Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of yes‐associated protein in interleukin‐13 induced nasal remodeling of chronic rhinosinusitis with nasal polyps

4. Alnahas S, Hagner S, Raifer H, et al. IL-17 and TNF-α are key mediators of moraxella catarrhalis triggered exacerbation of allergic airway inflammation. Front Immunol. 2017;8:1-11. 5. Rahman Fink N, Chawes BL, Thorsen J, et al. Neonates colonized with pathogenic bacteria in the airways have a low-grade systemic inflammation. Allergy. 2018;73(11):2150-2159. 6. Shimizu E, Ogawa Y, Saijo Y, et al. Commensal microflora in human conjunctiva; characteristics of microflora in the patients with chronic ocular graft-versus-host disease. Ocul Surf. 2019;17(2):265-271. SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section.
History of suicide attempts in patients with bipolar disorder type I: socio-demographic and clinical factors, quality of life and functioning

Abstract Introduction This study aims to evaluate sociodemographic and clinical factors, quality of life (QoL) and functioning associated with history of suicide attempts (SA) in a sample of bipolar disorder (BD) type I patients. Methods A total of 417 BD type I patients, with and without history of SA were recruited from two Brazilian specialized Mood Disorder Centers. They were assessed with a sociodemographic and clinical questionnaire, the Young Mania Rating Scale, the Hamilton Depression Rating Scale, the Structured Clinical Interviews for DSM-IV Axis I Disorders, the World Health Organization Quality of Life-BREF, and the Sheehan Disability Scale. Results One hundred and seventy-nine (42.9%) patients had a history of SA. There were no statistically significant sociodemographic differences between BD patients with and without a history of SA. Logistic regression found that lifetime hospitalization, comorbid anxiety disorders, depressive polarity in the first episode, current intensity of depressive symptoms, history of rapid cycling, family history of suicide and age at onset were significantly associated with SA in BD. Multiple linear regression showed that SA had no effect on QoL and functioning, which were affected mainly by comorbid anxiety disorders and current intensity of depressive symptoms, even in patients considered euthymic. Conclusion Suicidal behavior in patients with BD is a complex phenomenon and reflects a more severe course of illness. Patients with history of SA may have worse QoL and functional impairment not because of its direct effect, but because of the greater association with clinical factors related to poor prognosis.
The Pong Effect as a Robust Visual Illusion: Evidence From Manipulating Instructions

Visual perception is not always veridical but can be influenced by factors such as ease of acting, energetic cost, and even body type of the observer. This notion is called action-specific perception. Several effects of action capability on visual perception have been found, but there is much controversy as to whether these effects are truly perceptual. Because perception cannot be measured directly, resolving the controversy relies on ruling out alternative explanations through systematic testing. We combined one of the most robust action-specific effects (the Pong effect) with one of the primary suggestions for exploring an alternative explanation, namely whether the effect persists across instructions that emphasize different aspects of the task. The Pong effect was robust to the type of instructions. The results provide critical evidence that the Pong effect is truly perceptual, furthering the argument that a person’s ability to act can influence visual perception.
Repeat Administration of Bone Marrow-Derived Mesenchymal Stem Cells for Treatment of Amyotrophic Lateral Sclerosis

Background The aim of this study was to investigate repeated intrathecal injection of autologous bone marrow-derived mesenchymal stem cells (BM-D MSCs) to patients for treatment of sporadic amyotrophic lateral sclerosis (ALS). Material/Methods Autologous MSCs were isolated from the patients’ bone marrow, plated, expanded, harvested, and passaged. Stem cells from a single bone marrow collection were used for 3 injections per patient, given over a 3-month period. Outcomes were measured with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Participants were observed for a minimum of 6 months before transplantation to assess the natural course of ALS and for the same amount of time after transplantation to compare the rate of disease progression, estimated based on average monthly changes in ALSFRS-R scores. Data from 8 of the 15 participants eligible for the study were analyzed. Results The safety of the MSC injections was confirmed and various effects of the therapy were documented. In patients who had ALS with an inherently slow course, there were no significant changes in the rate of disease progression. In patients who had ALS with an inherently rapid course, slowing of the disease was noted following treatment with MSCs. However, because that subgroup was so small, it was not possible to assess whether the changes were statistically significant. Conclusions Identifying groups of patients who are not responding or potentially responding negatively to injection of MSCs may help prevent it from being offered to individuals who may not benefit from the therapy. One of the limitations of this treatment method is the amount of time required for long-lasting preparation of bone marrow-derived MSCs for a disease that is rapidly progressive. Therefore, it is worth looking for other allogeneic sources of stromal cells for these types of injections.
Identification of work accommodations and interventions associated with work productivity in adults with migraine: A scoping review

