Miracle-dz/UniFAR-FTUs huggingface dataset:
Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates

Bedaquiline drug resistance emergence assessment in multidrug-resistant-tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. ABSTRACT Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 μg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 μg/ml by BMD and 0.25 μg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 μg/ml and 0.5 μg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.
Comparative study of umbilical cord cross-sectional area in foetuses with isolated single umbilical artery and normal umbilical artery

Abstract Single umbilical artery (SUA) is one of the most common prenatal diagnoses in cases of foetal abnormality. This prospective study evaluated 77 foetuses with isolated SUAs and 77 healthy foetuses, both at 22–39 gestational weeks. We categorised gestational age into the second and third trimesters, measured the umbilical arterial blood flow parameters and calculated the umbilical vein (UV) area, umbilical artery (UA) area and UV area/UA area ratio. In the second and third trimesters, a higher UA area was obtained in the isolated SUA group than in the control group (p < .01). Furthermore, the isolated SUA group had a lower UV area/UA area ratio than the control group (p < .01), and a positive linear correlation was found between gestational age and UV area in both groups (p < .01). The presence of isolated SUAs was associated with low birth weight and a high prevalence of small for gestational age. IMPACT STATEMENT What is already known on this subject? Single umbilical artery (SUA) is one of the most common prenatally diagnosed foetal abnormalities and approximately 80% foetuses with SUA have isolated SUA, which is a soft indicator of chromosome abnormalities, congenital malformations and premature birth. Umbilical cord cross-sectional area can be evaluated prenatally by ultrasound imaging. Normal values increase with gestational age and foetal size in single pregnancies. Changes in umbilical cord thickness have been associated with complications during pregnancy. What do the results of this study add? The correlation between gestational age and umbilical vein area in the isolated single umbilical artery (SUA) group and control group was better than that between gestational age and umbilical artery area. UA area increased significantly in both groups before 28 weeks but not after 28 weeks, particularly in the isolated SUA group. What are the implications of these findings for clinical practice and/or further research? The study provides a reliable basis for maternal foetal monitoring during pregnancy in the isolated SUA and control groups. Objective assessment of the occurrence and development of foetuses with isolated single umbilical artery was performed.
The Regenerative Role of Gelatin in PLLA Electrospun Membranes for the Treatment of Chronic Massive Rotator Cuff Injuries.

Failing to regenerate native tendon tissue in chronic massive rotator cuff tears (CMRCTs) results in high retear rates after surgery. Gelatin is a hydrolyzed form of collagen which is bioactive and biocompatible. This study intends to investigate the suitability of integrating gelatin to PLLA fibrous membranes for promoting the healing of CMRCTs. PLLA/Gelatin electrospun membranes (PGEM) are fabricated using electrospinning technology. The FTIR, static contact angles are tested sequentially. Cytocompatibility is evaluated with rat tendon fibroblasts and human umbilical endothelial cells (HUEVCs) lines. CMRCTs rat models are established and assigned into three groups (the sham group, the repaired group, and the augmentation group) to perform histomorphological and biomechanical evaluations. Gelatin is successfully integrated into PLLA fibrous membranes by the electrospinning technique. In vitro studies indicate that PGEM shows a great cytocompatibility for rat tendon fibroblasts and HUEVCs. In vivo studies find that applications of PGEM significantly promote well-aligned collagen I fibers formation and enhance biomechanical properties of the repaired tendon in CMRCTs rat models. In summary, gelatin promotes tendon fibroblasts and HUEVCs adhesion, migration, and proliferation on the PLLA fibrous membranes, and PGEM may provide a great prospect for clinical application. This article is protected by copyright. All rights reserved.
Overlapping functions of RBBP4 and RBBP7 in regulating cell proliferation and histone H3.3 deposition during mouse preimplantation development

ABSTRACT Preimplantation development is critical for reproductive successes in mammals. Thus, it is important to understand how preimplantation embryogenesis is regulated. As a key event of preimplantation development, epigenetic reprogramming has been widely studied, yet how epigenetic complexes regulate preimplantation development remains largely unknown. Retinoblastoma binding protein 4 (RBBP4) and 7 (RBBP7) are integral components of epigenetic complexes including SIN3A, NuRD, and CoREST. Here, we demonstrate that double knockdown of Rbbp4 and 7, but not individually, causes embryonic lethality during the morula-to-blastocyst transition. Mechanistically, depletion of RBBP4 and 7 results in dysregulation of genes related to cell cycle, lineage development, and regulation of transcription, which is accompanied by cell cycle block, disrupted lineage specification and chromatin structure. Interestingly, RBBP4/7 depletion leads to a dramatic increase in H3.3 and H3K27ac abundance during morula-to-blastocyst transition. ChIP-seq analysis in early embryos and embryonic stem cells reveals enrichment of H3.3 at the promoter regions of RBBP4/7 target genes. In summary, our studies demonstrate the compensatory role of RBBP4/7 and reveal its potential mechanisms in preimplantation development. Summary sentence: RBBP4 and RBBP7 play a compensatory role in regulating cell proliferation, apoptosis, and histone H3.3 deposition during preimplantation development.
‘When I open it, I have to drink it all’: Push and pull factors shaping domestic alcohol consumption during the COVID‐19 pandemic UK Spring 2020 lockdown

