Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis B and C prevalence and risk factors among young men presenting to the Brazilian Army

Abstract Viral hepatitis is caused by different etiological agents with distinct epidemiological, clinical, and laboratory characteristics accounting for significant worldwide morbidity and mortality. Since 1996, the Brazilian Department of Sexually Transmitted Infections (STIs), Acquired Immune Deficiency Syndrome (AIDS) and Viral Hepatitis (DIAHV) in collaboration with the Ministry of Defense has been conducting periodic serosurveys of conscripts enlisted for the Brazilian army to assess STI prevalence and obtain data on knowledge and risk factors pertaining to STIs. This article aims to present the hepatitis B (hepatitis B surface antigen - HBsAg) and C (anti-HCV) seroprevalence estimates and risk factors as per the 8th edition of the Conscript Survey performed in 2016. This cross-sectional study was conducted among conscripts across Brazil aged 17 to 22 years from August to December 2016. It included a self-reported questionnaire and blood testing for syphilis, human immunodeficiency virus (HIV), and hepatitis B and C. In total 38,247 conscripts were enrolled; after applying exclusion criteria, 37,282 conscripts were included. The estimated HBsAg and anti-HCV prevalence rates were 0.22% and 0.28%, respectively. Higher HBsAg and anti-HCV prevalence rates were observed in the North Region (0.49%) and in the Central-west Region (0.65%), respectively. Regarding hepatitis B vaccination, 23.5% (n = 8412) of the individuals reported being unvaccinated and 47.4% (n = 16,970) did not know if they had been vaccinated. Among the anti-HCV positive conscripts, 53% (n = 51, 0.56%, P = .049) reported that they had never had sexual intercourse. Regarding self-reported STI status, most of the positive anti-HCV (n = 100, 0.29%, P < .01) and positive HBsAg (n = 76, 0.22%, P = .205) conscripts reported not having a STI. From those who tested positive for HBsAg, 89% (n = 42, 0.28%, P = .005) reported not making consistent use of condoms with steady partners. Our data suggest a low prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among Brazilian young men, and relatively low rates of self-reported HBV immunization. History of STIs, higher number of partners, inconsistent use of condoms, and lack of awareness of routes of transmission were significantly associated with HBV and HCV infections. To achieve the World Health Organization's goal of viral hepatitis elimination, access to hepatitis information, testing, and surveillance need to be improved.
Upper Limb Work-Related Musculoskeletal Disorders in Operating Room Nurses: A Multicenter Cross-Sectional Study

This study aimed to evaluate the association between personal and job characteristics and the risk of upper limb work-related musculoskeletal disorders (WMSDs) among operating room nurses (ORNs). To this end, we collected data from 148 ORNs working at 8 Italian hospitals and measured any upper limb disabilities experienced in the previous year using the Italian version of the disabilities of the arm, shoulder and hand (DASH) questionnaire. The associations between personal and job characteristics and risk of upper limb WMSDs were estimated by unconditional logistic regression models. The prevalence of upper limb WMSDs was 45.9%. Multivariate analysis showed the “female gender” and “monthly hours spent working as a scrub nurse” to be directly associated with a higher DASH score (adjusted OR for gender = 5.37, 95% CI: 1.65–17.51, p < 0.01; adjusted OR for monthly hours as scrub nurse = 3.09, 95% CI: 1.33–7.19, p < 0.01). Overall, our findings indicate that a full-time job (>120 h/month) as a scrub nurse significantly increases the risk of developing upper limb WMSDs among female ORNs. Thus, to reduce such risk in this particularly sensitive population, we recommend urgent implementation of ergonomic interventions on surgical equipment alongside job rotation and medical surveillance programs.
Trissolcus japonicus (Hymenoptera: Scelionidae) Causes Low Levels of Parasitism in Three North American Pentatomids Under Field Conditions

Abstract Trissolcus japonicus (Ashmead), an Asian parasitoid of Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), was first detected in North America in 2014. Although testing in quarantine facilities as a candidate for classical biological control is ongoing, adventive populations have appeared in multiple sites in the United States, Canada, and Europe. Extensive laboratory testing of T. japonicus against other North American pentatomids and H. halys has revealed a higher rate of parasitism of H. halys, but not complete host specificity. However, laboratory tests are necessarily artificial, in which many host finding and acceptance cues may be circumvented. We offered sentinel egg masses of three native pentatomid (Hemiptera: Pentatomidae) pest species (Chinavia hilaris (Say), Euschistus conspersus Uhler, and Chlorochroa ligata (Say)) in a field paired-host assay in an area with a well-established adventive population of T. japonicus near Vancouver, WA. Overall, 67% of the H. halys egg masses were parasitized by T. japonicus during the 2-yr study. Despite the ‘worst case’ scenario for a field test (close proximity of the paired egg masses), the rate of parasitism (% eggs producing adult wasps) on all three native species was significantly less (0.4–8%) than that on H. halys eggs (77%). The levels of successful parasitism of T. japonicus of the three species are C. hilaris > E. conspersus > C. ligata. The potential impact of T. japonicus on these pentatomids is probably minimal.
Binding of Monovalent and Bivalent Ligands by Transthyretin Causes Different Short- and Long-Distance Conformational Changes

