bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light and shade of multigene panel testing for hereditary cancer: Examples from the real world
Authors: Innella Giovanni , Ferrari Simona , Miccoli Sara , Turchetti Daniela 
Published: November 2024

Background: MultiGene Panel Testing (MGPT) allows for simultaneous analysis of multiple cancer-related genes, enabling the identification of pathogenic variants in genes beyond those that would be analyzed based on a specific phenotype. However, a relevant fraction of variants so identified has little or no clinical utility, raising the need for guidance in selecting genes to include in panels and for interpretation of the results. Methods: Taking advantage of seven real paradigmatic cases, we analyze some of the scenarios where MGPT constitutes a meaningful advantage for diagnosis, as well as situations where panel use increases the risk of misinterpretation or complicates result communication and management. Results: The use of MGPT facilitates prompt diagnosis in carriers of variants in rare genes (such as NTHL1), which would be diagnosed at a later stage if using a step-wise approach, as well as in carriers of bi-allelic variants (for instance in BRCA or MMR genes) leading to atypical phenotypes. Conversely, finding variants in moderate penetrance genes, such as ATM and CHEK2, may complicate interpretation and clinical management. Furthermore, for some of the genes included in MGPT, for instance NBN, the association with cancer risk has been questioned, leading to potentially misleading results. Conclusion: Taken together, the cases here described provide some examples of the benefits, as well as risks, involved by the use of MGPT, which may increase awareness among users and reinforce the need for establishing clear recommendations on genes to be included and management of the results.
The fascicular anatomy of the sciatic nerve may not influence the muscular activity of the biceps femoris after applying percutaneous electrical nerve stimulation: a randomized clinical trial
Authors: Páez-Rodríguez Joaquín , Olivo-Ruiz Ismael , Romero-Morales Carlos , De-la-Cruz-Torres Blanca 
Published: November 2024

Background: Electrical nerve stimulation is an effective therapeutic tool in the field of rehabilitation for the management of musculoskeletal conditions. Objective: To analyze the muscle activity of the short head of the biceps femoris (SHBF) and long head of the biceps femoris (LHBF) after the application of percutaneous electrical nerve stimulation to the common fibular versus tibial nerve compartment of the sciatic nerve. Methods: Thirty-eight healthy subjects received electrical stimulation (asymmetric biphasic rectangular waveforms) through a needle in the sciatic nerve. The sample was divided into two groups in which the technique was applied to the lateral compartment versus medial compartment of the nerve, respectively. The protocol used included 5 s of stimulation at a frequency of 100 Hz and a phase duration of 350 ms, followed by 55 s of rest, for 5 min. The electrical activity of the SHBF and LHBF and the muscle strength of the knee flexors was assessed by surface electromyography during isometric knee flexion in the prone position. Results: Neither group showed significant changes (p > 0.05) in any variable after the intervention compared with baseline values. Similarly, there were no significant differences in any of the study variables when comparing both groups (p > 0.05). Conclusion: Selective stimulation of the sciatic nerve by percutaneous electrical nerve stimulation had no measurable effects on muscle activity in the SHBF or LHBF, regardless of the approach applied. Trial registration number: NCT05549700 (ClinicalTrials.gov).
Clinical Outcomes Following Low-Dose Second-Generation “Ranger” Drug-Coated Balloon Angioplasty for Femoropopliteal Artery Disease
Authors: Soga Yoshimitsu , Takahara Mitsuyoshi , Iida Osamu , Kawasaki Daizo , Tobita Kazuki , Fujihara Masahiko 
Published: November 2024

