Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex History of Codiversification and Host Switching of a Newfound Soricid-Borne Orthohantavirus in North America

Orthohantaviruses are tightly linked to the ecology and evolutionary history of their mammalian hosts. We hypothesized that in regions with dramatic climate shifts throughout the Quaternary, orthohantavirus diversity and evolution are shaped by dynamic host responses to environmental change through processes such as host isolation, host switching, and reassortment. Jemez Springs virus (JMSV), an orthohantavirus harbored by the dusky shrew (Sorex monticola) and five close relatives distributed widely in western North America, was used to test this hypothesis. Total RNAs, extracted from liver or lung tissue from 164 shrews collected from western North America during 1983–2007, were analyzed for orthohantavirus RNA by reverse transcription polymerase chain reaction (RT-PCR). Phylogenies inferred from the L-, M-, and S-segment sequences of 30 JMSV strains were compared with host mitochondrial cytochrome b. Viral clades largely corresponded to host clades, which were primarily structured by geography and were consistent with hypothesized post-glacial expansion. Despite an overall congruence between host and viral gene phylogenies at deeper scales, phylogenetic signals were recovered that also suggested a complex pattern of host switching and at least one reassortment event in the evolutionary history of JMSV. A fundamental understanding of how orthohantaviruses respond to periods of host population expansion, contraction, and secondary host contact is the key to establishing a framework for both more comprehensive understanding of orthohantavirus evolutionary dynamics and broader insights into host–pathogen systems.
Highly diversified shrew hepatitis B viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses

Significance Hepatitis B viruses (HBVs) have existed for millions of years. We describe divergent HBV species in shrews, which are ancient insectivorous mammals. The shrew viruses corroborated ancient origins of mammalian HBV and showed mutations in genomic domains required for production of the hepatitis B e antigen, crucial for vertical transmission and chronicity of HBV in humans. Shrew HBV infection patterns showed important similarities with human HBV, and shrews might be susceptible to human HBV. In contrast, shrew HBVs could neither infect human cells nor use the canonical HBV receptor molecule for cellular entry. The discovery and characterization of shrew HBVs allow conceptualizing urgently needed new animal models relying on engineered shrew and human HBV homologs to elucidate HBV pathogenesis. Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those observed in HBeAg-negative human HBV. Deep sequencing and in situ hybridization suggest that HBeAg-negative shrew HBVs cause intense hepatotropic monoinfections and low within-host genomic heterogeneity. Geographical clustering and low MSHBV/CSHBV-specific seroprevalence suggest focal transmission and high virulence of shrew HBVs. HBeAg negativity is thus an ancient HBV infection pattern, whereas Ntcp usage for entry is not evolutionarily conserved. Shrew infection models relying on CSHBV/MSHBV revertants and human HBV will allow comparative assessments of HBeAg-mediated HBV pathogenesis, entry, and species barriers.
Excess Iron Enhances Purine Catabolism Through Activation of Xanthine Oxidase and Impairs Myelination in the Hippocampus of Nursing Piglets.

BACKGROUND Few studies have addressed the risk of nutritional iron overexposure in infancy. We previously found that excess dietary iron in nursing piglets resulted in iron overload in the liver and hippocampus and diminished socialization with novel conspecifics in a test for social novelty preference. OBJECTIVES This experiment aimed to identify metabolites and metabolic pathways affected by iron overload in the liver and hippocampus of nursing piglets. METHODS Liver and hippocampal tissues collected from 22-d-old piglets (Hampshire × Yorkshire crossbreed; 5.28 ± 0.53 kg body weight; 50% male) that received orally 0 (NI group) or 50 mg iron/(d · kg body weight) (HI group) from postnatal day (PD) 2 to PD21 were analyzed for mRNA and protein expression and enzyme activity of xanthine oxidase (XO). Untargeted metabolomics was performed using GC-MS. Expression of myelin basic protein (MBP) in the hippocampus was determined using western blot. RESULTS There were 108 and 126 metabolites identified in the hippocampus and liver, respectively. Compared with NI, HI altered 15 metabolites (P < 0.05, q < 0.2) in the hippocampus, including a reduction in myo-inositol (0.86-fold) and N-acetylaspartic acid (0.84-fold), 2 metabolites important for neuronal function and myelination. Seven metabolites involved in purine and pyrimidine metabolism (e.g., hypoxanthine, xanthine, and β-alanine) were coordinately changed in the hippocampus (P < 0.05, q < 0.2), suggesting that iron excess enhanced purine catabolism. The mRNA expression (2.3-fold) (P < 0.05) and activity of XO, a rate-limiting enzyme in purine degradation, was increased. Excess iron increased hippocampal lipid peroxidation by 74% (P < 0.05) and decreased MBP by 44% (P = 0.053). The hepatic metabolome was unaffected. CONCLUSIONS In nursing piglets, excess iron enhances hippocampal purine degradation through activation of XO, which may induce oxidative stress and alter energy metabolism in the developing brain.
Aqueous and ethanol extracts of Dracaena arborea (Wild) Link (Dracaenaceae) alleviate reproductive complications of diabetes mellitus in rats

