Miracle-dz/UniFAR-FTUs huggingface dataset:
Social vulnerability and the impact of policy responses to COVID‐19 on disabled people

Abstract In this paper, we propose a conceptual framework for understanding the impact of the policy responses to COVID‐19 on disabled people. These responses have overwhelmingly focused on individual vulnerability, which has been used as a justification for removing or restricting rights. This suggests the need to shift the attention towards the social determinants of disabled people's vulnerability. We do this by bringing literature on social vulnerability in disaster risk management or ‘disaster studies’ in contact with key concepts in disability studies such as the social model of disability, independent living, intersectionality, and biopower. Empirically, we draw on the findings of the global COVID‐19 Disability Rights Monitor (www.covid‐drm.org), as well as on reports from academic journals, civil society publications, and internet blogs. We put the proposed conceptual framework to work by developing a critical analysis of COVID‐19 policies in three interrelated areas—institutional treatment and confinement of disabled people, intersectional harms, and access to health care. Our conclusion links this analysis with strategies to address disabled people's social vulnerability in post‐pandemic reconstruction efforts. We make a case for policies that address the social, economic, and environmental conditions that disproportionately expose disabled people to natural disasters and hazards.
Injury rates in the National Football League during the 2020 COVID-19 season

ABSTRACT Objectives The National Football League (NFL) altered the 2020 season due to the COVID-19 pandemic, which resulted in canceled preseason games and a dynamic regular season schedule to accommodate for canceled games. The purpose of this study was to evaluate if the disrupted training and preseason schedule lead to increased injury rates as seen in other professional sports. We hypothesized that the overall injury rate would be higher in the 2020 season compared to the 2018–2019 seasons and that this increase will affect all body regions equally. Methods Publicly released NFL weekly injury reports were queried to identify players listed as out or placed on the injured reserve for at least one game in the 2018–2020 seasons. Injuries were categorized into upper extremity, lower extremity, spine/core, head, illness, not injury related and undisclosed injuries. Incidents per 1000 athlete exposures were calculated for the prior two seasons (2018–2019) and for the 2020 season separately. Percentage of injuries occurring in each position was calculated separately for the pre-COVID-19 (2018 and 2019) and post-COVID-19 (2020) cohorts. Incidence rate ratios (IRR) and confidence intervals were used to compare injury rates in 2018–2019 versus 2020. The z-test for proportions was used to determine significant differences between injury incidences. Results The overall incidence rate per 1000 athlete exposures in 2020 was not significantly different compared to pre-COVID-19 seasons (21.6 versus 23.1, IRR 0.94, 95% CI: 0.9–1.0 p > 0.999). The proportion of injuries by position did not change before and after COVID-19 either (p > 0.999). Out listings due to illness were significantly increased during the 2020 season (0.8 versus 0.3, IRR 2.8, 95% CI: 1.4–5.2, p = 0.004). Conclusion The incidence of NFL injuries did not significantly change in 2020. The distribution of injuries did not change with respect to position.
Anticoagulation Therapy for Portal Vein Thrombosis in Patients with Cirrhosis in a Tertiary Center Experience.

BACKGROUND AND AIMS The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates. METHODS This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events. RESULTS The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008). CONCLUSIONS In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.
Functional succinate dehydrogenase deficiency is a common adverse feature of clear cell renal cancer

