bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified triglyceride-glucose index indices are reliable markers for predicting risk of metabolic dysfunction-associated fatty liver disease: a cross-sectional study
Authors: Kim Ae Hee , Son Da-Hye , Lee Yong-Jae 
Published: January 2024

IntroductionMetabolic dysfunction–associated fatty liver disease (MAFLD) is newly proposed nomenclature, and its diagnosis involves an algorithm that can be complicated and impractical for clinicians in real-world clinical settings. Thus, we investigated the association between MAFLD and modified triglyceride-glucose index (TyG) indices to find a more concise, feasible method for predicting MAFLD in everyday clinical care.MethodsData were obtained from people who voluntarily underwent health check-ups at the Health Promotion Centre of Gangnam Severance Hospital, Yonsei University College of Medicine, from January 2017 to October 2020. Four indices were analyzed: TyG-body to mass index (BMI), TyG-waist circumference (WC), TyG, and the fatty liver index (FLI). The odds ratios for MAFLD according to each index were calculated using multiple logistic regression analyses, and the receiver operating characteristics curve (ROC) and area under the ROC were obtained to find the predictive powers of each index.ResultsThe final number of study participants was 22,391, 8,246 with MAFLD and 14,145 without MAFLD. The odds ratios (95% confidence intervals) from TyG-WC and TyG-BMI after adjusting for confounding variables were 12.484 (9.962–15.644) and 12.494 (9.790–15.946), respectively, for quartile 2, 54.332 (43.131–68.442) and 51.580 (40.495–65.699) for quartile 3, and 165.804 (130.243–211.076) and 128.592 (100.601–164.371) for quartile 4. The area under the ROC curve values for TyG-WC and TyG-BMI were 0.862 (0.857–0.867) and 0.867 (0.862–0.872), respectively.ConclusionThe modified TyG indices are highly reliable markers for predicting MAFLD that clinicians can easily and practically apply in everyday, real-world, clinical care settings.
Screening immune-related blood biomarkers for DKD-related HCC using machine learning
Authors: Chen Chao , Xie Zhinan , Ni Ying , He Yuxi 
Published: January 2024

BackgroundDiabetes mellitus is a significant health problem worldwide, often leading to diabetic kidney disease (DKD), which may also influence the occurrence of hepatocellular carcinoma (HCC). However, the relationship and diagnostic biomarkers between DKD and HCC are unclear.MethodsUsing public database data, we screened DKD secretory RNAs and HCC essential genes by limma and WGCNA. Potential mechanisms, drugs, and biomarkers for DKD-associated HCC were identified using PPI, functional enrichment, cMAP, and machine learning algorithms, and a diagnostic nomogram was constructed. Then, ROC, calibration, and decision curves were used to evaluate the diagnostic performance of the nomograms. In addition, immune cell infiltration in HCC was explored using CIBERSORT. Finally, the detectability of critical genes in blood was verified by qPCR.Results104 DEGs associated with HCC using WGCNA were identified. 101 DEGs from DKD were predicated on secreting into the bloodstream with Exorbase datasets. PPI analysis identified three critical modules considered causative genes for DKD-associated HCC, primarily involved in inflammation and immune regulation. Using lasso and RM, four hub genes associated with DKD-associated HCC were identified, and a diagnostic nomogram confirmed by DCA curves was established. The results of immune cell infiltration showed immune dysregulation in HCC, which was associated with the expression of four essential genes. PLVAP was validated by qPCR as a possible blood-based diagnostic marker for DKD-related HCC.ConclusionWe revealed the inflammatory immune pathways of DKD-related HCC and developed a diagnostic nomogram for HCC based on PLVAP, C7, COL15A1, and MS4A6A. We confirmed with qPCR that PLVAP can be used as a blood marker to assess the risk of HCC in DKD patients.
Evaluation of recombinant baculovirus clearance during rAAV production in Sf9 cells using a newly developed fluorescent-TCID50 assay
Authors: Luo Ningguang , Chen Xiangqun , Li Jinzhong , Huynh Derrick , Li Ying , Ou Li , Liu Shengjiang 
Published: January 2024