Abstract Introduction The closure of licensed venues during the COVID‐19 pandemic meant that most alcohol has been consumed at home during lockdown periods in the UK, a phenomenon that remains under‐researched despite the public health implications. Methods This article draws on a study consisting of online semi‐structured interviews and focus groups with 20 UK drinkers, conducted between the first and second 2020 UK lockdowns. The study aimed to explore changing and enduring UK drinking practices within home spaces during the pandemic. Results Our findings illuminate specific ways in which assemblages and contextual factors may come together to encourage or mitigate against the consumption of any (or excessive) volumes of alcohol at home during the lockdown. For example, the physical presence of alcohol bottles may both encourage consumption (e.g. compulsion to finish an open bottle of wine) and cue reflection on one's drinking (through the potentially confronting presence of empty bottles after domestic drinking). We also highlight the significance of the home as a space separate from—and different to—public drinking spaces. Discussion and Conclusions With the increasing normalisation of domestic drinking during a global pandemic, this paper illuminates several factors that may encourage or curtail domestic alcohol consumption and invites us to consider the importance of assemblages, space and context. Such findings have wider applicability; for example, consideration of specific (and perhaps unique) push and pull factors of home spaces could inform future alcohol policy, health promotion messages and how guidance around ‘moderation’ or risky drinking is communicated.
Language Brokering–Stress Transition Profiles and Marijuana Use in Mexican-Origin Adolescents

ABSTRACT Although Mexican-origin adolescents experience multiple contextual stressors (e.g., discrimination, economic stress, and foreigner stress) that may result in increased marijuana use, they actively engage in cultural practices (e.g., language brokering) that may protect them from adverse developmental outcomes. Yet, the joint influence of contextual stressors and language brokering on marijuana use has rarely been studied from a developmental perspective. Using a sample of 604 Mexican-origin adolescent brokers (54% female, Mage.Wave1 = 12.41), we examined how stability and change of language brokering–contextual stress (i.e., broker–stress) profiles across three waves are related to adolescent marijuana use. We hypothesized that adolescents with positive brokering experiences and lower contextual stress across three waves (i.e., those in the Stable Protective profile) would be the least likely to use marijuana. For brokering for mothers, the Stable Protective and the Change to Protective groups were less likely than other groups to use marijuana. For brokering for fathers, the Stable Protective group was the least likely to use marijuana and the Change to Protective group was less likely than the Risk at Any Wave group to use marijuana. Interventions could foster brokering-related positive feelings across the course of adolescence to reduce marijuana use among Mexican-origin adolescents.
The CCCH-Type Zinc Finger Antiviral Protein Relieves Immunosuppression of T Cells Induced by Avian Leukosis Virus Subgroup J via the NLP–PKC-δ–NFAT Pathway

