Miracle-dz/UniFAR-FTUs huggingface dataset:
Dendritic Cell Expression of Retinal Aldehyde Dehydrogenase-2 Controls Graft-versus-Host Disease Lethality

Recent studies have underscored the critical role of retinoic acid (RA) in the development of lineage-committed CD4 and CD8 T cells in vivo. We have shown that under acute graft-versus-host disease (GVHD) inflammatory conditions, RA is upregulated in the intestine and is proinflammatory, as GVHD lethality was attenuated when donor allogeneic T cells selectively expressed a dominant negative RA receptor α that blunted RA signaling. RA can function in an autocrine and paracrine fashion, and as such, the host cell lineage responsible for the production of RA metabolism and the specific RA-metabolizing enzymes that potentiate GVHD severity are unknown. In this study, we demonstrate that enhancing RA degradation in the host and to a lesser extent donor hematopoietic cells by overexpressing the RA-catabolizing enzyme CYP26A1 reduced GVHD. RA production is facilitated by retinaldehyde isoform-2 (RALDH2) preferentially expressed in dendritic cells (DCs). Conditionally deleted RA-synthesizing enzyme RALDH2 in host or to a lesser extent donor DCs reduced GVHD lethality. Improved survival in recipients with RALDH2-deleted DCs was associated with increased T cell death, impaired T effector function, increased regulatory T cell frequency, and augmented coinhibitory molecule expression on donor CD4+ T cells. In contrast, retinaldehydrogenase isoform-1 (RALDH1) is dominantly expressed in intestinal epithelial cells. Unexpectedly, conditional host intestinal epithelial cells RALDH1 deletion failed to reduce GVHD. These data demonstrate the critical role of both donor and especially host RALDH2+ DCs in driving murine GVHD and suggest RALDH2 inhibition or CYP26A1 induction as novel therapeutic strategies to prevent GVHD.
Intimate Partner Violence among Women with Disabilities in Uganda

Violence against women with disabilities is pervasive, yet a paucity of research examines intimate partner violence (IPV) experienced by women with disabilities in low- and middle-income countries. The purpose of this study is to document the prevalence and consequences of IPV exposure among Ugandan women with disabilities. Cross sectional data from the 2011 and 2016 Uganda Demographic and Health Surveys (UDHS) were used to study married and/or partnered women aged 15–49 who answered specific questions about lifetime intimate partner violence (N = 8592). Univariate and multivariate logistic regression models were used to investigate the relationship between disability, IPV, and indicators of maternal and child health. Compared to women without disabilities, women with disabilities were more likely to experience lifetime physical violence (odds ratio (OR) 1.4, p < 0.01), sexual violence (OR = 1.7, p < 0.01), and emotional abuse (1.4, p < 0.01) after controlling for sociodemographic and household characteristics. Study findings suggest that women with disabilities in Uganda may experience increased risk for IPV compared to women without disabilities, with concomitant risks to their health and the survival of their infants. Further research examining the prevalence and correlates of IPV in low- and middle-income countries is needed to address the needs and rights of women with disabilities.
Ammonium tetrathiomolybdate treatment of copper‐associated hepatopathy in dogs

Abstract Background Copper‐associated hepatopathy (CAH) is a common cause of liver disease in dogs. Although d‐penicillamine can be an effective treatment, some dogs fail treatment or develop adverse effects. Ammonium tetrathiomolybdate (TTM) has been used to treat pathologic copper accumulation in other species, but its therapeutic potential for CAH is unknown. Objectives To investigate short‐term safety and efficacy of TTM for treatment of CAH. Animals Ten dogs with CAH. Methods Prospective study. All dogs were treated with TTM PO for 6 weeks, and hepatic biopsies were performed after the treatment course. Dog experiencing initial decreases in hepatic copper concentrations ([Cu]H) received 6 additional weeks of TTM treatment and underwent 1 additional biopsy. Physical and laboratory examinations were performed every 2 weeks for study duration. Results Eight of 10 dogs had decreases in [Cu]H. Compared to baseline (median, 1606 μg/g; range, 572‐5158 μg/g), [Cu]H were decreased at 6 weeks (1033 μg/g, 450‐2975 μg/g; P = .04) and 12 weeks (931 μg/g, 218‐1677 μg/g; P = .02). Hepatic molybdenum concentrations increased >50‐fold (P < 0.001). Changes in histologic scores and hematologic and biochemical test results were variable and not significantly different from baseline. One dog developed presumed immune‐mediated anemia and thrombocytopenia, but it was unclear if this was related to TTM administration. Conclusions and Clinical Importance Results suggest that TTM can effectively decrease [Cu]H in some dogs with CAH. Larger studies are needed to determine the overall safety and efficacy of TTM for treating CAH and how it compares with current treatments.
Anthropogenic enhancements to production of highly oxygenated molecules from autoxidation

