Whitening

White-centered	Any	Macular	Peripheral	Any

Fatal (n = 21)

Mild		15 (71%)	8 		0	0 (	0 (


Cooking fuel	Numbers of patients	Cases vs non-eye-disease controls	Case vs non-cataract eye-disease patients	Case vs combined controls

	CS	NE	NC	a-OR (95% CI)	p- value*	a-OR (95% CI)	p- value*	a-OR (95% CI)	p- value*

Females

Family h/o cataract

No	53	66	67	1 (ref)	0.03	1 (ref)	0.02	1 (ref)	0.007

Y		14		2.14 (1.03		2.66		2.31 (1.25,


Monkey Species and ID	Protein(ng/ml)	Levels of p27 (ng/ml)	TCID50I.U./ml	Viral copy #x 107 per ml

SM-FYy	784.8	119.41	2.2355	3.13


Cut-off	Maxillary	Anterior ethmoid	Posterior ethmoid	Frontal	Sphenoid

>3 mm*	26	4	4	2	3.5

>4 mm*	25	3	2.8	1.4	3.2


	RMAP	Posterior PMR	Anterior PMR	P-value

(n = 23)	(n = 10)	(n = 6)


Center

Parameter	R2*	P*	Correlation

 p120-catenin membrane vs. β-catenin membrane	0.15	<0.01	positive

 vs. β-catenin cytoplasm	0.07	0.03	inverse

 p120-catenin cytoplasm vs. β-catenin membrane	0.13	<0.01	inverse

 vs. β-catenin cytoplasm	0.15	<0.01	positive

Invasive front

Parameter	R2*	P*	Correlation

 p120-catenin membrane vs. β-catenin membrane	0.33	<0.01	positive

 vs. E-cadherin membrane	0.60	<0.01	positive

 β-catenin membrane vs. E-cadherin membrane	0.29	<0.01	positive

Center

Parameter	R2*	P*

p120-catenin membrane vs. β-catenin membrane	0.15	<0.01

vs. β-catenin cytoplasm	0.07	0.03

p120-catenin cytoplasm vs. β-catenin membrane	0.13	<0.01

vs. β-catenin cytoplasm	0.15	<0.01

Invasive front

Parameter	R2*	P*

p120-catenin membrane vs. β-catenin membrane	0.33	<0.01

vs. E-cadherin membrane	0.60	<0.01

β-catenin membrane vs. E-cadherin membrane	0.29	<0.01

Center

Correlation

positive

inverse

inverse

positive

Invasive front

Correlation

positive

positive

positive


	Age and sex-adjusted

	Beta	95% CI	p	R2

Vascular risk factors (VRFs)

Hypertension	−0.049	(−0.617, 0.519)	0.87	0.04

Hypercholesterolemia	0.262	(−0.153, 0.676)	0.22	0.05

Diabetes mellitus	0.128	(−0.592, 0.848)	0.73	0.04

Overweight (BMI ≥25)	− 0.391	(− 0.840, 0.059)	0.09	0.04


Operation Mode	Operation Current	Power Consumption

Idle	2 mA	2 mAh

Data sampling	80 mA	0.178 mAh

Data transmitting	60 mA	0.067 mAh

Operation Mode	Operation Current

Idle	2 mA

Data sampling	80 mA

Data transmitting	60 mA

Power Consumption

2 mAh

0.178 mAh

0.067 mAh


Categories emerged	Positive valued	Negative valued

The degree of difficulty/demand of the studies	The degree of difficulty/demand was experienced as stimulating	The degree of difficulty/demand was experienced as too heavy

The teachers engagement	Very engaged teachers	Not engaged teachers

The organisation of the program	A stimulating organisation of the program was noticed	No stimulating organisation of the program was noticed

Contents in the studies associated to the profession	The certificate to be a nurse is attractive – long for working as a nurse	The certificate and the profession frightened the student

The attitude towards the studies	Having a positive attitude towards the studies	Having a negative attitude towards the studies

The study result achieved	Achieving a good study result	Not achieving a good study results

The life situation surrounding the studies	Having a good life situation	Having a bad life situation

Friendship during the studies	A good friendship is experienced	A bad or no friendship is experienced

emerged	 valued	ed

The degree of difficulty/demand of the studies	The degree of difficulty/demand was experienced as stimulating	The degree of difficulty/demand was experienced as too heavy

The teachers engagement	Very engaged teachers	Not engaged teachers

The organisation of the program	A stimulating organisation of the program was noticed	No stimulating organisation of the program was noticed

Contents in the studies associated to the profession	The certificate to be a nurse is attractive – long for working as a nurse	The certificate and the profession frightened the student

The attitude towards the studies	Having a positive attitude towards the studies	Having a negative attitude towards the studies

The study result achieved	Achieving a good study result	Not achieving a good study results

The life situation surrounding the studies	Having a good life situation	Having a bad life situation

Friendship during the studies	A good friendship is experienced	A bad or no friendship is experienced


 	Population	Intervention	Assessment tool(s)a	Analysis

Papers	Randomization	Justification of sample size	Control group	Allocation concealment	Underlying theory	Validity	Reliability	Intention-to-treat	Attrition rate

Alonso, Fernandez, Mataix et al. (1999)	No	Not mentioned	No	N/A	None	N/A	N/A	N/A	N/A

Beasley, Capossela, Brigham, Gunderson and Gortmaker (1997)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Bleakley (2010)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Dettle, Sagel and Chrysler (1994)	No	No	Yes (but no statistical comparison between groups)	Not mentioned	None	Not mentioned	Not mentioned	no	40% attrition;

No analysis of dropouts

Kittur, McMenamin and Knott (1990)	No	No	Yes	Not randomly assigned	None	N/A	N/A	N/A	N/A

Light (1987)	No	No	Yes (but no statistical comparison between groups)	Not randomly assigned	None	N/A	N/A	N/A	N/A

Milanés, Gonzalez, Hernandez, Arminio, Clesca and Rivas-Vetencourt (2003)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Nelson, Marymont, Durand, Reyes and Davis (1992)	Random cluster probability method	No	Yes	Not randomly assigned	None	Field testing of the questionnaire (but validity/reliability assessment not detailed)	N/A	N/A

Niday, Painter, Peak et al. (2007)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Riker and White (1995)	No	No	Yes	Not randomly assigned	None	N/A	N/A	N/A	N/A

Shafer, Durand, Hueneke, et al. (1998)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Stark, Wikoren and Martone (1994)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Taylor, Young and Kneteman (1997)	No	No	No	N/A	‘Change theory’ (not referenced)	N/A	N/A	N/A	N/A

Van Gelder, Van Hees, de Roey, Monbaliu, Aerts, Coosemans et al. (2006)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Wight, Cohen, Roels and Miranda (2000)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

	Population	Intervention	Assessment tool(s)a	Analysis

Papers	Randomization	Justification of sample size	Control group	Allocation concealment	Underlying theory	Validity	Reliability	Intention-to-treat	Attrition rate

Kittur, McMenamin and Knott (1990)	No	No	Yes	Not randomly assigned	None	N/A	N/A	N/A	N/A

Light (1987)	No	No	Yes (but no statistical comparison between groups)	Not randomly assigned	None	N/A	N/A	N/A	N/A

Milanés, Gonzalez, Hernandez, Arminio, Clesca and Rivas-Vetencourt (2003)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Nelson, Marymont, Durand, Reyes and Davis (1992)	Random cluster probability method	No	Yes	Not randomly assigned	None	Field testing of the questionnaire (but validity/reliability assessment not detailed)	N/A	N/A

Niday, Painter, Peak et al. (2007)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Riker and White (1995)	No	No	Yes	Not randomly assigned	None	N/A	N/A	N/A	N/A

Shafer, Durand, Hueneke, et al. (1998)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Stark, Wikoren and Martone (1994)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Taylor, Young and Kneteman (1997)	No	No	No	N/A	‘Change theory’ (not referenced)	N/A	N/A	N/A	N/A

Van Gelder, Van Hees, de Roey, Monbaliu, Aerts, Coosemans et al. (2006)	No	No	No	N/A	None	N/A	N/A	N/A	N/A

Wight, Cohen, Roels and Miranda (2000)	No	No	No	N/A	None	N/A	N/A	N/A	N/A


Parameter	Youth (n = 618)	Middle age (n = 613)	Senior (n = 279)

Total sample	Men	Women	Total sample	Men	Women	Total sample	Men	Women


Disease	Regimen	No. pts.	PFS	Efficacy	Ref.

Metastatic head and neck cancer	Vorinostat: 400 mg orally daily	13		SD 2 pts. OR 0%	[51]

Metastatic breast cancer	Vorinostat: 400 mg orally daily	14		SD 4 pts	[52]

Relapsed NSCLC	Vorinostat: 400 mg or 300 mg once daily on days 1–14 of the 21 day cycle	16	Median: 2.3 m. 	SD 57%	[53]

Metastatic prostate cancer	Vorinostat: 400 mg orally daily	27	Median: 2.8 m. 	SD 2 pts.	[54]

Ovarian or primary peritoneal carcinoma	Vorinostat: 400 mg orally daily	27		PR 1 pt.	[55]

Recurrent GBM 	Vorinostat: 200 mg p.o.twice a day for 14 days, followed by a 7-day rest period	66	6-m.-PFS: 9 of the first 52 patients	OR 2 pts.	[56]

Metastatic colorectal cancer	Vorinostat: 800 or 1,400 mg/day once a day × 3 days, every 2 weeks +5-FU: preceded by leucovorin, at 400 mg/m2 followed by a 46 h infusion at 2.400 mg/m2 on days 2–3 	58	PFS rate did not reach the threshold of 27 out of 43 patients	PR 1 pt.	[57]

Untreated stage IIIB or IV NSCLC	Vorinostat: 400 mg or Placebo on days 1 through 14 of each 3-week cycle +Carboplatin: AUC 6 +Paclitaxel: 200 mg/m2, both on day 3 of each 21-day cycle	94	Median: Vorinostat: 6.0 m. Placebo: 4.1 m. P = ns	RR Vorinostat: 34% Placebo: 12.5% P = 02	[58]

Advanced thyroid cancer	Vorinostat: 400 mg orally daily	19		SD 56% OR 0	[59]

Recurrent GBM	Vorinostat: 400 mg daily for 14 days of a 21-day cycle + Bortezomib: 1.3 mg/m2 intravenously on days 1,4, 8, and 11 of a 21-day cycle	37	Median: 1.5 m. 	PR 1 pt.	[60]

Disease

Metastatic head and neck cancer

Metastatic breast cancer

Relapsed NSCLC

Metastatic prostate cancer

Ovarian or primary peritoneal carcinoma

Recurrent GBM

Metastatic colorectal cancer

Untreated stage IIIB or IV NSCLC

Advanced thyroid cancer

Recurrent GBM

Regimen	No. pts.	PFS	Efficacy	Ref.

Vorinostat: 400 mg orally daily	13		SD 2 pts. OR 0%	[51]

Vorinostat: 400 mg orally daily	14		SD 4 pts	[52]

Vorinostat: 400 mg or 300 mg once daily on days 1–14 of the 21 day cycle	16	Median: 2.3 m.	SD 57%	[53]

Vorinostat: 400 mg orally daily	27	Median: 2.8 m.	SD 2 pts.	[54]

Vorinostat: 400 mg orally daily	27		PR 1 pt.	[55]

Vorinostat: 200 mg p.o.twice a day for 14 days, followed by a 7-day rest period	66	6-m.-PFS: 9 of the first 52 patients	OR 2 pts.	[56]

Vorinostat: 800 or 1,400 mg/day once a day × 3 days, every 2 weeks +5-FU: preceded by leucovorin, at 400 mg/m2 followed by a 46 h infusion at 2.400 mg/m2 on days 2–3	58	PFS rate did not reach the threshold of 27 out of 43 patients	PR 1 pt.	[57]

Vorinostat: 400 mg or Placebo on days 1 through 14 of each 3-week cycle +Carboplatin: AUC 6 +Paclitaxel: 200 mg/m2, both on day 3 of each 21-day cycle	94	Median: Vorinostat: 6.0 m. Placebo: 4.1 m. P = ns	RR Vorinostat: 34% Placebo: 12.5% P = 02	[58]

Vorinostat: 400 mg orally daily	19		SD 56% OR 0	[59]

Vorinostat: 400 mg daily for 14 days of a 21-day cycle + Bortezomib: 1.3 mg/m2 intravenously on days 1,4, 8, and 11 of a 21-day cycle	37	Median: 1.5 m.	PR 1 pt.	[60]


Bacteria, plasmid, or gene	Relevant features or sequence (5′–3′)	References or sources

Bacteria

 E. coli DH5α	endA1 glnV44 thi-1 recA1 relA1 gyrA96 deoR F- Φ80dlacZΔM15 Δ(lacZYA-argF)U169, hsdR17(rK- mK +), λ–	Invitrogen

 L. lactis NZ9000	MG1363 nisRK ΔpepN	NIZO [35, 36]

 Lb. plantarum ATCC 8014	Wild type	ATCC

Plasmid

 pNZ8148	pSH71 derivative, PnisA, CmR, nisin-controlled expression	NIZO [35, 36]

 pNZRK	pNZ8148 containing nisR and nisK genes	This work

 pNZ-IRFP713	pNZ8148 containing irfp713 gene	This work

 pNZ-IRFP682	pNZ8148 containing irfp682 gene	This work

 pNZRK-IRFP713	pNZ8148 containing irfp713, nisR and nisK genes	This work

 pMA-T-IRFP713	pMA-T containing irfp713 gene	This work

 pMSP3545	Emr, PnisA, nisRK, NcoI for translational fusion, ColE1 and pAMβ1 replicons	[37]

 pMSP3545-IRFP713	pMSP3545 containing irfp713 gene	This work

 pGEM::CP25-IRFP	pGEM-T Easy containing irfp713 gene under the control of CP25 promoter	[27]

