Miracle-dz/UniFAR-FTUs huggingface dataset:
A case report of PR-3-ANCA-positive glomerulonephritis with histological features of GPA associated with infectious endocarditis

Abstract Rationale: Several renal diseases are associated with infectious endocarditis. However, there are few reports on patients with granulomatosis with polyangiitis (GPA) associated with infectious endocarditis, and there is no consensus for appropriate treatment. Patients concerns: A 35 -years-old man with congenital ventricular septal defect presented severe anemia, hematuria and proteinuria. The blood and urine examinations showed elevated white blood cells (12,900 cells/μL), C-reactive protein level (13.1 mg/dL) and proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level (11.0 IU/mL), severe anemia (hemoglobin: 6.1 g/dL) and renal dysfunction [estimated glomerular filtration rate (eGFR): 12.7 ml/min.1. 78 m2 with hematuria and proteinuria]. Diagnoses: The patient was diagnosed with crescentic glomerulonephritis with histological features of GPA associated with infectious endocarditis by renal biopsy and transthoracic echocardiography. Interventions: Antibacterial drugs (ampicillin-sulbactam) were administrated. No immunomodulating agents were used because immunosuppressive drugs may worsen infectious endocarditis. Subsequently, renal function and urinary findings improved. However, infectious endocarditis was not improved. Therefore, valve replacements and ventricular septal closure surgery were conducted. Outcomes: Thereafter, his postoperative course was uneventful, renal function improved (eGFR: 64.3 ml/min.1.78 m2), and PR3-ANCA level normalized. Lessons: We reported a case report of PR3-ANCA positive glomerulonephritis with histological features of GPA associated with infectious endocarditis. Physicians might note this renal complication when they manage infectious endocarditis.
X-linked serotonin 2C receptor is associated with a non-canonical pathway for sudden unexpected death in epilepsy

Abstract Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic drive as a critical pathogenic step. Accordingly, the G protein-coupled, membrane serotonin receptor 5-HT2C inhibits forebrain and brainstem networks by exciting GABAergic interneurons, and deletion of this gene lowers the threshold for lethal evoked audiogenic seizures. Here, we characterize epileptogenesis throughout the lifespan of mice lacking X-linked, 5-HT2C receptors (loxTB Htr2c). We find that loss of Htr2c generates a complex, adult-onset spontaneous epileptic phenotype with a novel progressive hyperexcitability pattern of absences, non-convulsive, and convulsive behavioural seizures culminating in late onset sudden mortality predominantly in male mice. RNAscope localized Htr2c mRNA in subsets of Gad2+ GABAergic neurons in forebrain and brainstem regions. To evaluate the contribution of 5-HT2C receptor-mediated inhibitory drive, we selectively spared their deletion in GAD2+ GABAergic neurons of pan-deleted loxTB Htr2c mice, yet unexpectedly found no amelioration of survival or epileptic phenotype, indicating that expression of 5-HT2C receptors in GAD2+ inhibitory neurons was not sufficient to prevent hyperexcitability and lethal seizures. Analysis of human Sudden Unexpected Death in Epilepsy and epilepsy genetic databases identified an enrichment of HTR2C non-synonymous variants in Sudden Unexpected Death in Epilepsy cases. Interestingly, while early lethality is not reflected in the mouse model, we also identified variants mainly among male Sudden Infant Death Syndrome patients. Our findings validate HTR2C as a novel, sex-linked candidate gene modifying Sudden Unexpected Death in Epilepsy risk, and demonstrate that the complex epilepsy phenotype does not arise solely from 5-HT2C-mediated synaptic disinhibition. These results strengthen the evidence for the serotonin hypothesis of Sudden Unexpected Death in Epilepsy risk in humans, and advance current efforts to develop gene-guided interventions to mitigate premature mortality in epilepsy.
The importance of spawning behavior in understanding the vulnerability of exploited marine fishes in the U.S. Gulf of Mexico