The wild type protein, transthyretin (TTR), and over 120 genetic TTR variants are amyloidogenic and cause, respectively, sporadic and hereditary systemic TTR amyloidosis. The homotetrameric TTR contains two identical thyroxine binding pockets, occupation of which by specific ligands can inhibit TTR amyloidogenesis in vitro. Ligand binding stabilizes the tetramer, inhibiting its proteolytic cleavage and its dissociation. Here, we show with solution-state NMR that ligand binding induces long-distance conformational changes in the TTR that have not previously been detected by X-ray crystallography, consistently with the inhibition of the cleavage of the DE loop. The NMR findings, coupled with surface plasmon resonance measurements, have identified dynamic exchange processes underlying the negative cooperativity of binding of “monovalent” ligand tafamidis. In contrast, mds84, our prototypic “bivalent” ligand, which is a more potent stabilizer of TTR in vitro that occupies both thyroxine pockets and the intramolecular channel between them, has greater structural effects.
Intracellularly generated immunological gold nanoparticles for combinatorial photothermal therapy and immunotherapy against tumor.

Gold nanoparticle (AuNP) has been widely used in cancer photothermal therapy (PTT) for ablating accessible tumor, while it is insufficient for inhibiting tumor metastasis and relapse in current stage. Here, we first developed a novel immunological AuNP through intracellular generation and exocytosis for combinatorial PTT and immunotherapy. Melanoma B16F10 cells were employed to generate AuNPs firstly and then shed nanoparticle trapped vesicles to extracellular environment with retained tumor antigens (AuNP@B16F10). By further introducing the nanoparticles into dendritic cells (DCs), DC-derived AuNPs (AuNP@DCB16F10) were generated with enhanced biosafety, which can induce hyperthermia and provoke antitumor immune responses. This immunological nanoplatform demonstrated efficient inhibition or even eradication of primary tumor, tumor metastasis as well as tumor relapse, with significantly improved overall survival of mice. With our design, the intracellularly generated AuNPs with immunological property could act as an effective treatment modality for cancer.
Fabrication and biological activity of polycaproalctone/phlorotannin endotracheal tube to prevent tracheal stenosis: An in vitro and in vivo study.

Prolonged endotracheal intubation is the most common cause of tracheal stenosis, which may lead to serious airway obstruction. Development of an endotracheal tube coated with biomaterials that exhibit anti-inflammatory or anti-fibrogenic effects may prevent tracheal stenosis. This study demonstrates that an endotracheal tube coated with phlorotannin, which is present in extracts of the brown alga Ecklonia cava, can prevent tracheal stenosis in a rabbit model. An in vitro study shows that phlorotannin inhibits proliferation of human tracheal fibroblasts treated with transforming growth factor β1. Phlorotannin-coated endotracheal tubes show steady release of phlorotannin for up to 7 days, and removal of the tube 1 week after insertion reveals a reduction in both fibrogenesis and thickening of tracheal submucosa. Western blot analysis of tracheal tissues after removal of the phlorotannin-coated tube shows decreased protein expression levels of phenotypic markers of fibrosis such as collagen type I and α-smooth muscle actin. The ability of phlorotannin-coated endotracheal tube to prevent tracheal stenosis caused by endotracheal intubation indicates that phlorotannin may be considered as a candidate biomaterial for coating the cuff of endotracheal tubes to prevent tracheal stenosis.
A vicious cycle of β amyloid–dependent neuronal hyperactivation

