bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in NOTCH3 Gene may Promote the Clinical Presentation of Spinocerebellar Ataxia Type 37 Caused by Mutations in DAB1 Gene
Authors: Wang Zhao-Wei , Wang Li-Ping , Du Ye , Liu Qi 
Published: June 2021

Background: Autosomal dominant spinocerebellar ataxia type 37 (SCA37) and Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) result from DAB1 and NOTCH3 gene mutations, respectively.Methods: In addition to conventional diagnostic methods, next-generation sequencing (NGS) and Sanger sequencing were performed to define and confirm the DAB1 and NOTCH3 gene mutation for a Chinese pedigree. Bioinformatics analysis was also applied for the mutated DAB1 and NOTCH3 protein using available software tools.Results: Brain magnetic resonance imaging shows diffuse leukoencephalopathy and cerebellar atrophy in the proband. NGS and Sanger sequencing identified two novel heterozygous mutations: NM_021080:c.318T &gt; G (p.H106Q) in the DAB1 gene and NM_000435:c.3298C &gt; T (p.R1100C) in the NOTCH3 gene. Bioinformatics analysis suggested that the DAB1 and NOTCH3 gene mutations are disease-causing and may be responsible for the phenotypes.Conclusion: This is the first report of a pedigree with both SAC37 and CADASIL phenotypes carrying corresponding gene mutations. Mutations in the NOTCH3 gene may promote the clinical presentation of spinocerebellar ataxia type 37 caused by mutations in the DAB1 gene. In addition to general examinations, it is vital for physicians to apply molecular genetics to get an accurate diagnosis in the clinic, especially for rare diseases.
Distinct MicroRNA Profiles in the Perilymph and Serum of Patients With Menière's Disease
Authors: Shew Matthew , Wichova Helena , St. Peter Madeleine , Warnecke Athanasia , Staecker Hinrich 
Published: June 2021

Hypothesis: Menière's disease microRNA (miRNA) profiles are unique and are reflected in the perilymph and serum of patients.Background: Development of effective biomarkers for Menière's disease are needed. miRNAs are small RNA sequences that downregulate mRNA translation and play a significant role in a variety of disease states, ultimately making them a promising biomarker. miRNAs can be readily isolated from human inner ear perilymph and serum, and may exhibit disease-specific profiles.Methods: Perilymph sampling was performed in 10 patients undergoing surgery; 5 patients with Meniere's disease and 5 patients with otosclerosis serving as controls. miRNAs were isolated from the serum of 5 patients with bilateral Menière's disease and compared to 5 healthy age-matched controls. For evaluation of miRNAs an Agilent miRNA gene chip was used. Analysis of miRNA expression was carried out using Qlucore and Ingenuitey Pathway Analysis software. Promising miRNAs biomarkers were validated using qPCR.Results: In the perilymph of patients with Menière's disease, we identified 16 differentially expressed miRNAs that are predicted to regulate over 220 different cochlear genes. Six miRNAs are postulated to regulate aquaporin expression and twelve miRNAs are postulated to regulate a variety of inflammatory and autoimmune pathways. When comparing perilymph with serum samples, miRNA-1299 and−1270 were differentially expressed in both the perilymph and serum of Ménière's patients compared to controls. Further analysis using qPCR confirmed miRNA-1299 is downregulated over 3-fold in Meniere's disease serum samples compared to controls.Conclusions: Patients with Ménière's disease exhibit distinct miRNA expression profiles within both the perilymph and serum. The altered perilymph miRNAs identified can be linked to postulated Ménière's disease pathways and may serve as biomarkers. miRNA-1299 was validated to be downregulated in both the serum and perilymph of Menière's patients.
Staged Endovascular Treatment for Symptomatic Occlusion Originating From the Intracranial Vertebral Arteries in the Early Non-acute Stage
Authors: Duan Hongzhou , Chen Li , Shen Shengli , Zhang Yang , Li Chunwei , Yi Zhiqiang , Wang Yingjin , Zhang Jiayong , Li Liang 
Published: June 2021

