Miracle-dz/UniFAR-FTUs huggingface dataset:
Salicylic acid inducible nucleocytoplasmic shuttling of NPR1 fusion proteins in human cells

Ligand inducible proteins that enable precise and reversible control of nuclear translocation of passenger proteins have broad applications ranging from genetic studies in mammals to therapeutics that target diseases such as cancer and diabetes. One of the drawbacks of the current translocation systems is that the ligands used to control nuclear localization are either toxic or prone to crosstalk with endogenous protein cascades within live animals. We sought to take advantage of salicylic acid (SA), a small molecule that has been extensively used in humans. In plants, SA functions as a hormone that can mediate immunity and is sensed by the nonexpressor of pathogenesis‐related (NPR) proteins. Although it is well recognized that nuclear translocation of NPR1 is essential to promoting immunity in plants, the exact subdomain of Arabidopsis thaliana NPR1 (AtNPR1) essential for SA‐mediated nuclear translocation is controversial. Here, we utilized the fluorescent protein mCherry as the reporter to investigate the ability of SA to induce nuclear translocation of the full‐length NPR1 protein or its C‐terminal transactivation (TAD) domain using HEK293 cells as a heterologous system. HEK293 cells lack accessory plant proteins including NPR3/NPR4 and are thus ideally suited for studying the impact of SA‐induced changes in NPR1. Our results obtained using a stable expression system show that the TAD of AtNPR1 is sufficient to enable the reversible SA‐mediated nuclear translocation of mCherry. Our studies advance a basic understanding of nuclear translocation mediated by the TAD of AtNPR1 and uncover a biotechnological tool for SA‐mediated nuclear localization.
Identification of a canine coronavirus in Australian racing Greyhounds

Coronavirus infection can cause a range of syndromes, which in dogs can include mild-to-severe enteritis that generally resolves rapidly. Fatalities can occur from coinfection with other pathogens, including canine parvovirus. Between late December 2019 and April 2020, canine coronavirus (CCoV) was detected in Australian racing Greyhounds that displayed signs of gastrointestinal disease. The CCoV was genotyped using high-throughput sequencing, recovering 98.3% of a type IIb CCoV, generally thought to cause a mild but highly contagious enteric disease. The Australian CCoV was almost identical (99.9%, whole-genome sequence) to another CCoV associated with an outbreak of severe vomiting in dogs in the United Kingdom at the same time (December 2019–March 2020).
Longitudinal study of the cascading effects of racial discrimination on parenting and adjustment among African American youth

ABSTRACT Attachment theory posits that parenting plays akey role in children’s attachment and subsequent development. Given the normativity of racial discrimination on everyday life experiences of African American families, there is a need to integrate historical and socio-environmental processes in studies to understand how minoritized parents raise secure and stable children. Results from the current study revealed direct associations between mothers’ reports of discrimination and heightened depression and anxiety. Maternal discriminatory experiences were indirectly associated with more negative parenting and compromised parent-child relationship quality, through mothers’ psychological functioning. Elevated emotional and behavioral management problems among youth were directly associated with exposure to racial discrimination. Exposure to discrimination during middle childhood facilitated adapted or learned strategies to manage similar situations as youth transitioned into adolescence, with reduced patterns of depressive symptomology. No significant gender effects emerged. Implications for theoretical advancement and future research are provided.
Role of miR‐185‐5p as modulator of periostin synthesis and smooth muscle contraction in asthma

