Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of ventilation rate on recovery after cardiac arrest in a pediatric animal model

Aims To assess the impact of two different respiratory rates in hemodynamic, perfusion and ventilation parameters in a pediatric animal model of cardiac arrest (CA). Methods An experimental randomized controlled trial was carried out in 50 piglets under asphyxial CA. After ROSC, they were randomized into two groups: 20 and 30 respirations per minute (rpm). Hemodynamic, perfusion and ventilation parameters were measured 10 minutes after asphyxia, just before ROSC and at 5, 15, 30 and 60 minutes after ROSC. Independent medians test, Kruskal-Wallis test and χ2 test, were used to compare continuous and categorical variables, respectively. Spearman’s Rho was used to assess correlation between continuous variables. A p-value <0.05 was considered significant. Results Arterial partial pressure of carbon dioxide (PaCO2) was significantly lower in the 30 rpm group after 15 minutes (41 vs. 54.5 mmHg, p <0.01), 30 minutes (39.5 vs. 51 mmHg, p < 0.01) and 60 minutes (36.5 vs. 48 mmHg, p = 0.02) of ROSC. The percentage of normoventilated subjects (PaCO2 30–50 mmHg) was significantly higher in the 30 rpm group throughout the experiment. pH normalization occurred faster in the 30 rpm group with significant differences at 60 minutes (7.40 vs. 7.34, p = 0.02). Lactic acid levels were high immediately after ROSC in both groups, but were significantly lower in the 20 rpm group at 30 (3.7 vs. 4.7 p = 0.04) and 60 minutes (2.6 vs. 3.6 p = 0.03). Conclusions This animal model of asphyxial CA shows that a respiratory rate of 30 rpm is more effective to reach normoventilation than 20 rpm in piglets after ROSC. This ventilation strategy seems to be safe, as it does not cause hyperventilation and does not affect hemodynamics or cerebral tissue perfusion.
RNA-Bloom enables reference-free and reference-guided sequence assembly for single-cell transcriptomes

Despite the rapid advance in single-cell RNA sequencing (scRNA-seq) technologies within the last decade, single-cell transcriptome analysis workflows have primarily used gene expression data while isoform sequence analysis at the single-cell level still remains fairly limited. Detection and discovery of isoforms in single cells is difficult because of the inherent technical shortcomings of scRNA-seq data, and existing transcriptome assembly methods are mainly designed for bulk RNA samples. To address this challenge, we developed RNA-Bloom, an assembly algorithm that leverages the rich information content aggregated from multiple single-cell transcriptomes to reconstruct cell-specific isoforms. Assembly with RNA-Bloom can be either reference-guided or reference-free, thus enabling unbiased discovery of novel isoforms or foreign transcripts. We compared both assembly strategies of RNA-Bloom against five state-of-the-art reference-free and reference-based transcriptome assembly methods. In our benchmarks on a simulated 384-cell data set, reference-free RNA-Bloom reconstructed 37.9%–38.3% more isoforms than the best reference-free assembler, whereas reference-guided RNA-Bloom reconstructed 4.1%–11.6% more isoforms than reference-based assemblers. When applied to a real 3840-cell data set consisting of more than 4 billion reads, RNA-Bloom reconstructed 9.7%–25.0% more isoforms than the best competing reference-based and reference-free approaches evaluated. We expect RNA-Bloom to boost the utility of scRNA-seq data beyond gene expression analysis, expanding what is informatically accessible now.
Maximum Voluntary Ventilation and Its Relationship With Clinical Outcomes in Subjects With COPD