Background: The ideal treatment for patients who survive from acute vertebrobasilar artery occlusion but develop aggressive ischemic events despite maximal medical therapy in the early non-acute stage is unknown. This paper reports the technical feasibility and outcome of staged endovascular treatment in a series of such patients with symptomatic intracranial vertebral artery occlusion.Methods: Ten consecutive patients who presented with aggressive ischemic events in the early non-acute stage of intracranial vertebral artery occlusion from Jan 2015 to Nov 2020 were retrospectively reviewed. Among them, eight male and two female patients with a mean age of 66.7 years developed aggressive ischemic events, and the NIHSS score was elevated by a median of 7 points despite medical therapy. All patients received staged endovascular treatment 4–21 days from onset, at an average of 11 days. The strategy of staged treatment was as follows: first, a microwire was passed through the portion of the occlusion, which was then dilated with balloon inflation to maintain the perfusion above TICI grade 2b. Then, with the use of antiplatelet drugs, the residual intravascular thrombus was gradually eliminated by the continuous perfusion and an activated fibrinolytic system, leaving the residual stenosis. A second stage of angioplasty with stent implantation was subsequently performed if residual stenosis was ≥50%. The NIHSS scores and mRS scores were compared between pre- and post-endovascular treatment groups and in the follow-up period.Results: Technical success was achieved in 9 patients who received staged endovascular treatment (perforation occurred in one patient during the first stage). The NIHSS scores were significantly improved, with a median score 7 points lower on discharge compared with the scores for the most severe status. Favorable outcomes with mRS score ≤ 2 were achieved in 7 and 9 patients at the 3-month follow-up and the latest follow-up, respectively, which was better than the preoperative status.Conclusion: Staged endovascular treatment might be a safe, efficient, and viable option in carefully selected patients with symptomatic intracranial vertebral artery occlusion in the early non-acute stage. However, this needs to be confirmed by further investigation, preferably in a large, controlled setting.
Hypofractionated Volumetric-Modulated Arc Radiotherapy for Patients With Non-Small-Cell Lung Cancer Not Suitable for Surgery or Conventional Chemoradiotherapy or SBRT
Authors: Shen Junyue , Yang Dan , Chen Mailin , Jiang Leilei , Dong Xin , Li Dongming , Yu Rong , Yu Huiming , Shi Anhui 
Published: June 2021

BackgroundHypofractionated radiotherapy (HypoRT) has been used to pursue an alternative treatment regimen for patients with non-small-cell lung cancer (NSCLC) who are not eligible for stereotactic ablative radiotherapy (SABR), surgery or concurrent chemoradiotherapy (CCRT) and has shown good local control and safety. We analyzed the feasibility of using volumetric-modulated arc radiotherapy (VMAT) with the simultaneous integrated boost (SIB) technique to achieve high local control with few treatment-related toxicities.Patients and MethodsA total of 55 patients with stage I-IV NSCLC who were not candidates for SABR, surgery or CCRT were included in the present study. All patients received a prescribed dose of 60 to 66 Gy in 15 fractions. Local progression-free survival (LPFS), PFS, overall survival (OS), and toxicities were retrospectively analyzed.ResultsThirty-three patients (60.0%) had stage IV or recurrent disease in this study. The median follow-up time was 8 months (interquartile range: 5.0-16.3 months). The 1-year and 2-year OS rates were 84.3% and 69.9%, and the 1-year and 2-year LPFS rates were 91.0% and 63.0%. The median OS (mOS) and median LPFS (mLPFS) were not reached, and median PFS (mPFS) was 15 months. Twenty-eight (51.9%) patients had disease progression at the time of analysis. Of these, 7 (13.0%), 7 (13.0%) and 21 (38.9%) had local recurrence, locoregional failure and distant metastasis, respectively. All cases of local recurrence were found within the SIB region. Four patients had grade 2-3 pneumonitis, and 8 patients had grade 2-3 esophagitis. Patients with grade 2-3 esophagitis had significantly higher maximum dose and dose to 5 cm3 volume to esophagus than those with grade 0-1 esophagitis. No grade 4 or higher toxicity was observed.ConclusionThe 60 to 66 Gy in 15 fractions RT regimen provides favorable local control and survival with well-tolerated toxicities. Hypofractionated VMAT+SIB is an alternative treatment option for patients with NSCLC who cannot tolerate standard definitive therapy.
Comparative Risk of Renal Adverse Events in Patients Receiving Immune Checkpoint Inhibitors: A Bayesian Network Meta-Analysis
Authors: Liu Kang , Qin Zhongke , Xu Xueqiang , Li Ting , Ge Yifei , Mao Huijuan , Xing Changying 
Published: June 2021