IntroductionRecombinant adeno-associated virus (rAAV) vectors provide a safe and efficient means for in vivo gene delivery, although its large-scale production remains challenging. Featuring high manufacturing speed, flexible product design, and inherent safety and scalability, the baculovirus/Sf9 cell system offers a practical solution to the production of rAAV vectors in large quantities and high purity. Nonetheless, removal and inactivation of recombinant baculoviruses during downstream purification of rAAV vectors remain critical prior to clinical application.MethodsThe present study utilized a newly developed fluorescent-TCID50 (F-TCID50) assay to determine the infectious titer of recombinant baculovirus (rBV) stock after baculovirus removal and inactivation, and to evaluate the impact of various reagents and solutions on rBV infectivity.Results and discussionThe results showed that a combination of sodium lauryl sulfate (SLS) and Triton X-100 lysis, AAVx affinity chromatography, low pH hold (pH3.0), CsCl ultracentrifugation, and NFR filtration led to effective removal and/or inactivation of recombinant baculoviruses, and achieved a log reduction value (LRV) of more than 18.9 for the entire AAV purification process. In summary, this study establishes a standard protocol for downstream baculovirus removal and inactivation and a reliable F-TCID50 assay to detect rBV infectivity, which can be widely applied in AAV manufacturing using the baculovirus system.
Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios
Authors: George Noreen Grace , Rishi Bhavika , Singh Amitabh , Vishmaya Sree , Kumar Rakesh , Kushwaha Neetu , Kaur Manpreet , Bhardwaj Reena , Jain Ankur , Jain Aditi , Chaudhry Sumita , Misra Aroonima 
Published: January 2024

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis.Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cfDNA extraction kits. The probability of poor outcomes in high-risk groups and a cut-off value for risk stratification minimal residual disease (MRD) positivity and outcome prediction were derived.Results: Twenty-five patients diagnosed with AML and ALL were risk-stratified based on NCI risk stratification, and of these 25 patients, 4 patients were of standard risk (SR) and 1 patient was of intermediate risk (IR), while a majority of patients (80%) were of high risk (HR). Of these, four HR patients passed away. The ratio of cfDNA reduction at baseline and the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of the MRD status. A cfDNA ratio score of 2.6 or higher at diagnosis/remission predicted poor outcomes, with higher accuracy than conventional MRD detection by flow cytometry.Conclusion: A higher cfDNA ratio at diagnosis/remission or at baseline predicts poor outcomes in acute leukemia patients. This pilot study suggests that cfDNA ratio scoring may be a useful tool for predicting prognosis in acute leukemia patients, regardless of the MRD status.
Linear brain measurement: a new screening method for cognitive impairment in elderly patients with cerebral small vessel disease
Authors: Wang Jing , Lu Jinhua , He Mingqing , Song Ziyang , Dong Lingyan , Tang Haiying , Wang Yueju , Zhou Zheping 
Published: January 2024

