Miracle-dz/UniFAR-FTUs huggingface dataset:
Implementing Strassen's Algorithm with CUTLASS on NVIDIA Volta GPUs

Conventional GPU implementations of Strassen's algorithm (Strassen) typically rely on the existing high-performance matrix multiplication (GEMM), trading space for time. As a result, such approaches can only achieve practical speedup for relatively large, "squarish" matrices due to the extra memory overhead, and their usages are limited due to the considerable workspace. We present novel Strassen primitives for GPUs that can be composed to generate a family of Strassen algorithms. Our algorithms utilize both the memory and thread hierarchies on GPUs, reusing shared memory and register files inherited from GEMM, fusing additional operations, and avoiding extra workspace. We further exploit intra- and inter-kernel parallelism by batching, streaming, and employing atomic operations. We also develop a performance model for NVIDIA Volta GPUs to select the appropriate blocking parameters and predict the performance for GEMM and Strassen. Overall, our 1-level Strassen can achieve up to 1.11x speedup with a crossover point as small as 1,536 compared to cublasSgemm on a NVIDIA Tesla V100 GPU. With additional workspace, our 2-level Strassen can achieve 1.19x speedup with a crossover point at 7,680.
Clinical and quality of life improvements with golimumab or infliximab in a real-life ankylosing spondylitis population: the QUO-VADIS study.

OBJECTIVES The QUO VADIS study evaluated disease activity and health-related quality-of-life (HRQoL) in ankylosing spondylitis (AS) patients treated with golimumab (GLM) or infliximab (IFX, originator) during routine clinical care. METHODS This prospective observational study followed biologics-naïve AS patients newly treated with GLM or IFX for 6 months. Disease activity (BASDAI, BASFI, ASAS, and ASDAS) and HRQoL improvement (≥5 points of SF-36 Physical Component Summary [PCS] score; PCS response) were measured. A Classification and Regression Trees (CART) analysis evaluated association of baseline parameters with PCS response at 6 months. RESULTS 963 patients (mean age 43 years, 61% male, 64% HLA-B27 positive) received ≥1 dose of medication (78% GLM; 22% IFX). Disease activity was reduced; mean (SD) changes from baseline at month 6 of -2.7 (BASDAI) and -2.1 (BASFI) and 40% and 35% achievement of BASDAI50 and ASAS40 response, respectively, were observed. PCS response was achieved at month 6 in 52% of patients. Using CART analysis, baseline parameters (cut-off values) associated with HRQoL improvement were ASDAS (≥3.48), C-reactive protein (≥8.55 mg/L), age (≤35.5 years), and BASFI (≥1.15). This algorithm correctly identified 57.5% (sensitivity) of PCS responders (≥5 points) and 61.0% (specificity) of PCS non-responders (<5points) with ROC-AUC=0.61. Serious adverse events (AEs) occurred in 1.8% of patients; the most common AEs were infections (7.7%). CONCLUSIONS We demonstrated clinical and HRQoL improvements over 6 months in a large, real-world population of AS patients newly treated with GLM or IFX; higher ASDAS, elevated CRP, and younger age were associated with improvements in HRQoL and an overall more robust response.
FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid.

BACKGROUND & AIMS Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor, affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analogue and farnesoid X receptor agonist, on the intestinal microbiomes of humans and mice. METHODS We performed a phase I study in 24 healthy volunteers given OCA (5, 10, or 25 mg/d for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun meta-genomic sequencing. A Uniref90 high-stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavage fed daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S-tagged sequencing. Culture experiments were performed to determine the taxonomic-specific effects of bile acids and OCA on bacterial growth. RESULTS Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of gram-positive bacteria that are found in the small intestine and are components of the diet and oral microbiota. We found that bile acids decreased proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had lower endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared with mice fed water or vehicle. CONCLUSIONS In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that farnesoid X receptor activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome. ClinicalTrials.gov, NCT01933503.
Neonatal hyperlipidemia with pancreatitis: Novel gene mutation of lipoprotein lipase

Lipoprotein lipase (LPL) deficiency is an autosomal recessive metabolic disorder with varying presentation in infancy and childhood, whereas clinical manifestations are rare in neonatal period. The estimated prevalence is one in a million births. A 23-day-old baby was admitted with complaints of fever, vomiting, and lethargy. Blood sample drawn appeared lipemic. Lipemia retinalis was noted on funduscopic examination. Biochemical analysis revealed abnormal lipid profile with severe hypertriglyceridemia (10,300 mg/dL) and elevated serum lipase level (517 IU/L) indicative of LPL deficiency with acute pancreatitis. LPL deficiency was suspected and was confirmed by molecular genetic testing, which revealed a novel mutation in LPL gene. Dietary management and gemfibrozil were started following which serum triglyceride level decreased and serum lipase level normalized. The patient is following up regularly for growth and development monitoring.
Targeted Sequencing of Alzheimer Disease Genes in African Americans Implicates Novel Risk Variants

