Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitrogenases in Oxygen Minimum Zone Waters

Biological dinitrogen (N2) fixation is the pathway making the large pool of atmospheric N2 available to marine life. Besides direct rate measurements, a common approach to explore the potential for N2 fixation in the ocean is a screening-based targeting the key functional marker gene nifH, coding for a subunit of the nitrogenase reductase. As novel sequencing techniques improved, our understanding of the diversity of marine N2 fixers grew exponentially. However, one aspect of N2 fixation in the ocean is often underexplored, which are the two alternative types of the key enzyme of N2 fixation, the nitrogenase. Altogether there are three isoenzymes, the most common Mo-Fe nitrogenase Nif, the Fe-Fe nitrogenase Anf, and the V-Fe nitrogenase Vnf, which differ regarding their genetic organization, as well as their metal co-enzymes. While Mo is only available in the presence of at least traces of oxygen (O2), V and Fe are available if O2 is absent. Therefore, low O2 and anoxic ocean environments could be an ideal place to explore the diversity of the different isotypes of the nitrogenases. Most phylogenetic studies, however, were only based on the functional marker gene nifH, encoding for a subunit of the Nif nitrogenase, and thus limited in representing the diversity of alternative nitrogenases. Here, we screened metagenomes and -transcriptomes from O2 minimum zones off Peru, from the Bay of Bengal, and the anoxic Saanich Inlet to explore the diversity of genes involved in N2 fixation. We identified genes related to all three nitrogenases, and a generally increased diversity as compared to our previous nifH based on studies from OMZ waters. While we could not confirm gene expression of alternative nitrogenases from our transcriptomic, we detected diazotrophs harboring the genetic potential for alternative nitrogenases. We suggest that alternative nitrogenases may not be used under conditions present in those waters, however, depending on trace metal availability they may become active under future ocean deoxygenation.
Characterization of the Immunologic Phenotype of Dendritic Cells Infected With Herpes Simplex Virus 1

Due to viral envelope glycoprotein D binding to cellular membrane HVEM receptor, HSV-1 can infect certain dendritic cells, which becomes an event in the viral strategy to interfere with the host’s immune system. We previously generated the HSV-1 mutant strain M6, which produced an attenuated phenotype in mice and rhesus monkeys. The attenuated M6 strain was used to investigate how HSV-1 infection of dendritic cells interferes with both innate and adaptive immunity. Our study showed that dendritic cells membrane HVEM receptors could mediate infection of the wild-type strain and attenuated M6 strain and that dendritic cells infected by both viruses in local tissues of animals exhibited changes in transcriptional profiles associated with innate immune and inflammatory responses. The infection of pDCs and cDCs by the two strains promoted cell differentiation to the CD103+ phenotype, but varied transcriptional profiles were observed, implying a strategy that the HSV-1 wild-type strain interferes with antiviral immunity, probably due to viral modification of the immunological phenotype of dendritic cells during processing and presentation of antigen to T cells, leading to a series of deviations in immune responses, ultimately generating the deficient immune phenotype observed in infected individuals in the clinical.
The Neural Correlates of the Abnormal Implicit Self-Esteem in Major Depressive Disorder: An Event-Related Potential Study

Implicit self-esteem (ISE) has been considered a critical factor in the development and maintenance of major depressive disorder (MDD). Further investigating the event-related potential (ERP) characteristics underlying abnormal ISE in MDD would be helpful for understanding the neural mechanism of MDD. For this purpose, 32 MDD patients and 31 age- and sex-matched healthy controls (HCs) were enrolled in this study. The Rosenberg Self-Esteem Scale (RSES) was used to evaluate explicit self-esteem (ESE), and a self-esteem go/no-go association task (GNAT) was used to assess ISE. Electroencephalograms were synchronously recorded when performing the self-esteem GNAT. Behavioral data and ERP characteristics under different conditions were analyzed and compared within and across groups. The results showed that compared to HCs, MDD patients had significantly lower RSES scores and self-D scores of GNAT, which reflected lower levels of ESE and ISE, respectively. No significant correlation was found between RESE and self-D scores, and only RESE scores were significantly negatively correlated with the Hamilton Depression Rating Scale (HAMD) score. The averaged centroparietal go-P3 amplitude under the self-positive condition was significantly smaller in MDD than in HCs. Moreover, HCs had a significantly larger average centroparietal go-P3 amplitude in self-positive than in self-negative conditions, while this pattern was opposite in the MDD group. The neural activity patterns for other conditions were similar between MDD and HCs. Our results suggested that patients with MDD have a decreased level of both ESE and ISE, and ISE might be more independent of clinical symptoms. Decreased neural processing that implicitly associate self with positive conditions (and relatively increased implicit association between self and negative conditions) might be important neural correlates for abnormal ISE in MDD.
Evaluation of the Effectiveness and Efficiency of the East African Community Joint Assessment Procedure by Member Countries: The Way Forward

