bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telemedical management in patients waiting for transcatheter aortic valve implantation: the ResKriVer-TAVI study design
Authors: Mattig Isabel , Koehler Kerstin , Barzen Gina , Hiddemann Meike , Kugel Elias , Roemmelt Constantin , Mauckisch Verena , Vockeroth Clarissa , Stangl Karl , Hoppe Thomas , Koehler Friedrich , Dreger Henryk 
Published: January 2024

AimsThe majority of patients with severe aortic stenosis (AS) planned for transcatheter aortic valve implantation (TAVI) are elective outpatients. During the COVID-19 pandemic, the time between the heart team’s decision and TAVI increased due to limited healthcare resources. We therefore implemented telemedical approaches to identify AS patients at risk for clinical deterioration during the waiting time. The purpose of the prospective, randomized, controlled ResKriVer-TAVI study (DRKS00027842) is to investigate whether a digital concept of telemedical interventional management (TIM) in AS patients waiting for TAVI improves the clinical outcomes. In the present article, we report the study protocol of the ResKriVer-TAVI trial.MethodsResKriVer-TAVI will enroll AS patients planned for elective TAVI. Randomization to the TIM group or standard care will be made on the day of the heart team’s decision. TIM will include a daily assessment of weight, blood pressure, a 2-channel electrocardiogram, peripheral capillary oxygen saturation, and a self-rated health status until admission for TAVI. TIM will allow optimization of medical therapy or an earlier admission for TAVI if needed. Standard care will not include any additional support for patients with AS. All patients of the TIM group will receive a rule-based TIM including standard operating procedures when a patient is crossing prespecified values of a vital sign.ResultsThe primary endpoint consists of days lost due to cardiovascular hospitalization and death of any cause within 180 days after the heart team’s decision. Major secondary endpoints include all-cause mortality within 365 days, the number of telemedical interventions, and adherence to TIM. Follow-up visits will be conducted at admission for TAVI as well as 6 and 12 months after the heart team’s decision.ConclusionsResKriVer-TAVI will be the first randomized, controlled trial investigating a telemedical approach before TAVI in patients with AS. We hypothesize that primary and secondary endpoints of AS patients with TIM will be superior to standard care. The study will serve to establish TIM in the clinical routine and to increase the resilience of TAVI centers in situations with limited healthcare resources.
Combinatorial immune checkpoint blockade increases myocardial expression of NLRP-3 and secretion of H-FABP, NT-Pro-BNP, interleukin-1β and interleukin-6: biochemical implications in cardio-immuno-oncology
Authors: Quagliariello V. , Passariello M. , Bisceglia I. , Paccone A. , Inno A. , Maurea C. , Rapuano Lembo R. , Manna L. , Iovine M. , Canale M. L. , Scherillo M. , Ascierto P. A. , Gabrielli D. , De Lorenzo C. , Maurea N. 
Published: January 2024

BackgroundImmune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer. Myocarditis, vasculitis and endothelitis are rarely observed in these patients on monotherapy, however new combination therapies could expose patients to more adverse cardiovascular events.MethodsHuman cardiomyocytes co-cultured with human peripheral blood lymphocytes (hPBMCs) were exposed to monotherapy and combinatorial ICIs (PD-L1 and CTLA-4 or PD-1 and LAG-3 blocking agents, at 100 nM) for 48 h. After treatments, cardiac cell lysis and secretion of biomarkers of cardiotoxicity (H-FABP, troponin-T, BNP, NT-Pro-BNP), NLRP3-inflammasome and Interleukin 1 and 6 were determined through colorimetric and enzymatic assays. Mitochondrial functions were studied in cardiomyocyte cell lysates through quantification of intracellular Ca++, ATP content and NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) levels. Histone deacetylases type 4 (HDAC-4) protein levels were also determined in cardiomyocyte cell lysates to study potential epigenetic changes induced by immunotherapy regimens.ResultsBoth combinations of immune checkpoint inhibitors exert more potent cardiotoxic side effects compared to monotherapies against human cardiac cells co-cultured with human lymphocytes. LDH release from cardiac cells was 43% higher in PD-L1/CTLA-4 blocking agents, and 35.7% higher in PD-1/LAG-3 blocking agents compared to monotherapies. HDAC4 and intracellular Ca++ levels were increased, instead ATP content and Ndufs1 were reduced in myocardial cell lysates (p &lt; 0.001 vs. untreated cells). Troponin-T, BNP, NT-Pro-BNP and H-FABP, were also strongly increased in combination therapy compared to monotherapy regimen. NLRP3 expression, IL-6 and IL-1β levels were also increased by PDL-1/CTLA-4 and PD-1/LAG-3 combined blocking agents compared to untreated cells and monotherapies.ConclusionsData of the present study, although in vitro, indicate that combinatorial immune checkpoint blockade, induce a pro- inflammatory phenotype, thus indicating that these therapies should be closely monitored by the multidisciplinary team consisting of oncologists, cardiologists and immunologists.
Analysis of research trends (2014-2023) on oxidative stress and male fertility based on bibliometrics and knowledge graphs
Authors: Du Chao , Yu Yuexin , Fan Xinyue 
Published: January 2024