Dissecting hyperactivation in AD Progressive accumulation of amyloid β (Aβ) in the brain is a defining feature of Alzheimer's disease (AD). At late stages of AD, pathological Aβ accumulations cause neurodegeneration and cell death. However, neuronal dysfunction, consisting of an excessively increased activity in a fraction of brain neurons, already occurs in early stages of the disease. Zott et al. explored the cellular basis of this hyperactivity in mouse models of AD (see the Perspective by Selkoe). Aβ-mediated hyperactivation was linked to a defect in synaptic transmission exclusively in active neurons, with the most-active neurons having the highest risk of hyperactivation. Aβ-containing brain extracts from human AD patients sustained this vicious cycle, underscoring the potential relevance of this pathological mechanism in humans. Science, this issue p. 559; see also p. 540 The mechanism of β-amyloid–dependent neuronal hyperactivity in mouse models of Alzheimer’s disease is elucidated. β-amyloid (Aβ)–dependent neuronal hyperactivity is believed to contribute to the circuit dysfunction that characterizes the early stages of Alzheimer’s disease (AD). Although experimental evidence in support of this hypothesis continues to accrue, the underlying pathological mechanisms are not well understood. In this experiment, we used mouse models of Aβ-amyloidosis to show that hyperactivation is initiated by the suppression of glutamate reuptake. Hyperactivity occurred in neurons with preexisting baseline activity, whereas inactive neurons were generally resistant to Aβ-mediated hyperactivation. Aβ-containing AD brain extracts and purified Aβ dimers were able to sustain this vicious cycle. Our findings suggest a cellular mechanism of Aβ-dependent neuronal dysfunction that can be active before plaque formation.
OCTN2-Mediated Acetyl-l-Carnitine Transport in Human Pulmonary Epithelial Cells In Vitro

The carnitine transporter OCTN2 is associated with asthma and other inflammatory diseases. The aims of this work were (i) to determine carnitine uptake into freshly isolated human alveolar type I (ATI)-like epithelial cells in primary culture, (ii) to compare the kinetics of carnitine uptake between respiratory epithelial in vitro cell models, and (iii) to establish whether any cell line was a suitable model for studies of carnitine transport at the air-blood barrier. Levels of time-dependent [3H]-acetyl-l-carnitine uptake were similar in ATI-like, NCl-H441, and Calu-3 epithelial cells, whereas uptake into A549 cells was ~5 times higher. Uptake inhibition was more pronounced by OCTN2 modulators, such as l-Carnitine and verapamil, in ATI-like primary epithelial cells compared to NCl-H441 and Calu-3 epithelial cells. Our findings suggest that OCTN2 is involved in the cellular uptake of acetyl-l-carnitine at the alveolar epithelium and that none of the tested cell lines are optimal surrogates for primary cells.
Associations between physical activity and eating‐disorder psychopathology among individuals categorised with binge‐eating disorder and bulimia nervosa

While physical activity (PA) is known to have positive effects on psychological and physical health, little is understood about the association between non‐compensatory PA (ie, not compulsive or intended to control weight or shape) and psychopathology among individuals with eating‐disorder features. The present study explored associations between non‐compensatory PA and psychopathology among adults categorised with bulimia nervosa (BN) and binge‐eating disorder (BED). We further explored the association between compensatory PA and psychopathology among those who engaged in that form of “purging. ”
Intense Light-Mediated Circadian Cardioprotection via Transcriptional Reprogramming of the Endothelium

Consistent daylight oscillations and abundant oxygen availability are fundamental to human health. Here, we investigate the intersection between light-(Period 2, PER2) and oxygen-(hypoxia inducible factor, HIF1A) sensing pathways in cellular adaptation to myocardial ischemia. We demonstrate that intense light is cardioprotective via circadian PER2 amplitude enhancement, mimicking hypoxia elicited adenosine- and HIF1A-metabolic adaptation to myocardial ischemia under normoxic conditions. Whole-genome array from intense light exposed wildtype or Per2-/- mice and myocardial ischemia in endothelial-specific PER2 deficient mice uncover a critical role for intense light in maintaining endothelial barrier function via light-enhanced HIF1A transcription. A proteomics screen in human endothelia reveals a dominant role for PER2 in metabolic reprogramming to hypoxia via mitochondrial translocation, TCA cycle enzyme activity regulation and HIF1A transcriptional adaption to hypoxia. Translational investigation of intense light in human subjects identifies similar PER2 mechanisms, implicating the use of intense light for the treatment of cardiovascular disease. GRAPHICAL ABSTRACT
Structural basis of σ appropriation

Abstract Bacteriophage T4 middle promoters are activated through a process called σ appropriation, which requires the concerted effort of two T4-encoded transcription factors: AsiA and MotA. Despite extensive biochemical and genetic analyses, puzzle remains, in part, because of a lack of precise structural information for σ appropriation complex. Here, we report a single-particle cryo-electron microscopy (cryo-EM) structure of an intact σ appropriation complex, comprising AsiA, MotA, Escherichia coli RNA polymerase (RNAP), σ70 and a T4 middle promoter. As expected, AsiA binds to and remodels σ region 4 to prevent its contact with host promoters. Unexpectedly, AsiA undergoes a large conformational change, takes over the job of σ region 4 and provides an anchor point for the upstream double-stranded DNA. Because σ region 4 is conserved among bacteria, other transcription factors may use the same strategy to alter the landscape of transcription immediately. Together, the structure provides a foundation for understanding σ appropriation and transcription activation.
The Birth Satisfaction Scale-Revised Indicator (BSS-RI): a validation study in Iranian mothers