The vulnerability of a fish stock to becoming overfished is dependent upon biological traits that influence productivity and external factors that determine susceptibility or exposure to fishing effort. While a suite of life history traits are traditionally incorporated into management efforts due to their direct association with vulnerability to overfishing, spawning behavioral traits are seldom considered. We synthesized the existing biological and fisheries information of 28 fish stocks in the U.S. Gulf of Mexico to investigate relationships between life history traits, spawning behavioral traits, management regulations, and vulnerability to fishing during the spawning season. Our results showed that spawning behavioral traits were not correlated with life history traits but improved identification of species that have been historically overfished. Species varied widely in their intrinsic vulnerability to fishing during spawning in association with a broad range of behavioral strategies. Extrinsic vulnerability was high for nearly all species due to exposure to fishing during the spawning season and few management measures in place to protect spawning fish. Similarly, several species with the highest vulnerability scores were historically overfished in association with spawning aggregations. The most vulnerable species included several stocks that have not been assessed and should be prioritized for further research and monitoring. Collectively, the results of this study illustrate that spawning behavior is a distinct aspect of fish ecology that is important to consider for predictions of vulnerability and resilience to fisheries exploitation.
Increased Proportion of Dual-Positive Th2–Th17 Cells Promotes a More Severe Subtype of Asthma

Asthma is a heterogeneous disease, and abnormal activation of T cells is the driving link of asthma's pathophysiological changes. Dual-positive Th2–Th17 cells, as newly discovered T-helper cells, have the functions of Th2 and Th17 cells and can coproduce Th2 and Th17 cytokines. Previous studies have shown that dual-positive Th2–Th17 cells increase the chances of asthma and correlate with asthma severity. However, the exact role of dual-positive Th2–Th17 cells in asthma is not known. Since there is no mature differentiation method for dual-positive Th2–Th17 cells, the present study aimed to clarify the strict differentiation conditions and reveal how dual-positive Th2–Th17 cells regulate asthma phenotypes. In this study, we confirmed that IL-1β, IL-6, anti-IFN-γ, and IL-21 promoted biphenotypic cell differentiation. Moreover, more proportion of dual-positive Th2–Th17 cells can be obtained by conditioned differentiation of mouse CD4+ T cells after classical allergic asthma modeling. Before asthma modeling, adoptive dual-positive Th2–Th17 cells promoted T cells to differentiate into the same biphenotype cells and exacerbated the severity of asthma. Together, our results clarify the differentiation conditions of dual-positive Th2–Th17 cells and further confirm that it stimulates asthma T cells to differentiate into the same biphenotype cells, leading to exacerbation of asthma.
Calcineurin Activation by Prion Protein Induces Neurotoxicity via Mitochondrial Reactive Oxygen Species

Prion diseases are caused by PrPsc accumulation in the brain, which triggers dysfunctional mitochondrial injury and reactive oxygen species (ROS) generation in neurons. Recent studies on prion diseases suggest that endoplasmic reticulum (ER) stress induced by misfolding proteins such as misfolded prion protein results in activation of calcineurin. Calcineurin is a calcium-related protein phosphatase of type 2B that exists in copious quantities in the brain and acts as a critical nodal component in the control of cellular functions. To investigate the relationship between calcineurin and intracellular ROS, we assessed the alteration of CaN and ROS induced by prion peptide (PrP) 106-126. Human prion peptide increased mitochondrial ROS by activating calcineurin, and the inhibition of calcineurin activity protected mitochondrial function and neuronal apoptosis in neuronal cells. These results suggest that calcineurin plays a pivotal role in neuronal apoptosis by mediating mitochondrial injury and ROS in prion diseases.
Patients with Shock have only Few Clinical Characteristics Related to Etiology

