Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypic identification and classification of functional defecatory disorders using high-resolution anorectal manometry.

BACKGROUND & AIMS Disordered defecation is attributed to pelvic floor dyssynergia. However, clinical observations indicate a spectrum of anorectal dysfunctions. The extent to which these disorders are distinct or overlap is unclear; anorectal manometry might be used in diagnosis, but healthy persons also can have abnormal rectoanal pressure gradients during simulated evacuation. We aimed to characterize phenotypic variation in constipated patients through high-resolution anorectal manometry. METHODS We evaluated anorectal pressures, measured with high-resolution anorectal manometry, and rectal balloon expulsion time in 62 healthy women and 295 women with chronic constipation. Phenotypes were characterized by principal components analysis of high-resolution anorectal manometry. RESULTS Two healthy persons and 71 patients had prolonged (>180 s) rectal balloon expulsion time. A principal components logistic model discriminated healthy people from patients with prolonged balloon expulsion time with 75% sensitivity and a specificity of 75%. Four phenotypes discriminated healthy people from patients with abnormal balloon expulsion times; 2 phenotypes discriminated healthy people from those with constipation but normal balloon expulsion time. Phenotypes were characterized based on high anal pressure at rest and during evacuation (high anal), low rectal pressure alone (low rectal) or low rectal pressure with impaired anal relaxation during evacuation (hybrid), and a short anal high-pressure zone. Symptoms were not useful for predicting which patients had prolonged balloon expulsion times. CONCLUSIONS Principal components analysis of rectoanal pressures identified 3 phenotypes (high anal, low rectal, and hybrid) that can discriminate among patients with normal and abnormal balloon expulsion time. These phenotypes might be useful to classify patients and increase our understanding of the pathogenesis of defecatory disorders.
Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose‐response meta‐analysis

The association of overweight and obesity with premenopausal breast cancer remained unclear, ethnicity could play a role. A MEDLINE and PUBMED search of all studies on obesity and premenopausal breast cancer published from 2000 to 2010 was conducted. Dose‐response meta‐analysis was used to determine the risk of premenopausal breast cancer associated with different anthropometric measurements in different ethnic groups. For body mass index (BMI), each 5 kg m−2 increase was inversely associated with the risk of premenopausal breast cancer (RR = 0.95, 95% confidence interval [CI]: 0.94, 0.97). After stratification by ethnicity, the inverse association remained significant only among Africans (RR = 0.95, 95% CI: 0.91, 0.98) and Caucasians (RR = 0.93, 95% CI: 0.91, 0.95). In contrast, among Asian women, a significant positive association was observed. For waist‐to‐hip ratio (WHR), each 0.1 unit increase was positively associated with premenopausal breast cancer (RR = 1.08, 95% CI: 1.01, 1.16); the largest effect was detected in Asian women (RR = 1.19, 95% CI: 1.15, 1.24), while small effects of 5% and 6% were observed in African and Caucasian women, respectively. Our results suggest the importance of considering both fat distribution and ethnicity when studying premenopausal breast cancer.
Hypoadiponectinemia as an independent predictor for the progression of carotid atherosclerosis: a 5-year prospective study.

BACKGROUND Hypoadiponectinemia predicts the development of diabetes and hypertension, both being potent atherosclerotic risk factors. Whether adiponectin predicts the progression of early atherosclerosis remains unclear. In this 5-year prospective study, we examined the relationship between serum adiponectin and carotid intima media thickness (CIMT), a marker of subclinical atherosclerosis. METHODS A total of 265 subjects from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study, with no known cardiovascular disease, underwent CIMT measurement at baseline and at 5 years. RESULTS In all, 129 men and 136 women, aged 54.6±12.3 years, were studied. Median CIMT at baseline was 0.63 mm (interquartile range 0.52-0.73 mm) and increased to 0.67 mm (0.56-0.78 mm) after 5 years (P<0.001). CIMT increment correlated with baseline adiponectin, age, and smoking (all P<0.05) and baseline CIMT (P<0.001), but not with sex, fasting glucose, lipid profiles, hypertension, or diabetes. In multiple linear regression analysis, baseline serum adiponectin level was an independent predictor of CIMT increment β (standardized beta)=-0.17, P=0.015], after adjusting for age, smoking, baseline CIMT, hypertension, body mass index, fasting glucose, low-density lipoprotein cholesterol, and triglycerides. CONCLUSION Hypoadiponectinemia predicted CIMT progression, independent of known predictive factors such as age, smoking, hyperlipidemia, and hypertension.
Pro-angiogenic activity of TLRs and NLRs: a novel link between gut microbiota and intestinal angiogenesis.

