bluuebunny/crossref_metadata_2025_split huggingface dataset:
The competency index for clinical research professionals: a potential tool for competency-based clinical research academic program evaluation
Authors: Jones Carolynn Thomas , Liu Xin , Hornung Carlton A. , Fritter Jessica , Neidecker Marjorie V. 
Published: March 2024

BackgroundAccreditation of graduate academic programs in clinical research requires demonstration of program achievement of Joint Task Force for Clinical Trial Competence-based standards. Evaluation of graduate programs include enrollment, student grades, skills-based outcomes, and completion rates, in addition to other measures. Standardized measures of competence would be useful.MethodsWe used the Competency Index for Clinical Research Professionals (CICRP), in a separate-sample pretest-posttest study to measure self-confidence or self-efficacy in clinical research competency comparing cohorts of students entering and completing a master’s degree program in clinical research across three semesters (summer 2021 – spring 2022). CICRP is a 20-item Likert scale questionnaire (0 = Not at all confident; 10 = extremely confident).ResultsThe study sample of 110 students (54 in the entry course, 56 in the exit course) showed overall 80.9% entered the program with only a baccalaureate degree and 55.5% had no prior experience in managing clinical trial research. Cronbach alpha for the instrument showed a high level of content validity (range 0.93–0.98). Median CICRP item rating range at entry was [1, 6] and at exit [7, 10]. Mean CICRP total score (sum of 20 items) at entry was 72.7 (SD 41.9) vs. 167.0 (SD 21.1) at exit (p &lt; 0.001). Mean total score at program entry increased with increasing years of clinical trial management experience but attenuated at program exit.ConclusionThis is the first use of the CICRP for academic program evaluation. The CICRP may be a useful tool for competency-based academic program evaluation, in addition to other measures of program excellence.
Case report: A novel COL3A1 variant in a Colombian patient with isolated cerebrovascular involvement in vascular Ehlers–Danlos syndrome
Authors: Valencia-Cifuentes Valeria , Sinisterra-Díaz Stiven Ernesto , Quintana-Peña Valentina , Folleco Edgar , Nastasi-Catanese José A. , Pachajoa Harry , Fernández-Cubillos Juan P. 
Published: March 2024

IntroductionTo date, approximately 600 unique pathogenic variants have been reported in COL3A1 associated with vascular Ehlers–Danlos syndrome (vEDS). The objective of this study was to describe a patient with a novel variant in COL3A1 associated with vEDS.Case reportWe describe the clinical history and thorough phenotyping of a patient with brain aneurysms and identified a novel pathogenic variant in COL3A1. This male patient reported transient focal neurologic symptoms. Physical examination showed abnormal atrophic scarring, horizontal stretch marks under the arms, and an acrogeric appearance of the skin of the hands and feet. Brain imaging revealed extensive dilation of both internal carotids and the vertebrobasilar system. Molecular analysis identified a variant in COL3A1 (NM_000090.4):c.3058G&gt;T p.(Gly1020Cys), which was classified as likely pathogenic. Currently, the patient has never had an event concerning dissection/rupture of tissues that could be affected in this condition.ConclusionThis report demonstrates that exhaustive evaluation with clinical and genetic approaches should be considered in patients with vascular abnormalities. vEDS has a variable clinical presentation and often goes unrecognized, even though it is related to life-threatening complications and a shortened life expectancy. Diagnosis confirmed by genetic testing is crucial to determining appropriate surveillance, prevention, treatment, and genetic counseling.
Impact of Lianhua Qingwen on viral shedding in omicron mild/asymtomatic patients: a real-world study
Authors: Gai Xiaoyan , Yan Changjian , Wu Chaoling , Duan Zhonghui , Fan Jiarun , Yuan Shengren , Yang Ping , Bao Fang , Jing Hongmei , Cai Chao , Ma Yingmin , Zhang Weilong , Sun Yongchang 
Published: March 2024

BackgroundLianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context.MethodsWe conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset.ResultsThe study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations.ConclusionNo statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW’s efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.
Burnout among diabetes specialist registrars across the United Kingdom in the post-pandemic era
Authors: Agha Adnan , Basu Ansu , Anwar Eram , Hanif Wasim 
Published: March 2024