The aim of this study is to describe clinical variables and comorbidities in patients with shock, at arrival to the emergency department, and evaluate the diagnostic validity for different shock etiologies. This was a retrospective cohort study with tertiary analysis of data previously published in two other studies. The study population was all patients with shock, arriving to the emergency department at Odense University Hospital between 2000 and 2011. Shock was defined as systolic blood pressure ≤100mmHg and one or more organ failures. Patients were grouped according to discharge diagnoses and this method was manually validated through patient records. The diagnostic value of 26 clinical variables and 10 comorbidities were described and tested. We included 1553 patients and found statistical significant differences in 17 clinical variables. The diagnostic validity of the variables was very low except for CRP, temperature and hemoglobin which had moderate diagnostic value. We also found significant differences in prevalence of comorbidities (liver disease, cardiovascular disease, and chronic obstructive pulmonary disease) between patients with septic, cardiogenic, and hemorrhagic shock. We conclude that patients who arrived at the emergency department with septic, cardiogenic or hemorrhagic shock differed in some aspects, but even the strongest predictors could not discriminate completely between etiologies.
Insulin and IGF-2 support rat corneal endothelial cell growth and wound repair in the organ cultured tissue

Abstract The ability of insulin and IGF-2 to support wound repair in the organ-cultured rat corneal endothelium was investigated. Corneas given a circular transcorneal freeze injury, were explanted into organ cultures containing either insulin or IGF-2 and cultured up to72 h. Both factors increased [3H]-thymidine incorporation and mitotic levels compared to controls. Insulin’s ability to mediate wound closure without serum was dependent on its continuous presence in the medium. PKC was also investigated in endothelial repair using the PKC promoter phorbol 12-myristate 13-acetate (PMA). Concentrations between 10−6 and 10−8 M, PMA failed to accelerate wound closure. When injured endothelia were cultured in the presence of insulin and the PKC inhibitor H-7, wound closure was also unaffected. These results indicate that insulin and IGF-2 stimulate cell growth in injured rat corneal endothelium and that insulin without the benefit of serum promotes wound closure in situ independent of the PKC pathway.
Chemical-activity-based quality marker screening strategy for Viscum articulatum.

Viscum articulatum Burm. f is a parasitic plant rich in flavonoids, triterpenoids, and catechins and has a high nutritional value. It has been reported that drinking of V. articulatum can prevent cardiac diseases. In this study, six bioactive ingredients, including catechins, triterpenoids, and phenylpropanoid glycosides were determined in alcohol extracts of the plant by high-performance liquid chromatography. The anti-inflammatory and antioxidant activities of three catechins, two triterpenoids, and three combination drugs were measured in cardiomyocytes, and the results showed that the anti-inflammatory activity was significantly enhanced while retaining strong antioxidant activity when epicatechin and ursolic acid were used in combination. The main quality markers epicatechin and ursolic acid were screened based on the specificity of the genuine herb and a potent synergistic effect, and the lowest limitation contents of V. articulatum which could discriminate it from some other taxonomically similar materials were accordingly determined. This self-built lowest limitation content of the two screened quality markers could quickly and accurately reflect the efficacy in terms of the chemical composition, and reverse the disorderly market use of non-genuine herbs or confusing species for adulteration. This study is of some significance for market regulation, drug development, and clinical medication.
The effect of immunotherapy on cross-reactivity between house dust mite and other allergens in house dust mite -sensitized patients with allergic rhinitis

ABSTRACT Introduction House dust mite (HDM) is a main perennial allergen causing allergic rhinitis (AR). It has been shown that HDM cross-reacts with a variety of other allergens. Presently, allergen-specific immunotherapy (AIT) is an effective way for management of mono-sensitized HDM+ AR patients. However, management approaches to polysensitized HDM-sensitized AR patients are not standardized yet. Area covered This article reviews the data available in the literature for cross-reactivity between HDM and inhalant or food allergens, the diagnosis of cross-reactivity in HDM-sensitized AR patients, and the effect of immunotherapy on cross-reactivity in HDM-sensitized AR patients; which may help to develop effective therapeutic strategies for management of polysensitized HDM-sensitized AR patients in the future. Expert opinion Pan-allergen proteins such as tropomyosin, arginine kinase (AK), glutathione S-transferase (GST), and hemocyanin are responsible for cross-reactivity between HDM and other allergens. To distinguish genuine or cross-reactive sensitization, molecular- or component-resolved diagnosis is suggested to apply in HDM-sensitized AR patients. The effect of HDM immunotherapy to treat the associated cross-reactivity in HDM-sensitized AR patients is still contradictory, and might be dependent on the degree of homology between two allergens. Furthermore, targeting tropomyosin might be a promising way to treat HDM patients with allergen cross-reactivity Abbreviations AIT: allergen-specific immunotherapy; AK: arginine kinase; AR: allergic rhinitis; CRD: component-resolved diagnostics; Der f: Dermatophagoides farina; Der p: Dermatophagoides pteronyssinus; EAACI: European Academy of Allergy and Clinical Immunology; GST: glutathione S-transferase; GWAS: genome-wide association study; HDM: house dust mite; IgE: immunoglobulin E; RAST: radioallergosorbent test; sIgE: specific IgE; SIT: specific immunotherapy; SCIT: subcutaneous immunotherapy; SLIT: sublingual immunotherapy; SPT: skin prick test
Different responses of the oral, nasal and lung microbiomes to cigarette smoke