Gene

 irfp713	<underline>CCATGG</underline>CTGAGGGATCTGTAGCTCGTCAACCTGATTTACTTACTTGTGACGATGAACCTATTCATATTCCAGGTGCTATTCAACCACACGGACTTTTATTAGCTCTTGCCGCTGACATGACTATCGTCGCTGGATCAGATAATTTACCTGAATTGACTGGTTTAGCAATTGGAGCCCTTATTGGACGATCAGCAGCAGATGTTTTTGATTCAGAAACTCATAATCGTCTTACTATTGCATTGGCAGAACCTGGTGCTGCAGTAGGTGCTCCTATTACAGTAGGTTTCACTATGCGTAAGGATGCTGGTTTTATTGGTTCTTGGCATCGTCATGATCAACTTATTTTTTTAGAGTTGGAACCACCACAAAGAGACGTTGCAGAGCCTCAAGCTTTTTTTCGTCGTACTAATTCAGCAATTCGTAGACTTCAAGCTGCTGAAACTCTTGAATCTGCATGTGCAGCAGCAGCACAAGAGGTACGAAAAATTACAGGTTTTGATAGAGTTATGATTTACAGATTTGCCTCAGACTTTTCTGGTGAAGTAATCGCAGAGGATAGATGTGCCGAGGTTGAAAGTAAATTGGGATTGCATTATCCTGCCAGTACTGTTCCAGCCCAAGCACGTCGTCTTTATACTATTAATCCTGTTAGAATTATCCCAGATATTAATTATCGACCAGTTCCAGTTACTCCTGACTTAAATCCTGTAACTGGTAGACCTATTGACTTGTCATTTGCCATCTTACGATCTGTTTCACCTGTTCATTTAGAGTTTATGCGTAATATTGGTATGCATGGTACTATGTCTATCTCAATCCTTCGAGGAGAACGTTTATGGGGACTTATTGTTTGTCATCATAGAACACCTTATTATGTCGATTTAGATGGACGTCAAGCTTGTGAATTAGTTGCTCAAGTCTTGGCTTGGCAAATTGGTGTAATGGAAGAATAA<underline>TCTAGA</underline>	This work

Primers

 nisR-F	GATGATAAGCTGTCCAAAC	This work

 nisK-R	TTTAGGATAACTTCTGCCC	This work

 682-1F	CTCAGACTTTTCTGGTGTAGTAATCGCAGAGGATAG	This work

 682-2F	GCATTATCCTGCCAGTGCTGTTCCAGCCCAAGC	This work

 682-3F	CCATCTTACGATCTGTTTCACCTTGTCATTTAGAGTTTATGCG	This work

 682-1R	CTATCCTCTGCGATTACTACACCAGAAAAGTCTGAG	This work

 682-2R	GCTTGGGCTGGAACAGCACTGGCAGGATAATGC	This work

 682-3R	CGCATAAACTCTAAATGACAAGGTGAAACAGATCGTAAGATGG	This work

Bacteria, plasmid, or gene	Relevant features or sequence (5′–3′)	References or sources

L. lactis NZ9000	MG1363 nisRK ΔpepN	NIZO [35, 36]

Lb. plantarum ATCC 8014	Wild type	ATCC

Plasmid

pNZ8148	pSH71 derivative, PnisA, CmR, nisin-controlled expression	NIZO [35, 36]

pNZRK	pNZ8148 containing nisR and nisK genes	This work

pNZ-IRFP713	pNZ8148 containing irfp713 gene	This work

pNZ-IRFP682	pNZ8148 containing irfp682 gene	This work

pNZRK-IRFP713	pNZ8148 containing irfp713, nisR and nisK genes	This work

pMA-T-IRFP713	pMA-T containing irfp713 gene	This work

pMSP3545	Emr, PnisA, nisRK, NcoI for translational fusion, ColE1 and pAMβ1 replicons	[37]

pMSP3545-IRFP713	pMSP3545 containing irfp713 gene	This work

pGEM::CP25-IRFP	pGEM-T Easy containing irfp713 gene under the control of CP25 promoter	[27]

Gene

irfp713	CCATGGCTGAGGGATCTGTAGCTCGTCAACCTGATTTACTTACTTGTGACGATGAACCTATTCATATTCCAGGTGCTATTCAACCACACGGACTTTTATTAGCTCTTGCCGCTGACATGACTATCGTCGCTGGATCAGATAATTTACCTGAATTGACTGGTTTAGCAATTGGAGCCCTTATTGGACGATCAGCAGCAGATGTTTTTGATTCAGAAACTCATAATCGTCTTACTATTGCATTGGCAGAACCTGGTGCTGCAGTAGGTGCTCCTATTACAGTAGGTTTCACTATGCGTAAGGATGCTGGTTTTATTGGTTCTTGGCATCGTCATGATCAACTTATTTTTTTAGAGTTGGAACCACCACAAAGAGACGTTGCAGAGCCTCAAGCTTTTTTTCGTCGTACTAATTCAGCAATTCGTAGACTTCAAGCTGCTGAAACTCTTGAATCTGCATGTGCAGCAGCAGCACAAGAGGTACGAAAAATTACAGGTTTTGATAGAGTTATGATTTACAGATTTGCCTCAGACTTTTCTGGTGAAGTAATCGCAGAGGATAGATGTGCCGAGGTTGAAAGTAAATTGGGATTGCATTATCCTGCCAGTACTGTTCCAGCCCAAGCACGTCGTCTTTATACTATTAATCCTGTTAGAATTATCCCAGATATTAATTATCGACCAGTTCCAGTTACTCCTGACTTAAATCCTGTAACTGGTAGACCTATTGACTTGTCATTTGCCATCTTACGATCTGTTTCACCTGTTCATTTAGAGTTTATGCGTAATATTGGTATGCATGGTACTATGTCTATCTCAATCCTTCGAGGAGAACGTTTATGGGGACTTATTGTTTGTCATCATAGAACACCTTATTATGTCGATTTAGATGGACGTCAAGCTTGTGAATTAGTTGCTCAAGTCTTGGCTTGGCAAATTGGTGTAATGGAAGAATAATCTAGA	This work

Primers

nisR-F	GATGATAAGCTGTCCAAAC	This work

nisK-R	TTTAGGATAACTTCTGCCC	This work

682-1F	CTCAGACTTTTCTGGTGTAGTAATCGCAGAGGATAG	This work

682-2F	GCATTATCCTGCCAGTGCTGTTCCAGCCCAAGC	This work

682-3F	CCATCTTACGATCTGTTTCACCTTGTCATTTAGAGTTTATGCG	This work

682-1R	CTATCCTCTGCGATTACTACACCAGAAAAGTCTGAG	This work

682-2R	GCTTGGGCTGGAACAGCACTGGCAGGATAATGC	This work

682-3R	CGCATAAACTCTAAATGACAAGGTGAAACAGATCGTAAGATGG	This work


Predictors	Model 8	95% CI

Fixed effects

 Intercept	−0.81 *	(0.35)	−1.55	−0.09

 Ego gender	0.25	(0.51)	−0.80	1.30

 Change in activity scorea	0.38 **	(0.11)	0.16	0.59

 Change in contact frequencya	−0.71 ***	(0.17)	−1.03	−0.38

 Participant mean change in activity score	0.18	(0.24)	−0.31	0.68

 Participant mean change in contact frequency	−0.20	(0.27)	−0.76	0.35

 Gender × change in activity score	0.35 *	(0.15)	0.06	0.64

 Gender × change in contact frequency	0.51 *	(0.25)	0.03	1.00

Covariance parameters

 Random intercept (participants)	1.12 **	(0.38)	0.58	2.20

Predictors	Model 8	95% CI

Fixed effects

Intercept	−0.81 *	(0.35)	−1.55

Ego gender	0.25	(0.51)	−0.80

Change in activity scorea	0.38 **	(0.11)	0.16

Change in contact frequencya	−0.71 ***	(0.17)	−1.03

Participant mean change in activity score	0.18	(0.24)	−0.31

Participant mean change in contact frequency	−0.20	(0.27)	−0.76

Gender × change in activity score	0.35 *	(0.15)	0.06

Gender × change in contact frequency	0.51 *	(0.25)	0.03

Covariance parameters

Random intercept (participants)	1.12 **	(0.38)	0.58


miRNA	RT (Primer)	PCR (Forward primer)	PCR (Reverse primer)

mir-144	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCAGTACA	CGGCCGGTACAGTATAGATGA	GTGCAGGGTCCGAGGT

mir-106b*	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCGCAGCA	AATGCCGCACTGTGGGTACT	GTGCAGGGTCCGAGGT

mir-669k*	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCGCACAC	GCCCGGTGTGCATGTGTGTATAGTT	GTGCAGGGTCCGAGGT

mir-142-3p	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTCCATA	GCGCTGTAGTGTTTCCTACTT	GTGCAGGGTCCGAGGT

mir-223	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTGGGGT	CCGCCCGTGTCAGTTTGTCAAAT	GTGCAGGGTCCGAGGT

mir-210	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTCAGCC	AATCCTGTGCGTGTGACAGC	GTGCAGGGTCCGAGGT

mir-32*	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCAATATC	CGCGCGGCCAATTTAGTGTGTGT	GTGCAGGGTCCGAGGT

mir-669C	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCACACAC	CGCGCCATAGTTGTGTGTGGAT	GTGCAGGGTCCGAGGT

mir-466i-5p	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCCACACA	CGCCCTGTGTGTGTGTGTG	GTGCAGGGTCCGAGGT

mir-122*	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTTAGTG	CGCCCAAACGCCATTATCA	GTGCAGGGTCCGAGGT

mir-34C*	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCCCTGGC	GCCCAATCACTAACCACACA	GTGCAGGGTCCGAGGT

mir-541*	GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCAGTATG	ACACCCTGGCGAACACAGAATC	GTGCAGGGTCCGAGGT

U6		CTCGCTTCGGCAGCACA	AACGCTTCACGAATTTGCGT

RT (Primer)	PCR (Forward primer)	PCR (Reverse primer)

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCAGTACA	CGGCCGGTACAGTATAGATGA	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCGCAGCA	AATGCCGCACTGTGGGTACT	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCGCACAC	GCCCGGTGTGCATGTGTGTATAGTT	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTCCATA	GCGCTGTAGTGTTTCCTACTT	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTGGGGT	CCGCCCGTGTCAGTTTGTCAAAT	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTCAGCC	AATCCTGTGCGTGTGACAGC	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCAATATC	CGCGCGGCCAATTTAGTGTGTGT	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCACACAC	CGCGCCATAGTTGTGTGTGGAT	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCCACACA	CGCCCTGTGTGTGTGTGTG	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCTTAGTG	CGCCCAAACGCCATTATCA	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCCCTGGC	GCCCAATCACTAACCACACA	GTGCAGGGTCCGAGGT

GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCAGTATG	ACACCCTGGCGAACACAGAATC	GTGCAGGGTCCGAGGT

	CTCGCTTCGGCAGCACA	AACGCTTCACGAATTTGCGT


Quality Index items	Imamura et al. (1998)	Tillu and Gupta (1998)	Perez Millan and Foster (2001)

Reporting

1. Study hypothesis/aim/objective	1	1	1

2. Main outcomes	1	1	1

3. Characteristics of the participants	0	0	0

4. Interventions of interest	0	1	0

5. Distributions of principal confounders in each group	0	0	0

6. Main findings	0	1	1

7. Estimates of random variability for main outcomes	1	0	1

8. All the important adverse events that may be a consequence of intervention	0	0	0

9. Characteristics of patients lost to follow-up	0	1	1

10. Actual probability values for main outcomes	0	1	0

External validity

11. Were subjects who were asked to participate representative of the entire population from which they were recruited?	1	1	0

12. Were subjects who were prepared to participate representative of the entire population from which they were recruited?	0	0	0

13. Were the staff, places, and facilities representative of the treatment the majority of subjects received?	1	0	1

Internal validity (bias)

14. Was an attempt made to blind subjects to the intervention they received?	0	0	0

15. Was an attempt made to blind those measuring main outcomes of the intervention?	0	0	0

16. If any of the results of the study were based on"data dredging", was this made clear?	0	1	1

17. Do analyses adjust for different lengths of follow-up?	0	1	1

18. Were appropriate statistical tests used to assess the main outcomes?	1	1	1

19. Was compliance with the intervention reliable?	1	1	1

20. Were main outcome measures reliable and valid?	0	0	0

Internal validity (selection bias)

21. Were patients in different intervention groups recruited from the same population?	0	0	0

22. Were subjects in different intervention groups recruited over the same period of time?	0	0	0

23. Were subjects randomized to intervention groups?	0	0	0

24. Was the randomized intervention assignment concealed from both patients and staff until recruitment was complete and irrevocable?	0	0	0

* 25. Was there adequate adjustment for confounding in the analyses from which main findings were drawn?	x	x	x

26. Were losses of subjects to follow-up taken into account?	0	1	1

Power

* 27. Did the study have sufficient power to detect a clinically important effect where the probability for a difference due to chance was less than 5%?	x	x	x

Total score (/27)	7	12	11


Paraclinical findings	Number a(%)	Number b (%)

Chest X ray

Normal	98 (94,2)	57 (96,6)

Abnormal	6 (5,8)	3 (5,1)

Cardiomegaly	2 (1,9)	1 (1,7)

Enlargement of the superior mediastinum	3 (2,9)	1 (1,7)

Interstitial Syndrome	1 (1)	0

Spirometry

Normal	94 (90,4)	56

Restrictive profile	7 (6,7)	1 (1,7)

Obstructive ventilatory defect	3 (2,9)	2 (3,4)

Electrocardiogram

Normal	92 (88,5)	54

Abnormal	12 (11,5)	5 (8,5)

