bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Repeatedly Elevated Fatty Liver Index Is Associated With Increased Mortality: A Population-Based Cohort Study
Authors: Lee Chang-Hoon , Han Kyung-Do , Kim Da Hye , Kwak Min-Sun 
Published: March 2021

AimsNon-alcoholic fatty liver disease (NAFLD) has a dynamic disease course, therefore repeated measurements of NAFLD status could have benefits rather than single one. The aim of this study was to investigate the effects of persistent NAFLD on the incidence of myocardial infarction (MI) and stroke and all-cause mortality by using repeated measurement of fatty liver index (FLI).MethodsAbout 3 million subjects who had undergone the health screening four times from 2009 until 2013 were included. NAFLD was defined as an FLI ≥60. FLI points were defined as the number of times participants meeting the criteria of NAFLD (0–4). Outcomes included all-cause mortality, MI, and stroke.ResultsThe higher the FLI points, the higher the risk of all-cause mortality, MI, and stroke (P for trend &lt;0.001, all). Subjects with four FLI points had a higher risk of all-cause mortality (aHR, 1.86; 95% CI, 1.75–1.98; P &lt; 0.001), incidence of MI (aHR, 1.3; 95% CI, 1.21–1.40; P &lt; 0.001), and stroke (aHR, 1.27; 95% CI, 1.19–1.37; P &lt; 0.001) after adjustment for age, sex, smoking, alcohol consumption, income, hypertension, dyslipidemia, diabetes, body mass index, and physical activity. When the 1st and the last FLI were compared, the “incident NAFLD” group had a higher risk for death compared to the “no NAFLD” group (aHR, 1.46; 95% CI, 1.37–1.55), and the “regression of NAFLD” group had a decreased risk for death compared to the “persistent NAFLD” group (aHR, 0.83; 95% CI, 0.77–0.89).ConclusionRepeated evaluations of NAFLD status based on FLI measurements could help physicians identify higher-risk groups in terms of mortality, MI, and stroke. The association between FLI worsening or improvement and outcomes also suggests clinical benefits of the prevention and treatment of NAFLD.
Necroptosis Underlies Hepatic Damage in a Piglet Model of Lipopolysaccharide-Induced Sepsis
Authors: Xu Qiao , Guo Junjie , Li Xiangen , Wang Yang , Wang Dan , Xiao Kan , Zhu Huiling , Wang Xiuying , Hu Chien-An Andy , Zhang Guolong , Liu Yulan 
Published: March 2021

BackgroundNecroptosis is a newly recognized form of programmed cell death with characteristics of both necrosis and apoptosis. The role of necroptosis in hepatic damage during sepsis is poorly understood. In this study, we investigated the occurrence of necroptosis in hepatic damage, and its contribution to hepatic damage in a piglet model of lipopolysaccharide (LPS)-induced sepsis.MethodsTwo animal experiments were conducted. In trial 1, piglets were challenged with LPS and sacrificed at different time points after LPS challenge. In trial 2, piglets were pretreated with necrostatin-1, a specific inhibitor of necroptosis, prior to LPS challenge. Alterations in the hepatic structure and function, pro-inflammatory cytokine expression, and the necroptosis signaling pathway were investigated. Typical ultrastructural characteristics of cell necrosis was observed in the liver of LPS-challenged piglets.ResultsExpressions of critical components of necroptosis including kinases (RIP1, RIP3, and MLKL), mitochondrial proteins (PGAM5 and DRP1), and an intracellular damage-associated molecular pattern (HMGB1) were increased in the liver in a time-dependent manner, followed by hepatic inflammation, morphological damage, and dysfunction as manifested by elevated hepatic expression of IL-1β, IL-6 and TNF-α as well as increased serum AST and AKP activities and the AST/ALT ratio. Pretreatment with necrostatin-1 significantly reduced the expression of RIP1, RIP3 and MLKL as well as PGAM5, DRP1 and HMGB1, which subsequently led to obvious attenuation of hepatic inflammation and damage.ConclusionsOur study demonstrates that necroptosis occurs in the liver during sepsis and contributes to septic hepatic injury.
Autoimmune and Rheumatic Manifestations Associated With COVID-19 in Adults: An Updated Systematic Review
Authors: Tang Kuo-Tung , Hsu Bo-Chueh , Chen Der-Yuan 
Published: March 2021