Objective To identify factors associated with work productivity in adults with migraine, and accommodations or interventions to improve productivity or the workplace environment for them. Methods We conducted a scoping review by searching MEDLINE, Embase, PsycINFO, Cumulative Index of Nursing and Allied Heath Literature, and Web of Science from their inception to 14 October 2019 for studies of any design that assessed workplace productivity in adults with migraine. Results We included 26 articles describing 24 studies after screening 4139 records. Five prospective cohort studies showed that education on managing migraine in the workplace was associated with an increase in productivity of 29-36%. Two studies showed that migraine education and management in the workplace were associated with increased productivity (absenteeism decreased by 50% in one study). One prospective cohort study showed that occupational health referrals were associated with more than 50% reduction in absenteeism. Autonomy, social support, and job satisfaction were positively associated with productivity, while quantitative demands, emotional demands, job instability, and non-conducive work environment triggers are negatively associated with productivity in workers with migraine. Conclusion Despite migraine being the second leading cause of disability worldwide, there is a paucity of strong data on migraine-related work factors associated with productivity. Registration: None (scoping review)
Compliant Nano-Pliers as a Biomedical Tool at the Nanoscale: Design, Simulation and Fabrication

This paper presents the development of a multi-hinge, multi-DoF (Degrees of Freedom) nanogripper actuated by means of rotary comb drives and equipped with CSFH (Conjugate Surface Flexure Hinges), with the goal of performing complex in-plane movements at the nanoscale. The design approach, the simulation and a specifically conceived single-mask fabrication process are described in detail and the achieved results are illustrated by SEM images. The first prototype presents a total overall area of (550 × 550) μm2, an active clamping area of (2 × 4) μm2, 600 nm-wide circular curved beams as flexible hinges for its motion and an aspect ratio of about 2.5. These features allow the proposed system to grasp objects a few hundred nanometers in size.
Diverse cellular morphologies during lumen maturation in Anopheles gambiae larval salivary glands

Mosquitoes are the greatest animal threat to human health, causing hundreds of millions of infections and around 1 million deaths each year. All mosquito‐borne pathogens must traverse the salivary glands (SGs) to be transmitted to the next host, making this organ an ideal target for interventions. The adult SG develops from precursor cells located in the larval SG duct bud. Characterization of the larval SG has been limited. We sought to better understand larval SG architecture, secretion and gene expression. We developed an optimized method for larval SG staining and surveyed hundreds of larval stage 4 (L4) SGs using fluorescence confocal microscopy. Remarkable variation in SG cell and chromatin organization differed among individuals and across the L4 stage. Lumen formation occurred during L4 stage through secretion likely involving a coincident cellular apical lipid enrichment and extracellular vesicle‐like structures. Meta‐analysis of microarray data showed that larval SG gene expression is divergent from adult SGs, more similar to larval gastric cecae, but different from other larval gut compartments. This work highlights the variable cell architecture of larval Anopheles gambiae SGs and provides candidate targets for genetic strategies aiming to disrupt SGs and transmission of mosquito‐borne pathogens.
Genetic deciphering of the antagonistic activities of the melanin-concentrating hormone and melanocortin pathways in skin pigmentation