BACKGROUND: Previous studies have reported that maximum voluntary ventilation (MVV) may be better associated with commonly used outcomes in COPD than FEV1 and may provide information on respiratory mechanics. In this study, we aimed to investigate the relationship between MVV and clinical outcomes in COPD and to verify whether MVV predicts these outcomes better than FEV1. METHODS: We conducted a cross-sectional study involving individuals with COPD. Lung function was assessed with spirometry; maximum inspiratory and expiratory pressures (PImax and PEmax, respectively) were assessed with manuvacuometry; and functional exercise capacity was assessed with the 6-min-walk test (6MWT). Dyspnea was assessed with the modified Medical Research Council (mMRC) scale; functional status was assessed with the modified Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-m); and health status was assessed with the COPD Assessment Test (CAT). Correlations were verified with the Spearman coefficient, and stepwise multiple linear regression models investigated the predictors of clinical outcomes. RESULTS: Our study included 157 subjects: 82 males; median (interquartile range) age 66 (61–73) y; FEV1 46 (33–57) % predicted; 6MWT 86 (76–96) % predicted; PFSDQ-m total score 34 (14–57); and CAT total score 13 (7–19). Moderate correlations were found between MVV and PImax (r = 0.40), 6MWT (r = 0.50), mMRC (r = –0.56), and total scores on the PFSDQ-m (r = –0.40) and the CAT (r = –0.54). In the regression models, MVV was a predictor of almost all clinical outcomes, unlike FEV1. CONCLUSIONS: MVV correlates moderately with clinical outcomes commonly used in the evaluation of individuals with COPD, and MVV is a better predictor of respiratory muscle strength, functional exercise capacity, and patient-reported outcomes than FEV1.
Quantification of left ventricular contribution to stroke work by longitudinal and radial force-length loops

Left ventricular (LV) stroke work (SW) is calculated from the pressure-volume (PV) loop. PV loops do not contain information on longitudinal and radial pumping, leaving their contributions to SW unknown. A conceptual framework is proposed to derive the longitudinal and radial contributions to SW, using ventricular force-length loops reflecting longitudinal and radial pumping. The aim of this study was to develop and validate this framework experimentally and to explore these contributions in healthy controls and heart failure patients. Thirteen swine underwent cardiovascular magnetic resonance (CMR) and LV pressure catheterization at baseline (n = 7) or 1 wk after myocardial infarction (n = 6). CMR and noninvasive PV loop quantification were performed on 26 human controls and 14 patients. Longitudinal and radial forces were calculated as LV pressure multiplied by the myocardial surface areas in the respective directions. Length components were defined as the atrioventricular plane and epicardial displacements, respectively. Contributions to SW were calculated as the area within the respective force-length loop. Summation of longitudinal and radial SW had excellent agreement with PV loop-derived SW (ICC = 0.95, R = 0.96, bias ± SD = −4.5 ± 5.4%) in swine. Longitudinal and radial contributions to SW were ~50/50% in swine and human controls, and 44/56% in patients. Longitudinal pumping required less work than radial to deliver stroke volume in swine (6.8 ± 0.8 vs. 8.7 ± 1.2 mJ/mL, P = 0.0002) and in humans (11 ± 2.1 vs. 17 ± 4.7 mJ/mL, P < 0.0001). In conclusion, longitudinal and radial pumping contribute ~50/50% to SW in swine and human controls and 44/56% in heart failure patients. Longitudinal pumping is more energy efficient than radial pumping in delivering stroke volume. NEW & NOTEWORTHY A novel method for quantifying the contributions of longitudinal and radial pumping to stroke work using global left ventricular force-length loops was proposed and validated, which can be quantified noninvasively using cardiovascular magnetic resonance and brachial cuff pressure. We found that longitudinal and radial pumping contributes equally to stroke work in controls and 44/56% in heart failure patients, and that the longitudinal pumping is more energy efficient in delivering stroke volume than radial pumping.
Predicting Disease Severity and Outcome in COVID-19 Patients: A Review of Multiple Biomarkers.

