bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial
Authors: Barros Camila Miriam Suemi Sato , Freire Raissa Soares , Frota Elisângela , Rezende Santos Anna Gabriela , Farias Maria Eduarda Leão , Rodrigues Maria Gabriela Almeida , Silva Bernardo Maia , Prado Jeronimo Christiane Maria , Netto Rebeca Linhares Abreu , Silva Borba Mayla Gabriela , Baía-da-Silva Djane , Brito-Sousa José Diego , Xavier Mariana Simão , Araújo-Alexandre Marcia Almeida , Sampaio Vanderson Souza , Melo Gisely Cardoso , Arêas Guilherme Tinoco , Hajjar Ludhmila Abrahão , Monteiro Wuelton Marcelo , Gomes Naveca Felipe , Costa Fábio Trindade Maranhão , Val Fernando Fonseca Almeida , Lacerda Marcus Vinícius Guimarães ,   The Metcovid team
Published: February 2022

Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days.Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical–radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit.Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P &lt; 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission.Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis.Trial Registration:ClinicalTrials.gov, Identifier: NCT04343729.
Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer
Authors: Choudhury Yukti , Tan Min-Han , Shi Jun Li , Tee Augustine , Ngeow Kao Chin , Poh Jonathan , Goh Ruth Rosalyn , Mong Jamie 
Published: February 2022

BackgroundTissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging.MethodsPatients with suspected lung cancer (n = 71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 h of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples (tissue EGFR testing), where available. Concordance of clinically actionable mutations between methods and sample types was assessed.ResultsFor confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF, and MET. The overall sensitivity of sensitizing EGFR mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n = 37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a 1.9-fold increase in clinically relevant findings. The average turnaround time of plasma NGS was shorter than standard tissue testing (10 vs. 29.9 days, p &lt; 0.05).ConclusionsIn the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with a shorter time to results. This study outlines the clinical utility of complementary plasma mutation profiling in the routine management of lung cancer patients.
Self-Stigma in Parkinson's Disease: A 3-Year Prospective Cohort Study
Authors: Lin Junyu , Ou Ruwei , Wei Qianqian , Cao Bei , Li Chunyu , Hou Yanbing , Zhang Lingyu , Liu Kuncheng , Shang Huifang 
Published: February 2022

PurposeSelf-stigma is common in patients with Parkinson's disease (PD) and may lead to social isolation and delayed search for medical help. We conducted a 3-year prospective longitudinal study to investigate the development and evolution of self-stigma in patients with early stage PD and to explore the associated and predictive factors of self-stigma in PD.MethodA total of 224 patients with early stage PD (disease duration &lt;3 years) were enrolled at baseline and followed up annually for 3 consecutive years. Self-stigma was assessed by the stigma subscale of the Parkinson's Disease Questionnaire (items 23–26). The generalized estimating equation model was used to investigate the associated factors of self-stigma over 3 years, and the binary logistic model was used to explore the predictors of self-stigma in patients with PD without self-stigma at baseline.ResultsThe prevalence of self-stigma decreased from 58.0% at baseline to 49.2% after 3 years. The Hamilton Depression Rating Scale (HDRS) score was the only associated factor [B: 0.160 (1.106–0.214), P &lt; 0.001] of self-stigma over 3 years and the only predictor [OR: 1.252 (1.044–1.502), P = 0.015] of the onset of self-stigma.ConclusionSelf-stigma is very common in PD, but its prevalence tends to decrease as the disease progresses. Depression was the only associated and predictive factor of self-stigma in PD and could be an effective target of alleviating self-stigma.
Transfer of Soleus Muscular Branch of Tibial Nerve to Deep Fibular Nerve to Repair Foot Drop After Common Peroneal Nerve Injury: A Retrospective Study
Authors: Bao Bingbo , Wei Haifeng , Zhu Hongyi , Zheng Xianyou 
Published: February 2022