The genetic origin of human skin pigmentation remains an open question in biology. Several skin disorders and diseases originate from mutations in conserved pigmentation genes, including albinism, vitiligo, and melanoma. Teleosts possess the capacity to modify their pigmentation to adapt to their environmental background to avoid predators. This background adaptation occurs through melanosome aggregation (white background) or dispersion (black background) in melanocytes. These mechanisms are largely regulated by melanin-concentrating hormone (MCH) and α-melanocyte–stimulating hormone (α-MSH), two hypothalamic neuropeptides also involved in mammalian skin pigmentation. Despite evidence that the exogenous application of MCH peptides induces melanosome aggregation, it is not known if the MCH system is physiologically responsible for background adaptation. In zebrafish, we identify that MCH neurons target the pituitary gland-blood vessel portal and that endogenous MCH peptide expression regulates melanin concentration for background adaptation. We demonstrate that this effect is mediated by MCH receptor 2 (Mchr2) but not Mchr1a/b. mchr2 knock-out fish cannot adapt to a white background, providing the first genetic demonstration that MCH signaling is physiologically required to control skin pigmentation. mchr2 phenotype can be rescued in adult fish by knocking-out pomc, the gene coding for the precursor of α-MSH, demonstrating the relevance of the antagonistic activity between MCH and α-MSH in the control of melanosome organization. Interestingly, MCH receptor is also expressed in human melanocytes, thus a similar antagonistic activity regulating skin pigmentation may be conserved during evolution, and the dysregulation of these pathways is significant to our understanding of human skin disorders and cancers.
Genomic Analysis of Natural Rough Brucella melitensis Rev.1 Vaccine Strains: Identification and Characterization of Mutations in Key Genes Associated with Bacterial LPS Biosynthesis and Virulence

Brucella species are facultative intracellular bacteria that cause brucellosis, a zoonotic world-wide disease. The live attenuated B. melitensis Rev.1 vaccine strain is widely used for the control of brucellosis in the small ruminant population. However, Rev.1 induces antibodies against the O-polysaccharide (O-PS) of the smooth lipopolysaccharide thus, it is difficult to differentiate between infected and vaccinated animals. Hence, rough Brucella strains lacking the O-PS have been introduced. In the current study, we conducted a comprehensive comparative analysis of the genome sequence of two natural Rev.1 rough strains, isolated from sheep, against that of 24 Rev.1 smooth strains and the virulent reference strain B. melitensis 16M. We identified and characterized eight vital mutations within highly important genes associated with Brucella lipopolysaccharide (LPS) biosynthesis and virulence, which may explain the mechanisms underlying the formation of the Rev.1 rough phenotype and may be used to determine the mechanism underlying virulence attenuation. Further complementation studies aimed to estimate the specific role of these mutations in affecting Brucella morphology and virulence will serve as a basis for the design of new attenuated vaccines for animal immunization against brucellosis.
Atomic-Resolution Imaging of Fast Nanoscale Dynamics with Bright Microsecond Electron Pulses

Atomic-resolution electron microscopy is a crucial tool to elucidate the structure of matter. Recently, fast electron cameras have added the time domain to high-resolution imaging, allowing static images to be acquired as movies from which sample drift can later be removed computationally and enabling real-time observations of atomic-scale dynamics on the millisecond time scale. Even higher time resolution can be achieved with short electron pulses, yet their potential for atomic-resolution imaging remains unexplored. Here, we generate high-brightness microsecond electron pulses from a Schottky emitter whose current we briefly drive to near its limit. We demonstrate that drift-corrected imaging with such pulses can achieve atomic resolution in the presence of much larger amounts of drift than with a continuous electron beam. Moreover, such pulses enable atomic-resolution observations on the microsecond time scale, which we employ to elucidate the crystallization pathways of individual metal nanoparticles as well as the high-temperature transformation of perovskite nanocrystals.
Evaluation of targeted next-generation sequencing for detection of equine pathogens in clinical samples

