Miracle-dz/UniFAR-FTUs huggingface dataset:
Dissecting Genetic Control of HLA-DPB1 Expression and Its Relation to Structural Mismatch Models in Hematopoietic Stem Cell Transplantation

HLA expression levels have been suggested to be genetically controlled by single nucleotide polymorphisms (SNP) in the untranslated regions (UTR), and expression variants have been associated with the outcome of chronic viral infection and hematopoietic stem cell transplantation (HSCT). In particular, the 3′UTR rs9277534-G/A SNP in HLA-DPB1 has been associated with graft-versus-host-disease after HSCT (Expression model); however its relevance in different immune cells and its mode of action have not been systematically addressed. In addition, there is a strong though not complete overlap between the rs9277534-G/A SNP and structural HLA-DPB1 T cell epitope (TCE) groups which have also been associated with HSCT outcome (TCE Structural model). Here we confirm and extend previous findings of significantly higher HLA-DPB1 expression in B cell lines, unstimulated primary B cells, and monocytes homozygous for rs9277534-G compared to those homozygous for rs9277534-A. However, these differences were abrogated by interferon-γ stimulation or differentiation into dendritic cells. We identify at least seven 3′UTR rs9277534-G/A haplotypes differing by a total of 37 SNP, also characterized by linkage to length variants of a short tandem repeat (STR) in intron 2 and TCE group assignment. 3′UTR mapping did not show any significant differences in post-transcriptional regulation assessed by luciferase assays between two representative rs9277534-G/A haplotypes for any of eight overlapping fragments. Moreover, no evidence for alternative splicing associated with the intron 2 STR was obtained by RT-PCR. In an exemplary cohort of 379 HLA-DPB1 mismatched donor-recipient pairs, risk prediction by the Expression model and the Structural TCE model was 36.7% concordant, with the majority of discordances due to non-applicability of the Expression model. HLA-DPB1 from different TCE groups expressed in the absence of the 3′UTR at similar levels by transfected HeLa cells elicited significantly different mean alloreactive CD4+ T-cell responses, as assessed by CD137 upregulation assays in 178 independent cultures. Taken together, our data provide new insights into the cell type-specific and mechanistic basis of the association between the rs9277534-G/A SNP and HLA-DPB1 expression, and show that, despite partial overlap between both models in HSCT risk-prediction, differential alloreactivity determined by the TCE structural model occurs independently from HLA-DPB1 differential expression.
The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in patients with multiple myeloma

ABSTRACT Purpose: While recent studies described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells. In this study we examine the prognostic and predictive value of IKZF1/3 expression in T-cells in patients with MM stage III. Experimental design: We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and 50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined in vivo observations with in vitro assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients. Results: We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response in vitro and that the immunophenotype of patients with high IKZF3 expression shows features that are contrary to the changes induced by immunomodulatory drugs. Although we observed higher IKZF3 expression levels in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment. Conclusion: In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.
The Role of Social Support and the Neighborhood Environment on Physical Activity in Low-income, Mexican-American Women in South Texas

Objectives To determine the relationships between physical activity (PA), the neighborhood environment support for PA, and social support for PA among Mexican-American women living in South Texas. The Enlace study was a randomized controlled trial that tested the effectiveness of a promotora-led PA intervention among low-income Mexican origin women (n=614) living in colonias. Methods The dependent measures included accelerometer-measured average moderate to vigorous physical activity (MVPA) and sedentary breaks and the Community Health Activities Model Program for Seniors PA 41-item questionnaire. The independent measures included the Physical Activity and Neighborhood Environment Scale (PANES) and the 13-item Physical Activity Social Support (PASS) scale. Results Enlace participants were on average 40.4 (standard deviation, 10.3) years old, born in Mexico (86.1%), and uninsured (83.1%). Adjusted linear regression results indicated that each 1-point increment in the PANES overall score was associated with 0.050 (p<0.001) unit increase in sedentary break and a −0.043 (p=0.001) unit decrease in sedentary break duration. Both PANES (β=0.296; p=0.002) and PASS scores (β=0.076; p<0.001) were associated with weekly average self-reported MVPA. Interaction effects were observed between PASS scores and accelerometer-measured frequency of sedentary breaks and sedentary time duration. Conclusions The findings of this study indicate that the relationships between PA and built environment and social support are measure-dependent and suggest that reducing sedentary time in this population may require a closer assessment of social support for PA.
Rapid change of superconductivity and electron-phonon coupling through critical doping in Bi-2212

