Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of international metastatic renal cell carcinoma database consortium (IMDC) intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma

Majority of patients with clear-cell renal cell carcinoma (ccRCC) at first line (1L) treatment are classified in the intermediate-risk (IR) subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score. As these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment. Retrospective analysis was performed from IGReCC (Institut Gustave Roussy Renal Cell Carcinoma) database. Overall survival (OS) was defined from start of 1L therapy to death or last follow-up. A multivariable Cox model with backward selection procedure (α = 0.01) and a Classification and Regression Tree (CART) analysis were performed to identify which prognostic factors were associated to OS in IR patients. From 2005 to 2017, 777 patients with ccRCC were treated with an anti-VEGF 1L therapy. Among 571 evaluable patients for IMDC score, 290 (51%) were classified as IR. With median follow-up 5.8 years (min: 0, max: 12.4) 212 deaths (73%) were observed and median OS was 25 months. Only platelet count was significantly associated to OS (hazard ratio 1.88 [95% CI 1.27–2.88] p = 0.0017). Median OS for patients with PLT > UNL was 18 months [95% CI 12–23] versus 29 months [95% CI 21.4–35.7] for patients with normal PLT count. The selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis. Patients in the IR group have a heterogeneous prognosis. Elevated PLT count seems identifies a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC.
COVID-19 and Neutrophils: The Relationship between Hyperinflammation and Neutrophil Extracellular Traps

Coronavirus disease 2019 (COVID-19) is a virus-induced respiratory disease that may progress to acute respiratory distress syndrome (ARDS) and is triggered by immunopathological mechanisms that cause excessive inflammation and leukocyte dysfunction. Neutrophils play a critical function in the clearance of bacteria with specific mechanisms to combat viruses. The aim of this review is to highlight the current advances in the pathways of neutrophilic inflammation against viral infection over the past ten years, focusing on the production of neutrophil extracellular traps (NETs) and its impact on severe lung diseases, such as COVID-19. We focused on studies regarding hyperinflammation, cytokine storms, neutrophil function, and viral infections. We discuss how the neutrophil's role could influence COVID-19 symptoms in the interaction between hyperinflammation (overproduction of NETs and cytokines) and the clearance function of neutrophils to eliminate the viral infection. We also propose a more in-depth investigation into the neutrophil response mechanism targeting NETosis in the different phases of COVID-19.
Understanding patient-provider discordance in adolescents with lupus: The role of pain and antidepressant medication use

The current study examines depression and pain as potential contributors to patient-provider discordance in the assessment of lupus disease activity. The study conducted a secondary analysis of data obtained from the Childhood Arthritis and Rheumatology Research Alliance registry, with N = 859 adolescent participants. Assessments of pain, disease activity, and antidepressant medication use were collected from the patient and provider. Results indicated that depression might be underdiagnosed in pediatric lupus patients. While psychotropic medication and pain scores were independently related to greater patient-provider discordance regarding health status, pain mediated this relationship. Implications for treatment outcomes are discussed.
Syngas Production via High-Temperature Coelectrolysis of Steam and Carbon Dioxide

This paper presents results of recent experiments on simultaneous high-temperature electrolysis (coelectrolysis) of steam and carbon dioxide using solid-oxide electrolysis cells. Coelectrolysis is complicated by the fact that the reverse shift reaction occurs concurrently with the electrolytic reduction reactions. All reactions must be properly accounted for when evaluating results. Electrochemical performance of the button cells and stacks were evaluated over a range of temperatures, compositions, and flow rates. The apparatus used for these tests is heavily instrumented, with precision mass-flow controllers, on-line dewpoint and CO2 sensors, and numerous pressure and temperature measurement stations. It also includes a gas chromatograph for analyzing outlet gas compositions. Comparisons of measured compositions to predictions obtained from a chemical equilibrium coelectrolysis model are presented, along with corresponding polarization curves. Results indicate excellent agreement between predicted and measured outlet compositions. Cell area-specific resistance values were found to be similar for steam electrolysis and coelectrolysis. Coelectrolysis significantly increases the yield of syngas over the reverse water gas shift reaction equilibrium composition. The process appears to be a promising technique for large-scale syngas production.
Patient characteristics associated with COVID-19 positivity and fatality in Nigeria: retrospective cohort study

