Miracle-dz/UniFAR-FTUs huggingface dataset:
UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal Instability

This study explored potential biomarkers associated with Lauren classification of gastric cancer. We screened microarray datasets on gastric cancer with information of Lauren classification in gene expression omnibus (GEO) database, and compared differentially expressing genes between intestinal-type or diffuse-type gastric cancer. Four sets of microarray data (GSE2669, GSE2680, GDS3438, and GDS4007) were enrolled into analysis. By differential gene analysis, UBE2C, CDH1, CENPF, ERO1L, SCD, SOX9, CKS1B, SPP1, MMP11, and ANLN were identified as the top genes related to intestinal-type gastric cancer, and MGP, FXYD1, FAT4, SIPA1L2, MUC5AC, MMP15, RAB23, FBLN1, ANXA10, and ADH1B were genes related to diffuse-type gastric cancer. We comprehensively validated the biological functions of the intestinal-type gastric cancer related gene UBE2C and evaluated its clinical significance on 1,868 cases of gastric cancer tissues from multiple medical centers of Shanghai, China. The gain of copy number on 20q was found in 4 out of 5 intestinal-type cancer cell lines, and no similar copy number variation (CNV) was found in any diffuse-type cancer cell line. Interfering UBE2C expression inhibited cell proliferation, migration and invasion in vitro, and tumorigenesis in vivo. Knockdown of UBE2C resulted in G2/M blockage in intestinal-type gastric cancer cells. Overexpression of UBE2C activated ERK signal pathway and promoted cancer cell proliferation. U0126, an inhibitor of ERK signaling pathway reversed the oncogenic phenotypes caused by UBE2C. Moreover, overexpression of UBE2C was identified in human intestinal-type gastric cancer. Overexpression of UBE2C protein predicted poor clinical outcome. Taken together, we characterized a group of Lauren classification-associated biomarkers, and clarified biological functions of UBE2C, an intestinal-type gastric cancer associated gene. Overexpression of UBE2C resulted in chromosomal instability that disturbed cell cycle and led to poor prognosis of intestinal-type gastric cancer.
Survivin Measurement improves Clinical Prediction of Transition From Arthralgia to RA—Biomarkers to Improve Clinical Sensitivity of Transition From Arthralgia to RA

Background: Arthralgia often predates development of rheumatoid arthritis (RA). A set of joint symptoms commonly found in patients during their transition from arthralgia to RA, has been recently proposed. Aim: To combine clinical and serological markers and to improve recognition of imminent rheumatoid arthritis (RA) among patients with arthralgia. Methods: The total of 1,743 first-visit patients attending the rheumatology ward in Gothenburg for joint symptoms were identified during 12 consecutive months. Among those, 63 patients were classified as RA, 73 had undifferentiated arthritis and 180 had unexplained arthralgia. New RA cases, which prospectively developed during 48 months, comprised the preclinical (pre) RA group. The joint symptoms of the first-visit were analyzed aiming to distinguish patients with arthralgia and arthritis, and patients with pre-RA, who later developed the disease. The receiver operating characteristics curves were constructed. In the model, symptoms with the odds ratio >2.0 between the arthralgia and pre-RA were combined with information about RA-specific antibodies, C-reactive protein (CRP), and survivin in serum. Results: The proposed set of clinical symptoms distinguished the arthralgia patients from RA and pre-RA. Presence of survivin in serum showed strong association with clinical joint symptoms in arthralgia. A combination of symptoms in several small joint areas, increasing number of joints with symptoms, and patient's experience of swelling in small hand joints at the first visit identified pre-RA cases with 93% specificity. Grouping those symptoms with information about survivin, RA-specific antibodies, and CRP (or gender) in the final algorithm achieved 91% specificity and 55.2% of positive prediction for transition from arthralgia to RA. Conclusion: Clinical and serological parameters in combination aid recognition of imminent RA among arthralgia patients with appropriate sensitivity.
Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease

Objective To examine the independent and interactive influences of neuroimaging biomarkers on retrospective cognitive decline. Methods A total of 152 middle-aged and older adult participants with at least 2 clinical and cognitive assessments, a Clinical Dementia Rating score of 0 or 0.5, and a flortaucipir (18F-AV-1451) tau PET scan, a florbetapir (18F-AV-45) amyloid PET scan, and a structural MRI scan were recruited from the Knight Alzheimer Disease Research Center at Washington University in St. Louis. Cognition was assessed with standard measures reflecting episodic memory, executive functioning, semantic fluency, and processing speed. Results Results from retrospective longitudinal analyses showed that each biomarker had a univariate association with the global cognitive composite; however, when each marker was analyzed in a single statistical model, only tau was a significant predictor of global cognitive decline. There was an interaction between tau and amyloid such that tau-related cognitive decline was worse in individuals with high amyloid. There was also an interaction with hippocampal volume indicating that individuals with high levels of all 3 pathologies exhibited the greatest declines in cognition. Additional analyses within each cognitive domain indicated that tau had the largest negative influence on tests of episodic memory and executive functioning. Conclusions Together, these results suggest that increasing levels of tau most consistently relate to declines in cognition preceding biomarker collection. These findings support models of Alzheimer disease (AD) staging that suggest that elevated β-amyloid alone may be insufficient to produce cognitive change in individuals at risk for AD and support the use of multiple biomarkers to stage AD progression.
Neurophysiological Signatures of Temporal Coordination Between Retrosplenial Cortex and the Hippocampal Formation

Retrosplenial cortex (RSC) is heavily interconnected with a multitude of cortical regions and is directly connected with the hippocampal formation. As such, it is a likely coordinator of information transfer between the hippocampus (HPC) and cortex in the service of spatial cognition and episodic memory. The current work examined three potential temporal frameworks for retrosplenial–hippocampal communication, namely, theta frequency oscillations (6–12 Hz), sharp-wave/ripple events, and repeating, theta phase-locked shifts from low (30–65 Hz) to high (120–160 Hz) gamma frequency oscillations. From simultaneous recordings of single units and local field potentials (LFPs) in RSC and HPC, we report the presence of prominent theta, low-gamma, and high-gamma oscillations in the retrosplenial LFP. Retrosplenial and hippocampal theta rhythms were strongly coherent and subgroups of retrosplenial neurons exhibited either spiking at theta frequencies and/or spike-phase-locking to theta. Retrosplenial neurons were also phase-locked to local low- and high-gamma rhythms, and power in these frequency bands was coupled in a sequential fashion to specific phases of hippocampal and retrosplenial theta rhythms. Coordinated activity between the two regions also occurred during hippocampal sharp-wave/ripple events, where retrosplenial neuron populations were modulated in their spiking and retrosplenial LFPs exhibited sharp-wave-like events that co-occurred with those observed in HPC. These results identify several temporal windows of synchronization between RSC and HPC that may mediate cortico-hippocampal processes related to learning, memory, and spatial representation.
Staphylococcus aureus counters phosphate limitation by scavenging wall teichoic acids from other staphylococci via the teichoicase GlpQ

Staphylococcus aureus is part of the human nasal and skin microbiomes along with other bacterial commensals and opportunistic pathogens. Nutrients are scarce in these habitats, demanding effective nutrient acquisition and competition strategies. How S. aureus copes with phosphate limitation is still unknown. Wall teichoic acid (WTA), a polyol-phosphate polymer, could serve as a phosphate source, but whether S. aureus can utilize it during phosphate starvation remains unknown. S. aureus secretes a glycerophosphodiesterase, GlpQ, that cleaves a broad variety of glycerol-3-phosphate (GroP) headgroups of deacylated phospholipids, providing this bacterium with GroP as a carbon and phosphate source. Here we demonstrate that GlpQ can also use glycerophosphoglycerol derived from GroP WTA from coagulase-negative Staphylococcus lugdunensis, Staphylococcus capitis, and Staphylococcus epidermidis, which share the nasal and skin habitats with S. aureus. Therefore, S. aureus GlpQ is the first reported WTA-hydrolyzing enzyme, or teichoicase, from Staphylococcus. Activity assays revealed that unmodified WTA is the preferred GlpQ substrate, and the results from MS analysis suggested that GlpQ uses an exolytic cleavage mechanism. Importantly, GlpQ did not hydrolyze the ribitol-5-phosphate WTA polymers of S. aureus, underscoring its role in interspecies competition rather than in S. aureus cell wall homeostasis or WTA recycling. glpQ expression was strongly up-regulated under phosphate limitation, and GlpQ allowed S. aureus to grow in the presence of GroP WTA as the sole phosphate source. Our study reveals a novel and unprecedented strategy of S. aureus for acquiring phosphate from bacterial competitors under the phosphate-limiting conditions in the nasal or skin environments.
Fréchet ChemNet Distance: A Metric for Generative Models for Molecules in Drug Discovery