BackgroundThe old adults have high incidence of cognitive impairment, especially in patients with cerebral small vessel disease (CSVD). Cognitive impairment is not easy to be detected in such populations. We aimed to develop clinical prediction models for different degrees of cognitive impairments in elderly CSVD patients based on conventional imaging and clinical data to determine the better indicators for assessing cognitive function in the CSVD elderly.Methods210 CSVD patients were screened out by the evaluation of Magnetic Resonance Imaging (MRI). Then, participants were divided into the following three groups according to the cognitive assessment results: control, mild cognitive impairment (MCI), and dementia groups. Clinical data were collected from all patients, including demographic data, biochemical indicators, carotid ultrasound, transcranial Doppler (TCD) indicators, and linear measurement parameters based on MRI.ResultsOur results showed that the brain atrophy and vascular lesions developed progressive worsening with increased degree of cognitive impairment. Crouse score and Interuncal distance/Bitemporal distance (IUD/BTD) were independent risk factors for MCI in CSVD patients, and independent risk factors for dementia in CSVD were Crouse Score, the pulsatility index of the middle cerebral artery (MCAPI), IUD/BTD, and Sylvian fissure ratio (SFR). Overall, the parameters with high performance were the IUD/BTD (OR 2.28; 95% CI 1.26–4.10) and SFR (OR 3.28; 95% CI 1.54–6.91), and the AUC (area under the curve) in distinguishing between CSVD older adults with MCI and with dementia was 0.675 and 0.724, respectively. Linear brain measurement parameters had larger observed effect than other indexes to identify cognitive impairments in CSVD patients.ConclusionThis study shows that IUD/BTD and SFR are good predictors of cognitive impairments in CSVD elderly. Linear brain measurement showed a good predictive power for identifying MCI and dementia in elderly subjects with CSVD. Linear brain measurement could be a more suitable and novel method for screening cognitive impairment in aged CSVD patients in primary healthcare facilities, and worth further promotion among the rural population.
Incidence of central retinal artery occlusion peaks in winter season
Authors: Gassel Caroline J. , Andris Wolfgang , Poli Sven , Bartz-Schmidt Karl Ulrich , Dimopoulos Spyridon , Wenzel Daniel A. 
Published: January 2024

IntroductionStroke incidence exhibits seasonal trends, with the highest occurrences observed during winter. This study investigates the incidence of central retinal artery occlusion (CRAO), a stroke equivalent of the retina, and explores its monthly and seasonal variations, as well as potential associations with weather and ambient air pollutants.MethodsA retrospective search of medical records spanning 15 years (January 2008–December 2022) was conducted at the University Eye Hospital Tübingen, Germany, focusing on diagnosed cases of CRAO. Incidences were evaluated on a monthly and seasonal basis (winter, spring, summer, fall). Weather data (temperature, precipitation, atmospheric pressure) and concentrations of ambient air pollutants [fine particulate matter (PM2.5), coarse particulate matter (PM10), nitrogen dioxide (NO2), and ozone (O3)], were analyzed for a potential association with CRAO incidence.ResultsOut of 432 patients diagnosed with CRAO between 2008 and 2022, significantly varying incidences were observed monthly (p = 0.025) and seasonally (p = 0.008). The highest rates were recorded in February and winter, with the lowest rates in June and summer. Concentrations of NO2, PM2.5 and lower ambient air temperature (average, minimum, maximum) showed significant correlations with CRAO incidence.DiscussionThis comprehensive 15-year analysis reveals a pronounced winter peak in CRAO incidence, with the lowest occurrences in summer. Potential associations between CRAO incidence and ambient air pollutants and temperature underscore the importance of considering seasonal trends and call for further investigations to elucidate contributing factors, potentially leading to targeted preventive strategies and public health interventions.
Psychometrics assessment of ethical decision-making around end-of-life care scale for adolescents in the final stage of life
Authors: Mohammadi Fateme , Masoumi Seyedeh Zahra , Khazaei Salman , Hosseiny Seyyed Mohammad Mahdi 
Published: January 2024