The genetic architecture of late-onset Alzheimer disease (AD) in African Americans (AAs) differs from that in persons of European ancestry. In addition to APOE, genome-wide association studies (GWASs) of AD in AA samples have implicated ABCA7, COBL, and SLC10A2 as AA-AD risk genes. Previously, we identified by whole exome sequencing a small number of AA AD cases and subsequent genotyping in a large AA sample of AD cases and controls association of AD risk with a pair of rare missense variants in AKAP9. In this study, we performed targeted deep sequencing (including both introns and exons) of approximately 100 genes previously linked to AD or AD-related traits in an AA cohort of 489 AD cases and 472 controls to find novel AD risk variants. We observed association with an 11 base-pair frame-shift loss-of-function (LOF) variant in ABCA7 (rs567222111) for which the evidence was bolstered when combined with data from a replication AA cohort of 484 cases and 484 controls (OR = 2.42, p = 0.022). We also found association of AD with a rare 9 bp deletion (rs371245265) located very close to the AKAP9 transcription start site (rs371245265, OR = 10.75, p = 0.0053). The most significant findings were obtained with a rare protective variant in F5 (OR = 0.053, p = 6.40 × 10-5), a gene that was previously associated with a brain MRI measure of hippocampal atrophy, and two common variants in KIAA0196 (OR = 1.51, p<8.6 × 10-5). Gene-based tests of aggregated rare variants yielded several nominally significant associations with KANSL1, CNN2, and TRIM35. Although no associations passed multiple test correction, our study adds to a body of literature demonstrating the utility of examining sequence data from multiple ethnic populations for discovery of new and impactful risk variants. Larger sample sizes will be needed to generate well-powered epidemiological investigations of rare variation, and functional studies are essential for establishing the pathogenicity of variants identified by sequencing.
Distance–decay differs among vertical strata in a tropical rainforest

Assemblage similarity decays with geographic distance-a pattern known as the distance-decay relationship. While this pattern has been investigated for a wide range of organisms, ecosystems and geographical gradients, whether these changes vary more cryptically across different forest strata (from ground to canopy) remains elusive. Here, we investigated the influence of ground vs. arboreal assemblages to the general distance-decay relationship observed in forests. We seek to explain differences in distance-decay relationships between strata in the context of the vertical stratification of assemblage composition, richness and abundance. We surveyed for a climate-sensitive model organism, amphibians, across vertical rainforest strata in Madagascar. For each tree, we defined assemblages of ground-dwelling, understory, or canopy species. We calculated horizontal distance-decay in similarity across all trees, and across assemblages of species found in different forest strata (ground, understory and canopy). We demonstrate that within stratum comparisons exhibit a classic distance-decay relationship for canopy and understory communities but no distance-decay relationships for ground communities. We suggest that differences in horizontal turnover between strata may be due to local scale habitat and resource heterogeneity in the canopy, or the influence of arboreal traits on species dispersal and distribution. Synthesis. Biodiversity patterns in horizontal space were not consistent across vertical space, suggesting that canopy fauna may not play by the same set of "rules" as their conspecifics living below them on the ground. Our study provides compelling evidence that the above-ground amphibian assemblage of tropical rainforests is the primary driver of the classical distance-decay relationship.
Typology and Circuitry of Suppressed-by-Contrast Retinal Ganglion Cells

Retinal ganglion cells (RGCs) relay ~40 parallel and independent streams of visual information, each encoding a specific feature of a visual scene, to the brain for further processing. The polarity of a visual neuron’s response to a change in contrast is generally the first characteristic used for functional classification: ON cells increase their spike rate to positive contrast; OFF cells increase their spike rate for negative contrast; ON-OFF cells increase their spike rate for both contrast polarities. Suppressed-by-Contrast (SbC) neurons represent a less well-known fourth category; they decrease firing below a baseline rate for both positive and negative contrasts. SbC RGCs were discovered over 50 years ago, and SbC visual neurons have now been found in the thalamus and primary visual cortex of several mammalian species, including primates. Recent discoveries of SbC RGCs in mice have provided new opportunities for tracing upstream circuits in the retina responsible for the SbC computation and downstream targets in the brain where this information is used. We review and clarify recent work on the circuit mechanism of the SbC computation in these RGCs. Studies of mechanism rely on precisely defined cell types, and we argue that, like ON, OFF, and ON-OFF RGCs, SbC RGCs consist of more than one type. A new appreciation of the diversity of SbC RGCs will help guide future work on their targets in the brain and their roles in visual perception and behavior.
Rebound thymic hyperplasia after bone marrow transplantation in children with haemato-oncological diseases

