Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of Antibiotic-Resistant Escherichia coli Isolated from Swine Faeces and Lagoons in Bulgaria

Antimicrobial resistance (AMR) is a worldwide health problem affecting humans, animals, and the environment within the framework of the “One Health” concept. The aim of our study was to evaluate the prevalence of pathogenic strains of the species Escherichia coli (E. coli), their AMR profile, and biofilm-forming potential. The isolated strains from three swine faeces and free lagoons (ISO 16654:2001/Amd 1:2017) were confirmed using Phoenix M50 and 16S rDNA PCR. The antibiotic sensitivity to 34 clinically applied antibiotics was determined by Phoenix M50 and the disc diffusion method, according to the protocols of the CLSI and EUCAST. We confirmed the presence of 16 E. coli isolates, of which 87.5% were multi-drug-resistant and 31.25% performed strong biofilms. The possibility for the carrying and transmission of antibiotic-resistance genes to quinolones (qnr), aminoglycosides (aac(3)), β-lactamase-producing plasmid genes ampC, and blaSHV/blaTEM was investigated. We confirmed the carrying of blaSHV/blaTEM in one and ampC in seven isolates. The strains were negative for the virulence genes (ETEC (LT, STa, and F4), EPEC (eae), and STEC/VTEC (stx and stx2all)). The results should contribute to the development of effective measures for limitation and control on the use of antibiotics, which is a key point in the WHO action plan.
Hepatic Proteomic Analysis Reveals That Enhanced Carboxylic Acid Metabolism and Oxidoreduction Promote Muscle and Fat Deposition in Muscovy Duck

Simple Summary Liver plays an important role in lipid synthesis and muscle growth in poultry. The current study measured the growth traits and the proteome of Muscovy duck liver at 14, 28, 42, and 56 days, aiming at exploring the key regulatory proteins for intramuscular fat deposition and muscle growth. The results showed that Muscovy duck grew most rapidly at 28 vs. 42 days of age, subcutaneous and abdominal fat were deposited rapidly, but intramuscular fat content decreased. At the same time, the abundance of liver proteins regarding the tricarboxylic acid cycle and oxidoreduction increased significantly. This study provides a profile of the fat deposition and liver proteome for Muscovy duck. Abstract Liver is responsible for 90% of lipid synthesis in poultry; thus, it plays an important role in the growth of Muscovy ducks, which have a high fat deposition ability in a time-dependent manner. Therefore, male Muscovy ducks at 14, 28, 42, and 56 days were selected for body weight (BW), carcass weight (CW), subcutaneous fat thickness (SFT), abdominal fat weight (AFW), intramuscular fat content (IMF), and breast muscle fiber (BMF) diameter and density determination. Two-dimensional electrophoresis (2-DE) combining liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) was used to analyze proteomic changes in liver at each stage. The BW, CW, AFW, SFT, and BMF diameter and density were significantly increased, while IMF content was significantly decreased at 28 to 42 days of age (p < 0.05). There were 57 differentially abundant protein (DEP) spots representing 40 proteins identified among the ages, in which 17, 41 and 4 spots were differentially abundant at 14 vs. 28, 28 vs. 42, and 42 vs. 56, respectively. Gene Ontology enrichment analysis found that DEPs were mostly enriched in the oxidation-reduction process, carboxylic acid metabolism, etc. Protein–protein interaction showed that catalase (CAT), triosephosphate isomerase (TPI), and protein disulfide-isomerase (PDI) were the key proteins responsible for the growth of Muscovy duck. In conclusion, 28 to 42 days of age is the crucial period for Muscovy ducks, and the ability of metabolism and antioxidants were significantly enhanced in liver.
Antibiotic Use and Fatal Outcomes among Critically Ill Patients with COVID-19 in Tacna, Peru

