Miracle-dz/UniFAR-FTUs huggingface dataset:
Case Report: Whole-Genome Sequencing of Serially Collected Haemophilus influenzae From a Patient With Common Variable Immunodeficiency Reveals Within-Host Evolution of Resistance to Trimethoprim-Sulfamethoxazole and Azithromycin After Prolonged Treatment With These Antibiotics

We report within-host evolution of antibiotic resistance to trimethoprim-sulfamethoxazole and azithromycin in a nontypeable Haemophilus influenzae strain from a patient with common variable immunodeficiency (CVID), who received repeated or prolonged treatment with these antibiotics for recurrent respiratory tract infections. Whole-genome sequencing of three longitudinally collected sputum isolates during the period April 2016 to January 2018 revealed persistence of a strain of sequence type 2386. Reduced susceptibility to trimethoprim-sulfamethoxazole in the first two isolates was associated with mutations in genes encoding dihydrofolate reductase (folA) and its promotor region, dihydropteroate synthase (folP), and thymidylate synthase (thyA), while subsequent substitution of a single amino acid in dihydropteroate synthase (G225A) rendered high-level resistance in the third isolate from 2018. Azithromycin co-resistance in this isolate was associated with amino acid substitutions in 50S ribosomal proteins L4 (W59R) and L22 (G91D), possibly aided by a substitution in AcrB (A604E) of the AcrAB efflux pump. All three isolates were resistant to aminopenicillins and cefotaxime due to TEM-1B beta-lactamase and identical alterations in penicillin-binding protein 3. Further resistance development to trimethoprim-sulfamethoxazole and azithromycin resulted in a multidrug-resistant phenotype. Evolution of multidrug resistance due to horizontal gene transfer and/or spontaneous mutations, along with selection of resistant subpopulations is a particular risk in CVID and other patients requiring repeated and prolonged antibiotic treatment or prophylaxis. Such challenging situations call for careful antibiotic stewardship together with supportive and supplementary treatment. We describe the clinical and microbiological course of events in this case report and address the challenges encountered.
Serum Vitamin D Insufficiency in Hospitalized Full-Term Neonates at a Tertiary Hospital in Eastern China

Objective This study explored the status of serum vitamin D in hospitalized full-term neonates at a tertiary hospital in eastern China. Methods A prospective study was conducted among 471 hospitalized full-term neonates at the Children's Hospital of Soochow University between January 1 and June 20, 2020. Perinatal clinical data, serum 25-hydroxyvitamin D (25(OH)D3), laboratory examinations, serum calcium levels, and immune function were obtained and analyzed. We explored and analyzed the risk factors for vitamin D insufficiency or deficiency, and we also attempted to determine correlations between vitamin D and its influence on immunity. Results The mean serum 25(OH)D3 was 33.65±6.07ng/ml.The prevalence of vitamin D insufficiency was 28.24%,vitamin D sufficiency was 71.76%, there was no vitamin D deficiency. The serum 25-(OH)D3 in singleton neonate was higher than twins or multiple infants (t = −10.918, P = 0.000). The serum 25-(OH)D3 were higher in neonates who born in spring and summer than in winter (H = 13.443, P = 0.001). The serum 25-(OH)D3 in appropriate for gestational age (AGA) and large for gestational age (LGA) neonates were higher than small for gestational age (SGA) (H = 7.686, P = 0.021). The serum 25-(OH)D3 were higher in neonates whose mothers had no underlying diseases than those with certain immunological and infectious diseases (F = 12.417, P = 0.000). The serum 25-(OH)D3 in neonates whose mothers had none or one perinatal complication were higher than those with two or more (F = 13.299, P = 0.000). The neonates with eosinophils ≤5% or normal platelet counts or serum Ca++ ≥0.9 mmol/L have higher serum 25-(OH)D3. Neonates born in winter were at risk for vitamin D insufficiency, and the incidence of infectious pneumonia, sepsis, cytomegalovirus infection, and hypocalcemia in the vitamin D insufficiency group were higher than sufficiency group (P < 0.05). The serum CD3+, CD3+CD4+, and IgA levels in vitamin D sufficiency neonates were significantly higher than those in insufficiency group (P < 0.05). Conclusion The prevalence of vitamin D insufficiency was 28.24%, and birth in winter was a risk factor for vitamin D insufficiency in hospitalized full-term neonates in Suzhou area. Neonates with infectious pneumonia, sepsis, cytomegalovirus infection, and hypocalcemia exhibited a high risk of vitamin D insufficiency. The serum CD3+, CD3+CD4+, and IgA levels in neonates with vitamin D insufficiency were lower.
Physical Exercise-Induced Astrocytic Neuroprotection and Cognitive Improvement Through Primary Cilia and Mitogen-Activated Protein Kinases Pathway in Rats With Chronic Cerebral Hypoperfusion

