Miracle-dz/UniFAR-FTUs huggingface dataset:
A Prolonged Outbreak of Human Adenovirus A31 (HAdV-A31) Infection on a Pediatric Hematopoietic Stem Cell Transplantation Ward with Whole Genome Sequencing Evidence of International Linkages

A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. ABSTRACT A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS). HAdV-A31 specimens/DNA obtained from four international pediatric HSCT centers also underwent WGS. During the SK outbreak period (27 October 2014 to 31 October 2018), 17/20 HAdV-A31 isolates formed a distinct clade with 0 to 8 mutations between the closest neighbors. Surveillance before and after the outbreak detected six additional HAdV-A31 HSCT cases; three of the four sequenced cases clustered within the outbreak clade. Two SK outbreak isolates were identical to sequences from two patients in an outbreak in England. Three SK non-outbreak sequences also had high sequence similarity to strains from three international centers. Environmental PCR testing of the HSCT ward showed significant adenovirus contamination. Despite intense infection control efforts, we observed re-occurrence of infection with the outbreak strain. Severe but nonfatal infection was observed more commonly with HAdV-A31 compared to other genotypes, except HAdV-C1. Our findings strongly implicate nosocomial spread of HAdV-A31 over 10 years on a HSCT unit and demonstrate the value of WGS in defining and mapping the outbreak. Close linkages among strains in different countries suggest international dissemination, though the mechanism is undetermined. This large, extended outbreak emphasizes the pre-eminent role of HAdV-A31 in causing intractable pediatric HSCT outbreaks of severe illness worldwide.
Nosiheptide Harbors Potent In Vitro and Intracellular Inhbitory Activities against Mycobacterium tuberculosis

This study is aimed at chemotherapy for MDR-TB, mainly to explore the anti-TB activity of the existing chemotherapeutic reagent. We found that NOS has potent inhibitory activities against M. tuberculosis in vitro regardless of the drug-resistant profile. Furthermore, NOS also showed the long PAE and partial synergistic effect with INH and is nontoxic, providing support for its promise as a drug candidate for drug-resistant tuberculosis treatment. ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) is often associated with poor clinical outcomes. In this study, we evaluated the potential of nosiheptide (NOS) as a new drug candidate for treating Mycobacterium tuberculosis infections, including MDR-TB. The antimicrobial susceptibility testing was performed to determine the MICs of NOS against 18 reference strains of slowly growing mycobacteria (SGM) and 128 clinical isolates of M. tuberculosis. The postantibiotic effects (PAE) and interaction with other antituberculosis drugs of NOS were also evaluated using M. tuberculosis H37Rv. Fifteen out of the 18 tested reference strains of SGM had MICs far below 1 μg/mL. From the 128 M. tuberculosis clinical isolates, the MIC50 and MIC90 were 0.25 μg/mL and 1 μg/mL, respectively; the tentative epidemiological cutoff (ECOFF) was defined at 1 μg/mL. Furthermore, a Lys89Thr mutation was found in one M. tuberculosis isolate with a MIC of NOS >8 μg/mL. After 24 h of incubation, NOS at 1 μg/mL inhibited 25.79 ± 1.22% of intracellular bacterial growth, which was comparable with the inhibitory rate of 25.71 ± 3.67% achieved by rifampin at 2 μg/mL. Compared to rifampicin and isoniazid (INH), NOS had a much longer PAE, i.e., a value of about 16 days. In addition, a partial synergy between NOS and INH was observed. NOS has potent inhibitory activities against M. tuberculosis in vitro as well as in macrophages. Furthermore, the long PAE and partial synergistic effect with INH, in addition to the added safety of long-term use as a feed additive in husbandry, provide support for NOS being a promising drug candidate for tuberculosis treatment. IMPORTANCE This study is aimed at chemotherapy for MDR-TB, mainly to explore the anti-TB activity of the existing chemotherapeutic reagent. We found that NOS has potent inhibitory activities against M. tuberculosis in vitro regardless of the drug-resistant profile. Furthermore, NOS also showed the long PAE and partial synergistic effect with INH and is nontoxic, providing support for its promise as a drug candidate for drug-resistant tuberculosis treatment.
Deactivating attachment strategies associate with early processing of facial emotion and familiarity in middle childhood: an ERP study

