Miracle-dz/UniFAR-FTUs huggingface dataset:
SIBLING- AND FAMILY-LEVEL CLUSTERING OF UNDERWEIGHT CHILDREN IN NORTHERN INDIA

Summary Child undernutrition remains a major child health and developmental issue in low- and middle-income countries. The concentration (clustering) of underweight children among siblings at the family level is known to exist in India. This study examined the extent and covariates of clustering of underweight children at the sibling and family level in Uttar Pradesh, the largest state of northern India. Clustering of underweight (low weight-for-age) children was assessed using data on 7533 under-five children from the National Family Health Survey (NFHS) conducted in 2005–06, analysed using binary logistic and binomial regression models. Related bio-demographic, socioeconomic and health care variables were used as covariates in the models. The odds of being underweight for the index child were about two times higher (OR=2.34, p<0.001) if any of the siblings within the household was malnourished or underweight. A longer birth interval increased the odds of a child being underweight. The odds of underweight were significantly lower (OR=0.69, p<0.001) for children born to normal-weight mothers compared with those born to underweight mothers. Similarly, the odds of underweight were significantly lower (OR=0.49, p=0.01) for children born to educated mothers (high school and above) compared with those born to illiterate mothers. The results of the binomial regression model suggested that the deviations between observed and expected number of children were positive (3.09, 3.78 and 2.71) for 1, 2 and 2+ underweight children within the households of underweight women, indicating the concentration of underweight children among underweight/malnourished mothers. Underweight children were found to be clustered among underweight mothers with multiple underweight siblings. The findings suggest that policy interventions need to focus on underweight mothers with multiple underweight children.
Is parity a risk factor for excessive weight gain during pregnancy and postpartum weight retention? A systematic review and meta‐analysis

The aim of this study was to systematically review and meta‐analyse the associations between parity, pre‐pregnancy body mass index (BMI), gestational weight gain (GWG) and, when included, postpartum weight retention (PPWR). Papers reporting associations between parity and BMI and/or GWG in adult women were eligible: 2,195 papers were identified, and 41 longitudinal studies were included in the narrative synthesis; 17 studies were included in a meta‐analysis. Findings indicated that parity was associated positively with pre‐pregnancy BMI. In contrast, the role of parity in GWG was less clear; both positive and negative relationships were reported across studies. Parity was not associated directly with PPWR. This pattern of results was supported by our meta‐analysis with the only significant association between parity and pre‐pregnancy BMI. Overall, parity was associated with higher pre‐pregnancy BMI; however, the role of parity in GWG and PPWR remains unclear, and it is likely that its influence is indirect and complex. Further research to better understand the contribution of parity to maternal obesity is warranted.
Triangular Resection for Repair of Mitral Regurgitation Due to Degenerative Disease

p egenerative mitral valve disease is now the most common cause of mitral regurgitation in an aging Western opulation because of a decline in postinflammatory rheuatic valve pathology.1 The diagnosis of mitral valve proapse caused by leaflet degeneration can easily be made by chocardiography. Recent guidelines and publications ave underlined the importance of the early echocardioraphic diagnosis and quantification of mitral regurgitaion leading to prompt surgical correction of moderate-toevere regurgitation before the onset of left ventricular LV) dilation and decreased LV function. This is also the ase in asymptomatic patients.2 Mitral repair offers the dvantage of improved perioperative and long-term surival, greater regression of LV dimension, and the mainteance of LV function. Mitral repair has durability at least quivalent to replacement and offers the freedom from ong-term anticoagulation. Despite the advantages of miral valve repair, it is currently only performed in roughly 0% of patients undergoing operation for mitral regurgiation in the United States according to the Society of horacic Surgeons’ voluntary database. The remaining ajority undergo mitral valve replacement. This practice ay be due to the assumption that reparative techniques re complicated. Some of the more intricate procedures reviously popularized have led to the perception that itral valve repair is an elitist operation and may not be ndertaken successfully by the community cardiac sureon. The purpose of this article is to familiarize all cardiac urgeons with a more user-friendly, reproducible, and duable valve repair. Mitral regurgitation secondary to degenerative valve disase is most commonly caused by segmental leaflet prolapse ue to ruptured or elongated chordae tendineae. Statistically, he middle of the posterior leaflet, or P2, is the most common ulprit and, fortuitously, also the easiest leaflet to repair. The echniques for the repair of this particular lesion will be decribed. A durable repair can be performed in approximately 8% of patients with a mortality of less than 1%. 3
Precision in Central Venous Catheter Tip Placement: A Review of the Literature