BACKGROUND & AIMS In intestinal inflammation the gut microbiota induces an innate immune response by activating epithelial and immune cells that initiate or maintain inflammation. We investigated whether the microbiota also can activate local microvascular cells and induce angiogenesis. METHODS Human intestinal microvascular endothelial cells (HIMEC) and human intestinal fibroblasts (HIF) were exposed to bacterial ligands specific for Toll-like receptor (TLR)2/6 and 4, and NOD1 and NOD2, and cell proliferation, migration, transmigration, tube formation, and production of pro-angiogenic factors were measured. The ability of the ligands to induce ex vivo vessel sprouting in an aortic ring assay and in vivo angiogenesis using a collagen gel assay also were assessed. RESULTS Bacterial ligands induced proliferation, migration, transmigration, tube formation of HIMEC, vessel sprouting, and in vivo angiogenesis; they also stimulated production of angiogenic factors from HIMEC and HIF, and HIF-derived angiogenic factors promoted HIMEC proliferation. To various degrees, all ligands induced angiogenic responses, but these were ligand- and cell type-dependent. Responses were mediated through receptor interacting protein-2 (RIP2)- and tumor necrosis factor receptor-associated factor 6 (TRAF6)-dependent signaling, involved the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways and the up-regulation of vascular endothelial growth factor receptor 2 (VEGF-R2) and focal adhesion kinase (FAK). Knockdown of RIP2 and TRAF6 by RNA interference and neutralization of interleukin-8, basic fibroblast growth factor, and vascular endothelial growth factor inhibited TLR-/NOD-like receptor-induced HIMEC angiogenesis. CONCLUSIONS The gut microbiota can selectively activate mucosal endothelial and mesenchymal cells to promote specific angiogenic responses in a TLR- and NOD-like receptor-dependent fashion. This innate immunity-mediated response may expand the mucosal microvascular network, foster immune cell recruitment, and contribute to chronic intestinal inflammation.
THE IMPACT OF MATERNAL BIRTH MONTH ON REPRODUCTIVE PERFORMANCE: CONTROLLING FOR SOCIO-DEMOGRAPHIC CONFOUNDERS

Summary Based on a 1900 census sample of 34,166 post-reproductive females (≥45 years), the birth month effect was put to the test, for both lifetime fertility as well as child survival, controlling for maternal birth cohort (1826–1835, 1836–1845, 1846–1855), Duncan's SEI, urbanity, nativity, literacy and marital duration. Testing for potential cohort effects did not indicate a temporal trend in fertility by maternal birth month (seasonal Mann-Kendall test, p=0.578), while a minute increase in offspring survival was detected (p<0.001, Sen's estimator of slope=0.02, 95% CI=0.02 to 0.03). Further analyses of the maternal birth month effect on child survival were therefore seized. For lifetime fertility, ANOVA results indicated that maternal birth month was a major predictor for total offspring count (F11, 33606=1809.0, p<0.001), accounting for 37.2% of the total variability. In addition to main effects, a statistically significant interaction effect was observed (F538, 33606=2.2, p<0.001), with a corresponding effect size of η2=0.40. Planned contrasts revealed that birth-month-specific differences in fertility achieved statistical significance (F11, 31798=1712.9, p<0.001), while post-hoc multiple comparisons for literacy and nativity displayed an inverse relationship with fertility, which meets demographic expectations. Controlling for all factors of interest, models of cohort-specific offspring counts (independent ANOVAs for 1826–1835: F157, 3467=26.3, p<0.001; 1836–1845: F182, 10299=75.5, p<0.001; 1846–1855: F199, 19859=137.9, p<0.001) indicated that women born in the first half of the year (particularly, January, February, April and May) achieved above-average parity, while those born in the latter half (namely, July, October, November and December) displayed markedly lower fertility averages. These monthly disparities are in line with previous observations and appear to be linked to seasonal optimal ripening of the oocyte or seasonal preovulatory over-ripeness ovopathy (Jongbloet, 1992).
Does obesity affect knee cartilage? A systematic review of magnetic resonance imaging data

