Miracle-dz/UniFAR-FTUs huggingface dataset:
The use of organs from hepatitis C virus-viremic donors into uninfected recipients

Purpose of review There has been an ongoing disparity between the number of organs available for solid organ transplantation (SOT) relative to the need. This has resulted in significant waitlist mortality, may affect transplant outcomes due to transplants being performed on sicker patients and may even increase healthcare costs due to extended hospital stays. Transplanting organs from hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R−) is now a reality, due to the advent of highly affective direct-acting antivirals (DAAs) which not only have very high efficacy, but also a favorable side effect and drug–drug interaction profile. Recent findings Data from multiple centers reporting outcomes of kidney, liver, heart, lung and liver-kidney transplant during the past few years reveal that SOT from HCV-infected donors into noninfected recipients is safe, efficacious and can result in excellent recipient outcomes, with an opportunity to decrease the time on the waitlist, waitlist mortality and to improve outcomes after transplant due to less morbidity at the time of surgery. When livers are the transplanted organ, 8–12 weeks of DAA treatment will be required. For other organs, 2–4 weeks is likely sufficient. The available DAAs have profiles such that patients with all genotypes, with or without renal insufficiency an on renal replacement therapy and those who fail treatment may be successfully treated, with a sustained virologic response rate of more than 95%. Based upon the available data, starting DAAs shortly after transplant will likely limit posttransplant complications. that This will require cooperation between the transplant team, transplant hospital and insurer providing medication coverage. Summary SOT from HCV infected recipients is safe, is associated with excellent outcomes and should be considered for recipients who would benefit from receiving an organ earlier than they would if they waited for an organ from an uninfected donor.
Instagram as a Window to Societal Perspective on Mental Health, Gender, and Race: Observational Pilot Study

Background Gender and race are known to impact attitudes toward mental health topics and help-seeking behavior. Men and minorities are more likely to cite stigma as a reason for not seeking help for mental health concerns, which is of particular relevance given the high rate of suicide in men and challenges of historic proportion currently facing minority communities. Instagram provides a platform to discuss mental health, though a lack of male and minority representation may further alienate these populations. Objective We aimed to investigate whether men and nonwhite individuals are underrepresented in Instagram photos tagged with #mentalhealth (compared to photos tagged with #health) to better understand how gender and race-based representations are manifested on this popular social media platform and discuss the implications. Methods Three investigators of different genders and racial backgrounds met on nine different days via teleconference to analyze a total of 215 publicly available Instagram photos tagged with #mentalhealth and 215 with #health. These photos were generated using Instagram’s search function, and search results were sorted by most recently published at the time of data collection. For each photo, the three investigators recorded their observations about the gender (male versus female) and race (white versus nonwhite versus racially unclassifiable) of subjects featured in the photo, which they did not discuss with other investigators. Chi-squared analysis was performed on each investigator’s data set to compare the frequency of male versus female and white versus nonwhite subjects identified in each hashtag category. Kappa interrater agreement was calculated for each investigator pair, category (gender or race), and hashtag. Results All three investigators observed significantly more female as compared to male subjects in photos tagged with #mentalhealth (X2=14.4, P<.001 for all investigators) while observing no significant difference between numbers of male and female subjects in photos tagged with #health (X2=1.533, P=.22; X2=1.241, P=.27; X2=0.096, P=.76). All three investigators identified significantly more white than nonwhite subjects in photos tagged with both #health and #mentalhealth (X2 values range from 11.912 to 98.927, P<.001 for all). Kappa interrater agreement revealed almost perfect agreement for gender (kappa=0.908-0.992) with the agreement for race ranging from 0.614 to 0.822, depending on hashtag and rater pair. Conclusions Women are featured more frequently than men in Instagram photos tagged with #mentalhealth. The topic of #health, meanwhile, is not gendered this way. Low visibility of mental health among men may both represent and exacerbate existing stigma and barriers to care. White subjects are featured significantly more frequently than nonwhite subjects in photos tagged with both #mentalhealth and #health. Directed interventions using the Instagram platform may be indicated to increase the visibility of underrepresented groups and break the cycle of stigma.
Divergent Effects of G2019S and R1441C LRRK2 Mutations on LRRK2 and Rab10 Phosphorylations in Mouse Tissues

