Miracle-dz/UniFAR-FTUs huggingface dataset:
Mild Cystic Fibrosis Lung Disease Is Associated with Bacterial Community Stability

While much research supports a polymicrobial view of the CF airway, one in which the community is seen as the pathogenic unit, only controlled experiments using model bacterial communities can unravel the mechanistic role played by different communities. This report uses a large data set to identify a small number of communities as a starting point in the development of tractable model systems. ABSTRACT Microbial communities in the airways of persons with CF (pwCF) are variable, may include genera that are not typically associated with CF, and their composition can be difficult to correlate with long-term disease outcomes. Leveraging two large data sets characterizing sputum communities of 167 pwCF and associated metadata, we identified five bacterial community types. These communities explain 24% of the variability in lung function in this cohort, far more than single factors like Simpson diversity, which explains only 4%. Subjects with Pseudomonas-dominated communities tended to be older and have reduced percent predicted FEV1 (ppFEV1) compared to subjects with Streptococcus-dominated communities, consistent with previous findings. To assess the predictive power of these five communities in a longitudinal setting, we used random forests to classify 346 additional samples from 24 subjects observed 8 years on average in a range of clinical states. Subjects with mild disease were more likely to be observed at baseline, that is, not in the context of a pulmonary exacerbation, and community structure in these subjects was more self-similar over time, as measured by Bray-Curtis distance. Interestingly, we found that subjects with mild disease were more likely to remain in a mixed Pseudomonas community, providing some support for the climax-attack model of the CF airway. In contrast, patients with worse outcomes were more likely to show shifts among community types. Our results suggest that bacterial community instability may be a risk factor for lung function decline and indicates the need to understand factors that drive shifts in community composition. IMPORTANCE While much research supports a polymicrobial view of the CF airway, one in which the community is seen as the pathogenic unit, only controlled experiments using model bacterial communities can unravel the mechanistic role played by different communities. This report uses a large data set to identify a small number of communities as a starting point in the development of tractable model systems. We describe a set of five communities that explain 24% of the variability in lung function in our data set, far more than single factors like Simpson diversity, which explained only 4%. In addition, we report that patients with severe disease experienced more shifts among community types, suggesting that bacterial community instability may be a risk factor for lung function decline. Together, these findings provide a proof of principle for selecting bacterial community model systems.
Effects of quetiapine administration on sperm quality and testicular histology

Abstract Quetiapine is one of the most commonly prescribed antipsychotics to treat schizophrenia in adults, in particular. In this study, quetiapine’s effects were assessed on healthy sperm production in rats at repeated-pharmacological doses. Additionally, the effects of quetiapine on oxidative status and hormonal balance were also evaluated in rats. Quetiapine was administered to rats orally at 10, 20, and 40 mg/kg body weight doses for 28 days. At the end of this period, body and organ weights were measured, sperm concentration, motility, and morphology were determined, sperm damage was assessed, and histopathological analysis of testicular tissue was performed. Additionally, serum FSH, LH, and testosterone levels as male reproductive hormones were measured. Catalase, superoxide dismutase, glutathione, and malondialdehyde levels were determined for evaluating the oxidative status of testicular tissue. The findings obtained in this study showed that relative epididymis weights and sperm concentration decreased and abnormal sperm morphology increased in quetiapine-administered rats. Irregularity of typical architecture of the seminiferous tubules and germinal cell disorganization was observed in testicular sections of 20 and 40 mg/kg quetiapine-administered rats. Further, serum LH and testosterone levels decreased in 20 and 40 mg/kg quetiapine-administered rats. Additionally, decreased catalase and superoxide dismutase activities in testicular tissue of quetiapine-administered rats and increased malondialdehyde levels in testicular tissue of 40 mg/kg quetiapine-administered rats were measured. In conclusion, quetiapine treatment decreased sperm quality, altered hormone levels, and induced oxidative stress may be considered potential contributors to this adverse effect.
Comparison of unilateral and bilateral puncture percutaneous kyphoplasty in the treatment of osteoporotic vertebral compression fractures