Overuse of antibiotics during the Coronavirus Disease 2019 (COVID-19) pandemic could increase the selection of extensively resistant bacteria (XDR). However, it is unknown what impact they could have on the evolution of patients, particularly critically ill patients. This study aimed to evaluate the characteristics and impact of ICU-acquired infections in patients with COVID-19. A retrospective cohort study was conducted, evaluating all patients with critical COVID-19 admitted to the intensive care unit (ICU) of a hospital in Southern Peru from 28 March 2020 to 1 March 2021. Of the 124 patients evaluated, 50 (40.32%) developed a healthcare-associated infection (HAI), which occurred at a median of 8 days (IQR 6–17) after ICU admission. The proportion of patients with HAI that required ceftriaxone was significantly higher; the same was true for the use of dexamethasone. Forty bacteria isolations (80%) were classified as XDR to antibiotics, with the most common organisms being Acinetobacter baumannii (54%) and Pseudomonas aeruginosa (22%); 33% (41/124) died at the ICU during the follow-up. In the adjusted analysis, healthcare-associated infection was associated with an increased risk of mortality (aHR= 2.7; 95% CI: 1.33–5.60) and of developing acute renal failure (aRR = 3.1; 95% CI: 1.42–6.72). The incidence of healthcare infection mainly by XDR pathogens is high in critically ill patients with COVID-19 and is associated with an increased risk of complications or death.
Functional Interactions between Entorhinal Cortical Pathways Modulate Theta Activity in the Hippocampus

Simple Summary The activity in the hippocampus is characterized by a strong oscillation at theta frequency that organizes the neuronal firing. We have recently shown that different theta oscillations are present in the hippocampus, opening the possibility to multiple interactions between theta rhythms. In this work, we analyzed the functional connectivity between theta generators during the exploration of a known environment with or without a novel stimulus. The directionality of the interactions was determined using tools based on Granger causality and transfer entropy. We found significant interactions between activity components originated in CA3 and in layers II and III of the entorhinal cortex. During exploration with a novel stimulus, the connectivity from the entorhinal cortex layer II increased, while the influence of CA3 decreased. These results suggest that the entorhinal cortex layer II may drive theta interactions and synchronization in the hippocampus during novelty exploration. Abstract Theta oscillations organize neuronal firing in the hippocampus during context exploration and memory formation. Recently, we have shown that multiple theta rhythms coexist in the hippocampus, reflecting the activity in their afferent regions in CA3 (Schaffer collaterals) and the entorhinal cortex layers II (EC-II, perforant pathway) and III (EC-III, temporoammonic pathway). Frequency and phase coupling between theta rhythms were modulated by the behavioral state, with synchronized theta rhythmicity preferentially occurring in tasks involving memory updating. However, information transmission between theta generators was not investigated. Here, we used source separation techniques to disentangle the current generators recorded in the hippocampus of rats exploring a known environment with or without a novel stimulus. We applied analytical tools based on Granger causality and transfer entropy to investigate linear and non-linear directed interactions, respectively, between the theta activities. Exploration in the novelty condition was associated with increased theta power in the generators with EC origin. We found a significant directed interaction from the Schaffer input over the EC-III input in CA1, and a bidirectional interaction between the inputs in the hippocampus originating in the EC, likely reflecting the connection between layers II and III. During novelty exploration, the influence of the EC-II over the EC-III generator increased, while the Schaffer influence decreased. These results associate the increase in hippocampal theta activity and synchrony during novelty exploration with an increase in the directed functional connectivity from EC-II to EC-III.
Surgical Margins in Canine Cutaneous Soft-Tissue Sarcomas: A Dichotomous Classification System Does Not Accurately Predict the Risk of Local Recurrence

