Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational modeling of in vivo and in vitro protein‐DNA interactions by multiple instance learning

Motivation: The study of transcriptional regulation is still difficult yet fundamental in molecular biology research. While the development of both in vivo and in vitro profiling techniques have significantly enhanced our knowledge of transcription factor (TF)‐DNA interactions, computational models of TF‐DNA interactions are relatively simple and may not reveal sufficient biological insight. In particular, supervised learning based models for TF‐DNA interactions attempt to map sequence‐level features (k‐mers) to binding event but usually ignore the location of k‐mers, which can cause data fragmentation and consequently inferior model performance. Results: Here, we propose a novel algorithm based on the so‐called multiple‐instance learning (MIL) paradigm. MIL breaks each DNA sequence into multiple overlapping subsequences and models each subsequence separately, therefore implicitly takes into consideration binding site locations, resulting in both higher accuracy and better interpretability of the models. The result from both in vivo and in vitro TF‐DNA interaction data show that our approach significantly outperform conventional single‐instance learning based algorithms. Importantly, the models learned from in vitro data using our approach can predict in vivo binding with very good accuracy. In addition, the location information obtained by our method provides additional insight for motif finding results from ChIP‐Seq data. Finally, our approach can be easily combined with other state‐of‐the‐art TF‐DNA interaction modeling methods. Availability and Implementation: http://www.cs. utsa.edu/˜jruan/MIL/ Contact: jianhua.ruan@utsa.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Measuring Outcomes of Psychological Well-Being within Paediatric Health Settings

There are many widely used, validated patient reported outcome measures for physical and mental health. However, capturing outcomes from young people living with chronic health conditions presents a challenge, needing to take the complex interplay of physical and mental health into consideration. The authors found that regularly used outcome measures for child and adolescent emotional well-being in paediatric settings largely fall into two groups: paediatric quality of life and child and adolescent mental health measures. The applicability and potential for use of these measures within this context is discussed. Whilst offering some utility, neither approach leaves sufficient space for young people’s individual experiences of illness and treatment. The scope of using alternative qualitative approaches that capture the rich stories and experiences of young people living with chronic illnesses is considered.
Exploiting CELLULOSE SYNTHASE (CESA) Class Specificity to Probe Cellulose Microfibril Biosynthesis1[OPEN]

Mutagenesis reveals which CESA protein classes have the greatest influence on the regulation of cellulose microfibril biosynthesis in the Arabidopsis secondary cell wall. Cellulose microfibrils are the basic units of cellulose in plants. The structure of these microfibrils is at least partly determined by the structure of the cellulose synthase complex. In higher plants, this complex is composed of 18 to 24 catalytic subunits known as CELLULOSE SYNTHASE A (CESA) proteins. Three different classes of CESA proteins are required for cellulose synthesis and for secondary cell wall cellulose biosynthesis these classes are represented by CESA4, CESA7, and CESA8. To probe the relationship between CESA proteins and microfibril structure, we created mutant cesa proteins that lack catalytic activity but retain sufficient structural integrity to allow assembly of the cellulose synthase complex. Using a series of Arabidopsis (Arabidopsis thaliana) mutants and genetic backgrounds, we found consistent differences in the ability of these mutant cesa proteins to complement the cellulose-deficient phenotype of the cesa null mutants. The best complementation was observed with catalytically inactive cesa4, while the equivalent mutation in cesa8 exhibited significantly lower levels of complementation. Using a variety of biophysical techniques, including solid-state nuclear magnetic resonance and Fourier transform infrared microscopy, to study these mutant plants, we found evidence for changes in cellulose microfibril structure, but these changes largely correlated with cellulose content and reflected differences in the relative proportions of primary and secondary cell walls. Our results suggest that individual CESA classes have similar roles in determining cellulose microfibril structure, and it is likely that the different effects of mutating members of different CESA classes are the consequence of their different catalytic activity and their influence on the overall rate of cellulose synthesis.
Association between serum concentrations of 25-hydroxyvitamin D3 and periodontal disease in the US population.