BackgroundOxidative stress (OS) is considered one of the major factors affecting male fertility, and research in this field has seen constant growth year by year. Currently, around 700 relevant papers are published each year, with a trend of further growth. Therefore, this study systematically summarizes the literature published in the last decade from a bibliometric perspective, revealing the dynamic development of the field, identifying research hotspots, analyzing future trends, and providing reference for further research.MethodsRelevant literature on oxidative stress and male fertility was retrieved from the Web of Science Core Collection (WoSCC) database, covering the timespan from 2014 to 2023 and including two types, articles and reviews. CiteSpace and VOSviewer were used for bibliometric analysis, including cluster analysis, co-occurrence analysis, co-citation analysis, and burst analysis of countries/regions, institutions, journals, authors, references, and keywords.ResultsThis paper studied a total of 5,301 papers involving 107 countries/regions, with China having the highest number of publications (898 papers) and the United States having the highest centrality (0.62). Burst analysis of journal citations revealed the emergence of many new journals (e.g., Antioxidants-Basel, Front Endocrinol) after 2021, indicating continuous expansion and development in this field. Cluster analysis of co-cited references and co-occurring keywords divided the research into areas such as oxidative stress and male infertility, oxidative stress level detection, and antioxidants. The keywords associated with research hotspots shifted from oxidative stress detection, sperm DNA damage, apoptosis, and redox potential to DNA methylation, embryonic development, infection, polyunsaturated fatty acids, and antioxidants.ConclusionBibliometric methods provide an intuitive reflection of the development process in the field of oxidative stress and male fertility, as well as the analysis of research hotspots in different periods. Research on oxidative stress and embryonic development, as well as antioxidant health management, may become hotspots in future research.
Early ultrasonic vocalization deficits and related thyroarytenoid muscle pathology in the transgenic TgF344-AD rat model of Alzheimer’s disease
Authors: Rudisch Denis Michael , Krasko Maryann N. , Barnett David G. S. , Mueller Kimberly D. , Russell John A. , Connor Nadine P. , Ciucci Michelle R. 
Published: January 2024