Aim of the study To evaluate prevalence of rebound thymic hyperplasia (RTH) after bone marrow transplantation (BMT) in paediatric patients with haemato-oncological diseases. Material and methods Between February 2013 and December 2017, BMT was performed in 189 paediatric patients with haemato-oncological diseases in our institution. Fifty-six patients who underwent at least two chest computed tomography (CT) exams performed before and after BMT were included in the study. Maximum transverse and anterior-posterior (AP) diameters and CT attenuation of the thymus were measured on axial images. Thymic enlargement was considered when both transverse and AP diameters increased. RTH was defined as the presence of thymic enlargement on CT after BMT relative to the CT taken before. Results Twenty of 56 patients (36%) demonstrated RTH (12 boys, 8 girls; age range = 4-18 years; median age = 9.8 years). In 20 patients with RTH, seven patients (35%) were diagnosed with ALL, five patients (25%) with thalassemia, two patients (10%) with AML, and one patient (5%) with various diseases. Mean follow-up period between pre-BMT CT and BMT was 46 days, which was 239 days between BMT and post-BMT CT. Mean thymic transverse and AP diameters were 9 mm and 16 mm, respectively, before BMT, which were 17 mm and 33 mm after BMT. Mean HU was 57 on contrast enhanced and 35 on unenhanced images before BMT, which were 59 and 36, respectively, after BMT. Conclusions RTH is common finding after BMT in children with various haemato-oncological diseases and should be taken under consideration in paediatric patients after BMT.
TFEB-driven endocytosis coordinates MTORC1 signaling and autophagy

ABSTRACT The mechanistic target of rapamycin kinase complex 1 (MTORC1) is a central cellular kinase that integrates major signaling pathways, allowing for regulation of anabolic and catabolic processes including macroautophagy/autophagy and lysosomal biogenesis. Essential to these processes is the regulatory activity of TFEB (transcription factor EB). In a regulatory feedback loop modulating transcriptional levels of RRAG/Rag GTPases, TFEB controls MTORC1 tethering to membranes and induction of anabolic processes upon nutrient replenishment. We now show that TFEB promotes expression of endocytic genes and increases rates of cellular endocytosis during homeostatic baseline and starvation conditions. TFEB-mediated endocytosis drives assembly of the MTORC1-containing nutrient sensing complex through the formation of endosomes that carry the associated proteins RRAGD, the amino acid transporter SLC38A9, and activate AKT/protein kinase B (AKT p-T308). TFEB-induced signaling endosomes en route to lysosomes are induced by amino acid starvation and are required to dissociate TSC2, re-tether and activate MTORC1 on endolysosomal membranes. This study characterizes TFEB-mediated endocytosis as a critical process leading to activation of MTORC1 and autophagic function, thus identifying the importance of the dynamic endolysosomal system in cellular clearance. Abbreviations: CAD: central adrenergic tyrosine hydroxylase-expressing-a-differentiated; ChIP-seq: chromosome immunoprecipitation sequencing; DAPI: 4ʹ,6-diamidino-2-phenylindole; DMSO: dimethyl sulfoxide; EDTA: ethylenediaminetetraacetic acid; EEA1: early endosomal antigen 1; EGF: epidermal growth factor; FBS: fetal bovine serum; GFP: green fluorescent protein; GTPase: guanosine triphosphatase; HEK293T: human embryonic kidney 293 cells expressing a temperature-sensitive mutant of the SV40 large T antigen; LAMP: lysosomal-associated membrane protein; LYNUS: lysosomal nutrient-sensing complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3 alpha/beta; MTOR: mechanistic target of rapamycin kinase; MTORC: mechanistic target of rapamycin kinase complex; OE: overexpression; PH: pleckstrin homology; PtdIns(3,4,5)P3: phosphatidylinositol 3,4,5-trisphosphate; RRAGD: Ras related GTPase binding D; RHEB: Ras homolog enriched in brain; SLC38A9: solute carrier family 38 member 9; SQSTM1: sequestosome 1; TFEB: transcription factor EB; TSC2: tuberous sclerosis 2; TMR: tetramethylrhodamine; ULK1: unc-51 like kinase 1; WT: wild type
LncRNA DGCR5 suppresses neuronal apoptosis to improve acute spinal cord injury through targeting PRDM5