Right atrial hypertrophy	10 (9,6)	4 (6,8)

Arrhythmia	2 (1,9)	1 (1,7)

Paraclinical findings	Number a(%)	Number b (%)

Right atrial hypertrophy	10 (9,6)	4 (6,8)

Arrhythmia	2 (1,9)	1 (1,7)


PANTHER Pathways	Annotated	Dapulian (DT_DC)	Landrace (LT_LC)

Significant	Expected	Fold Enrichment	p-Value	Significant	Expected	Fold Enrichment	p-Value

Angiogenesis (P00005)	147	27	13.37	2.02	6.50 × 10−4	27	14.56	1.85	2.16 × 10−3

Cholecystokinin receptor(CCKR) signaling map (P06959)	155	30	14.1	2.13	1.43 × 10−4	23	15.35	1.5	4.00 × 10−2

Epidermal growth factor (EGF) receptor signaling pathway (P00018)	134	24	12.19	1.97	1.73 × 10−3	23	13.27	1.73	9.35 × 10−3

Fibroblast growth factor (FGF) signaling pathway (P00021)	124	21	11.28	1.86	5.97 × 10−3	19	12.28	1.55	4.47 × 10−2

Parkinson disease (P00049)	104	20	9.46	2.11	1.82 × 10−3	23	10.3	2.23	4.26 × 10−4

PI3 kinase pathway (P00048)	45	10	4.09	2.44	9.36 × 10−3	11	4.46	2.47	6.18 × 10−3

Ras Pathway (P04393)	80	22	7.28	3.02	7.76 × 10−6	14	7.92	1.77	3.17 × 10−2

T cell activation (P00053)	83	16	7.55	2.12	4.81 × 10−3	15	8.22	1.82	2.11 × 10−2

Toll receptor signaling pathway (P00054)	59	10	5.37	1.86	4.69 × 10−2	11	5.84	1.88	3.63 × 10−2

Ubiquitin proteasome pathway (P00060)	65	11	5.91	1.86	3.89 × 10−2	13	6.44	2.02	1.48 × 10−2

Gonadotropin releasing hormone receptor pathway (P06664)	223	41	20.28	2.02	3.09 × 10−5	–	–	–	–

Apoptosis signaling pathway (P00006)	129	24	11.73	2.05	1.06 × 10−3	–	–	–	–

Fas signaling pathway (P00020)	41	11	3.73	2.95	1.65 × 10−3	–	–	–	–

Vascaular endothelial growth factor (VEGF) signaling pathway (P00056)	61	13	5.55	2.34	4.71 × 10−3	–	–	–	–

Integrin signaling pathway (P00034)	153	24	13.92	1.72	8.50 × 10−3	–	–	–	–

p53 pathway feedback loops 2 (P04398)	53	11	4.82	2.28	1.06 × 10−2	–	–	–	–

De novo purine biosynthesis (P02738)	46	10	4.18	2.39	1.08 × 10−2	–	–	–	–

Oxidative stress response (P00046)	29	7	2.64	2.65	1.83 × 10−2	–	–	–	–

Transforming growth factor beta(TGF-β) signaling pathway (P00052)	90	15	8.19	1.83	2.04 × 10−2	–	–	–	–

Hypoxia response via HIF activation (P00030)	30	7	2.73	2.57	2.15 × 10−2	–	–	–	–

Platelet derived growth factor (PDGF) signaling pathway (P00047)	141	21	12.82	1.64	2.17 × 10−2	–	–	–	–

Interleukin signaling pathway (P00036)	101	16	9.19	1.74	2.56 × 10−2	–	–	–	–

Inflammation mediated by chemokine and cytokine signaling pathway (P00031)	228	30	20.74	1.45	3.19 × 10−2	–	–	–	–

Heme biosynthesis (P02746)	14	4	1.27	3.14	4.04 × 10−2	–	–	–	–

Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade (P00032)	35	7	3.18	2.2	4.35 × 10−2	–	–	–	–

p53 pathway (P00059)	92	14	8.37	1.67	4.60 × 10−2	–	–	–	–

Coenzyme A biosynthesis (P02736)	11	–	–	–	–	5	1.09	4.59	5.21 × 10−3

Salvage pyrimidine ribonucleotides (P02775)	13	–	–	–	–	5	1.29	3.88	1.02 × 10−2

B cell activation (P00010)	68	–	–	–	–	13	6.74	1.93	2.05 × 10−2

General transcription regulation (P00023)	34	–	–	–	–	8	3.37	2.38	2.19 × 10−2

Lysine biosynthesis (P02751)	6	–	–	–	–	3	0.59	>5	2.25 × 10−2

Insulin/insulin-like growth factor (IGF) pathway-protein kinase B signaling cascade (P00033)	49	–	–	–	–	10	4.85	2.06	2.67 × 10−2

Angiotensin II-stimulated signaling through G proteins and β-arrestin (P05911)	30	–	–	–	–	7	2.97	2.36	3.20 × 10−2

Notch signaling pathway (P00045)	40	–	–	–	–	8	3.96	2.02	4.88 × 10−2


Diagnosis

Guillain-Barré syndrome, n (%)	26 (63.4)

Autoimmune encephalitis, n (%)	6 (14.6)

Miller-Fisher syndrome, n (%)	2 (4.9)

Chronic relapsing inflammatory optic neuropathy (CRION), n (%)	1 (2.4)

Multiple sclerosis, n (%)	1 (2.4)

Parainfectious myelitis, n (%)	1 (2.4)

Myasthenia gravis, n (%)	1 (2.4)

Anti-Yo-associated paraneoplastic cerebellar degeneration, n (%)	1 (2.4)

Anti-Hu-associated polyneuropathy, n (%)	1 (2.4)

Neuromyelitis optica, n (%)	1 (2.4)


Variables	Algorithm

P(X) = base rate of event for person X	Produce a time series for C and S events:

P(X|Y) = rate of event for X given Y did

P(X|X) = probability of event repetition	Do 1000 timesIf rand < P(C)C outputs event (=1)Else if rand < P(C|C) and C = 1C outputs eventOtherwiseC outputs no event (=0)If rand < P(S|C) and C = 1S outputs event (=1)Else if rand < P(S)S outputs eventElse if rand < P(S|S) and S = 1S outputs eventOtherwiseS outputs no event (=0)


	Disability screening but not in regression model	In regression model	p Value	Number of missing values/4219 (%)

Allocation to intervention in original trial	316/901 (35%)	1786/3318 (54%)	<0.001

Household appliance score: none of assets on list	475/901 (53%)	1754/3318 (53%)	0.801

Household appliance score: most expensive assets	58/901 (6%)	187/3318 (6%)

Positive disability screen	73/901 (8%)	241/3318 (7%)	0.395

Included in initial regression model but dropped from final model

 Four skilled antenatal care visits	87/901 (10%)	296/3315 (9%)	0.501	3 (<1%)

 Possible symptoms of preeclampsia	499/873 (57%)	1697/3210 (53%)	0.024	136 (3%)

 Delivery room heated	681/901 (76%)	2651/3318 (80%)	0.005	0

 Infant had fever in neonatal period	156/901 (17%)	489/3318 (15%)	0.057	0

Retained in final logistic regression model

 Maternal underweight (BMI<18∙5)	89/675 (13%)	382/3318 (12%)	0.220	226 (5%)

 Mother cohabited with husband when <16 years old	178/716 (25%)	812/3318 (24%)	0.827	185 (4%)

 Skilled birth attendant	18/733 (3%)	91/3318 (3%)	0.664	168 (4%)

 Infant size ‘very small’	12/901 (1%)	108/3318 (3%)	0.002	0

 Infant illness: diarrhoea and repeated vomiting	46/901 (5%)	159/3318 (5%)	0.698	0

 Mean weight in grams at 1 month (SD)	4395(963) n=335	4271(898) n=3318	0.017	566 (13%)

	Disability screening but not in regression model	In regression model	p Value	Number of missing values/4219 (%)

Allocation to intervention in original trial	316/901 (35%)	1786/3318 (54%)	<0.001

Household appliance score: none of assets on list	475/901 (53%)	1754/3318 (53%)	0.801

Household applian	58/9	187

	Disability screening but not in regression model	In regression model	p Value	Number of missing values/4219 (%)

ce score: most expensive assets	01 (6%)	/3318 (6%)

Positive disability screen	73/901 (8%)	241/3318 (7%)	0.395

Included in initial regression model but dropped from final model

Four skilled antenatal care visits	87/901 (10%)	296/3315 (9%)	0.501	3 (<1%)

Possible symptoms of preeclampsia	499/873 (57%)	1697/3210 (53%)	0.024	136 (3%)

Delivery room heated	681/901 (76%)	2651/3318 (80%)	0.005	0

Infant had fever in neonatal period	156/901 (17%)	489/3318 (15%)	0.057	0

Retained in final logistic regression model

Maternal underweight (BMI<18∙5)	89/675 (13%)	382/3318 (12%)	0.220	226 (5%)

Mother cohabited with husband when <16 years old	178/716 (25%)	812/3318 (24%)	0.827	185 (4%)

Skilled birth attendant	18/733 (3%)	91/3318 (3%)	0.664	168 (4%)

Infant size ‘very small’	12/901 (1%)	108/3318 (3%)	0.002	0

Infant illness: diarrhoea and repeated vomiting	46/901 (5%)	159/3318 (5%)	0.698	0

Mean weight in grams at 1 month (SD)	4395(963) n=335	4271(898) n=3318	0.017	566 (13%)


Prediction set	Published [14]	BRAKER1/soft-masked

Number of protein coding genes predicted	20,964	15,747

Mean protein length (amino acids)	218.8	344.5

Number of single exon genes	1,728	2,326

Mean number of exons per genea	5.9	7.8

Proportion of noncanonical (GC-AG) introns	8.87%	0.79%

Percentage mapping to publicly available transcriptome reads

Sanger ESTs	80.45%	84.26%

Roche 454 reads	37.18%	58.03%

BUSCO score for proteome

Complete	47.8%	94%

Fragmented	34.7%	4.3%

Number of proteins with no hits in Uniref90	8,962	2,889

Protein singletons in clustering	5,442	1,112

Conserved, single-copy orthologuesb

Total	2,089	2,330

Missing	377	141

Expanded	184	84

Prediction set	Published [14]	BRAKER1/soft-masked

Conserved, single-copy orthologuesb

Total	2,089	2,330

Missing	377	141

Expanded	184	84


Organism	Group	tag	Lanes in Figure 2

Gallus gallus	Animals	CACTCACAAGCTCGACGTACAC	1 and 8

Canis familiaris	Animals	CAGACAGCACTCGTTCGTACAC	2 and 9

Arabidopsis thaliana	Plants	GACTGAACGTGCTCTGCTACTG	3 and 10

Sulfolobus acidocaldarius str. DSM639	Crenarchaeota	CAGTCACAGCACACGAGTACAC	4 and 11

Bartonella henselae str. Houston-1	Alphaproteobacteria	CAGACACGAGCAACGACTACAC	5 and 12

Bartonella henselae str. UGA 8	Alphaproteobacteria	CAGACACGAGCAACGACTACAC	6 and 13

Anabaena PCC7120	Cyanobacteria	CACTCTGTGCTCGTTGCTACAC	(Figure 3)

Synechocystis PCC 6803	Cyanobacteria	CAGACAGCAAGCAGCACTACAC	(Figure 3)


Parameter	Responders (n = 15)	Nonresponders (n = 13)

	Baseline	Before INO	P value	Baseline	Before INO	P value

Leucocytes (106/ml)	10.4 ± 4.4	1.6 ± 1.0†	≤ 0.01	8.8 ± 2.4	0.9 ± 0.3* †	≤ 0.01

Neutrophils (%)	56 ± 12	65 ± 14	0.074	53 ± 10	48 ± 17*	0.45

Macrophage (%)	44 ± 12	34 ± 15	0.064	47 ± 10	51 ± 17*	0.45

Thrombocytes (106/ml)	408 ± 77	185 ± 54†	≤ 0.01	355 ± 61	175 ± 68†	≤ 0.01


Breast Clinicopathological details	Cancer	Fibroadenoma	Normal

Number of patients	103	35	30

Median Patient Age yrs	56 (35-90)	44 (17-62)	46.5 (24-58)

Menopausal Status

Post	72

Pre	32

Histological Subtype

Invasive Ductal	78

Invasive Lobular	11

Other	14

Intrinsic Subtype

Luminal A (ER/PR+, HER2/neu-)	42

Luminal B (ER/PR+, HER2/neu+)	18

HER2 Over expressing (ER-, PR-, HER2/neu+)	16

Triple-Negative (ER-, PR-, HER2/neu-)	16

Unknown	11

Tumour Grade

1	5

2	32

3	55

Tumour size

1	19

2	39

3	10

UICC Stage

Stage 1	23

Stage 2	36

Stage 3	21

Stage 4	10


	Participants from wards with high staff moralea (n = 12)	Participants from wards with low staff moralea (n = 9)

Gender	50 % (6/12) male; 50 % (6/12) female	89 % (8/9) male; 11 % (1/9) female

Age	25 % (3/12) 16–17 years	22 % (2/9) 18–25 years

8 % (1/12) 18–25 years	33 % (3/9) 26–35 years

25 % (3/12) 26–35 years	11 % (1/9) 36–45 years

16 % (2/12) 36–45 years	33 % (3/9) 46–55 years

8 % (1/12) 46–55 years

16 % (2/12) 56–65 years

Ethnicity	50 % (6/12) British or White British	33 % (3/9) British or White British