BackgroundImmune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.MethodsWe carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.ResultsNinety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3–5 RAEs, acute kidney injury (AKI), and grade 3–5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29–0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02–2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.ConclusionsAmong ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3–5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3–5 AKI.Systematic Review RegistrationPROSPERO, identifier CRD42020197039.
Co-Occurring Potentially Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer
Authors: Zhao Yiming , Wang Shuyuan , Yang Zhengyu , Dong Yu , Wang Yanan , Zhang Lele , Hu Hai , Han Baohui 
Published: June 2021

BackgroundSeveral oncogenic drivers in non-small cell lung cancer (NSCLC) are considered actionable with available or promising targeted therapies. Although targetable drivers rarely overlap with each other, there were a minority of patients harboring co-occurring actionable oncogenic targets, whose clinical characteristics and prognosis are not yet clear.MethodsA total of 3,077 patients with NSCLC who underwent molecular analysis by NGS were included, and their demographic and clinical data were retrospectively collected.ResultsOur study found that the frequency of NSCLC patients harboring co-occurring potentially actionable alterations was approximately 1.5% (46/3077); after excluding patients with EGFR-undetermined mutations, the incidence was 1.3% (40/3077); 80% (37/46) harbored both EGFR mutations and other potentially actionable drivers such as MET amplification (21.6%; 8/37) and alterations in ERBB2 including mutations (27%; 10/37) and amplification (21.6%; 8/37); other combinations of potentially actionable drivers including alterations in ERBB2, KRAS, MET, ALK, and RET were also identified. Additionally, de novo MET/ERBB2 amplification in patients harboring EGFR-mutant NSCLC treated with first-generation EGFR tyrosine kinase inhibitors (TKIs) was associated with shorter PFS (p &lt; 0.05). The efficacy of TKIs in NSCLC patients harboring other co-occurring potentially actionable drivers varied across different molecular subtypes.ConclusionsApproximately 1.5% of NSCLCs harbored co-occurring potentially actionable oncogenic drivers, commonly involving EGFR mutations. Co-occurring actionable targets may impact the efficacy of TKIs; therefore, future clinical trials in these patients should be anticipated to tailor the combination or sequential treatment strategies.
Healthcare Utilization of Complex Chronically Ill Children Managed by a Telehealth-Based Team
Authors: Braun Lindsay , Steurer Martina , Henry Duncan 
Published: June 2021

Objectives: Medical advances have improved survival of critically ill children, increasing the number that have substantial ongoing care needs. The first aim of this study was to compare healthcare utilization of children with complex chronic conditions across an extensive geographic area managed by a predominantly telehealth-based team (FamiLy InteGrated Healthcare Transitions—FLIGHT) compared to matched historical controls. The second aim was to identify risk factors for healthcare utilization within the FLIGHT population.Methods: We performed a retrospective cohort study of all patients enrolled in the care management team. First, we compared them to age- and technology-based matched historic controls across medical resource-utilization outcomes. Second, we used univariable and multivariable linear regression models to identify risk factors for resource utilization within the FLIGHT population.Results: Sixty-four FLIGHT patients were included, with 34 able to be matched with historic controls. FLIGHT patients had significantly fewer hospital days per year (13.6 vs. 30.3 days, p = 0.02) and shorter admissions (6.0 vs. 17.3 days, p = 0.02) compared to controls. Within the telehealth managed population, increased number of technologies was associated with more admissions per year (coefficient 0.90, CI 0.05 – 1.75) and hospital days per year (16.83, CI 1.76 – 31.90), although increased number of complex chronic conditions was not associated with an increase in utilization.Conclusion: A telehealth-based care coordination team was able to significantly decrease some metrics of healthcare utilization in a complex pediatric population. Future study is warranted into utilization of telemedicine for care coordination programs caring for children with medical complexity.
Contractile Properties of MHC I and II Fibers From Highly Trained Arm and Leg Muscles of Cross-Country Skiers
Authors: Gejl Kasper Degn , Hvid Lars G. , Andersson Erik P. , Jensen Rasmus , Holmberg Hans-Christer , Ørtenblad Niels 
Published: June 2021