Background: For almost a decade, the East African Community has implemented the Medicines Regulatory Harmonization (EAC-MRH) programme among its member states to harmonise technical requirements and standards for medical products regulation, jointly conduct scientific review of medical product dossiers to assess safety, efficacy and quality, inspect pharmaceutical manufacturing sites and streamline decision-making processes. This initiative enables the cost-effective use of limited resources and efficient and effective delivery of regulatory services to be determined, thus instilling transparency and accountability in all stakeholders, optimising the pharmaceutical market and economic development and improving access to safe, high-quality, effective medicines in the region. The aim of this study was to evaluate the effectiveness and efficiency of the current operating model of the EAC-MRH initiative, including challenges faced and to identify opportunities for improvement. Methods: The Process Effectiveness and Efficiency Rating (PEER) questionnaire, which was used to identify the benefits, challenges, and suggestions for improving performance of EAC-MRH initiative, was completed by assessors representing seven EAC authorities in the joint assessment procedure. Semi-structured interviews were also carried out to validate the responses. Results: This initiative has been of considerable value as it moves toward achieving its main objectives of shorter timelines for approval of medicines, information sharing among regulators and capacity building for assessments, resulting in quicker access and increased availability of medicines for patients in the region. However, the key challenges identified that have hindered effectiveness and efficiency were the lack of a centralised submission and tracking system; inadequate human resources, manufacturers’ failure to submit the exact same dossier to all countries of interest; lack of an integrated information management system; lack of information on national medical regulatory authority or EAC websites; and challenges in monitoring and tracking assessment reports. Conclusion: The use of a robust information technology system for the central tracking of EAC products is essential to address the identified challenges and improve regulatory effectiveness and efficiency. One central point for payment is needed to expedite the process and to ensure transparency and the availability of information on decision making on national and regional websites. Other key strategies for enhancement include improving the capacity of assessors, work and information sharing and a coordination mechanism for the regional joint assessment, with the eventual establishment of a regional medicine agency.
Aggression, Aggression-Related Psychopathologies and Their Models

Neural mechanisms of aggression and violence are often studied in the laboratory by means of animal models. A multitude of such models were developed over the last decades, which, however, were rarely if ever compared systematically from a psychopathological perspective. By overviewing the main models, I show here that the classical ones exploited the natural tendency of animals to defend their territory, to fight for social rank, to defend themselves from imminent dangers and to defend their pups. All these forms of aggression are functional and adaptive; consequently, not necessarily appropriate for modeling non-natural states, e.g., aggression-related psychopathologies. A number of more psychopathology-oriented models were also developed over the last two decades, which were based on the etiological factors of aggression-related mental disorders. When animals were exposed to such factors, their aggressiveness suffered durable changes, which were deviant in the meaning that they broke the evolutionarily conserved rules that minimize the dangers associated with aggression. Changes in aggression were associated with a series of dysfunctions that affected other domains of functioning, like with aggression-related disorders where aggression is just one of the symptoms. The comparative overview of such models suggests that while the approach still suffers from a series of deficits, they hold the important potential of extending our knowledge on aggression control over the pathological domain of this behavior.
Electrochemical Sensor for Hydrogen Peroxide Based on Prussian Blue Electrochemically Deposited at the TiO2-ZrO2–Doped Carbon Nanotube Glassy Carbon-Modified Electrode

In this investigation, a hydrogen peroxide (H2O2) electrochemical sensor was evaluated. Prussian blue (PB) was electrodeposited at a glassy carbon (GC) electrode modified with titanium dioxide– and zirconia-doped functionalized carbon nanotubes (TiO2.ZrO2-fCNTs), obtaining the PB/TiO2.ZrO2-fCNTs/GC-modified electrode. The morphology and structure of the nanostructured material TiO2.ZrO2-fCNTs was characterized by transmission electron microscopy, the specific surface area was determined via Brunauer–Emmett–Teller, X-ray diffraction, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The electrochemical properties were studied by cyclic voltammetry and chronoamperometry. Titania-zirconia nanoparticles (5.0 ± 2.0 nm) with an amorphous structure were directly synthesized on the fCNT walls, aged during periods of 20 days, obtaining a well-dispersed distribution with a high surface area. The results indicated that the TiO2.ZrO2-fCNT–nanostructured material exhibits good electrochemical properties and could be tunable by enhancing the modification conditions and method of synthesis. Covering of the nanotubes with TiO2-ZrO2 nanoparticles is one of the main factors that affected immobilization and sensitivity of the electrochemical biosensor. The electrode modified with TiO2-ZrO2 nanoparticles with the 20-day aging time was superior regarding its reversibility, electric communication, and high sensitivity and improves the immobilization of the PB at the electrode. The fabricated sensor was used in the detection of H2O2 in whey milk samples, presenting a linear relationship from 100 to 1,000 μmol L−1 between H2O2 concentration and the peak current, with a quantification limit (LQ) of 59.78 μmol L−1 and a detection limit (LD) of 17.93 μmol L−1.
Microaggressions: Prevalence and Perspectives of Residents and Fellows in Post-Graduate Medical Education in Kuwait