Chronic cerebral hypoperfusion (CCH) is closely related to vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). The neuroinflammation involving astrocytes is an important pathogenic mechanism. Along with the advancement of the concept and technology of astrocytic biology, the astrocytes have been increasingly regarded as the key contributors to neurological diseases. It is well known that physical exercise can improve cognitive function. As a safe and effective non-drug treatment, physical exercise has attracted continuous interests in neurological research. In this study, we explored the effects of physical exercise on the response of reactive astrocytes, and its role and mechanism in CCH-induced cognitive impairment. A rat CCH model was established by 2 vessel occlusion (2VO) and the wheel running exercise was used as the intervention. The cognitive function of rats was evaluated by morris water maze and novel object recognition test. The phenotypic polarization and the primary cilia expression of astrocytes were detected by immunofluorescence staining. The activation of MAPKs cascades, including ERK, JNK, and P38 signaling pathways, were detected by western blot. The results showed that physical exercise improved cognitive function of rats 2 months after 2VO, reduced the number of C3/GFAP-positive neurotoxic astrocytes, promoted the expression of S100A10/GFAP-positive neuroprotective astrocytes, and enhanced primary ciliogenesis. Additionally, physical exercise also alleviated the phosphorylation of ERK and JNK proteins induced by CCH. These results indicate that physical exercise can improve the cognitive function of rats with CCH possible by promoting primary ciliogenesis and neuroprotective function of astrocytes. The MAPKs signaling cascade, especially ERK and JNK signaling pathways may be involved in this process.
Transactivation of TrkB Receptors by Oxytocin and Its G Protein-Coupled Receptor

Brain-derived Neurotrophic Factor (BDNF) binds to the TrkB tyrosine kinase receptor, which dictates the sensitivity of neurons to BDNF. A unique feature of TrkB is the ability to be activated by small molecules in a process called transactivation. Here we report that the brain neuropeptide oxytocin increases BDNF TrkB activity in primary cortical neurons and in the mammalian neocortex during postnatal development. Oxytocin produces its effects through a G protein-coupled receptor (GPCR), however, the receptor signaling events that account for its actions have not been fully defined. We find oxytocin rapidly transactivates TrkB receptors in bath application of acute brain slices of 2-week-old mice and in primary cortical culture by increasing TrkB receptor tyrosine phosphorylation. The effects of oxytocin signaling could be distinguished from the related vasopressin receptor. The transactivation of TrkB receptors by oxytocin enhances the clustering of gephyrin, a scaffold protein responsible to coordinate inhibitory responses. Because oxytocin displays pro-social functions in maternal care, cognition, and social attachment, it is currently a focus of therapeutic strategies in autism spectrum disorders. Interestingly, oxytocin and BDNF are both implicated in the pathophysiology of depression, schizophrenia, anxiety, and cognition. These results imply that oxytocin may rely upon crosstalk with BDNF signaling to facilitate its actions through receptor transactivation.
Appropriateness and Associated Factors of Stress Ulcer Prophylaxis for Surgical Inpatients of Orthopedics Department in a Tertiary Hospital: A Cross-Sectional Study