Purpose: To reveal the rate of 1-year freedom from restenosis and to determine the factors associated with the restenosis risk in femoropopliteal (FP) lesions treated with a Ranger drug-coated balloon (DCB) in real-world clinical settings. Methods: This multicenter, prospective observational study enrolled 1131 patients and 1453 de novo or restenotic FP lesions (mean age=75±9 years; female=35.3%, mean lesion length=19.2±16.0 cm; chronic total occlusion [CTO]=33.7%; severe calcification=33.7%) that underwent successful Ranger DCB angioplatsy between March 2021 and December 2022. Results: The primary endpoint was 1-year freedom from restenosis and its associated factors. Bail-out stenting was performed in 5.3%. During the follow-up, restenosis was detected in 249 cases. Freedom from restenosis by the Kaplan-Meier analysis was estimated to be 85.2% and 81.0% at 12 and 14 months, whereas freedom from target lesion revascularization (TLR) was 91.7% and 90.0% at 12 and 14 months. The patterns of restenosis were focal (39.2%), tandem (12.3%), diffuse (17.2%), and occlusive (31.3%). Independent risk factors of restenosis were female sex, diabetes mellitus, no runoff, history of revascularization, lesion length ≥25 cm, and CTO. Conclusions: Our study demonstrated that 1-year freedom from restenosis after Ranger DCB for FP lesions in a real-world clinical setting was acceptable. Independent predictors of restenosis were female gender, diabetes mellitus, no runoff, history of revascularization, lesion length ≥25 cm, and CTO. Clinical Impact Our study demonstrated the true performance of Ranger DCB in real-world practice, with a very low rate of bail-out stenting and no use of atherectomy devices. In addition, it also elucidated morphologies associated with restenosis and the risk factors for restenosis after DCB. Freedom from re-stenosis and TLR at 1-year after Range DCB angioplasty was 84.5% and 91.5%. Two thirds of restenosis had a non-occlusive pattern, and independent predictors of restenosis were female gender, diabetes mellitus, no runoff, history of revascularization, lesion length ≥25 cm, and CTO.
Sonography-Guided Endovascular Retrieval of Fractured Angiocatheter in Brachial Artery: A Case Report
Authors: Chen Yen-Yang 
Published: November 2024

Background The insertion of an angiocatheter into a peripheral artery for continuous hemodynamic monitoring is a widely employed clinical practice. Fracture of a angiocatheter retained in an artery, though infrequent, presents a challenge in clinical management, particularly in critically ill patients. Surgical exploration for retrieval is generally required, as fluoroscopy-guided endovascular methods are precluded due to the radiolucency of catheters. Case report This case report demonstrates the successful retrieval of a fractured catheter from the brachial artery of an 85-year-old critically ill patient through the utilization of endovascular techniques guided by sonography. Key considerations include selecting an appropriate snare system diameter and ensuring real-time sonographic visualization to prevent displacement of the fractured segment. Conclusion This case illustrates the feasibility and safety of sonography-guided endovascular retrieval as an alternative to surgical intervention for fractured angiocatheters. The proposed strategy demonstrates its applicability in similar clinical scenarios.
Effectiveness and safety outcomes after long-term (54 weeks) vedolizumab therapy for Crohn’s disease: a prospective, real-world observational study including patient-reported outcomes (POLONEZ II)
Authors: Liebert Ariel , Kłopocka Maria , Michalak Agata , Cichoz-Lach Halina , Talar-Wojnarowska Renata , Domz.ał-Magrowska Danuta , Konecki Łukasz , Filipiuk Aleksandra , Krogulecki Michał , Kopertowska-Majchrzak Maria , Stawczyk-Eder Kamila , Waszak Katarzyna , Eder Piotr , Zagórowicz Edyta , Smoła Izabela , Wojciechowski Krzysztof , Drygała Szymon 
Published: November 2024

Background:The Crohn’s Disease (CD) Activity Index (CDAI), Inflammatory Bowel Disease (IBD) Questionnaire (IBDQ), and IBD-Fatigue (IBD-F) scale are useful patient-reported outcome (PRO) tools for assessing the treatment benefits of vedolizumab (VDZ) beyond clinical trial endpoints in patients with CD.Objectives:To assess clinical response, clinical remission, steroid-free remission, changes from baseline for PROs, and safety in a real-world cohort of patients with moderate-to-severe active CD treated with VDZ.Design:POLONEZ II was a multicenter, observational, prospective study across 10 Polish centers from April 2020 to October 2023 for 54 weeks in patients with CD eligible for reimbursed VDZ.Methods:Primary endpoints at week 54 (W54) were clinical response (⩾70-point reduction in CDAI and >25% reduction vs baseline), remission (CDAI score ⩽150), and steroid-free remission. Other outcomes were changes in PROs (CDAI score and health-related quality of life) and safety. Kaplan–Meier survival analyses were performed.Results:Of 98 patients with CD, the mean age was 35.2 years, 57.1% were male, and 72.4% had an ileocolonic disease. At W54 ( n = 98), 63.3% of patients achieved clinical response, 48.0% remission, and 36.0% steroid-free remission. The durability of clinical response, remission, and steroid-free remission (W14–W54) were 68.9%, 62.9%, and 57.1%, respectively. By W54, a significant reduction in the PROs, such as the total CDAI score ( p < 0.001), stool frequency ( p < 0.001), abdominal pain score ( p < 0.001), IBDQ ( p < 0.001), IBD-F ( p < 0.05), and fatigue impact on daily activities ( p < 0.001), was observed. During VDZ treatment, arthralgia (23.7%–8.7%) and anemia (22.6%–15.9%) decreased between baseline and W54. Non-serious adverse events (SAEs; 12.2%), SAEs (7.1%), and VDZ-related rash (1.0%) were reported. Mean CD-related hospitalization duration decreased from baseline (10.2 days) to the end of the study (5.3 days).Conclusion:POLONEZ II demonstrated long-term real-world benefits of VDZ toward effectiveness, safety, and improved PROs and patients’ quality of life.Trial registration:ENCePP (EUPAS32716).
The Fragility of Statistically Significant Binary Outcomes for Treating Achilles Tendinopathy: A Systematic Review of Randomized Trials
Authors: Anaspure Omkar S. , Patel Shiv , Baumann Anthony N. , Newsom Andrew , Anastasio Albert T. , Amendola Annunziato 
Published: November 2024

