Miracle-dz/UniFAR-FTUs huggingface dataset:
N‐methyl‐d‐aspartate (NMDA) receptor genetics: The power of paralog homology and protein dynamics in defining dominant genetic variants

Predicting genotype‐to‐phenotype correlations from genomic variants has been challenging, particularly for genes that have a complex balance of dominant and recessive inheritance for phenotypes. Variants in NMDA receptor components GRIN1, GRIN2A, and GRIN2B cause a myriad of dominant disease phenotypes, with the most common being epilepsy and autism spectrum disorder. Starting from the analysis of a variant of uncertain significance (VUS, GRIN2A G760S), we realized the need for tools to map dominant variants for the components of the NMDA receptor. Some variants within GRIN1, GRIN2A, and GRIN2B exert dominant epilepsy and developmental delay, yet other amino acid variants are conserved and predicted to alter protein function but do not have dominant phenotypes. Common variant annotation tools are not powered to determine pathogenic dominant outcomes. To address this gap, we integrated sequence and structural analyses for GRIN1, GRIN2A, and GRIN2B. Using this approach, we determined that paralog homology mapping and topology can segregate dominant variants, with an elevation of intermolecular contacts between the subunits. Furthermore, demonstrating the general utility of our methodology, we show that 25 VUS within ClinVar also reach a dominant variant annotation, including the GRIN2A G760S variant. Our work suggests paralog homology and protein topology as a powerful strategy within the receptor complex to resolve dominant genetic variants relative to variants that would fit a recessive inheritance, requiring two damaging variants. These strategies should be tested in additional dominant genetic disorders to determine the broader utility.
Genomic Epidemiology and Characterization of Methicillin-Resistant Staphylococcus aureus from Bloodstream Infections in China

As a developing country, China has an unbalanced health care system due to regional differences in economic development. However, China is also a country worthy of study with regard to the population dynamics of MRSA within the more resource-rich health care systems. ABSTRACT Since 2010, methicillin-resistant Staphylococcus aureus (MRSA) ST59 began to increase in prevalence in China, gradually replacing ST239 and has become the dominant clone in most hospitals in China. Here, we investigated the changing epidemiology, phylogenetic reconstruction, and genomic characterization of MRSA clones in China to identify the genomic driving factors in the prevalence of ST59. Most MRSA isolates were identified as ST59 (36.98%; 277/749), which increased from 25.09% in 2014 to 35.53% in 2019. The phylogenetic analysis of the 749 MRSA isolates showed a high level of diversity and the copresence of hospital-associated, community-associated, livestock-associated, and hypervirulent clones. Furthermore, minimum spanning trees revealed that ST59 MRSA clones from different hospitals and regions were integrated, suggesting that frequent exchanges had occurred between regions and hospitals. ST59 clones displayed higher susceptibility to antimicrobials than did ST239 and ST5 MRSA clones, indicating that resistance to non-β-lactam and fluoroquinolone antibiotics may be not critical for the epidemic success of ST59 clones. Virulence factors detection showed that sak and chp genes enriched in MRSA ST59 may be associated with the enhanced spreading success of ST59, whereas qacA may have contributed to the predominance of ST5 in East China. Our refined analysis of different clones among ST239, ST5, ST59, and ST398 demonstrated the existence of potential driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement. IMPORTANCE As a developing country, China has an unbalanced health care system due to regional differences in economic development. However, China is also a country worthy of study with regard to the population dynamics of MRSA within the more resource-rich health care systems. In this study, we carried out genomic analysis to investigate the genomic epidemiology and characterization of MRSA isolated from bloodstream infections over a timespan of 6 years. Our refined analysis of different MRSA clones among ST59, ST5, ST239, and ST398 demonstrated the existence of driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement.
mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional αβ and γδ T cells in Kidney Transplantation