17 % (2/12) White & Black Caribbean	22 % (2/9) Black African

8 % (1/12) Indian	11 % (1/9) Caribbean

8 % (1/12) White other	11 % (1/9) Black other

8 % (1/12) Black other	11 % (1/9) Asian

8 % (1/12) Mixed ethnicity	11 % (1/9) Mixed ethnicity

Ward type	25 % (3/12) Female acute ward	33 % (3/9) Male psychiatric intensive care unit

	25 % (3/12) Mixed gender recovery unit	33 % (3/9) Male acute ward

	25 % (3/12) Mixed gender child and adolescent unit	33 % (3/9) Mixed gender acute ward

	25 % (3/12) Male rehabilitation unit


Parameter		BSP	Control	P

Gender	Male	62	65	>0.05

	Female	38	35

Age	≤40	33	29	>0.05

	>41	67	71

Etiology	Trauma	31	31	>0.05

	Other	69	69


	Group 1 (n = 33) admitted to HSS	Group 2 (n = 27) admitted to RS	P valuea)

Total number	Mean per patient	SD	Total number	Mean per patient	SD

Specialist health care services

In-patient days (total number)	245	7.4	12.1	300	11.1	22.1	0.872

Number in-patient days at HSS	118	3.6	7.0	156	5.8	11.7	0.621

Number in-patient days at RS	117	3.5	6.4	131	4.9	11.4	0.813

Number in-patient days other hospitals	10	0.3	1.0	13	0.5	1.5	0.952

Out-patient/X-ray consult. (total number)	70	2.1	3.0	37	1.4	2.3	0.201

Out-patient/X-ray consultations at HSS	26	0.8	1.4	6	0.2	0.5	0.044*

Out-patient/X-ray consultations at RS	29	0.9	1.3	16	0.6	1.0	0.318

Out-patient/X-ray consult. other hospitals	15	0.5	0.9	15	0.6	1.4	0.752

Municipal health care services

Nursing homes (days)	355	10.8	30.0	524	19.4	50.0	0.078

Home care total (hours)	2415	73.2	136.2	3019	111.8	245.6	0.796

Home nursing (hours)	1983	60.1	117.6	2669	98.9	227.4	0.856

Practical help (hours)	432	13.1	26.4	350	13.0	24.0	0.970

GP office consultations (number)	470	14.2	11.8	352	13.0	13.3	0.562

GP consultations (number)	263	8.0	7.2	193	7.2	7.6	0.612

Nurse consultations (number)	207	6.3	7.4	159	5.9	7.4	0.976


Stage	Serum creatinine criteria

1	1.5-1.9 times baseline

OR

≥ 26.5 5 μmol/l (0.3 mg/dl) increase within 48 hoursa

2	2.0-2.9 times baseline

3	≥ 3.0 times baseline

OR

Increase in serum creatinine to ≥ 354 μmol/l (4.0 mg/dl)b

OR

Initiation of renal replacement therapy

Serum creatinine criteria

1.5-1.9 times baseline

OR

≥ 26.5 5 μmol/l (0.3 mg/dl) increase within 48 hoursa

2.0-2.9 times baseline

≥ 3.0 times baseline

OR

Increase in serum creatinine to ≥ 354 μmol/l (4.0 mg/dl)b

OR

Initiation of renal replacement therapy


DMFT component	Disabledmean ± SD	Normalmean ± SD	t-value	df	P value

Deca	0.64 ± 1.32	1.06	2.	234	0.0


Factors	Categories	No. of patients (%)	P value

Gender	Female	465(27.1)	0.301

	Male	1250(72.9)

age		57.5 ± 10.9	<0.001

Past medical history	No	1258(73.4)	0.022

	Yes	457(26.6)

Family history of gastric cancer	No	1431(83.4)	0.431

	Yes	284(16.6)

Location of tumor	Lower third	1086(63.3)	<0.001

	Middle third	281(16.4)

	Upper third	193(11.3)

	Whole stomach	155(9.03)

Eradicative degree of surgery	Utterly	809(47.8)	<0.001

	Relatively	473(27.6)

	Palliative	433(25.2)

Tumor size(mm)	<40	364(21.2)	<0.001

	≥40	1315(78.8)

Stage	I	301(17.5)	<0.001

	II	425(24.8)

	III	497(29.0)

	IV	492(28.7)

Combined evisceration	No	1323(77.1)	<0.001

	Yes	392(22.9)

Histologic grade	Well differentiated	521(30.3)	<0.001

	Moderately differentiated	253(14.8)

	Poorly differentiated	941(54.9)

Depth of invasion	T1	145(8.5)	<0.001

	T2	879(51.3)

	T3	549(32.0)

	T4	142(8.3)

Lymph node status	N0	629(36.7)	<0.001

	N1	717(41.8)

	N2	272(15.9)

	N3	97(5.7)

Factors	Categories	No. of patients (%)	P value

	Upper third	193(11.3)

	Whole stomach	155(9.03)

Eradicative degree of surgery	Utterly	809(47.8)	<0.001

	Relatively	473(27.6)

	Palliative	433(25.2)

Tumor size(mm)	<40	364(21.2)	<0.001

	≥40	1315(78.8)

Stage	I	301(17.5)	<0.001

	II	425(24.8)

	III	497(29.0)

	IV	492(28.7)

Combined evisceration	No	1323(77.1)	<0.001

	Yes	392(22.9)

Histologic grade	Well differentiated	521(30.3)	<0.001

	Moderately differentiated	253(14.8)

	Poorly differentiated	941(54.9)

Depth of invasion	T1	145(8.5)	<0.001

	T2	879(51.3)

	T3	549(32.0)

	T4	142(8.3)

Lymph node status	N0	629(36.7)	<0.001

	N1	717(41.8)

	N2	272(15.9)

	N3	97(5.7)


Method	Algorithm	False positive rate	False negative rate

MEMSAT-SVM	SVM	0.00%	0.44%

MEMSAT3	NN	0.50%	0.50%

SOSUI	Hydrophobicity analysis	0.33%	1.10%

OCTOPUS	NN + HMM	0.00%	2.51%

PHOBIUS	HMM	2.72%	0.44%


	Denmark	Norway	Sweden

TKA

 Mean	146	70	143

 Median	132	53	105

 Range	1–345	1–275	1–527

UKA

 Mean	35	19	30

 Median	29	16	24

 Range	1–85	1–57	1–104

TKA

Mean

Median

Range

UKA

Mean

Median

Range


Parameter	HR	95 % CI	P

Disease-free survival: Cox regression model

TNM stage			0.06

 III-IV (vs. I-II)	2.528	1.299–4.921

Tumor differentiation			0.021

 Poor (vs. Well/moderate)	1.785	1.089–2.925

AREG expression			0.168

 Positive (vs. Negative)	1.418	0.863–2.331

AREG/EGFR coexpression			0.587

 Negative (vs. Positive)	0.922	0.687–1.237

Overall survival: Cox regression model

Tumor size			0.485

 T3-4 (vs. T1-2)	1.24	0.677–2.271

TNM stage			0.03

 III-IV (vs. I-II)	2.25	1.081–4.684

Tumor differentiation			0.004

 Poor (vs. Well/moderate)	2.125	1.277–3.537

Resection margins			0.045

 Positive (vs. Negative)	1.84	1.277–3.537

Lymph node metastasis			0.417

 Yes (vs. No)	1.233	0.743–2.048

AREG expression			0.03

 Positive (vs. Negative)	1.822	1.058–3.137


Comparison	CTCs	ctDNA	Exosomes

Origin	Includes apoptotic tumor and viable tumor cells from a primary or metastatic tumor [71, 73].	Includes cfDNA, from the viable tumor cells or from CTCs [17, 219, 221, 224, 225].	Includes DNA, proteins, lipids, RNAs and metabolites and are discharged by all cells including tumor cells [333, 336, 352, 355–357].

Bio-banked samples used for study	Frozen plasma, urine and other biofluids cannot be used for study of CTCs [116].	Frozen plasma, urine and other biofluids can be used for study of cfDNA [116, 260].	Frozen plasma, urine and other biofluids can be used for study of exosomes [260].

Stability	Unstable [114, 116, 117]	Stable [116]	Very stable [334]

Genetic materials	DNA and RNA [117, 122, 123]	DNA [17, 219, 221]	DNA and RNA [355, 357, 359–361]

Analytic Techniques	CellSearch [84, 148–150, 180, 182, 190], Microfluidic [187, 181], SE-iFISH [186], MetaCell [184], Immunofluorescence [181, 185, 188], ScreenCell [185], ISET Test [188, 190] etc.	dPCR [289], CAPP-Seq [293], TAM-Seq [276], ddPCR [290, 307, 308, 310], COLD-PCR [167], Safe-Seq [294], NGS [299, 308–310], BEAMing [291, 292], WGA [297, 298] etc.	Ultracentrifugation [387, 386, 389–391, 393], ExoChip [392], Precipitation [386], Size-based isolation [386], Immunoaffinity-based isolation [386], Microfluidics-based isolation etc [386].

Morphological study and functional study of tumor cells ex vivo	Yes [128, 129, 188, 190, 206, 210, 213, 214]	No	No

Analysis of protein location on tumor cells	Yes [101, 102]	No	No

Identification of mutations	Yes [165, 185, 187]	Yes [306, 319]	Yes [387, 390, 393]

Identification of epigenetic changes	Yes [414, 415]	Yes [322–325]	Yes [357]

Analysis of RNA transcription profiles	Yes [157, 192]	No	Yes [359–361, 367]

Proteomics Analysis	Yes [157]	No	Yes [367, 387, 392]

Analysis tumor heterogeneity	Yes [206]	Yes [332]	No

Use as drug delivery vehicle	No	No	Yes [406, 410]


	Label	Start	Name	Function	References

ldRNA	BSU_misc_RNA_3	119855	ldlJ	Ribosomal protein L10 leader mRNA sequence	26101249

suRNA	BSU_misc_RNA_7	486092	swaO	ATP‐, cyclic di‐AMP‐sensing riboswitch	25086507, 25086509

CDS	BSU04785	528025	cmpA	Factor allowing degradation of SpoIVA by ClpXP	26387458

suRNA	BSU_misc_RNA_65	532642	sncO	ICEBs1 mobile element: conserved small untranslated RNA	20525796, 22505685

suRNA	BSU_misc_RNA_66	559610	sncZ	No identified function: borders undefined	20525796

suRNA	BSU_misc_RNA_8	626446	aswA	Adenine riboswitch	25573585

CDS	BSU09958	1071402	sscA	Spore assembly and germination protein	21670523

CDS	BSU09959	1071613	sscB	Spore assembly and germination protein	21670523

suRNA	BSU_misc_RNA_67	1233405	roxS	Small regulatory RNA (NO regulated)	28436820

CDS	BSU12815	1348356	spoIISC	Three component toxin/antitoxin/antitoxin SpoIISABC, antitoxin C	25039482, 26300872, 27294956

Riboswitch	BSU_misc_RNA_16	1376328	guwA	Guanidinium riboswitch	28212758

Riboswitch	BSU_misc_RNA_68	1395622	swmG	Magnesium riboswitch (modest affinity)	28455443

Riboswitch	BSU_misc_RNA_87	1410633	mnrW	Manganese ion riboswitch	25794618, 25794619

Riboswitch	BSU_misc_RNA_88	1457005	gswA	Riboswitch regulating ptsGHI expression via GlcT binding	15155854, 22750856

suRNA	BSU_misc_RNA_69	1483557	fsrA	Regulatory RNA controlling iron‐dependent metabolism	24576839

suRNA	BSU_misc_RNA_70	1534070	srrA	Small regulatory RNA and messenger RNA (arginine metabolism)	27449348

CDS	BSU14629	1534120	rgpA	Regulator of GapA synthesis	27449348

CDS	BSU15140	1580622	rsmH	16S rRNA m4C1402 methyltransferase	27711192

suRNA	BSU_misc_RNA_89	1780554	surX	sigW‐dependent	23155385

CDS	BSU17845	1916955	yzzP	No identified function, present in some S. pneumoniae strains	27144405

CDS	BSU18978	2069883	bsrE	Type I toxin (BsrE/AsrE)	26940229

suRNA	BSU_misc_RNA_74	2070115	asrE	Small regulatory antitoxin RNA, toxin‐antitoxin type I system (BsrE/AsrE)	26940229

CDS	BSU19749	2146053	yoyG	Putative toxin of a type I toxin family (sporulation operon)	20156992, 21670523

fCDS	BSU20049	2160397	nrdFBc	Phage SP beta nucleoside diphosphate reductase minor subunit (C‐terminus)	23391036

fCDS	BSU20051	2161778	nrdFBn	Phage SP beta nucleoside diphosphate reductase minor subunit (N‐terminus)	23391036

suRNA	BSU_ncRNA_1	2208880	aimX	Small RNA controlling lysogeny of phage SPbeta	28099413

CDS	BSU20850	2208980	aimP	Arbitrium lysis /lysogeny regulatory peptide (GMPRGA)	28099413

CDS	BSU20860	2210154	aimR	Arbitrium peptide sensor regulator	28099413

asRNA	BSU_misc_RNA_90	2219849	apbT	Antisense RNA of Toxin SpbT	24576839

CDS	BSU21000	2219960	spbT	Toxin	24576839

suRNA	BSU_misc_RNA_91	2472880	pswI	Proline T‐box riboswitch upstream of porI	21233158

suRNA	BSU_misc_RNA_82	2773783	surF	Expressed under sporulation conditions	25790031

ldRNA	BSU_misc_RNA_43	2855915	ldlU	Ribosomal protein L21 leader mRNA sequence	27381917