ABSTRACT Neurophysiological evidence suggests associations between attachment and the neural processing of emotion expressions. This study asks whether this relationship is also evident in middle childhood, and how it is affected by facial familiarity. Attachment strategies (deactivation, hyperactivation) were assessed in 51 children (9 - 11 years) using a story stem completion task. Event-related potentials (ERPs) were recorded during children's passive viewing of mother and stranger emotional faces (angry/happy). At the stage of facial information encoding (N250), attachment deactivation was associated with a pattern pointing to increased vigilance towards angry faces. Further, the attention-driven LPP was increased to happy mother faces as highly salient stimuli overall, but not in children scoring high on deactivation. These children did not discriminate between mothers’ facial emotions and showed a general attentional withdrawal from facial stimuli. While our results on attachment deactivation support a two-stage processing model, no effect of hyperactivation was found.
Persistent Borrelia burgdorferi Sensu Lato Infection after Antibiotic Treatment: Systematic Overview and Appraisal of the Current Evidence from Experimental Animal Models

Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted by Ixodes tick species living in the temperate climate zones of the Northern Hemisphere. The clinical manifestations of Lyme borreliosis are diverse and treated with oral or intravenous antibiotics. SUMMARY Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted by Ixodes tick species living in the temperate climate zones of the Northern Hemisphere. The clinical manifestations of Lyme borreliosis are diverse and treated with oral or intravenous antibiotics. In some patients, long-lasting and debilitating symptoms can persist after the recommended antibiotic treatment. The etiology of such persisting symptoms is under debate, and one hypothesis entails persistent infection by a subset of spirochetes after antibiotic therapy. Here, we review and appraise the experimental evidence from in vivo animal studies on the persistence of B. burgdorferi sensu lato infection after antibiotic treatment, focusing on the antimicrobial agents doxycycline and ceftriaxone. Our review indicates that some in vivo animal studies found sporadic positive cultures after antibiotic treatment. However, this culture positivity often seemed to be related to inadequate antibiotic treatment, and the few positive cultures in some studies could not be reproduced in other studies. Overall, current results from animal studies provide insufficient evidence for the persistence of viable and infectious spirochetes after adequate antibiotic treatment. Borrelial nucleic acids, on the contrary, were frequently detected in these animal studies and may thus persist after antibiotic treatment. We put forward that research into the pathogenesis of persisting complaints after antibiotic treatment for Lyme borreliosis in humans should be a top priority, but future studies should most definitely also focus on explanations other than persistent B. burgdorferi sensu lato infection after antibiotic treatment.
Phase I trial of myeloablative conditioning with 3‐day total marrow and lymphoid irradiation for leukemia

This prospective phase I trial aimed to determine the recommended dose of 3‐day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end‐point of this single‐institution dose escalation study was the recommended TMLI dose based on the frequency of dose‐limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose‐limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35–48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow‐up period after HSCT was 575 days (range, 253–1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3‐day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14–25). One‐year overall and disease‐free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post‐HSCT. The recommended dose of 3‐day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.
Longitudinal investigation of executive function development employing task-based, teacher reports, and fNIRS multimethodology in 4- to 5-year-old children

Increased focus on resting-state functional connectivity (rsFC) and the use and accessibility of functional near-infrared spectroscopy (fNIRS) have advanced knowledge on the interconnected nature of neural substrates underlying executive function (EF) development in adults and clinical populations. Less is known about the relationship between rsFC and developmental changes in EF during preschool years in typically developing children, a gap the present study addresses employing task-based assessment, teacher reports, and fNIRS multimethodology. This preregistered study contributes to our understanding of the neural basis of EF development longitudinally with 41 children ages 4–5. Changes in prefrontal cortex (PFC) rsFC utilizing fNIRS, EF measured with a common task-based assessment (Day-Night task), and teacher reports of behavior (BRIEF-P) were monitored over multiple timepoints: Initial Assessment, 72 h follow-up, 1 Month Follow-up, and 4 Month Follow-up. Measures of rsFC were strongly correlated 72 h apart, providing evidence of high rsFC measurement reliability using fNIRS with preschool-aged children. PFC rsFC was positively correlated with performance on task-based and report-based EF assessments. Children’s PFC functional connectivity at rest uniquely predicted later EF, controlling for verbal IQ, age, and sex. Functional connectivity at rest using fNIRS may potentially show the rapid changes in EF development in young children, not only neurophysiologically, but also as a correlate of task-based EF performance and ecologically-relevant teacher reports of EF in a classroom context.
Superficial CD34 Positive Fibroblastic Tumour with Myxoid Stroma