Background:Numerous cases of the coronavirus disease 2019 (COVID-19) with autoimmune and rheumatic manifestations have been reported. Despite the available reviews that summarized its autoimmune/rheumatic manifestations, a systematic approach is still lacking. Therefore, we conducted a comprehensive systematic review in order to give an overview upon these rare but clinically significant manifestations.Methods:We performed a literature search of PubMed and EMBASE as of October 9, 2020. All articles relevant to either systemic or organ-specific autoimmune and rheumatic manifestations potentially associated with COVID-19 were collected. The reviewed literature were limited to adults ≥18 years.Results:Although most of the existing evidence was based on case reports or case series without a long-term follow-up, a variety of autoimmune/rheumatic manifestations were associated with COVID-19. The manifestations that have a consistent association with COVID-19 include autoimmune cytopenia, cutaneous vasculitis, encephalitis, and Guillain-Barre syndrome. Such association is conflicting as regards to antiphospholipid syndrome, hemophagocytic lymphohistiocytosis, and myasthenia gravis.Conclusion:Our systematic review indicated the potential of the COVID-19 virus to trigger a myriad of autoimmune and rheumatic manifestations, which should be considered amid global efforts to combat COVID-19.
Biosilicate® Glass-Ceramic Foams From Refined Alkali Activation and Gel Casting
Authors: Bernardo Enrico , Elsayed Hamada , Romero Acacio Rincon , Crovace Murilo C. , Zanotto Edgar D. , Fey Tobias 
Published: March 2021

Biosilicate® glass-ceramics are among the most valid alternatives to 45S5 Bioglass. They combine a similar bioactivity and bioresorbability as the 45S5 with superior mechanical strength, owing to the crystallization of a Na–Ca silicate phase. This crystallization may be experienced upon viscous flow sintering of fine glass powders, thus configuring a sinter-crystallization process. As crystallization is seldom complete, sintering can also be applied to semicrystalline powders. The sintering/crystallization combination may be exploited for shaping highly porous bodies, to be used as scaffolds for bone tissue engineering, in the form of foams. The present study aims at exploring a gel-casting process, based on the room temperature foaming of powders suspended in a “weakly alkaline” (1 M NaOH) aqueous solution, followed by sintering at 1,000°C. The gelation of suspensions is attributed to the formation of hydrated compounds, later decomposed upon firing. Amorphous powders provided more intense gelation than semicrystalline ones, promoted a more homogeneous foaming, and stimulated a substantial crystallization upon firing. The homogeneity of foamed samples was assessed using micro-tomography and was further improved by casting foamed suspensions (“foam casting”) before setting.
Neurocognitive Trajectories After 72 Weeks of First-Line Anti-retroviral Therapy in Vietnamese Adults With HIV-HCV Co-infection
Authors: Paul Robert H. , Shikuma Cecilia M. , Chau Nguyen Van Vinh , Ndhlovu Lishomwa C. , Thanh Nguyen Tat , Belden Andrew C. , Chow Dominic C. , Chew Glen M. , Premeaux Thomas A. , Ly Vo Trieu , McBride Joseph A. D. , Bolzenius Jacob D. , Le Thuy 
Published: March 2021

Background: Long-term neurocognitive outcomes following first-line suppressive anti-retroviral therapy (ART) remain uncertain for individuals with HIV and hepatitis C (HCV) co-infection. The study examined neurocognitive performance before and after 72 weeks of ART using repeated multivariate analyses and latent trajectory models.Methods: One hundred and sixty adults with chronic, untreated HIV infection (n = 80 with HCV co-infection and n = 80 HIV mono-infected) and 80 demographically similar healthy controls were recruited from the Hospital for Tropical Diseases in Ho Chi Minh City and the surrounding community, respectively. Neurocognitive measures (adapted for use in Vietnam) and liver enzyme tests were compared across groups at baseline. Repeated multivariate and group-based trajectory analyses (GBTA) examined neurocognitive subgroup profiles of the co-infected individuals after 72 weeks of de novo efavirenz- (n = 41) or raltegravir-based (n = 39) ART.Results: Baseline analyses revealed worse motor function in HIV-HCV co-infected individuals compared to both comparison groups. Longitudinal analyses revealed improved neurocognitive performance by week 48 for most participants regardless of treatment arm. GBTA identified a subgroup (35% of HIV-HCV sample) with persistent motor impairment despite otherwise successful ART. Higher HIV viral load and lower CD4+ T cell count at baseline predicted persistent motor dysfunction. Liver indices and ART regimen did not predict neurocognitive outcomes in HIV-HCV co-infected individuals.Conclusions: Most HIV-HCV co-infected individuals achieve normative neurocognitive performance after 48 weeks of de novo suppressive ART. However, individuals with more severe HIV disease prior to ART exhibited motor impairment at baseline and 72 weeks after otherwise successful treatment. Interventions aimed at improving motor symptoms at the time of HIV treatment onset may improve long-term clinical outcomes in HIV-HCV co-infected adults.
Is the Depth of Invasion a Marker for Elective Neck Dissection in Early Oral Squamous Cell Carcinoma?
Authors: Aaboubout Yassine , van der Toom Quincy M. , de Ridder Maria A. J. , De Herdt Maria J. , van der Steen Berdine , van Lanschot Cornelia G. F. , Barroso Elisa M. , Nunes Soares Maria R. , ten Hove Ivo , Mast Hetty , Smits Roeland W. H. , Sewnaik Aniel , Monserez Dominiek A. , Keereweer Stijn , Caspers Peter J. , Baatenburg de Jong Robert J. , Bakker Schut Tom C. , Puppels Gerwin J. , Hardillo José A. , Koljenović Senada 
Published: March 2021