To examine the role of smoking on the bacterial community composition of the upper and the lower respiratory tract, a monocentric, controlled prospective study was performed, including healthy smokers, ex-smokers and never-smokers. Smokers were further grouped according to their smoking history. Bacterial diversity was analysed using a molecular barcoding approach based on directly extracted DNA. Our study shows for the first time distinct bacterial response patterns in the upper and lower respiratory tract to cigarette smoking leading to a higher abundance of opportunistic pathogens. The clinical significance of these dysbioses for health needs to be further explored.
Progress in soybean functional genomics over the past decade

Summary Soybean is one of the most important oilseed and fodder crops. Benefiting from the efforts of soybean breeders and the development of breeding technology, large number of germplasm has been generated over the last 100 years. Nevertheless, soybean breeding needs to be accelerated to meet the needs of a growing world population, to promote sustainable agriculture and to address future environmental changes. The acceleration is highly reliant on the discoveries in gene functional studies. The release of the reference soybean genome in 2010 has significantly facilitated the advance in soybean functional genomics. Here, we review the research progress in soybean omics (genomics, transcriptomics, epigenomics and proteomics), germplasm development (germplasm resources and databases), gene discovery (genes that are responsible for important soybean traits including yield, flowering and maturity, seed quality, stress resistance, nodulation and domestication) and transformation technology during the past decade. At the end, we also briefly discuss current challenges and future directions.
Nuclear translocation of MTL5 from cytoplasm requires its direct interaction with LIN9 and is essential for male meiosis and fertility

Meiosis is essential for the generation of gametes and sexual reproduction, yet the factors and underlying mechanisms regulating meiotic progression remain largely unknown. Here, we showed that MTL5 translocates into nuclei of spermatocytes during zygotene-pachytene transition and ensures meiosis advances beyond pachytene stage. MTL5 shows strong interactions with MuvB core complex components, a well-known transcriptional complex regulating mitotic progression, and the zygotene-pachytene transition of MTL5 is mediated by its direct interaction with the component LIN9, through MTL5 C-terminal 443–475 residues. Male Mtl5c-mu/c-mu mice expressing the truncated MTL5 (p.Ser445Arg fs*3) that lacks the interaction with LIN9 and is detained in cytoplasm showed male infertility and spermatogenic arrest at pachytene stage, same as that of Mtl5 knockout mice, indicating that the interaction with LIN9 is essential for the nuclear translocation and function of MTL5 during meiosis. Our data demonstrated MTL5 translocates into nuclei during the zygotene-pachytene transition to initiate its function along with the MuvB core complex in pachytene spermatocytes, highlighting a new mechanism regulating the progression of male meiosis.
Magnetic resonance imaging findings in focal‐onset status epilepticus

Magnetic resonance imaging (MRI) is commonly used in the diagnostic work‐up for status epilepticus (SE). The purpose of this study was to characterize MRI features in SE patients and determine their association with clinical and electroencephalography (EEG) findings. The mid‐term consequences of baseline MRI features were also analysed.
Assessment of a Novel, 22-lead Mobile Electrocardiogram in Elite, Adolescent Footballers