Asthma is a chronic respiratory disease produced by an aberrant immune response that originates with breathing difficulties and cough, through airway remodeling. The above pathophysiological events of asthma emerge the regulators of effectors, like epigenetics, which include microRNAs (miRNAs) who perform post‐transcriptional regulation, controlling diverse pathways in respiratory diseases. The objective of the study was to determine how miR‐185‐5p regulates the secretion of periostin by airway structural cells, and smooth muscle cells contraction, both related to airway remodeling in asthma. We used miR‐185‐5p mimic and inhibitors in bronchial smooth muscle cells (BSMCs) and small airway epithelial cells (SAECs) from healthy subjects. Gene expression and protein levels of periostin (POSTN), CDC42, and RHOA were analyzed by RT‐PCR and ELISA/Western blot, respectively. BSMC contractility was analyzed using cell‐embedded collagen gels and measurement of intracellular calcium was performed using Fura‐2. Additionally, miR‐185‐5p and periostin expression were evaluated in sputum from healthy and asthmatics. From these experiments, we observed that miR‐185‐5p modulation regulates periostin mRNA and protein in BSMCs and SAECs. A tendency for diminished miR‐185‐5p expression and higher periostin levels was seen in sputum cells from asthmatics compared to healthy, with an inverse correlation observed between POSTN and miR‐185‐5p. Inhibition of miR‐185‐5p produced higher BSMCs contraction induced by histamine. Calcium mobilization was not modified by miR‐185‐5p, showing that miR‐185‐5p role in BSMC contractility is performed by regulating CDC42 and RhoA pro‐contractile factors instead. In conclusion, miR‐185‐5p is a modulator of periostin secretion by airway structural cells and of smooth muscle contraction, which can be related to asthma pathophysiology, and thus, might be a promising therapeutic target.
Longitudinal association of midlife vision impairment and depressive symptoms: the study of Women's Health Across the Nation, Michigan site

Supplemental Digital Content is available in the text Abstract Objective: Poor vision affects physical health but the relationship with depressive symptoms among midlife adults (40-65 y), who often present with early stage vision impairment (VI), is not well understood. The goal of this study was to assess the impact of vision on depressive symptoms during midlife. Methods: The Michigan site of the Study of Women's Health Across the Nation conducted assessments of distance visual acuity at six consecutive, near-annual follow-up visits. At each visit, depressive symptoms (Center for Epidemiological Studies-Depression Scale) were assessed. VI was defined as mild (20/30-20/60) or moderate-severe (20/70 or worse). Multivariable logistic regression models using generalized estimating equations were used to assess the association of VI and reporting of depressive symptoms at the subsequent visit. Results: At analytic baseline, the mean age of participants (N = 226) was 50.0 years (standard deviation = 2.6). More than half (53.5%) of women had mild VI and 8.0% had moderate-severe VI. Adjusting for age, preexisting depressive symptoms, race, education, economic strain, body mass index, and smoking, participants with mild and moderate-severe VI had 68% (95% C (0.97-2.90)) and 2.55-fold (95% CI 1.13-5.75) higher odds of reporting depressive symptoms at their subsequent study visit as compared with women without VI. Further adjustment for diabetes, hypertension, and osteoarthritis attenuated the estimates and the associations were no longer statistically significant. Conclusion: VI was associated with increased odds of future depressive symptoms among mid-life women. Timely detection and appropriate correction of VI may be important to consider in maintaining the mental health status of midlife women.
OutbreakFlow: Model-based Bayesian inference of disease outbreak dynamics with invertible neural networks and its application to the COVID-19 pandemics in Germany

Mathematical models in epidemiology are an indispensable tool to determine the dynamics and important characteristics of infectious diseases. Apart from their scientific merit, these models are often used to inform political decisions and interventional measures during an ongoing outbreak. However, reliably inferring the epidemical dynamics by connecting complex models to real data is still hard and requires either laborious manual parameter fitting or expensive optimization methods which have to be repeated from scratch for every application of a given model. In this work, we address this problem with a novel combination of epidemiological modeling with specialized neural networks. Our approach entails two computational phases: In an initial training phase, a mathematical model describing the epidemic is used as a coach for a neural network, which acquires global knowledge about the full range of possible disease dynamics. In the subsequent inference phase, the trained neural network processes the observed data of an actual outbreak and infers the parameters of the model in order to realistically reproduce the observed dynamics and reliably predict future progression. With its flexible framework, our simulation-based approach is applicable to a variety of epidemiological models. Moreover, since our method is fully Bayesian, it is designed to incorporate all available prior knowledge about plausible parameter values and returns complete joint posterior distributions over these parameters. Application of our method to the early Covid-19 outbreak phase in Germany demonstrates that we are able to obtain reliable probabilistic estimates for important disease characteristics, such as generation time, fraction of undetected infections, likelihood of transmission before symptom onset, and reporting delays using a very moderate amount of real-world observations.
Population-Based Prevalence of Ocular Chlamydia trachomatis Infection among Infants in the Trachoma Endemic Amhara Region, Ethiopia