CDS	BSU28475	2910746	lysCB	Beta subunit of aspartokinase II	1980002

ldRNA	BSU_misc_RNA_47	2953550	ldlT	Ribosomal protein L20 leader mRNA sequence	23611891

ldRNA	BSU_misc_RNA_93	3035589	ldsD	Ribosomal protein S4 leader mRNA sequence	23611891

asRNA	BSU_ncRNA_2	3335545	auzJ	Putative antisense RNA for YuzJ putative toxin (toxin I signature)	20156992, 21670523

suRNA	BSU_misc_RNA_94	4169919	mswM	Manganese riboswitch	25794618, 25794619


Characteristic	Beijing	Chongqing	Guangzhou	Total

	n	%	n	%	n	%	n	%

Number of children	10,372	42.70%	9,846	40.53%	4,072	16.77%	24,290

Response rate	98.60%		97.21%		90.90%		96.62%

Gender


Top 16 most significant in order	Chemical shift (ppm)	I/II stage of CRC vs healthy controls	Related metabolomic pathway

VIPa	p-valueb	Variations vs HC

Choline	3.19(s)	2.25	0.000	↓	Choline metabolism, Lipid metabolism

Phenylalanine	3.19(m)3.98(dd)	2.251.43	0.0000.004	↓↓	Amino acid metabolism, Phenylalanine metabolism

Asparagine	2.80(dd)	1.90	0.000	↓	Urea metabolism, Amino acid metabolism

Isocitrate	3.98(d)	1.84	0.005	↓	TCA cycle

Cysteine	3.97(dd)3.06(m)	1.841.70	0.0030.000	↓↓	Amino acid metabolism, Glutamate Metabolism, Glutathione Metabolism

Hippurate	3.96(d)	1.84	0.005	↓	Gut microflora metabolism

Dimethyl sulfone	3.138(s)	1.72	0.000	↓	Gut microflora metabolism, Endogenous methanethiol metabolism

Creatinine	3.03(s)4.05(s)	1.701.43	0.0070.003	↓↓	Urea metabolism, Creatinine metabolism

Alanine	1.46(d)	1.67	0.017	↓	Amino acid metabolism, Gluconeogenesis

Methylamine	2.59(s)	1.12	0.018	↓	Gut microflora metabolism, Disulfiram Pathway

Homocysteine	2.14(m)	1.76	0.014	↑	Amino acid metabolism, Methionine metabolism

Glutamine	2.12(m)3.76(t)	1.761.53	0.0010.017	↑↑	Glutaminolysis, TCA cycle

cis-Aconitate	3.43(d)	1.64	0.043	↑	TCA cycle, Glyoxylate, Dicarboxylate metabolism

Acetoacetate	2.27(s)3.43(s)	1.591.64	0.0090.043	↑↑	Fatty acid metabolism, TCA cycle

trans-Aconitate	3.74(s)	1.54	0.019	↑	TCA cycle

Guanidoacetate	3.78(s)	1.53	0.017	↑	Urea metabolism

Top 16 most significant in order	Chemical shift (ppm)

Choline	3.19(s)

Phenylalanine	3.19(m)3.98(dd)

Asparagine	2.80(dd)

Isocitrate	3.98(d)

Cysteine	3.97(dd)3.06(m)

Hippurate	3.96(d)

Dimethyl sulfone	3.138(s)

Creatinine	3.03(s)4.05(s)

Alanine	1.46(d)

Methylamine	2.59(s)

Homocysteine	2.14(m)

Glutamine	2.12(m)3.76(t)

cis-Aconitate	3.43(d)

Acetoacetate	2.27(s)3.43(s)

trans-Aconitate	3.74(s)

Guanidoacetate	3.78(s)

I/II stage of CRC vs healthy controls	Related metabolomic pathway

VIPa	p-valueb	Variations vs HC

2.25	0.000	↓	Choline metabolism, Lipid metabolism

2.251.43	0.0000.004	↓↓	Amino acid metabolism, Phenylalanine metabolism

1.90	0.000	↓	Urea metabolism, Amino acid metabolism

1.84	0.005	↓	TCA cycle

1.841.70	0.0030.000	↓↓	Amino acid metabolism, Glutamate Metabolism, Glutathione Metabolism

1.84	0.005	↓	Gut microflora metabolism

1.72	0.000	↓	Gut microflora metabolism, Endogenous methanethiol metabolism

1.701.43	0.0070.003	↓↓	Urea metabolism, Creatinine metabolism

1.67	0.017	↓	Amino acid metabolism, Gluconeogenesis

1.12	0.018	↓	Gut microflora metabolism, Disulfiram Pathway

1.76	0.014	↑	Amino acid metabolism, Methionine metabolism

1.761.53	0.0010.017	↑↑	Glutaminolysis, TCA cycle

1.64	0.043	↑	TCA cycle, Glyoxylate, Dicarboxylate metabolism

1.591.64	0.0090.043	↑↑	Fatty acid metabolism, TCA cycle

1.54	0.019	↑	TCA cycle

1.53	0.017	↑	Urea metabolism


Characteristic	HIV infected patients	Normal controls

Subject no.	32	35

Age (years, mean ± SD)	34 ± 6	36 ± 6

Male (No, %)	15 (46.9%)	15 (42.9%)

Han Ethnic (No, %)	32 (100%)	35 (100%)

CD4 (cells/μL, mean ± SD)	331 ± 235	N/A

VL [log copies/mL (mean ± SD)]	4.15 ± 1.09	N/A

Time since diagnosis (weeks, mean, range)	65 (1–336)	N/A


Model mechanism	Symbol	Mathematical expressions

First-order decay (n=1)	F1	(1–α)

Second-order decay (n=2)	F2	(1– α)2

Third-order decay (n=3)	F3	0.5 · (1– α)3

Avrami-Erofeev (n=2)	A2	2 · (1– α) · [–ln(1– α)]0.5


Preamble

These recommendations are relevant to all practitioners and organizations communicating the new Canadian Physical Activity Guidelines for Youth. These recommendations should be used to create a clear understanding of the new Canadian Physical Activity Guidelines for Youth and to construct and to deliver messages that promote achievement of the guidelines.

Recommendations

Target Audience	Messages should separately target younger youth (12-14 yrs) and their parents and older youth (15-17 yrs) and their parents.

Clarification Messages	Clarification messages should: a) provide concise and clear descriptions of the guidelines and physical activity, b) define different levels of physical activity intensity (e.g., vigorous, vs. moderate), c) identify physical activity opportunities, d) include information about where to access more information about physical activity, e) indicate that science has evolved since the release of the old guidelines and that the new guidelines reflect latest evidence about physical activity, f) address the semantic differences between the old and new guidelines (e.g., up to 90 minutes vs. at least 60 minutes), and g) provide a wide variety of examples of physical activity – from active living to sport.

Motivational Messages	Motivational messages should emphasize a) parents’ pivotal role in encouraging and supporting their youth’s physical activity, b) a variety of benefits that physical activity offers including emotional, developmental, physical and academic benefits, c) that physical activity can be a collective-social movement that promotes community, active living and the environment, d) the importance of planning physical activity by parents and youth, e) strategies for overcoming barriers to physical activity, and f) empowering youth to choose how they will meet the guidelines.

Examples

60 minutes every day! As a parent, you can help your teen get there.

Move your teen to move more.

Life looks better with physical activity.

Pick a time. Pick a place. Move your teens to move more.

Pick a time. Pick a place. How you want to get active is up to you!

Plan ahead for roadblocks!

Expand your horizons! How you want to get active is up to you!

Channels of Delivery	Messages should be disseminated to parents through websites, mass media campaigns featuring celebrities, magazines and news articles, and smart phone applications.

Messages should be disseminated to youth through websites, promotional materials within their school, public service announcements featuring celebrities, social media, smart phone applications, and community organizations and events.

Motivational Messages	Move your teen to move more.

Life looks better with physical activity.

Pick a time. Pick a place. Move your teens to move more.

Pick a time. Pick a place. How you want to get active is up to you!

Plan ahead for roadblocks!

Expand your horizons! How you want to get active is up to you!

Channels of Delivery	Messages should be disseminated to parents through websites, mass media campaigns featuring celebrities, magazines and news articles, and smart phone applications.

Messages should be disseminated to youth through websites, promotional materials within their school, public service announcements featuring celebrities, social media, smart phone applications, and community organizations and events.


Gene	Variant	Position	OR	Common/Rare	Domain	Variant domain effect	Effect on AP	Ref

C3	R102G	19:6718387	1.7–2.6	Common	Macroglobulin 1	Decreased binding efficiency of C3b to its inhibitor CFH decreasing CFH’s cofactor activity	Increased AP	[20, 65]

C3	P314L	19:6713262	1.5	Common	Macroglobulin 3	Decreased binding efficiency of C3b to its inhibitor CFH decreasing CFH’s cofactor activity	Increased AP	[65]

C3	K155Q	19:6718146	2.8–3.8	Rare	Macroglobulin 2	Reduces binding to FH and C3b proteolytic cleavage by CFI	Increase C3 convertase production	[59, 65]

CFB	R32Q	6:31914180	0.32	Common	Ba	Reduced affinity for C3b and reduced hemolytic activity	Decrease formation of C3 convertase; reduced AP	[130]

CFB	L9H	6:31914024	0.37	Common	Signal peptide	Affects secretion of CFB	Decrease formation of C3 convertase; reduced AP	[12]

CFH	Y402H	1:196659291	2.45–5.57	Common	Complement control protein 7	Affects binding to GAG heparin sulfate, sialic acid, and C-reactive protein	Reduces ability of CFH to degrade C3: increased AP	[131]

CFH	R1210C	1:196716375	23.11	Rare	Complement control protein 20	Defective binding to C3b, C3d, and heparin	Impaired CFH attachment to host surfaces; reduces AP regulation	[58]

CFH	R53C	1:196642206		Rare	Complement control protein 1	Reduced accelerating activity for AP C3 convertase	Altered CFH-mediated cofactor activity or decay-accelerating activity; increased AP	[63]

CFH	D90G	1:196643011		Rare	Complement control protein 2	Alters CFI cofactor activity	Decreased cofactor-mediated inactivation; increased AP	[63]

CFH	I62V	1:196642233	1.95–2.79	Common	Complement control protein 2	Binds more efficiently to C3b	Enhanced cofactor activity and increased formation of iC3b; reduced AP	[63]

CFH	N1050Y	1:196712596	0.4	Common	Complement control protein 18	Possibly affects GAG and sialic acid binding	Increased AP	[62]

CFHR1/3	CFHR1/3del		0.29	Common	n/a	n/a	Reduces cofactor activity for CFI and inhibits C5 convertase; reduced AP	[13] [132–135]

CFI	G119R	4:110685820	22.2	Rare	Scavenger receptor cysteine-rich	Perturbs interdomain packing and stability of CFI	Diminished ability to degrade C3b; increased formation of C5 convertase; increased AP	[19]

CFI	G188A	4:110682768		Rare	Scavenger receptor cysteine-rich	Perturbs interdomain packing and stability of CFI	Diminished ability to degrade C3b; increased formation of C5 convertase; increased AP	[19]

C9	P167S	5:39331894	2.2	Rare	Membrane attack complex/perforin	Alters oligomerization and possibly inhibits C9's lytic activity	Affects binding with CD59; alters pore formation	[59]


Alcohol consumption	MTHFR genotype	Cases n (%)	Controls n (%)	Age-adjusted OR (95% CI)

Low	CC	3 (8)	29 (20)	1.00 (ref)

Low	CT + TT	5 (14)	39 (27)	1.25 (0.28–5.65)

High	CC	14 (38)	31 (21)	4.43 (1.15–17.05)

High	CT + TT	15 (41)	47 (32)	3.10 (0.83–11.65)

p-interaction (multiplicative)			0.51

p-interaction (additive)			0.58


Model	Fatal + non-fatal events	Fatal events

	Women	Men	Women	Men

Cru	1.16	1.05 (0.96	1.27(1.04–1.55	1.24 (


Formulation	Hardness (kg/cm2)	Friability (%)	%Drug content	Disintegration time (sec.)

S	3.6±0.	0.61±0.	98.99±0	67.4±1.