IntroductionBurnout syndrome is a condition resulting from chronic work-related stress exposure and can be identified by the presence of one or more of the three classic dimensions of burnout, i.e., emotional exhaustion, depersonalization, and lack of personal accomplishment, which negatively impact physician health and productivity.ObjectiveThis study aimed to identify burnout among Diabetes and Endocrinology Specialty Training Registrars (DStRs) across the United Kingdom.Design/settingIt was a Cross-sectional observational study after ethical approval ERSC_2022_1166, utilizing the gold standard Maslach Burnout Inventory to measure burnout syndrome, and to determine self-reported stressors and compare them with the results of our previous survey in 2018.ParticipantsOver 430 DStRs across the United Kingdom were invited electronically through their deanery representatives and specialty training bodies.ResultsUsing Google Forms™ to gather data, we were able to collect 104 completed surveys. Results revealed that 62.5% (n = 65) of participants have burnout (5% increase from the previous survey in 2018), 38.6% (n = 40) have high emotional exhaustion, and 44.2% (n = 46) feel a lack of personal accomplishment. “General Internal Medicine specific workload” was the most common self-reported stressor reported by 87.5% (n = 91) of participants, whereas bullying/harassment and discrimination at work were reported by 35.6% (n = 37) and 30.77% (n = 32) of participants, respectively. Using multivariable logistic regression model, personal stress (OR, 4.00; 95% CI, 1.48–10.86; p = 0.006) had significant, while Bullying/harassment (OR, 3.75; 95% CI, 0.93–15.12; p = 0.063) had marginal impact on the presence of burnout.ConclusionDiabetes and Endocrinology Specialty Training Registrars frequently experience burnout syndrome, which has increased over the last 4 years. However, organizational changes can help identify, prevent, and treat physician burnout.Trial registrationNCT05481021 available at https://ichgcp.net/clinical-trials-registry/NCT05481021.
Genomic and biological control of Sclerotinia sclerotiorum using an extracellular extract from Bacillus velezensis 20507
Authors: Cheng Yunqing , Lou Hanxiao , He Hongli , He Xinyi , Wang Zicheng , Gao Xin , Liu Jianfeng 
Published: March 2024

IntroductionSclerotinia sclerotiorum is a known pathogen that harms crops and vegetables. Unfortunately, there is a lack of effective biological control measures for this pathogen. Bacillus velezensis 20507 has a strong antagonistic effect on S. Sclerotiorum; however, the biological basis of its antifungal effect is not fully understood.MethodsIn this study, the broad-spectrum antagonistic microorganisms of B. velezensis 20507 were investigated, and the active antifungal ingredients in this strain were isolated, purified, identified and thermal stability experiments were carried out to explore its antifungal mechanism.ResultsThe B. velezensis 20507 genome comprised one circular chromosome with a length of 4,043,341 bp, including 3,879 genes, 185 tandem repeats, 87 tRNAs, and 27 rRNAs. Comparative genomic analysis revealed that our sequenced strain had the closest genetic relationship with Bacillus velezensis (GenBank ID: NC 009725.2); however, there were significant differences in the positions of genes within the two genomes. It is predicted that B. velezensis 20507 encode 12 secondary metabolites, including difficidin, macrolactin H, fengycin, surfactin, bacillibactin, bacillothiazole A-N, butirosin a/b, and bacillaene. Results showed that B. velezensis 20507 produced various antagonistic effects on six plant pathogen strains: Exserohilum turcicum, Pyricularia oryzae, Fusarium graminearum, Sclerotinia sclerotiorum, Fusarium oxysporum, and Fusarium verticillioides. Acid precipitation followed by 80% methanol leaching is an effective method for isolating the antifungal component ME80 in B. velezensis 20507, which can damage the membranes of S. sclerotiorum hyphae and has good heat resistance. Using high-performance liquid chromatography, and Mass Spectrometry analysis, it is believed that fengycin C72H110N12O20 is the main active antifungal substance.DiscussionThis study provides new resources for the biological control of S. Sclerotiorum in soybeans and a theoretical basis for further clarification of the mechanism of action of B. velezensis 20507.
Adaptive fuzzy control for tendon-sheath actuated bending-tip system with unknown friction for robotic flexible endoscope
Authors: Ren Fan , Wang Xiangyu , Yu Ningbo , Han Jianda 
Published: March 2024