Significance Statement It has been reported that mTOR inhibitors (mTORis) are associated with a reduction in the incidence of cytomegalovirus (CMV) infection in organ transplant patients who are CMV seropositive (R+), but a mechanistic explanation has been lacking to date. This work showed that a dysfunctional T-cell phenotype (CD85j+ PD-1+) was associated with a higher risk of uncontrolled CMV infection after transplantation in patients who were R+, and that mTORis reduced CMV incidence and severity by reinvigorating αβ and γδ T-cell function. Dysfunctional T-cell phenotype could represent a new biomarker to predict post-transplantation infection in patients who are R+ and to stratify patients who should benefit from treatment with mTORis. Visual Abstract Background The reported association of mTOR-inhibitor (mTORi) treatment with a lower incidence of cytomegalovirus (CMV) infection in kidney transplant recipients (KTR) who are CMV seropositive (R+) remains unexplained. Methods The incidence of CMV infection and T-cell profile was compared between KTRs treated with mTORis and mycophenolic acid (MPA), and in vitro mTORi effects on T-cell phenotype and functions were analyzed. Results In KTRs who were R+ and treated with MPA, both αβ and γδ T cells displayed a more dysfunctional phenotype (PD-1+, CD85j+) at day 0 of transplantation in the 16 KTRs with severe CMV infection, as compared with the 17 KTRs without or with spontaneously resolving CMV infection. In patients treated with mTORis (n=27), the proportion of PD-1+ and CD85j+ αβ and γδ T cells decreased, when compared with patients treated with MPA (n=44), as did the frequency and severity of CMV infections. mTORi treatment also led to higher proportions of late-differentiated and cytotoxic γδ T cells and IFNγ-producing and cytotoxic αβ T cells. In vitro, mTORis increased proliferation, viability, and CMV-induced IFNγ production of T cells and decreased PD-1 and CD85j expression in T cells, which shifted the T cells to a more efficient EOMESlow Hobithigh profile. In γδ T cells, the mTORi effect was related to increased TCR signaling. Conclusion Severe CMV replication is associated with a dysfunctional T-cell profile and mTORis improve T-cell fitness along with better control of CMV. A dysfunctional T-cell phenotype could serve as a new biomarker to predict post-transplantation infection and to stratify patients who should benefit from mTORi treatment. Clinical Trial registry name and registration number: Proportion of CMV Seropositive Kidney Transplant Recipients Who Will Develop a CMV Infection When Treated With an Immunosuppressive Regimen Including Everolimus and Reduced Dose of Cyclosporine Versus an Immunosuppressive Regimen With Mycophenolic Acid and Standard Dose of Cyclosporine A (EVERCMV), NCT02328963
Energy-Transfer Pathways and Triplet Lifetime Manipulation in a Zinc Porphyrin/F8BT Hybrid Polymer

Triplet states are ubiquitous in organic electronics and their properties are increasingly being exploited to enhance device efficiencies. The difficulty in accurately probing triplet states dictates that more fundamental understanding is required of their properties. In this work, a hybrid co-polymer of poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT) with 10% by weight zinc porphyrin was synthesized and a transient absorption spectroscopy study performed. It was observed that a dual energy-transfer mechanism was active, whereby the ultimate fate of each photogenerated F8BT singlet exciton depended upon its distance to a porphyrin unit. F8BT excitons generated within the bulk of the F8BT polymer showed typical F8BT photophysics, with the small proportion of F8BT triplets created able to diffuse to and undergo triplet energy transfer to the porphyrin units. In contrast, F8BT singlet excitons formed within their diffusion length to a porphyrin unit displayed singlet energy transfer, followed by intersy.
The Effects of the Urea and Mixture-T on Residual Oil Gasification Into Methane Under Reservoir Simulation System

A simulation reservoir system was designed to study the process of transforming residual oil into methane by indigenous microbes under initial pressure 10MPa, 55oC and the simulation time was 465 days. The Urea was used with four levels (U), U1 0mg/L, U2 200mg/L, U3 300mg/L, U4 400mg/L. the mixture-T (surfactant Tween 80 and complexing agent EDTA, proportion was 5:1) had five levels: 0CMC(Critical Micelle Concentration), 0.5CMC, 1CMC, 2CMC, 3CMC. The CMC was 14mg/L and the sterile treatments were control. When the urea concentration was 300mg/L or 400mg/L, the methane yield were both highest and the difference was not significant. When the additives mixture-T amount reached CMC, the methane yield was highest and among 1CMC, 2CMC and 3CMC treatments the difference was not significant. Meanwhile the urea and mixture T had additive effect on methane yield(3CMC-U4 treatment was highest), and oil removal efficiency had similar trend.
Occult Hepatitis B virus (HBV) infection and challenges for hepatitis elimination: A literature review

Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum or liver but negativity for hepatitis B surface antigen. OBI, which is thought to be maintained by host, immunological, viral and/or epigenetic factors, is one of the most challenging clinical features in the study of viral hepatitis. Currently, there is no validated detection test for OBI. It is believed that OBI is widely distributed throughout the world, with a higher prevalence in populations at high‐risk HBV, but the detailed worldwide prevalence patterns are unknown. We conducted a survey of recently published studies on OBI rates across all continents. High prevalence rates of OBI are observed in some specific groups, including patients with hepatitis C virus, human immunodeficiency virus co‐infection or hepatocellular carcinoma. In 2016, the World Health Organization adopted strategies to eliminate viral hepatitis by 2030, but the difficulties in detecting and treating OBI currently challenge this goal. Subjects with OBI can transmit HBV, and episodes of reactivation can occur. Further studies to understanding the mechanisms that drive the development of OBI are needed and can contribute to efforts at eliminating viral hepatitis.
Local Tobacco 21 Policies are Associated With Lower Odds of Tobacco Use Among Adolescents.

INTRODUCTION Tobacco 21 (T21) policies have shown promise in reducing cigarette use among adolescents. This study examined whether local T21 policies affected adolescent use of a variety of tobacco products and whether results differed by grade level. METHODS We used repeated cross-sectional data from eighth, ninth, and eleventh-grade respondents to the 2016 (n = 107 981) and 2019 (n = 102 196) Minnesota Student Surveys. Generalized estimating equations modeled eight adolescent tobacco use outcomes in 2019 (past 30-day use of any tobacco, cigarettes, cigars, e-cigarettes, hookah, chewing tobacco, flavored tobacco, and multiple products) by T21 exposure, defined as respondents' attendance at a school within a jurisdiction with T21 policy implementation between the two surveys. Models controlled for demographic characteristics and product-specific baseline tobacco use at the school level in 2016 and were stratified by grade. RESULTS After adjusting for baseline tobacco use and other demographics, T21-exposed eighth and ninth-grade students had significantly lower odds of tobacco use than unexposed peers in five of eight models, i.e. any tobacco (aOR = 0.80, 95% CI: 0.74, 0.87), cigarettes (aOR = 0.81, 95% CI: 0.67, 0.99), e-cigarettes (aOR = 0.78, 95% CI: 0.71, 0.85), flavored tobacco (aOR = 0.79, CI: 0.70, 0.89), and dual/poly tobacco (aOR = 0.77, 95% CI: 0.65, 0.92). T21-exposed eleventh-grade students did not differ significantly in their odds of any tobacco use outcomes relative to their unexposed peers. CONCLUSIONS T21 exposure is associated with lower odds of multiple forms of tobacco use, particularly among younger adolescent populations, supporting the implementation of T21 policies to reduce tobacco use in this population.
Oxidative stress response and programmed cell death guided by NAC013 modulate pithiness in radish taproots