BackgroundAlzheimer’s disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and aggregation of β-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life. Because clinical diagnosis occurs in the mid-stage of the disease, characterizing the prodrome and early stages in humans is currently challenging. To overcome these challenges, we use the validated TgF344-AD (F344-Tg(Prp-APP, Prp-PS1)19/Rrrc) transgenic rat model that manifests cognitive, behavioral, and neuropathological dysfunction akin to AD in humans.ObjectivesThe overarching goal of our work is to test the central hypothesis that pathology and related behavioral deficits such as communication dysfunction in part manifest in the peripheral nervous system and corresponding target tissues already in the early stages. The primary aims of this study are to test the hypotheses that: (1) changes in ultrasonic vocalizations (USV) occur in the prodromal stage at 6 months of age and worsen at 9 months of age, (2) inflammation as well as AD-related pathology can be found in the thyroarytenoid muscle (TA) at 12 months of age (experimental endpoint tissue harvest), and to (3) demonstrate that the TgF344-AD rat model is an appropriate model for preclinical investigations of early AD-related vocal deficits.MethodsUSVs were collected from male TgF344-AD (N = 19) and wildtype (WT) Fischer-344 rats (N = 19) at 6 months (N = 38; WT: n = 19; TgF344-AD: n = 19) and 9 months of age (N = 18; WT: n = 10; TgF344-AD: n = 8) and acoustically analyzed for duration, mean power, principal frequency, low frequency, high frequency, peak frequency, and call type. RT-qPCR was used to assay peripheral inflammation and AD-related pathology via gene expressions in the TA muscle of male TgF344-AD rats (n = 6) and WT rats (n = 6) at 12 months of age.ResultsThis study revealed a significant reduction in mean power of ultrasonic calls from 6 to 9 months of age and increased peak frequency levels over time in TgF344-AD rats compared to WT controls. Additionally, significant downregulation of AD-related genes Uqcrc2, Bace2, Serpina3n, and Igf2, as well as downregulation of pro-inflammatory gene Myd88 was found in the TA muscle of TgF344-AD rats at 12 months of age.DiscussionOur findings demonstrate early and progressive vocal deficits in the TgF344-AD rat model. We further provide evidence of dysregulation of AD-pathology-related genes as well as inflammatory genes in the TA muscles of TgF344-AD rats in the early stage of the disease, confirming this rat model for early-stage investigations of voice deficits and related pathology.
Association between gastroesophageal reflux disease and stroke: a bidirectional Mendelian randomization study
Authors: Meng Decheng , Zhang Xin , Yu Wenfei , Yin Guoliang , Chen Suwen , Liu Hongshuai , Wang Linya , Zhang Fengxia 
Published: January 2024

ObjectiveSome previous studies have suggested a potential link between stroke and gastroesophageal reflux disease (GERD). We used a two-sample bidirectional Mendelian randomization (MR) method to explore the causal relationship between stroke and GERD.DesignSummary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. Single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for stroke (n = 446,696) and its common subtypes ischemic stroke (IS) (n = 440,328), large vessel stroke (LVS) (n = 410,484), small vessel stroke (SVS) (n = 198,048), and cardioembolic stroke (CES) (n = 413,304) were obtained from the MEGASTROKE consortium. The data on intracerebral hemorrhage (ICH) (n = 721,135) come from the UK Biobank. Instrumental variables (IVs) for lacunar stroke (LS) (n = 474,348) and GERD (n = 602,604) were screened from publicly available genetic summary data. The inverse variance weighted (IVW) method was used as the main MR method. Pleiotropy was detected by the MR-Egger intercept test, MR pleiotropy residual sum and outlier, and leave-one-out analysis. Cochran Q statistics were used as supplements to detect pleiotropy.ResultsWe found that GERD can causally increase the risk of stroke [IVW odds ratio (OR): 1.22, 95% confidence interval (CI): 1.13–1.32, p = 1.16 × 10−6] and its common subtypes IS (OR: 1.19, 95% CI: 1.10–1.30, p = 3.22 × 10−5), LVS (OR: 1.49, 95% CI: 1.21–1.84, p = 1.47 × 10−4), and LS (OR: 1.20, 95% CI: 1.001–1.44, p = 0.048). Several important risk factors for stroke have also been implicated in the above causal relationship, including type 2 diabetes, sleep apnea syndrome, high body mass index, high waist-to-hip ratio, and elevated serum triglyceride levels. In reverse MR analysis, we found that overall stroke (OR: 1.09, 95% CI: 1.004–1.19, p = 0.039) and IS (OR: 1.10, 95% CI: 1.03–1.17, p = 0.007) have the causal potential to enhance GERD risk.ConclusionThis MR study provides evidence supporting a causal relationship between GERD and stroke and some of its common subtypes. We need to further explore the interconnected mechanisms between these two common diseases to better prevent and treat them.
Digital assessment of speech in Huntington disease
Authors: Nunes Adonay S. , Pawlik Meghan , Mishra Ram Kinker , Waddell Emma , Coffey Madeleine , Tarolli Christopher G. , Schneider Ruth B. , Dorsey E. Ray , Vaziri Ashkan , Adams Jamie L. 
Published: January 2024

