Miracle-dz/UniFAR-FTUs huggingface dataset:
Drivers of Antibiotic Use in Poultry Production in Bangladesh: Dependencies and Dynamics of a Patron-Client Relationship

Background: There is increasing concern around the use of antibiotics in animal food production and the risk of transmission of antimicrobial resistance within the food chain. In many low and middle-income countries, including Bangladesh, the commercial poultry sector comprises small-scale producers who are dependent on credit from poultry dealers to buy day-old chicks and poultry feed. The same dealers also supply and promote antibiotics. The credit system is reliant upon informal relationships among multiple actors as part of social capital. This paper aims to describe dependencies and relationships between different actors within unregulated broiler poultry production systems to understand the social and contextual determinants of antibiotic use in low-resource settings. Methods: We used a cross-sectional qualitative design including in-depth interviews among purposefully selected commercial poultry farmers (n = 10), poultry dealers (n = 5), sales representatives of livestock pharmaceutical companies (n = 3) and the local government livestock officer as a key-informant (n = 1). We describe the food production cycle and practices relating to credit purchases and sales using social capital theory. Findings: Poultry dealers provide credit and information for small-scale poultry farmers to initiate and operate their business. In return for credit, farmers are obliged to buy poultry feed and medicine from their dealer and sell their market-ready poultry to that same dealer. All farms applied multiple antibiotics to poultry throughout the production cycle, including banned antibiotics such as colistin sulfate. The relationship between dealers and poultry farmers is reciprocal but mostly regulated by the dealers. Dealers were the main influencers of decision-making by farmers, particularly around antibiotic use as an integral part of the production cycle risk management. Our findings suggest that strategies to improve antibiotic stewardship and responsible use should exploit the patron-client relationship which provides the social and information network for small-scale farmers. Conclusion: Social capital theory can be applied to the patron-client relationship observed among poultry farmers and dealers in Bangladesh to identify influences on decision making and antibiotic use. Within unregulated food production systems, strategies to promote the prudent use of antibiotics should target commercial feed producers and livestock pharmaceutical manufacturers as a first step in developing a sustainable poultry value chain.
Job Loss or Income Loss: How the Detrimental Effect of Unemployment on Men's Life Satisfaction Differs by Immigration Status

Driven by the ongoing debate of job loss vs. income loss in understanding the detrimental effect of unemployment, this study examines how perceptions of unemployment and the resulting levels of life satisfaction differ by immigration status. Based on a countrywide longitudinal dataset in the UK, findings show that immigrant men's life satisfaction suffers more from the detrimental effect of job loss per se, whereas that of native-born men suffers more in the pecuniary respect, which is mainly driven by perceived financial strain, instead of objective income loss. By further examining the heterogeneity among immigrant men themselves, we find similar differences between recent non-EU immigrant men and the rest of the group. While job loss causes a deeper decline in life satisfaction for recent non-EU immigrant men, income loss causes a deeper decline in life satisfaction for recent EU and established immigrant men. We attribute those differences to the extent to which one's legal status in the country is vulnerable to unemployment.
Dexmedetomidine Alleviated Endoplasmic Reticulum Stress via Inducing ER-phagy in the Spinal Cord of Neuropathic Pain Model

Studies demonstrated that spinal autophagy was impaired in spinal nerve ligation (SNL) rats. However, the relationship of endoplasmic reticulum (ER) stress and ER-phagy and whether dexmedetomidine (DEX) modulates ER-phagy remain unclear. In this study, male Sprague–Dawley (SD) rats and the SNL animal model were used. 4-Phenylbutyric acid (4-PBA), tunicamycin (TM), rapamycin (RAP), and 3-methyladenine (3-MA) were intrathecally administered, respectively to demonstrate the relationship of ER stress and ER-phagy. Dexmedetomidine (30 μg/kg) was administered as treatment. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests were performed to evaluate nociceptive hypersensitivity. Protein expressions were examined by Western blot, and the location of glucose-regulated protein 78 (Grp78) was examined by immunofluorescence staining. SNL induced ER stress and ER-phagy impairment. ER stress was altered in rostral ventromedial medulla (RVM); 4-phenylbutyric acid induced analgesic effect via inhibiting ER stress and unfolded protein response (UPR) pathways to induce ER-phagy; tunicamycin led to worsening pain through enhancing ER stress and UPR pathways to further impair ER-phagy. Rapamycin provided analgesic effect through enhancing ER-phagy to relieve SNL-induced ER stress and UPR pathway activation; 3-methyladenine deteriorated pain via further impairing ER-phagy to aggravate ER stress. Dexmedetomidine provided analgesic effect through elevating ER-phagy. In conclusion, ER stress led to ER-phagy impairment in the spinal cord of SNL rats and participated in the nociceptive descending system. ER-phagy impairment was both a trigger and an effector of ER stress via UPR pathways in SNL rats. Dexmedetomidine targeted ER-phagy to provide analgesic effect.
Leptospira Seroprevalence Among Ugandan Slaughter Cattle: Comparison of Sero-Status With Renal Leptospira Infection