Objective Microaggression prevalence in post-graduate medical education is unknown in Kuwait. The objective is to determine the prevalence of and capture the perspectives on microaggression among post-graduate trainees in Kuwait. Materials and Methods This is a cross-sectional study of an anonymous online survey targeting residents and fellows in Kuwait. Data collected included demographics, level of training, country of training, microaggression experience, types, and response. Univariate and multivariate analyses were performed using the Chi-square test and binary logistic regression, respectively. Results A total of 319 participants (69.1% females) included 52% junior residents, 39.2% senior residents, and 8.78% fellows. Forty-three percent were aware of the microaggression definition. The percentage was significantly higher in respondents from Gulf/Middle East Countries (57.9%) than from Kuwait. Approximately three-quarters experienced microaggressions. Senior residents were more likely to report exposure to microaggressions [Odds ratio (OR) = 2.4, P < 0.05] and had higher odds of exposure than juniors (OR = 9.85, P < 0.05). Exposure to microaggressions was highest in surgery/surgical specialties. The most common act of microaggression was verbal, followed by invalidation/dismissal of thoughts/ideas, and then acts of discrimination. Of those who experienced microaggressions, two-thirds thought that the experience had a psychological effect on them. Both groups reported low confidence in dealing with microaggressions (Gulf/Middle East Countries 18.8% and Kuwait 30.1%); the difference was not statistically significant. Conclusions Microaggressions are common among post-graduate medical trainees in Kuwait. Implementation of strategies to manage it is necessary. Further research on its impact on medical-training outcomes is needed.
Daily Contributors of Tinnitus Loudness and Distress: An Ecological Momentary Assessment Study

Background Tinnitus is a heterogeneous condition which may be associated with moderate to severe disability, but the reasons why only a subset of individuals is burdened by the condition are not fully clear. Ecological momentary assessment (EMA) allows a better understanding of tinnitus by capturing the fluctuations of tinnitus symptoms, such as distress and loudness, and psychological processes, such as emotional arousal, overall stress, mood, and concentration and how these variables interact over time. Whether any of those variables have an influence over the next day, that is, whether any of these variables are auto- or cross-correlated, is still unanswered. Objectives Assess whether behavioral and symptom-related data from tinnitus users from the TrackYourTinnitus (TYT) mobile app have an impact on tinnitus loudness and distress on subsequent days. Methods Anonymized data was collected from 278 users of the iOS or Android TYT apps between 2014 and 2020. Tinnitus-related distress, tinnitus loudness, concentration level, mood, emotional arousal, and overall stress level were assessed using either a slider or the Wong-Baker Pain FACES scale via a daily survey. Three modeling strategies were used to investigate whether tinnitus loudness and distress are affected by previous days symptoms or psychological processes: auto- and cross correlations, regressions with elastic net regularization, and subgrouping within group iterative multiple model estimation (S-GIMME). Results No autocorrelation or cross-correlation was observed at the group level between the variables assessed. However, application of the regression models with elastic net regularization identified individualized predictors of tinnitus loudness and distress for most participants, with the models including contemporaneous and lagged information from the previous day. S-GIMME corroborated these findings by identifying individualized predictors of tinnitus loudness and distress from the previous day. Discussion We showed that tinnitus loudness and tinnitus distress are affected by the contemporaneous and lagged dynamics of behavioral and emotional processes measured through EMA. These effects were seen at the group, and individual levels. The relevance EMA and the implications of the insights derived from it for tinnitus care are discussed, especially considering current trends toward the individualization of tinnitus care.
Problematic Social Media Use and Intensive Social Media Use Among Academic Students During the COVID-19 Pandemic: Associations With Social Support and Life Satisfaction

The need for interaction that arose given the social distancing imposed on people by governments during the COVID-19 has increased the use of social media (SM). The current study distinguishes between two different patterns of SM use: problematic and intensive, and examines the impact of each specific type of SM on social and mental aspects (i.e., social support, loneliness, and life satisfaction). The sample included 363 higher education students. Data were gathered during a second lockdown using Partial Least Squares—Structural Equation Modeling. The model indicated two different trajectories corresponding to the two types of SM users: Intensive users reported having more family support, whereas problematic users tended to feel lonely, reported having low life satisfaction, and had less support from friends. This study may allude to the possible positive role of SM use, especially during social distancing, in alleviating social and mental burdens in times of crisis.
Early Transcriptional Response to Monensin in Sensitive and Resistant Strains of Eimeria tenella