Superficial CD34 positive fibroblastic tumor is a rare low-grade neoplasm of the skin and subcutis with indolent behavior. This entity has been included in the current World Health Organisation (WHO) classification of soft tissue tumors. Pathological diagnosis can be challenging due to significant morphological overlap with other entities and the large spectrum of CD34 positive tumors. We report a case in a twenty-five male which showed characteristic diagnostic features, but in addition showed myxoid stroma. The presence of myxoid stroma has not been previously emphasized in this entity and broadens the histologic differential diagnosis significantly to include myxoid soft tissue tumors. A subset of these tumors harbor PRDM10-rearrangements, but a defining molecular feature has not yet been described, highlighting the need for further molecular characterization of this potentially genetically heterogenous tumor. Awareness of this entity among surgeons and pathologists is important to prevent misclassification as an aggressive sarcoma and avoid over-treatment.
Human Dendritic Cells Transmit Enterovirus A71 via Heparan Sulfates to Target Cells Independent of Viral Replication

EV-A71 is an emerging neurotropic virus that is of emerging concern and can result in polio-like illness. The exact mechanism of how EV-A71 results in neurological symptoms are unknown. ABSTRACT Enterovirus A71 (EV-A71) is a causative agent of life-threatening neurological diseases in young children. EV-A71 is highly infectious but it remains unclear how the virus disseminates from primary entry sites—the mucosa of the respiratory tract or the intestine—to secondary replication sites—skin or brain. Here, we investigated the role of dendritic cells (DCs) in EV-A71 dissemination. DCs reside in the mucosa of the airway and gut, and migrate to lymphoid tissues upon activation and, therefore, could facilitate EV-A71 dissemination to secondary replication sites. Monocyte-derived DCs were not permissive to different genotypes of EV-A71 but, notably, coculture with EV-A71-susceptiblle RD99 cells led to very efficient infection of RD99 cells. Notably, EV-A71 transmission of DCs to RD99 was independent of viral replication as a replication inhibitor did not affect transmission. Soluble heparin blocked EV-A71 transmission by DCs to RD99 cells, in contrast to antibodies against known attachment receptor DC-SIGN. These results strongly suggest that DCs might be a first target for EV-A71 and involved in viral dissemination via heparan sulfates and heparin derivatives might be an effective treatment to attenuate dissemination. IMPORTANCE EV-A71 is an emerging neurotropic virus that is of emerging concern and can result in polio-like illness. The exact mechanism of how EV-A71 results in neurological symptoms are unknown. In particular, the early dissemination of the virus from primary replication sites (airway and intestine) to secondary sites (central nervous system and skin) needs to be elucidated. There is evidence pointing toward a role for dendritic cells (DC) in EV-A71 transmission. Moreover, heparan sulfate (HS) binding mutations are observed in patients with severe diseases. Therefore, we evaluated the potential role of HS on DC in transmission. We find that HS are critical for transmitting EV-A71 by DC to target cells. Our data are consistent with other clinical and in vitro observations highlighting the importance of HS in EV-A71-induced disease.
Predictors of personal recovery for individuals with schizophrenia spectrum disorders living in the community.

INTRODUCTION Personal recovery is a complex construct frequently used as outcome measure in people with schizophrenia spectrum disorders. This study examined potential predictors of personal recovery using the two most common assessment tools for people with schizophrenia spectrum disorders living in the community: the Chinese version of the Questionnaire about the Process of Recovery and the Chinese version of the Recovery Assessment Scale. METHODS Ninety-one individuals (57 women) diagnosed with schizophrenia spectrum disorders participated in the study (mean age: 47.41 ± 9.41 years). All participants lived in the community and received community psychiatric services. The participants were evaluated via interviews, questionnaires, and standardized assessments. Potential predictors included four domains: personal, disease-related, functional, and social. Stepwise multiple linear regression was used to analyze the potential predictors of the recovery and recovery assessment scale. RESULTS Resilience and social support were the only significant predictors of the Chinese versions of the Questionnaire about the Process of Recovery and Chinese version of the Recovery Assessment Scale. The primary predictor of the Chinese version of the Questionnaire about the Process of Recovery was social support from family and institutional staff. Conversely, resilience was the major predictor of the Chinese version of the Recovery Assessment Scale. DISCUSSION For people with schizophrenia spectrum disorders living in the community, social support and resilience significantly predicted personal recovery. Age, educational level, and disease-related and functional factors were not significant predictors of personal recovery. Therefore, it is important to develop successful personal recovery-oriented practices that enhance resilience and promote social support.
Thermal adaptation of pelage in desert rodents balances cooling and insulation