Abstract The 12-lead electrocardiogram is a key component of cardiac screening in elite adolescent footballers. Current technology hampers mobile electrocardiogram monitoring that could reduce the time-to-diagnosis in symptomatic athletes. Recently, a 22-lead mobile electrocardiogram monitor, CardioSecur (Personal MedSystems GmbH), has been approved for use in adults. In this study, the differences in parameter accuracy between CardioSecur’s 22-lead electrocardiogram and the gold standard 12-lead electrocardiogram were assessed in elite adolescent footballers (n=31) using Bland-Altman and paired t-tests/Wilcoxon analysis. Agreement between the two devices was clinically acceptable for heart rate (bias=− 0.633 bpm), PR Interval (bias=− 1.73 ms), Bazzett’s corrected QTc interval (bias=2.03 ms), T-wave axis (bias=6.55°), P-wave duration (bias=− 0.941 ms), Q-wave amplitude (bias=0.0195 mV), Q-wave duration (bias=1.98 ms), rhythm (bias=0.0333), ST-segment (bias=− 0.0629), J-point analysis (bias=− 0.01) and extended T wave and QRS duration analysis. Unsatisfactory agreement was observed in QRS axis (bias=− 19.4°), P-wave axis (bias=− 0.670°), QRS amplitude (bias=− 0.660 mV), P-wave amplitude (bias=0.0400 mV) and T-wave amplitude (bias=− 0.0675 mV). CardioSecur’s 22-lead electrocardiogram agrees with the gold standard in rhythm, durations, T-wave determination in all leads assessed, permitting its use in adolescent footballers for immediate pitch- or track-side analysis.
Evaluating the role of Approach-Avoidance Training on action-tendencies in individuals with skin-picking disorder: A preliminary randomized experiment

Abstract Background and aims Pathological skin-picking (PSP) or excoriation disorder is a destructive behavior that affects 1-2% of the general population. The purpose of this pilot study was to evaluate the effect of a computerized behavior modification task on action-tendencies (i.e., approach or avoidance) in adults with PSP. We aimed to modify these action-tendencies by having participants with PSP complete the Approach-Avoidance Training (AAT) task, using a joystick to simulate an approach (=pull) or avoidance (=push) response. Method Forty-five participants diagnosed with PSP were randomized to one of three training conditions: (1) Avoidance Training (AvT; n = 15), (2) Approach Training (ApT; n = 15), or (3) Placebo Training (PT; n = 15). We hypothesized that after training, those in the AvT would have the greatest reduction in behavioral approach (i.e., their overall reaction time [RT] to approach pictures of irregular skin stimuli). Results Results of the pre-training assessment task revealed a positive correlation between behavioral approach to irregular skin stimuli and skin-picking severity as assessed by the Skin Picking Scale-Revised (SPS-R). After training, a lower behavioral approach and urges to pick were found in the AvT and PT groups, while those in the ApT reported higher behavioral approach and urges to pick. At two-week follow-up, no significant changes on the SPS-R were reported between groups. Discussion Our preliminary data suggest that the AAT is a promising avenue of research to develop as a cognitive intervention to address an excessive behavioral approach tendency that characterizes skin-picking problems.
DRAMP 3.0: an enhanced comprehensive data repository of antimicrobial peptides

Abstract Stapled antimicrobial peptides are an emerging class of artificial cyclic peptide molecules which have antimicrobial activity and potent structure stability. We previously published the Data Repository of Antimicrobial Peptides (DRAMP) as a manually annotated and open-access database of antimicrobial peptides (AMPs). In the update of version 3.0, special emphasis was placed on the new development of stapled AMPs, and a subclass of specific AMPs was added to store information on these special chemically modified AMPs. To help design low toxicity AMPs, we also added the cytotoxicity property of AMPs, as well as the expansion of newly discovered AMP data. At present, DRAMP has been expanded and contains 22259 entries (2360 newly added), consisting of 5891 general entries, 16110 patent entries, 77 clinical entries and 181 stapled AMPs. A total of 263 entries have predicted structures, and more than 300 general entries have links to experimentally determined structures in the Protein Data Bank. The update also covers new annotations, statistics, categories, functions and download links. DRAMP is available online at http://dramp.cpu-bioinfor.org/.