Equine infectious disease outbreaks may have profound economic impact, resulting in losses of millions of dollars of revenue as a result of horse loss, quarantine, and cancelled events. Early and accurate diagnosis is essential to limit the spread of infectious diseases. However, laboratory detection of infectious agents, especially the simultaneous detection of multiple agents, can be challenging to the clinician and diagnostic laboratory. Next-generation sequencing (NGS), which allows millions of DNA templates to be sequenced simultaneously in a single reaction, is an ideal technology for comprehensive testing. We conducted a proof-of-concept study of targeted NGS to detect 62 common equine bacterial, viral, and parasitic pathogens in clinical samples. We designed 264 primers and constructed a bioinformatics tool for the detection of targeted pathogens. The designed primers were able to specifically detect the intended pathogens. Results of testing 27 clinical samples with our targeted NGS assay compared with results of routine tests (assessed as a group) yielded positive percent agreement of 81% and negative percent agreement of 83%, overall agreement of 81%, and kappa of 0.56 (moderate agreement). This moderate agreement was likely the result of low sensitivity of some primers. However, our NGS assay successfully detected multiple pathogens in the clinical samples, including some pathogens missed by routine techniques.
Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty

Objective Gonadotropin-releasing hormone agonist (GnRHa) treatment improves the potential for gaining height in patients with central precocious puberty (CPP). However, most studies have focused on girls because CPP in boys is relatively rare. Therefore, we aimed to determine the effect of GnRHa treatment on auxological outcomes in boys with CPP. Methods Eighty-five boys with CPP were treated with leuprolide or triptorelin acetate 3.75 mg over 2 years. Anthropometry, bone age, sexual maturity rating, and predicted adult height (PAH) were assessed every 6 months. Furthermore, 20 boys were followed up after treatment discontinuation until achievement of the final adult height (FAH). Results The mean chronological age (CA) and bone age (BA) of the patients with CPP at treatment initiation were 9.5 ± 0.5 years and 11.7 ± 0.9 years, respectively. The mean duration of treatment was 2.87 ± 0.63 years. The PAH at treatment initiation was 172.1 cm (-0.23 ± 1.05 PAH standard deviation score). The PAH at treatment discontinuation (176.2 ± 6.6 cm) was significantly higher than the pretreatment PAH. In addition, the mean final adult height in the 20 boys who were followed up after discontinuation of treatment was 173.4 ± 5.8 cm, which was significantly higher than the initial PAH (170.1 ± 4.5 cm; p = 0.006). In multivariate analysis, the height gain (the difference between the FAH and PAH at treatment initiation) significantly correlated with the target height. Conclusion Long-term GnRHa treatment significantly improved the growth potential and FAH in boys with CPP.
Intermittent and continuous energy restriction result in similar weight loss, weight loss maintenance, and body composition changes in a 6 month randomized pilot study

Poor adherence is a barrier to successful weight control. Intermittent energy restriction (IER) provides an alternative approach to those for whom daily energy restriction is not ideal. This study assessed changes in weight, body composition, and macronutrient intake for an IER and a continuous energy restriction (CONT) approach within a multicomponent weight management intervention. We randomized 35 adults with overweight/obesity (BMI = 31.2 ± 2.4 kg/m2) to CONT or IER for 24 weeks (12‐week weight loss intervention and 12 weeks of weight loss maintenance). Diets were delivered within a multimodal weight management program including weekly group meetings with a registered dietitian, increased physical activity, and a comprehensive lifestyle change program. Retention and adherence were similar for CONT and IER. Weight, BMI, fat mass, percentage body fat, waist circumference, hip circumference, blood pressure, and heart rate all decreased after 24 weeks (all, P < .01), but there were no main effects of group (all, P > .27). Weight loss was clinically relevant in both CONT (11.38 ± 7.9%) and IER (9.37 ± 9.7%), and the proportion of each group achieving 5% weight loss was 82 and 61% (P = .16), respectively. Participant satisfaction was high in both groups. The results from this study (a) support the feasibility of IER as an alternative for weight loss and weight loss maintenance, (b) indicate that IER is an effective alternative to CONT for weight control and improvements in body composition, and (c) emphasize the importance of intensive lifestyle interventions with ongoing support for effective behaviour modification.
1-Bromopropane-induced apoptosis in OVCAR-3 cells via oxidative stress and inactivation of Nrf2