IntroductionLittle is known about potential differences in contractile properties of muscle fibers of the same type in arms and legs. Accordingly, the present study was designed to compare the force-generating capacity and Ca2+ sensitivity of fibers from arm and leg muscles of highly trained cross-country skiers.MethodSingle muscle fibers of m. vastus lateralis and m. triceps brachii of eight highly trained cross-country skiers were analyzed with respect to maximal Ca2+-activated force, specific force and Ca2+ sensitivity.ResultThe maximal Ca2+-activated force was greater for myosin heavy chain (MHC) II than MHC I fibers in both the arm (+62%, P &lt; 0.001) and leg muscle (+77%, P &lt; 0.001), with no differences between limbs for each MHC isoform. In addition, the specific force of MHC II fibers was higher than that of MHC I fibers in both arms (+41%, P = 0.002) and legs (+95%, P &lt; 0.001). The specific force of MHC II fibers was the same in both limbs, whereas MHC I fibers from the m. triceps brachii were, on average, 39% stronger than fibers of the same type from the m. vastus lateralis (P = 0.003). pCa50 was not different between MHC I and II fibers in neither arms nor legs, but the MHC I fibers of m. triceps brachii demonstrated higher Ca2+ sensitivity than fibers of the same type from m. vastus lateralis (P = 0.007).ConclusionComparison of muscles in limbs equally well trained revealed that MHC I fibers in the arm muscle exhibited a higher specific force-generating capacity and greater Ca2+ sensitivity than the same type of fiber in the leg, with no such difference in the case of MHC II fibers. These distinct differences in the properties of fibers of the same type in equally well-trained muscles open new perspectives in muscle physiology.
The Relationship Between Decisional Regret and Well-Being in Patients With and Without Depressive Disorders: Mediating Role of Shared Decision-Making
Authors: Xu Richard Huan , Zhou Ling-ming , Wang Dong 
Published: June 2021

Background: The objectives of this study were two-fold: (1) to assess the relationship between patients' decisional regret and their well-being and (2) to examine the mediated effect of shared decision-making (SDM) on this relationship.Methods: A cross-sectional survey was conducted in five cities in Southern China. Patients were asked to fill out questionnaires assessing their decisional regret, SDM, subjective well-being, and depressive status. Mediation analysis was used to investigate the effect of SDM on the relationship between patients' decisional regret and their subjective well-being.Results: The findings showed significant direct negative effects of decisional regret on subjective well-being and SDM. For non-depressive patients, SDM exerted a significant and indirect effect on reducing the negative influence of decisional regret on subjective well-being.Conclusions: Findings suggest that implementation of SDM can decrease patients' decisional regret and improve their well-being; however, there is a need to examine their depressive status as part of routine healthcare.
Coding Public Health Interventions for Health Technology Assessments: A Pilot Experience With WHO's International Classification of Health Interventions (ICHI)
Authors: Wübbeler Markus , Geis Sebastian , Stojanovic Jovana , Elliott Lise , Gutierrez-Ibarluzea Iñaki , Lenoir-Wijnkoop Irene 
Published: June 2021