SUMMARY Radish, Raphanus sativus L. , is an important root crop that is cultivated worldwide. Owing to its evolutionary proximity to Arabidopsis thaliana, radish can be used as a model root crop in research on the molecular basis of agronomic traits. Pithiness is a significant defect that reduces the production of radish with commercial value; however, traditional breeding to eliminate this trait has thus far been unsuccessful. Here, we performed transcriptomics and genotype‐by‐sequencing (GBS)‐based quantitative trait locus (QTL) analyses of radish inbred lines to understand the molecular basis of pithiness in radish roots. The transcriptome data indicated that pithiness likely stems from the response to oxidative stress, leading to cell death of the xylem parenchyma during the root‐thickening process. Subsequently, we narrowed down a list of candidates responsible for pithiness near a major QTL and found polymorphisms in a radish homologue of Arabidopsis ANAC013 (RsNAC013), an endoplasmic reticulum bound NAC transcription factor that is targeted to the nucleus to mediate the mitochondrial retrograde signal. We analysed the effects of polymorphisms in RsNAC013 using Arabidopsis transgenic lines overexpressing RsNAC013 alleles as well as in radish inbred lines bearing these alleles. This analysis indicated that non‐synonymous variations within the coding sequence result in different levels of RsNAC013 activities, thereby providing a genetic condition for root pithiness. The elevated oxidative stress or hypoxia that activates RsNAC013 for mitochondrial signalling enhances this process. Collectively, this study serves as an exemplary case of translational research taking advantage of the extensive information available from a model organism.
Use of virtual and augmented reality-based interventions in health education to improve dementia knowledge and attitudes: an integrative review

Objectives Immersive technologies such as virtual (VR) and augmented reality (AR) can potentially help health professionals and trainees understand psychological symptoms and responsive behaviours associated with dementia within a safe and supportive learning environment. This integrative review sought to ascertain the types of VR and AR-based interventions used in dementia education and training and its efficacy to improve knowledge and attitudes of health professionals or trainees. Design The protocol was submitted to PROSPERO and literature published from 2000 onwards was searched in eight databases: CINAHL, MEDLINE, Web of Science, Cochrane, Embase, PsycINFO, ERIC and Scopus. A total of 19 articles were included and assessed with the Mixed Methods Appraisal Tool. Methodological quality varied across studies. Results VR rather than AR-based intervention are used in dementia education and training for health professional and trainees. Immersive virtual learning potentially enhance knowledge, attitudes, empathy and sensitivity of health professionals and trainees. Conclusions While promising, there remains a lack of conclusive and robust evidence to fully recommend the introduction and inclusion of immersive virtual learning in dementia education and training. Additional rigorously designed research studies with larger sample sizes are needed to confirm the benefits on attitudes, empathy, sensitivity and knowledge. PROSPERO registration number CRD42020182083.
Transgender and nonbinary individuals and ICT-driven information practices in response to transexclusionary healthcare systems: a qualitative study

OBJECTIVE This qualitative research examines how transgender and gender nonbinary (T/GNB) persons from South Carolina navigate informational barriers within healthcare systems. This navigation can be described through the lens of information practices, or how T/GNB participants create, seek, use, and share information to achieve desired healthcare outcomes. Special focus is given to the roles of Information and Communication Technologies (ICTs) in shaping these practices. MATERIALS AND METHODS The research utilizes participant data from semistructured interviews and focus groups conducted with 26 T/GNB individuals focusing on their health information practices. Data analysis utilized emic/etic coding and the constant comparative method to identify themes describing transexclusionary information barriers and respondent ICT-led information practices. RESULTS Findings note healthcare systems producing cisnormativity by design resulting in T/GNB individuals viewing healthcare spaces as exclusionary. Exclusionary barriers included over reliance on medical, expert authority ignoring T/GNB embodiment, and a lack of contextual perspective to identities. In response, T/GNB seek, create, use, and share information via ICTs to challenge exclusionary practices. DISCUSSION T/GNB ICT use addresses systemic barriers within healthcare systems suggesting a need to reframe healthcare systems through the lens of design justice, one that values T/GNB agency in understanding and producing health knowledge. CONCLUSION While many healthcare providers are not intentionally being transexclusionary, the design of healthcare information systems rely on cisnormative values, thus excluding many T/GNB from accessing healthcare in comfortable and safe ways. Shifting toward the values and practices of T/GNB as informed by ICT use will afford healthcare providers ways to undo barriers to care.
Effectiveness of current perioperative telemonitoring on postoperative outcome in patients undergoing major abdominal surgery: A systematic review of controlled trials