Reproductive dysfunction is one of the most prevalent diabetes complications. Draceana arborea is known to enhance sexual function in diabetic rats, but the underlying mechanisms have not been thoroughly elucidated. This study examined the effects of D. arborea on some reproductive complications of diabetes in rats. Aqueous and ethanol (500 and 100 mg/kg respectively) extracts of D. arborea, Sildenafil citrate (1.44 mg/kg), trimethylamine‐N‐oxide (TMAO, 20 mg/kg) and distilled water (10 ml/kg) were orally administered for 28 days to streptozotocin‐induced diabetic rats. Glycaemia, body and reproductive organ masses, fertility parameters, total proteins, antioxidant enzymes activities, serum and testicular testosterone and the histology of the testes and epididymis were determined. Results revealed significant decreases in body and absolute and relative masses of testes, epididymis, seminal vesicles, prostate and vas deferens, fertility parameters, epididymal and testicular total proteins, serum and testicular testosterone levels as well as antioxidant enzymes activities. Interestingly, while having minor anti‐hyperglycaemic effects, these abnormalities associated with testicular and epididymal alterations were alleviated by D. arborea especially the aqueous extract (500 mg/kg). These outcomes provided evidence of the androgenic properties of D. arborea in diabetic rats, which could be useful for a better management of sexual dysfunctions in diabetic patients.
Overexpression of Peroxidase Gene GsPRX9 Confers Salt Tolerance in Soybean

Peroxidases play prominent roles in antioxidant responses and stress tolerance in plants; however, their functions in soybean tolerance to salt stress remain unclear. Here, we investigated the role of a peroxidase gene from the wild soybean (Glycine soja), GsPRX9, in soybean tolerance to salt stress. GsPRX9 gene expression was induced by salt treatment in the roots of both salt-tolerant and -sensitive soybean varieties, and its relative expression level in the roots of salt-tolerant soybean varieties showed a significantly higher increase than in salt-sensitive varieties after NaCl treatment, suggesting its possible role in soybean response to salt stress. GsPRX9-overexpressing yeast (strains of INVSc1 and G19) grew better than the control under salt and H2O2 stress, and GsPRX9-overexpressing soybean composite plants showed higher shoot fresh weight and leaf relative water content than control plants after NaCl treatment. Moreover, the GsPRX9-overexpressing soybean hairy roots had higher root fresh weight, primary root length, activities of peroxidase and superoxide dismutase, and glutathione level, but lower H2O2 content than those in control roots under salt stress. These findings suggest that the overexpression of the GsPRX9 gene enhanced the salt tolerance and antioxidant response in soybean. This study would provide new insights into the role of peroxidase in plant tolerance to salt stress.
The Association of Sport and Exercise Activities With Cardiovascular Disease Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND This study assessed the independent associations between participation in self-reported sport and exercise activities and incident cardiovascular disease (CVD). METHODS Data were from 13,204 participants in the Atherosclerosis Risk in Communities Study cohort (1987-2015). Baseline sport and exercise activities were assessed via the modified Baecke questionnaire. Incident CVD included coronary heart disease, heart failure, or stroke. Multivariable-adjusted Cox proportional hazard models assessed the association of participation in specific sport and exercise activities at enrollment with risk of CVD. RESULTS During a median follow-up time of 25.2 years, 30% of the analytic sample (n = 3966) was diagnosed with incident CVD. In fully adjusted models, participation in racquet sports (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.61-0.93), aerobics (HR 0.75; 95% CI, 0.63-0.88), running (HR 0.68; 95% CI, 0.54-0.85), and walking (HR 0.89; 95% CI, 0.83-0.95) was significantly associated with a lower risk of CVD. There were no significant associations for bicycling, softball/baseball, gymnastics, swimming, basketball, calisthenics exercises, golfing with cart, golfing with walking, bowling, or weight training. CONCLUSIONS Participation in specific sport and exercises may substantially reduce the risk for CVD.
Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot‐Marie‐Tooth disease