The evolution of the host defense system is driven synchronously in the process of resisting virus invasion. Accordingly, host innate defense factors effectively work to suppress virus replication. ABSTRACT The CCCH-type zinc finger antiviral protein (ZAP) can recognize and induce the degradation of mRNAs and proteins of certain viruses, as well as exerting its antiviral activity by activating T cells. However, the mechanism of ZAP that mediates T cell activation during virus infection remains unclear. Here, we found a potential function of ZAP that relieves immunosuppression of T cell induced by avian leukosis virus subgroup J (ALV-J) via a novel signaling pathway that involves norbin-like protein (NLP), protein kinase C delta (PKC-δ), and nuclear factor of activated T cell (NFAT). Specifically, ZAP expression activated T cells by promoting the dephosphorylation and nuclear translocation of NFAT. Furthermore, knockdown of ZAP weakened the reactivity and antiviral response of T cells. Mechanistically, ZAP reduced PKC-δ activity by upregulating and reactivating NLP by competitively binding with viral protein. Knockdown of NLP decreased the dephosphorylation of PKC-δ by ZAP expression. Moreover, we show that knockdown of PKC-δ reduced the phosphorylation levels of NFAT and enhanced its nuclear translocation. Taken together, these data revealed that ZAP relieves immunosuppression caused by ALV-J and mediates T cell activation through the NLP–PKC-δ–NFAT pathway. IMPORTANCE The evolution of the host defense system is driven synchronously in the process of resisting virus invasion. Accordingly, host innate defense factors effectively work to suppress virus replication. However, it remains unclear whether the host innate defense factors are involved in antiviral immune responses against the invasion of immunosuppressive viruses. Here, we found that CCCH-type zinc finger antiviral protein (ZAP) effectively worked in resistance to immunosuppression caused by avian leukosis virus subgroup J (ALV-J), a classic immunosuppressive virus. Evidence showed that ZAP released the phosphatase activity of NLP inhibited by ALV-J and further activated NFAT by inactivating PKC-δ. This novel molecular mechanism, i.e., ZAP regulation of the antiviral immune response by mediating the NLP–PKC-δ–NFAT pathway, has greatly enriched the understanding of the functions of host innate defense factors and provided important scientific ideas and a theoretical basis for research on immunosuppressive viruses and antiviral immunity.
Striatal necrosis caused by Lichtheimia ramosa in a neonatal calf

A 12-day-old male calf that did not want breast milk from birth died following neurological signs such as staggering. Postmortem examination revealed bleeding and encephalomalacia in the left striatum and frontal lobe. Histopathologically, necrotic granulomatous encephalitis with numerous fungi was detected. The fungi were positively stained with anti-Rhizomucor mouse monoclonal antibodies. Lichtheimia ramosa was detected in formalin-fixed paraffin-embedded samples of the affected tissue by molecular methods. To the best of our knowledge, striatal necrosis caused by L. ramosa in a neonatal calf has not been reported. This study provides the first evidence of striatal necrosis caused by L. ramosa in a neonatal calf.
A calcium channel blocker, manoalide exerts an anti-allergic inflammatory effect through attenuating NF-κB activity

Abstract Background Many people are troubled by allergic inflammation including ocular allergic diseases, anaphylaxis, allergic rhinitis, atopic dermatitis, and eczema. Consequently, finding medications for use in allergic inflammation therapy is crucial in human health. Manoalide, a marine natural product isolated as an anti-bacterial metabolite from Luffariella variabilis, is a calcium channel blocker. However, its latent ability as an anti-allergic inflammatory agent has not yet been reported. Our research aimed to elucidate whether manoalide exerts an anti-allergic inflammatory effect in the human mast cell line, HMC-1. Methods Herein, we investigated the immunoregulatory effects and molecular mechanisms of manoalide in HMC-1 cells. Results Manoalide significantly alleviated secretion of the inflammatory cytokines interleukin (IL)-1β, thymic stromal lymphopoietin, tumor necrosis factor-α, IL-6, and IL-8 via blockage of caspase-1 without cytotoxicity in activated HMC-1 cells. Activation of nuclear factor-κB increased by mast cell stimulation was attenuated by treatment with manoalide. In addition, we demonstrated that manoalide treatment remarkably attenuated the activation of mitogen-activated protein kinases in activated-HMC-1 cells. Conclusions Taken together, our findings indicate manoalide has an anti-allergic inflammatory role, and we propose that manoalide might have potential as a novel anti-allergic inflammatory agent.
RNA multimerization as an organizing force for liquid–liquid phase separation

RNA interactions are exceptionally strong and highly redundant. As such, nearly any two RNAs have the potential to interact with one another over relatively short stretches, especially at high RNA concentrations. This is especially true for pairs of RNAs that do not form strong self-structure. Such phenomena can drive liquid–liquid phase separation, either solely from RNA–RNA interactions in the presence of divalent or organic cations, or in concert with proteins. RNA interactions can drive multimerization of RNA strands via both base-pairing and tertiary interactions. In this article, we explore the tendency of RNA to form stable monomers, dimers, and higher order structures as a function of RNA length and sequence through a focus on the intrinsic thermodynamic, kinetic, and structural properties of RNA. The principles we discuss are independent of any specific type of biomolecular condensate, and thus widely applicable. We also speculate how external conditions experienced by living organisms can influence the formation of nonmembranous compartments, again focusing on the physical and structural properties of RNA. Plants, in particular, are subject to diverse abiotic stresses including extreme temperatures, drought, and salinity. These stresses and the cellular responses to them, including changes in the concentrations of small molecules such as polyamines, salts, and compatible solutes, have the potential to regulate condensate formation by melting or strengthening base-pairing. Reversible condensate formation, perhaps including regulation by circadian rhythms, could impact biological processes in plants, and other organisms.
Proposal of Zooshikellaceae fam. nov. to accommodate the genera Zooshikella and Spartinivicinus and reclassification of Zooshikella marina as a later heterotypic synonym of Zooshikella ganghwensis based on whole genome sequence analysis.