CONTEXT An abundance of clinical reports focused on specific laboratory parameters have been reported on COVID-19, but a systematic analysis synthesizing these findings has not been performed. OBJECTIVE To review and summarize the current available literature on the predictive role of various biomarkers in COVID-19 patients. DATA SOURCES A literature search was performed using databases including PubMed, medRxiv, and bioRxiv. A total of 72 papers were reviewed including 54 peer reviewed papers and 18 non-peer reviewed preprints. CONCLUSIONS While non-specific, acute phase reactants including CRP, ferritin, SAA, and procalcitonin were reported as sensitive markers of acute COVID-19 disease. Significantly elevated WBC count, marked lymphopenia, decreased CD3, CD4 or CD8 T-lymphocyte counts, high neutrophil count, thrombocytopenia, and markedly elevated inflammatory biomarkers were associated with severe disease and the risk of developing sepsis with rapid progression. Trends observed by serial laboratory measurements during hospitalization including progressive decrease of lymphocyte count, thrombocytopenia, elevated CRP, procalcitonin, increased liver enzymes, decreased renal function, and coagulation derangements were more common in critically ill patient groups and associated with a high incidence of clinical complications. Elevated IL-6 level and markedly increased SAA were most often reported in severely and critically ill patients. Indicators of systemic inflammation such as neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation (SII) index or COVID-19 Severity Score may be utilized to predict disease severity, outcome, and mortality. Interpretation of the data reported in the studies reviewed here is limited due to study design (mostly retrospective), limited sample size, and a lack of defined clinical criteria.
Moving Towards Ideal and Appropriate Models of Anticoagulation Management Service

It is now known that thrombotic disorders such as venous thromboembolism, ischemic stroke, and myocardial infarction contribute significantly to global morbidity and mortality. Anticoagulation service must respond to this new development. Warfarin has continued to provide the backbone for anticoagulation service for decades but with considerable drawbacks. The introduction of nonVitamin K oral anticoagulants (NOACs) has created new challenges. This article seeks to discuss how the establishment of appropriate models of anticoagulation could contain the draw backs of the old anticoagulants and improve on the compliance, availability, affordability, and accessibility of newer anticoagulants. Successful anticoagulation has always been defined by a scientific balancing of the risk of thrombosis and the complication of hemorrhage. To be able to maintain such optimal anticoagulation requires rational drug prescription (physician factor), institutelization of monitoring of therapy (anticoagulation clinic factor) as well as active participation of patients receiving therapy (patient factor). New models of service can be created out of this triad in a bid to replace the old routine medical care model. New models of anticoagulation service should include appropriately trained professionals such as Physicians, Pharmacists, Clinical Pharmacologists, Nurses, and Laboratory Scientists who are knowledgeable in diagnostic, management, and monitoring of anticoagulation. The different models of anticoagulation service discussed in this article clearly demonstrate the need for restructuring of this life saving service particularly in the era of NOAC. Newer models of care that should provide safe, efficacious, and cost-effective services are needed.
Risuteganib Protects against Hydroquinone–induced Injury in Human RPE Cells

Purpose Cigarette smoking has been implicated in the pathogenesis of AMD. Integrin dysfunctions have been associated with AMD. Herein, we investigate the effect of risuteganib (RSG), an integrin regulator, on RPE cell injury induced by hydroquinone (HQ), an important oxidant in cigarette smoke. Methods Cultured human RPE cells were treated with HQ in the presence or absence of RSG. Cell death, mitochondrial respiration, reactive oxygen species production, and mitochondrial membrane potential were measured by flow cytometry, XFe24 analyzer, and fluorescence plate reader, respectively. Whole transcriptome analysis and gene expression were analyzed by Illumina RNA sequencing and quantitative PCR, respectively. F-actin aggregation was visualized with phalloidin. Levels of heme oxygenase-1, P38, and heat shock protein 27 proteins were measured by Western blot. Results HQ induced necrosis and apoptosis, decreased mitochondrial bioenergetics, increased reactive oxygen species levels, decreased mitochondrial membrane potential, increased F-actin aggregates, and induced phosphorylation of P38 and heat shock protein 27. HQ, but not RSG alone, induced substantial transcriptome changes that were regulated by RSG cotreatment. RSG cotreatment significantly protected against HQ-induced necrosis and apoptosis, prevented HQ-reduced mitochondrial bioenergetics, decreased HQ-induced reactive oxygen species production, improved HQ-disrupted mitochondrial membrane potential, reduced F-actin aggregates, decreased phosphorylation of P38 and heat shock protein 27, and further upregulated HQ-induced heme oxygenase-1 protein levels. Conclusions RSG has no detectable adverse effects on healthy RPE cells, whereas RSG cotreatment protects against HQ-induced injury, mitochondrial dysfunction, and actin reorganization, suggesting a potential role for RSG therapy to treat retinal diseases such as AMD.
Dengue in a crowded megacity: Lessons learnt from 2019 outbreak in Dhaka, Bangladesh