Charcot‐Marie‐Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation‐dependent probe amplification (MLPA) testing in all patients and next‐generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.
Interteam Cooperation and Competition and Boundary Activities: The Cross-Level Mediation of Team Goal Orientations

Drawing on Dragoni’s cross-level model of state goal orientation, this research aims to examine the cross-level mediating effect of team goal orientation on the relationships between interteam cooperation and competition and three forms of boundary activities. Study 1 tested the proposed mediating relationships by collecting survey data from 249 members of 45 South Korean work teams. Additionally, we conducted a two-wave longitudinal study (Study 2) on 188 undergraduate students to replicate the relationships between three types of team goal orientation and their relevant forms of boundary activities. In Study 1, we found positive associations between interteam cooperation and team learning goal orientation, and between interteam competition and team performance-prove and performance-avoid goal orientations. Team learning and performance-prove goal orientations were positively related to boundary spanning and reinforcement. As predicted, team learning goal orientation had a stronger relationship with boundary spanning than team performance-prove goal orientation, whereas team performance-prove goal orientation had a stronger relationship with boundary reinforcement than team learning goal orientation. While team learning goal orientation mediated the relationship between interteam cooperation and boundary spanning and reinforcement, team performance-prove goal orientation mediated the relationship between interteam competition and boundary spanning and reinforcement. The results of Study 2 demonstrated the positive lagged effects of team performance-prove goal orientation on boundary reinforcement and of team performance-avoid goal orientation on boundary buffering.
Spermatogenesis disorder is associated with mutations in the ligand‐binding domain of an androgen receptor

Androgens play a key role in spermatogenesis, and their functions are mediated by the androgen receptor (AR). Some mutations in the AR gene have the potential to alter the primary structure and function of the protein. The aim of this study was to investigate the AR gene mutations in a cohort of males with idiopathic azoospermia referred to Royan Institute. Fifty‐one biopsy samples were obtained for routine clinical purposes from 15 men with hypospermatogenesis (HS), 17 patients with maturation arrest (MA) and 19 patients with Sertoli cell‐only syndrome (SCOS). The AR cDNAs were prepared from tissue mRNAs and were sequenced. One synonymous variant and three nonsynonymous protein coding single nucleotide polymorphisms (nsSNPs) were detected. Protein structure prediction demonstrated that the S815I and M746T nonsynonymous variants would affect protein structure and its normal function. Our study suggests that mutations in the AR gene would change or disturb the receptor's normal activity. Although these variations may influence spermatogenesis, it is difficult to say that they lead to a lack of spermatogenesis.
A randomized controlled trial of group cognitive remediation therapy for anorexia nervosa: Effects on set-shifting tasks for inpatient adults and adolescents.

OBJECTIVE The aim of this randomized controlled trial with a parallel design was to evaluate the effect of brief, cognitive remediation therapy (CRT) for anorexia nervosa (AN) on set-shifting. METHOD Two hundred seventy-five inpatient adults and adolescents with AN (mean age = 23.1; SD = 12.7) were randomly assigned (using simple randomization procedures) to either a CRT or control condition. All participants received treatment as usual; however, the CRT condition completed five CRT group sessions in lieu of other group therapies provided on the unit. Set-shifting abilities were evaluated by: (a) neuropsychological measures and (b) experimental cognitive behavior therapy thought records. Blinding of group assignment occurred during baseline assessment and ended following group commencement. RESULTS Data from 135 CRT and 140 control condition participants were analyzed. On all neuropsychological measures, results revealed no between group condition effects, but did show statistically significant time effects, with medium to large effect sizes. Thought record analysis revealed a significant condition by age interaction effect where adults in the CRT condition generated significantly more alternative thoughts and had stronger believability of alternative thoughts than children, a trend that was not found in the control condition. This yielded moderate to large effect sizes of.0. 56 and 0.72, respectively. DISCUSSION Based on traditional neuropsychological measures, these findings do not suggest a differential effect of CRT for AN in the format applied. However, results suggest that CRT may have some increased beneficial cognitive effect for adults, as compared to children, based on thought record analysis.
The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Abstract Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.
A national study for regional variation of inpatient ECT utilization from 4,411 hospitals across the United States.