Objective Despite the increasing disease burden, there is a dearth of context-specific evidence on the risk factors for COVID-19 positivity and subsequent death in Nigeria. Thus, the study objective was to identify context-specific factors associated with testing positive for COVID-19 and fatality in Nigeria. Design Retrospective cohort study. Setting COVID-19 surveillance and laboratory centres in 36 states and the Federal Capital Territory reporting data to the Nigeria Centre for Disease Control. Participants Individuals who were investigated for SARS-CoV-2 using real-time PCR testing during the study period 27 February–8 June 2020. Methods COVID-19 positivity and subsequent mortality. Multivariable logistic regression analyses were performed to identify factors independently associated with both outcome variables, and findings are presented as adjusted ORs (aORs) and 95% CIs. Results A total of 36 496 patients were tested for COVID-19, with 10 517 confirmed cases. Of 3215 confirmed cases with available clinical outcomes, 295 died. Factors independently associated with COVID-19 positivity were older age (p value for trend<0.0001), male sex (aOR 1.11, 95% CI 1.04 to 1.18) and the following presenting symptoms: cough (aOR 1.23, 95% CI 1.13 to 1.32), fever (aOR 1.45, 95% CI 1.45 to 1.71), loss of smell (aOR 7.78, 95% CI 5.19 to 11.66) and loss of taste (aOR 2.50, 95% CI 1.60 to 3.90). An increased risk of mortality following COVID-19 was observed in those aged ≥51 years, patients in farming occupation (aOR 7.56, 95% CI 1.70 to 33.53) and those presenting with cough (aOR 2.06, 95% CI 1.41 to 3.01), breathing difficulties (aOR 5.68, 95% CI 3.77 to 8.58) and vomiting (aOR 2.54, 95% CI 1.33 to 4.84). Conclusion The significant risk factors associated with COVID-19 positivity and subsequent mortality in the Nigerian population are similar to those reported in studies from other countries and should guide clinical decisions for COVID-19 testing and specialist care referrals.
Nasal Carriage by Staphylococcus aureus among Healthcare Workers and Students Attending a University Hospital in Southern Brazil: Prevalence, Phenotypic, and Molecular Characteristics

Background Staphylococcus aureus can asymptomatically colonize the human anterior nares and skin, and nasal colonization by this bacterium represents a potential risk for development of invasive infections. The aim of this study was to determine the prevalence of S. aureus nasal carriage among healthcare workers and students attending a university hospital and to characterize the isolates phenotypically and molecularly. Methods A cross-sectional study was performed with 324 volunteers. Cultures from nasal samples were obtained and S. aureus isolates were characterized according to their antimicrobial susceptibility profile and four virulence factors-encoding genes. MRSA isolates were characterized regarding their oxacillin/cefoxitin susceptibility, SCCmec, and REP-PCR types. Potential risks for S. aureus and MRSA carriage were analyzed. Results Of 324 nasal samples, 42.9% were identified as S. aureus, of which 28.8% were MRSA. S. aureus carriers were significantly higher in males and students (OR = 2.898, 95%CI 1.553–5.410); however, no variables were associated with MRSA carriage. All isolates were susceptible to vancomycin and the highest rate of resistance was observed for penicillin (90.6%). All isolates harbored the coa gene, and 97.8%, the icaA gene; 15.8% and 6.5% were positive for tst and lukS-PV/lukF-PV genes, respectively. Among MRSA isolates, 45% carried the mecA gene but were phenotypically susceptible to oxacillin/cefoxitin; two harbored the tst and none had lukS-PV/lukF-PV genes. All MRSAs were distributed into six SCCmec types and type I (62.5%) was the most frequent. REP-PCR typing identified four main clusters among MRSA isolates. Conclusion High prevalence of healthcare workers and students were identified as nasal carriers of S. aureus exhibiting different antimicrobial resistance profiles, including mecA-positive oxacillin-susceptible S. aureus (OS-MRSA) and the presence of virulence-encoding genes. Both cohorts may represent potential sources for the emergence of a successful S. aureus strain highly adapted to the hospital environment.
A Significant Association of Upper Limb Muscle Strength with Thyroid Function in Overweight and Obese Population: A Study of the Sixth Korea National Health and Nutrition Examination Survey (KNHANES 2014-2015)