Background: Stress ulcer prophylaxis (SUP) prescribed in patients admitted to surgical wards with a low risk of stress-related mucosal disease (SRMD) accounted for a considerable proportion of improper use of proton pump inhibitors (PPIs). This study aimed to analyze the appropriateness of SUP prescribing patterns and identify its associated factors in the orthopedics department of a tertiary hospital in the Northwestern China. Methods: In this cross-sectional study, information regarding the demographic and clinical characteristics of 1,200 fracture inpatients who underwent surgical operations from January 2020 to August 2021 were collected from medical records. Established criteria were used to assess the appropriateness of the prescribing pattern for SUP, and the incidence of inappropriate SUP medication was calculated. Logistic regression analyses were used to identify factors associated with inappropriate SUP medication. Results: Approximately, 42.4% of the study population was interpreted as inappropriate prescription of SUP. A total of 397 (33.1%) patients received SUP without a proper indication (overprescription), and the incidence of inappropriate SUP medication was calculated to be 43.11 per 100 patient-days. In addition, 112 (9.3%) inpatients for whom SUP was indicated did not receive SUP (underprescription). PPIs were prescribed in 96.1% of the inpatients who used acid suppression therapy (AST), and intravenous PPIs accounted for 95.3% thereof. In a multivariate logistic regression analysis, age above 65 years and prolonged hospitalization were associated with overprescription of SUP. Increased number of drugs excluding PPIs, the concurrent use of systemic corticosteroids, comorbidity of hypertension, and unemployed or retired status in inpatients were associated with a reduced likelihood of overprescription for SUP. Conversely, prolonged hospitalization, the concurrent use of systemic corticosteroids or anticoagulants, and unemployed status in inpatients were positively associated with underprescription of SUP. Conclusion: There was a high prevalence of inappropriate SUP prescription among noncritically ill inpatients of fracture who underwent surgical operations. We delineated the associated factors with inappropriate SUP medication, which indicated that more information was required for clinicians about rationality and efficiency of their prescribing practices. Effective intervention strategies should be executed by clinical pharmacists to reduce improper SUP medication.
Effects of Total Sulfur Amino Acids on Growth Performance, Immunity, and Meat Yield in Broilers Fed Diets With and Without Antibiotics

Two experiments were conducted to evaluate the effects of digestible sulfur amino acids (SAA) on performance, carcass yield, immunity, and amino acid transporters in broilers fed diets with or without an antibiotic growth promoter (AGP). In experiment 1, a total of 250 1-day-old Cobb500 male chicks were assigned to battery cages with two levels of AGP (0 and 0.05% bacitracin) and five levels of SAA (0.7, 0.8, 0.9, 1.0, and 1.1%) for 21 d. In experiment 2, a total of 900 1-day-old Cobb500 male chicks were assigned to floor pens with two levels of AGP and three levels of SAA for the starter (0.7, 0.8, and 0.9%) or finisher phase (0.52, 0.62, and 0.72%) for 42 d. In experiment 1, from 0 to 7 d, the body weight gain (BWG) was the lowest for birds fed 0.7% SAA. The AGP significantly decreased the feed conversion ratio (FCR), and birds fed 0.9 and 1.1% SAA had significantly lower FCR than 0.7% SAA. From 8 to 14 d, for the AGP-fed birds, the lowest BWG was observed in the 0.7% SAA group. In birds not fed AGP, birds fed 0.8% SAA had higher BWG than 0.7 and 1.1% SAA. Birds fed 0.7% SAA diet had lower feed intake (FI) than 0.8% SAA and higher FCR than 0.8, 0.9, and 1.0% SAA. In experiment 2, from 0 to 21 d, the lowest BWG and the highest FCR were observed in birds fed 0.7% SAA, whereas birds fed 0.9% SAA had the highest BWG and lowest FCR. From 22 to 42 d, FCR was lower for birds fed AGP, and for birds fed 0.72%. Interactions between the factors were found for FI and BWG. The whole thigh and wing weights were the highest for 0.62% SAA, and the pectoralis major weight was higher for birds fed 0.62% SAA than those fed 0.52% SAA. There was an interaction between SAA and AGP for Lat1 (large neutral amino acid transporter) expression, and AGP-fed birds had higher expression of ileal interleukin 1β (Il−1β gene). The interleukin 10 (Il-10) expression was upregulated in the ileum. There was an interaction between factors for sodium-dependent neutral amino acid transporter B [0] AT1 (SLC6A19) expression. The results suggested that both AGP and SAA supplementation would affect the growth performance of the broilers.
Untangling the Knots of Regulatory T Cell Therapy in Solid Organ Transplantation

