Miracle-dz/UniFAR-FTUs huggingface dataset:
Independent and Cooperative Roles of Adaptor Molecules in Proximal Signaling during FcεRI-Mediated Mast Cell Activation

ABSTRACT Activation through FcεRI, a high-affinity IgE-binding receptor, is critical for mast cell function during allergy. The formation of a multimolecular proximal signaling complex nucleated by the adaptor molecules SLP-76 and LAT1 is required for activation through this receptor. Based on previous T-cell studies, current dogma dictates that LAT1 is required for plasma membrane recruitment and function of SLP-76. Unexpectedly, we found that the recruitment and phosphorylation of SLP-76 were preserved in LAT1−/− mast cells and that SLP-76−/− and LAT1−/− mast cells harbored distinct functional and biochemical defects. The LAT1-like molecule LAT2 was responsible for the preserved membrane localization and phosphorylation of SLP-76 in LAT1−/− mast cells. Although LAT2 supported SLP-76 phosphorylation and recruitment to the plasma membrane, LAT2 only partially compensated for LAT1-mediated cell signaling due to its decreased ability to stabilize interactions with phospholipase Cγ (PLCγ). Comparison of SLP-76−/− LAT1−/− and SLP-76−/− mast cells revealed that some functions of LAT1 could occur independently of SLP-76. We propose that while SLP-76 and LAT1 depend on each other for many of their functions, LAT2/SLP-76 interactions and SLP-76-independent LAT1 functions also mediate a positive signaling pathway downstream of FcεRI in mast cells.
Treatment with combined dabrafenib and trametinib in BRAFV600E-mutated metastatic malignant melanoma: a case of long-term complete response after treatment cessation

Here, we report the case of a patient, diagnosed with BRAFV600E-mutated metastatic malignant melanoma M1a, who achieved a complete metabolic response after 7 months of treatment with the combination of dabrafenib and trametinib. After 31 months, the treatment was interrupted for patient’s decision. To date October 2017, 18 months after the interruption of the treatment with the combination of dabrafenib and trametinib, follow-up Positron Emission Tomography (PET) scans are still documenting complete metabolic response.
Low serum phosphate as an independent predictor of increased infection-related mortality in dialysis patients: A prospective multicenter cohort study

Background The role of mineral metabolism in mortality among dialysis patients has received increased attention, but some aspects remain unclear. The aim of the present study was to investigate the prognostic value of serum calcium and phosphate levels for all-cause mortality and cause-specific mortality in dialysis patients. Methods Patients on hemodialysis and peritoneal dialysis were enrolled from a multicenter prospective cohort study in Korea (NCT00931970). The patients were divided into low, normal, and high groups according to their baseline serum calcium or phosphate levels. Cox proportional analysis and a proportional hazards model for the subdistribution of a competing risk were used to calculate hazard ratios (HRs) for the association of serum calcium and phosphate levels with all-cause and cause-specific mortality. Time-dependent values of calcium and phosphate were also evaluated to assess the effect of longitudinal change in mineral metabolism parameters on mortality types. Results A total of 3,226 dialysis patients were followed up for a mean of 19.8 ± 8.2 months. Infection was the most common cause of death. Low serum phosphate was significantly associated with all-cause and infection-related death using time-dependent values (HR, 1.43 [95% confidence interval (CI), 1.06–1.93], P = 0.02, and HR, 1.66 [95% CI, 1.02–2.70], P = 0.04, respectively). Low serum phosphate was associated with significantly higher infection-related mortality, especially in patients older than 65 years or on dialysis more than one year or with serum albumin lower than 3.9 g/dL (HR, 2.06 [95% CI, 1.13–3.75], P = 0.02, HR, 2.19 [95% CI, 1.20–4.01], P = 0.01, and HR, 1.77 [95% CI, 1.00–3.13], P = 0.05, respectively). Multinomial logistic regression analysis results suggested that low serum albumin, creatinine, and body mass index correlated with low serum phosphate. Conclusions Low serum phosphate in dialysis patients was an independent risk factor for infection-related death, especially in elderly patients. Persistently low serum phosphate might be a nutritional biomarker to predict increased susceptibility to infection and in turn worse outcomes in dialysis patients.
Impact of Preoperative Depression on Hospital Consumer Assessment of Healthcare Providers and Systems Survey Results in a Lumbar Fusion Population