Abstract Objective Birth Satisfaction Scale-Revised Indicator (BSS-RI) is a short selfreport instrument designed to measure satisfaction of the childbearing women’s experiences of labour and its outcomes. The aim of this study was to examine the reliability and validity of the Persian version of BSS-RI in Iranian mothers. Methods This cross-sectional study was conducted on 396 mothers in Tehran, Iran, between July and September 2017. The mothers were administered the BSS-RI, and a demographic questionnaire. Internal consistency of the BSS-RI was examined with Cronbach’s alpha, construct validity was evaluated via exploratory factor analysis (EFA), and divergent validity was examined by correlating the BSS-RI with gestational age. Results The EFA results demonstrated a two-factor structure corresponding to the Stress of Childbearing and Quality of Care domains of the structure proposed by provider. The Cronbach’s alpha for Stress of Childbearing and Quality of Care subscales and total BSS-RI were 0.665, 0.847, and 0.563, respectively. The mean of BSS-RI total score was 6.16 (SD = 2.60), and the Stress of Childbearing and Quality of Care subscales were 2.71 (SD = 2.39), and 3.45 (SD = 1.11), respectively. The BSS-RI showed no significant correlation with the gestational age, confirming divergent validity. Conclusion Like the original English version, the Persian version of the BSS-RI is a reliable and valid instrument for measuring birth satisfaction in Iranian mothers. It can also be used as short and easy to administer tool for assessment of birth satisfaction in large sample survey research.
Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer’s disease

Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.
CD4 T cells target colorectal cancer antigens upregulated by oxaliplatin

Immune checkpoint blockade has proven its efficacy in hypermutated subtypes of metastatic colorectal cancers (mCRC). Immunogenic potential can also be observed with conventional chemotherapies, but this property has never been explored thoroughly in CRC patients. The CRC therapeutic arsenal includes oxaliplatin, a well‐characterized platinum drug already described as immunogenic. Here, we investigated the impact of the oxaliplatin‐based treatment on mCRC immunopeptidome. We demonstrated that oxaliplatin‐resistant CRC cell lines overexpressed telomerase reverse transcriptase (TERT), colorectal‐associated‐tumor antigen‐1 (COA‐1) and mesothelin tumor‐associated antigens. We identified new HLA class‐II‐restricted and promiscuous peptides derived from COA‐1 and mesothelin. The two naturally processed peptides COA‐1331‐345 and Meso366‐380 appear to be the most immunogenic in mCRC patients. A prospective cohort of 162 mCRC patients enabled us to explore the impact of oxaliplatin exposure on the antitumor‐specific immune response. Interestingly, chemotherapy‐naive mCRC patients present high immune CD4 T‐cell responses directed against TERT, COA‐1 and mesothelin‐derived peptides. These antitumor T‐cell responses were maintained after 3 months of oxaliplatin‐based treatment. Altogether, these findings highlight the interest of immunostimulatory agents to improve the management of chemoresistant mCRC patients. Finally, the high frequency of immune responses targeting the new immunogenic peptides derived from COA‐1 and mesothelin support their use in immunomonitoring strategies.
ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity

Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins.
Generics in transplantation medicine: Randomized comparison of innovator and substitution products containing mycophenolate mofetil

Objective: Mycophenolate mofetil (MMF) is widely used as an immunosuppressant for the prophylaxis of acute organ rejection in recipients of solid organ transplants. Materials and methods: We have compared, in healthy subjects, the pharmacokinetics of mycophenolic acid when MMF was administered in the form of the innovator product CellCept (F. Hoffmann-La Roche Ltd.) or one of three commercially available generics, Renodapt (Biocon Ltd.), Mycept (Panacea Biotec), or Cellmune (Cipla Ltd.). The study was powered to detect a 20% difference in mean formulation performance measures, but not to formally evaluate bioequivalence. Geometric mean ratios of maximum concentrations (Cmax) and areas under plasma concentration-time curves were calculated. Results: Comparing generics against each other, the differences in point estimates of the geometric mean ratios of Cmax of two of the comparisons were either borderline within (Renodapt/Cellmune) or clearly outside (Mycept/Cellmune) a region of 80 – 125% around the reference mean, indicating that bioequivalence between these generics may be difficult to show. Conclusion: Physicians in the field of transplantation should be aware of the potential risk of altering the therapeutic outcome when switching from one preparation of MMF to another. ClinicalTrials.gov identifier: NCT02981290.
Long‐term morbidity of respiratory viral infections during chemotherapy in children with leukaemia

Respiratory viruses are a common cause of infection in immunosuppressed children undergoing cancer therapy. Pulmonary sequelae have been documented following respiratory viral infections (RVIs) in hematopoietic stem cell transplant (HSCT) recipients; however potential late effects in children undergoing nonmyeloablative chemotherapy have not been investigated.