Objectives: To compare the clinical efficacy of unilateral and bilateral puncture PKP in the treatment of OVCFs and explored whether there is a difference in the efficacy of unilateral and bilateral puncture PKP after surgery. Methods: A total of 98 patients with OVCFs treated by PKP from August 2016 to June 2018 were selected. There were 62 cases in the unilateral puncture group and 36 cases in the bilateral puncture group. The operation time, the amount of bone cement injection, the height of the anterior edge of the vertebral body and the visual analog scale (Visual Analog Scale, VAS) scores before and after the operation were analyzed, and whether the differences between the 2 groups were statistically significant was analyzed. Results: All patients were followed up completely. The operation time and the number of X-ray fluoroscopies of the unilateral puncture group were significantly reduced compared to those of the bilateral group, and the difference was statistically significant (p<0.05). In terms of the bone cement injection volume, the average injection volume of the bilateral group was greater than that of the unilateral group, and the difference was statistically significant (p<0.05); the postoperative VAS scores of the 2 groups of patients were significantly improved, and the difference was statistically significant compared with that before surgery (p<0.05) but that of the unilateral group was not statistically significant compared with that of the bilateral group (p>0.05). The height of the anterior edge of the vertebral body in both groups was significantly improved compared with that before the operation, and the difference was statistically significant (p<0.05). Conclusion: Unilateral and bilateral puncture PKP can achieve good clinical efficacy in the treatment of osteoporotic vertebral compression fractures, but unilateral PKP has the advantages of short operation time and low X-ray exposure.
Role of B Cells in Responses to Checkpoint Blockade Immunotherapy and Overall Survival of Cancer Patients

The role of B cells in the tumor microenvironment and B-cell–mediated antitumor immune responses remains relatively understudied. Recent seminal studies have discovered that B cells and associated tertiary lymphoid structures correlate with responses to checkpoint blockade immunotherapy and are prognostic for overall survival of cancer patients. B-cell subsets have remarkable functional diversity and include professional antigen-presenting cells, regulatory cells, memory populations, and antibody-producing plasma cells. Importantly, secreted antibodies can independently activate innate immune responses and induce the cancer immunity cycle. Thus, B cells and B-cell–mediated antibody responses comprise the largely underappreciated second arm of the adaptive immune system and certainly deserve further attention in the field of oncology. Here, we review the known functions of B cells in the tumor microenvironment, the contribution of B cells to the antitumor activity of immunotherapies, and the role of B cells in the overall survival of cancer patients.
Pervasive transcription of the mitochondrial genome in Candida albicans is revealed in mutants lacking the mtEXO RNase complex

ABSTRACT The mitochondrial genome of the pathogenic yeast Candida albicans displays a typical organization of several (eight) primary transcription units separated by noncoding regions. Presence of genes encoding Complex I subunits and the stability of its mtDNA sequence make it an attractive model to study organellar genome expression using transcriptomic approaches. The main activity responsible for RNA degradation in mitochondria is a two-component complex (mtEXO) consisting of a 3ʹ-5ʹ exoribonuclease, in yeasts encoded by the DSS1 gene, and a conserved Suv3p helicase. In C. albicans, deletion of either DSS1 or SUV3 gene results in multiple defects in mitochondrial genome expression leading to the loss of respiratory competence. Transcriptomic analysis reveals pervasive transcription in mutants lacking the mtEXO activity, with evidence of the entire genome being transcribed, whereas in wild-type strains no RNAs corresponding to a significant fraction of the noncoding genome can be detected. Antisense (‘mirror’) transcripts, absent from normal mitochondria are also prominent in the mutants. The expression of multiple mature transcripts, particularly those translated from bicistronic mRNAs, as well as those that contain introns is affected in the mutants, resulting in a decreased level of proteins and reduced respiratory complex activity. The phenotype is most severe in the case of Complex IV, where a decrease of mature COX1 mRNA level to ~5% results in a complete loss of activity. These results show that RNA degradation by mtEXO is essential for shaping the mitochondrial transcriptome and is required to maintain the functional demarcation between transcription units and non-coding genome segments.
Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy

Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68–1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68–1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68–1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8+ T cells to mediate protection against SIV challenge.
A Novel Cooperative Metallo-β-Lactamase Fold Metallohydrolase from Pathogen Vibrio vulnificus Exhibits β-Lactam Antibiotic-Degrading Activities