BackgroundSpeech changes are an early symptom of Huntington disease (HD) and may occur prior to other motor and cognitive symptoms. Assessment of HD commonly uses clinician-rated outcome measures, which can be limited by observer variability and episodic administration. Speech symptoms are well suited for evaluation by digital measures which can enable sensitive, frequent, passive, and remote administration.MethodsWe collected audio recordings using an external microphone of 36 (18 HD, 7 prodromal HD, and 11 control) participants completing passage reading, counting forward, and counting backwards speech tasks. Motor and cognitive assessments were also administered. Features including pausing, pitch, and accuracy were automatically extracted from recordings using the BioDigit Speech software and compared between the three groups. Speech features were also analyzed by the Unified Huntington Disease Rating Scale (UHDRS) dysarthria score. Random forest machine learning models were implemented to predict clinical status and clinical scores from speech features.ResultsSignificant differences in pausing, intelligibility, and accuracy features were observed between HD, prodromal HD, and control groups for the passage reading task (e.g., p &lt; 0.001 with Cohen’d = −2 between HD and control groups for pause ratio). A few parameters were significantly different between the HD and control groups for the counting forward and backwards speech tasks. A random forest classifier predicted clinical status from speech tasks with a balanced accuracy of 73% and an AUC of 0.92. Random forest regressors predicted clinical outcomes from speech features with mean absolute error ranging from 2.43–9.64 for UHDRS total functional capacity, motor and dysarthria scores, and explained variance ranging from 14 to 65%. Montreal Cognitive Assessment scores were predicted with mean absolute error of 2.3 and explained variance of 30%.ConclusionSpeech data have the potential to be a valuable digital measure of HD progression, and can also enable remote, frequent disease assessment in prodromal HD and HD. Clinical status and disease severity were predicted from extracted speech features using random forest machine learning models. Speech measurements could be leveraged as sensitive marker of clinical onset and disease progression in future clinical trials.
Case report: Movement analysis in oncological rehabilitation: proposal of a kinematic and surface electromyographic protocol in breast oncology
Authors: Bongiorno Giulia , Tomasi Andrea , Vigni Giulio , Rizzardo Alessandro , Biancuzzi Helena , Dal Mas Francesca , Bednarova Rym , Miceli Luca 
Published: January 2024

IntroductionBreast cancer disease often affects the ipsilateral shoulder joint, with pain and joint limitation. Proper pain management, which can be obtained using, for example, pulsed radiofrequency of the suprascapular nerve, can help the physiotherapist mitigate patient pain. The modern technologies of kinematic analysis and surface electromyography of movement analysis can give further support in building a personalized rehabilitation program, based on the quantitative study of movement, in this case of the upper limb.MethodsA brief case report was conceived to develop and test the evolution of a shoulder joint analysis protocol based on an inertial accelerometer and non-invasive surface electromyography.ResultsAn analysis algorithm was defined to adapt to the needs of patients operated on at the breast based on a kinematic component (ROM - range of movement - and Jerk index) and an electromyographic one (study of muscle behavior in groups of four). The coactivations were also evaluated, both as an average value and in graphical form, to offer the physiotherapist a complete overview of the movement of the upper limb.DiscussionThe promising protocol results underline its strengths, including the simplicity of use, combined with the reduced time required for processing the reports and the portability of the PC-sensors complex, making these analyses potentially valuable for patient care.
Screening and surveillance of esophageal cancer by magnifying endoscopy with narrow band imaging improves the survival of hypopharyngeal cancer patients
Authors: Chung Chen-Shuan , Wu Chia-Yun , Lin Yu-Hsuan , Lo Wu-Chia , Cheng Ping-Chia , Hsu Wan-Lun , Liao Li-Jen 
Published: January 2024