Significance Government organizations set standards for permissible levels of atmospheric particulate matter (PM) due to its adverse effects on human health and the environment. Unimolecular reactions that efficiently produce organic PM are suppressed by NOx, allowing for potential increases in PM mass due to controls on anthropogenic NOx. Using laboratory experiments and observations of the atmosphere, we assemble a conceptual understanding of how PM from unimolecular organic reactions is affected by NOx. We demonstrate that the NOx penalty on PM yield can be offset by reductions in oxidant abundance. As a result, PM from unimolecular reactions is predicted to decrease as NOx is controlled, consistent with declines in ambient organic aerosol observed in the United States between 1990 and today. Atmospheric oxidation of natural and anthropogenic volatile organic compounds (VOCs) leads to secondary organic aerosol (SOA), which constitutes a major and often dominant component of atmospheric fine particulate matter (PM2.5). Recent work demonstrates that rapid autoxidation of organic peroxy radicals (RO2) formed during VOC oxidation results in highly oxygenated organic molecules (HOM) that efficiently form SOA. As NOx emissions decrease, the chemical regime of the atmosphere changes to one in which RO2 autoxidation becomes increasingly important, potentially increasing PM2.5, while oxidant availability driving RO2 formation rates simultaneously declines, possibly slowing regional PM2.5 formation. Using a suite of in situ aircraft observations and laboratory studies of HOM, together with a detailed molecular mechanism, we show that although autoxidation in an archetypal biogenic VOC system becomes more competitive as NOx decreases, absolute HOM production rates decrease due to oxidant reductions, leading to an overall positive coupling between anthropogenic NOx and localized biogenic SOA from autoxidation. This effect is observed in the Atlanta, Georgia, urban plume where HOM is enhanced in the presence of elevated NO, and predictions for Guangzhou, China, where increasing HOM-RO2 production coincides with increases in NO from 1990 to 2010. These results suggest added benefits to PM2.5 abatement strategies come with NOx emission reductions and have implications for aerosol–climate interactions due to changes in global SOA resulting from NOx interactions since the preindustrial era.
A Cytosolic Bypass and G6P Shunt in Plants Lacking Peroxisomal Hydroxypyruvate Reductase1[OPEN]

Triose phosphate isomerase inhibition in plants lacking peroxisomal hydroxypyruvate reductase is overcome by exporting triose phosphate and importing Glc 6 P, but this stimulates a Glc 6 P shunt and cyclic electron flow. The oxygenation of ribulose 1,5-bisphosphate by Rubisco is the first step in photorespiration and reduces the efficiency of photosynthesis in C3 plants. Our recent data indicate that mutants in photorespiration have increased rates of photosynthetic cyclic electron flow around photosystem I. We investigated mutant lines lacking peroxisomal hydroxypyruvate reductase to determine if there are connections between 2-phosphoglycolate accumulation and cyclic electron flow in Arabidopsis (Arabidopsis thaliana). We found that 2-phosphoglycolate is a competitive inhibitor of triose phosphate isomerase, an enzyme in the Calvin-Benson cycle that converts glyceraldehyde 3-phosphate to dihydroxyacetone phosphate. This block in metabolism could be overcome if glyceraldehyde 3-phosphate is exported to the cytosol, where cytosolic triose phosphate isomerase could convert it to dihydroxyacetone phosphate. We found evidence that carbon is reimported as glucose-6-phosphate, forming a cytosolic bypass around the block of stromal triose phosphate isomerase. However, this also stimulates a glucose-6-phosphate shunt, which consumes ATP, which can be compensated by higher rates of cyclic electron flow.
Antithrombotics from the Sea: Polysaccharides and Beyond