ObjectiveThe depth of invasion (DOI) is considered an independent risk factor for occult lymph node metastasis in oral cavity squamous cell carcinoma (OCSCC). It is used to decide whether an elective neck dissection (END) is indicated in the case of a clinically negative neck for early stage carcinoma (pT1/pT2). However, there is no consensus on the cut-off value of the DOI for performing an END. The aim of this study was to determine a cut-off value for clinical decision making on END, by assessing the association of the DOI and the risk of occult lymph node metastasis in early OCSCC.MethodsA retrospective cohort study was conducted at the Erasmus MC, University Medical Centre Rotterdam, The Netherlands. Patients surgically treated for pT1/pT2 OCSCC between 2006 and 2012 were included. For all cases, the DOI was measured according to the 8th edition of the American Joint Committee on Cancer guideline. Patient characteristics, tumor characteristics (pTN, differentiation grade, perineural invasion, and lymphovascular invasion), treatment modality (END or watchful waiting), and 5-year follow-up (local recurrence, regional recurrence, and distant metastasis) were obtained from patient files.ResultsA total of 222 patients were included, 117 pT1 and 105 pT2. Occult lymph node metastasis was found in 39 of the 166 patients who received END. Univariate logistic regression analysis showed DOI to be a significant predictor for occult lymph node metastasis (odds ratio (OR) = 1.3 per mm DOI; 95% CI: 1.1–1.5, p = 0.001). At a DOI of 4.3 mm the risk of occult lymph node metastasis was &gt;20% (all subsites combined).ConclusionThe DOI is a significant predictor for occult lymph node metastasis in early stage oral carcinoma. A NPV of 81% was found at a DOI cut-off value of 4 mm. Therefore, an END should be performed if the DOI is &gt;4 mm.
The Diagnostic and Immunotherapeutic Value of CD248 in Renal Cell Carcinoma
Authors: Zhang Keying , Xu Chao , Liu Shaojie , Jiang Yao , Zhao Xiaolong , Ma Shanjin , Li Yu , Yang Fa , Wang Yan , Meng Ping , Shi Changhong , Han Donghui , Wen Weihong , Qin Weijun 
Published: March 2021

Background: Renal cell carcinoma (RCC) is the most common malignancy in the urinary system. Despite substantial improvements in available treatment options, the survival outcome of advanced RCC is unsatisfactory. Identifying novel biomarkers to assist in early diagnosis and to screen patients who are sensitive to immunotherapy would be beneficial. CD248 is a promising candidate that deserves to be investigated.Methods: The Cancer Genome Atlas (TCGA) data set and clinical specimens were adopted to analyze the expression of CD248 between normal and tumor tissues. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors and construct a CD248-based prognostic signature. The correlation among the present signature, tumor-infiltrating immune cells (TIICs), the tumor mutation burden (TMB), and immunomodulatory molecules was evaluated. The weighted gene co-expression network analysis (WGCNA), the enrichment analysis, and the miRNA correlation analysis were performed to explore the underlying mechanism of CD248 in the progression of RCC.Results: The overexpression of CD248 in RCC was related to a poor prognosis, and a CD248-based prognostic signature could precisely stratify patients with RCC with different survival outcomes regardless of the training or testing cohort. The present signature could reflect the immunosuppressive landscape of RCC (i.e., increased infiltration of regulatory T cells and upregulated immune checkpoints), accompanied by deteriorated clinicopathologic indexes. The TMB and immunostimulatory molecules expression also increased with the risk score generated from the present signature. CD248 co-expressed gene sets were identified through the WGCNA algorithm, and several immunosuppressive Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched. The result of CD248-correlated miRNA further emphasized the importance of CD248 in RCC.Conclusion: CD248 is a valuable biomarker to improve the diagnostic and therapeutic efficiency of RCC. The immunosuppressive effect of CD248 co-expressed genes may provide insight for the present study, and miRNA would help to reveal the mechanism of the expressive regulation of CD248.
Automatic Extraction of Recurrent Patterns of High Dominant Frequency Mapping During Human Persistent Atrial Fibrillation
Authors: Li Xin , Chu Gavin S. , Almeida Tiago P. , Vanheusden Frederique J. , Salinet João , Dastagir Nawshin , Mistry Amar R. , Vali Zakariyya , Sidhu Bharat , Stafford Peter J. , Schlindwein Fernando S. , Ng G. André 
Published: March 2021