Vibrio vulnificus is a pathogen that accounts for one of the highest mortality rates and is responsible for most reported seafood-related illnesses and deaths worldwide. Owing to the threats of pathogens with β-lactamase activity, it is important to identify and characterize β-lactamases with clinical significance. In this study, the protein sequence of the metallo-β-lactamase (MBL) fold metallohydrolase from V. vulnificus (designated Vmh) was analyzed, and its oligomeric state, β-lactamase activity, and metal binding ability were determined. ABSTRACT Vibrio vulnificus is a pathogen that accounts for one of the highest mortality rates and is responsible for most reported seafood-related illnesses and deaths worldwide. Owing to the threats of pathogens with β-lactamase activity, it is important to identify and characterize β-lactamases with clinical significance. In this study, the protein sequence of the metallo-β-lactamase (MBL) fold metallohydrolase from V. vulnificus (designated Vmh) was analyzed, and its oligomeric state, β-lactamase activity, and metal binding ability were determined. BLASTp analysis indicated that the V. vulnificus Vmh protein showed no significant sequence identity with any experimentally identified Ambler class B MBLs or enzymes containing the MBL protein fold; it was also predicted to have a signal peptide of 19 amino acids at its N terminus and an MBL protein fold from amino acid residues 23 to 216. Recombinant V. vulnificus Vmh protein was overexpressed and purified. Analytical ultracentrifugation and electrospray ionization-mass spectrometry (MS) data demonstrated its monomeric state in an aqueous solution. Recombinant V. vulnificus Vmh protein showed broad degrading activities against β-lactam antibiotics, such as penicillins, cephalosporins, and imipenems, with kcat/Km values ranging from 6.23 × 102 to 1.02 × 104 M−1 s−1. The kinetic reactions of this enzyme exhibited sigmoidal behavior, suggesting the possibility of cooperativity. Zinc ions were required for the enzyme activity, which was abolished by adding the metal chelator EDTA. Inductively coupled plasma-MS indicated that this enzyme might bind two zinc ions per molecule as a cofactor.
Performance of the sōna Aspergillus Galactomannan Lateral Flow Assay in a Cancer Patient Population

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna Aspergillus galactomannan lateral flow assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad galactomannan enzyme immunoassay (GM EIA). ABSTRACT The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna Aspergillus galactomannan lateral flow assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad galactomannan enzyme immunoassay (GM EIA). Serum and bronchoalveolar lavage (BAL) fluid samples received for GM EIA testing between March and August 2019 were included. Positive and negative percent agreement (PPA and NPA) were calculated for the GM LFA compared to the GM EIA. Discrepant analysis was performed by review of the patient‘s medical records assessing for any evidence of a fungal infection. Five hundred thirty-three samples (85 BAL samples and 448 serum samples) from 379 patients were included in the study. The overall PPA and NPA were 100% (95% confidence interval [CI], 72.2 to 100%) and 97.5% (95% CI, 95.5 to 98.4%), respectively. Fourteen of 24 samples were positive by LFA only. The sensitivity of the GM LFA for proven and probable invasive aspergillosis (IA) was 100% (95% CI, 51.0 to 100%) and 87.5% (95% CI, 55.9 to 99.4%), with a specificity of 95.5% (95% CI, 92.3 to 97.2%) and 96.2% (95% CI, 93.4 to 97.7%), respectively. The sensitivity of the GM EIA for proven and probable IA was 25% (95% CI, 1.28 to 69.9%) and 62.5% (95% CI, 30.6 to 86.3%), with a specificity of 98.2% (95% CI, 96.2 to 99.1%) and 99.2% (95% CI, 97.7 to 99.8%), respectively. The Aspergillus GM LFA outperformed the Aspergillus GM EIA for the detection of the galactomannan antigen in our patient population. The simplicity and rapid time to results makes the Aspergillus GM LFA easy to implement in a wide range of laboratory settings.
Acute Retinal Necrosis as a presenting ophthalmic manifestation in COVID 19 recovered patients

ABSTRACT Purpose: Infection by the SARS-CoV2 virus results in an immune dysregulated state which can predispose to reactivation of Herpes viruses. This report describes the development of Acute Retinal Necrosis (ARN) in two patients who had recovered from SARS-CoV2 infection. Methods: Observational report of two consecutive patients who presented with ARN after having recovered from SARS-CoV-2 infection. Results: Case 1 was a 5-year-old child with extensive peripheral necrotizing retinitis. Case 2 was a 61-year-old gentlemen with bilateral retinal detachment with sieve-like breaks and optic atrophy. Both patients had recovered from SARS- Cov-2 infection 1 month ago. PCR from vitreous sample of both patients was positive for Herpes simplex virus. Case 1 was treated with oral valacyclovir. Case 2 underwent surgery in both eyes for retinal detachment Conclusion: Immune dysregulation after COVID-19 infection can result in reactivation of herpesvirus and may lead to development of ARN
Utilization of Airway Pressure Release Ventilation as a Rescue Strategy in COVID-19 Patients: A Retrospective Analysis