ABSTRACT. Infants ages < 6 months do not receive azithromycin as part of trachoma control and thus may serve as an infection reservoir in persistently endemic districts. The aim of this study was to determine the population-based Chlamydia trachomatis infection prevalence and infectious load among infants ages 1–12 months in persistently trachoma endemic districts in Amhara, Ethiopia. Across six districts, 475 infants were enumerated, and of these 464 (97.7%) were swabbed for infection testing. The C. trachomatis infection prevalence in the study area among infants was 0.2% (95% CI: 0.0–1.5). Among children ages 0–5 years positive for C. trachomatis, the median load was 31 elementary bodies (EB) (Inter quartile range: 7–244 EB), and the infection-positive infant had a load of 7,755 EB. While it is worth reconsidering azithromycin treatment recommendations for the potential mortality benefits, these results do not support lowering the treatment age for trachoma control.
Distinct displacement of the superficial and deep fascial layers of the iliotibial band during a weight shift task in runners: An exploratory study

Motion of the fascial layers of the iliotibial band (ITB), as a reinforcement of the deep fascia lata, is likely to be relevant for its function and mechanical behaviour. This exploratory study aimed to evaluate the ITB fascial layers displacement during a weight shift task. Thirteen pain‐free runners performed a 6‐second standing weight shift task. B‐mode ultrasound imaging using an automated fascicle tracking algorithm was used to measure proximal and distal displacement of superficial and deep ITB layers at the middle region. To study the potential contributors to individual variation of fascial motion, we recorded the activity of five hip/thigh muscles with electromyography (EMG), thigh/pelvis/trunk position with accelerometers, and centre of pressure with a force plate. Linear regressions estimated the relationship between displacement of fascial layers and hip/trunk angles. Independent t‐tests or Fisher's exact tests compared EMG and movement‐related parameters between participants who demonstrated motion of the fascia in the proximal and distal directions. Thickness of the ITB and the loose connective tissue between its layers were calculated. Proximal displacement was observed in six (−4.1 ± 1.9 mm [superficial]) and two (−6.2 ± 2.0 mm [deep]) participants. Distal displacement was observed for seven participants for each layer (3.1 ± 1.1 mm [superficial]; 3.6 ± 1.3 mm [deep]). Four participants did not show displacement of the deep layer. Trunk lateral flexion and gluteus medius muscle activity were determinants of proximal motion of the superficial layer. Loose connective tissue was thinner in participants without displacement of the deep layer. Displacement of the ITB fascial layers varies between individuals. Variation related to differences in joint movements and muscle activity. This study highlights the complex interaction between fascia and movement.
Comparative examination of pinniped craniofacial musculature and its role in aquatic feeding