Background Perioperative telemonitoring of patients undergoing major surgery might lead to improved postoperative outcomes. The aim of this systematic review is to evaluate the effectiveness of current perioperative telemonitoring interventions on postoperative clinical, patient-reported, and financial outcome measures in patients undergoing major surgery. Methods For this systematic review, PubMed, CINAHL, and Embase databases were searched for eligible articles published between January 1, 2009 and March 15, 2021. Studies were eligible as they described: (P) patients aged 18 years or older who underwent major abdominal surgery, (I) perioperative telemonitoring as intervention, (C) a control group receiving usual care, (O) any type of postoperative clinical, patient-reported, or financial outcome measures, and (S) an interventional study design. Results The search identified 2958 articles of which 10 were eligible for analysis, describing nine controlled trials of 2438 patients. Perioperative telemonitoring comprised wearable biosensors (n = 3), websites (n = 3), e-mail (n = 1), and mobile applications (n = 2). Outcome measures were clinical (n = 8), patient-reported (n = 5), and financial (n = 2). Results show significant improvement of recovery time, stoma self-efficacy and pain in the early postoperative phase in patients receiving telemonitoring. Other outcome measures were not significantly different between the groups. Conclusion Evidence for the effectiveness of perioperative telemonitoring in major surgery is scarce. There is a need for good quality studies with sufficient patients while ensuring that the quality and usability of the technology and the adoption in care processes are optimal.
IMSANZ 2021 INTERNAL MEDICINE SOCIETY OF AUSTRALIA AND NEW ZEALAND ANNUAL SCIENTIFIC MEETING

Methods: Patients who received DOACs during admission under a general medical unit over a two-year period were retrospectively studied. Appropriateness of the dosing regimen was verified against the recommendations of the Australian Therapeutic Guidelines. Following index admission, patients were followed for 12 months or for the duration of treatment (if the latter was less than 12 months) for bleeding and thrombotic complications. The relevant data were obtained by review of medical records.
Cutaneous silent period in ulnar neuropathy at the elbow

The cutaneous silent period (CSP) reflects the function of A‐delta sensory fibers. There are few studies on CSP in nerve entrapment syndromes. This study aims to evaluate the neurophysiological abnormalities of small‐diameter sensory fibers in ulnar neuropathy at the elbow (UNE) by means of CSP.
Dorsomedial Striatal Activity Tracks Completion of Behavioral Sequences in Rats

Abstract For proper execution of goal-directed behaviors, individuals require both a general representation of the goal and an ability to monitor their own progress toward that goal. Here, we examine how dorsomedial striatum (DMS), a region pivotal for forming associations among stimuli, actions, and outcomes, encodes the execution of goal-directed action sequences that require self-monitoring of behavior. We trained rats to complete a sequence of at least five consecutive lever presses (without visiting the reward port) to obtain a reward and recorded the activity of individual cells in DMS while rats performed the task. We found that the pattern of DMS activity gradually changed during the execution of the sequence, permitting accurate decoding of sequence progress from neural activity at a population level. Moreover, this sequence-related activity was blunted on trials where rats did not complete a sufficient number of presses. Overall, these data suggest a link between DMS activity and the execution of behavioral sequences that require monitoring of ongoing behavior.
[Purification and Characterization of Pectinase from Aspergillus ustus BL5]*

Pectinase is an enzyme that could hydrolyze pectin into galacturonic acid. Natural pectinase was produced by microbes such as bacteria, yeast, fungi and Actinomycetes. Application of pectinase in industry were mainly in juice industry, textile, pulp, tea, cocoa and coffee fermentation. In this research, we conducted purification and characterization of pectinase produced by Aspergillus ustus BL5 in submerged fermentation using commercial pectin. The result showed that the optimum of pectinase production was reached at 120 hours fermentation process with specific activity 0.59 U/mg. The crude extract of pectinase was then concentrated using PEG 6000 and purified by Sephadex G -75 gel filtration chromatography. There were 2 fractions contained pectinase which the activity was 4.15 U/mg (pectinase A) and 3.3 U/mg (pectinase B), respectively. Compare to crude extract, the yield product of pectinase A and B increased 6.94 and 5.53 times, respectively. The purified pectinase A have optimum temperature at 50 C and optimun pH at 5.