Background: Airway Pressure Release Ventilation (APRV) is a pressure controlled intermittent mandatory mode of ventilation characterized by prolonged inspiratory time and high mean airway pressure. Several studies have demonstrated that APRV can improve oxygenation and lung recruitment in patients with Acute Respiratory Distress Syndrome (ARDS). Although most patients with COVID-19 meet the Berlin criteria for ARDS, hypoxic respiratory failure due to COVID-19 may differ from traditional ARDS as patients often present with severe, refractory hypoxemia and significant variation in respiratory system compliance. To date, no studies investigating APRV in this patient population have been published. The aim of this study was to evaluate the effectiveness of APRV as a rescue mode of ventilation in critically ill patients diagnosed with COVID-19 and refractory hypoxemia. Methods: We conducted a retrospective analysis of patients admitted with COVID-19 requiring invasive mechanical ventilation who were treated with a trial of APRV for refractory hypoxemia. PaO2/FIO2 (P/F ratio), ventilatory ratio and ventilation outputs before and during APRV were compared. Results: APRV significantly improved the P/F ratio and decreased FIO2 requirements. PaCO2 and ventilatory ratio were also improved. There was an increase in tidal volume per predicted body weight during APRV and a decrease in total minute ventilation. On multivariate analysis, higher inspiratory to expiratory ratio (I: E) and airway pressure were associated with greater improvement in P/F ratio. Conclusions: APRV may improve oxygenation, alveolar ventilation and CO2 clearance in patients with COVID-19 and refractory hypoxemia. These effects are more pronounced with higher airway pressure and inspiratory time.
Oxidation of Chloride Ion on Platinum Electrode: Dynamics of Electrode Passivation and its Effect on Oxidation Kinetics

Kinetics of oxidation of chloride ion is studied on both active platinum electrode and that undergoing transient passivation. Experiments are conducted in concentrated NaCl solution at rotating disk electrode. It is observed that on the active platinum electrode, oxidation is very fast, and hence the current density is controlled by the ohmic resistance of the solution. Electrode kinetics becomes important only when the electrode is passivated to a significant extent. Kinetics of chloride oxidation on the electrode undergoing passivation is modeled using the Butler–Volmer equation, in which the contribution from the ohmic resistance of the solution is incorporated. Two regimes of passivation are identified. The first is the fast regime corresponding to the formation of the platinum oxide monolayer. In this regime, the rate of passivation is first order in the concentration of the metal sites on the surface. In the slow passivation regime, the exchange current density for chloride oxidation is found to var.
CARACTERIZAÇÃO HIDRÁULICA DE UM TUBO GOTEJADOR

The hydraulic performance of Rain Bird drip tape was evaluated. The drip tape is made of flexible polyethylene with 225 microns wall thickness and long path emitters spaced at 0,30m. The drip tape was tested with different inlet pressures to determine the hydraulic characteristics: coefficient of manufacturing variation, emitter flow equation, rupture resistance, friction head loss equation, friction head loss factor and maximum lateral length. The average coefficient of manufacturing variation was 1,97% and turbulent flow was observed on the emitter (discharge exponent 0,4563). The internal diameter of drip tape increased with the increase in pressure and the rupture resistance failed at 206,0kPa. The value of friction head loss factor decreased as the pressure increased to the same number of emitters. The maximum lateral length obtained by the statistical approach was found to be highly dependent on the inlet pressure head, the slope of the lateral and the coefficient of variation of pressure head along the lateral line.
Does Sex Influence Outcomes in Myocardial Infarction With Nonobstructive Coronary Arteries?

We examined differences in clinical profiles, predictors, and outcomes among patients with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCAs) by sex. Data of 259 (132 males and 127 females) patients with MINOCA were consecutively collected. The primary clinical end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke, heart failure, and angina rehospitalization. Female patients with MINOCA were likely to be older than male patients with higher non-ST elevation myocardial infarction rate. Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels were higher in female patients while male patients were more likely to have a smoking history, greater ST elevation myocardial infarction rate, higher diastolic blood pressure, and more alcohol use. During the 2-year follow-up, the incidence of MACE in males and females was similar (18% vs 20.2%, respectively; P = .673). The multivariable predictors of MACE in the female group were age, hypertension, and left ventricular ejection fraction (LVEF), whereas diabetes, smoking, and LVEF were multivariable predictors of MACE in the male group. In conclusion, there were differences in the clinical profiles between sexes. Clinical outcome was similar between male and female patients with MINOCA, whereas predictive risk factors varied.