Conspiring interactions in a cuprate More than 30 years after the discovery of high-temperature superconductivity in copper oxides, its mechanism remains a mystery. Electron pairing mediated solely by lattice vibrations—phonons—is thought to be insufficient to account for the high transition temperatures. He et al. found a rapid and correlated increase of the superconducting gap and electron-phonon interactions as the chemical composition of their bismuth-based cuprate samples was varied across a critical doping concentration. The interplay of electron-phonon with electron-electron interactions may lead to enhanced transition temperatures. Science, this issue p. 62 Angle-resolved photoemission uncovers an interplay between various types of interaction in a cuprate superconductor. Electron-boson coupling plays a key role in superconductivity for many systems. However, in copper-based high–critical temperature (Tc) superconductors, its relation to superconductivity remains controversial despite strong spectroscopic fingerprints. In this study, we used angle-resolved photoemission spectroscopy to find a pronounced correlation between the superconducting gap and the bosonic coupling strength near the Brillouin zone boundary in Bi2Sr2CaCu2O8+δ. The bosonic coupling strength rapidly increases from the overdoped Fermi liquid regime to the optimally doped strange metal, concomitant with the quadrupled superconducting gap and the doubled gap-to-Tc ratio across the pseudogap boundary. This synchronized lattice and electronic response suggests that the effects of electronic interaction and the electron-phonon coupling (EPC) reinforce each other in a positive-feedback loop upon entering the strange-metal regime, which in turn drives a stronger superconductivity.
Enhancing Cultural Sensitivity in a Community Health Care Setting for LGBTQ Patients

ABSTRACT Lesbian, gay, bisexual, transgender, or queer (LGBTQ)-identified individuals, particularly transgender individuals, experience significant health inequities such as increased risk for chronic health conditions and mental health concerns. Discrimination by health care professionals is a major deterrent for LGBTQ individuals to seek health care. The purpose of the article is to offer practice recommendations using targeted community actions to enhance LGBTQ cultural sensitivity in community health care settings. Strategic planning, assessment for readiness to change, environmental strengths, weaknesses, opportunities, and threats analysis, and use of community resources are recommended as part of a basic model for change in a community setting. Outcomes are measured using a cultural competency tool.
Rare variants of the FMN riboswitch class in Clostridium difficile and other bacteria exhibit altered ligand specificity

Many bacteria use flavin mononucleotide (FMN) riboswitches to control the expression of genes responsible for the biosynthesis and transport of this enzyme cofactor or its precursor, riboflavin. Rare variants of FMN riboswitches found in strains of Clostridium difficile and some other bacteria typically control the expression of proteins annotated as transporters, including multidrug efflux pumps. These RNAs no longer recognize FMN, and differ from the original riboswitch consensus sequence at nucleotide positions normally involved in binding of the ribityl and phosphate moieties of the cofactor. Representatives of one of the two variant subtypes were found to bind the FMN precursor riboflavin and the FMN degradation products lumiflavin and lumichrome. Although the biologically relevant ligand sensed by these variant FMN riboswitches remains uncertain, our findings suggest that many strains of C. difficile might use rare riboswitches to sense flavin degradation products and activate transporters for their detoxification.
Psychotic experiences are associated with health anxiety and functional somatic symptoms in preadolescence.