Background. As skeletal muscle is one of main targets of thyroid hormone signalling, an association of thyroid function and muscle strength could be expected. The aim of study is to evaluate the association of free thyroxine (FT4) and thyrotropin (TSH) with upper limb muscle strength, measured by hand grip strength, in subjects with normal FT4 from national representative data. The study utilized the sixth edition of the Korea National Health and Nutrition Examination Survey. After exclusion of subjects with FT4 level out of normal range, a history of thyroid disease or cerebral disease, restricted activity, and incomplete data, a total of 3503 were recruited (age range 19–80 years, 51% male). FT4 positively correlated with upper limb muscle strength (β coefficient = −12.84, p < 0.001), while TSH did negatively (β coefficient = −0.37, p=0.002). After adjusting for confounding factors, statistical significance disappeared. However, among subjects with BMI above 23 kg/m2, a negative correlation of TSH with upper limb muscle strength was found in a younger age group (19–39 years old) (β coefficient = −0.56, p=0.021), while FT4 positively correlated with upper limb muscle strength (β coefficient = 3.24, p=0.019) in an older group (above 40 years old). In overweight and obese subjects, a significant association of thyroid function with upper limb muscle strength was observed in nation-wide representative data. High TSH in a younger group and low FT4 in an older group could be risk factors for decreased upper limb muscle strength in obese population.
Effect of methylprednisolone in severe and critical COVID-19: Analysis of 102 cases

BACKGROUND The coronavirus disease 2019 (COVID-19) outbreak has brought great challenges to public health. Aggravation of COVID-19 is closely related to the secondary systemic inflammatory response. Glucocorticoids are used to control severe diseases caused by the cytokine storm, owing to their anti-inflammatory effects. However, glucocorticoids are a double-edged sword, as the use of large doses has the potential risk of secondary infection and long-term serious complications, and may prolong virus clearance time. Nonetheless, the risks and benefits of glucocorticoid adjuvant therapy for COVID-19 are inconclusive. AIM To determine the effect of methylprednisolone in severe and critically ill patients with COVID-19. METHODS This single-center retrospective study included 102 adult COVID-19 patients admitted to a ward of a designated hospital in Wuhan, Hubei Province from January to March 2020. All patients received general symptomatic treatment and organ function support, and were given different respiratory support measures according to their conditions. In case of deterioration, considering the hyperinflammatory state of the patients, methylprednisolone was intravenously administered at 0.75-1.5 mg/kg/d, usually for less than 14 d. Patient vital signs and oxygenation were closely monitored, in combination with imaging and routine blood tests such as C-reactive protein, biochemical indicators (liver and kidney function, myocardial enzymes, electrolytes, etc.), and coagulation function. Patient clinical outcomes were discharge or death. RESULTS A total of 102 severe and critically ill COVID-19 patients were included in this study. They were divided into treatment (69, 67.6%) and control groups (33, 32.4%) according to methylprednisolone use. Comparison of baseline data between the two groups showed that the treatment group patients had higher aspartic acid aminotransferase, globulin, hydroxybutyrate dehydrogenase, and lactate dehydrogenase. There was no significant difference in other baseline data between the two groups. With regard to prognosis, 29 (78.4%) patients in the treatment group died as opposed to 40 (61.5%) in the control group. The mortality was higher in the treatment group than in the control group; however, according to the log-rank test and the Kaplan–Meier survival curve, the difference in mortality between both groups was insignificant (P = 0.655). The COX regression equation was used to correct the variables with differences, and the results showed that methylprednisolone treatment did not improve prognosis. CONCLUSION Methylprednisolone treatment does not improve prognosis in severe and critical COVID-19 patients.
A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study