Peak torque (Nm)	Mean ± SD

Session 1

Quadriceps right

Concentric at 60os−1	229.4 ± 37.5

Isometric	257.8 ± 46.9

Eccentric at 60os−1	303.0 ± 63.6

Hamstrings right

Concentric at 60os−1	125.0 ± 27.3

Isometric	138.1 ± 34.1

Eccentric at 60os−1	171.5 ± 33.8

Quadriceps left

Concentric at 60os−1	219.4 ± 36.5

Isometric	236.0 ± 43.9

Eccentric at 60os−1	267.8 ± 58.8

Hamstrings left

Concentric at 60os−1	129.3 ± 26.6

Isometric	129.8 ± 33.5

Eccentric at 60os−1	162.2 ± 36.4


	Strain detected

Pathogen	Only by BC	Only by SeptiFast	Both methods

S.aureus (MSSA)	0	3	3

S.aureus (MRSA)	2	0	4

S.pneumoniae	0	1	0

Streptococcus spp.	0	2	1

Enterococcus faecalis	0	1	0

Enterococcus faecium	2	0	0

Enterobacter aerogenes/cloacae	0	3	1

Escherichia coli	0	3	9

Klebsiella pneumoniae/oxytoca	1	5	1

Pseudomonas aeruginosa	1	4	1

Candida albicans	0	1	0

Candida tropicalis	0	1	1

Sub-total	6	24	21

Not detectable by SeptiFast	5	0	0

Total	11	24	21

	Strain detected

Pathogen	Only by BC	Only by SeptiFast

S.aureus (MSSA)	0	3

S.aureus (MRSA)	2	0

S.pneumoniae	0	1

Streptococcus spp.	0	2

Enterococcus faecalis	0	1

Enterococcus faecium	2	0

Enterobacter aerogenes/cloacae	0	3

Escherichia coli	0	3

Klebsiella pneumoniae/oxytoca	1	5

Pseudomonas aeruginosa	1	4

Candida albicans	0	1

Candida tropicalis	0	1

Sub-total	6	24

Not detectable by SeptiFast	5	0

Total	11	24

Strain detected

Both methods

3

4

0

1

0

0

1

9

1

1

0

1

21

0

21


Negative binomial counts > 0	Univariate	Multivariable


Year	Authors	Age, gender	Concurrent malignancy (location)	Past history of recurrence	Diagnostic modality

2015	Jerraya H, et al.	59, F	Insulinoma (pancreas)	NA	NA

2015	Jung SY, et al.	11, F	Insulinoma (pancreas)	Non	US, CT, MRI

2009	Wheeler YY, et al.	62, M	Renal cell carcinoma (right kidney)	Non	CECT

2015	Present case	23, M	SCS (abdominal)	Abdominal	US, CECT, MRI

Year	Authors	Age, gender	Concurrent malignancy (location)	Past history of recurrence	Diagnostic modality

2015	Jung SY, et al.	11, F	Insulinoma (pancreas)	Non	US, CT, MRI

2009	Wheeler YY, et al.	62, M	Renal cell carcinoma (right kidney)	Non	CECT

2015	Present case	23, M	SCS (abdominal)	Abdominal	US, CECT, MRI


 	LOO AUC (SE)	Sensitivity	Specificity	Median number of peaks per LOO iteration	Mean number of peaks per LOO iteration (SD)

Lymph node status

 Negative vs Positive	0.95 (0.03)	73.9	91.7	1	1 (0)

Histological subtype

 Squamous ca. vs adenoca.	0.88 (0.05)	88.2	59.0	1	1 (0)

 Squamous ca. vs adsq ca.	0.85 (0.06)	84.6	100	4	3.8 (0.9)

 Adenoca. vs adsq ca.	0.94 (0.06)	94.1	100	1	0.9 (0.3)

LVSI

 Negative vs Positive	0.81 (0.06)	78.1	73.1	1	1 (0)

Recurrence

 Negative vs Positive	0.92 (0.04)	79.2	90.0	3	3 (0)

	LOO AUC (SE)	Sensitivity	Specificity

Lymph node status

Negative vs Positive	0.95 (0.03)	73.9	91.7

Histological subtype

Squamous ca. vs adenoca.	0.88 (0.05)	88.2	59.0

Squamous ca. vs adsq ca.	0.85 (0.06)	84.6	100

Adenoca. vs adsq ca.	0.94 (0.06)	94.1	100

LVSI

Negative vs Positive	0.81 (0.06)	78.1	73.1

Recurrence

Negative vs Positive	0.92 (0.04)	79.2	90.0

Median number of peaks per LOO iteration	Mean number of peaks per LOO iteration (SD)

Lymph node status

1	1 (0)

Histological subtype

1	1 (0)

4	3.8 (0.9)

1	0.9 (0.3)

LVSI

1	1 (0)

Recurrence

3	3 (0)


	Annual expenses ($)

Annual cost of mobile health clinic	565,700

Total annual visits	4,848

Total visits discounted by 20%	3,878

Cost per visit	117

Cost of preventable emergency department visit [9]	923

Cost avoided per mobile clinic visit	806

Annual projected costs avoided	3,125,668

Annual cost of mobile health clinic

Total annual visits

Total visits discounted by 20%

Cost per visit

Cost of preventable emergency department visit [9]

Cost avoided per mobile clinic visit

Annual projected costs avoided


Primer	Gene	Sequence	Fragment size (bp)

rpoB-FS		TGGTCCGCTTGCACGAGGGTCAGA

	rpoB		758

rpoB-RS		CAGGAAGGGAATCATCGCGG

katG-FS		TGCAGATGGGGCTGATCTACG

	katG	ACCCATGTCTCGGTGGATCAG	596

katG-RS

inhA-FS		ACATACCTGCTGCGCAAT

	inhA	TCACATTCGACGCCAAAC	400

inhA-RS


Toxo DB typea	No. of isolates	Designation

9, (Chinese1)	1	TgDgCo4

10 (Type I)	2	TgCtCo 2, 7

14	6	TgDgCo9,12,15,18; TgCkCo2;TgCtco14

18	3	TgCtCo 12, 13; TgDgCo3

23	1	TgDgCo19

28	2	TgCtCo 1; TgCkCo5

29	5	TgDgCo1,2,10,20; TgCkCo20

38	13	TgCkCo6,8,10,12,13,15,21,23,24; TgCtCo 4,10,11; TgDgCo17

40	1	TgCtCo5x

44	3	TgDgCo5,6,11

46	3	TgDgCo8,14,16

61	2	TgCtCo 5,6

62	2	TgCtCo3,9

79	1	TgDgCo13

101	1	TgCtCo15

122	1	TgDgCo7

128	1	TgCtCo8

178	1	TgCkCo4

179	2	TgCkCo17,22

188	1	TgCkCo9

Toxo DB typea	No. of isolates	Designation

122	1	TgDgCo7

128	1	TgCtCo8

178	1	TgCkCo4

179	2	TgCkCo17,22

188	1	TgCkCo9


Region-based test result	Truth

	True HA	True H0	Total

p-value < Threshold: reject null hypothesis	A	C	A + C

p-value ≥ Threshold: do not reject null hypothesis	B	D	B + D

Total	A + B	C + D


	Informatively cued letter-parity task	Non-informatively cued letter-parity task	Informatively cued color-shape task

	Young	Older	Young	Older	Young	Older

Hits

TS	89 ± 7	67 ± 15	87 ± 6	67 ± 15	93 ± 6	73 ± 16

TR	88 ± 6	70 ± 15	88 ± 7	71 ± 13	94 ± 5	77 ± 15

Errors

TS	10 ± 7	29 ± 14	13 ± 6	31 ± 15	7 ± 6	26 ± 15

TR	12 ± 5	27 ± 13	11 ± 6	28 ± 12	5 ± 4	21 ± 13

RT

TS	769 ± 145	1095 ± 171	1016 ± 156	1311 ± 148	611 ± 129	1038 ± 188

	Informatively cued letter-parity task	Non-informatively cued letter-parity task	Informatively cued color-shape task

	Young	Older	Young	Older	Young	Older

TR	762 ± 147	1063 ± 158	997 ± 160	1282 ± 143	575 ± 110	1005 ± 229

SC

	7 ± 53	32 ± 61	19 ± 62	28 ± 78	36 ± 41	33 ± 103

MC

	164 ± 109	309 ± 132	402 ± 109	510 ± 109	89 ± 84	338 ± 192


Items	Cu NPs	Cu MPs

Shape	Spherical	Spherical

Primary sizea	32.7 ± 10.5 nm	25.3 ± 6.6 μm

Hydrodynamic size (nm)b	pH 1.5	n.a	n.a

pH 6.5	516 ± 116.9	n.a

pH 7.8	334 ± 128.3	n.a

Surface area (m2/g)c	14.7	0.16

Zeta potential (mV)d	pH 1.5	25.5 ± 0.8	n.a

pH 6.5	1.32 ± 1.2	n.a

pH 7.8	−6.2 ± 0.2	n.a

Items

Shape

Primary sizea

Hydrodynamic size (nm)b

Surface area (m2/g)c

Zeta potential (mV)d

Items	Cu NPs	Cu MPs

Shape	Spherical	Spherical

Primary sizea	32.7 ± 10.5 nm	25.3 ± 6.6 μm

pH 1.5	n.a	n.a

pH 6.5	516 ± 116.9	n.a

pH 7.8	334 ± 128.3	n.a

Surface area (m2/g)c	14.7	0.16

pH 1.5	25.5 ± 0.8	n.a

pH 6.5	1.32 ± 1.2	n.a

pH 7.8	−6.2 ± 0.2	n.a


Category label	Observed average	Infit MNSQ	Outfit MNSQ	Structure calibration

6	16.12	.93	.94	20.07


 	β intercept (standardised coefficient)	P value

Height	0.094	0.48

Weight	0.003	0.98

Fat%	0.058	0.53

Physical activity	0.215	<0.01

Age of onset of diabetes	0.16	0.09

Duration of diabetes	−0.046	0.56

HbA1c	−0.451	<0.01

Insulin dose	0.20	0.07

Calcium intake	0.05	0.53

25(OH) vitamin D3	−0.003	0.964

Alkaline phosphatase	−0.19	0.09

PTH 	−0.026	0.71

IGF-1	0.31	<0.01

Testosterone	0.14	0.12

SHBG	0.11	0.24

	β intercept (standardised coefficient)	P value

Age of onset of diabetes	0.16	0.09

Duration of diabetes	−0.046	0.56

HbA1c	−0.451	<0.01

Insulin dose	0.20	0.07

Calcium intake	0.05	0.53

25(OH) vitamin D3	−0.003	0.964

Alkaline phosphatase	−0.19	0.09

PTH	−0.026	0.71

IGF-1	0.31	<0.01

Testosterone	0.14	0.12

SHBG	0.11	0.24


Parameter	Meaning	Value

kphr	Phosphorylation of RsbR	0.1 / 1

kdpr	Dephosphorylation of RsbR-P	0.06

kphs	Phosphorylation of RsbS	0.4

kdps	Dephosphorylation of RsbS-P	1


	Sex	Age	Pituitary MRI	Internal carotid RMI	Other characteristics	Molecular studies	References

1	N	N	Not specified (except for normal posterior pituitary).	Absence of ICA and carotid canal.	Not specified.	NP	[14]

2	M	18 m	Pituitary hypoplasia.	Anomaly of right ICA.	TSH, GH, ACTH deficiency. Central diabetes insipidus. Possible hypogonadism.	NP	[13]

3	F	5 m	Absence of anterior pituitary and ectopic pituitary posterior lobe.	Absence of right common carotid artery, right ICA, right anterior cerebral artery.	TSH, ACTH and GH deficiency. No evidence of diabetes insipidus. Genitalia were normal. Single central maxillary incisor.	NP	[7]

4	M	23 year	Absence of anterior pituitary and ectopic pituitary posterior lobe.	Absence of right ICA and carotid canal and A1 segment of the right anterior cerebral artery.	Congenital microphthalmia with cataract and coloboma of the right eye, encephalocele. Hormonal substitution treatments not specified.	NP	[5]

5	M	37 year	Absence of anterior pituitary.	Hypoplasia of right ICA and carotid canal.	Amblyopia of the left eye caused by an optic nerve coloboma, encephalocele. Hormonal substitution treatments not specified.	NP	[5]

6	F	29 year	Pituitary hypoplasia and ectopic pituitary posterior lobe.	Absence of right ICA, carotid canal, and A1 segment of the right anterior cerebral artery.	TSH, ACTH, and GH deficiency. No evidence of diabetes insipidus. Hypogonadism. Chiari I malformation with syringomyelia.	NP	[9]

7	M	5 year	Absence of anterior pituitary and ectopic pituitary posterior lobe.	Absence of left ICA and carotid canal, A1 segment of the left anterior cerebral artery and the anterior communicating artery.	Retrognathia, microphallus, and cryptorchidism. TSH, ACTH, GH deficiency, but no evidence of diabetes insipidus. Possibile hypogonadism.	NP	[10]

8	M	11 year	Pituitary hypoplasia	Absence of left ICA and carotid canal; hypoplasia of A1 segment of left anterior cerebral artery	TSH, ACTH, GH deficiency. Central diabetes insipidus. Microphallus with possible hypogonadism.	NP	[6]

9	F	10 year	Hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk	Agenesis of the left ICA and the left carotid canal	GH, TSH, gonadotropin deficiency. No evidence of diabetes insipidus. Born out of a consanguineous marriage.	No HESX1, LHX4, OTX2 mutations	[8]

10	F	7 month	Adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity	Absence of the left ICA	Desaturation episodes, recurrent respiratory infections. Short hands and feet. GH, ACTH and TSH deficiency.	17q24.2 deletion	[3]

11	F	2 year	Adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity	Absence of the right ICA	GH, TSH, and gonadotropin deficiency. No clinical evidence of diabetes insipidus.	NP	[11]

12	M	3 week	Absence of anterior pituitary with ectopic posterior pituitary	Absence of the left ICA and carotid canal	GH, TSH, ACTH and gonadotropin deficiency. Microphallus.	NP	[12]

13	M	17 year	Adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity	Agenesis of the left ICA	GH deficiency. No other pituitary deficiencies. No clinical evidence of diabetes insipidus.	Normal array-CGH	Our case


#	SET I (8-week-old)	Summary

1	Control diet (CD)	Peliosis, nuclear dysplasia and nuclear retreat.

2	CD + Quercetin	Small & large lymphoplasmacytic clusters.

3	CD + δ-Tocotrienol	Large lymphoplasmacytic (LP) cluster, Councilman body.

4	CD + Dexamethasone	Councilman body, nuclear retreat and dysplasia, microvesicular steatosis, large lymphoplasmacytic (LP) cluster, closed sinusoids, cytoplasmic condensation.

	SET II (46-week-old)	Summary

5	Control diet (CD)	LP clusters, nuclear Retreat and dysplasia, microvesicular steatosis.

6	CD + Quercetin	Coucilman body, nuclear dysplasia and nuclear retreat.

7	CD + δ-Tocotrienol	Small & large Lymphoplasmacytic clusters.

8	CD + Dexamethasone	Small LP cluster, Councilman body, nuclear Retreat and dysplasia cytoplasmic condensation.

#	SET I (8-week-old)	Summary

1	Control diet (CD)	Peliosis, nuclear dysplasia and nuclear retreat.

2	CD + Quercetin	Small & large lymphoplasmacytic clusters.

3	CD + δ-Tocotrienol	Large lymphoplasmacytic (LP) cluster, Councilman body.

4	CD + Dexamethasone	Councilman body, nuclear retreat and dysplasia, microvesicular steatosis, large lymphoplasmacytic (LP) cluster, closed sinusoids, cytoplasmic condensation.