Dengue is a mosquito-borne viral disease commonly reported in the tropical regions of the world. The presence of two mosquito vectors (Aedes aegypti is highly urban, while A. albopictus is less urban) throughout the year makes dengue fever an endemic disease in a number of countries. Among the predicting variables, a rise of temperature and rainfall have shown to be associated with the number of dengue cases [1]. While relatively less emphasized compared to the climatic factors, mass movement is particularly important during large-scale outbreaks. This article presents a case based on the available data from the 2019 outbreak in Bangladesh, where the dengue fever was initially concentrated in Dhaka, the capital city.
Phase I and Pharmacokinetic Study of Romidepsin in Patients with Cancer and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study

Purpose: Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting. Patients and Methods: Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 + 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose. Results: Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n = 12), mild (n = 8), moderate (n = 5), and severe (n = 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2). Conclusions: Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.
Weeds and weed control methods in sugarcane: a case study of Khyber Pakhtunkhwa Pakistan.

The present research was initiated to find out the farmers’ perception of weeds and their control in sugarcane. Two districts i.e Mardan and Charsadda were selected as a sample of the study. Data were collected from 336 sugarcane growers through pre-tested interview schedule. It was observed that overwhelming majority of 96 % of the sample respondents reported Scandix spp. was considered as a weed problem followed by Sorghum halepense as reported by 89% and 85% of the sample respondents considering the Cirsium arvense as the biggest weed problem locally known as “Ghanaki”. Both mechanical and manual weed control methods were reported by all the respondents. Pests such as whitefly, mites, bugs etc. were reported on their sugarcane crop by 88% followed by rates and bore responded by 85% and 62% respectively. Use of pesticides was reported by 70 % respondents. It is recommended that farmers must be aware of the proper weed management through adequate trainings and demonstration of mechanical eco-friendly pesticides application. Moreover, Agricultural Educational institution may be involved to educate farmers in weeds and their control measures.
Postacute inpatient rehabilitation for COVID-19

This case describes the successful pulmonary rehabilitation of a premorbidly independent female in the early 80s who was admitted for acute respiratory distress syndrome secondary to COVID-19 requiring 14 days of intubation. Patient was admitted to the acute rehabilitation unit 1 month after hospitalisation. Patient initially had poor endurance and was only able to ambulate with a front wheel walker for 150 feet, and also had tachycardia and decreased oxygen saturation after ambulation. During patient’s rehabilitation course, therapy was focused on improving activity tolerance. Ten days after admission, patient was able to ambulate without an assistive device for 250 feet and with a rollator for over 900 feet. Patient also showed improvement in gait speed, heart rate, oxygen saturation after ambulation and incentive spirometer volume. This case demonstrates that pulmonary rehabilitation is an important component of inpatient care for patients with COVID-19 to improve functional exercise capacity and aerobic capacity.
PCBs in Food.

We measured the concentrations of 205 polychlorinated biphenyl (PCB) congeners in 26 food items: beef steak, butter, canned tuna, catfish, cheese, eggs, french fries, fried chicken, ground beef, ground pork, hamburger, hot dog, ice cream, liver, luncheon meat, margarine, meat-free dinner, milk, pizza, poultry, salmon, sausage, shrimp, sliced ham, tilapia, and vegetable oil. Using Diet History Questionnaire II, we calculated the PCB dietary exposure in mothers and children participating in the AESOP Study in East Chicago, Indiana, and Columbus Junction, Iowa. Salmon had the highest concentration followed by canned tuna, but fish is a minor contributor to exposure. Other animal proteins are more important sources of PCB dietary exposure in this study population. Despite the inclusion of few congeners and food types in previous studies, we found evidence of a decline in PCB concentrations over the last 20 years. We also found strong associations of PCB congener distributions with Aroclors in most foods and found manufacturing by-product PCBs, including PCB11, in tilapia and catfish. The reduction in PCB levels in food indicates that dietary exposure is comparable to PCB inhalation exposures reported for the same study population.
Challenges and Controversies to Testing for COVID-19