Abstract Background Long term venous catheters have been used to deliver specialized therapies since 1968. The ideal tip position of a central venous catheter provides reliable venous access with optimal therapeutic delivery, while minimizing short-and long-term complications. Ideal position limits have evolved and narrowed over time, making successful placement difficult and unreliable when depending exclusively on the landmark technique. Objective To review and analyze contemporary literature and calculate an overall accuracy rate for first attempt placement of a PICC catheter in the ideal tip position. Methods Key PICC placement terms were used to search the database PubMED-indexed for MEDLINE in June and October, 2009. The selection of studies required: a patient cohort without tip placement guidance technology; a documented landmark technique to place catheter tips; data documenting initial catheter placement and, that the lower third of the SVC and the cavo-atrial junction (CAJ) were included in the placement criteria. With few exceptions, articles written between 1993 and 2009 met the stated selection criteria. A composite of outcomes associated with tip placement was analyzed, and an overall percent proficiency of accurate catheter tip placement calculated. Results Nine studies in eight articles met the selection criteria and were included for analysis. Rates of first placement success per study ranged from 39% to 75%, with the majority (7/9) being single center studies. The combined overall proficiency of these studies calculated as a weighted average was 45.87%.
Inter‐individual differences in weight change following exercise interventions: a systematic review and meta‐analysis of randomized controlled trials

Previous reports of substantial inter‐individual differences in weight change following an exercise intervention are often based solely on the observed responses in the intervention group. Therefore, we aimed to quantify the magnitude of inter‐individual differences in exercise‐mediated weight change. We synthesized randomized controlled trials (RCTs) of structured, supervised exercise interventions. Fourteen electronic databases were searched for relevant studies published up to March 2017. Search terms focused on structured training, RCTs and body weight. We then sifted these results for those RCTs (n = 12, 1500 participants) that included relevant comparator group data. Standard deviations (SDs) of weight change were extracted, thereby allowing the SD for true inter‐individual differences in weight loss to be calculated for each study. Using a random effects meta‐analysis, the pooled SD (95% CI) for true individual responses was 0.8 (−0.9 to 1.4) kg. The 95% prediction interval (based on 2SDs) for true inter‐individual responses was −2.8 to 3.6 kg. The probability (% chance) that the true individual response variability would be clinically meaningful (>2.5 kg) in a future study in similar settings was 23% (‘unlikely’). Therefore, we conclude that evidence is limited for the notion that there are clinically important individual differences in exercise‐mediated weight change.
piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells

Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose constant threats to genomic integrity. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. Pezic et al. show the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in mammalian germ cells. The analyses reveal that the piRNA pathway targets full-length elements of actively transposing LINE families but not the copious small fragments present throughout the genome.
R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal

Cai et al. find that Rspo1 cooperates with another hormonal mediator, Wnt4, to promote mammary stem cell (MaSC) self-renewal through Wnt/β-catenin signaling. Hormonal treatment that stimulates the expression of both Rspo1 and Wnt4 can completely substitute for exogenous Wnt proteins, potently expand MaSCs, and maintain their full development potential in transplantation. This study shows that hormones can induce a collaborative local niche environment for stem cells.
A post-translational regulatory switch on UPF1 controls targeted mRNA degradation