The genus Spartinivicinus, affiliated to the class Gammaproteobacteria, is an important marine member that produces prodiginines. Currently, its taxonomic assignment to family level is not well presented. Phylogeny of 16S rRNA gene sequences indicated that Spartinivicinus forms a monophyletic clade with Zooshikella, which is neighboured by Aestuariirhabdus of the family Aestuariirhabdaceae and another monophyletic clade of the family Endozoicomonadaceae. The 16S rRNA gene of Spartinivicinus ruber S2-4-1HT had sequence similarities to those of Aestuariirhabdus litorea GTF13T, Zooshikella members and Endozoicomonas members of 93.4%, 93.2-93.4 and <92.5 %, respectively. Phylogenomic analysis based on 120 bacterial conserved single-copy genes highly supported placing Spartinivicinus as a sister member of Zooshikella, neighboured by Aestuariirhabdaceae and Endozoicomonadaceae members, indicating that Spartinivicinus and Zooshikella could be considered to belong to the same family. Thus, Zooshikellaceae fam. nov. is proposed to accommodate the two genera. Colonies of Spartinivicinus and Zooshikella are red-pigmented, which is different from Aestuariirhabdus (pale-yellow pigmented). The major respiratory quinone of S. ruber was ubiquinone (Q-9), similar to Zooshikella, but distinct from Aestuariirhabdus (Q-9 and Q-8). The predominant fatty acids and polar lipids of Spartinivicinus also showed a similar patterns to Zooshikella, but they were different from Aestuariirhabdus. Lastly, Spartinivicinus possessed a genome size of 6.68 Mbp and DNA G+C content of 40.1mol%, similar to Zooshikella, but much larger than Aestuariirhabdus. In addition, the 16S rRNA genes of Z. ganghwensis JC2044T and Z. marina JC333T possess sequence similarity of 99.79 %. Whole genome comparisons indicated that they shared 79.8 % digital DNA-DNA hybridization, 97.78 % average nucleotide identity and 97.31 % average amino acid identity values. Activities of catalase and oxidase for the two strains were positive. Hydrolysis of skimmed milk and Tweens (40, 60 and 80) was positive. Interestingly, the two strains produced different kinds of prodiginines. We propose that Z. marina is a later heterotypic synonym of Zooshikella ganghwensis.
Manganese exposure causes movement deficit and changes in the protein profile of the external globus pallidus in Sprague Dawley rats

Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.
Genome Sequences of West Nile Virus Reference Materials

We report the sequences of two West Nile virus (WNV) strains (lineages 1 and 2) developed by the Paul-Ehrlich-Institut as reference materials. The materials are calibrated against the 1st World Health Organization WNV RNA International Standard and are intended for use in nucleic acid technology assays supporting transfusion safety. ABSTRACT We report the sequences of two West Nile virus (WNV) strains (lineages 1 and 2) developed by the Paul-Ehrlich-Institut as reference materials. The materials are calibrated against the 1st World Health Organization WNV RNA International Standard and are intended for use in nucleic acid technology assays supporting transfusion safety.
Treatment clinical trial – three types – for children with fluency disorders and stuttering

ABSTRACT Purpose To present a treatment clinical trial, involving three types of treatment for chronic developmental stuttering (CDS), to verify whether they present indicators and sufficient information to establish an effective and safe benefit-risk relationship. Methods The study included 252 children between 2 and 12 years old, who underwent assessment and treatment for CDS. Among the selected children, 93 met the established inclusion criteria. After obtaining the scores for the risk of CDS (Protocol for the Risk of Developmental Stuttering), all children were assessed according to their fluency profile and the severity level of stuttering. The children underwent treatment for CDS Green, Yellow and Red Programs. The treatment chosen for each child was based on the analysis of the risk for CDS. Results All therapeutic programs presented positive results in the post-treatment assessment considering the analyzed parameters, with the exception of word repetition, sound prolongation at the end of words, and intrusion of sounds/word segments. Conclusion The tested therapeutic programs – green, yellow, and red – were efficient for most of the participants. The direct intervention used in the Red Program was highly efficient in promoting fluent speech. This result suggests that for most of the patients with a higher risk of developing the chronic form of stuttering, the use of specific fluency promotion techniques is indicated.