Mutations in LRRK2 cause familial Parkinson’s disease and common variants increase disease risk. LRRK2 kinase activity and cellular localization are tightly regulated by phosphorylation of key residues, primarily Ser1292 and Ser935, which impacts downstream phosphorylation of its substrates, among which Rab10. A comprehensive characterization of LRRK2 activity and phosphorylation in brain as a function of age and mutations is missing. Here, we monitored Ser935 and Ser1292 phosphorylation in midbrain, striatum, and cortex of 1, 6, and 12 months-old mice carrying G2019S and R1441C mutations or murine bacterial artificial chromosome (BAC)-Lrrk2-G2019S. We observed that G2019S and, at a greater extent, R1441C brains display decreased phospho-Ser935, while Ser1292 autophosphorylation increased in G2019S but not in R1441C brain, lung, and kidney compared to wild-type. Further, Rab10 phosphorylation, is elevated in R1441C carrying mice, indicating that the effect of LRRK2 mutations on substrate phosphorylation is not generalizable. In BAC-Lrrk2-G2019S striatum and midbrain, Rab10 phosphorylation, but not Ser1292 autophosphorylation, decreases at 12-months, pointing to autophosphorylation and substrate phosphorylation as uncoupled events. Taken together, our study provides novel evidence that LRRK2 phosphorylation in mouse brain is differentially impacted by mutations, brain area, and age, with important implications as diagnostic markers of disease progression and stratification.
Recombinant Myxoma Virus-Derived Immune Modulator M-T7 Accelerates Cutaneous Wound Healing and Improves Tissue Remodeling

Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or “fine tune” the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.
Using breath analysis as a screening tool to detect gastric cancer: a systematic review

Breath analysis has emerged as an experimental method of non-invasive screening of gastric cancer and identification of individuals suitable for confirmatory, diagnostic upper gastrointestinal endoscopy. We aimed to evaluate the accuracy and applicability of breath analysis for gastric cancer detection in adults. We searched MEDLINE, EMBASE, BIOSIS, CENTRAL, and Compendex up to 27 September 2020 for original studies analysing exhaled breath to detect gastric cancer in patients. Summary sensitivity and specificity analyses were obtained using a hierarchical bivariate method. Non-quantitative results were descriptively summarized. Risk of bias was assessed using the QUADAS-2 tool. This study protocol was pre-registered in PROSPERO (CRD42020139422). Twenty-four studies were included. Within these, breath analysis technologies most commonly used were mass spectrometry (MS)-based methods; other methods included volatile organic compound sensors and silicon nanowire field effect transistors. Fourteen studies (total n = 3028) involving all technologies reported quantitative results, with sensitivities ranging from 67%–100% and specificities from 71%–98%. The summary sensitivity across six studies utilizing MS-based breath analysis methods was 82.4% (95% CI: 78%–86%); summary specificity was 91.3% (95% CI: 83%–96%). Based on these values, we estimated that screening with MS-based breath tests could lower the number needed to screen (NNS) by more than eight-fold in the 15 countries with the highest prevalence of gastric cancer. Breath analysis is a promising method for gastric cancer detection with good diagnostic performance and potential to decrease the NNS for endoscopy-based gastric cancer detection. However, due to the heterogeneity of breath analysis technologies, rigorous studies with standardized, reproducible methods are needed to evaluate the clinical applicability of these technologies.
The impact of socioeconomic status on the utilization of total hip arthroplasty during 1995–2017: 104,055 THA cases and 520,275 population controls from national databases in Denmark