Purpose: Identifying targets for catheter ablation remains challenging in persistent atrial fibrillation (persAF). The dominant frequency (DF) of atrial electrograms during atrial fibrillation (AF) is believed to primarily reflect local activation. Highest DF (HDF) might be responsible for the initiation and perpetuation of persAF. However, the spatiotemporal behavior of DF remains not fully understood. Some DFs during persAF were shown to lack spatiotemporal stability, while others exhibit recurrent behavior. We sought to develop a tool to automatically detect recurrent DF patterns in persAF patients.Methods: Non-contact mapping of the left atrium (LA) was performed in 10 patients undergoing persAF HDF ablation. 2,048 virtual electrograms (vEGMs, EnSite Array, Abbott Laboratories, USA) were collected for up to 5 min before and after ablation. Frequency spectrum was estimated using fast Fourier transform and DF was identified as the peak between 4 and 10 Hz and organization index (OI) was calculated. The HDF maps were identified per 4-s window and an automated pattern recognition algorithm was used to find recurring HDF spatial patterns. Dominant patterns (DPs) were defined as the HDF pattern with the highest recurrence.Results: DPs were found in all patients. Patients in atrial flutter after ablation had a single DP over the recorded time period. The time interval (median [IQR]) of DP recurrence for the patients in AF after ablation (7 patients) decreased from 21.1 s [11.8 49.7 s] to 15.7 s [6.5 18.2 s]. The DF inside the DPs presented lower temporal standard deviation (0.18 ± 0.06 Hz vs. 0.29 ± 0.12 Hz, p &lt; 0.05) and higher OI (0.35 ± 0.03 vs. 0.31 ± 0.04, p &lt; 0.05). The atrial regions with the highest proportion of HDF region were the septum and the left upper pulmonary vein.Conclusion: Multiple recurrent spatiotemporal HDF patterns exist during persAF. The proposed method can identify and quantify the spatiotemporal repetition of the HDFs, where the high recurrences of DP may suggest a more organized rhythm. DPs presented a more consistent DF and higher organization compared with non-DPs, suggesting that DF with higher OI might be more likely to recur. Recurring patterns offer a more comprehensive dynamic insight of persAF behavior, and ablation targeting such regions may be beneficial.
Staying Ahead of the Epidemiologic Curve: Evaluation of the British Columbia Asthma Prediction System (BCAPS) During the Unprecedented 2018 Wildfire Season
Authors: Henderson Sarah B. , Morrison Kathryn T. , McLean Kathleen E. , Ding Yue , Yao Jiayun , Shaddick Gavin , Buckeridge David L. 
Published: March 2021