BACKGROUND Health anxiety (HA) is an increasing public health problem related to increased health service costs, and associated with functional somatic symptoms (FSS) and considerable personal suffering. Abnormal bodily experiences which may resemble HA and FSS are common in psychotic disorders, but a potential link between HA and psychosis vulnerability in childhood is largely unexplored. The current study estimates the association between subclinical psychotic experiences (PE) and HA and FSS in a general population cohort of preadolescents. METHODS The study population consisted of 1,572 11-12-year-old children from the Copenhagen Child Cohort 2000. PE were comprehensibly assessed as either present or not present using the Kiddie Schedule of Affective Disorders and Schizophrenia psychosis section. HA and FSS were assessed by self-report on validated questionnaires. Additional variables on general psychopathology, puberty, and chronic somatic illness were also obtained. RESULTS Psychotic experiences were associated with the top 10% high scores of HA (Odds Ratio (OR) 3.2; 95% CI: 2.1-4.8) and FSS (OR 4.6; 95% CI: 3.1-6.9) in univariate analyses. After mutual adjustment, the association was reduced to (HA: OR 2.3; 95% CI: 1.5-3.5; FSS: OR 3.7; 95% CI: 2.4-4.7), suggesting interdependence. Further adjustment for potential confounders and general psychopathology only reduced the associations slightly: HA OR 2.2 (95% CI: 1.4-3.4); FSS OR 3.3 (95% CI: 2.1-5.2). Secondary analyses of subdimensions of HA showed that PE were associated with fears (OR 3.0; 95% CI: 2.0-4.6) and daily impact of HA symptoms (OR 5.0; 95% CI: 3.4-7.5), but not help seeking (OR 1.2; 95% CI: 0.7-2.1). CONCLUSIONS This is the first study to investigate the associations between PE and HA and FSS, respectively. PE were significantly associated with HA and FSS over and above general psychopathology in preadolescence. Individuals with PE expressed high levels of health-related fears and daily impact, but no corresponding help-seeking behavior.
Excellent Glycemic Control Maintained by Open-Source Hybrid Closed-Loop AndroidAPS During and After Sustained Physical Activity.

OBJECTIVE Officially licensed hybrid closed-loop systems are not currently available worldwide; therefore, open-source systems have become increasingly popular. Our aim was to assess the safety, feasibility, and efficacy of an open-source hybrid closed-loop system (AndroidAPS) versus SmartGuard® technology for day-and-night glucose control in children under extreme sports conditions. RESEARCH DESIGN AND METHODS Twenty-two children (16 girls, 6-15 years of age, median HbA1c 56 ± 9 mmol/mol) were enrolled in this pivotal winter sports camp study. The participants were divided into two groups using either the AndroidAPS or SmartGuard technology. Physical exertion was represented by all-day alpine skiing. The primary endpoints were mean glucose level, time below the threshold of 3.9 mmol/L, and time within the target range of 3.9 to 10 mmol/L. RESULTS The children using the AndroidAPS had significantly lower mean glycemia levels (7.2 ± 2.7 vs. 7.7 ± 2.8 mmol/L; 129.6 ± 49 vs. 138.6 ± 50 mg/dL, P < 0.042) than the children using the SmartGuard. The proportion of time below the target (median 5.0% ± 2.5% vs. 3.0% ± 2.3%, P = 0.6) and in the target zone (63% ± 9.5% vs. 63% ± 18%, P = 0.5) did not significantly differ. The AndroidAPS group experienced more frequent malfunctions of the cannula set (median 0.8 ± 0.4 vs. 0.2 ± 0.4, P = 0.02), which could have affected the results. No significant difference was found in the amount of carbohydrates consumed for the prevention and treatment of hypoglycemia [median 40 ± 23 vs. 25 ± 29 g/(patient ·3 days)]. No episodes of severe hypoglycemia or other serious adverse events were noted. CONCLUSIONS This pilot study showed that the AndroidAPS system was a safe and feasible alternative to the SmartGuard Technology.
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis

The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.
Heart Anatomy of Rhincodon typus: Three‐Dimensional X‐Ray Computed Tomography of Plastinated Specimens

In this study, we examined the structure of the heart of the whale shark, Rhincodon typus, using a plastination technique and three‐dimensional X‐ray computer tomography (3DCT). Inspection of the atrium revealed a symmetric distribution of the pectinate muscles attached to the commissures of the sino‐atrial valve, suggesting some functional advantages. The majority of the ventricular wall comprised spongiosa, and compacta accounted for only ~3% of the entire thickness. There were three major fiber orientations in the spongiosa: the fibers on the endocardial side formed trabeculae that were aligned with the blood flow tract, whereas those on the epicardial side formed a circular pattern around the flow tract. Transmural myofibers connected the inner and outer layers in the spongiosa, which may serve as an intraventricular conduction pathway. Plastination and 3DCT is a powerful combination that allowed for multifaceted visualization of the internal structure of rare heart specimens in a nondestructive manner. Anat Rec, 301:1801–1808, 2018. © 2018 Wiley Periodicals, Inc.
Towards Fast and Energy-Efficient Binarized Neural Network Inference on FPGA