	SET II (46-week-old)	Summary

5	Control 	LP clusters, nuclear Retreat and dysplasia, micr

#	SET I (8-week-old)	Summary

	diet (CD)	ovesicular steatosis.

6	CD + Quercetin	Coucilman body, nuclear dysplasia and nuclear retreat.

7	CD + δ-Tocotrienol	Small & large Lymphoplasmacytic clusters.

8	CD + Dexamethasone	Small LP cluster, Councilman body, nuclear Retreat and dysplasia cytoplasmic condensation.


Acronym	Description	Source

GDP	Gross Domestic Product per capita (PPS$), i.e. a measure of the economic activity and of the wealth of a country.	(1)

Real GDP Growth rate	The growth rate of the GDP in terms of volume (%), values determined by the prices of the previous year, and thus computed volume changes are imposed on the level of a reference year so that price movements will not inflate the growth rate.	(2)

Government Debt	General government gross debt (% of GDP, million EUR).	(1)

U	Unemployment rate (%), i.e. the percentage of unemployed people in the active population.	(3)


Variable	Mean	95% CI

Children seen per day	1.8	1.8-1.9

Time spent on seeing children (hrs)/day	0.4	20.9-21.1

No of Health education activities/day	2.5	2.3-2.6

Time spent on IEC (hrs)	0.2	11.4-12.8

Follow-ups/day	**2.6	2.4-2.8

Hours on follow-up/child	1.7	1.5-1.8

Total hours spent on CCMm activities/day	*4.8	3.9-5.3


Study	Cell type	Treatment	Time points	Array

Expression profiling studies on 3T3-L1 cell line

Guo et al. 2000 [14]	3T3-L1	DMI	0h, 6d	18k mouse cDNA filter arrays

Soukas et al. 2000 [15]	3T3-L1	DMI	PC,0h,6h,12h,24h,2d,3d, 4d, 7d,28d	Affymetrix mouse Mu11k

Ross et al. 2002 [16]	3T3-L1	DMI|DMI+Wnt-1↑	0h, 16h, 32h, 2d, d14	Affymetrix mouse U74A

Burton et al. 2002 [17]	3T3-L1	DMI	0h,2h,8h,16h,24h	AffymetrixmouseMu11k

Burton et al. 2004 [18]	3T3-L1	DMI|DMI+TSA	0h,2h,8h,16h,24h,d2,d4	Affymetrix mouse U74A

Jessen at al. 2002 [19]	3T3-L1	DMI	0h, 1d, 4d, 7d	Affymetrix Mu11kB| U74Av2

Gerhold et al. 2002 [20]	3T3-L1	DMI+TZD|nTZD	0h, PA 6hT, PA 48hT, AD 6hT, AD 48hT	4k Affymetrix mouse mu6800

Hsiao et al. 2004 [21]	3T3-L1	TZDs	AD 24hT	Affymetrix mouse U74Av2

Hackl et al. 2005 [22]	3T3-L1	DMI	PC,0h,6h,12h,24h,2d,3d,4d,7d,14d	27K mouse cDNA microarray

Liu et al. 2005 [23]	3T3-L1	DMI|DI		Affymetrix mouse MOE430A

Pantoja et al. 2005 [24]	3T3-L1	D↔M I| M↔D I		38 k MEEBO microarray oligo set

Adipogenesis expression studies on other mouse cell models including over-expression and knock out strategies

Huo et al. 2006 [25]	3T3-F442A	GH		Affymetrix mouse U74Av2

Akerblad et al. 2005 [26]	NIH-3T3	Ebf1↑|Pparg↑		Affymetrix mouse U74Av2

Baudry et al. 2006 [27]	PKB-/-MEF			22k Affy mouse MOE430A

Christian et al. 2005 [28]	RIPKO			Affymetrix mouse MOE430 2.0

Otto TC et al. 2007 [29]	C3H10T1/2	Bmp4↑		Affymetrix mouse MOE430 2.0

Tseng et al. 2005 [30]	IRSKO PA			Affymetrix mouse U74Av2

Timmons et al. 2007 [31]	wPA, bPA		0d, 1d, 4d, 8d	Affymetrix mouse U74Av2

Adipogenesis of human cell models

Hung et al. 2004 [32]	hMSC	DMI	0h,3d	8k human Universochip

Sekiya et al. 2004 [33]	hMSC		0h,1d,7d,14d,21d	12k Affymetrix human U95Av2

Nakamura et al. 2003 [34]	hMSC			3.4k focused cDNA microarray

Scheideler et al. 2008 [35]	hMADS	DMI+ROS	PC,-2d, 0h, 8h, 1d, 2d, 5d, 10d, 15d	30k human spotted oligo array

Urs et al. 2004 [36]	PA|AD			19K human cDNA microarray

Study	Cell type	Treatment	Time points	Array

Expression profiling studies on 3T3-L1 cell line

Guo et al. 2000 [14]	3T3-L1	DMI	0h, 6d	18k mouse cDNA filter arrays

Soukas et al. 2000 [15]	3T3-L1	DMI	PC,0h,6h,12h,24h,2d,3d, 4d, 7d,28d	Affymetrix mouse Mu11k

Ross et al. 2002 [16]	3T3-L1	DMI|DMI+Wnt-1↑	0h, 16h, 32h, 2d, d14	Affymetrix mouse U74A

Burton et al. 2002 [17]	3T3-L1	DMI	0h,2h,8h,16h,24h	AffymetrixmouseMu11k

Burton et al. 2004 [18]	3T3-L1	DMI|DMI+TSA	0h,2h,8h,16h,24h,d2,d4	Affymetrix mouse U74A

Jessen at al. 2002 [19]	3T3-L1	DMI	0h, 1d, 4d, 7d	Affymetrix Mu11kB| U74Av2

Gerhold et al. 2002 [20]	3T3-L1	DMI+TZD|nTZD	0h, PA 6hT, PA 48hT, AD 6hT, AD 48hT	4k Affymetrix mouse mu6800

Hsiao et al. 2004 [21]	3T3-L1	TZDs	AD 24hT	Affymetrix mouse U74Av2

Hackl et al. 2005 [22]	3T3-L1	DMI	PC,0h,6h,12h,24h,2d,3d,4d,7d,14d	27K mouse cDNA microarray

Liu et al. 2	3T3-L1	DMI|D		Affymetrix mouse

005 [23]		I		MOE430A

Pantoja et al. 2005 [24]	3T3-L1	D↔M I| M↔D I		38 k MEEBO microarray oligo set

Adipogenesis expression studies on other mouse cell models including over-expression and knock out strategies

Huo et al. 2006 [25]	3T3-F442A	GH		Affymetrix mouse U74Av2

Akerblad et al. 2005 [26]	NIH-3T3	Ebf1↑|Pparg↑		Affymetrix mouse U74Av2

Baudry et al. 2006 [27]	PKB-/-MEF			22k Affy mouse MOE430A

Christian et al. 2005 [28]	RIPKO			Affymetrix mouse MOE430 2.0

Otto TC et al. 2007 [29]	C3H10T1/2	Bmp4↑		Affymetrix mouse MOE430 2.0

Tseng et al. 2005 [30]	IRSKO PA			Affymetrix mouse U74Av2

Timmons et al. 2007 [31]	wPA, bPA		0d, 1d, 4d, 8d	Affymetrix mouse U74Av2

Adipogenesis of human cell models

Hung et al. 2004 [32]	hMSC	DMI	0h,3d	8k human Universochip

Sekiya et al. 2004 [33]	hMSC		0h,1d,7d,14d,21d	12k Affymetrix human U95Av2

Nakamura et al. 2003 [34]	hMSC			3.4k focused cDNA microarray

Scheideler et al. 2008 [35]	hMADS	DMI+ROS	PC,-2d, 0h, 8h, 1d, 2d, 5d, 10d, 15d	30k human spotted oligo array

Urs et al. 2004 [36]	PA|AD			19K human cDNA microarray


Characteristic	Crude odds ratios with 95% confidence interval	Adjusted odds ratios with 95% confidence interval

Age above 25 years	1.65 (1.33-2.04)*	.74 (.54-1.02)

Age 24 years & below -Ref

Income 5001 NPR or above	.85 (.71-1.00)	1.30 (1.04-1.62)**

5000 NPR or less/month- Ref

Education secondary or higher	.35 (.27-.44)*	.41 (.31-.55)*

Uneducated or Primary level- Ref

Hindu religion	.15 (.09-.24)*	.09 (.05-.18)*

Non-Hindu - Ref

≥ 3 Children	2.48 (1.93-3.19)*	2.05 (1.56-2.71)*

≤ 2 Children - Ref

Desire more children	.78 (.62-.99)**	.72 (.55-.95)**

No more desire - Ref

Men attempt domestic violence	1.87 (1.56-2.24)*	1.29 (1.04-1.61)**

Not attempt - Ref

Associated factors for male decision making to contraceptive use (N = 2394)

Age above 25 years	1.63 (1.30-2.05)*	1.57 (1.15-2.14)**

Age 24 years & below -Ref

Income 5001 NPR or above	1.09 (.92-1.30)	.67 (.54-.82)*

5000 NPR or less/month- Ref

Education secondary or higher	4.54 (3.53-5.84)*	4.11 (3.12 - 5.42)*

Uneducated or Primary level- Ref

Hindu religion	2.32 (1.70-3.16)*	1.43 (.95-2.16)

Non-Hindu - Ref

Non-Indigenous ethnicity	2.40 (1.85 -3.10)*	1.49 (1.06-2.10)**

Indigenous ethnicity - Ref

≥ 3 Children	.67 (.54-.82)*	.70 (.55-.88)**

≤ 2 Children - Ref

Desire more children	.64 (.50-.82)*	.66 (.50-.87)**

No more desire - Ref

Men attempt domestic violence	.62 (.52-.73)*	.83 (.68-1.02)

Not attempt - Ref


		cELISA

		Positive	Negative	Total

T. equi (A)

 IFAT	Positive	48	7	55

Negative	10	43	53

Total	58	50	108

B. caballi (B)

 IFAT	Positive	4	16	20

Negative	3	85	88

Total	7	101	108

		cELISA

		Positive	Negative	Total

IFAT	Positive	48	7	55

Negative	10	43	53

Total	58	50	108

B. caballi (B)

IFAT	Positive	4	16	20

Negative	3	85	88

Total	7	101	108


	Aniso nucleosis (±)	Large cherry red nucleoli (±)	Small cherry red nucleoli (±)	Large cells (±)	Mesothelial like sheets (±)	3 dimensional cluster (±)

Malignant	7/4	9/2	2/9	4/7	5/6	11/0

Non-malignant	17/26	1/42	20/23	39/4	21/22	NA

p value	*	0.0252	*	*	*	<0.0001

	Aniso nucleosis (±)	Large cherry red nucleoli (±)	Small cherry red nucleoli (±)	Large cells (±)	Mesothelial like sheets (±)	3 dimensional cluster (±)

Non-malignant	17/26	1/42	20/23	39/4	21/22	NA

p value	*	0.0252	*	*	*	<0.0001


Variables	Disability Beta (SD)	T	Anxiety	t	Depression	t

Ag	0.011 (0.016	0.7	−0.046 (	−3.24 *	−0.014


	No DGE

n = 70

Age, years	62 (51–69)

Gender

female	24	(34%)

male	46	(66%)

BMI	24,6 ± 3,8

Diagnosis

Malignant	54	(77%)

Ductal adenocarcinoma	31	(44%)

Ampullary carcinoma	10	(14%)

Distal bile duct carcinoma	7	(10%)

Benign	16	(23%)

Pancreatitis	13	(19%)

DM	pre	12	(17%)

	post	15	(21%)

Alcohol		19	(27%)

Smoker		31	(44%)

Weight loss		32	(46%)

Preoperative biliary drainage	43	(61%)

Cholangitis		20	(29%)


Review	Professional background (code used in the quotes)	Knowledge of the clinical area	DTA-related knowledge	Systematic review methods	Academic role within university	Policy- making experience

Galactomannan detection for invasive aspergillosis in immune-compromized patients	Hematologist (H1)	Yes	Good	Some	Yes	Yes

 	Hematologist (H2)	Yes	Good	Some	Yes	Yes

Policy maker (PM1)	No	Some	Good	Yes	Yes

Systematic reviewer (SR1)	No	Little	Good	Yes	No

Health economist (HE1)	No	Little	Good	No	No

Systematic reviewer (SR2)	No	Good	Good	Yes	Yes

Physical examination for lumbar radiculopathy due to disc herniation in patients with low back pain	GP (GP1)	Yes	Little	Little	No	No

GP (GP2)	Yes	Little	Little	No	No

Physiotherapist (PH1)	Yes	Little	Good	Yes	No

GP (GP3)	Yes	Good	Good	No	Yes

Physiotherapist (PH2)	Yes	Good	Good	Yes	Yes

Policy maker (PM2)	Yes	Good	Good	Yes	Yes

 	Policy maker (PM3)	No	Some	Good	Yes	Yes

MRI versus CT for detection of acute vascular lesions in patients presenting with stroke symptoms	Radiologist (R1)	Yes	Little	Little	No	No

Systematic reviewer (SR3)	No	Little	Some	No	No

Health economist (HE2)	No	Good	Good	No	Yes

Health economist (HE3)	No	Little	Some	No	No

Systematic reviewer (SR4)	No	Little	Good	Yes	No

Systematic reviewer (SR5)	No	Good	Good	Yes	No

Systematic reviewer (SR6)	Yes	Some	Good	Yes	No

Policy maker (PM4)	Yes	Good	Good	Yes	Yes

Review	Professional background (code used in the quotes)	Knowledge of the clinical area	DTA-related knowledge	Systematic review methods	Academic role within university	Policy- making experience

Galactomannan detection for invasive aspergillosis in immune-compromized patients	Hematologist (H1)	Yes	Good	Some	Yes	Yes