Despite evidence of both human and animal Leptospira exposures in Uganda, the epidemiology of the disease is still not well-investigated. Contact with animals and their environments have been pointed out as potential source of infection with Leptospira species in humans; and cattle may be an important reservoir in Uganda. In this cross-sectional study, we estimated the prevalence of anti-Leptospira antibodies by the standard microscopic agglutination test (MAT); and associated risk factors among slaughtered cattle. We also compared the performance of the MAT used in this study against a lipL32 based real time PCR (qPCR) assay previously conducted on the kidneys and urine of the same slaughter cattle as tested in this reported study. Of 500 cattle sampled, 27.8% (95% CI 23.9–32.0) tested positive (titer ≥ 100) to at least one Leptospira serovar, with the majority of seropositive cattle reacting to serovars Tarassovi (sg Tarassovi) (11.6%), Sejroe (Sg Sejroe) (7.8%), and Australis (Sg Australis) (5.2%). Older animals had 2.8 times (95% CI 1.0–8.2, p-value 0.055) greater odds of being seropositive than younger ones (<1.5 years). The sensitivity and specificity of the MAT over the qPCR were 65.9% (95% CI 50.1–79.5) and 75.9% (95% CI 71.7–79.7), respectively; with a negative predictive value of 95.8% and positive predictive value of 20.9%. In conclusion, slaughter cattle in this study were significantly exposed to pathogenic Leptospira species of mainly the Tarassovi, Sejroe, and Australis serogroups, with seroprevalence being higher among older cattle. The high specificity and negative predictive value of MAT as used in this study when compared to the qPCR assay may imply a rather strong association between seronegativity and absence of renal Leptospira infection. However, MAT predictability for renal Leptospira infection may be interpreted cautiously since predictive values of diagnostic tests are dependent on prevalence.
Household Pet Ownership and the Microbial Diversity of the Human Gut Microbiota

The human gut microbiome has a great deal of interpersonal variation due to both endogenous and exogenous factors, like household pet exposure. To examine the relationship between having a pet in the home and the composition and diversity of the adult gut microbiome, we conducted a case-control study nested in a larger, statewide study, the Survey of the Health of Wisconsin. Stool samples were collected from 332 participants from unique households and analyzed using 16S rRNA sequencing on the Illumina MiSeq. One hundred and seventy-eight participants had some type of pet in the home with dogs and cats being the most prevalent. We observed no difference in alpha and beta diversity between those with and without pets, though seven OTUs were significantly more abundant in those without pets compared to those with pets, and four were significantly more abundant in those with pets. When stratifying by age, seven of these remained significant. These results suggest that pet ownership is associated with differences in the human gut microbiota. Further research is needed to better characterize the effect of pet ownership on the human gut microbiome.
Upstream ORFs Influence Translation Efficiency in the Parasite Trypanosoma cruzi

It is generally accepted that the presence of ORFs in the 5′ untranslated region of eukaryotic transcripts modulates the production of proteins by controlling the translation initiation rate of the main CDS. In trypanosomatid parasites, which almost exclusively depend on post-transcriptional mechanisms to regulate gene expression, translation has been identified as a key step. However, the mechanisms of control of translation are not fully understood. In the present work, we have annotated the 5′UTRs of the Trypanosoma cruzi genome both in epimastigotes and metacyclic trypomastigotes and, using a stringent classification approach, we identified putative regulatory uORFs in about 9% of the analyzed 5′UTRs. The translation efficiency (TE) and translational levels of transcripts containing putative repressive uORFs were found to be significantly reduced. These findings are supported by the fact that proteomic methods only identify a low number of proteins coded by transcripts containing repressive uORF. We additionally show that AUG is the main translation initiator codon of repressive uORFs in T. cruzi. Interestingly, the decrease in TE is more pronounced when the uORFs overlaps the main CDS. In conclusion, we show that the presence of the uORF and features such as initiation codon and/or location of the uORFs may be acting to fine tune translation levels in these parasites.
BRD4 Inhibition by AZD5153 Promotes Antitumor Immunity via Depolarizing M2 Macrophages