ObjectiveCommon peroneal nerve (CPN) injury that leads to foot drop is difficult to manage and treat. We present a new strategy for management of foot drop after CPN injury. The soleus muscular branch of the tibial nerve is directly transferred to the deep fibular nerve, providing partial restoration of motor function.MethodsWe retrospectively reviewed eight patients treated for CPN injury between 2017 and 2019. The soleus muscular branch of the tibial nerve was transferred to the deep fibular nerve to repair foot drop. Electrophysiology was conducted, and motor function was assessed. Motor function was evaluated by measuring leg muscle strength during ankle dorsiflexion using the British Medical Research Council (BMRC) grading system and electromyography (EMG).ResultsIn 10–15 months postoperatively, EMG revealed newly appearing electrical potentials in the tibialis anterior, extensor hallucis longus, and extensor toe longus muscle (N = 7). Two patients achieved BMRC grade of M4 for ankle dorsiflexion, 2 patients achieved M3, 1 patient achieved M2, and 2 patients achieved M1. Four patients showed good functional recovery after surgery and could walk and participate in activities without ankle-foot orthotics.ConclusionSurgical transfer of the soleus muscular branch of the tibial nerve to the deep fibular nerve after CPN injury provides variable improvements in ankle dorsiflexion strength. Despite variable strength gains, 50% of patients achieved BMRC M3 or greater motor recovery, which enabled them to walk without assistive devices.
Trends in the Utilization of Teleneurology and Other Healthcare Resources Prior to and During the COVID-19 Pandemic in an Urban, Tertiary Health System
Authors: Kummer Benjamin R. , Agarwal Parul , Sweetnam Chloe , Robinson-Papp Jessica , Blank Leah J. , Katz Sand Ilana , Naasan Georges , Palmese Christina A. , Jimenez-Shahed Joohi , Grant Jihan , Patterson Shanna , Navis Alison , Stein Laura K. , Jetté Nathalie 
Published: February 2022

BackgroundPatient groups traditionally affected by health disparities were less likely to use video teleneurology (TN) care during the initial COVID-19 pandemic surge in the United States. Whether this asymmetry persisted later in the pandemic or was accompanied with a loss of access to care remains unknown.MethodsWe conducted a retrospective cohort study using patient data from a multicenter healthcare system in New York City. We identified all established pediatric or adult neurology patients with at least two prior outpatient visits between June 16th, 2019 and March 15th, 2020 using our electronic medical record. For this established pre-COVID cohort, we identified telephone, in-person, video TN or emergency department visits and hospital admissions for any cause between March 16th and December 15th, 2020 (“COVID period”). We determined clinical, sociodemographic, income, and visit characteristics. Our primary outcome was video TN utilization, and our main secondary outcome was loss to follow-up during the COVID period. We used multivariable logistic regression to model the relationship between patient-level characteristics and both outcomes.ResultsWe identified 23,714 unique visits during the COVID period, which corresponded to 14,170 established patients from our institutional Neurology clinics during the pre-COVID period. In our cohort, 4,944 (34.9%) utilized TN and 4,997 (35.3%) were entirely lost to follow-up during the COVID period. In the adjusted regression analysis, Black or African-American race [adjusted odds ratio (aOR) 0.60, 97.5%CI 0.52–0.70], non-English preferred language (aOR 0.49, 97.5%CI 0.39–0.61), Medicaid insurance (aOR 0.50, 97.5%CI 0.44–0.57), and Medicare insurance (aOR 0.73, 97.5%CI 0.65–0.83) had decreased odds of TN utilization. Older age (aOR 0.98, 97.5%CI 0.98–0.99), female sex (aOR 0.90 97.5%CI 0.83–0.99), and Medicaid insurance (aOR 0.78, 0.68–0.90) were associated with decreased odds of loss to follow-up.ConclusionIn the first 9 months of the COVID-19 pandemic, we found sociodemographic patterns in TN utilization that were similar to those found very early in the pandemic. However, these sociodemographic characteristics were not associated with loss to follow-up, suggesting that lack of TN utilization may not have coincided with loss of access to care.
Animal and Plant Protein Food Sources in Indonesia Differ Across Socio-Demographic Groups: Socio-Cultural Research in Protein Transition in Indonesia and Malaysia
Authors: Khusun Helda , Februhartanty Judhiastuty , Anggraini Roselynne , Mognard Elise , Alem Yasmine , Noor Mohd Ismail , Karim Norimah , Laporte Cyrille , Poulain Jean-Pierre , Monsivais Pablo , Drewnowski Adam 
Published: February 2022