Binarized Neural Network (BNN) removes bitwidth redundancy in classical CNN by using a single bit (-1/+1) for network parameters and intermediate representations, which has greatly reduced the off-chip data transfer and storage overhead. However, a large amount of computation redundancy still exists in BNN inference. By analyzing local properties of images and the learned BNN kernel weights, we observe an average of ~78% input similarity and ~59% weight similarity among weight kernels, measured by our proposed metric in common network architectures. Thus there does exist redundancy that can be exploited to further reduce the amount of on-chip computations. Motivated by the observation, in this paper, we proposed two types of fast and energy-efficient architectures for BNN inference. We also provide analysis and insights to pick the better strategy of these two for different datasets and network models. By reusing the results from previous computation, much cycles for data buffer access and computations can be skipped. By experiments, we demonstrate that 80% of the computation and 40% of the buffer access can be skipped by exploiting BNN similarity. Thus, our design can achieve 17% reduction in total power consumption, 54% reduction in on-chip power consumption and 2.4× maximum speedup, compared to the baseline without applying our reuse technique. Our design also shows 1.9× more area-efficiency compared to state-of-the-art BNN inference design. We believe our deployment of BNN on FPGA leads to a promising future of running deep learning models on mobile devices.
Urbanization and humidity shape the intensity of influenza epidemics in U.S. cities

Seasonal flu by ZIP code Influenza virus strikes communities in northern latitudes during winter, straining health care provision almost to the breaking point. Change in environmental humidity is a key driver, but many other seasonal and social factors contribute. Dalziel et al. obtained a geographical distribution of doctor visits for influenza-like illness for more than 600 U.S. cities (see the Perspective by Wallinga). Some ZIP codes regularly experienced sharply defined peaks of cases, or intense epidemics, and others showed a longer, more diffuse influenza season. The surges tended to occur in smaller cities with less residential density and lower household incomes. Larger, more densely populated cities had more-diffuse epidemics, presumably because of higher rates of personal contact, which makes influenza transmission less subject to climate variation. Science, this issue p. 75; see also p. 29 Seasonal flu epidemics are more diffuse in larger cities and more intense in smaller cities, where climate has a stronger influence on transmission. Influenza epidemics vary in intensity from year to year, driven by climatic conditions and by viral antigenic evolution. However, important spatial variation remains unexplained. Here we show predictable differences in influenza incidence among cities, driven by population size and structure. Weekly incidence data from 603 cities in the United States reveal that epidemics in smaller cities are focused on shorter periods of the influenza season, whereas in larger cities, incidence is more diffuse. Base transmission potential estimated from city-level incidence data is positively correlated with population size and with spatiotemporal organization in population density, indicating a milder response to climate forcing in metropolises. This suggests that urban centers incubate critical chains of transmission outside of peak climatic conditions, altering the spatiotemporal geometry of herd immunity.
A Disposable Photovoltaic Patch Controlling Cellular Microenvironment for Wound Healing

Electrical stimulation (ES) is known to affect the wound healing process by modulating skin cell behaviors. However, the conventional clinical devices that can generate ES for promoting wound healing require patient hospitalization due to large-scale of the extracorporeal devices. Herein, we introduce a disposable photovoltaic patch that can be applied to skin wound sites to control cellular microenvironment for promoting wound healing by generating ES. In vitro experiment results show that exogenous ES could enhance cell migration, proliferation, expression of extracellular matrix proteins, and myoblast differentiation of fibroblasts which are critical for wound healing. Our disposable photovoltaic patches were attached to the back of skin wound induced mice. Our patch successfully provided ES, generated by photovoltaic energy harvested from the organic solar cell under visible light illumination. In vivo experiment results show that the patch promoted cutaneous wound healing via enhanced host-inductive cell proliferation, cytokine secretion, and protein synthesis which is critical for wound healing process. Unlike the current treatments for wound healing that engage passive healing processes and often are unsuccessful, our wearable photovoltaic patch can stimulate regenerative activities of endogenous cells and actively contribute to the wound healing processes.