Secondarily aquatic tetrapods have many unique morphologic adaptations for life underwater compared with their terrestrial counterparts. A key innovation during the land‐to‐water transition was feeding. Pinnipeds, a clade of air‐breathing marine carnivorans that include seals, sea lions, and walruses, have evolved multiple strategies for aquatic feeding (e.g., biting, suction feeding). Numerous studies have examined the pinniped skull and dental specializations for underwater feeding. However, data on the pinniped craniofacial musculoskeletal system and its role in aquatic feeding are rare. Therefore, the objectives of this study were to conduct a comparative analysis of pinniped craniofacial musculature and examine the function of the craniofacial musculature in facilitating different aquatic feeding strategies. We performed anatomic dissections of 35 specimens across six pinniped species. We describe 32 pinniped craniofacial muscles—including facial expression, mastication, tongue, hyoid, and soft palate muscles. Pinnipeds broadly conform to mammalian patterns of craniofacial muscle morphology. Pinnipeds also exhibit unique musculoskeletal morphologies—in muscle position, attachments, and size—that likely represent adaptations for different aquatic feeding strategies. Suction feeding specialists (bearded and northern elephant seals) have a significantly larger masseter than biters. Further, northern elephant seals have large and unique tongue and hyoid muscle morphologies compared with other pinniped species. These morphologic changes likely help generate and withstand suction pressures necessary for drawing water and prey into the mouth. In contrast, biting taxa (California sea lions, harbor, ringed, and Weddell seals) do not exhibit consistent craniofacial musculoskeletal adaptations that differentiate them from suction feeders. Generally, we discover that all pinnipeds have well‐developed and robust craniofacial musculature. Pinniped head musculature plays an important role in facilitating different aquatic feeding strategies. Together with behavioral and kinematic studies, our data suggest that pinnipeds’ robust facial morphology allows animals to switch feeding strategies depending on the environmental context—a critical skill in a heterogeneous and rapidly changing underwater habitat.
Quality of Life and Psychopathology in Lichen Planus: A Neglected Disease Burden

The disease burden of lichen planus and its impact on patients’ quality of life have not been well studied. The aim of this mono-centre cross-sectional study was to investigate these factors. From June to September 2020, an anonymous survey was posted to 253 patients, who were diagnosed with lichen planus in our outpatient clinic from January 2018 to June 2020. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI), the EuroQol 5-dimension 3-level score, and further quality of life indicators. Beck Depression Inventory II was used to evaluate symptoms of depression. A total of 100 patients completed and returned the survey. Lichen planus affected quality of life in 78% of cases. DLQI was higher for multiple localizations (r = 0.454, p < 0.001). Patients with genital lichen planus had a significantly higher DLQI (mean ± standard deviation (SD) 8.68 ± 6.96) than patients who were not affected in the genital area (5.01 ± 5.49; p = 0.009). DLQI was also significantly higher for ungual lichen planus (9.83 ± 7.6; not affected: 5.65 ± 5.84; p-value 0.039), and for cutaneous LP (mean 8.1, SD 6.22; not affected: 5.63 ± 6.12; p-value 0.045). Twenty-nine percent of patients had mild to moderate symptoms of depression, and 6% had severe symptoms of depression. Depression and reduced quality of life are an undetected and relevant burden affecting patients with lichen planus.
An Empirical Study on Adaptive Inference for Pretrained Language Model

Adaptive inference has been proven to improve bidirectional encoder representations from transformers (BERT)’s inference speed with minimal loss of accuracy. However, current work only focuses on the BERT model and lacks exploration of other pretrained language models (PLMs). Therefore, this article conducts an empirical study on the application of adaptive inference mechanism in various PLMs, including generative pretraining (GPT), GCNN, ALBERT, and TinyBERT. This mechanism is verified on both English and Chinese benchmarks, and experimental results demonstrated that it is able to speed up by a wide range from 1 to 10 times if given different speed thresholds. In addition, its application on ALBERT shows that adaptive inference can work with parameter sharing, achieving model compression and acceleration simultaneously, while the application on TinyBERT proves that it can further accelerate the distilled small model. As for the problem that too many labels make adaptive inference invalid, this article also proposes a solution, namely label reduction. Finally, this article open-sources an easy-to-use toolkit called FastPLM to help developers adopt pretrained models with adaptive inference capabilities in their applications.
AoP-LSE: Antioxidant Proteins Classification Using Deep Latent Space Encoding of Sequence Features