IntroductionHealthcare professionals have a critical role in ethical decision-making around end-of-life care. Properly evaluating the ethical decision-making of health care professionals in end-of-life care requires reliable, tailored, and comprehensive assessments. The current study aimed to translate and assess psychometrically a Persian version of the ethical decision making in end-of-life care scale for Iranian adolescents in the final stages of life.MethodsThe present study investigates the methodology and multicenter research. 310 healthcare professionals who treat/care for adolescents at the end of life were selected from 7 cities in Iran. The original version of the end-of-life care decision-making scale was translated into Persian using the forward-backward translation method, and its psychometric properties were evaluated using COSMIN criteria.ResultsExploratory factor analysis revealed that the factor loadings of the items ranged from 0.68 to 0.89, all of which were statistically significant. Furthermore, three factors had eigenvalues greater than 1, accounting for 81.64% of the total variance. Confirmatory factor analysis indicated a proper goodness of fit in the hypothesized factor structure. The internal consistency reliability of the tool was assessed in terms of its homogeneity, yielding a Cronbach's alpha coefficient of 0.93.ConclusionThe Persian version of the End-of-Life Care Decision-Making Scale demonstrates satisfactory validity and reliability among healthcare professionals working with adolescents in the final stages of life. Therefore, nursing managers can utilize this tool to measure and evaluate ethical decision-making in end-of-life care for adolescents in the final stages of life and identify the most appropriate strategies, including educational interventions, to improve ethical decision-making in end-of-life care if necessary.
Unraveling the impact of nitric oxide, almitrine, and their combination in COVID-19 (at the edge of sepsis) patients: a systematic review
Authors: Wang Ying , Yu Qian , Tian Yuan , Ren Shiying , Liu Liping , Wei Chaojie , Liu Renli , Wang Jing , Li Dong , Zhu Kun 
Published: January 2024

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a large number of critically ill and severe COVID-19 patients meet the diagnostic criteria for sepsis and even septic shock. The treatments for COVID-19 patients with sepsis are still very limited. For sepsis, improving ventilation is one of the main treatments. Nitric oxide (NO) and almitrine have been reported to improve oxygenation in patients with “classical” sepsis. Here, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of NO, almitrine, and the combination of both for COVID-19 (at the edge of sepsis) patients.Method: A systematic search was performed on Embase, PubMed, the Cochrane Library, the Web of Science, Wanfang Data, and China National Knowledge Infrastructure. Randomized clinical trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports in COVID-19 patients with suspected or confirmed sepsis were performed. Study characteristics, patient demographics, interventions, and outcomes were extracted from eligible articles.Results: A total of 35 studies representing 1,701 patients met eligibility criteria. Inhaled NO did not affect the mortality (OR 0.96, 95% CI 0.33–2.8, I2 = 81%, very low certainty), hospital length of stay (SMD 0.62, 95% CI 0.04–1.17, I2 = 83%, very low certainty), and intubation needs (OR 0.82, 95% CI 0.34–1.93, I2 = 56%, very low certainty) of patients with COVID-19 (at the edge of sepsis). Meanwhile, almitrine did not affect the mortality (OR 0.44, 95% CI 0.17–1.13, low certainty), hospital length of stay (SMD 0.00, 95% CI -0.29–0.29, low certainty), intubation needs (OR 0.94, 95% CI 0.5–1.79, low certainty), and SAEs (OR 1.16, 95% CI 0.63–2.15, low certainty). Compared with pre-administration, the PaO2/FiO2 of patients with NO (SMD-0.87, 95% CI -1.08–0.66, I2 = 0%, very low certainty), almitrine (SMD-0.73, 95% CI-1.06–0.4, I2 = 1%, very low certainty), and the combination of both (SMD-0.94, 95% CI-1.71–0.16, I2 = 47%, very low certainty) increased significantly.Conclusion: Inhaled NO, almitrine, and the combination of the two drugs improved oxygenation significantly, but did not affect the patients’ mortality, hospitalization duration, and intubation needs. Almitrine did not significantly increase the patients’ SAEs. Well-designed high-quality studies are needed for establishing a stronger quality of evidence.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367667, identifier CRD42022367667.
The efficacy of bevacizumab combined with platinum-containing chemotherapy in the treatment of advanced non-small cell lung cancer in China: a systematic review and meta-analysis of randomized clinical trials
Authors: Han Guangsu , Li Chenlu , Yi Ping 
Published: January 2024