High-grade serous ovarian cancer (HGSOC), with its high recurrence rates, urges for reasonable therapeutic strategies that can prolong overall survival. A tumor microenvironment (TME) discloses prognostic and prospective information on cancer, such as the expression level of PD-1 or PD-L1. However, in HGSOC, the impact of the therapies aiming at these targets remains unsatisfying. Tumor-associated macrophages (TAMs) in HGSOC make up a large part of the TMEs and transform between diverse phenotypes under different treatments. AZD5153 inhibiting BRD4, as a potential therapeutic strategy for HGSOC, was demonstrated to confer controversial plasticity on TAMs, which shows the need to uncover its impact on TAMs in HGSOC. Therefore, we established models for TAMs and TAMs co-culturing with T lymphocytes in vitro. Via RT-PCR and flow cytometry, we find that AZD5153 resets TAMs from M2-type macrophages to M1-like macrophages, consequently promoting pro-inflammatory cytokine secretion and thus activating CD8+ cytotoxic T lymphocytes (CTLs) in vitro. This modification occurs on MAF transcripts in TAMs and modified by BRD4, which is the target of AZD5153. Importantly, the 3-D microfluid model demonstrates that AZD5153 sensitizes ovarian cancer to anti-PD-L1 therapy. Our results clarify that besides eliminating tumor cells directly, AZD5153 works as a regulator of the TAM phenotype, providing a novel strategy combining AZD5153 and PD-1/PD-L1 antibody that could benefit HGSOC patients.
Resilience as a Mediator Between Interpersonal Risk Factors and Hopelessness in Depression

Several studies investigated the role of resilience as a mediating factor for psychopathological phenotypes. The aim of the current study is to explore the putative role of resilience as a mediator between different vulnerability factors and depressive symptoms. One hundred and fifty patients with a major depressive disorder diagnosis have been evaluated on the basis of humiliation (Humiliation Inventory), adverse past family experiences (Risky Family Questionnaire), hopelessness (Beck Hopelessness Scale), and resilience (Resilience Scale for Adult) scores. A multiple regression analysis and a bootstrapping method were carried out to assess the hypothesis that resilience could mediate the relationships between these risk factors as predictors and hopelessness as a dependent variable. Our results show that resilience has a mediating role in the relationship between several risk factors that are specifically involved in interpersonal functioning and hopelessness. The main limitations of the study are the cross-sectional nature of the study, the use of self-report instruments, the lack of personality assessment, and the consideration of the resilience as a unique construct. The understanding of the mechanisms through which resilience mediates the effects of different interpersonal risk factors is crucial in the study of depression. In fact, future prevention-oriented studies can also be carried out considering the mediating role of resilience between interpersonal risk factors and depressive symptoms.
A Pilot Study of CPR Quality Comparing an Augmented Reality Application vs. a Standard Audio-Visual Feedback Manikin