Background and purpose — In Denmark, all citizens are guaranteed free access to medical care, which should minimize socioeconomic status (SES) inequalities. We examined the association between SES and the utilization of total hip arthroplasty (THA) by age and over time. Patients and methods — Data on education, income, liquid assets, and occupation on 104,055 THA cases and 520,275 population controls were obtained from Danish health registers. We used logistic regression to estimate adjusted odds ratios (aOR) for THA with 95% confidence intervals (CI). Results — Risk (CI) of THA was higher for 45–55-year-olds with lowest vs. highest education (aOR 1.4 [1.3–1.5]), and for those with lowest vs. highest income (aOR 1.1 [1.0–1.2]). The association between education and income and higher risk of THA decreased with increasing age. The risk of THA was lower for persons with lowest vs. highest liquid assets in all age groups and time periods. The risk of THA was higher for persons with lowest education in 1995–2000 (aOR 1.2 [1.1-1.3]), but diminished in 2013–2017 (aOR 1.0 [1.0–1.0]). For those on lowest income there was a higher risk of THA in 1995–2000 (aOR 1.2 [1.1–1.3]), changing to lower risk in 2013–2017 (aOR 0.8 [0.8–0.9]). Interpretation — In a society where all citizens are guaranteed free access to medical care, we observed a social inequality in regard to the risk of THA with a development over time and in relation to age in most of our SES markers, showing a need for more patient involvement by implementing more focused interventions targeted to the most vulnerable patient groups identified as currently living alone, on low income, and with a low level of liquid assets.
Population Graph-Based Multi-Model Ensemble Method for Diagnosing Autism Spectrum Disorder

With the advancement of brain imaging techniques and a variety of machine learning methods, significant progress has been made in brain disorder diagnosis, in particular Autism Spectrum Disorder. The development of machine learning models that can differentiate between healthy subjects and patients is of great importance. Recently, graph neural networks have found increasing application in domains where the population’s structure is modeled as a graph. The application of graphs for analyzing brain imaging datasets helps to discover clusters of individuals with a specific diagnosis. However, the choice of the appropriate population graph becomes a challenge in practice, as no systematic way exists for defining it. To solve this problem, we propose a population graph-based multi-model ensemble, which improves the prediction, regardless of the choice of the underlying graph. First, we construct a set of population graphs using different combinations of imaging and phenotypic features and evaluate them using Graph Signal Processing tools. Subsequently, we utilize a neural network architecture to combine multiple graph-based models. The results demonstrate that the proposed model outperforms the state-of-the-art methods on Autism Brain Imaging Data Exchange (ABIDE) dataset.
Bone marrow mesenchymal stem cells-derived exosomal microRNA-150-3p promotes osteoblast proliferation and differentiation in osteoporosis.

BACKGROUND/AIM At present, much more studies have focused on the role of microRNAs (miRNAs) in osteoporosis, but the more specific role of miR-150-3p in osteoporosis still needs full exploration. We aim to investigate the role of miR-150-3p in osteoporosis and explore the related mechanisms. METHODS Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which exosomes were isolated. Osteoporosis models were established by ovariectomy and injected with transfected BMSCs exosomes. Bone formation markers in serum, histopathological changes and miR-150-3p, runt-related transcription factor 2 (Runx2) and Osterix expression, and bone status markers in femoral tissues were detected. Osteoblasts were isolated and co-cultured with the transfected BMSCs-derived exosomes. Osteoblast proliferation, cell differentiation and apoptosis, along with miR-150-3p, Runx2 and Osterix expression in osteoblasts were detected. RESULTS In vivo experiment demonstrated that miR-150-3p, Runx2 and Osterix expression were decreased while bone formation markers were decreased in osteoporosis. BMSCs exosomes attenuated osteoporosis which was further improved by up-regulated miR-150-3p in exosomes while impaired by down-regulated miR-150-3p in exosomes. In vitro experiments declared decreased miR-150-3p, Runx2 and Osterix expression, suppressed proliferation and encouraged apoptosis in osteoblasts in osteoporosis. BMSCs exosomes promoted osteoblast proliferation and differentiation and inhibited apoptosis, which was strengthened by raised exosomal miR-150-3p while disrupted by inhibited exosomal miR-150-3p. CONCLUSION Our study elucidates that exosomal miR-150-3p promotes osteoblast proliferation and differentiation in osteoporosis and provides a new clue for the treatment of patients with osteoporosis.
Proteomic Investigations of Two Pakistani Naja Snake Venoms Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles

Latest advancement of omics technologies allows in-depth characterization of venom compositions. In the present work we present a proteomic study of two snake venoms of the genus Naja i.e., Naja naja (black cobra) and Naja oxiana (brown cobra) of Pakistani origin. The present study has shown that these snake venoms consist of a highly diversified proteome. Furthermore, the data also revealed variation among closely related species. High throughput mass spectrometric analysis of the venom proteome allowed to identify for the N. naja venom 34 protein families and for the N. oxiana 24 protein families. The comparative evaluation of the two venoms showed that N. naja consists of a more complex venom proteome than N. oxiana venom. Analysis also showed N-terminal acetylation (N-ace) of a few proteins in both venoms. To the best of our knowledge, this is the first study revealing this posttranslational modification in snake venom. N-ace can shed light on the mechanism of regulation of venom proteins inside the venom gland. Furthermore, our data showed the presence of other body proteins, e.g., ankyrin repeats, leucine repeats, zinc finger, cobra serum albumin, transferrin, insulin, deoxyribonuclease-2-alpha, and other regulatory proteins in these venoms. Interestingly, our data identified Ras-GTpase type of proteins, which indicate the presence of extracellular vesicles in the venom. The data can support the production of distinct and specific anti-venoms and also allow a better understanding of the envenomation and mechanism of distribution of toxins. Data are available via ProteomeXchange with identifier PXD018726.
Ferroptosis Mediates Cuprizone-Induced Loss of Oligodendrocytes and Demyelination

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. Cuprizone (CZ), a copper chelator, is widely used to study demyelination and remyelination in the CNS, in the context of MS. However, the mechanisms underlying oligodendrocyte (OL) cell loss and demyelination are not known. As copper-containing enzymes play important roles in iron homeostasis and controlling oxidative stress, we examined whether chelating copper leads to disruption of molecules involved in iron homeostasis that can trigger iron-mediated OL loss. We show that giving mice (male) CZ in the diet induces rapid loss of OL in the corpus callosum by 2 d, accompanied by expression of several markers for ferroptosis, a relatively newly described form of iron-mediated cell death. In ferroptosis, iron-mediated free radicals trigger lipid peroxidation under conditions of glutathione insufficiency, and a reduced capacity to repair lipid damage. This was further confirmed using a small-molecule inhibitor of ferroptosis that prevents CZ-induced loss of OL and demyelination, providing clear evidence of a copper-iron connection in CZ-induced neurotoxicity. This work has wider implications for disorders, such as multiple sclerosis and CNS injury. SIGNIFICANCE STATEMENT Cuprizone (CZ) is a copper chelator that induces demyelination. Although it is a widely used model to study demyelination and remyelination in the context of multiple sclerosis, the mechanisms mediating demyelination is not fully understood. This study shows, for the first time, that CZ induces demyelination via ferroptosis-mediated rapid loss of oligodendrocytes. This work shows that chelating copper with CZ leads to the expression of molecules that rapidly mobilize iron from ferritin (an iron storage protein), that triggers iron-mediated lipid peroxidation and oligodendrocyte loss (via ferroptosis). Such rapid mobilization of iron from cellular stores may also play a role in cell death in other neurologic conditions.
Evaluation of Stylosanthes scabra Accessions as Forage Source for Ruminants: Growth Performance, Nutritive Value and In Vitro Ruminal Fermentation