Background: Platinum-based dual-drug first-line chemotherapy is commonly employed in the treatment of patients with advanced non-small cell lung cancer (NSCLC), although its clinical efficacy is limited. Bevacizumab can antagonize vascular endothelial cell growth factor (VEGF), which inhibit tumor angiogenesis and prevent tumor invasion and development. However, a comprehensive meta-analysis evaluating the effectiveness and safety of combining bevacizumab with platinum-based chemotherapy in advanced NSCLC patients is lacking.Methods: Randomized controlled trials (RCTs) investigating the combination therapy of bevacizumab and platinum-based chemotherapy for treating advanced NSCLC were searched across six databases. Data on objective response rate (ORR), disease control rate (DCR), 1-year survival rate, 2-year survival rate, 3-year survival rate, VEGF levels, and side effects were synthesized. Relative risk degree (RR) along with 95% confidence interval (CI) was used as statistical analysis measures for binary outcomes while continuous variables were analyzed using mean difference (MD) along with 95% CI. Heterogeneity was evaluated by Chi-squared and I2 tests. If there was heterogeneity, subgroup analysis was performed. Sensitivity analysis of the main outcome measures and assessment of publication bias were also performed.Results: According to our screening criteria, a total of Forty-nine RCTs were included, involving data from 4268 patients. The results of this analysis showed that compared with platinum-containing chemotherapy alone, bevacizumab combined with platinum-containing chemotherapy significantly improved ORR (RR [95% CI], 1.53 [1.44, 1.63], p &lt; 0.00001), DCR (RR [95% CI], 1.24 [1.19, 1.29], p &lt; 0.0001), 1-year survival rate (RR [95% CI], 1.34 [1.15, 1.57], p = 0.0003), 2-year survival rate (RR [95% CI], 2.16 [1.35, 3.43], p = 0.001), 3-year survival rate (RR [95% CI], 2.00 [1.21, 3.30], p = 0.007). In addition, bevacizumab with platinum-containing chemotherapy observably decreased the VEGF levels (RR [95% CI], −67.35 [−91.46, −43.25], p &lt; 0.00001).Conclusion: Combination therapy involving bevacizumab demonstrated improved antitumor effects compared to chemotherapy alone in terms of ORR, DCR, 1-year survival rate, 2-year survival rate, 3-year survival rate, and VEGF levels without an increased incidence of adverse reactions. These analyses’ results can provide clinicians guidance when selecting appropriate treatments for patients diagnosed with advanced non-small cell lung cancer.
Scale development to evaluate differences between concern about falling and fear of falling: the concern and fear of falling evaluation
Authors: Takla Taylor N. , Matsuda Patricia N. , Herring Tracy E. , Daugherty Ana M. , Fritz Nora E. 
Published: January 2024

PurposeIndividuals with multiple sclerosis (MS) experience fear of falling (FOF), which is associated with negative health and quality-of-life consequences. Prior research has used FOF and concern about falling (CAF) interchangeably, but persons with MS report that CAF and FOF represent separate constructs that lie on a continuum. Unfortunately, no scale exists to understand the differences between CAF and FOF. Therefore, we developed a novel questionnaire, the Concern and Fear of Falling Evaluation (CAFFE), in which respondents rank their CAF and FOF on a continuum across various activities. This study aims to describe the scale development process and examine its psychometric properties.MethodsIn a single online survey, MS participants responded to demographic questionnaires, indicated whether they experience CAF and FOF, and completed the CAFFE. Psychometric evaluation of the CAFFE involved internal consistency, split-half cross validation, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA).ResultsOut of 1,025 respondents, 64.6% reported CAF and 47.2% reported FOF. The EFA yielded a two-factor solution encompassing activities in open (factor 1) and closed environments (factor 2). The CFA replicated this two-factor solution and the CAFFE demonstrated excellent internal consistency (α = 0.98).ConclusionThe 27-item CAFFE is a highly reliable and valid measure capturing the tipping point at which point CAF moves to FOF. Future research should seek to define the tipping point from the MS community, as CAF may be an adaptive mechanism, whereas FOF may be a maladaptive behavior.