Study Design. A retrospective cohort study at a single institution. Objective. To determine the effect of preoperative depression on Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey scores in a lumbar fusion population. Summary of Background Data. HCAHPS surveys are used to assess the quality of the patient experience, and directly influences reimbursement for hospital systems and spine surgeons nationwide. Untreated depression has been linked to worse functional outcomes in spine surgery. We, however, aimed to elucidate whether HCAHPS survey responses were different in depressed patients. Methods. Prospectively collected functional outcome data including Patient Health Questionnaire 9, EuroQol five dimensions, and Pain Disability Questionnaire were analyzed preoperatively. Preoperative Patient Health Questionnaire 9 scores of greater than or equal to 10 (moderate to severe depression) defined our depressed cohort of patients. HCAHPS responses were obtained for each individual, allowing for real-world analysis of outcomes in this population. Results. In our 237 patient cohort, depressed patients were younger, female; were on full disability; and had lower scores on EuroQol five dimensions and Pain Disability Questionnaire preoperatively. Approximately 73.2% of depressed patients felt doctors treated them with respect, compared to 88.8% of patients without depression (P = 0.005). Also, depressed patients felt nurses treated them with less respect (P = 0.014) and that physicians did not listen to them as carefully (P = 0.029). Multivariate regression analysis revealed that patients with preoperative depression had higher odds of patients feeling less respected by both physicians and nurses. Multivariate analysis also revealed that depression was an independent predictor of lower patient satisfaction with nursing response to their needs. Conclusion. In patients undergoing lumbar fusion, preoperative depression was shown to have negative effect on patient experience measured by the HCAHPS survey. These results suggest that depression may be a modifiable risk factor for poor hospital experience. Level of Evidence: 3
Angiostrongylus cantonensis Meningitis and Myelitis, Texas, USA

Infection with Angiostrongylus cantonensis roundworms is endemic in Southeast Asia and the Pacific Basin. A. cantonensis meningitis and myelitis occurred in summer 2013 in a child with no history of travel outside of Texas, USA. Angiostrongyliasis is an emerging neurotropic helminthic disease in Texas and warrants increased awareness among healthcare providers.
Two interacting atoms in an optical lattice site with anharmonic terms

We propose an easy to use model for interacting atoms in an optical lattice. This model allows for the whole range of weakly to strongly interacting atoms, and it includes the coupling between relative and center-of-mass motions via anharmonic lattice terms. We apply this model to a high-precision spin-dynamics experiment, and we discuss the corrections due to atomic interactions and the anharmonic coupling. Under suitable experimental conditions, energy can be transferred between the relative and center-of-mass motions, and this allows for creation of Feshbach molecules in excited lattice bands.
External beam radiotherapy in differentiated thyroid carcinoma: A systematic review

External beam radiotherapy (EBRT) is not a first line treatment in differentiated thyroid carcinoma (DTC), but is recommended as an adjuvant treatment in certain cases. The evidence for EBRT in DTC is limited. A comprehensive literature search was performed. Data on patient demographics, disease stage, treatment characteristics, and outcomes were collected from included articles after quality appraisal. Sixteen articles met the inclusion criteria, with a pooled population of 5114. Only 1 study was prospective and there were no randomized controlled trials. Most of the evidence suggests that EBRT improves locoregional control in patients at high risk of locoregional recurrence. This was corroborated by analysis of pooled patient data. Available evidence suggests an improvement in locoregional control when EBRT is used in patients over the age of 45 at high risk for locoregional recurrence. However, there is a need for long‐term prospective multicenter research on the subject. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2297–E2305, 2016
Functional trade‐offs and the phylogenetic dispersion of seed traits in a biodiversity hotspot of the Mountains of Southwest China