IntroductionThe tendon-sheath actuated bending-tip system (TAB) has been widely applied to long-distance transmission scenes due to its high maneuverability, safety, and compliance, such as in exoskeleton robots, rescue robots, and surgical robots design. Due to the suitability of operation in a narrow or tortuous environment, TAB has demonstrated great application potential in the area of minimally invasive surgery. However, TAB involves highly non-linear behavior due to hysteresis, creepage, and non-linear friction existing on the tendon routing, which is an enormous challenge for accurate control.MethodsConsidering the difficulties in the precise modeling of non-linearity friction, this paper proposes a novel fuzzy control scheme for the Euler-Lagrange dynamics model of TAB for achieving tracking performance and providing accurate friction compensation. Finally, the asymptotic stability of the closed-loop system is proved theoretically and the effectiveness of the controller is verified by numerical simulation carried out in MATLAB/Simulink.ResultsThe desired angle can be reached quickly within 3 s by adopting the proposed controller without overshoot or oscillation in Tracking Experiment, demonstrating the regulation performance of the proposed control scheme. The proposed method still achieves the desired trajectory rapidly and accurately without steady-state errors in Varying-friction Experiment. The angle errors generated by external disturbances are &lt; 1 deg under the proposed controller, which returns to zero in 2 s in Anti-disturbance Experiment. In contrast, comparative controllers take more time to be steady and are accompanied by oscillating and residual errors in all experiments.DiscussionThe proposed method is model-free control and has no strict requirement for the dynamics model and friction model. It is proved that advanced tracking performance and real-time response can be guaranteed under the presence of unknown bounded non-linear friction and time-varying non-linear dynamics.
The identification of a novel shared therapeutic target and drug across all insulin-sensitive tissues under insulin resistance
Authors: Xu Jinyuan , Zhu Lilin , Xu Jie , Lin Kailong , Wang Juan , Bi Yan-long , Xu Guo-Tong , Tian Haibin , Gao Furong , Jin Caixia , Lu Lixia 
Published: March 2024

BackgroundTo identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs.MethodsThree datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was carried out to determine the “most significant trait-related genes” (MSTRGs). Enrichment analysis and PPI network were performed to find common features and novel hub genes in ISTs. The shared genes of DEGs and genes between DEGs and MSTRGs across four ISTs were identified as key IR therapeutic target. The Attie Lab diabetes database and obese rats were used to verify candidate genes. A medical drug-gene interaction network was conducted by using the Comparative Toxicogenomics Database (CTD) to find potential targeted drugs. The candidate drug was validated in Hepa1-6 cells.ResultsLipid metabolic process, mitochondrion, and oxidoreductase activity as common features were enriched from ISTs under an obese context. Thirteen shared genes (Ubd, Lbp, Hp, Arntl, Cfd, Npas2, Thrsp., Tpx2, Pkp1, Sftpd, Mthfd2, Tnfaip2, and Vnn3) of DEGs across ISTs were obtained and confirmed. Among them, Ubd was the only shared gene between DEGs and MSTRGs across four ISTs. The expression of Ubd was significantly upregulated across four ISTs in obese rats, especially in the liver. The IR Hepa1-6 cell models treated with dexamethasone (Dex), palmitic acid (PA), and 2-deoxy-D-ribose (dRib) had elevated expression of Ubd. Knockdown of Ubd increased the level of p-Akt. A lowing Ubd expression drug, promethazine (PMZ) from CTD analysis rescued the decreased p-Akt level in IR Hepa1-6 cells.ConclusionThis study revealed Ubd, a novel and shared IR molecular signature across four ISTs, as an effective biomarker and provided new insight into the mechanisms of IR. PMZ was a candidate drug for IR which increased p-Akt level and thus improved IR by targeting Ubd and downregulation of Ubd expression. Both Ubd and PMZ merit further clinical translational investigation to improve IR.
Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy
Authors: Rajeswaren Vivian , Wagner Brandie D. , Patnaik Jennifer L. , Mandava Naresh , Mathias Marc T. , Manoharan Niranjan , de Carlo Forest Talisa E. , Gnanaraj Ramya , Lynch Anne M. , Palestine Alan G. ,   the University of Colorado Retina Research Group
Published: March 2024

IntroductionTumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD.MethodsWe examined plasma levels of TNF-α and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-α and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers.ResultsThere were 97 GA, 199 iAMD patients and 139 controls. TNF-α was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p&lt;0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p&lt;0.01. There was a significant positive correlation between TNF-α and VEGF in GA (0.46, p&lt;0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and VEGF in any group.DiscussionThese findings suggest TNF-α and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and VEGF may function as systemic biomarkers for disease development.
Reliability and modality analysis of patellar height measurement in pediatric knee
Authors: Kwak Yoon Hae , Park Soo-Sung , Huser Aaron J. , Kim Keunho , Koh Yong-Gon , Nam Ji-Hoon , Kang Kyoung-Tak 
Published: March 2024