Simple Summary Histological evaluation of surgical margins is crucial for correct prognostication and adjuvant treatment recommendation after excision of soft tissue sarcoma (STS) in dogs. Incompletely excised STS have a high risk of local recurrence (LR), while completely excised STS without other negative prognostic factors are generally associated with a good prognosis. However, guidelines are lacking on how to manage STS excised with clean but close margins (CbCM), although some authors advocated their inclusion in the tumor-free margin group. This retrospective study investigates the impact of CbCM on LR of canine STS. Ninety-eight surgical excised canine STS at first presentation were included. Cumulative incidence of LR was estimated for each category of margins (tumor-free, infiltrated, CbCM), and after grouping CbCM alternatively in the tumor-free and infiltrated category. Cumulative incidence of LR at three years differed significantly between the three categories, and it was estimated to be 42% with infiltrated margins, 23% with CbCM, 7% with tumor-free margins. Both when CbCM were grouped with infiltrated margins or with tumor-free margins, the incidence of LR was statistically different. The rate of LR with CbCm was greater than with tumor-free margins. The category CbCM may be considered as a separate prognostic category. Abstract Adjuvant treatments are recommended in dogs with incompletely excised cutaneous soft-tissue sarcoma (STS) to reduce the risk of local recurrence (LR), although guidelines are lacking on how to manage clean but close margins (CbCM). This retrospective study investigates the impact of CbCM on LR of canine STS. Ninety-eight surgically excised canine STS at first presentation were included. Tissue samples were routinely trimmed and analyzed. Cumulative incidence of LR was estimated for each category of margins (tumor-free, infiltrated, CbCM), and included CbCM in the tumor-free and infiltrated category, respectively. The prognostic impact on LR was then adjusted for relevant prognostic factors. Cumulative incidence of LR at three years differed significantly between the three categories (p = 0.016), and was estimated to be 42% with infiltrated margins, 23% with CbCM, 7% with tumor-free margins. Both when CbCM were grouped with infiltrated margins (p = 0.033; HR = 5.05), and when CbCM were grouped with tumor-free margins (p = 0.011; HR = 3.13), a significant difference between groups was found. STS excised with infiltrated margins had the greatest risk of LR. The rate of LR with CbCm was greater than recurrence rate of tumor-free margins. The category CbCM may be considered as a separate prognostic category.
A Nature-Inspired Nrf2 Activator Protects Retinal Explants from Oxidative Stress and Neurodegeneration

Oxidative stress (OS) plays a key role in retinal dysfunctions and acts as a major trigger of inflammatory and neurodegenerative processes in several retinal diseases. To prevent OS-induced retinal damage, approaches based on the use of natural compounds are actively investigated. Recently, structural features from curcumin and diallyl sulfide have been combined in a nature-inspired hybrid (NIH1), which has been described to activate transcription nuclear factor erythroid-2-related factor-2 (Nrf2), the master regulator of the antioxidant response, in different cell lines. We tested the antioxidant properties of NIH1 in mouse retinal explants. NIH1 increased Nrf2 nuclear translocation, Nrf2 expression, and both antioxidant enzyme expression and protein levels after 24 h or six days of incubation. Possible toxic effects of NIH1 were excluded since it did not alter the expression of apoptotic or gliotic markers. In OS-treated retinal explants, NIH1 strengthened the antioxidant response inducing a massive and persistent expression of antioxidant enzymes up to six days of incubation. These effects resulted in prevention of the accumulation of reactive oxygen species, of apoptotic cell death, and of gliotic reactivity. Together, these data indicate that a strategy based on NIH1 to counteract OS could be effective for the treatment of retinal diseases.
Adverse Events Related to Off-Label Drugs Using Spontaneous Adverse Event Reporting Systems

Purpose The purpose of this study was to investigate the adverse events (AEs) related to the use of off-label drugs. Materials and Methods A cross-sectional study was carried out using available data pertaining to off-label drug were sourced from U.S. FDA spontaneous adverse drug reaction reporting database (FAERS) and Korea Adverse Event Reporting System database (KIDS-KD) for the years 2014 to 2018. The number and frequencies of AE cases were calculated. Disproportionality was analyzed using the proportional reporting ratio (PRR), the reporting odds ratio (ROR), the information component (IC), and the empirical Bayes geometric mean (EBGM) methods. Results The reported AEs associated with off-label drug use were more common among older patients compared with younger patients. Gastric nonspecific symptoms and therapeutic procedure (4.16–4.57%) and haemorrage term (4.16–5.29%) were the most common AE symptoms and antithrombotic agents and immunosuppressants were the drugs most commonly reported to cause AEs in FAERS. Secondary term events (43.45–48.62%) including inappropriate schedule of drug administration and medication error were the most common AEs, and immunosuppressants and antipsychotics were the most common AE-related drugs from KIDS-KD. The numbers of reported AEs in new drug categories such as other antineoplastic agents trended to increase from 2014 to 2018 in both datasets. Conclusion The numbers of reported AEs with off-label drug increased annually. AEs associated with off-label drugs may have a significant impact on older patients. Healthcare experts should be concerned about prescriptions of off-label drugs, especially anticoagulants and newly developed drugs such as immunosuppressants and antineoplastic agents.
Mental Health Care Professionals’ Appraisal of Patients’ Use of Web-Based Access to Their Electronic Health Record: Qualitative Study