Marine organisms exhibit some advantages as a renewable source of potential drugs, far beyond chemotherapics. Particularly, the number of marine natural products with antithrombotic activity has increased in the last few years, and reports show a wide diversity in scaffolds, beyond the polysaccharide framework. While there are several reviews highlighting the anticoagulant and antithrombotic activities of marine-derived sulfated polysaccharides, reports including other molecules are sparse. Therefore, the present paper provides an update of the recent progress in marine-derived sulfated polysaccharides and quotes other scaffolds that are being considered for investigation due to their antithrombotic effect.
Recently-qualified general practitioners’ perceptions and experiences of General Practice Specialty Training (GPST) in deprived areas of NHS Scotland – a qualitative study

ABSTRACT NHS Scotland faces significant challenges in delivering the Scottish Government’s 2020 Strategy for Healthcare. GP recruitment and retention are problematic for deprived area practices (DAPs). Recently-qualified GPs are more likely to join practices in areas where they have trained and so it is important to encourage GP training in deprived areas. This study aimed to identify the perceptions and experiences of recently-qualified GPs who had trained in DAPs. A grounded theory approach was used with 14 GPs interviewed in focus groups and in-depth interviews. Six themes were identified: allocation to training practices in deprived areas and anxieties about working there, positive training experiences, attributes of trainers, consultation differences, preferences for large practice teams and health centres, and future career plans. GPs were very positive about their training experiences in DAPs and appreciated their trainer and training practice. One concern was of the limited experience of patient-centred consulting which they felt weakened their performance in the Clinical Skills Assessment (CSA) component of the MRCGP examination. Rotations between affluent and deprived areas would benefit General Practice Specialty Trainees (GPSTs) particularly with the CSA examination. Training authorities should encourage and support practices in deprived areas to become training practices and encourage GPSTs to train there.
Evidence that prenatal testosterone transfer from male twins reduces the fertility and socioeconomic success of their female co-twins

Significance In litter-bearing species, females exposed to prenatal testosterone from male littermates exhibit altered traits. In humans, rising twinning rates may be exposing a growing subset of females to similar effects. Data on all twin births in Norway between 1967 and 1978 show that females exposed in utero to a male co-twin have a decreased probability of graduating from high school (15.2%), completing college (3.9%), and being married (11.7%), and have lower fertility (5.8%) and life-cycle earnings (8.6%). These relationships remain unchanged among females whose male co-twin died soon after birth, implicating prenatal testosterone exposure rather than being raised with a male sibling. These findings support the hypothesis that being exposed to a male co-twin in utero can have lasting effects on females. During sensitive periods in utero, gonadal steroids help organize biological sex differences in humans and other mammals. In litter-bearing species, chromosomal females passively exposed to prenatal testosterone from male littermates exhibit altered physical and behavioral traits as adults. The consequences of such effects are less well understood in humans, but recent near-doubling of twinning rates in many countries since 1980, secondary to advanced maternal age and increased reliance on in vitro fertilization, means that an increasing subset of females in many populations may be exposed to prenatal testosterone from their male co-twin. Here we use data on all births in Norway (n = 728,842, including 13,800 twins) between 1967 and 1978 to show that females exposed in utero to a male co-twin have a decreased probability of graduating from high school (15.2%), completing college (3.9%), and being married (11.7%), and have lower fertility (5.8%) and life-cycle earnings (8.6%). These relationships remain unchanged among the subsets of 583 and 239 females whose male co-twin died during the first postnatal year and first 28 days of life, respectively, supporting the interpretation that they are due primarily to prenatal exposure rather than to postnatal socialization effects of being raised with a male sibling. Our findings provide empirical evidence, using objectively measured nation-level data, that human females exposed prenatally to a male co-twin experience long-term changes in marriage, fertility, and human capital. These findings support the hypothesis of in utero testosterone transfer between twins, which is likely affecting a small but growing subset of females worldwide.
Effects of Maltodextrins on the Kinetics of Lycopene and Chlorogenic Acid Degradation in Dried Tomato