ABSTRACT Spinal cord injury (SCI) usually results in neurological damage. DGCR5 is closely related to neurological disorders, and this study aims to explore its role in neuronal apoptosis in acute SCI. The ASCI model was established in rats, and the Basso, Beattie, and Bresnahan (BBB) scoring was used to assess the neurological function. The expression of RNA and protein was quantified by quantitative real-time PCR (qRT-PCR) and western blotting, respectively. The oxygenglucose deprivation (OGD) was performed upon neurons and apoptosis was evaluated by flow cytometry. The interaction and binding between DGCR5 and PRDM5 was detected with RNA pull-down and RIP assay, respectively. DGCR5 was down-regulated in ASCI model rat and in neurons treated with hypoxia. Over-expression of DGCR5 inhibited neuronal apoptosis. Interaction between DGCR5 negatively regulated PRDM5 protein expression by binding and interacting with it. DGCR5 inhibited neuronal apoptosis through PRDM5. Over-expressed DGCR5 ameliorated ASCI in rat. DGCR5 suppresses neuronal apoptosis through directly binding and negatively regulating PRDM5, and thereby ameliorating ASCI.
Screening of Serum Biomarkers for Distinguishing between Latent and Active Tuberculosis Using Proteome Microarray.

OBJECTIVE To identify potential serum biomarkers for distinguishing between latent tuberculosis infection (LTBI) and active tuberculosis (TB). METHODS A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays (ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve (ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability. RESULTS Microarray results showed that levels of 152 Mycobacterium tuberculosis (Mtb)-antigen- specific IgG were significantly higher in active TB patients than in LTBI patients (P < 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher areas under the curve (AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability. CONCLUSION Several antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.
Stress‐induced alterations in oocyte transcripts are further expressed in the developing blastocyst

The oocyte achieves its developmental competence through the lengthy process of folliculogenesis. It can therefore potentially be exposed to various stressors while enclosed in the follicle. Oocyte maturation relies mainly on maternal sources. These include nuclear, cytoplasmic, and molecular maturation, which involve DNA and RNA organization. Maternal transcripts are dominant through the first embryonic cleavages, up until embryonic genome activation. Thus, it is suggested that any perturbations during oocyte storage, in particular of the maternal transcripts, might lead to genetic and/or epigenetic changes, which might be further expressed in the developing embryo. The review discusses the effects of three representative stressors—environmental heat stress, endocrine‐disrupting compounds (phthalates), and inflammatory stress (mastitis)—shown to be involved in reduced fertility. The review highlights the carryover response from the oocyte to the developing embryo; it includes intracellular and molecular disruptive mechanisms with an emphasis on maternal transcripts. The review provides insights into the oocyte’s cellular and molecular responses with an emphasis on the effects of various stressors on the maternal (nuclear and mitochondrial) transcripts and the association with embryonic development. A comparison between stressors might clarify, at least in part, a few open questions. For instance, (a) whether stress‐induced alterations share the same mechanism and if so (b) whether this mechanism involves alterations of maternal transcripts; (c) whether stress‐induced alterations in the maternal transcript are further expressed at the developing blastocyst stage, that is, after embryonic genome activation.
Distinct Roles for Two Chromosome 1 Loci in Ethanol Withdrawal, Consumption, and Conditioned Place Preference

We previously identified a region on chromosome 1 that harbor quantitative trait loci (QTLs) with large effects on alcohol withdrawal risk using both chronic and acute models in mice. Here, using newly created and existing QTL interval-specific congenic (ISC) models, we report the first evidence that this region harbors two distinct alcohol withdrawal QTLs (Alcw11and Alcw12), which underlie 13% and 3–6%, respectively, of the genetic variance in alcohol withdrawal severity measured using the handling-induced convulsion. Our results also precisely localize Alcw11 and Alcw12 to discreet chromosome regions (syntenic with human 1q23.1–23.3) that encompass a limited number of genes with validated genotype-dependent transcript expression and/or non-synonymous sequence variation that may underlie QTL phenotypic effects. ISC analyses also implicate Alcw11and Alcw12 in withdrawal-induced anxiety-like behavior, representing the first evidence for their broader roles in alcohol withdrawal beyond convulsions; but detect no evidence for Alcw12 involvement in ethanol conditioned place preference (CPP) or consumption. Our data point to high-quality candidates for Alcw12, including genes involved in mitochondrial respiration, spatial buffering, and neural plasticity, and to Kcnj9 as a high-quality candidate for Alcw11. Our studies are the first to show, using two null mutant models on different genetic backgrounds, that Kcnj9 −/− mice demonstrate significantly less severe alcohol withdrawal than wildtype littermates using acute and repeated exposure paradigms. We also demonstrate that Kcnj9 −/− voluntarily consume significantly more alcohol (20%, two-bottle choice) than wildtype littermates. Taken together with evidence implicating Kcnj9 in ethanol CPP, our results support a broad role for this locus in ethanol reward and withdrawal phenotypes. In summary, our results demonstrate two distinct chromosome 1 QTLs that significantly affect risk for ethanol withdrawal, and point to their distinct unique roles in alcohol reward phenotypes.