Numerous preclinical studies have provided solid evidence supporting adoptive transfer of regulatory T cells (Tregs) to induce organ tolerance. As a result, there are 7 currently active Treg cell-based clinical trials in solid organ transplantation worldwide, all of which are early phase I or phase I/II trials. Although the results of these trials are optimistic and support both safety and feasibility, many experimental and clinical unanswered questions are slowing the progression of this new therapeutic alternative. In this review, we bring to the forefront the major challenges that Treg cell transplant investigators are currently facing, including the phenotypic and functional diversity of Treg cells, lineage stability, non-standardized ex vivo Treg cell manufacturing process, adequacy of administration route, inability of monitoring and tracking infused cells, and lack of biomarkers or validated surrogate endpoints of efficacy in clinical trials. With this plethora of interrogation marks, we are at a challenging and exciting crossroad where properly addressing these questions will determine the successful implementation of Treg cell-based immunotherapy in clinical transplantation.
Anti-Müllerian Hormone Signal Transduction involved in Müllerian Duct Regression

Over seventy years ago it was proposed that the fetal testis produces a hormone distinct from testosterone that is required for complete male sexual development. At the time the hormone had not yet been identified but was invoked by Alfred Jost to explain why the Müllerian duct, which develops into the female reproductive tract, regresses in the male fetus. That hormone, anti-Müllerian hormone (AMH), and its specific receptor, AMHR2, have now been extensively characterized and belong to the transforming growth factor-β families of protein ligands and receptors involved in growth and differentiation. Much is now known about the downstream events set in motion after AMH engages AMHR2 at the surface of specific Müllerian duct cells and initiates a cascade of molecular interactions that ultimately terminate in the nucleus as activated transcription factors. The signals generated by the AMH signaling pathway are then integrated with signals coming from other pathways and culminate in a complex gene regulatory program that redirects cellular functions and fates and leads to Müllerian duct regression.
Childhood Maltreatment Influences Autonomic Regulation and Mental Health in College Students

Childhood maltreatment history may influence autonomic reactivity and recovery to stressors. Hypothetically, the maltreatment history may contribute to a retuned autonomic nervous system that is reflected in a novel metric, vagal efficiency (VE), designed to assess the functional efficiency of vagal cardioinhibitory pathways on heart rate. We explored whether VE mediates the well-documented relationship between maltreatment history and psychiatric symptoms. We also investigated the relationship between measures of autonomic regulation in response to the physical and emotional challenges and psychiatric symptoms. Participants (n = 167) completed self-report measures of psychiatric symptoms and had continuous beat-to-beat heart rate monitored before, during, and after physical and emotional stressors. Participants with maltreatment histories exhibited lower VE, which mediated the association of maltreatment history and the psychiatric symptoms of anxiety and depression. Consistent with prior literature, there were significant associations between maltreatment history and autonomic reactivity (i.e., heart rate and respiratory sinus arrhythmia) during emotional and physical challenges; however, when VE was entered as a covariate these associations were no longer statistically significant. Blunted VE may reflect a neural pathway through which maltreatment retunes autonomic regulation and provides a neurophysiological platform that increases mental health risk.
Why Do Humans—and Some Animals—Love to Dance?

Have you ever lost yourself in dance? Or have you bounced your foot or wiggled with the rhythm of music? Do you find yourself smiling when you do so? You are not alone! From a simple drumbeat to popular rock-and-roll, the sound of music makes people of all ages move along in time to the beat. We see people tapping, clapping, and bouncing when listening to their favorite songs at a concert hall or on their phones. The urge to move with music has been part of all cultures across the world for as long as we have been studying humans. There are even some animal species that like to dance! Why is this? In this article, we explain what it is about music that makes us want to move—and what is happening in our brains when we do. Let us dive into the science behind dance.
Effect of a Single Simulated 500 m Saturation Dive on Lung Function