Background: Guidelines-based cardiopulmonary resuscitation (CPR) during in-hospital cardiac arrest is a significant predictor of survival, yet the quality of healthcare provider (HCP) CPR (e.g., nurses, physicians etc.) has been shown to be poor. Studies have found that providing HCPs with simulated CPR refresher trainings can improve their CPR quality, however, no studies have compared the use of an augmented reality (AR) CPR refresher training with a standard audio-visual (AV) feedback manikin to improve HCP training. Objectives: In our pilot study, HCPs were randomized to a refresher CPR simulation training with either our AR CPR training application (CPReality) or a standard AV feedback manikin. All subjects completed 2 min of CPR on their respective CPR training modalities, followed by an additional 2 min post-simulation CPR evaluation with no feedback. We hypothesized that the AR CPR training application would confer improved CPR quality defined as chest compression rate and depth compared with the standard AV feedback training. Results: Between January 2019 and May 2019, 100 HCPs were enrolled (50 in the CPReality cohort and 50 in the standard AV manikin cohort). The mean chest compression (CC) rate for all subjects during the intervention was 118 ± 15 cpm, and CC depth was 50 ± 8; post-intervention the CC rate was 120 ± 13 and CC depth was 51 ± 8. The mean CC rate for those trained with CPReality was 121 ± 3 compared with the standard CPR manikin training which was 114 ± 1 cpm (p < 0.006); CC depth was 48 ± 1 mm vs. 52 ± 1 (p = 0.007), respectively. Post-simulation CPR quality with no feedback showed a mean CC rate for the CPReality application at 122 ± 15 cpm compared with the standard CPR manikin at 117 ± 11 cpm (p = 0.09); depth was 49 ± 8 mm vs. 52 ± 8 (p = 0.095), respectively. In the post-survey, 79% of CPReality subjects agreed that the AR application provided a realistic patient presence compared with 59% (p = 0.07) of subjects in the standard CPR manikin cohort. Conclusions: In a randomized trial of an AR CPR training application compared with a standard CPR manikin training, the AR CPR application did not improve the quality of CPR performed during a CPR refresher training compared with the standard training in HCPs. Future studies should investigate the use of this and other digital technologies for CPR training and education.
Science Collaboration for Capacity Building: Advancing Technology Transfer Through a Treaty for Biodiversity Beyond National Jurisdiction

Marine technology transfer and capacity building are key elements in the development of a historic new agreement for the conservation and sustainable use of marine biodiversity in areas beyond national jurisdiction (BBNJ agreement) under the United Nations Convention on the Law of the Sea (UNCLOS). This vast, deep ocean area remains largely unexplored and poorly understood. Scientific knowledge gaps impede informed decision-making, and most countries lack the capacity to participate in ocean science activities in ABNJ or to benefit from discoveries of new ocean life, habitats, and processes. Consequently, science must play a central role in capacity building aspirations, however, the link between technology transfer and marine scientific research has yet to be examined in depth. Here, we examine the UNCLOS framework for marine technology transfer and highlight linkages with marine scientific research, identifying four capacity building themes: access to data, information and knowledge; equipment; training; and collaboration. We provide examples to illustrate current practices and identify gaps in implementation. We show that marine technology transfer and marine scientific research link in principle and in practice. We propose ways that the BBNJ agreement could strengthen the international framework for the transfer of marine technology in order to boost marine scientific research collaboration, fill knowledge gaps, and strengthen capacity through inclusive international participation.
Identifying BAP1 Mutations in Clear-Cell Renal Cell Carcinoma by CT Radiomics: Preliminary Findings

To evaluate the potential application of computed tomography (CT) radiomics in the prediction of BRCA1-associated protein 1 (BAP1) mutation status in patients with clear-cell renal cell carcinoma (ccRCC). In this retrospective study, clinical and CT imaging data of 54 patients were retrieved from The Cancer Genome Atlas–Kidney Renal Clear Cell Carcinoma database. Among these, 45 patients had wild-type BAP1 and nine patients had BAP1 mutation. The texture features of tumor images were extracted using the Matlab-based IBEX package. To produce class-balanced data and improve the stability of prediction, we performed data augmentation for the BAP1 mutation group during cross validation. A model to predict BAP1 mutation status was constructed using Random Forest Classification algorithms, and was evaluated using leave-one-out-cross-validation. Random Forest model of predict BAP1 mutation status had an accuracy of 0.83, sensitivity of 0.72, specificity of 0.87, precision of 0.65, AUC of 0.77, F-score of 0.68. CT radiomics is a potential and feasible method for predicting BAP1 mutation status in patients with ccRCC.
Sub-Exome Target Sequencing in a Family With Syndactyly Type IV Due to a Novel Partial Duplication of the LMBR1 Gene: First Case Report in Fujian Province of China