Maltodextrins (MD) are frequently used as processing aids in tomato drying. The aim of this study was to investigate the effect of the addition of MD on the stability of lycopene and chlorogenic acid, which are the main lipophilic and hydrophilic antioxidants in processed tomato, respectively. Tomato powder added with 10% MD (dextrose equivalents, DE 12) and a control tomato powder were stored in the water activity (aw) range 0.17–0.56, for 180 d at 30 °C. At the aw level of 0.17, which was below the monolayer moisture content (Mo), chlorogenic acid was stable, while lycopene content decreased faster in tomato added with MD than in control tomato, probably due to a decrease in matrix hydrophilicity and greater oxygen diffusion in the oil phase. Maximum stability occurred in both tomato powders at aw of 0.3, that was in close proximity to Mo (first-order rate constant for lycopene, k = 7.0 × 10−3 d−1 in tomato added with MD). At high aw levels, MD increased the rate of lycopene degradation with respect to the control, possibly by hampering its regeneration by chlorogenic acid, which conversely was found to be more stable than in the control tomato.
Targeted delivery of tacrolimus to T cells by pH‐responsive aptamer‐chitosan‐ poly(lactic‐co‐glycolic acid) nanocomplex

Tacrolimus (TAC) acts as an inhibitor of calcineurin, which inhibits the production of interleukin‐2. In this study, we aimed to design a targeted delivery platform with poly (lactide‐co‐glycolide; PLGA) nanoparticles modified with chitosan (CS) and CD8AP17s aptamer (Apt). MOLT‐4 cells as CD8 positive and JURKAT cells as CD negative were adopted to investigate the efficacy of the proposed delivery system in vitro. The particle size and Ζ potential of the TAC‐PLGA‐CS‐Apt nanocomplex were 345 nm and 13.7 mV, respectively. Release study showed an efficient TAC release from complex in citrate buffer (pH 5.5). The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay showed that TAC‐PLGA‐CS‐Apt nanocomplex was highly selective toward MOLT‐4 cells. Complex increased the cellular uptake of TAC in MOLT‐4 cells (target) while reducing its cytotoxicity in JURKAT cells (nontarget). Our study showed that complex nanoconjugate could efficiently deliver TAC into MOLT‐4 cells as a model of cytotoxic T cell and it could be considered as a potential candidate for TAC delivery.
Antimicrobial Susceptibility Testing of Leptospira spp. in the Lao People’s Democratic Republic Using Disk Diffusion

Abstract. Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the Leptospira genus, which are fastidious, slow-growing organisms. Antimicrobial susceptibility data are limited; traditionally, the organisms have not been culturable on solid media. The recent development of Leptospira Vanaporn Wuthiekanun (LVW) agar, which facilitates rapid growth of Leptospira spp. , provides the opportunity for antimicrobial susceptibility testing. Eighty-three Leptospira spp. clinical isolates originating from patients in Laos between 2006 and 2016 were tested against six antimicrobials (azithromycin, ceftriaxone, ciprofloxacin, doxycycline, gentamicin, and penicillin G) using disk diffusion on LVW agar. Quality control was undertaken using American Type Culture Collection (ATCC) reference strains with known susceptibilities on both standard media and LVW agar. All Leptospira spp. isolates produced large zones of inhibition around each of the six antimicrobials. All zones were greater than 25 mm: gentamicin produced the smallest zones (median 35 mm; interquartile range 30 mm–37 mm) and azithromycin produced the largest zones (median 85 mm; interquartile range 85 mm–85 mm). Zones produced by non-leptospiral ATCC reference strains on LVW agar were within 2 mm of accepted strain-specific quality control range on standard media. Antimicrobial activity on LVW agar appears to be similar to that on standard media. As there are no published susceptibility guidelines for the Leptospira genus, zone interpretation was subjective. Leptospira Vanaporn Wuthiekanun agar enabled antimicrobial susceptibility testing of multiple Leptospira isolates on solid media; the large zone sizes observed suggest that resistance has not emerged to these six antimicrobials in Lao Leptospira spp.
Risk of cervical dysplasia among human papillomavirus-infected women in Korea: a multicenter prospective study