The new wave of successful generative models in machine learning has increased the interest in deep learning driven de novo drug design. However, method comparison is difficult because of various flaws of the currently employed evaluation metrics. We propose an evaluation metric for generative models called Fréchet ChemNet distance (FCD). The advantage of the FCD over previous metrics is that it can detect whether generated molecules are diverse and have similar chemical and biological properties as real molecules.
Metabolic Syndrome, Thyroid Function and Autoimmunity - The PORMETS Study

Background: The prevalence of thyroid dysfunction and autoimmunity in the Portuguese population has not yet been estimated. However, the national prevalence of the metabolic syndrome re-mains high. The association of thyroid pathology with cardiovascular risk has been addressed but is still unclear. Our study aimed to evaluate the prevalence of thyroid dysfunction and autoimmunity and to assess the associations of thyroid-stimulating hormone and thyroid hormones and antibodies with meta-bolic syndrome, its components, and other possible determinants in a national sample. Material and Methods: The present study included a subsample of 486 randomly selected participants from a nationwide cross-sectional study sample of 4095 adults. A structured questionnaire was adminis-tered on past medical history and socio-demographic and behavioural characteristics. Blood pressure and anthropometric measurements were collected, and the serum lipid profile, glucose, insulin, hs-CRP, TSH, FT4, FT3 and thyroid antibodies were measured. Results: In our sample, the prevalence of hypothyroidism, hyperthyroidism and undiagnosed dysfunc-tion was 4.9%, 2.5% and 72.2%, respectively. Overall, the prevalence of positivity for the thyroid perox-idase and thyroglobulin antibodies was 11.9% and 15.0%, respectively. A positive association was found between free triiodothyronine and metabolic syndrome (OR: 2.019; 95% CI: 1.196, 3.410). Additionally, thyroid peroxidase antibodies had a negative association with metabolic syndrome (OR: 0.465; 95% CI: 0.236, 0.917) and its triglyceride component (OR: 0.321; 95% CI: 0.124, 0.836). Conclusion: The prevalence of undiagnosed thyroid dysfunction and autoimmunity was high. Thyroid peroxidase antibodies were negatively associated with metabolic syndrome and its triglyceride compo-nent, whereas the free triiodothyronine level was positively associated with metabolic syndrome.
The functional anatomy of the shoulder of the savannah monitor lizard (Varanus exanthematicus)

The excursions of the scapulocoracoid and forelimb and the activity of 18 shoulder muscles were studied by simultaneous cineradiography and electromyography in Savannah Monitor lizards (Varanus exanthematicus) walking on a treadmill at speeds of 0.7–1.1 km/hour. During the propulsive phase, the humerus moves anteroposteriorly 40–55° and rotates a total of 30–40°. Simultaneously, the coracoid translates posteriorly along the tongue‐and‐groove coracosternal joint by a distance equivalent to about 40% the length of the coracoid.
Influence of patient characteristics on preventive service delivery and general practitioners’ preventive performance indicators: A study in patients with hypertension or diabetes mellitus from Hungary