Phenotypic convergence across distantly related taxa can be driven by similar selective pressures from the environment or intrinsic constraints. The roles of these processes on physiological strategies, such as homeothermy, are poorly understood. We studied the evolution of thermal properties of mammalian pelage in a diverse community of rodents inhabiting the Mojave Desert, USA. We used a heat flux device to measure the thermal insulation of museum specimens and determined whether thermal properties were associated with habitat preferences while assessing phylogenetic dependence. Species that prefer arid habitats exhibited lower conductivity and thinner pelage relative to species with other habitat preferences. Despite being thinner, the pelage of arid species exhibited comparable insulation to the pelage of the other species due to its lower conductivity. Thus, arid species have insulative pelage while simultaneously benefitting from thin pelage that promotes convective cooling. We found no evidence of intrinsic constraints or phylogenetic dependence, indicating pelage readily evolves to environmental pressures. Thermoregulatory simulations demonstrated that arid specialists reduced energetic costs required for homeothermy by 14.5% by evolving lower conductivity, providing support for adaptive evolution of pelage. Our study indicates that selection for lower energetic requirements of homeothermy has shaped evolution of pelage thermal properties.
Bayesian multivariate logistic regression for superiority and inferiority decision-making under observable treatment heterogeneity

The effects of treatments may differ between persons with different characteristics. Addressing such treatment heterogeneity is crucial to investigate whether patients with specific characteristics are likely to benefit from a new treatment. The current paper presents a novel Bayesian method for superiority decision-making in the context of randomized controlled trials with multivariate binary responses and heterogeneous treatment effects. The framework is based on three elements: a) Bayesian multivariate logistic regression analysis with a P\'olya-Gamma expansion; b) a transformation procedure to transfer obtained regression coefficients to a more intuitive multivariate probability scale (i.e., success probabilities and the differences between them); and c) a compatible decision procedure for treatment comparison with prespecified decision error rates. Procedures for a priori sample size estimation under a non-informative prior distribution are included. A numerical evaluation demonstrated that decisions based on a priori sample size estimation resulted in anticipated error rates among the trial population as well as subpopulations. Further, average and conditional treatment effect parameters could be estimated unbiasedly when the sample was large enough. Illustration with the International Stroke Trial dataset revealed a trend towards heterogeneous effects among stroke patients: Something that would have remained undetected when analyses were limited to average treatment effects.
Alleviating Adversarial Attacks on Variational Autoencoders with MCMC

Variational autoencoders (VAEs) are latent variable models that can generate complex objects and provide meaningful latent representations. Moreover, they could be further used in downstream tasks such as classification. As previous work has shown, one can easily fool VAEs to produce unexpected latent representations and reconstructions for a visually slightly modified input. Here, we examine several objective functions for adversarial attack construction proposed previously and present a solution to alleviate the effect of these attacks. Our method utilizes the Markov Chain Monte Carlo (MCMC) technique in the inference step that we motivate with a theoretical analysis. Thus, we do not incorporate any extra costs during training, and the performance on non-attacked inputs is not decreased. We validate our approach on a variety of datasets (MNIST, Fashion MNIST, Color MNIST, CelebA) and VAE configurations ($\beta$-VAE, NVAE, $\beta$-TCVAE), and show that our approach consistently improves the model robustness to adversarial attacks.
Map-Assisted Constellation Design for mmWave WDM With OAM in Short-Range LOS Environment

We consider a system that integrates positioning and single-user millimeter wave (mmWave) communication, where the communication part adopts wavelength division multiplexing (WDM) and orbital angular momentum (OAM). This paper addresses the multi-dimensional constellation design in short-range line-of-sight (LOS) environment, with stable communication links. We propose a map-assisted method to quantify the system parameters based on positions and reduce real-time computing overhead. We explore the possibility of using a few patterns in the maps, and investigate its performance loss. We first investigate the features of OAM beams, and find that the link gain ratio between any two sub-channels remains unchanged at some specific positions. Then, we prove that a fixed constellation can be adopted for the positions where the link gain matrices are sufficiently close to be proportional. Moreover, we prove that the system can adopt a fixed power vector to generate a multi-dimensional constellation if the difference between fixed power vector and optimal power vector is small. Finally, we figure out that the constellation design for all receiver positions can be represented by a few constellation sets.