Nonsense-mediated mRNA decay (NMD) controls the quality of eukaryotic gene expression and also degrades physiologic mRNAs. Here, Kurosaki et al. mapped phosphorylated UPF1-binding sites and found them to be enriched on NMD target 3′ UTRs along with SMG5 and SMG7. ATPase/helicase-deficient UPF1 manifests high levels of RNA binding and disregulated hyperphosphorylation. 3′ UTR-associated UPF1 undergoes regulated phosphorylation, providing a binding platform for mRNA-degradative activities.
Effect of subacute ruminal acidosis on milk fat concentration, yield and fatty acid profile of dairy cows receiving soybean oil

The objective of this study was to investigate the effect of ruminal infusion of soybean oil (SBO) with either a moderate- or high-forage diet on fat concentration, yield and composition in milk from dairy cows. Six rumen-fistulated Holstein dairy cows (639±51 kg body weight, 140±59 days in milk) were used in the study. Cows were randomly assigned to one of two dietary treatments, a high forage:concentrate (HFC, 74:26) or a moderate forage:concentrate (MFC, 56:44) total mixed ration. Cows were fed at 08.00 and 13.00 h and pulse-dosed ruminally at 13.00 h over a 10-min duration with 2% of diet dry matter of SBO. Ruminal pH was recorded continuously. Cows receiving the MFC treatment had lower daily mean ruminal pH and ruminal pH was below 6·0 for a longer duration compared with the HFC treatment (640 vs. 262 min/d, P<0·05). Cows receiving the MFC treatment had a greater reduction (diet by week interaction, P<0·05) in milk fat concentration and yield than cows receiving the HFC treatment (42 vs. 22% and 45 vs. 21%, respectively). Additionally, cows receiving the MFC diet had a greater reduction in milk fat concentration (g/100 g FA) of FA C16 (17 vs. 9%), trans-10 18:1 (159 vs. 21%) and trans-9, cis-11 conjugated linoleic acid (121 vs. 55%) (P<0·05) compared with cows receiving the HFC diet. This study demonstrated that cows fed the MFC diet had lower ruminal pH and showed a greater rate of milk fat depression when infused with SBO.
Distraction osteogenesis versus orthognathic surgery for the treatment of maxillary hypoplasia in cleft lip and palate patients: a systematic review.

OBJECTIVE To compare the effectiveness of distraction osteogenesis to orthognathic surgery for the treatment of maxillary hypoplasia in individuals with cleft lip and palate. METHOD A systematic review of prospective randomized, quasi-randomized or controlled clinical trials. MEDLINE, EMBASE, Scopus, Web of Science, CINAHL, CENTRAL, trial registers and grey literature were searched. Hand searching of five relevant journals was completed. Two reviewers independently completed inclusion assessment. Data extraction and risk of bias assessment were completed by a single reviewer and checked by a second reviewer. RESULTS Five publications all reporting different outcomes of a single randomized controlled trial are included within the review. The quality of the evidence was low with a high risk of bias. Both surgical interventions produce significant soft tissue improvement. Horizontal relapse of the maxilla was statistically significantly greater following orthognathic surgery. There was no statistically significant difference in speech and velo-pharyngeal function between the interventions. Maxillary distraction initially lowered social self-esteem, but this improved with time resulting in higher satisfaction with life in the long term. CONCLUSIONS The low quality of evidence included within the review means there is insufficient evidence to conclude whether there is a difference in effectiveness between maxillary distraction and osteotomy for the treatment of cleft-related maxillary hypoplasia. There is a need for further high-quality randomized controlled trials to allow conclusive recommendations to be made.
Phenotype-genotype correlations of facial width and height proportions in patients with Class II malocclusion.