Background Patients in a range of health care sectors can access their medical health records using a patient portal. In mental health care, the use of patient portals among mental health care professionals remains low. Mental health care professionals are concerned that patient access to electronic health records (EHRs) will negatively affect the patient’s well-being and privacy as well as the professional’s own workload. Objective This study aims to provide insights into the appraisal work of mental health care professionals to assess and understand patient access to their EHRs through a patient portal. Methods We conducted a qualitative study that included 10 semistructured interviews (n=11) and a focus group (n=10). Participants in both the interviews and the focus group were mental health care professionals from different professional backgrounds and staff employees (eg, team leaders and communication advisors). We collected data on their opinions and experiences with the recently implemented patient portal and their attempts to modify work practices. Results Our study provides insights into mental health care professionals’ appraisal work to assess and understand patient access to the EHR through a patient portal. A total of four topics emerged from our data analysis: appraising the effect on the patient-professional relationship, appraising the challenge of sharing and registering delicate information, appraising patient vulnerability, and redefining consultation routines and registration practices. Conclusions Mental health care professionals struggle with the effects of web-based patient access and are searching for the best ways to modify their registration and consultation practices. Our participants seem to appraise the effects of web-based patient access individually. Our study signals the lack of systematization and communal appraisal. It also suggests various solutions to the challenges faced by mental health care professionals. To optimize the effects of web-based patient access to EHRs, mental health care professionals need to be involved in the process of developing, implementing, and embedding patient portals.
The Etiology of Pneumonia in HIV-uninfected Children in Kilifi, Kenya

Supplemental Digital Content is available in the text. Background: In the 1980s, Streptococcus pneumoniae and Haemophilus influenzae were identified as the principal causes of severe pneumonia in children. We investigated the etiology of severe childhood pneumonia in Kenya after introduction of conjugate vaccines against H. influenzae type b, in 2001, and S. pneumoniae, in 2011. Methods: We conducted a case–control study between August 2011 and November 2013 among residents of the Kilifi Health and Demographic Surveillance System 28 days to 59 months of age. Cases were hospitalized at Kilifi County Hospital with severe or very severe pneumonia according to the 2005 World Health Organization definition. Controls were randomly selected from the community and frequency matched to cases on age and season. We tested nasal and oropharyngeal samples, sputum, pleural fluid, and blood specimens and used the Pneumonia Etiology Research for Child Health Integrated Analysis, combining latent class analysis and Bayesian methods, to attribute etiology. Results: We enrolled 630 and 863 HIV-uninfected cases and controls, respectively. Among the cases, 282 (44%) had abnormal chest radiographs (CXR positive), 33 (5%) died in hospital, and 177 (28%) had diagnoses other than pneumonia at discharge. Among CXR-positive pneumonia cases, viruses and bacteria accounted for 77% (95% CrI: 67%–85%) and 16% (95% CrI: 10%–26%) of pneumonia attribution, respectively. Respiratory syncytial virus, S. pneumoniae and H. influenza, accounted for 37% (95% CrI: 31%–44%), 5% (95% CrI: 3%–9%), and 6% (95% CrI: 2%–11%), respectively. Conclusions: Respiratory syncytial virus was the main cause of CXR-positive pneumonia. The small contribution of H. influenzae type b and pneumococcus to pneumonia may reflect the impact of vaccine introductions in this population.
MrIML: Multi‐response interpretable machine learning to model genomic landscapes