The coronavirus disease (COVID-19) pandemic has placed the clinical laboratory and testing for SARS-CoV-2 front and center in the worldwide discussion of how to end the outbreak. Clinical laboratories have responded by developing, validating, and implementing a variety of molecular and serologic assays to test for SARS-CoV-2 infection. This has played an essential role in identifying cases, informing isolation decisions, and helping to curb the spread of disease. However, as the demand for COVID-19 testing has increased, laboratory professionals have faced a growing list of challenges, uncertainties, and, in some situations, controversy, as they have attempted to balance the need for increasing test capacity with maintaining a high-quality laboratory operation. ABSTRACT The coronavirus disease (COVID-19) pandemic has placed the clinical laboratory and testing for SARS-CoV-2 front and center in the worldwide discussion of how to end the outbreak. Clinical laboratories have responded by developing, validating, and implementing a variety of molecular and serologic assays to test for SARS-CoV-2 infection. This has played an essential role in identifying cases, informing isolation decisions, and helping to curb the spread of disease. However, as the demand for COVID-19 testing has increased, laboratory professionals have faced a growing list of challenges, uncertainties, and, in some situations, controversy, as they have attempted to balance the need for increasing test capacity with maintaining a high-quality laboratory operation. The emergence of this new viral pathogen has raised unique diagnostic questions for which there have not always been straightforward answers. In this commentary, the author addresses several areas of current debate, including (i) the role of molecular assays in defining the duration of isolation/quarantine, (ii) whether the PCR cycle threshold value should be included on patient reports, (iii) if specimen pooling and testing by research staff represent acceptable solutions to expand screening, and (iv) whether testing a large percentage of the population is feasible and represents a viable strategy to end the pandemic.
Cytomegalovirus (CMV) infection in HIV/AIDS patients and diagnostic values of CMV-DNA detection across different sample types.

BACKGROUND Cytomegalovirus (CMV) is a common herpesvirus that has spread throughout the human population. It can easily cause organ damage in individuals who are immunocompromised. While many studies have examined the virology and immunology of simple CMV infection, few articles have described the unique immunological features of patients with HIV-CMV coinfection. METHODS CMV infection was detected in 808 HIV/AIDS inpatients in our center from January 2017 to October 2019, and the relevant data from these patients were retrospectively analyzed. HIV-RNA, CD4+ T lymphocyte count, CMV-DNA, and related antibodies were measured in all patients. The positive rates of CMV-DNA in blood, urine, and cerebrospinal fluid (CSF) were compared. The positive rates between anti-CMV-immunoglobulin M (IgM) antibody and CMV-DNA in blood were compared. The correlation between immune status and CMV positive rate was analyzed based on the CD4+ T lymphocyte count. RESULTS The overall positive rate of CMV infection in HIV/AIDS patients was 29.05%. The positive rate of CMV-DNA in urine, blood, and CSF samples was 25.27%, 26.01%, and 5.70%, respectively, and showed no significant difference between urine and blood. However, plasma CMV-IgM antibody level was significantly different between the urine and blood. The absolute CD4+ T lymphocyte count and the HIVRNA level were significantly different between the CMV-infected group and the non-CMV infected group. CONCLUSIONS Low CD4+ T lymphocyte count and high HIV-1 viral load are risk factors for CMV infection in HIV/AIDS patients. Detection of urine or plasma CMV-DNA by using real-time fluorescence quantitative polymerase chain reaction (PCR) is highly valuable in screening CMV infection in HIV/AIDS patients, while detection of blood CMV IgG and CMV IgM levels has limited clinical value.