Syndactyly is one of the most frequent hereditary limb malformations with clinical and genetical complexity. Autosomal dominant syndactyly type IV (SD4) is a rare form of syndactyly, caused by heterozygous mutations in a sonic hedgehog (SHH) regulatory element (ZRS) which resides in intron 5 of the LMBR1 gene on chromosome 7q36.3. SD4 is characterized by complete cutaneous syndactyly of the fingers, accompanied by cup-shaped hands due to flexion of the fingers and polydactyly. Here, for the first time, we reported a large Chinese family from Fujian province, manifesting cup-shaped hands consistent with SD4 and intrafamilial heterogeneity in clinical phenotype of tibial and fibulal shortening, triphalangeal thumb-polysyndactyly syndrome (TPTPS). We identified a novel duplication of ∼222 kb covering exons 2–17 of the LMBR1 gene in this family by sub-exome target sequencing. This case expands our new clinical understanding of SD4 phenotype and again confirms the feasibility to detect copy number variation by sub-exome target sequencing.
Molecular Characteristics of Klebsiella pneumoniae Isolates From Outpatients in Sentinel Hospitals, Beijing, China, 2010–2019

Background: Klebsiella pneumoniae is an opportunistic pathogen associated with community-acquired and nosocomial infections. Since 2010, K. pneumoniae testing has been included into an existing diarrhea-syndrome surveillance system for estimating the prevalence of K. pneumoniae in diarrhea-syndrome patients, assessing antibiotic susceptibility, and investigating molecular characteristics of K. pneumoniae. Methods: Klebsiella pneumoniae strains were isolated from stool specimens from diarrhea-syndrome outpatients in Beijing, China. Isolates were tested for antibiotic susceptibility, and phylogenetic relationships were explored though whole genome sequence analysis. Multi-locus sequence type (MLST) alleles were extracted from the whole genome sequence (WGS) data. A maximum likelihood tree was generated by MEGAX. Genomes were annotated by Prokka; core genes were produced by Roary; a maximum likelihood phylogenetic tree was generated using FastTree. Results: Forty-four K. pnuemoniae strains were isolated from 2010 to July 2019; of these 37 were K. pneumoniae and seven were K. variicola. Antibiotic susceptibility testing showed that all 44 strains were sensitive to gentamicin, imipenem, amikacin, meropenem, kanamycin; 97.73% were sensitive to cefoxitin andlavo-ofloxacin; the highest antibiotic resistance rate was 79.55%, which was to ampicillin. We found three extended-spectrum beta-lactamase (ESBL) producing strains; we identified high-virulence ST types, including ST307 and ST65; and we found that ST23 has been the epidemic clone since 2010. MLST and core genome sequence analysis showed two distinct clusters of 44 K. pnuemoniae; 40 alleles were identified in core genome sequence analysis, while 36 alleles were identified in MLST typing. Conclusions: There is an urgent need for epidemiological and molecular studies to understand the dynamics of antibiotic resistance and virulence gene transmission to guide strategies for K. pneumoniae surveillance. WGS analysis provided high discrimination power and reliable and robust data useful for molecular epidemiology.
A Novel TBX1 Variant Causing Hypoparathyroidism and Deafness

Abstract Background The TBX1 gene encodes the T-box 1 protein that is a transcription factor involved in development. Haploinsufficiency of the TBX1 gene is reported to cause features similar to DiGeorge syndrome. The TBX1 gene is located within the DiGeorge syndrome region, and studies support that the TBX1gene is responsible for most of the features of the phenotype of hemizygous deletion of chromosome 22q11.2. In this study, we report a family of 4 (a father with 3 children) who presented with congenital hypoparathyroidism and hypocalcemia, facial asymmetry, deafness, normal intelligence, and no cardiac involvement. Methods We performed whole genome sequencing, computational structural analysis of the mutants, and gene expression studies for all affected family members. Results Whole genome sequencing revealed a paternal inherited novel heterozygous variant, c. 1158_1159delinsT p.(Gly387Alafs*73), in the exon 9 isoform C TBX1 gene, causing a loss of nuclear localization sequence (NLS) and transactivation domain (TAD) with no change in gene expression and resulted in a DiGeorge-like phenotype. Conclusion A pathogenic variant in the TBX1 gene exon 9 C that predicted to cause a loss in the NLS region and most of TAD leads to variable features of hypoparathyroidism, distinctive facial features, deafness, and no cardiac involvement. In addition, our report and previous reports indicate the presence of a wide phenotypic spectrum of TBX1 genetic variants and the consistent absence of cardiac involvement in the case of pathogenic variants on exon 9 isoform C TBX1 gene.