We introduce a new R package “MrIML” (“Mister iml”; Multi‐response Interpretable Machine Learning). MrIML provides a powerful and interpretable framework that enables users to harness recent advances in machine learning to quantify multilocus genomic relationships, to identify loci of interest for future landscape genetics studies, and to gain new insights into adaptation across environmental gradients. Relationships between genetic variation and environment are often nonlinear and interactive; these characteristics have been challenging to address using traditional landscape genetic approaches. Our package helps capture this complexity and offers functions that fit and interpret a wide range of highly flexible models that are routinely used for single‐locus landscape genetics studies but are rarely extended to estimate response functions for multiple loci. To demonstrate the package's broad functionality, we test its ability to recover landscape relationships from simulated genomic data. We also apply the package to two empirical case studies. In the first, we model genetic variation of North American balsam poplar (Populus balsamifera, Salicaceae) populations across environmental gradients. In the second case study, we recover the landscape and host drivers of feline immunodeficiency virus genetic variation in bobcats (Lynx rufus). The ability to model thousands of loci collectively and compare models from linear regression to extreme gradient boosting, within the same analytical framework, has the potential to be transformative. The MrIML framework is also extendable and not limited to modelling genetic variation; for example, it can quantify the environmental drivers of microbiomes and coinfection dynamics.
Treating Critically Ill Patients Experiencing SARS-CoV-2 Severe Infection with Ig-M and Ig-A Enriched Ig-G Infusion

SARS-CoV-2 in patients who need intensive care unit (ICU) is associated with a mortality rate ranging from 10 to 40–45%, with an increase in morbidity and mortality in presence of sepsis. We hypothesized that IgM and IgA enriched immunoglobulin G may support the sepsis-related phase improving patient outcome. We conducted a retrospective case–control study on 47 consecutive patients admitted to our ICU. At the time of admission, patients received anticoagulants (heparin sodium) together with the standard supportive treatment. We decided to add IgM and IgA enriched immunoglobulin G to the standard therapy. Patients receiving IgM and IgA enriched immunoglobulin G were compared with patients with similar baseline characteristics and treatment, receiving only standard therapy. The mortality resulted significantly higher in patients treated with standard therapy only (56.5 vs. 37.5%, p < 0.01) and, at day 7, the probability of dying was 3 times higher in this group. Variable life adjustment display (VLAD) was 2.4 and −2.2 (in terms of lives saved in relation with those expected and derived from Simplified Acute Physiology Score II) in the treated and not treated group, respectively. The treatment based on IgM and IgA enriched immunoglobulin G infusion seems to give an advantage on survival in SARS-CoV-2 severe infection.
Analysis of biological models to predict clinical outcomes based on HLA-DPB1 disparities in unrelated transplantation.

HLA compatibility is a key factor for survival after unrelated hematopoietic cell transplantation (HCT). HLA-A, B, C, DRB1 and DQB1 are usually matched between donor and recipient. By contrast, HLA-DPB1 mismatches are frequent although it is feasible to optimize donor selection and DPB1 matching with prospective typing. Yet, because classical DPB1 allele mismatches are often unavoidable, several biological models have been developed to predict the optimal DPB1 mismatch combination for less graft versus host disease (GVHD) and better overall survival. In 909 recipient/donor pairs, we analyzed the role of three biological models: T-Cell Epitopes (TCE) based on the immunogenicity of DPB1, cell surface expression of DPB1 molecules based on a SNP located in 3'UTR regulatory region and the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model based on the presentation of allogeneic peptides derived from mismatched HLA, compared to the classical allele mismatch. Matching for both DPB1 alleles remains the best option to prevent acute GVHD. In the situation of one DPB1 allele mismatch, the donor associated with the lowest acute GVHD risks is mismatched for an allele with low expression profile in the recipient, followed by a permissive TCE3/4 mismatch and/or the absence of PIRCHE II potential against the recipient. In the context of two DPB1 mismatches, the same considerations apply for a permissive TCE3/4 mismatch and no PIRCHE II. By combining the biological models, the most favorable DPB1 constellation can be defined. This approach will help optimizing donor selection and improve post-HSCT complications and patient prognosis.