	Hematologist (H2)	Yes	Good	Some	Yes	Yes

Policy maker (PM1)	No	Some	Good	Yes	Yes

Systematic reviewer (SR1)	No	Little	Good	Yes	No

Health economist (HE1)	No	Little	Good	No	No

Systematic reviewer (SR2)	No	Good	Good	Yes	Yes

Physical examination for lumbar radiculopathy due to disc herniation in patients with low back pain	GP (GP1)	Yes	Little	Little	No	No

GP (GP2)	Yes	Little	Little	No	No

Physiotherapist (PH1)	Yes	Little	Good	Yes	No

GP (GP3)	Yes	Good	Good	No	Yes

Physiotherapist (PH2)	Yes	Good	Good	Yes	Yes

Policy maker (PM2)	Yes	Good	Good	Yes	Yes

	Policy maker (PM3)	No	Some	Good	Yes	Yes

MRI versus CT for detection of acute vascul	Radiologist (R1)	Yes	Little	Little	No	No

Systematic reviewer (SR3)	No	Little	Some	No	No

Health economist (HE2)	No	Good	Good	No	Yes

Health economist (HE3)	No	Little	Some	No	No

Systematic reviewer (SR4)	No	Little	Good	Yes	No

Systematic reviewer (SR5)	No	Good	Good	Yes	No

Systematic revie		S	G	Ye	No

ar lesions in patients presenting with stroke symptoms	wer (SR6)	Yes	ome	ood	s

Policy maker (PM4)	Yes	Good	Good	Yes	Yes


Variable	Cases (n=454)

Age (years)	61.04 ± 10.81

Female/male	167/287

Smoking (No/Yes)	184/270

Drinking (No/Yes)	329/125

Diabetes (No/Yes)	295/159

FPG (mmol/l)	6.40 ± 1.65

Hypertension (No/Yes)	185/269

BMI (kg/m2)	27.77 ± 3.11

Total cholesterol (mmol/l)	4.81 ± 1.05

HDL (mmol/l)	1.13 ± 0.33

LDL (mmol/l)	2.89 ± 0.88


	$3000 single	12 mo. spacing	60 mo. spacing	$1000 single

$30


Question	Session	n	≥ 4 (%)

I believe the work in this session is relevant for professional nurses	1	52	98

2	49	84

I believe the work in this session is relevant for me as an individual	1	52	96

2	49	88

Overall I am satisfied with this session	1	49	94

2	49	76

Question	Session

I believe the work in this session is relevant for professional nurses	1

2

I believe the work in this session is relevant for me as an individual	1

2

Overall I am satisfied with this session	1

2


Algorithms	MAPE (%)	RMSPE (%)	Error of RUL prediction

INW–ESN (dynamica)	9.32	7.27	23 min

INW–ESN (static)	17.14	14.64	Failed

RNN (dynamica)	16.38	13.44	138 min

ESN (dynamica)	14.60	10.87	161 min

ELM (static)	13.91	9.48	69 min

Algorithms	MAPE (%)	RMSPE (%)	Error of RUL prediction

INW–ESN (static)	17.14	14.64	Failed

RNN (dynamica)	16.38	13.44	138 min

ESN (dynamica)	14.60	10.87	161 min

ELM (static)	13.91	9.48	69 min


PCR	Forward (F) primer/reverse (R) primer (5′–3′)	PCR mixture	Cycling conditions

rDNA21	Nest1 F: GCTGTAGGTGAACCTGCAGCAGCTGGATCATT	50 μL reaction; 5 μL DNA from filter papers (or 5 μL N1), 25 μL QIAGEN HotStar Taq Master Mix (QIAGEN), 0.3 μM primers	95°C, 15 minutes

Nest1 R: GCGGGTAGTCCTGCCAAACACTCAGGTCTG	35–40 cycles

Nest2 F: GCAGCTGGATCATTTTCC	94°C, 0.5 minutes

Nest2 R: AACACTCAGGTCTGTAAAC	58°C, 0.5 minutes

	72°C, 1.5 minutes

	60°C, 1 minutes

	75°C, 10 minutes

ITS222	F: GGGAGAAGCTCTATTGTG	25 μL reaction; 1 μL N2 product from rDNA PCR, KCl buffer (15 mM MgCl2, Bioline, London, UK), 2 mM deoxynucleotide triphosphates, 0.4 μM primers, 1U Taq polymerase	94°C, 2 minutes

R: ACACTCAGGTCTGTAAAC	40 cycles

	94°C, 20 seconds

	53°C, 30 seconds

	72°C, 1 minutes

	72°C, 10 minutes

kDNA6	Nest1 F: C/GA/GTA/GCAGAAAC/TCCCGTTCA	50 μL reaction; 5 μL DNA from filter papers (OR 5 μL N1), 25 μL QIAGEN HotStar Taq Master Mix, 0.3 μM primers	95°C, 15 minutes

Nest1 R: ATTTTTCG/CGA/TTTT/CGCAGAACG	30 cycles at

Nest2 F: ACTGGGGGTTGGTGTAAAATAG	94°C, 1 minutes

Nest2 R: TCGCAGAACGCCCCT	55°C, 1 minutes

	72°C, 1.5 minutes

	60°C, 1 minutes

	75°C,10 minutes

rDNA21		50 μL reaction; 5 μL DNA from filter papers (or 5 μL N1), 25 μL QIAGEN HotStar Taq Master Mix (QIAGEN), 0.3 μM primers	75°C, 10 minutes

ITS222	F: GGGAGAAGCTCTATTGTG	25 μL reaction; 1 μL N2 product from rDNA PCR, KCl buffer (15 mM MgCl2, Bioline, London, UK), 2 mM deoxynucleotide triphosphates, 0.4 μM primers, 1U Taq polymerase	94°C, 2 minutes

R: ACACTCAGGTCTGTAAAC	40 cycles

	94°C, 20 seconds

	53°C, 30 seconds

	72°C, 1 minutes

	72°C, 10 minutes

kDNA6	Nest1 F: C/GA/GTA/GCAGAAAC/TCCCGTTCA	50 μL reaction; 5 μL DNA from filter papers (OR 5 μL N1), 25 μL QIAGEN HotStar Taq Master Mix, 0.3 μM primers	95°C, 15 minutes

Nest1 R: ATTTTTCG/CGA/TTTT/CGCAGAACG	30 cycles at

Nest2 F: ACTGGGGGTTGGTGTAAAATAG	94°C, 1 minutes

Nest2 R: TCGCAGAACGCCCCT	55°C, 1 minutes

	72°C, 1.5 minutes

	60°C, 1 minutes

	75°C,10 minutes


Treatments	Reaction time in seconds (mean ± SEM)

0 min	15 min	30 min	45 min	60 min

Control (normal saline)	4.25 ± 0.57	4.50 ± 0.34	4.42 ± 0.45	4.58 ± 0.44	5.17 ± 0.80

Morphine sulfate	6.50 ± 1.22	11.04 ± 0.73∗ab	11.92 ± 0.84∗ab	12.83 ± 0.35∗ab	13.33 ± 0.83∗ab

Treatments	Reaction time in seconds (mean ± SEM)

0 min	15 min	30 min	45 min	60 min

Sodium salicylate	4.13 ± 0.54	5.29 ± 0.57	6.75 ± 0.62∗a	5.75 ± 0.56	6.79 ± 1.24

Quercus infectoria (galls) extract	6.67 ± 0.85a	7.04 ± 0.67a	8.04 ± 0.73a	7.00 ± 0.92a	6.67 ± 0.86


Items_Details	Number of genes	Adjusted p-Valuea	Genes

Signaling pathways

Focal adhesion	27	1.8E-08	ITGA1, MAPK1, comP, ITGA6, ERBB2, LAMA2, CCND2, BCAR1, DIAPH1, PTEN, ITGA2, SPP1, ACTB, LAMC1, CAPN2, COL4A1, EGFR, VAV2, THBS4, ITGA9, THBS2, PTK2, PIK3CG, VEGFA, fn1, PPP1CB, VAV3

Regulation of actin cytoskeleton	27	3.5E-08	PIP4K2A, ITGA1, MAPK1, ARPC2, ITGA6, ITGB2, ARPC1B, F2R, BCAR1, DIAPH1, GNA12, ITGA2, NCKAP1L, GSN, ACTB, TMSB4X, EGFR, VAV2, ITGA9, CD14, PTK2, Kras, BAIAP2, PIK3CG, fn1, PPP1CB, VAV3

ECM-receptor interaction	14	5.8E-06	ITGA1, comP, ITGA6, LAMA2, ITGA2, GP1BB, SPP1, LAMC1, COL4A1, THBS4, ITGA9, THBS2, AGRN, fn1

Adherens junction	12	2.7E-05	MAPK1, PARD3, CTNNA3, ACP1, ERBB2, PTPRJ, ACTB, EGFR, BAIAP2, CREBBP, SORBS1, PVRL3

Metabolic pathways

Valine, leucine and isoleucine degradation	12	2.3E-07	ALDH3A2, BCAT1, OXCT1, EHHADH, IVD, BCKDHB, ECHS1, ACADSB, HADHA, PCCB, AUH, ALDH2

Lysine degradation	9	0.0002	MLL5, ALDH3A2, EHHADH, NSD1, WHSC1L1, ECHS1, HADHA, setmar, ALDH2

Purine metabolism	16	0.00033	NUDT2, Pgm2, GMPR2, POLR2G, ENPP1, RRM2B, FHIT, GUCY1A3, ADA, NT5C2, NME6, PGM1, PRPS2, ATIC, NT5E, POLR3E

beta-Alanine metabolism	6	0.00088	ALDH3A2, EHHADH, ECHS1, CARNS1, HADHA, ALDH2

Arginine and proline metabolism	8	0.0014	ALDH3A2, ACY1, P4HA1, GLUD1, CARNS1, AMD1, ALDH4A1, ALDH2

Fatty acid metabolism	7	0.0014	ALDH3A2, EHHADH, ECHS1, ACADSB, ACSL4, HADHA, ALDH2

Cellular processes

Phagosome	21	9.2E-08	comP, CTSS, ATP6V1C1, ITGB2, ITGA2, PIK3C3, ACTB, CYBB, CYBA, TFRC, THBS4, CD14, THBS2, NCF4, NCF2, DYNC1I2, EEA1, FCGR2B, MRC1, TUBA8, TUBA4A

Protein processing in endoplasmic reticulum	21	7E-07	nsfl1c, BAG2, UBE4B, PARK2, SAR1B, HSPH1, SEC24D, DNAJC1, CAPN2, DDOST, BCAP31, HSPA2, PDIA3, CUL1, UBE2D4, HERPUD1, EDEM2, DNAJA1, DERL1, CKAP4, TUSC3

mRNA surveillance pathway	13	0.000016	SAP18, PPP2R5A, CPSF6, CLP1, PPP2R2A, PAPOLA, PAPOLB, PPP2CB, Fip1l1, ETF1, HBS1L, CPSF3, CSTF2T

Endocytosis	20	3.61E-05	RAB11FIP5, PARD3, KIT, F2R, DNM2, EHD1, RABEP1, ARRB2, GRK5, DNM1L, FOLR1, EGFR, TFRC, HSPA2, WWP1, ZFYVE16, SMAP2, EEA1, epn1, FAM125B

Items_Details	Number of genes	Adjusted p-Valuea	Genes

Phagosome	21	9.2E-08	comP, CTSS, ATP6V1C1, ITGB2, ITGA2, PIK3C3, ACTB, CYBB, CYBA, TFRC, THBS4, CD14, THBS2, NCF4, NCF2, DYNC1I2, EEA1, FCGR2B, MRC1, TUBA8, TUBA4A

Protein processing in endoplasmic reticulum	21	7E-07	nsfl1c, BAG2, UBE4B, PARK2, SAR1B, HSPH1, SEC24D, DNAJC1, CAPN2, DDOST, BCAP31, HSPA2, PDIA3, CUL1, UBE2D4, HERPUD1, EDEM2, DNAJA1, DERL1, CKAP4, TUSC3

mRNA surveillance pathway	13	0.000016	SAP18, PPP2R5A, CPSF6, CLP1, PPP2R2A, PAPOLA, PAPOLB, PPP2CB, Fip1l1, ETF1, HBS1L, CPSF3, CSTF2T

Endocytosis	20	3.61E-05	RAB11FIP5, PARD3, KIT, F2R, DNM2, EHD1, RABEP1, ARRB2, GRK5, DNM1L, FOLR1, EGFR, TFRC, HSPA2, WWP1, ZFYVE16, SMAP2, EEA1, epn1, FAM125B


		N	Zinc concentration	N	Height for age z score (mean ± sd)

Cuba	STH uninfected	160	112.55 (88.3–136.0) a	1251	0.11 ± 0.97

	STH infected	70	113.35 (94.4–143.7) a	117	−0.31 ± 1.16

Cambodia	STH uninfected	1239	7.74 ± 1.70 b	1450	−1.81 ± 1.05

	STH infected	254	7.52 ± 1.70 b	296	−1.84 ± 1.09

		N	Zinc concentration	N	Height for age z score (mean ± sd)

	STH infected	70	113.35 (94.4–143.7) a	117	−0.31 ± 1.16

Cambodia	STH uninfected	1239	7.74 ± 1.70 b	1450	−1.81 ± 1.05

	STH infected	254	7.52 ± 1.70 b	296	−1.84 ± 1.09


Covariate

LBC1936 (n = 920, nevents = 135)

Age (years)

Sex (female)

Telomere length

Hannum age

LBC1921 (n = 414, nevents = 280)

Age (years)

Sex (female)

Telomere length

Hannum age

LBC1921 + LBC1936 (n = 1344, nevents = 415)

Age (years)

Sex (female)

Telomere length

Hannum age