Significance This study demonstrates that underexpression of succinate dehydrogenase (SDH) subunits resulting in accumulation of oncogenic succinate is a common, adverse, epigenetic modulating feature in clear cell renal cell carcinoma (ccRCC), during pathogenesis and progression. The study sheds light on the mechanisms of down-regulation of SDH subunits in ccRCC and deciphers the consequent oncogenic effects. It shows that functional SDH deficiency is a common feature of ccRCC (∼80% of all kidney cancers), and not just limited to the 0.05 to 0.5% of kidney cancers with germline SDH mutations. Reduced succinate dehydrogenase (SDH) activity resulting in adverse succinate accumulation was previously considered relevant only in 0.05 to 0.5% of kidney cancers associated with germline SDH mutations. Here, we sought to examine a broader role for SDH loss in kidney cancer pathogenesis/progression. We report that underexpression of SDH subunits resulting in accumulation of oncogenic succinate is a common feature in clear cell renal cell carcinoma (ccRCC) (∼80% of all kidney cancers), with a marked adverse impact on survival in ccRCC patients (n = 516). We show that SDH down-regulation is a critical brake in the TCA cycle during ccRCC pathogenesis and progression. In exploring mechanisms of SDH down-regulation in ccRCC, we report that Von Hippel-Lindau loss-induced hypoxia-inducible factor–dependent up-regulation of miR-210 causes direct inhibition of the SDHD transcript. Moreover, shallow deletion of SDHB occurs in ∼20% of ccRCC. We then demonstrate that SDH loss-induced succinate accumulation contributes to adverse loss of 5-hydroxymethylcytosine, gain of 5-methylcytosine, and enhanced invasiveness in ccRCC via inhibition of ten-eleven translocation (TET)-2 activity. Intriguingly, binding affinity between the catalytic domain of recombinant TET-2 and succinate was found to be very low, suggesting that the mechanism of succinate-induced attenuation of TET-2 activity is likely via product inhibition rather than competitive inhibition. Finally, exogenous ascorbic acid, a TET-activating demethylating agent, led to reversal of the above oncogenic effects of succinate in ccRCC cells. Collectively, our study demonstrates that functional SDH deficiency is a common adverse feature of ccRCC and not just limited to the kidney cancers associated with germline SDH mutations.
Early adolescent psychological adaptation differences by stress-coping profiles: a latent transition analysis

ABSTRACT Background & Objectives This study sought to reveal adolescent coping profiles by focusing on the combination of help-seeking and active/passive coping styles, and to compare affective and school adaptation levels across different profiles. Design One-year longitudinal data were collected from 695 Japanese secondary-school students (359 males, 330 females, and 6 unknowns) every semester. All participants reported their positive/negative affect and school adaptation. Only those who experienced any personal problem in the past month completed self-report measures including four stress-coping strategies use. Methods Latent transition analysis (LTA) was conducted to identify stress-coping profiles and their transitions, conducting Tukey’s tests to examine the association between the profiles and psychological adaptability. Results LTA suggested a seven-class solution. One of the profiles represented participants who did not report any stressor during the past month, and the other six classes were sorted by the amount of help-seeking (low, moderate, and high) and active/passive coping style. The results indicated that simultaneous use of help-seeking and active coping was important for school adaptation and affect balance. Low-adaptation profiles showed high stability during the investigation period. Conclusions Findings suggest that clinicians should assess and intervene with help-seeking and stress-coping styles before or during early adolescence.
Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.

BACKGROUND Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. METHODS In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. RESULTS A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. CONCLUSIONS Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).
Applications of the versatile CRISPR‐Cas13 RNA targeting system

CRISPR‐Cas are adaptable natural prokaryotic defense systems that act against invading viruses and plasmids. Among the six currently known major CRISPR‐Cas types, the type VI CRISPR‐Cas13 is the only one known to exclusively bind and cleave foreign RNA. Within the last couple of years, this system has been adapted to serve numerous, and sometimes not obvious, applications, including some that might be developed as effective molecular therapies. Indeed, Cas13 has been adapted to kill antibiotic‐resistant bacteria. In a cell‐free environment, Cas13 has been used in the development of highly specific, sensitive, multiplexing‐capable, and field‐adaptable detection tools. Importantly, Cas13 can be reprogrammed and applied to eukaryotes to either combat pathogenic RNA viruses or in the regulation of gene expression, facilitating the knockdown of mRNA, circular RNA, and noncoding RNA. Furthermore, Cas13 has been harnessed for in vivo RNA modifications including programmable regulation of alternative splicing, A‐to‐I and C to U editing, and m6A modifications. Finally, approaches allowing for the detection and characterization of RNA‐interacting proteins have also been demonstrated. Here, we provide a comprehensive overview of the applications utilizing CRISPR‐Cas13 that illustrate its versatility. We also discuss the most important limitations of the CRISPR‐Cas13‐based technologies, and controversies regarding them.
Factors Associated With Variation in Pediatric Systemic Lupus Erythematosus Care Delivery