Introduction: An important requirement for successful public health interventions is a standardized classification in order to make these health technologies comparable in all contexts and recognized by all parties. The WHO International Classification of Health Interventions (ICHI), including an integrated public health component, has been developed to propose such an international standard.Methods: To test (a) the translation of public health interventions to ICHI codes and (b) the technical handling and general coding in public health, we used a set of public health interventions from a recent cross-sectional survey among Health Technology Assessment professionals.Results: Our study showed that handling of the ICHI interface is stable, that there is a need for specificity and adequate detail of intervention descriptions and desired outcomes to code adequately with ICHI and that the professional background of the coder, as well as his/her sex might influence the selection of codes.Conclusion: International Classification of Health Interventions provides a good coverage of public health interventions. However, the broader character of system wide interventions, often involving a variety of institutions and stakeholders, may present a challenge to the application of ICHI coding. Based on this experience, we would tailor future surveys more specifically to the needs of the classification and we advise training for health professionals before coding with ICHI. Standards of reporting will likely strengthen insights about the efficiency of primary prevention interventions and thus benefit long-term health of populations and structured HTA reporting process.
Prognostic Nomogram of Prognosis-Related Genes and Clinicopathological Characteristics to Predict the 5-Year Survival Rate of Colon Cancer Patients
Authors: Huang Chao , Zhao Jiefeng , Zhu Zhengming 
Published: June 2021

Background: The Cancer Genome Atlas (TCGA) has established a genome-wide gene expression profile, increasing our understanding of the impact of tumor heredity on clinical outcomes. The aim of this study was to construct a nomogram using data from the TCGA regarding prognosis-related genes and clinicopathological characteristics to predict the 5-years survival rate of colon cancer (CC) patients.Methods: Kaplan–Meier and Cox regression analyses were used to identify genes associated with the 5-years survival rate of CC patients. Cox regression was used to analyze the relationship between the clinicopathological features and prognostic genes and overall survival rates in patients with CC and to identify independent risk factors for the prognosis of CC patients. A nomogram for predicting the 5-years survival rate of CC patients was constructed by R software.Results: A total of eight genes (KCNJ14, CILP2, ATP6V1G2, GABRD, RIMKLB, SIX2, PLEKHA8P1, and MPP2) related to the 5-years survival of rate CC patients were identified. Age, stage, and PLEKHA8P1 were independent risk factors for the 5-years survival rate in patients with CC. The accuracy, sensitivity and specificity of the nomogram model constructed by age, TNM staging, and PLEKHA8P1 for predicting the 5-years survival of rate CC patients were 83.3, 83.97, and 85.79%, respectively.Conclusion: The nomogram can correctly predict the 5-year survival rate of patients with CC, thus aiding the individualized decision-making process for patients with CC.
Mechanistic Model and Optimization of the Diclofenac Degradation Kinetic for Ozonation Processes Intensification
Authors: Acosta-Angulo Bryan , Lara-Ramos Jose , Diaz-Angulo Jennyfer , Mueses Miguel Angel , Machuca-Martínez Fiderman 
Published: June 2021

This work focused on estimating the rate constants for three ozone-based processes applied in the degradation of diclofenac. The ozonation (Oz) and its intensification with catalysis (COz) and photocatalysis (PCOz) were studied. Three mathematical models were evaluated with a genetic algorithm (GA) to find the optimal values for the kinetics constants. The Theil inequality coefficient (TIC) worked as a criterion to assess the models’ deviation. The diclofenac consumption followed a slow kinetic regime according to the Hatta number (Ha<0.3). However, it strongly contrasted with earlier studies. The obtained values for the volumetric rate of photon absorption (VRPA) corresponding to the PCOz process (1.75×10−6 & 6.54×10−7 Einstein L−1 min−1) were significantly distant from the maximum (2.59×10−5 Einstein L−1 min−1). The computed profiles of chemical species proved that no significant amount of hydroxyl radicals was produced in the Oz, whereas the PCOz achieved the highest production rate. According to this, titanium dioxide significantly contributed to ozone decomposition, especially at low ozone doses. Although the models’ prediction described a good agreement with the experimental data (TIC<0.3), the optimization algorithm was likely to have masked the rate constants as they had highly deviated from already reported values.