BACKGROUND Periodontal disease (PD) is a common chronic inflammatory disease and an important risk factor for tooth loss. Vitamin D might affect periodontal disease risk via an effect on bone mineral density (BMD) or via immunomodulatory effects. OBJECTIVE The objective was to evaluate whether serum 25-hydroxyvitamin D(3) [25(OH)D(3)] concentrations are associated with PD in the third National Health and Nutrition Examination Survey. DESIGN We analyzed data on periodontal attachment loss (AL) and serum 25(OH)D(3) concentrations from 11 202 subjects aged > or =20 y. Mean AL was modeled in a multiple linear regression with quintile of serum 25(OH)D(3) concentration as an independent variable. The model was stratified by age and sex and was adjusted for age within age groups, race or ethnicity, smoking, diabetes, poverty income ratio, body mass index, estrogen use, and gingival bleeding. RESULTS 25(OH)D(3) concentrations were significantly and inversely associated with AL in men and women aged > or =50 y. Compared with men in the highest 25(OH)D(3) quintile, those in the lowest quintile had a mean AL that was 0.39 mm (95% CI: 0.17, 0.60 mm) higher; in women, the difference in AL between the lowest and highest quintiles was 0.26 mm (0.09, 0.43 mm). In men and women younger than 50 y, there was no significant association between 25(OH)D(3) and AL. The BMD of the total femoral region was not associated with AL and did not mediate the association between 25(OH)D(3) and AL. CONCLUSIONS Low serum 25(OH)D(3) concentrations may be associated with PD independently of BMD. Given the high prevalence of PD and vitamin D deficiency, these findings may have important public health implications.
A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Recently, many genome‐wide profiling studies provided insights into the molecular make‐up of major cancer types. The deeper understanding of these genetic alterations and their functional consequences led to the discovery of novel therapeutic opportunities improving clinical management of cancer patients. While tissue‐based molecular patient stratification is the gold standard for precision medicine, it has certain limitations: Tissue biopsies are invasive sampling procedures carrying the risk of complications and may not represent the entire tumor due to underlying genetic heterogeneity. In this context, complementary characterization of genetic information in the blood of cancer patients can serve as minimal‐invasive ‘liquid biopsy’. Fragments of circulating cell‐free DNA (cfDNA) are released from tissues of healthy individuals as well as cancer patients. The fraction of cfDNA that is released from primary tumors or metastases (i.e. circulating tumor DNA, ctDNA) represents genetic aberrations in cancer cells, which are a potential source for diagnostic, prognostic, and predictive biomarkers. Recent studies have demonstrated technical feasibility and clinical applications including detection of drug targets and resistance mutations as well as longitudinal monitoring of tumors under therapy. To this end, a variety of pre‐analytical procedures for blood processing, isolation and quantification of cfDNA are being employed and several analytical methods and technologies ranging from PCR‐based single locus assays to genome‐wide approaches are available, which considerably differ in sensitivity, specificity, and throughput. However, broad implementation of ctDNA analysis in daily clinical practice requires a thorough understanding of theoretical, technical, and biological concepts and necessitates standardization and validation of pre‐analytical and analytical procedures across different technologies. Here, we review the pertinent literature and discuss the advantages and limitations of available methodologies and their potential applications in molecular diagnostics.
Direct nutrition intervention and the control of diarrheal diseases in preschool children.

This is a report of the reduction in frequency of diarrheal disease in malnourished school children, which was an unanticipated result of a nutrition intervention program in Candelaria, Colombia, during 1964-65. In a late 1963 baseline study all preschool children were weighed and measured and the mothers interviewed. Mothers of the malnourished were invited to participate in a supplementation program. Weekly records were kept of the episodes, and diarrheal disease decreased in the 182 children observed for a full calendar year. Each malnourished child was given 1 pound of dried skimmed milk (DSM) per week. In the 6-week program the mothers were educated about food and nutrition. At monthly intervals the children were weighed and measured. Among the 101 children with first degree malnutrition at the start of the program, almost two-thirds had improved; of the 72 with second degree malnutrition, three-fourths improved; and, all of the 9 with third degree malnutriton improved after the first year. Mothers commented that after receiving supplement for about 6 weeks their children had less diarrhea. Exclusive breastfeeding plays a protective role against diarrhea in the early months of life. The association between nutritional status and diarrheal disease is stronger than that of environmental sanitation.
Noradrenergic control of central oxytocin release during lactation in rats.