OBJECTIVES To characterize soft-tissue facial height and width variation in Class II malocclusion and test for correlations with genes HMGA2, AJUBA, and ADK. SETTING AND SAMPLE POPULATION Nine facial proportions were estimated from 2D frontal repose photographs of 330 Caucasian adults with Class II malocclusion. MATERIAL AND METHODS After adjustments for age and gender, the facial proportions were submitted to a principal component analyses (PCA). The most meaningful phenotypic variations were correlated with SNPs rs7924176 (ADK), rs17101923 (HMGA2), and rs997154 (AJUBA) genotyped in 106 individuals. RESULTS Principal component analyses resulted in four principal components (PCs), which explained 75% of total variation. PC1 captured variation in the intercanthus distance and explained 28% of total variation. PC2 explained 21% of the variations in facial taper and facial index. PC3 explained 14% and reflected variations in the vertical dimension of the lower face. PC4 explained 12% and captured variations in distance between the eyes, width of the commissures, and the length of the superior aspect of the lower face height corresponding to the vertical dimension of the philtrum of the upper lip. A suggestive association (p<0.05) was observed between PC4 and rs997154 corroborating the role of AJUBA in variation of facial dimensions. CONCLUSION 2D frontal photographs can be used to derive quantitative measures of soft-tissue phenotypes that are of clinical relevance. The methods described are suitable for discovery and replication of associations between genotypes and malocclusion phenotypes.
The SAGA coactivator complex acts on the whole transcribed genome and is required for RNA polymerase II transcription

The SAGA coactivator complex contains distinct chromatin-modifying activities and is recruited by DNA-bound activators to regulate the expression of a subset of genes. Bonnet et al. discovered that SAGA acetylates the promoters and deubiquitinates the transcribed region of all expressed genes. SAGA also plays a critical role for RNA polymerase II recruitment at all expressed genes. This study uncovers a new function for SAGA as a bona fide cofactor for all RNA polymerase II transcription.
Structural basis for corepressor assembly by the orphan nuclear receptor TLX

The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Zhi et al. report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. Mutations that weaken the TLX–Atrophin interaction compromise the repressive activity of TLX. In addition, mutations of corresponding residues in other members of this class of receptors diminish their repressor activities.
The poly(A)-binding protein Nab2 functions in RNA polymerase III transcription

Reuter et al. show that Nab2, a poly(A)-binding protein important for correct poly(A) tail length and nuclear mRNA export, is present at all RNA polymerase III (RNAPIII) transcribed genes. Nab2 is required for the occupancy of RNAPIII and TFIIIB at target genes.
Microvessel density and VEGF, HIF-1α expression in primary oral melanoma: correlation with prognosis.

OBJECTIVE To understand the role of angiogenesis and hypoxia in cancer progression of primary oral melanoma (POM). MATERIALS AND METHODS Sixteen malignant primary melanomas were immunostained with markers CD34, VEGF and HIF-1α. Stained cells were counted in the invasive front and inside the tumour, and the differences were compared and correlated with histological parameters and disease-specific survival of the patients. RESULTS Tumour invasive front showed increased MVD and increased vessel VEGF and HIF-1α expression compared with the intratumoural compartment. No such differences were seen in tumoural melanocytes of the two compartments. Positive correlations were observed between CD34 and VEGF, CD34 and HIF-1α and VEGF and HIF-1α expression in invasive front vessels. CD34 expression was statistically correlated with the level of infiltration. A significant trend to worse disease-free survival was also determined with increased invasive front vessel expression of CD34, VEGF and HIF-1α. CONCLUSIONS Our data highlight the importance of the invasive margin in POM biology. The high angiogenic activity and endothelial VEGF and HIF-1α expression in invasive front vessels have a significant impact on patient survival and future agents targeted against VEGF pathway may represent a novel and effective therapeutic opportunity. Larger studies are needed to further address our findings.
Replacing wheat with canola meal and maize grain in the diet of lactating dairy cows: Feed intake, milk production and cow condition responses