There is increasing evidence for the effect of obesity on knee osteoarthritis (OA), although the association between obesity, particularly body composition, and knee osteoarthritis, using magnetic resonance imaging (MRI) to examine knee structure, has not been examined. We systematically evaluated the evidence for the relationship between obesity and knee cartilage assessed by MRI. We performed an electronic search of MEDLINE and EMBASE up to December 2012. Included studies investigated the association between obesity and the development and/or progression of knee cartilage changes using MRI. The studies were ranked according to their methodological score and best‐evidence synthesis was performed to summarize the results Twenty‐two studies were identified for inclusion, of which 7 were cross‐sectional, 13 were longitudinal and 2 had both cross‐sectional and longitudinal components. Seven cross‐sectional and eight longitudinal studies were of high quality. Best‐evidence synthesis showed consistent, yet limited evidence for a detrimental effect of body mass index (BMI) and fat mass on knee cartilage. This review identified a consistent detrimental effect of obesity, particularly related to elevated BMI and fat mass on cartilage defects. The strength of evidence was limited by the paucity of high‐quality cohort studies examining this question. By further examining the mechanisms for these different effects, new strategies can be developed to prevent and treat knee OA.
Meta‐analysis on night shift work and risk of metabolic syndrome

This study aims to quantitatively summarize the association between night shift work and the risk of metabolic syndrome (MetS), with special reference to the dose–response relationship with years of night shift work. We systematically searched all observational studies published in English on PubMed and Embase from 1971 to 2013. We extracted effect measures (relative risk, RR; or odd ratio, OR) with 95% confidence interval (CI) from individual studies to generate pooled results using meta‐analysis approach. Pooled RR was calculated using random‐ or fixed‐effect model. Downs and Black scale was applied to assess the methodological quality of included studies. A total of 13 studies were included. The pooled RR for the association between ‘ever exposed to night shift work’ and MetS risk was 1.57 (95% CI = 1.24–1.98, pheterogeneity = 0.001), while a higher risk was indicated in workers with longer exposure to night shifts (RR = 1.77, 95% CI = 1.32–2.36, pheterogeneity = 0.936). Further stratification analysis demonstrated a higher pooled effect of 1.84 (95% CI = 1.45–2.34) for studies using the NCEP‐ATPIII criteria, among female workers (RR = 1.61, 95% CI = 1.10–2.34) and the countries other than Asia (RR = 1.65, 95% CI = 1.39–1.95). Sensitivity analysis confirmed the robustness of the results. No evidence of publication bias was detected. The present meta‐analysis suggested that night shift work is significantly associated with the risk of MetS, and a positive dose–response relationship with duration of exposure was indicated.
Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews

Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews was conducted. For inclusion, reviews had to compare pregnant women of healthy weight with women with obesity, and measure a health outcome for mother and/or baby. Authors conducted full‐text screening, quality assurance using the AMSTAR tool and data extraction steps in pairs. Narrative analysis of the 22 reviews included show gestational diabetes, pre‐eclampsia, gestational hypertension, depression, instrumental and caesarean birth, and surgical site infection to be more likely to occur in pregnant women with obesity compared with women with a healthy weight. Maternal obesity is also linked to greater risk of preterm birth, large‐for‐gestational‐age babies, foetal defects, congenital anomalies and perinatal death. Furthermore, breastfeeding initiation rates are lower and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy weight women. These adverse outcomes may result in longer duration of hospital stay, with concomitant resource implications. It is crucial to reduce the burden of adverse maternal and foetal/child outcomes caused by maternal obesity. Women with obesity need support to lose weight before they conceive, and to minimize their weight gain in pregnancy.
Risk of cancer in cases of suspected lynch syndrome without germline mutation.

BACKGROUND & AIMS Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. METHODS We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups. RESULTS The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval [CI], 3.58-9.54; SIR for LLS, 2.12; 95% CI, 1.16-3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27-0.79; P < .001). CONCLUSIONS The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives.
Sensory influences on food intake control: moving beyond palatability

The sensory experience of eating is an important determinant of food intake control, often attributed to the positive hedonic response associated with certain sensory cues. However, palatability is just one aspect of the sensory experience. Sensory cues based on a food's sight, smell, taste and texture are operational before, during and after an eating event. The focus of this review is to look beyond palatability and highlight recent advances in our understanding of how certain sensory characteristics can be used to promote better energy intake control. We consider the role of visual and odour cues in identifying food in the near environment, guiding food choice and memory for eating, and highlight the ways in which tastes and textures influence meal size and the development of satiety after consumption. Considering sensory characteristics as a functional feature of the foods and beverages we consume provides the opportunity for research to identify how sensory enhancements might be combined with energy reduction in otherwise palatable foods to optimize short‐term energy intake regulation in the current food environment. Moving forward, the challenge for sensory nutritional science will be to assess the longer‐term impact of these principles on weight management.
From the BMI paradox to the obesity paradox: the obesity–mortality association in coronary heart disease