Abstract The diversity of traits associated with plant regeneration is often shaped by functional trade‐offs where plants typically do not excel at every function because resources allocated to one function cannot be allocated to another. By analyzing correlations among seed traits, empirical studies have shown that there is a trade‐off between seedling development and the occupation of new habitats, although only a small range of taxa have been tested; whether such trade‐off exists in a biodiverse and complex landscape remains unclear. Here, we amassed seed trait data of 1,119 species from a biodiversity hotspot of the Mountains of Southwest China and analyzed the relationship between seed mass and the number of seeds and between seed mass and time to germination. Our results showed that seed mass was negatively correlated with seed number but positively correlated with time to germination. The same trend was found regardless of variation in life‐form and phylogenetic conservatism. Furthermore, the relation between seed mass and other seed traits was randomly dispersed across the phylogeny at both the order and family levels. Collectively, results suggest that there is a functional trade‐off between seedling development and new habitat occupation for seed plants in this region. Larger seeds tend to produce fewer seedlings but with greater fitness compared to those produced by smaller seeds, whereas smaller seeds tend to have a larger number of seeds that germinate faster compared to large‐seeded species. Apart from genetic constraints, species that produce large seeds will succeed in sites where resource availability is low, whereas species with high colonization ability (those that produce a high number of seeds per fruit) will succeed in new niches. This study provides a mechanistic explanation for the relatively high levels of plant diversity currently found in a heterogeneous region of the Mountains of Southwest China.
Acceptability of Iron- and Zinc-Biofortified Pearl Millet (ICTP-8203)-Based Complementary Foods among Children in an Urban Slum of Mumbai, India

Biofortification, a method for increasing micronutrient content of staple crops, is a promising strategy for combating major global health problems, such as iron and zinc deficiency. We examined the acceptability of recipes prepared using iron- and zinc-biofortified pearl millet (FeZnPM) (~80 ppm Fe, ~34 ppm Zn, varietal ICTP-8203), compared to conventional pearl millet (CPM) (~20 ppm Fe, ~19 ppm Zn) in preparation for an efficacy trial. Our objective was to examine the acceptability of FeZnPM compared to CPM among young children and mothers living in the urban slums of Mumbai. Standardized traditional feeding program recipes (n = 18) were prepared with either FeZnPM or CPM flour. The weight (g) of each food product was measured before and after consumption by children (n = 125) and the average grams consumed over a 3-day period were recorded. Mothers (n = 60) rated recipes using a 9-point hedonic scale. Mean intakes and hedonic scores of each food product were compared using t-tests across the two types of pearl millet. There were no statistically significant differences in consumption by children (FeZnPM: 25.27 ± 13.0 g; CPM: 21.72 ± 6.90 g) across the food products (P = 0.28). Overall mean hedonic scores for all recipes were between 7 to 9 points. CPM products were rated higher overall (8.22 ± 0.28) compared to FeZnPM products (7.95 ± 0.35) (P = 0.01). FeZnPM and CPM were similarly consumed and had high hedonic scores, demonstrating high acceptability in this population. These results support using these varieties of pearl millet in a proposed trial [http://Clinicaltrials.gov ID: NCT02233764; Clinical Trials Registry of India (CTRI), reference number REF/2014/10/007731, CTRI number CTRI/2015/11/006376] testing the efficacy of FeZnPM for improving iron status and growth.
Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review