Background: Randomized controlled trials (RCTs) are the gold standard for treatment efficacy, but foot and ankle RCTs are often small or inconsistent. The Fragility Index (FI) evaluates the stability of significant findings. This study assessed the fragility of RCT outcomes for Achilles tendon pathology (ATP) interventions. Methods: This systematic review queried PubMed up to May 14, 2024, for RCTs on ATP interventions. RCTs with significant binary outcomes were included. Two reviewers assessed eligibility, extracted data, calculated FIs, and evaluated risk of bias. Frequency-weighted means were used for narrative synthesis. Results: Eleven RCTs with 4506 patients (mean cohort size: 409.64 ± 160.54) and a mean age of 36.97 ± 13.51 years (n = 4356; 96.67%) were included, covering 24 binary outcomes. The median FI across all outcomes was 3 (interquartile range 1-4; mean 3.92), indicating that changing the outcome of just a few patients could shift a study’s results from statistically significant to nonsignificant. Trials having an FI ≤3 comprised 58.33%. Three outcomes (12.5%) had an FI of zero after recalculating P values using the two-sided Fisher exact test. Half of the outcomes were robust. No RCT reported FIs or adjusted significance for multiple testing. Most studies (81.82%) performed 2 or more statistical tests, with an average of 30.81 ± 41.28 P values reported per study. The overall risk of bias was low in 1 study (9.09%) and moderate in 7 (63.64%). Most studies had low risk of bias in randomization (72.73%) and missing outcome data (90.91%). Conclusion: The FI assesses the fragility of statistically significant binary results, revealing that many ATP RCTs have fragile outcomes due to small sample sizes. A median FI of 3 means that changing the outcome of 3 patients could shift a study’s results from statistically significant to nonsignificant.
Etiology and Clinical Profile of Pediatric Acquired Demyelination Syndromes of the Central Nervous System: An Ambispective Longitudinal Study from South India
Authors: Sugumar Kiruthiga , Chidambaram Aakash Chandran , Ramamoorthy Jaikumar Govindaswamy 
Published: November 2024

Background Pediatric acquired demyelinating disorders (pADS) are diverse disorders with varied clinical presentations and literature regarding them is far and few. Materials and methods This ambispective study included 46 children with pADS who presented between 2016 and 2021 to our institution. Results The most common form was acute demyelinating encephalomyelitis (ADEM) (41.3%). The most common symptom was limb weakness (45.6%). During follow-up, regression of milestones was observed in 3(7.5%) children, and seizures were seen in 4(10%) children. Except for two children, all others could perform activities of daily living. Residual weakness was seen in six children. Recurrence of pADS was seen in five children. Conclusion ADEM was the most common pADS, and 20% had residual deficits. Though mortality is rare in these groups of conditions, morbidity is significantly high, which can be reduced with proper and early treatment with immunosuppressants.
Hyperoside induces ferroptosis in chronic myeloid leukemia cells by targeting NRF2
Authors: Wei Junyi , Chai Quanyou , Qin Yuqiao , Li Long , Guo Chunling , Lu Zhaoyang , Liu Huimin 
Published: November 2024

Abstract
Background
Hyperoside (quercetin-3-O-β-D-galactopyranoside) is a flavonol glycoside compound derived from plants in the Hypericum and Crataegus genera that reportedly exhibits an array of anti-inflammatory, antioxidant, and antitumor properties such that it has been used to treat various diseases. Whether it can serve as an effective treatment for chronic myeloid leukemia (CML) cells, however, has yet to be established. The present study was thus devised to assess the therapeutic effects of hyperoside on CML cells and to clarify the underlying mechanism of action.