BACKGROUND We conducted a study to examine regional variation in the utilization of inpatient electroconvulsive therapy (ECT) across the United States, and its impact on length of hospital stay and cost. METHODS Analysis of the Nationwide Inpatient Sample databases to compare patient and hospital characteristics, and regional variation of ECT administration across different regions of the United States. RESULTS The study included 41,055 inpatients who had ECT from 4,411 hospitals. Electroconvulsive therapy use is significantly higher in the Midwest. A higher proportion of females (65.2%) than males received ECT across the United States. Medicaid beneficiaries were less likely to undergo ECT compared with patients with Medicare (52.2%) or private insurance (32%). Electroconvulsive therapy was used mainly for mood disorders (84.3%). There were marked reductions of inpatient costs ($25,298 to $38,244) and average hospital stay (16 days) when ECT was initiated within the first 5 days of admission compared with later during the hospitalization. CONCLUSIONS There is a wide variability of utilization of ECT, depending on the region, type of hospital, and type of insurance carrier. The utilization of ECT services is reduced across the United States. Appropriate utilization of this effective treatment can greatly help patients who are not responding to standard therapeutics, reduce overall health care cost and length of stay, and, most importantly, alleviate suffering.
Anticipated nostalgia: Looking forward to looking back

ABSTRACT Anticipated nostalgia is a new construct that has received limited empirical attention. It concerns the anticipation of having nostalgic feelings for one’s present and future experiences. In three studies, we assessed its prevalence, content, emotional profile, and implications for self-regulation and psychological functioning. Study 1 revealed that anticipated nostalgia most typically concerns interpersonal relationships, and also concerns goals, plans, current life, and culture. Further, it is affectively laden with happiness, sadness, bittersweetness, and sociality. Studies 2 and 3 assessed the implications of anticipated nostalgia for self-regulation and psychological functioning. In both studies, positive evaluation of a personal experience was linked to stronger anticipated nostalgia, and anticipated nostalgia was linked to savouring of the experience. In Study 3, anticipated nostalgia measured prior to an important life transition predicted nostalgia a few months after the transition, and post-transition nostalgia predicted heightened self-esteem, social connectedness, and meaning in life.
Retinal and optic nerve degeneration in liver X receptor β knockout mice

Significance Optic neuritis, an inflammatory disease of the optic nerve, leads to death of retinal ganglion cells (RGC) and impaired vision. Both LXRα and LXRβ are expressed in the retina and optic nerve. The present study reveals that deletion of LXRβ from the mouse genome leads to loss of RGC. Immunostaining of LXRβ knockout mouse eyes showed that loss of AQP4 expression and activation of microglia in the optic nerve precedes the loss of RGC. The conclusion is that RGC loss is secondary to optic nerve degeneration and that LXRβ is a promising target for the treatment of retinal neurodegenerative diseases. The retina is an extension of the brain. Like the brain, neurodegeneration of the retina occurs with age and is the cause of several retinal diseases including optic neuritis, macular degeneration, and glaucoma. Liver X receptors (LXRs) are expressed in the brain where they play a key role in maintenance of cerebrospinal fluid and the health of dopaminergic neurons. Herein, we report that LXRs are expressed in the retina and optic nerve and that loss of LXRβ, but not LXRα, leads to loss of ganglion cells in the retina. In the retina of LXRβ−/− mice, there is an increase in amyloid A4 and deposition of beta-amyloid (Aβ) aggregates but no change in the level of apoptosis or autophagy in the ganglion cells and no activation of microglia or astrocytes. However, in the optic nerve there is a loss of aquaporin 4 (AQP4) in astrocytes and an increase in activation of microglia. Since loss of AQP4 and microglial activation in the optic nerve precedes the loss of ganglion cells, and accumulation of Aβ in the retina, the cause of the neuronal loss appears to be optic nerve degeneration. In patients with optic neuritis there are frequently AQP4 autoantibodies which block the function of AQP4. LXRβ−/− mouse is another model of optic neuritis in which AQP4 antibodies are not detectable, but AQP4 function is lost because of reduction in its expression.