Despite a strong association between body weight and mortality in the general population, clinical evidence suggests better clinical outcome of overweight or obese individuals with established coronary heart disease. This finding has been termed the ‘obesity paradox’, but its existence remains a point of debate, because it is mostly observed when body mass index (BMI) is used to define obesity. Inherent limitations of BMI as an index of adiposity, as well as methodological biases and the presence of confounding factors, may account for the observed findings of clinical studies. In this review, our aim is to present the data that support the presence of a BMI paradox in coronary heart disease and then explore whether next to a BMI paradox a true obesity paradox exists as well. We conclude by attempting to link the obesity paradox notion to available translational research data supporting a ‘healthy’, protective adipose tissue phenotype. © 2016 World Obesity
Nutritional interventions or exposures in infants and children aged up to 3 years and their effects on subsequent risk of overweight, obesity and body fat: a systematic review of systematic reviews

This study, performed as part of the international EarlyNutrition research project (http://www.project‐earlynutrition.eu), provides a systematic review of systematic reviews on the effects of nutritional interventions or exposures in children (up to 3 years of age) on the subsequent risk of obesity, overweight and adiposity. Electronic databases (including MEDLINE, Embase and Cochrane Library) were searched up until September 2015. Forty systematic reviews were included. A consistent association of breastfeeding with a modest reduction in the risk of later overweight and obesity in childhood and adulthood was found (the odds decreased by 13% based on high‐quality studies), but residual confounding cannot be excluded. Lowering the protein content of infant formula is a promising intervention to reduce the risk of later overweight and obesity in children. There is no consistent evidence of an association of the age of introducing complementary foods, sugar‐sweetened beverage or energy intake in early childhood with later overweight/obesity, but there are some indications of an association of protein intake during the complementary feeding period with later overweight/obesity. There was inadequate evidence to determine the effects of other nutritional interventions or exposures, including modifications of infant formula composition, fat intake or consumption of different food groups.
Smart approaches for assessing free‐living energy expenditure following identification of types of physical activity

Accurate assessment of physical activity and energy expenditure has been a research focus for many decades. A variety of wearable sensors have been developed to objectively capture physical activity patterns in daily life. These sensors have evolved from simple pedometers to tri‐axial accelerometers, and multi sensor devices measuring different physiological constructs. The current review focuses on how activity recognition may help to improve daily life energy expenditure assessment. A brief overview is given about how different sensors have evolved over time to pave the way for recognition of different activity types. Once the activity is recognized together with the intensity of the activity, an energetic value can be attributed. This concept can then be tested in daily life using the independent reference technique doubly labeled water. So far, many studies have been performed to accurately identify activity types, and some of those studies have also successfully translated this into energy expenditure estimates. Most of these studies have been performed under standardized conditions, and the true applicability in daily life has rarely been addressed. The results so far however are highly promising, and technological advancements together with newly developed algorithms based on physiological constructs will further expand this field of research.
Sex/gender differences in neural correlates of food stimuli: a systematic review of functional neuroimaging studies

Sex and gender differences in food perceptions and eating behaviours have been reported in psychological and behavioural studies. The aim of this systematic review was to synthesize studies that examined sex/gender differences in neural correlates of food stimuli, as assessed by functional neuroimaging. Published studies to 2016 were retrieved and included if they used food or eating stimuli, assessed patients with functional magnetic resonance imaging or positron emission tomography, and compared activation between men and women. Fifteen studies were identified. In response to visual food cues, women, compared with men, showed increased activation in the frontal, limbic and striatal areas of the brain as well as the fusiform gyrus while fasted. Differences in neural response to gustatory stimuli were inconsistent. This suggests that women may be more reactive to visual food stimuli, especially when hungry. However, findings are based on a small number of studies, and additional research is needed to establish a more definitive explanation and conclusion.
3D chromatin interactions organize Yan chromatin occupancy and repression at the even-skipped locus

Long-range integration of transcriptional inputs is critical for gene expression, yet the mechanisms are poorly understood. Here, Webber et al. investigate how cis-regulatory elements at the even-skipped (eve) locus coordinate heart-specific gene expression. Targeted deletions of regions bound by the repressor Yan define two novel enhancers that contribute repressive inputs to stabilize tissue-specific output from a third enhancer. This study provides a new paradigm for chromatin-level integration of repressive inputs with specific patterning information to achieve robust gene expression.