Methods
Cellular viability, proliferative activity, migration, and apoptotic death were respectively analyzed through CCK-8, EDU, transwell, and flow cytometry assays. RNA-seq and bioinformatics approaches were further employed to evaluate the mechanisms through which hyperoside influences CML cells, while analyses of reactive oxygen species (ROS) and free iron were detected with commercial kits. Transmission electron microscopy was used to assess mitochondrial morphology. Molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) approaches were also used to explore the ability of hyperoside to target NRF2.

Results
From a mechanistic perspective, hyperoside was able to inhibit SLC7A11/GPX4 signaling in a manner that was abrogated by the ferroptosis inhibitor ferrostatin-1. NRF2 was also closely associated with the inactivation of the SLC7A11/GPX4 axis mediated by hyperoside such that overexpressing NRF2 ablated the benefits associated with hyperoside treatment.

Conclusions
The present analyses indicate that hyperoside can target the NRF2/SLC7A11/GPX4 axis to induce ferroptotic CML cell death.
Novel Multipoint-drive Rotary Actuator for Extraterrestrial Celestial Ultrasonic Driller
Authors: Deng Naiwen , Han Guangchao , Zhu Shuqi , Zhang Xingwang , Pang Yong , Bai Wei 
Published: November 2024

AbstractUltrasonic drilling has emerged as a prominent technique in extraterrestrial environments due to its advantageous features. However, its application in extraterrestrial sampling missions is constrained by challenges such as drilling, chip removal efficiency, and high and low temperature adaptability. Addressing these limitations, this study introduces a novel multi-point driven rotary helical longitudinal torsion horn. The initial phase involved a detailed analysis of the actuator’s structure and operational principle. Subsequently, the actuator’s vibration mode and elliptical motion trajectory were validated through finite element simulation. The study further explores a methodology for adjusting the parameters of the helical groove and the displacement amplitude of the impact head. Following the theoretical analysis, prototypes of the actuator and drill were fabricated. Their adaptability to high and low temperatures, as well as their output characteristics, were rigorously tested. Experimental results demonstrate that with an increase in temperature, the dynamic impedance of the actuator initially rises before decreasing, while the mechanical quality factor exhibits the opposite trend. Notably, the concurrent activation of points P1 and P2 significantly enhances the no-load speed, achieving a maximum of 506 revolutions per minute (r/min). Under conditions of power below 35 W and a drilling pressure of 10 N, the drilling speed achieved in basalt is 6.2 millimeters per minute (mm/min). The proposed multipoint-driven actuator can effectively improve the drilling and chip removal efficiency of the driller, which is an important application prospect in future extraterrestrial drilling missions.
Prevalence and uptake of vaping among people who have quit smoking: a population study in England, 2013-2024
Authors: Jackson Sarah E. , Brown Jamie , Kock Loren , Shahab Lion 
Published: November 2024

AbstractBackgroundVaping prevalence has increased rapidly in England since 2021. This study estimated trends between 2013 and 2024 in vaping among ex-smokers, overall and among those who did not use e-cigarettes to support their quit attempt.MethodsData were collected via nationally-representative, monthly cross-sectional surveys in England, October 2013 to May 2024. We analysed data from 54,251 adults (≥ 18y) who reported having tried to stop smoking in the past year or having stopped smoking more than a year ago. Logistic regression estimated associations between time and e-cigarette use.ResultsAcross the period, there were increases in the use of e-cigarettes to support attempts to stop smoking (from 26.9% [24.0–30.0%] in October 2013 to 41.4% [37.7–45.2%] in May 2024), in current vaping among ≥ 1y ex-smokers (1.9% [1.5–2.5%] to 20.4% [18.7–22.2%]), and in late uptake of vaping after smoking cessation (i.e., current vaping among people who quit smoking before e-cigarettes started to become popular in 2011; 0.4% [0.2–0.8%] to 3.7% [2.8–4.9%]). These increases were non-linear, with much of the difference occurring since mid-2021, and were greatest at younger ages (e.g., current vaping among ≥ 1y ex-smokers reached 58.9% among 18-year-olds vs. 10.7% among 65-year-olds).ConclusionsVaping prevalence increased substantially among adult ex-smokers in England over the past decade, particularly at younger ages. While this is likely to have been largely driven by increased use of e-cigarettes in quit attempts and continued use thereafter, there was also evidence of increased uptake of vaping among those who had been abstinent from smoking for many years.
Characteristics of helicopter hoist operations with intubated patients: a retrospective analysis of a Norwegian physician staffed SAR helicopter service
Authors: Skaiaa Sven Christjar , Roslin André , Heggland Torfinn , Heian Sigurd , Elden Trond , Åreskjold Øivind , Iversen Hanne Rikstad , Jakobsen Dag Stian , Sabel Mads , Berve Per Olav 
Published: November 2024