Atherosclerosis is a multifactorial disease triggered and sustained by different risk factors such as dyslipidemia, arterial hypertension, diabetes mellitus, smoke, etc. Since a couple of decades, a pivotal role for inflammation in its pathogenesis has been recognized and proved at molecular levels, and already described in many animal models. Despite all this knowledge, due to the complexity of the specific inflammatory process subtending atherosclerosis and to the fact that inflammation is also a protective response against microorganisms, no anti-inflammatory therapy has been rendered available in the therapeutic armamentarium against atherosclerosis and vascular events till 2017 when canakinumab in the first ad-hoc randomized clinical trial (RCT) proved for the first time that targeting specifically inflammation lowers cardiovascular (CV) events. From the genetic side, in the 90's and early 2000, several genetic markers in inflammatory pathway have been explored searching for an association with athero-thrombosis which gave seldom consistent results. Then, in the genomic era, plenty of genetic markers covering most of the genome have been analyzed at once without a priori information. The results coming from genome wide association studies (GWAS) have pinpointed some loci closed to inflammatory molecules consistently associated with atherosclerosis and CV consequences revamping the strict link between inflammation and atherosclerosis and suggesting some tailored target therapy. Whole-exome and whole-genome sequencing will come soon showing new and old loci associated with atherosclerosis suggesting new molecular targets or underlying which inflammatory pathway could be most attractive to target for blocking atherosclerosis even in its early stages.
Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells

Purpose: Previously, we showed that adoptive transfer of in vivo vaccine-primed and ex vivo (anti-CD3/anti-CD28) costimulated autologous T cells (ex-T) at day +12 after transplant increased CD4 and CD8 T-cell counts at day +42 and augmented vaccine-specific immune responses in patients with myeloma. Here, we investigated the safety and kinetics of T-cell recovery after infusing ex-T at day +2 after transplant. Experimental Design: In this phase I/II two-arm clinical trial, 50 patients with myeloma received autografts after high-dose melphalan followed by infusions of ex-T at day +2 after transplant. Patients also received pretransplant and posttransplant immunizations using a pneumococcal conjugate vaccine only (arm B; n = 24) or the pneumococcal conjugate vaccine plus an HLA-A2–restricted multipeptide vaccine for HLA-A2+ patients (arm A; n = 26). Results: The mean number of T cells infused was 4.26 × 1010 (range, 1.59-5.0). At day 14 after transplant, the median CD3, CD4, and CD8 counts were 4,198, 1,545, and 2,858 cells/μL, respectively. Interleukin (IL)-6 and IL-15 levels increased early after transplant and IL-15 levels correlated significantly to day 14 T-cell counts. Robust vaccine-specific B- and T-cell responses were generated. T-cell infusions were well tolerated with no effect on hematopoietic recovery. Eight patients (16%) developed a T-cell “engraftment syndrome” characterized by diarrhea and fever that was clinically and histopathologically indistinguishable from grade 1 to 3 acute graft-versus-host disease (GVHD) of the gastrointestinal tract (seven patients) and/or grade 1 to 2 cutaneous GVHD (four patients). Conclusions: Adoptive T-cell transfers achieve robust T-cell recovery early after transplant and induce moderate-to-severe autologous GVHD in a subset of patients.
Intimate partner violence in urban Pakistan: prevalence, frequency, and risk factors

Background: Intimate partner violence (IPV) is an important public health issue with severe adverse consequences. Population-based data on IPV from Muslim societies are scarce, and Pakistan is no exception. This study was conducted among women residing in urban Karachi, to estimate the prevalence and frequency of different forms of IPV and their associations with sociodemographic factors. Methods: This cross-sectional community-based study was conducted using a structured questionnaire developed by the World Health Organisation for research on violence. Community midwives conducted face-to-face interviews with 759 married women aged 25–60 years. Results: Self-reported past-year and lifetime prevalence of physical violence was 56.3 and 57.6%, respectively; the corresponding figures for sexual violence were 53.4% and 54.5%, and for psychological abuse were 81.8% and 83.6%. Violent incidents were mostly reported to have occurred on more than three occasions during the lifetime. Risk factors for physical violence related mainly to the husband, his low educational attainment, unskilled worker status, and five or more family members living in one household. For sexual violence, the risk factors were the respondent’s low educational attainment, low socioeconomic status of the family, and five or more family members in one household. For psychological violence, the risk factors were the husband being an unskilled worker and low socioeconomic status of the family. Conclusion: Repeated violence perpetrated by a husband towards his wife is an extremely common phenomenon in Karachi, Pakistan. Indifference to this type of violence against women stems from the attitude that IPV is a private matter, usually considered a justifiable response to misbehavior on the part of the wife. These findings point to serious violations of women’s rights and require the immediate attention of health professionals and policymakers.
Comparison of sediment transport models on river Omi, South-Western Nigeria