The bromoalkane, 1-bromopropane (1-BP), may damage the reproductive system though oxidative stress, while the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in regulating intracellular antioxidant levels against oxidative stress. This study explored the role of oxidative stress and the Nrf2 signaling pathway in mediating the reproductive toxicity of 1-BP using the ovarian carcinoma cell line OVCAR-3 as an in vitro model of the human ovary. OVCAR-3 cells were treated with 1, 5, 10 and 15 mM 1-BP. After 24 h, the cellular reactive oxygen species and malondialdehyde concentrations significantly increased, while the superoxide dismutase activity decreased; translocation of Nrf2 from the cytosol to the nucleus as well as downstream protein expression of Nrf2-regulated genes heme oxygenase-1 and Bcl-2 was inhibited. Apoptosis was also observed, accompanied by increased caspase-3 and caspase-9 activity. The antioxidant vitamin C alleviated 1-BP-induced apoptosis by inhibiting caspase activity activating the Nrf2 signaling pathway. These findings suggested that 1-BP induced oxidative stress and apoptosis in OVCAR-3 cells through inactivation of Nrf2 signaling.
Brexanolone: A Novel Drug for the Treatment of Postpartum Depression

Objectives: To review the pharmacology, efficacy, and safety of Brexanolone and define its role in the treatment of postpartum depression. Date Sources: A MEDLINE/PubMed search was conducted (1980-May 2020) using the following keywords: postpartum depression, antidepressants, pharmacologic therapy, drug therapy, and brexanolone to identify relevant articles. Study Selection/Data Extraction: Literature search was limited to human studies published in the English language. Phase I, II, and III studies evaluating the pharmacology, efficacy, safety of brexanolone for postpartum depression were included. Bibliographies of relevant articles evaluating postpartum depression and treatment were reviewed for additional citations and background information. Data Synthesis: Brexanolone is a soluble, proprietary, injectable formulation of allopregnanolone, a neuroactive steroid that modulates neuronal excitability. Allopregnanolone levels increase during pregnancy and decrease substantially after birth. These fluctuations have profound effects on anxiety and depression. Three clinical trials established the efficacy and safety of brexanolone in the treatment of postpartum depression. In all 3 trials, brexanolone had an acceptable safety profile and was well tolerated. The most common adverse effects were loss of consciousness, sedation, dry mouth, headache, dizziness, and flushing. Due to sudden loss of consciousness and excessive sedation, continuous pulse oximetry is recommended. Conclusion: Brexanolone has a novel mechanism of action and appears to be safe and effective for the treatment of moderate to severe postpartum depression. At present, high cost, serious adverse effects, and restricted access may limit its use in clinical practice.
Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins

Ricin, produced from the castor beans of Ricinus communis, is a cytotoxin that exerts its action by inactivating ribosomes and causing cell death. Accidental (e.g., ingestion of castor beans) and/or intentional (e.g., suicide) exposure to ricin through the oral route is an area of concern from a public health perspective and no current licensed medical interventions exist to protect from the action of the toxin. Therefore, we examined the oral toxicity of ricin in Balb/C mice and developed a robust food deprivation model of ricin oral intoxication that has enabled the assessment of potential antitoxin treatments. A lethal oral dose was identified and mice were found to succumb to the toxin within 48 h of exposure. We then examined whether a despeciated ovine F(ab′)2 antibody fragment, that had previously been demonstrated to protect mice from exposure to aerosolised ricin, could also protect against oral intoxication. Mice were challenged orally with an LD99 of ricin, and 89 and 44% of mice exposed to this otherwise lethal exposure survived after receiving either the parent anti-ricin IgG or F(ab′)2, respectively. Combined with our previous work, these results further highlight the benefit of ovine-derived polyclonal antibody antitoxin in providing post-exposure protection against ricin intoxication.