This research paper describes the effect of partially replacing wheat with maize grain and canola meal on milk production and body condition changes in early lactation Holstein-Friesian dairy cows consuming a grass silage-based diet over an 83-d period. Two groups of 39 cows were stratified for age, parity, historical milk yield and days in milk (DIM), and offered one of two treatment diets. The first treatment (CON) reflected a typical diet used by Western Australian dairy producers in summer and comprised (kg DM/cow per d); 8 kg of annual ryegrass silage, 6 kg of crushed wheat (provided once daily in a mixed ration), 3·6 kg of crushed lupins (provided in the milking parlour in two daily portions) and ad libitum lucerne haylage. The second treatment diet (COMP) was identical except the 6 kg of crushed wheat was replaced by 6 kg of a more complex concentrate mix (27% crushed wheat, 34% maize grain and 37% canola meal). Lucerne haylage was provided independently in the paddock to all cows, and no pasture was available throughout the experiment. The COMP group had a greater mean overall daily intake (22·5 vs 20·4 kg DM/cow) and a higher energy corrected milk (ECM) yield (29·2 vs 27·1 kg/cow; P = 0·047) than the CON cows. The difference in overall intake was caused by a higher daily intake of lucerne haylage in COMP cows (4·5 vs 2·3 kg DM/cow). The CON group had a higher concentration of milk fat (42·1 vs 39·3 g/kg; P = 0·029) than COMP cows. Milk protein yield was greater in COMP cows (P < 0·021); however, milk fat yield was unaffected by treatment. It is concluded that partially replacing wheat with canola meal and maize grain in a grass silage-based diet increases voluntary DMI of conserved forage and consequently yields of ECM and milk protein.
Levels of sirolimus in saliva and blood following mouthwash application.

OBJECTIVES Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with antiproliferative activity. Its systemic administration is currently evaluated for the management of squamous cell carcinoma and various oral disorders. Topical oral application can enhance availability, efficacy and improve safety and compliance. Our objective was to evaluate the release profile and the safety of a sirolimus mouthwash. SUBJECTS AND METHODS A sirolimus mouthwash (0.05 mg ml(-1) ) was applied to ten healthy male volunteers. Saliva and blood samples were taken after rinsing. Mass spectrometry and chemiluminescent microparticle immunoassay were used to determine saliva and blood levels of sirolimus. A topical oral release profile measurement and safety evaluation were performed. RESULTS After rinsing with the mouthwash, a classic immediate release profile was noted in the oral cavity. Extremely high initial sirolimus levels rapidly declined over a 4-hour period. Systemic exposure was limited, with a maximum level significantly lower than therapeutic doses, and safety was confirmed. CONCLUSIONS A single rinse with sirolimus mouthwash leads to high transient levels of the drug in the saliva. Although levels were variable, a therapeutic concentration was achieved topically along with minimal systemic absorption. These results broaden the potential clinical use of oral topical rapalogs.
EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex

Shapira et al. show that EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes. They identified the histone reader protein DPF3 as a brown fat-selective component of the BAF complex that was required for brown fat gene programming and mitochondrial function.
Rumination time as a potential predictor of common diseases in high-productive Holstein dairy cows

We examined the hypothesis that rumination time (RT) could serve as a useful predictor of various common diseases of high producing dairy cows and hence improve herd management and animal wellbeing. We measured the changes in rumination time (RT) in the days before the recording of diseases (specifically: mastitis, reproductive system diseases, locomotor system issues, and gastroenteric diseases). We built predictive models to assess the association between RT and these diseases, using the former as the outcome variable, and to study the effects of the latter on the former. The average Pseudo-R 2 of the fitted models was moderate to low, and this could be due to the fact that RT is influenced by other additional factors which have a greater effect than the predictors used here. Although remaining in a moderate-to-low range, the average Pseudo-R 2 of the models regarding locomotion issues and gastroenteric diseases was higher than the others, suggesting the greater effect of these diseases on RT. The results are encouraging, but further work is needed if these models are to become useful predictors.
Integrating Health and Social Care Teams in Salford

Salford City Council and Salford Primary Care Trust have established eight ‘integrated health and social care teams’ across the city, supporting older people and vulnerable adults. Teams are aligned with GP practice‐based commissioning clusters. The evaluation of the initial pilot identified success factors, barriers and lessons learnt in order to plan and roll out systematic implementation across the city. The evaluation and subsequent staff development programme supporting change management were designed and delivered in partnership with Manchester Business School. Improved access to and delivery of services were achieved.