Noradrenergic systems regulate the systemic release of oxytocin (OT) in lactating rats. However, a role for norepinephrine (NE) in release of OT within the magnocellular nuclei during suckling has not been established. These studies were designed to determine 1) if suckling induces NE release in the supraoptic (SON) and paraventricular (PVN) nuclei of conscious rats and 2) the role of NE in the central, intranuclear release of OT within these nuclei. Female Holtzman rats were implanted with microdialysis probes adjacent to the PVN or SON on lactation days 8- 12. The following day, the pups were isolated from the dams for 4 h. Microdialysis probes were perfused with artificial cerebrospinal fluid (ACSF) or with ACSF containing an α- or a β-adrenergic receptor antagonist. Dialysate was collected before, during, and after suckling and analyzed for NE or OT. In an additional experiment, an α- or β-adrenergic agonist was administered via the microdialysis probes into the PVN in nonsuckled, lactating rats. Extracellular NE increased in the PVN during suckling but was not detectable in the SON. OT concentrations in dialysates from the PVN and SON significantly increased during suckling. Blockade of either α- (in both PVN and SON) or β- (PVN) adrenergic receptors prevented the suckling-induced increase in central OT release. OT release was increased in nonsuckled, lactating rats by central application of either an α- or β-adrenergic agonist. These data demonstrate that intranuclear NE release is increased in the PVN by suckling and that subsequent stimulation of both α- and β-noradrenergic receptors mediates intranuclear OT release.
Early infant feeding and growth status of US-born infants and children aged 4-71 mo: analyses from the third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND There is controversy over what growth references to use in evaluating breast-fed infants and concern about whether never-breast-fed infants are at risk of overweight in childhood. OBJECTIVE The objective of this study was to determine whether infants who are exclusively breast-fed for 4 mo differ in average size from infants who are fed in other ways and whether such differences persist through age 5 y. DESIGN Data from the third National Health and Nutrition Examination Survey (NHANES III) were linked to birth certificates of US-born infants and children. Feeding groups were defined on the basis of feeding patterns over the first 4 mo of life: exclusively breast-fed for 4 mo, partially breast-fed, breast-fed for <4 mo, and never breast-fed. Growth status, indexed as internally derived z scores (SD units) for weight, length (height), weight-for-length (height), midupper arm circumference, and triceps skinfold thickness, was compared among feeding groups. RESULTS The final sample consisted of 5594 non-Hispanic white, non-Hispanic black, and Mexican American infants and children aged 4-71 mo. Of these, 21% were exclusively breast-fed for 4 mo, 10% were partially breast-fed, 24% were breast-fed for <4 mo, and 45% were never breast-fed. At 8-11 mo, infants who were exclusively breast-fed for4 mo had adjusted mean z scores for weight (-0.21; -0.2 kg), weight-for-length (-0.27), and midupper arm circumference (-0.15) that differed significantly from zero (P < 0. 05). By 12-23 mo, the differences had dissipated; there were no significant differences subsequent to 5 y. Triceps skinfold thickness was not related to early infant feeding. CONCLUSION Infants who were exclusively breast-fed for 4 mo weighed less at 8-11 mo than did infants who were fed in other ways, but there were few other significant differences in growth status through age 5 y associated with early infant feeding.
Analyzing the resting state functional connectivity in the human language system using near infrared spectroscopy

We have evaluated the use of phase synchronization to identify resting state functional connectivity (RSFC) in the language system in infants using functional near infrared spectroscopy (fNIRS). We used joint probability distribution of phase between fNIRS channels with a seed channel in the language area to estimate phase relations and to identify the language system network. Our results indicate the feasibility of this method in identifying the language system. The connectivity maps are consistent with anatomical cortical connections and are also comparable to those obtained from functional magnetic resonance imaging (fMRI) functional connectivity studies. The results also indicate left hemisphere lateralization of the language network.
Preoperative unintended weight loss and low body mass index in relation to complications and length of stay after cardiac surgery.

BACKGROUND Several studies reported increased adverse outcomes after cardiac surgery in patients with low body mass index (BMI; in kg/m(2)). Little is known yet, however, about the effect of preoperative unintended weight loss (UWL) in cardiac surgery patients. OBJECTIVE We explored the prevalence and effect of UWL in view of low BMI and vice versa adjusted for a validated set of preoperative risks, inflammatory activity, and duration of extracorporeal circulation on postoperative adverse outcome. DESIGN A prospective cohort study was performed. Nutritional data of cardiac surgery patients were collected within 24 h of admission and linked to the standard postoperative complication registration database. RESULTS The cohort consisted of 331 cases. Multivariate logistic regression analyses showed that preoperative UWL of >or=10% in the past 6 mo (>or=10%UWLin6m) was associated with a prolonged length of stay in the hospital independent from low BMI [odds ratio (OR): 7.06; 95% CI: 1.78, 28.04]. Preoperative BMI <or= 21.0 was associated with an increased incidence of postoperative infections and prolonged stay in the intensive care unit independent from >or=10%UWLin6m (OR: 4.62; 95% CI: 1.20, 17.82; and OR: 5.27; 95% CI: 1.28, 21.76, respectively). Preoperative undernutrition in cardiac surgery patients (>or=10%UWLin6m or BMI <or= 21.0 or both) was present in 9.1% of the study population (4.3% and 4.8%, respectively). CONCLUSIONS From this study, we recommend special attention for cardiac surgery patients with preoperative >or=10%UWLin6m or BMI <or= 21.0 because both variables are independently related to adverse outcomes. Preoperative referral to a dietitian for further diagnostic assessment and nutritional treatment is strongly recommended.
Pattern-Reconfigurable Cylindrical Dielectric Resonator Antenna Based on Parasitic Elements