Background: Whether deep saturation diving causes injury to lung function remains controversial and the mechanism is unclear. The present study aimed to evaluate the effects of a 500 m simulated single saturation dive on lung function. Methods: A retrospective study was performed in nine professional divers who spent 176 h in a high-pressure environment simulating a depth of 500-m saturation dive (51 atm, 5.02 Mpa). Pulmonary function parameters were investigated and compared before and on 3 days after the dive. Results: Nine professional divers aged (36 ± 7) years were enrolled. Three days after the dive, the parameters related to expiratory flow (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)) were decreased; the parameters related to small airway function (forced expiratory flow at 50%, 75% of FVC exhaled and forced mid-expiratory flow) were decreased compared with those before the dive (both p < 0.05). Additionally, after the dive, the parameters related to pulmonary diffusion function were decreased compared with those before the dive (both p < 0.05). The parameters related to lung volume (residual volume, vital capacity and total lung volume) and those related to respiratory exertion (peak expiratory flow and forced expiratory flow at 75% of FVC exhaled) were not significantly different between after and before the dive. Two divers with small airway dysfunction before the dive had obstructive ventilatory dysfunction after the dive. Additionally, mild obstructive ventilatory dysfunction in three divers before the dive became severe after the dive. After a bronchial dilation test, five divers showed improvement of FEV1, which ranged from 0.10 to 0.55 L. Chest radiographs and echocardiography of all divers were normal after diving. Conclusion: 500 m simulated saturation diving induces a decrease in small airway function and diffusion function. This injury may be associated with small airway and diffusion membrane lesions.
Stepped Geomorphology Shaped the Phylogeographic Structure of a Widespread Tree Species (Toxicodendron vernicifluum, Anacardiaceae) in East Asia

Species’ phylogeographic patterns reflect the interplay between landscape features, climatic forces, and evolutionary processes. Here, we used two chloroplast DNA (cpDNA) markers (trnL and trnL-F) to explore the role of stepped geomorphology in shaping the phylogeographic structure of Toxicodendron vernicifluum, an economically important tree species widely distributed in East Asia. The range-wide pattern of sequence variation was analyzed based on a dataset including 357 individuals from China, together with published sequences of 92 individuals mainly from Japan and South Korea. We identified five chloroplast haplotypes based on seven substitutions across the 717-bp alignment. A clear east-west phylogeographic break was recovered according to the stepped landforms of mainland China. The wild trees of the western clade were found to be geographically restricted to the “middle step”, which is characterized by high mountains and plateaus, while those of the eastern clade were confined to the “low step”, which is mainly made up of hills and plains. The two major clades were estimated to have diverged during the Early Pleistocene, suggesting that the cool glacial climate may have caused the ancestral population to retreat to at least two glacial refugia, leading to allopatric divergence in response to long-term geographic isolation. Migration vector analyses based on the outputs of ecological niche models (ENMs) supported a gradual range expansion since the Last Interglacial. Mountain ranges in western China and the East China Sea land bridge were inferred to be dispersal corridors in the western and eastern distributions of T. vernicifluum, respectively. Overall, our study provides solid evidence for the role of stepped geomorphology in shaping the phylogeographic patterns of T. vernicifluum. The resulting east-west genetic discontinuities could persist for a long time, and could occur at a much larger scale than previously reported, extending from subtropical (e.g., the Xuefeng Mountain) to warm-temperate China (e.g., the Taihang Mountain).
Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments

Background: Target therapies play more and more important roles in gastrointestinal stromal tumors (GISTs) and melanoma with the advancement of clinical drugs that overcome the resistance caused by gene mutations. c-KIT gene mutations account for a large portion of GIST patients, which are known to be sensitive or resistant to tyrosine kinase inhibitors. However, the role rare mutations play in drug efficacy and progression-free duration remains elusive. Methods: Two rare mutations were identified using Sanger sequencing from the GIST and melanoma cases. Cell experiments were further carried out to demonstrate their role in the imatinib resistance. Results: c-KIT c.1926delA p.K642S*FS mutation in primary and recurrent GIST patients and c-KIT c.1936T>G p.Y646D point mutation in melanoma patients in exon 13 were first demonstrated to be novel targets resistant to imatinib agent. Conclusion: c-KIT mutations c.1926delA and c.1936T>G in exon 13 are clinically significant targets that exhibit resistance to imatinib. This study provides guidance to GIST and melanoma treatments.