Background: The modular British Columbia Asthma Prediction System (BCAPS) is designed to reduce information burden during wildfire smoke events by automatically gathering, integrating, generating, and visualizing data for public health users. The BCAPS framework comprises five flexible and geographically scalable modules: (1) historic data on fine particulate matter (PM2.5) concentrations; (2) historic data on relevant health indicator counts; (3) PM2.5 forecasts for the upcoming days; (4) a health forecasting model that uses the relationship between (1) and (2) to predict the impacts of (3); and (5) a reporting mechanism.Methods: The 2018 wildfire season was the most extreme in British Columbia history. Every morning BCAPS generated forecasts of salbutamol sulfate (e.g., Ventolin) inhaler dispensations for the upcoming days in 16 Health Service Delivery Areas (HSDAs) using random forest machine learning. These forecasts were compared with observations over a 63-day study period using different methods including the index of agreement (IOA), which ranges from 0 (no agreement) to 1 (perfect agreement). Some observations were compared with the same period in the milder wildfire season of 2016 for context.Results: The mean province-wide population-weighted PM2.5 concentration over the study period was 22.0 μg/m3, compared with 4.2 μg/m3 during the milder wildfire season of 2016. The PM2.5 forecasts underpredicted the severe smoke impacts, but the IOA was relatively strong with a population-weighted average of 0.85, ranging from 0.65 to 0.95 among the HSDAs. Inhaler dispensations increased by 30% over 2016 values. Forecasted dispensations were within 20% of the observed value in 71% of cases, and the IOA was strong with a population-weighted average of 0.95, ranging from 0.92 to 0.98. All measures of agreement were correlated with HSDA population, where BCAPS performance was better in the larger populations with more moderate smoke impacts. The accuracy of the health forecasts was partially dependent on the accuracy of the PM2.5 forecasts, but they were robust to over- and underpredictions of PM2.5 exposure.Conclusions: Daily reports from the BCAPS framework provided timely and reasonable insight into the population health impacts of predicted smoke exposures, though more work is necessary to improve the PM2.5 and health indicator forecasts.
Comparison of Retrospective and Prospective Falls Reporting Among Community-Dwelling Older People: Findings From Two Cohort Studies
Authors: Romli Muhammad Hibatullah , Mackenzie Lynette , Tan Pey June , Chiew Re On , Tan Shun Herng , Tan Maw Pin 
Published: March 2021

Background:While prospective recording is considered as the gold standard, retrospective recall is widely utilized for falls outcomes due to its convenience. This brings about the concern on the validity of falls reporting in Southeast Asian countries, as the reliability of falls recall has not previously been studied. This study aimed to evaluate the reliability of retrospective falls recall compared to prospective falls recording.Methods:A secondary analysis of data from two prospective recording methods, falls diary and falls calendar, from two different research projects were obtained and analyzed. Retrospective falls recall was collected either through phone interview or follow-up clinic by asking the participants if they had fallen in the past 12 months.Results:Two-hundred-sixty-eight and 280 elderly participated in the diary and calendar groups, respectively. Moderate (46%) and poor (11%) return rates were found on completed diary and calendar recording. Under-(32%) and overreporting (24%) of falls were found in diary compared to only 4% of overreporting for the calendar. Retrospective recall method achieved 57% response rate for the diary group (followed up at clinic) and 89% for the calendar group (followed up via telephone interview). Agreement between retrospective and prospective reporting was moderate for the diary (kappa =0.44;p&lt; 0.001) and strong for the calendar (kappa = 0.89;p&lt; 0.001).Conclusion:Retrospective recall is reliable and acceptable in an observation study within healthy community older adults, while the combination of retrospective and prospective falls recording is the best for an intervention study with frailer older population. Telephone interview is convenient, low cost, and yielded a high response rate.
Do Drug Accessibility and OOP Burden Affect Health-Related Quality of Life of Patients With Chronic Diseases? — EQ-5D-5L Evaluation Evidence From Five Districts in China
Authors: Tang Shaoliang , Gong Ying , Liu Meixian , Yang Duoer , Tang Kean 
Published: March 2021

Purpose: The dependence of patients with chronic diseases on drugs may affect their health-related quality of life (HRQoL). This study aims to assess the relationship between the direct economic burden caused by out-of-pocket (OOP) payments, drug accessibility, sociodemographic characteristics, and health-related quality of life.Methods: 1,055 patients with chronic diseases from Gansu, Hebei, Sichuan, Zhejiang, and Tianjin were investigated. Data collection included basic conditions and economic and health insurance conditions of patients with chronic diseases. The CLAD and Tobit regression models were used to analyze and compare the health-related quality of life and influencing factors of patients with chronic diseases in five districts. Differentiated analysis was conducted through sub-sample regression to explore the variable health effects of patients with single and multiple diseases.Results: A total of 1,055 patients with chronic diseases participated in the study, 54.4% of whom were women. The overall average utility score was 0.727, of which Sichuan Province was the highest with 0.751. Participants reported the highest proportion of pain/discomfort problems, while patients reported the least problems with self-care. The improvement of drug accessibility and the reduction of the burden of out-of-pocket expenses have significant positive effects on HRQoL. Various sociodemographic factors such as age and gender also have significant impact on HRQoL of patients with chronic diseases. HRQoL of patients with multiple chronic diseases is more affected by various influencing factors than that of patients with single disease.Conclusion: In order to improve the quality of life of patients with chronic diseases, it is of great importance to ensure the accessibility of drugs and reduce patients' medication burden. Future focus should shift from preventing and controlling chronic diseases as individual diseases to meeting the comprehensive health needs of people suffering from multiple diseases.