Abstract Background: Regular primary healthcare (PHC) performance monitoring to produce a set of performance indicators for provider effectiveness is a fundamental method for improving guideline adherence but there are potential negative impacts of the inadequate application of this approach. Since performance indicators can reflect patient characteristics and working environments, as well as PHC team contributions, inadequate monitoring practices can reduce their effectiveness in the prevention of cardiometabolic disorders. Objectives: To describe the influence of patients’ characteristics on performance indicators of PHC preventive practices in patients with hypertension or diabetes mellitus. Methods: This cross-sectional analysis was based on a network of 165 collaborating GPs. A random sample of 4320 adults was selected from GP’s patient lists. The response rate was 97.3% in this survey. Sociodemographic status, lifestyle, health attitudes and the use of recommended preventive PHC services were surveyed by questionnaire. The relationship between the use of preventive services and patient characteristics were analysed using hierarchical regression models in a subsample of 1659 survey participants with a known diagnosis of hypertension or diabetes mellitus. Results: Rates of PHC service utilization varied from 18.0% to 97.9%, and less than half (median: 44.4%; IQR: 30.8–62.5) of necessary services were used by patients. Patient attitude was as strong of an influencing factor as demographic properties but was remarkably weaker than patient socioeconomic status. Conclusion: These findings emphasize that PHC performance indicators have to be evaluated concerning patient characteristics.
Timing Training in Female Soccer Players: Effects on Skilled Movement Performance and Brain Responses

Although trainers and athletes consider “good timing skills” critical for optimal sport performance, little is known in regard to how sport-specific skills may benefit from timing training. Accordingly, this study investigated the effects of timing training on soccer skill performance and the associated changes in functional brain response in elite- and sub-elite female soccer players. Twenty-five players (mean age 19.5 years; active in the highest or second highest divisions in Sweden), were randomly assigned to either an experimental- or a control group. The experimental group (n = 12) was subjected to a 4-week program (12 sessions) of synchronized metronome training (SMT). We evaluated effects on accuracy and variability in a soccer cross-pass task. The associated brain response was captured by functional magnetic resonance imaging (fMRI) while watching videos with soccer-specific actions. SMT improved soccer cross-pass performance, with a significant increase in outcome accuracy, combined with a decrease in outcome variability. SMT further induced changes in the underlying brain response associated with observing a highly familiar soccer-specific action, denoted as decreased activation in the cerebellum post SMT. Finally, decreased cerebellar activation was associated with improved cross-pass performance and sensorimotor synchronization. These findings suggest a more efficient neural recruitment during action observation after SMT. To our knowledge, this is the first controlled study providing behavioral and neurophysiological evidence that timing training may positively influence soccer-skill, while strengthening the action-perception coupling via enhanced sensorimotor synchronization abilities, and thus influencing the underlying brain responses.
Binarized Convolutional Neural Networks for Efficient Inference on GPUs

Convolutional neural networks have recently achieved significant breakthroughs in various image classification tasks. However, they are computationally expensive, which can make their feasible implementation on embedded and low-power devices difficult. In this paper convolutional neural network binarization is implemented on GPU-based platforms for real-time inference on resource constrained devices. In binarized networks, all weights and intermediate computations between layers are quantized to +1 and −1, allowing multiplications and additions to be replaced with bit-wise operations between 32-bit words. This representation completely eliminates the need for floating point multiplications and additions and decreases both the computational load and the memory footprint compared to a full-precision network implemented in floating point, making it well-suited for resource-constrained environments. We compare the performance of our implementation with an equivalent floating point implementation on one desktop and two embedded GPU platforms. Our implementation achieves a maximum speed up of $7.4\times$ with only 4.4 % loss in accuracy compared to a reference implementation.
Speaker Recognition from Raw Waveform with SincNet

Deep learning is progressively gaining popularity as a viable alternative to i-vectors for speaker recognition. Promising results have been recently obtained with Convolutional Neural Networks (CNNs) when fed by raw speech samples directly. Rather than employing standard hand-crafted features, the latter CNNs learn low-level speech representations from waveforms, potentially allowing the network to better capture important narrow-band speaker characteristics such as pitch and formants. Proper design of the neural network is crucial to achieve this goal.This paper proposes a novel CNN architecture, called SincNet, that encourages the first convolutional layer to discover more meaningful filters. SincNet is based on parametrized sinc functions, which implement band-pass filters. In contrast to standard CNNs, that learn all elements of each filter, only low and high cutoff frequencies are directly learned from data with the proposed method. This offers a very compact and efficient way to derive a customized filter bank specifically tuned for the desired application.Our experiments, conducted on both speaker identification and speaker verification tasks, show that the proposed architecture converges faster and performs better than a standard CNN on raw waveforms.
Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin

Significance Most antibiotics do not interfere with viral infections. Rifampicin is a notable exception, as it inhibits several poxviruses, including the causative agent of smallpox. However, the inhibition of viral assembly is unrelated to the antibacterial activity of rifampicin against microbial RNA polymerases. Here, we reveal how the antibiotic prevents the recruitment of an essential scaffolding protein to nascent viral membranes. Based on these results, we provide a structural model of membrane assembly that is distinct from budding through cellular membranes and is most likely conserved in many large DNA viruses. Together, the mechanism of membrane assembly and structural models provide avenues to develop broad spectrum inhibitors against human and animal poxviruses. Poxviruses are large DNA viruses that cause disease in animals and humans. They differ from classical enveloped viruses, because their membrane is acquired from cytoplasmic membrane precursors assembled onto a viral protein scaffold formed by the D13 protein rather than budding through cellular compartments. It was found three decades ago that the antibiotic rifampicin blocks this process and prevents scaffold formation. To elucidate the mechanism of action of rifampicin, we have determined the crystal structures of six D13–rifamycin complexes. These structures reveal that rifamycin compounds bind to a phenylalanine-rich region, or F-ring, at the membrane-proximal opening of the central channel of the D13 trimer. We show by NMR, surface plasmon resonance (SPR), and site-directed mutagenesis that A17, a membrane-associated viral protein, mediates the recruitment of the D13 scaffold by also binding to the F-ring. This interaction is the target of rifampicin, which prevents A17 binding, explaining the inhibition of viral morphogenesis. The F-ring of D13 is both conserved in sequence in mammalian poxviruses and essential for interaction with A17, defining a target for the development of assembly inhibitors. The model of the A17–D13 interaction describes a two-component system for remodeling nascent membranes that may be conserved in other large and giant DNA viruses.
Carbon Gain Limitation Is the Primary Mechanism for the Elevational Distribution Limit of Myriophyllum in the High-Altitude Plateau

Temperature comprises a major driver for species distribution and physiological processes in alpine plants. For all terrestrial plant species tested to date, elevation associated decreases in temperature have been observed to influence the balance between carbon acquisition and usage; restricting the upper limit of most alpine trees (i.e., treeline). However, such a carbon source-sink balance has not been tested in any alpine aquatic plants, which is an important component of the alpine aquatic ecosystem. The Myriophyllum species inhabits a broad range of habitats across the high-altitude plateau. Three Myriophyllum species (Myriophyllum spicatum, Myriophyllum verticillatum, and Myriophyllum sibiricum) from 12 water bodies at elevational gradients between 2766 and 5111 m were collected in the Qinghai-Tibetan Plateau. The late growing seasonal concentrations of non-structural carbohydrates (NSC) in the leaves were measured to find how high-altitude conditions influence the carbon balance in aquatic plants. Regression tree analysis separated the 12 water bodies into two groups according to water turbidity (seven water bodies with high turbidity and five water bodies with low turbidity). Overall, leaf NSC concentrations (primarily starch) decreased significantly with increasing elevation in widely distributed M. spicatum and M. verticillatum. Regression tree analysis indicated that water turbidity (i.e., shady environment) was a strong determinant of leaf NSC. In the low turbidity group (<3.5 NTU), leaf NSC concentrations decreased with increasing elevation; however, in the high turbidity group (>3.5 NTU), leaf NSC concentrations were low and had no association with elevation. Unlike most recent studies in tree species, which show low temperatures limited growth at high-elevations, our results demonstrated that carbon gain limitation is the primary mechanism for the elevational distribution limit of Myriophyllum species in the Qinghai-Tibetan Plateau. Moreover, water turbidity moderated the effects of low temperature by masking the expected carbon limitation trend. Therefore, at least two environmental factors (i.e., temperature and light availability) induced photosynthesis decreases might explain the NSC responses for aquatic plants in response to elevation.