A novel pattern-reconfigurable cylindrical dielectric resonator antenna is presented. By the incorporation of four p-i-n diode switches and four parasitic elements, the mode of dielectric resonator excited by the probe changed. The antenna’s radiation patterns can be shaped to concentrate energy in four specific directions, while minimizing the gain in other unwanted directions without affecting the impedance bandwidth of the antenna for its complete symmetry in structure. The antenna switches its radiation patterns among four reconfigurable modes with orthogonal directions at azimuth plane covering a bandwidth of several 870 MHz and exhibiting a high maximum gain of 9.74 dBi. A fully functional prototype has been designed, fabricated, and tested. The measured results of the reflection coefficient, radiation patterns, and realized gain verify the effectiveness of the proposed pattern switching concept for cylindrical dielectric resonator antenna. These capabilities make the antenna suitable for smart wireless devices in next generation communication systems as it can enhance the radio frequency front-end flexibility and performance by adding pattern diversity, especially for muti-input-muti-output systems in multipath environments.
Seven-year stability of indicators of obesity and adipose tissue distribution in the Canadian population.

BACKGROUND The prevention of obesity appears to be a better approach than treatment; thus, the prediction of future obesity from current status is important. OBJECTIVE The aim of the study was to examine the stability of adiposity and adipose tissue distribution (ATD) in the Canadian population. DESIGN The sample included 1048 males and 1063 females aged 7-69 y at baseline from the Campbell's Survey, a 7-y follow-up of the Canada Fitness Survey. Indicators of adiposity included body mass index (BMI), sum of 5 skinfold thicknesses (SF5), and waist circumference (Waist), whereas indicators of ATD included the ratio of trunk to extremity skinfold thicknesses adjusted for SF5 (TER(adj)), and Waist adjusted for BMI (Waist(adj)). RESULTS Interage correlations ranged from 0.53 to 0.91 for BMI, from -0.09 to 0.72 for SF5, from 0.24 to 0.89 for Waist, from 0.23 to 0.73 for TER(adj), and from 0.18 to 0.77 for Waist(adj). Correlations for BMI were higher than for SF5, suggesting that fat-free mass may contribute to the stability of BMI. Although lower than those for BMI, correlations for indicators of ATD were significant, indicating a propensity to retain an android or gynoid pattern. Furthermore, the average percentage of participants remaining in the lower or upper quintiles for the various indicators ranged from 37.8% to 66.7% in males and from 47.0% to 65.3% in females, indicating that those in the lower and upper portions of the distribution tend to remain there. CONCLUSION Obesity and ATD showed significant stability over 7 y in the Canadian population.
Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid.

BACKGROUND Dietary fatty acids may be associated with diabetes but are difficult to measure accurately. OBJECTIVE We aimed to investigate the associations of fatty acids in plasma and diet with diabetes incidence. DESIGN This was a prospective case-cohort study of 3737 adults aged 36-72 y. Fatty acid intake (/kJ) and plasma phospholipid fatty acids (%) were measured at baseline, and diabetes incidence was assessed by self-report 4 y later. Logistic regression excluding (model 1) and including (model 2) body mass index and waist-hip ratio was used to calculate odds ratios (ORs) for plasma phospholipid and dietary fatty acids. RESULTS In plasma phospholipid, positive associations with diabetes were seen for stearic acid [OR model 1, highest versus lowest quintile: 4.14 (95% CI: 2.65, 6.49), P for trend < 0.0001] and total saturated fatty acids [OR model 1: 3.76 (2.43, 5.81), P for trend < 0.0001], whereas an inverse association was seen for linoleic acid [OR model 1: 0.22 (0.14, 0.36), P for trend < 0.0001]. Dietary linoleic [OR model 1: 1.77 (1.19, 2.64), P for trend = 0.002], palmitic [OR model 1: 1.65 (1.12, 2.43), P for trend = 0.012], and stearic [OR model 1: 1.46 (1.00, 2.14), P for trend = 0.030] acids were positively associated with diabetes incidence before adjustment for body size. Within each quintile of linoleic acid intake, cases had lower baseline plasma phospholipid linoleic acid proportions than did controls. CONCLUSIONS Dietary saturated fat intake is inversely associated with diabetes risk. More research is required to determine whether linoleic acid is an appropriate dietary substitute.
Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression

BACKGROUND Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. OBJECTIVE AND RATIONALE We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. SEARCH METHODS We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. OUTCOMES We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression. WIDER IMPLICATIONS Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes. PROSPERO REGISTRATION NUMBER CRD42017056524.