Simple Summary Livestock production under smallholder farmers is limited by scarcity of good quality forage throughout the year. Therefore, there is a need to evaluate alternative forage crops to improve poor quality of the available forage source. Stylosanths scabra (Shrubby Stylo) is an important drought tolerant forage legume suitable for seasonally dry environments. It is a shrubby, erect legume with a long tap root system that make the species drought tolerant and able to produce moderate high quality forage under rain fed condition. Hence, Stylosanthes scabra is a good candidate species that need to be tested as an alternative forage source for smallholder farmers in tropical and subtropical climatic conditions often prone to drought and frost, owing to their biomass yield and nutritive value. Abstract Feed shortage is the main cause of poor production performance in livestock under smallholder farmer’s in South Africa. Therefore, this study evaluated the growth performance, nutritive value and in vitro ruminal fermentation of Stylosanthes scabra accessions in climatic condition of Pretoria, South Africa as potential forage sources in order to improve feed quality and subsequently livestock production. Stylosanthes scabra accessions were planted in 6 m2 plots following a complete randomized block design with three replicates per accession. The plants were allowed to grow to full maturity after which forage was harvested and yield, chemical composition, phenolic compounds, in vitro organic matter digestibility (IVOMD) and in vitro ruminal fermentation characteristic were determined. Forage yield of accessions ranged between 4.3 to 5.3 t ha−1 in dry matter (DM), and only twelve accessions were identified to be adaptable over the three-year evaluation under rain-fed. Accessions 140, 9281, 11,252, 11,595, 11,604 and 11,625 were consistent in terms of forage yield over the three years Significant differences among accessions were observed for crude protein (CP), neutral detergent fiber (NDF), IVOMD, metabolizable energy, metabolizable energy yield, gas production, total phenols, total hydrolysable tannins and total condensed tannins. Principal component and clustering analysis showed that accessions 11,255 and 11,625 are distinct in their characteristics as compared to the rest of the accessions, and both accessions are suitable forage source for animals since they contain low NDF with good forage production and crude protein content. However, there is a need for further study to integrate these accessions into the feeding systems in order to improve livestock production.
Physiological and social synchrony as markers of PTSD and resilience following chronic early trauma

Although resilience is a key topic in clinical theory and research, few studies focused on biobehavioral mechanisms that underpin resilience. Guided by the biobehavioral synchrony frame, we examined the dynamic interplay of physiological and behavioral synchrony as marker of risk and resilience in trauma‐exposed youth.
Agrobacterium T-DNA integration in somatic cells does not require the activity of DNA polymerase theta.

Integration of Agrobacterium tumefaciens T-(transferred) DNA into the plant genome is the last step required for stable plant genetic transformation. The mechanism of T-DNA integration remains controversial, although scientists have proposed the participation of various non-homologous end-joining (NHEJ) pathways. Recent evidence suggests that in Arabidopsis, DNA polymerase θ (PolQ) may be a crucial enzyme involved in T-DNA integration. We conducted quantitative transformation assays of wild-type and polQ mutant Arabidopsis and rice, analyzed T-DNA/plant DNA junction sequences, and (for Arabidopsis) measured the amount of integrated T-DNA in mutant and wild-type tissue. Unexpectedly, we were able to generate stable transformants of all tested lines, although the transformation frequency of polQ mutants was ~20% that of wild-type plants. T-DNA/plant DNA junctions from these transformed rice and Arabidopsis polQ mutants closely resembled those from wild-type plants, indicating that loss of PolQ activity does not alter the characteristics of T-DNA integration events. polQ mutant plants show growth and developmental defects, perhaps explaining previous unsuccessful attempts at their stable transformation. We suggest that either multiple redundant pathways function in T-DNA integration, and/or that integration requires some yet unknown pathway.