The processes of sediment transport, scour, and deposition in an alluvial channel are extremely complex. Theoretical developments of sediment transport functions for different flow and sediment conditions are based on assumptions of different degrees of complexity [1]. Some of the simplified assumptions are based on idealized laboratory conditions that may not be true for the much more complicated natural river systems [2,3]. Ahmed & Medhaat [4] and Chang [5] opined that sediment transport is an important part in the quantitave and qualitative management of river engineering. The rate of sediment transport in water bodies depends on availability of transport materials and transport capability of the water bodies. For a scientific approach to sedimentation, morphology and behaviour of the river must be understood. Morphology (of river) is a field of science which deals with the change of river plan form and cross sections due to sedimentation and erosion. In this field, dynamics of flow and sediment transport are the principal elements [6]. The morphological studies, therefore, play an important role in planning, designing and maintaining river engineering structures. In recent years, there has been a growing awareness about the need for taking up morphological study of rivers in the country, especially with particular reference to their unique problems [7,8].
Longitudinal network structure of depression symptoms and self-efficacy in low-income mothers

Maternal depression was recently conceptualized as a network of interacting symptoms. Prior studies have shown that low self-efficacy, as an index of maternal functioning, is one important source of stress that worsens depression. We have limited information, however, on the specific relationships between depression symptoms and self-efficacy. In this study, we used regularized partial correlation networks to explore the multivariate relationships between maternal depression symptoms and self-efficacy over time. Depressed mothers (n = 306) completed the Center for Epidemiological Studies Depression (CES-D) scale at four time points, between four and eight weeks apart. We estimated (a) the network structure of the 20 CES-D depression symptoms and self-efficacy for each time point, (b) determined the centrality or structural importance of all variables, and (c) tested whether the network structure changed over time. In the resulting networks, self-efficacy was mostly negatively connected with depression symptoms. The strongest relationships among depression symptoms were ‘lonely—sleep difficulties’ and ‘inability to get going—crying’. ‘Feeling disliked’ and ‘concentration difficulty’ were the two most central symptoms. In comparing the network structures, we found that the network structures were moderately stable over time. This is the first study to investigate the network structure and their temporal stability of maternal depression symptoms and self-efficacy in low-income depressed mothers. We discuss how these findings might help future research to identify clinically relevant symptom-to-symptom relationships that could drive maternal depression processes, and potentially inform tailored interventions. We share data and analytical code, making our results fully reproducible.
A fast small‐sample kernel independence test for microbiome community‐level association analysis

To fully understand the role of microbiome in human health and diseases, researchers are increasingly interested in assessing the relationship between microbiome composition and host genomic data. The dimensionality of the data as well as complex relationships between microbiota and host genomics pose considerable challenges for analysis. In this article, we apply a kernel RV coefficient (KRV) test to evaluate the overall association between host gene expression and microbiome composition. The KRV statistic can capture nonlinear correlations and complex relationships among the individual data types and between gene expression and microbiome composition through measuring general dependency. Testing proceeds via a similar route as existing tests of the generalized RV coefficients and allows for rapid p‐value calculation. Strategies to allow adjustment for confounding effects, which is crucial for avoiding misleading results, and to alleviate the problem of selecting the most favorable kernel are considered. Simulation studies show that KRV is useful in testing statistical independence with finite samples given the kernels are appropriately chosen, and can powerfully identify existing associations between microbiome composition and host genomic data while protecting type I error. We apply the KRV to a microbiome study examining the relationship between host transcriptome and microbiome composition within the context of inflammatory bowel disease and are able to derive new biological insights and provide formal inference on prior qualitative observations.