IntroductionVarious measurement methods and imaging technique are in use to measure patellar height in pediatric patients. However, there is no gold standard as to which measurement method and modality are the most reliable for pediatric patients. Therefore, the aim of this study was to determine the inter-observer reliability, intra-observer reliability, and applicability of various patellar height measurement methods in pediatric knee. Additionaly, we analyzed the reliability across different imaging modalities.MethodsTotal 450 pediatric patients (age: 5–18 years) were evaluated using lateral knee radiographs and magnetic resonance imaging (MRI). The patellar height ratios were measured using five methods. Five methods were Insall–Salvati (IS), Koshino–Sugimoto (KS), Blackburne–Peel (BP), modified Insall–Salvati (MIS), and Caton–Deschamps (CD). The patients were categorized into two age groups: P (ages 5–13) and Q (ages 14–18). Each measurement was conducted twice by two raters. The intra-observer reliability, inter-observer reliability and inter-modality reliability were calculated. In addition, applicability was defined as the possibility to apply each measurement method to each age group.ResultsThe KS method showed the highest inter-observer reliability and intra-observer reliability when using MRI for both age groups. The inter-observer reliability and intra-observer reliability of the IS for lateral knee radiographs was highest among all observers for group Q. The CD method showed the highest inter-observer reliability in group P, while the KS showed the highest intra-observer reliability in group P using lateral radiographs. The KS method showed the highest inter-modality reliability in group P, while the IS showed the highest inter-modality reliability in group Q. The KS method was applicable to all patients when using lateral knee radiography, and the IS method was applicable to all patients when using MRI.ConclusionsOur results show that the reliability of various measurement method and imaging technique differed based on pediatric knee age group when measuring patellar height. Therefore, in the case of pediatric patients, reliability measurement methods and imaging techniques according to the patient's age should be applied.
Optimum programmed intermittent epidural bolus interval time of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL: a randomized controlled trial
Authors: Mei Zhong , Wang Qingtao , Song Shaobo , Lu Wenying , Yu Jing 
Published: March 2024

Background:The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of manual and PCEA boluses. We, therefore, conducted this study to determine the effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL in 90% of subjects (EI90), without the use of patient-controlled epidural analgesia (PCEA).Methods:A total of 80 subjects were included in the final statistical analysis from 23 August 2022 to 22 November 2022. The subjects were randomly assigned to one of four different PIEB time intervals: 40, 50, 60, and 70 min (groups 40, 50, 60, and 70), respectively. The primary outcome was the effective epidural labor analgesia, defined as no use of PCEA bolus or a manual bolus until the end of the first stage of labor or within 6 hours after loading dose administration. The PIEB EI90 (95% CI) between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL was estimated using probit regression.Results:The effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL in 90% of subjects without the use of PCEA was 45.4 (35.5–50.5) minutes using probit regression. No statistical differences were found in the proportion of subjects with Bromage score &gt; 0, hypotension, pruritus, nausea, and vomiting between groups. However, the highest sensory block (pinprick) in the 40-min group was significantly higher than that in the other groups.Conclusion:The estimated value for EI90 for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5–50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice.
Hyper-Kamiokande construction status and prospects
Authors: Abe Ko , Tanaka Hide-Kazu 
Published: March 2024

The Hyper-Kamiokande (Hyper-K) project is the world’s leading international neutrino and nucleon decay experiment comprising a next-generation underground water Cherenkov detector and upgraded Japan Proton Accelerator Research Complex (J-PARC) neutrino beam. It will provide an enormous potential to discover the leptonic charge-parity violation, to investigate the Grand Unified Theory by proton decay exploration, and to determine the neutrino mass ordering. Further, Hyper-K will significantly enhance the capability to observe solar neutrinos and neutrinos from other astronomical sources in comparison with its predecessors. After the budget approval in January 2020, the Hyper-K project officially began, and the operation is expected to start in 2027. The excavations of a 2.0 km long access tunnel and the tunnels for the detector facility have been completed. In October 2022 it was started the excavation of one of the world’s largest underground caverns to suite the HK detector. This article discusses the status and the prospects of the Hyper-K detector construction.