BackgroundPlant-based diets in lower-income countries are often associated with inadequate protein nutrition and adverse health outcomes.ObjectiveTo examine the diversity of protein food sources, in both animal and plant, across diverse socio-demographic groups in Indonesia as compared to Malaysia.DesignThe SCRiPT (Socio Cultural Research in Protein Transition) study was based on population-based samples recruited in Indonesia (N = 1665) and in Malaysia (N = 1604). Data from 24-h in-person dietary recalls in each country were used to construct the frequency counts of protein sources by food group. Protein sources were defined as fish, poultry, red meat (beef, pork, and mutton), eggs, dairy, and plants (cereals, pulses, and tubers). The percent reported frequencies for animal and plant proteins were compared across socio-demographic strata and by country. Analyses were based on one-way Anovas and general linear model regressions adjusting for covariates.ResultsAnimal protein frequency counts were 34% of total in Indonesia, but 50% in Malaysia's. Higher reported consumption frequencies for poultry and red meat in both countries were associated with urban living, greater modernization, and higher socioeconomic status, with stronger social gradients observed in Indonesia. Reported fish consumption was higher in Indonesia than in Malaysia. Fish was more likely to be listed by rural island populations in Indonesia and was associated with lower education and incomes. Consumption frequencies for plant-based proteins were associated with lower socio-economic status in Indonesia and in Malaysia.ConclusionsMore affluent groups in both countries reported higher frequencies for meat, eggs, and dairy as opposed to fish. Greater economic development in Southeast (SE) Asia is associated with more animal protein, particularly from poultry, which may displace fish, the traditional source of high quality protein for the region.
Cumulative Betel Quid Chewing and the Risk of Significant Liver Fibrosis in Subjects With and Without Metabolic Syndrome
Authors: Chou Yu-Tsung , Sun Zih-Jie , Shen Wei-Chen , Yang Yi-Ching , Lu Feng-Hwa , Chang Chih-Jen , Li Chung-Yi , Wu Jin-Shang 
Published: February 2022

BackgroundBetel quid chewing is associated with metabolic disorders, oral cancer, cardiovascular disease, and chronic liver diseases. Metabolic syndrome (MetS) is also a factor associated with liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, studies on the relationship between betel quid and liver fibrosis while also considering MetS are lacking. The aim of this study was thus to investigate the association of betel quid chewing and liver fibrosis with MetS.MethodsA total of 9,221 subjects were enrolled after excluding subjects &lt;18 years of age, with past history of chronic liver diseases, cancer, significant alcohol consumption, and incomplete data. Betel nut chewing habit was classified into three groups: none, former-chewing, and current-chewing, and cumulative exposure was calculated by multiplying the duration with the quantity. Liver fibrosis was evaluated based on the NAFLD fibrosis score (NFS), which is a composite score of age, hyperglycemia, BMI, platelet count, albumin, and the AST/ALT ratio. Significant liver fibrosis was defined as NFS ≥-1.455.ResultsAfter adjusting for other variables, MetS was positively associated with significant liver fibrosis. Subjects with both MetS and betel quid chewing had a higher associated risk of significant liver fibrosis than those with neither MetS nor betel quid chewing (adjusted OR: 3.03, 95% CI: 2.04–4.50,p&lt; 0.001). Betel quid chewing was associated with significant liver fibrosis (adjusted OR: 2.00, 95% CI: 1.14–3.49,p= 0.015) in subjects with MetS, but not in subjects without.ConclusionMetabolic syndrome increased the associated risk of significant liver fibrosis. Cumulative betel quid exposure increased the associated risk of significant liver fibrosis in subjects with MetS, but not in subjects without.
Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer
Authors: El Ahanidi Hajar , El Azzouzi Meryem , Hafidi Alaoui Chaimae , Tetou Mohammed , Bensaid Mounia , Chaoui Imane , Benbacer Laila , Hassan Ilias , Oukabli Mohamed , Michaud Katarzyna , Ameur Ahmed , Al Bouzidi Abderrahmane , El Mzibri Mohammed , Jandus Camilla , Attaleb Mohammed 
Published: February 2022

BackgroundTumor recurrence and progression in non-muscle invasive bladder cancer (NMIBC), therapy failure, and severe side effects in muscle invasive bladder cancer (MIBC) are the major challenges in the clinical management of bladder cancer (BC). Here, we identify new molecular targetable signatures to improve BC patients’ stratification and the outcome of current immunotherapies.Material and MethodsIn a prospective cohort of 70 BC patients, we assessed the genetic and molecular regulation of TERT in maintaining telomere length in parallel to immune checkpoint and microRNA expression.ResultsTERT was undetectable in healthy bladder tissues but upregulated in invasive BC stages and high tumor grade. Its expression was linked with the combined effect of the C250T mutation and THOR hypermethylation, associated with progressing tumors and maintaining of telomere length. In the same cohort, PD-L1 scored highest in NMIBC, while PD-L2 was upregulated in MIBC. We also show that miR-100-5p and 138-5p were highly expressed in healthy bladder specimens and cell line, while expression decreased in the BC tissues and BC cell lines. In line with the binding prediction for these miRNAs on target genes, miRs 100-5p and 138-5p expression strongly inverse correlated with TERT, PD-L1, and PD-L2 expression, but not PD1.ConclusionWe identify a loop involving TERT, PD1-ligands, and miR-138-5p in BC, that might represent not only a useful biomarker for improved diagnosis and patients’ stratification but also as a promising axis that might be therapeutically targeted in situ.
Associations of DDX60L With the Clinical Features and Prognosis of Hepatocellular Carcinoma
Authors: Ye Ziqi , Zhang Xin , Zhang Yanfang , Liu Linqing , Xuan Zixue , Huang Ping 
Published: February 2022