Eimeria parasites are the causative agents of coccidiosis, a common parasitic disease in poultry and livestock that causes significant economic losses to the animal husbandry industry. Ionophore coccidiostats, such as monensin and salinomycin, are widely used for prophylaxis of coccidiosis in poultry. Unfortunately, widespread drug resistance has compromised their efficacy. As a result, there is an increasing need to understand the targets and resistance mechanisms to anticoccidials. However, how Eimeria parasite genes respond to ionophores remains unclear. In this study, resistance to monensin was induced in E. tenella through serial generations of selection. Both sensitive and resistant E. tenella sporozoites were treated with 5 μg/ml monensin for 0, 2, and 4 h, respectively. Gene transcription profiles were then compared by high-throughput sequencing. The results showed that protein translation-related genes were significantly downregulated after drug induction. A total of 1,848 DEGs were detected in the sensitive strain after 2 h of exposure, whereas only 31 were detected in the resistant strain. Among these DEGs in the sensitive strain, genes associated with protein degradation were significantly upregulated, supporting the autophagy-like parasite killing theory. Then, 4 h of exposure resulted in additional 626 and 621 DEGs for sensitive and resistant strains, respectively. This result implies that the gene transcription in sensitive strain is more susceptible to monensin treatment. Our results provide gene expression landscapes of E. tenella following monensin treatment. These data will contribute to a better understanding of the mechanism of drug resistance to polyether ionophores in coccidia.
Hepatitis B Virus Reactivation and Mycobacterial Infections Associated With Ustekinumab: A Retrospective Study of an International Pharmacovigilance Database

Background: Reports were recently published on hepatitis B virus reactivation (HBVr), tuberculosis (TB), and atypical mycobacterial infection (AMI) in patients with ustekinumab treatment. However, the literature is limited to case reports and series. The study was aimed to investigate their relationships by using an extensive population-based database. Methods: Using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database, we collected all cases of HBVr, TB, and AMI between 1 January 2009 and 30 September 2021, for ustekinumab and other drugs. Disproportionality was analyzed using the reporting odds ratio (ROR), which was considered significant when the lower limit of the 95% confidence interval (95% CI) was >1. Results: Of the 18,760,438 adverse cases reported to FAERS for all drugs, 56,581 cases had been exposed to ustekinumab. Adverse events of HBVr, TB, and AMI were reported in 21, 210, and 20 cases, respectively. The ROR for HBVr with ustekinumab was 2.33 (95% CI, 1.52–3.58), for TB was 5.09 (95% CI, 4.44–5.84), and for AMI was 2.09 (95% CI, 1.35–3.24). In the ustekinumab exposure group, no death occurred in patients with HBVr, but one patient experienced life-threatening liver failure. For those with TB, 24 cases experienced hospitalization and 2 deaths occurred. No death occurred in patients with AMI but eight experienced hospitalization. Conclusion: We identified positive signals between ustekinumab exposure and HBVr, TB, and AMI in FAERS. Although these complications are rare, clinicians using ustekinumab should be aware of the risks.
Prognostic Value of Ishak Fibrosis Stage: Findings from the HALT-C Trial

Background and Aims Studies of the prognostic value of Ishak fibrosis stage are lacking. We utilized multi-year follow-up of the Hepatitis C Antiviral Long Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C.
The Detection Method of Potato Foliage Diseases in Complex Background Based on Instance Segmentation and Semantic Segmentation

Potato early blight and late blight are devastating diseases that affect potato planting and production. Thus, precise diagnosis of the diseases is critical in treatment application and management of potato farm. However, traditional computer vision technology and pattern recognition methods have certain limitations in the detection of crop diseases. In recent years, the development of deep learning technology and convolutional neural networks has provided new solutions for the rapid and accurate detection of crop diseases. In this study, an integrated framework that combines instance segmentation model, classification model, and semantic segmentation model was devised to realize the segmentation and detection of potato foliage diseases in complex backgrounds. In the first stage, Mask R-CNN was adopted to segment potato leaves in complex backgrounds. In the second stage, VGG16, ResNet50, and InceptionV3 classification models were employed to classify potato leaves. In the third stage, UNet, PSPNet, and DeepLabV3+ semantic segmentation models were applied to divide potato leaves. Finally, the three-stage models were combined to segment and detect the potato leaf diseases. According to the experimental results, the average precision (AP) obtained by the Mask R-CNN network in the first stage was 81.87%, and the precision was 97.13%. At the same time, the accuracy of the classification model in the second stage was 95.33%. The mean intersection over union (MIoU) of the semantic segmentation model in the third stage was 89.91%, and the mean pixel accuracy (MPA) was 94.24%. In short, it not only provides a new model framework for the identification and detection of potato foliage diseases in natural environment, but also lays a theoretical basis for potato disease assessment and classification.