IntroductionPatients with head and neck cancer may develop a second primary neoplasm (SPN) of the esophagus due to field cancerization. This study investigated the impacts of esophageal cancer screening using magnifying endoscopy with narrow-band imaging (ME-NBI) on the outcomes of hypopharyngeal cancer patients.MethodsPatients with hypopharyngeal cancer diagnosed from 2008 to 2021 in a tertiary hospital were reviewed retrospectively. Screening and surveillance using ME-NBI examination of the esophagus were divided into three patterns: (1) ME-NBI never performed or more than 6 months after diagnosis of index primary hypopharyngeal cancer, (2) ME-NBI within 6 months only, and (3) ME-NBI within 6 months and regular surveillance.ResultsA total of 261 were reviewed and 21 (8%) patients were in stage I, 20 (8%) in stage II, 27 (10%) in stage III, 116 (44%) in stage IVA, 65 (25%) in stage IVB, and 12 (5%) in stage IVC. Sixty-seven (26%) patients had SPN (50 esophagus, 10 oral cavity, 3 oropharynx, 2 nasopharynx, 1 larynx and 1 lung). Among esophageal SPN, 35 (70%) and 15 (30%) patients developed synchronous and metachronous neoplasia, respectively. In multivariate Cox regression analysis, advanced stages III and IV (compared with stages I and II, HR: 1.86, 1.18-2.95, p=0.008), ME-NBI examination of the esophagus received within 6 months and regular surveillance (HR: 0.53, 0.36-0.78, p=0.001) were independent factors affecting the overall survival of patients with hypopharyngeal cancer.DiscussionOur findings demonstrated that screening and surveillance of esophageal SPN by ME-NBI improves the survival of patients with hypopharyngeal cancer.
Evaluating autobiographical skills and their relationship with suggestibility in children: development and validation of the Children Recalling Autobiographical Memory
Authors: Vagni Monia , Giostra Valeria , Simione Luca 
Published: January 2024

IntroductionAutobiographical narrative skills and resistance to suggestibility factors are central aspects in children’s testimony. While the assessment of suggestibility relies on standardized questionnaire, no such an instrument exists to reliably assess autobiographical skills in children. This aspect is further important when considering that the development of such skills seems to be related to the suggestibility, that is, suggestibility would be reduced in presence of higher autobiographical skills. However, no direct test of this relationship is available in literature, also due to the lack of quantitative instruments for assessing autobiographical skills.MethodsTo fulfill both these methodological and theoretical issues, in this study a new tool was validated to measure the main autobiographical narrative skills (Where, What, When, Who, and How) in relation to both Retrospective Memory and Prospective Memory: the Children Recalling Autobiographical Memory (CRAM). We recruited a sample of 321 children aged 7–16 years.Results and discussionThe result of the EFA analysis showed one-factor model, and revealed also good fit indexes and internal reliability. After validating this new tool, we further used it to test our main hypothesis, that is, children with higher autobiographical memory skills were less vulnerable to interrogative suggestibility as assessed by Gudjonsson Suggestibility Scale 2 (GSS2). A hierarchical linear regression model showed a reduction in suggestibility with age and level of autobiographical skills. Moreover, the level of such skills moderate the effect of age, such as only in presence of high or moderate level of autobiographical skills the age significantly reduces the level of suggestibility.
The Effectiveness and Cost-Effectiveness of Community Diagnostic Centres: A Rapid Review
Authors: Wale Alesha , Okolie Chukwudi , Everitt Jordan , Hookway Amy , Shaw Hannah , Little Kirsty , Lewis Ruth , Cooper Alison , Edwards Adrian 
Published: January 2024

Objectives: To examine the effectiveness of community diagnostic centres as a potential solution to increasing capacity and reducing pressure on secondary care in the UK.Methods: A comprehensive search for relevant primary studies was conducted in a range of electronic sources in August 2022. Screening and critical appraisal were undertaken by two independent reviewers. There were no geographical restrictions or limits to year of publication. A narrative synthesis approach was used to analyse data and present findings.Results: Twenty primary studies evaluating twelve individual diagnostic centres were included. Most studies were specific to cancer diagnosis and evaluated diagnostic centres located within hospitals. The evidence of effectiveness appeared mixed. There is evidence to suggest diagnostic centres can reduce various waiting times and reduce pressure on secondary care. However, cost-effectiveness may depend on whether the diagnostic centre is running at full capacity. Most included studies used weak methodologies that may be inadequate to infer effectiveness.Conclusion: Further well-designed, quality research is needed to better understand the effectiveness and cost-effectiveness of community diagnostic centres.