ObjectiveAlthough the pathogenesis of hepatocellular carcinoma (HCC) is still unclear, hepatitis C virus (HCV) infection is considered a common cause of HCC. It has been reported that DDX60L can inhibit HCV replication, but its role in HCC is still poorly understood.MethodsThe expression levels of DDX60L in HCC tissues and in tissues adjacent to the tumor and their correlation with the clinicopathological features of patients were analyzed. We also used Kaplan–Meier curves of overall survival (OS) with Cox regression analysis and log-rank test to investigate the prognostic value of DDX60L in HCC. We further performed cell proliferation, Transwell, and wound healing assays to elucidate the role of DDX60L in HCC using the siRNA-DDX60L Hep3B or HCCLM3 cell line.ResultsUnivariate analysis showed that sex, Edmondson grade, microvascular invasion, tumor stage (III–IV/I–II), AFP, and DDX60L expression were strongly associated with the prognosis of HCC patients. The results of multivariate analysis further suggested that DDX60L might be an independent prognostic factor for OS in patients with HCC (Pmoderate/low = 0.015, Phigh/low = 0.011). The low DDX60L expression in HCC patients with no-metastasis, age ≥55 years, tumor size &lt;5 cm, Edmondson grade = I–II, microvascular invasion, no cirrhosis, HBV positivity, tumor stage = III–IV, AFP &gt;20 μg/L, and multiple tumor was associated with poorer prognosis (P &lt;0.05). Moreover, the expression of DDX60L was significantly lower in HCC samples (N = 285) than in the normal tissues adjacent to the tumor (N = 167, P &lt;0.001). There were no HCV-related HCC patients in this study. Additionally, we found that DDX60L knockdown can promote the proliferation of Hep3B cells, migration and invasion ability of Hep3B and HCCLM3 cells.ConclusionWe found that the downregulation of DDX60L expression correlated with poor prognosis in patients with HCC, which may be independent of the HCV-related pathway. Furthermore, DDX60L significantly inhibited the proliferation of Hep3B cells, migration and invasion of Hep3B and HCCLM3 cells. Therefore, DDX60L can serve as a prognostic biomarker and therapeutic target for HCC.
Development and Validation of a Novel Model to Predict Regional Lymph Node Metastasis in Patients With Hepatocellular Carcinoma
Authors: Chen Xiaoyuan , Lu Yiwei , Shi Xiaoli , Han Guoyong , Zhao Jie , Gao Yun , Wang Xuehao 
Published: February 2022

BackgroundThe evaluation of the nodal status of hepatocellular carcinoma (HCC) is a classic but controversial topic. This study aimed to investigate the incidence of lymph node metastasis (LNM), explore the role of lymph node dissection (LND), and develop and validate a novel model to predict LNM in patients with HCC, not other specified (NOS).MethodsThe study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) was calculated using the Joinpoint regression. Survival analyses adopted the competing risk model. The nomogram was constructed based on the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm and validated by calibration curves. The area under the receiver operating characteristic curve (AUROC) was obtained to compare prognostic performance. Decision curve and clinical impact curve analyses were introduced to examine the clinical value of the models.ResultsA total of 8,829 patients were finally enrolled in this study, and 1,346 (15.2%) patients received LND. The LND rate showed no noticeable fluctuation in the last decade, with an APC of 0.5% (P=0.593). LNM was identified in 56 (4.2%) patients and confirmed an independent prognostic factor of HCC patients (P=0.005). There were 2,497 lymph nodes retrieved, and 93 (3.7%) of them were positive. After propensity score matching, LND indicated no direct oncologic benefit and did not worsen competing risks. Moreover, an increased number of lymph nodes retrieved could not improve prognoses. 1,346 patients with LND were further randomly divided into the training and validation sets with the ratio of 1:1. Race, tumor size, clinical T stage, extrahepatic bile duct invasion, and tumor grade were independent risk factors for LNM. The constructed model was well calibrated and showed good discrimination power and net benefits in clinical practice.ConclusionLNM is an independent prognostic factor in HCC, but routine LND seems to be unnecessary in HCC patients. The constructed model could predict the presence of LNM in HCC patients with good performance, which is meaningful to patient stratification and individual treatment strategies optimization.