Background Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, several questions were raised regarding the impact of COVID-19 at the start of the pandemic. Objective This paper presents the protocol of a study that aims to prospectively evaluate patients with IMRD and a confirmed COVID-19 diagnosis (using criteria provided by the Brazilian Ministry of Health). Methods The study comprised a prospective, observational cohort (patients with IMRD and COVID-19) and a comparison group (patients with only IMRD), with a follow-up time of 6 months to evaluate differences in health outcomes. The primary outcomes will be changes in IMRD disease activity after SARS-CoV-2 infection at 4 time points: (1) at baseline, (2) within 4-6 weeks after infection, (3) at 3 months after the second assessment (±15 days), and (4) at 6 months (±15 days). The secondary outcomes will be the progression rate to moderate or severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death, and therapeutic changes related to IMRD. Two outcomes—pulmonary and thromboembolic events in patients with both IMRD and SARS-CoV-2 infection—are of particular interest and will be monitored with close attention (clinical, laboratory, and function tests as well as imaging). Results Recruitment opened in May 2020, with 1300 participants recruited from 43 sites as of November 2020. Patient recruitment will conclude by the end of December 2020, with follow-up occurring until April 2021. Data analysis is scheduled to start after all inclusion data have been collected, with an aim to publish a peer-reviewed paper in December 2020. Conclusions We believe this study will provide clinically relevant data on the general impact of COVID-19 on patients with IMRD. Trial Registration Brazilian Registry of Clinical Trials RBR-33YTQC; http://www.ensaiosclinicos. gov.br/rg/RBR-33ytqc/ International Registered Report Identifier (IRRID) DERR1-10.2196/24357
Azacitidine decreases reactive oxygen species production in peripheral white blood cells: A case report

BACKGROUND In myelodysplastic syndrome (MDS), oxidative stress is closely related to iron overload and DNA damage. A recent study suggested the possibility that increased oxidative stress causes not only iron overload but also disease progression of MDS with DNA damage. We present a case of MDS with decreased reactive oxygen species (ROS) production in peripheral white blood cells (WBCs) and decreased diacron-reactive oxygen metabolites (d-ROMs) in serum after azacitidine therapy. CASE SUMMARY A 74-year-old man presented to the hematological department with the chief complaint of anemia. His vital signs were within normal limits at admission with a heart rate of 80 bpm and blood pressure of 135/60 mmHg. Laboratory tests indicated pancytopenia, a WBC count of 2190 cells/µL, a hemoglobin level of 6.2 g/dL and a platelet count of 7.4 × 104/µL. The patient was diagnosed with MDS with fibrosis after a bone marrow examination. This case showed decreased ROS production in WBCs, d-ROMs in serum and Wilms’ tumor 1 after azacitidine therapy, after which his hematopoiesis recovered. CONCLUSION Azacitidine therapy can improve hematopoiesis and decrease ROS and d-ROM production.
Induction of HO-1 by 5, 8-Dihydroxy-4′,7-Dimethoxyflavone via Activation of ROS/p38 MAPK/Nrf2 Attenuates Thrombin-Induced Connective Tissue Growth Factor Expression in Human Cardiac Fibroblasts

Heme oxygenase-1 (HO-1) has been shown to exert as an antioxidant and anti-inflammatory enzyme in cardiovascular inflammatory diseases. Flavonoids have been demonstrated to display anti-inflammatory and antioxidant effects through the induction of HO-1. 5,8-Dihydroxy-4′,7-dimethoxyflavone (DDF), one of the flavonoid compounds, is isolated from Reevesia formosana. Whether DDF induced HO-1 expression on human cardiac fibroblasts (HCFs) remained unknown. Here, we found that DDF time- and concentration-dependently induced HO-1 protein and mRNA expression, which was attenuated by pretreatment with reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) in HCFs. DDF-enhanced ROS generation was attenuated by NAC, but not by either diphenyleneiodonium chloride (DPI, Nox inhibitor) or MitoTempol (mitochondrial ROS scavenger). Interestingly, pretreatment with glutathione (GSH) inhibited DDF-induced HO-1 expression. The ratio of GSH/GSSG was time-dependently decreased in DDF-treated HCFs. DDF-induced HO-1 expression was attenuated by an inhibitor of p38 MAPK (p38i VIII) or siRNA, but not by MEK1/2 (PD98059) or JNK1/2 (SP600125). DDF-stimulated p38 MAPK phosphorylation was inhibited by GSH or p38i VIII. Moreover, DDF-induced HO-1 expression was mediated through Nrf2 phosphorylation and translocation into the nucleus which was attenuated by NAC or p38 siRNA. DDF also stimulated antioxidant response element (ARE) promoter activity which was inhibited by NAC, GSH, or p38i VIII. Interaction between Nrf2 and the ARE-binding sites on the HO-1 promoter was revealed by chromatin immunoprecipitation assay, which was attenuated by NAC, GSH, or p38i VIII. We further evaluated the functional effect of HO-1 expression on the thrombin-induced fibrotic responses. Our result indicated that the induction of HO-1 by DDF can attenuate the thrombin-induced connective tissue growth factor expression. These results suggested that DDF-induced HO-1 expression is, at least, mediated through the activation of the ROS-dependent p38 MAPK/Nrf2 signaling pathway in HCFs. Thus, the upregulation of HO-1 by DDF could be a candidate for the treatment of heart fibrosis.
High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages

Background: The association between obesity and colorectal cancer (CRC) risk has been well established. This relationship appears to be more significant in men than in women, which may be attributable to sex hormones. However, controlled animal studies to substantiate these claims and the mechanisms involved are lacking. Materials and Methods: MC38 murine colon adenocarcinoma cells were injected subcutaneously into high-fat diet (HFD) fed male, female and ovariectomized (OVX) female C57BL/6 mice. Results: HFD increased tumor growth (main effect) that was consistent with metabolic perturbations (P < 0.01). HFD OVX mice exhibited the most significant tumor growth compared to HFD male and female mice (p < 0.05) and this was associated with increased subcutaneous adipose tissue (p < 0.05). Further, the subcutaneous adipose tissue depots within HFD OVX mice exhibited more severe macrophage associated inflammation compared to female (P < 0.01), but not male mice. Conditioned media from subcutaneous adipose tissue of HFD OVX contained higher IGF-1 levels compared to male (P < 0.01), but not female mice. Finally, HFD OVX mice had increased M2-like gene expression in their tumor-associated macrophages (TAMs) compared to female mice (P < 0.01). Conclusions: This work provides evidences suggesting adiposity, adipose specific IGF-1, macrophage associated adipose inflammation, and TAMs as potential mechanisms driving obesity-enhanced CRC in females lacking ovarian hormones.
Robot-Assisted versus Conventional Open Kidney Transplantation: A Meta-Analysis

Background Perioperative and follow-up outcomes for patients that received robot-assisted kidney transplant (RAKT), compared to patients that received conventional open kidney transplant (OKT), remain unknown. We performed a meta-analysis of controlled studies to compare the safety and efficacy of RAKT versus OKT. Methods Systematic searching of PubMed, Embase, and Cochrane Library databases was performed to identify relevant randomized or nonrandomized controlled studies. Perioperative, in-hospital, and follow-up outcomes were summarized. A random-effect model incorporating the potential heterogeneity was used to synthesize the results. Results Six nonrandomized controlled studies including 263 patients with RAKT and 804 patients with OKT were included. Pooled results showed that compared to those that received OKT, patients that received RAKT had significant higher rewarming time (mean difference (MD): 20.8 min, p < 0.001) and total ischemia time (MD: 17.8 min, p = 0.008) but a lower incidence of surgical site infection (SSI, risk ratio (RR): 0.22, p = 0.03). The incidence of delayed graft function was comparable between groups (RR: 1.10, p = 0.82), and the length of hospital stay was similar (MD: -2.03 days, p = 0.21). During a follow-up of 31 months, patients that received RAKT and OKT had similar serum creatinine levels (MD: 10.12 mmol/L, p = 0.42) and similar incidences of graft rejection (RR: 1.16, p = 0.53), graft failure (RR: 0.94, p = 0.79), and all-cause mortality (RR: 1.16, p = 0.77). Conclusion Current evidence from nonrandomized studies suggests that RAKT is associated with a lower risk of SSI and similar midterm functional and clinical efficacy compared to OKT. Randomized studies are needed to validate these findings.