Patients with pediatric systemic lupus erythematosus (pSLE) and mixed connective tissue disease (MCTD) receive only a fraction of recommended care. Using published quality indicators and guidelines, we developed a 13‐item pediatric lupus care index (p‐LuCI) to quantify the proportion of recommended clinical evaluations and comorbidity prevention interventions completed and the timeliness of follow‐up. Our objective was to assess baseline index performance and identify sources of p‐LuCI variation.
Clinically significant medication errors in surgical units detected by clinical pharmacist: A real‐life study

Medication errors (MEs) and adverse drug events (ADEs) are major public health issues in hospitals because of their consequences for patient morbidity-mortality and their economic costs. ME is defined as ‘any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer’. MEs may account for up to 28% of emergency department visits. In addition, the incidence of ADEs is statistically higher in the surgical units compared with the medical departments and are particularly high in orthopaedic and trauma surgery units. ADE is defined as an injury resulting from the use of a drug. Given the preventability, frequency, and potential association of MEs with adverse patient outcomes, strategies for detecting ME and preventable ADE are of utmost importance. One strategy for preventing hospital MEs and preventable ADEs is the integration of clinical pharmacists into the medical teams of the care units and the development of clinical pharmacy activities such as medication reconciliation. Consequently, the aim of our study was to evaluate the prevalence of clinically significant ME in surgical units and investigate the impact of clinical pharmacists’ intervention on ME correction.
Poziotinib for Patients With HER2 Exon 20 Mutant Non–Small-Cell Lung Cancer: Results From a Phase II Trial

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with HER2 exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study. PATIENTS AND METHODS Patients with advanced HER2 exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans were performed at least 28 days from initial radiologic response. RESULTS Thirty patients received poziotinib treatment. At baseline, 90% of patients received prior platinum-based chemotherapy and 53% had two lines or more prior systemic therapies. As of data cutoff on March 1, 2021, the confirmed objective response rate was 27% (95% CI, 12 to 46). Responses were observed across HER2 exon 20 mutation subtypes. The median duration of response was 5.0 months (95% CI, 4.0 to not estimable). The median progression-free survival was 5.5 months (95% CI, 4.0 to 7.0). The median overall survival was 15 months (95% CI, 9.0 to not estimable). The most common grade 3 treatment-related adverse events were skin rash (47%) and diarrhea (20%). There was one possible treatment-related death because of pneumonitis. CONCLUSION Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received platinum-based chemotherapy.
Numerical study of particle transport and deposition in porous media

The objective of the present research was to numerically investigate the transport and deposition of particles in porous media at the pore scale. Firstly, a developed coupled lattice Boltzmann method (LBM) and discrete element method (DEM) is used to simulate the fluid-particle flow. LBM is employed to describe the fluid flow around fibers whereas DEM is used to deal with the particle dynamics. The corresponding method is two-way coupling in the sense that particle motion affects the fluid flow and reciprocally. It allowed us to predict the capture efficiency and pressure drop at the initial stage of filtration process. The quality factor is also calculated for determining the filtration performance. Secondly, we focus on the study the capture efficiency of single fiber with circular, diamond and square cross-section, respectively. The results of LBM-DEM for filtration process of single circular fiber agree well with the empirical correlation. The impaction of particles on the front side of square-shaped fiber is more favorable than those on circular and diamond cases. However, diamond fiber exhibits a good filtration performance. Then the variations of quality factor due to the different orientation angle and aspect ratio of rectangular fiber were studied using LBM-DEM. For each case, we have found the optimal value of the windward area to which corresponds a maximum value of the quality factor. The comparison of the performance of the different forms of fibers shows that the largest quality factor is obtained for square fiber oriented with angle π/4.Finally, the influence of the arrangement of fiber on filtration performance is analyzed by considering the staggered configuration. Simulations conducted for several particle size and density show that the diamond with staggered array performs better for large particles and high particle-to-fluid density ratio in terms of quality factor. The present study provide an insight to optimize the filtration process and predict filtration performance.
A random forest model based on core genome allelic profiles of MRSA for penicillin plus potassium clavulanate susceptibility prediction

Treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) infections remains problematic in clinical practice because therapeutic options are limited. Penicillin plus potassium clavulanate combination (PENC) was shown to have potential for treating some MRSA infections. We investigated the susceptibility of MRSA isolates and constructed a drug susceptibility prediction model for the phenotype of the PENC. We determined the minimum inhibitory concentration of PENC for MRSA (n=284) in a teaching hospital (SRRSH-MRSA). PENC susceptibility genotypes were analysed using a published genotyping scheme based on the mecA sequence. mecA expression in MRSA isolates was analysed by qPCR. We established a random forest model for predicting PENC-susceptible phenotypes using core genome allelic profiles from cgMLST analysis. We identified S2-R isolates with susceptible mecA genotypes but PENC-resistant phenotypes; these isolates expressed mecA at higher levels than did S2 MRSA (2.61 vs 0.98, P<0.05), indicating the limitation of using a single factor for predicting drug susceptibility. Using the data of selected UK-sourced MRSA (n=74) and MRSA collected in a previous national survey (NA-MRSA, n=471) as a training set, we built a model with accuracies of 0.94 and 0.93 for SRRSH-MRSA and UK-sourced MRSA (n=287, NAM-MRSA) validation sets. The AUROC of this model for SRRSH-MRSA and NAM-MRSA was 0.96 and 0.97. Although the source of the training set data affects the scope of application of the prediction model, our data demonstrated the power of the machine learning approach in predicting susceptibility from cgMLST results.
Fraxetin suppresses reactive oxygen species‐dependent autophagy by the PI3K/Akt pathway to inhibit isoflurane‐induced neurotoxicity in hippocampal neuronal cells

Isoflurane, a common volatile anesthetic, has been widely used to provide general anesthesia in operations. However, exposure to isoflurane may cause widespread neurotoxicity in the developing animal brain. Fraxetin, a natural coumarin derivative extracted from the bark of Fraxinus rhynchophylla, possesses versatile pharmacological properties including anti‐oxidative, anti‐inflammatory, and neuroprotective effects. However, the effect and action mechanism of fraxetin on neurotoxicity induced by isoflurane are unknown. Reactive oxygen species (ROS) generation, cell viability, lactate dehydrogenase (LDH) release, and apoptosis were estimated by 2′,7′‐dichlorofluorescin‐diacetate (DCFH‐DA) staining, MTT, LDH release, and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end‐labeling (TUNEL) staining assays, respectively. The protein levels of light chain 3 (LC3)‐I, LC3‐II, p62, protein kinase B (Akt), and phosphorylated Akt (p‐Akt) were detected by western blot analysis. Isoflurane induced ROS, LDH release, apoptosis, and autophagy, but inhibited the viability in HT22 cells, which were overturned by fraxetin or ROS scavenger N‐acetyl‐L‐cysteine. Fraxetin suppressed isoflurane‐induced PI3K/Akt inactivation in HT22 cells. PI3K/Akt inactivation by LY294002 resisted the effects of fraxetin on isoflurane‐induced autophagy and autophagy‐modulated neurotoxicity in HT22 cells. In conclusion, fraxetin suppressed ROS‐dependent autophagy by activating the PI3K/Akt pathway to inhibit isoflurane‐induced neurotoxicity in hippocampal neuronal cells.