Abstract
Background
Timely medical management and evacuation of critically ill or injured patients from austere environments or maritime vessels is often achieved by helicopter hoist operations. When indicated, intubation is performed onsite to restore and sustain patient physiology and to facilitate safe transport. We aimed to describe the characteristics of helicopter hoist operations (HHOs) with intubated patients in a physician staffed SAR helicopter service and to identify learning points for future missions.

Methods
The Norwegian national SAR database and local medical journal systems on six SAR helicopter bases were searched for data on hoisted intubated patients from January 2011 to April 2024.

Results
From a total of 18,710 missions, we registered 2,423 helicopter hoist operations with patients as human external cargo. In 54 hoist operations (2%) the patients were intubated prior to hoisting. We observed an increasing number of both HHOs in general and HHOs with intubated patients over time. The intubated HHO patients were in an overall critical state, with a median NACA score of 6 and a median GCS of 3 before intubation. Trauma was the main cause of intubation (n = 32). Twenty-five patients presented with cardiac arrest, 13 of whom were hoisted with an ongoing mechanical chest compression device. During the hoist operation, 34 patients were ventilated manually, and 20 patients were connected to an automatic ventilator. Monitoring of vital parameters during hoisting varied from none to fully monitored patients including invasive arterial blood pressure. Twenty-eight patients, seven of whom presented with initial cardiac arrest, survived to hospital discharge.

Conclusions
HHOs with intubated patients are rare but increasingly occurring events in our service. Owing to the infrequency, complexity and risk factors involved, these operations should be governed by specific operating procedures and trained regularly to be performed safely. HHOs with intubated patients represents a favourable alternative in situations where terrestrial transport is associated with significant time delay or additional risk to the patient or the rescuers.
Self-assessed performance-based function test versus patient-reported outcome measures for knee and hip osteoarthritis
Authors: Kiadaliri Ali , Sirard Paulina , Dahlberg Leif E. , Lohmander L. Stefan 
Published: November 2024

Abstract
Background
Physical function constitutes a key component of outcome assessment for almost all osteoarthritis interventions. The aim was to compare physical function measured using a self-assessed performance-based test versus self-reported function using questionnaires among individuals with knee or hip osteoarthritis (OA) participating in a digital exercise and education therapy.

Methods
We analysed data from individuals aged 40 + years participating in the digital program. We extracted data on the self-assessed 30-second chair stand test (30s CST) and the function subscales of Knee injury/Hip disability and Osteoarthritis Outcome Score 12 (KOOS-12/HOOS-12) at enrolment and 3- (n = 10884) and 12-month (n = 3554) follow-ups. Participants completed Numeric Rating Scale (NRS) pain, EQ-5D-5L, and an external anchor: global rating of change scale. Correlations were assessed using the Spearman correlation coefficient, responsiveness using standardized response mean (SRM) and receiver operating characteristic (ROC) curves, and agreement using weighted percent of agreement and weighted Gwet’s agreement coefficient.

Results
Correlations were weak between the 30s CST and KOOS-12/HOOS-12 function (r < 0.35 for raw and r < 0.20 for change scores). Correlations with NRS pain and EQ-5D-5L were stronger for the KOOS-12/HOOS-12 function subscale than for 30s CST. Greater internal (SRM > 1 vs. SRM < 0.5) and lower external responsiveness were observed for the 30s CST versus the KOOS-12/HOOS-12 function, even though external responsiveness was generally inadequate for both (the area under the ROC curves < 0.7). The direction of change was similar for the two function measures for about 70% of subjects with moderate agreement between them (weighted Gwet’s agreement coefficient range 0.45 to 0.50).

Conclusion
Weak correlations and moderate agreements between function measured using performance-based test and self-reported using KOOS-12/HOOS-12 in people with knee or hip OA suggest that they may capture different aspects of functional abilities in this population.