Objective Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, which progresses from precursor lesions with no symptom if left untreated. We compared the risk of cervical dysplasia among HPV-positive Korean women based on HPV types and infection patterns. Methods We observed participants of a 5-year multicenter prospective cohort study, comprising HPV-positive women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion of the cervix at their enrollment. Follow-ups, comprising cytology and HPV DNA testing results, were included in the final analysis. Incidence was calculated for each infection pattern (persistent infection, incidental infection, and clearance). To investigate cervical dysplasia risk, we used Cox proportional hazard models adjusted for variables that were significantly different among infection patterns. From April 2010 to September 2017, 71 of 1,027 subjects developed cervical dysplasia more severe than high-grade squamous intraepithelial lesion of the cervix. Results Of these 71 subjects, persistent infection, incidental infection, and clearance were noted in 30, 39, and 2 individuals, respectively. Based on changes in DNA results during follow-up, cumulative incidence was 27.2%, 10.4%, and 0.5% for persistent infection, incidental infection, and clearance, respectively. Compared to clearance, the adjusted hazard ratios for cervical dysplasia were 51.6 and 24.1 for persistent and incidental infections, respectively (p<0.001). Conclusion Individuals persistently infected with the same HPV types during the follow-up period had the highest risk of severe cervical dysplasia. Hence, it is necessary to monitor HPV types and infection patterns to prevent severe cervical precancerous lesions.
Content Reporting in Post-Stroke Therapeutic Circuit-Class Exercise Programs in randomized control trials

ABSTRACT Background: Therapeutic exercise in the form of group circuit-class training can improve mobility and gait while being cost-effective among patients who survived a stroke. Accurate clinical replication of interventions, especially when they are effective, is needed to advance research and treatment. However, replication is difficult when reporting is not detailed. Objective: The objective of this study was to assess the quality of reporting of interventions within the selected studies using three different scales and to assess the criterion validity between the scales. Methods: Two independent assessors used the CERT, the CONTENT scale, and TIDieR checklist to review the quality of reporting of 16 randomized controlled trials (RCTs) from a recent Cochrane Review. Assessments were done independently before a consensus was reached with an experienced third reviewer mediating any disagreements. Criterion validity between the three quality reporting tools was measured using weighted Cohen’s kappa coefficients. Results: The mean (±SD) for the CERT was 9.31 (±1.66) out of 19 points; the TIDieR checklist was 8.81 (±1.33) out of 12 points; and the CONTENT was 4.82 (±1.22) out of 9 points for the 16 included RCTs. The CERT and CONTENT scale had a fair agreement (k = 0.455, p = 0.064), while both CERT and CONTENT had only slight agreement with TIDieR (k = 0.143, p = 0.267; k = 0.200, p = 0.182, respectively). Conclusions: The results of this study indicate a lack of reporting from the 16 RCTs on post-stroke therapeutic circuit-class exercise programs. This presents a major barrier to knowledge translation and clinical implementation of effective exercise programs for stroke rehabilitation.
Importance of out‐of‐pocket costs for adult patients with atopic dermatitis in France

Currently, few studies investigated the economic burden of atopic dermatitis (AD) in adult patients and specifically the estimation of out‐of‐pocket costs. Patients with skin disorders primarily use comfort care to ease dryness, itch or pain, and the costs of comfort care are not subject to any reimbursement from mandatory or complementary insurance.