It is of utmost importance to develop a computational method for accurate prediction of antioxidants, as they play a vital role in the prevention of several diseases caused by oxidative stress. In this correspondence, we present an effective computational methodology based on the notion of deep latent space encoding. A deep neural network classifier fused with an auto-encoder learns class labels in a pruned latent space. This strategy has eliminated the need to separately develop classifier and the feature selection model, allowing the standalone model to effectively harness discriminating feature space and perform improved predictions. A thorough analytical study has been presented alongwith the PCA/tSNE visualization and PCA-GCNR scores to show the discriminating power of the proposed method. The proposed method showed a high MCC value of 0.43 and a balanced accuracy of 76.2%, which is superior to the existing models. The model has been evaluated on an independent dataset during which it outperformed the contemporary methods by correctly identifying the novel proteins with an accuracy of 95%.
Indicators of publicly funded prescription opioid use among persons with traumatic spinal cord injury in Ontario, Canada

Objective: To describe the proportion and identify predictors of community-dwelling individuals with traumatic spinal cord injury (TSCI) who were dispensed ≥1 publicly funded opioid in the year after injury using a retrospective cohort study. Setting: Ontario, Canada. Participants, Interventions, Outcome Measures: We used administrative data to identify predictors of receiving publicly funded prescription opioids during the year after injury for individuals who were injured between April 2004 and March 2015. Our outcome was modeled using robust Poisson multivariable regression and we reported adjusted relative risks (aRR) with 95% confidence intervals. Results: In our retrospective cohort of 934 individuals with TSCI who were eligible for the provincial drug program, 510 (55%) received ≥1 prescription opioid in the year after their injury. Most individuals were male (71%) and the median age was 63 years (interquartile range: 42–72). Being male (aRR 1.15, 95% confidence interval [CI] 1.01–1.31), having chronic obstructive pulmonary disease (aRR 1.25, 95% CI 1.05–1.50), and using prescription opioids before injury (aRR 1.46, 95% CI 1.29–1.66) were significantly associated with receiving opioids in the year after TSCI. Short durations of hospital stay after injury were also identified as being a significant risk factor of outpatient opioid use (aRR = 1.28, 95% CI = 1.08–1.51) when compared to longer hospital stays. Conclusion: This study presented evidence showing that most individuals eligible for Ontario’s public drug program who experienced a TSCI used opioids in the year following their injury. Due to the paucity of research on this population and their potential for elevated risks of adverse events, it is important for additional studies to be conducted on opioid use in this population to understand short-term and long-term risks and benefits.
Designing of cytotoxic T lymphocyte-based multi-epitope vaccine against SARS-CoV2: a reverse vaccinology approach

Abstract SARS-CoV2 is a single-stranded RNA virus, gaining much attention after it out broke in China in December 2019. The virus rapidly spread to several countries around the world and caused severe respiratory illness to humans. Since the outbreak, researchers around the world have devoted maximum resources and effort to develop a potent vaccine that would offer protection to uninfected individuals against SARS-CoV2. Reverse vaccinology is a relatively new approach that thrives faster in vaccine research. In this study, we constructed Cytotoxic T Lymphocytes (CTL)-based multi-epitope vaccine using hybrid epitope prediction methods. A total of 121 immunogenic CTL epitopes were screened by various sequence-based prediction methods and docked with their respective HLA alleles using the AutoDock Vina v1.1. 2. In all, 17 epitopes were selected based on their binding affinity, followed by the construction of multi-epitope vaccine by placing the appropriate linkers between the epitopes and tuberculosis heparin-binding hemagglutinin (HBHA) adjuvant. The final vaccine construct was modeled by the I-TASSER server and the best model was further validated by ERRAT, ProSA, and PROCHECK servers. Furthermore, the molecular interaction of the constructed vaccine with TLR4 was assessed by ClusPro 2.0 and PROtein binDIng enerGY prediction (PRODIGY) server. The immune simulation analysis confirms that the constructed vaccine was capable of inducing long-lasting memory T helper (Th) and CTL responses. Finally, the nucleotide sequence was codon-optimized by the JCAT tool and cloned into the pET21a (+) vector. The current results reveal that the candidate vaccine is capable of provoking robust CTL response against the SARS-CoV2. Communicated by Ramaswamy H. Sarma