bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-institutional retrospective cohort of adult-onset medulloblastoma in the modern era
Authors: Bonm Alipi V , Rutenberg Michael S , Therkelsen Kate E , Herbst John , Sanaf Anurag , Sherwood Marissa A , Rhee John Y , McGranahan Tresa M , Cimino Patrick J , Gonzalez Castro L Nicolas , Tsang Derek S , Karajannis Matthias A , Nagpal Seema , Amdur Robert J , Shih Helen , Barber Jason , Taylor Lynne P 
Published: December 2024

Abstract

Background
Adult onset medulloblastoma (aMB) is a rare tumor with limited available evidence. We present a large multi-institutional retrospective cohort of aMB patients treated in the modern era, with an emphasis on understanding the role of chemotherapy at initial diagnosis.

Methods
We included 267 consecutive patients with aMB treated at 7 different institutions from 2000-present, controlling for chemotherapy regimen and cycles received.

Results
Treatment factors were highly intercorrelated with one another and with treating institution. Concurrent chemotherapy was not associated with overall survival (OS). Adjuvant chemotherapy was associated with OS on univariable analyses (HR = 0.55, P = .029) and on multivariable analysis when adjusting for risk status (HR 0.55, P = .026) but not when also adjusting for treating institution. Proton craniospinal irradiation was associated with improved survival on univariable (HR = 0.50, P = .019) and multivariable analysis adjusting for risk status (HR = 0.51, P = .024) but not when treating institution was also considered. On subgroup analysis, adjuvant chemotherapy was associated with improved survival in M0 (HR = 0.55, P = .043) but not M1 disease, in patients with subtotal resection (HR = 0.43, P = .048) but not those with GTR. Similarly, progression-free survival was improved with chemotherapy in patients with M0 (HR = 0.57, P = .032) but not M1 disease, and in patients with subtotal (HR = 0.50, P = .054) but not gross total resection.

Conclusions
There was no benefit of concurrent chemotherapy. Adjuvant chemotherapy was associated with improved overall survival and this effect was driven by select subgroups, specifically those with M0 disease and those with residual tumor. We could not confirm that these associations are independent of the treating institution.
Navigating UK internal medicine training applications: 10 essential tips
Authors: Khalid Sara , Heather Thomas , Palin Victoria , Brown Oliver I , Drozd Michael 
Published: December 2024

Abstract
Internal medicine training applications in the UK have become increasingly competitive. This article provides ten tips for optimizing internal medicine training applications covering portfolio development, teaching experience, project selection, and interview preparation. We outline strategies for maximizing application scores through efficient resource allocation, effective project selection, and structured interview preparation. These tips are designed to help candidates navigate the competitive selection process while developing skills valuable for their future medical careers.
Exploring the Italian Population’s attitudes toward health data sharing for healthcare purpose and scientific research: a cross-sectional study
Authors: Scaioli G , Lo Moro G , Martella M , Mara A , Varì M G , Previti C , Rolfini E , Scacchi A , Bert F , Siliquini R 
Published: December 2024

Abstract

Background
This study aimed to explore the Italian population’s knowledge and perceptions regarding health data storage and sharing for treatment and research and to identify factors associated with citizens’ attitudes toward data storage and sharing.

Methods
A cross-sectional questionnaire, distributed to 1389 participants, collected sociodemographic information, assessed knowledge and gauged attitudes toward sharing data for treatment and research. Descriptive analyses and logistic regressions were performed to examine the associations between sociodemographic factors and knowledge/attitudes about data storage and sharing.

Results
Most respondents wrongly believed that healthcare providers could access personal health–related data across the entire national territory, while 94% expressed willingness to share personal health data nationwide. A substantial percentage of respondents (73%) fully agreed that storing and sharing personal health–related data could improve research and quality of care.
Males and younger individuals (&lt;41 years) were likelier to have higher data-sharing knowledge. Lower educational-level respondents exhibited lower positive attitudes towards sharing health data for treatment and research purposes.

Conclusions
The results provide valuable insights for policymakers, healthcare professionals and researchers seeking to improve data management, promote collaboration and leverage the full potential of health data for personalized care and scientific advancements.
iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases
Authors: Li Huirong , Sharma Ruchi , Bharti Kapil 
Published: December 2024

Abstract
Retinal pigment epithelium (RPE) atrophy is a significant cause of human blindness worldwide, occurring in polygenic diseases such as age-related macular degeneration (AMD) and monogenic diseases such as Stargardt diseases (STGD1) and late-onset retinal degeneration (L-ORD). The patient-induced pluripotent stem cells (iPSCs)-derived RPE (iRPE) model exhibits many advantages in understanding the cellular basis of pathological mechanisms of RPE atrophy. The iRPE model is based on iPSC-derived functionally mature and polarized RPE cells that reproduce several features of native RPE cells, such as phagocytosis of photoreceptor outer segments (POS) and replenishment of visual pigment. When derived from patients, iRPE are able to recapitulate critical cellular phenotypes of retinal degenerative diseases, such as the drusen-like sub-RPE deposits in the L-ORD and AMD models; lipid droplets and cholesterol accumulation in the STGD1 and AMD models. The iRPE model has helped discover the unexpected role of RPE in understanding retinal degenerative diseases, such as a cell-autonomous function of ABCA4 in STGD1. The iRPE model has helped uncover the pathological mechanism of retinal degenerative diseases, including the roles of alternate complement cascades and oxidative stress in AMD pathophysiology, abnormal POS processing in STGD1 and L-ORD, and its association with lipid accumulation. These studies have helped better understand—the role of RPE in retinal degenerative diseases, and molecular mechanisms underlying RPE atrophy, and have provided a basis to discover therapeutics to target RPE-associated diseases.
tPA‐GFP is a reliable probe for detecting compound exocytosis in human pancreatic β‐cells
Authors: Makam Aishwarya A. , Sharma Shruti , Nagle Prajwal , Sundaram Nandhini M. , Prasad Vidya Mangala , Gandasi Nikhil R. 
Published: December 2024

AbstractPancreatic β‐cells secrete insulin stored in large dense core vesicles (LDCV) by fusion of vesicle and plasma membrane during a process called insulin exocytosis. Insulin secretion is biphasic with a fast first phase and a sustained second phase. Previous studies have pointed out that exocytosis of insulin can occur via (1) single LDCVs fusing with the plasma membrane to release their content or (2) multiple vesicles are involved during a process called compound exocytosis. Compound exocytosis represents a specialized form of secretion in which vesicles undergo homotypic fusion either before (multi‐vesicular exocytosis) or continuous fusion in a sequential manner from (sequential exocytosis) within the same site at the plasma membrane. We see that the number of multi‐vesicles is few and not localized in the vicinity of the plasma membrane. Studying the kinetics of this process and correlating it with biphasic insulin secretion is not possible since there are no specific probes to detect them. It is challenging to identify compound exocytosis with probes that exist for simple exocytosis. To advance our understanding, we need a fluorescent probe that could detect secretory vesicles undergoing compound exocytosis and allow us to distinguish it from other modes of exocytosis. Here, we used two cargo proteins (NPY and tPA) labeled with different fluorescent proteins (mCherry GFP and eGFP) and employed total internal reflection fluorescence microscopy (TIRF‐M) to capture distinct single‐granule and multi‐granular fusion events. We identified tPA‐GFP as a better probe for studying compound exocytosis, as it can detect both simple and sequential exocytosis reliably. Using these probes, we have studied the kinetics of compound exocytosis in human β‐cells. These observations, with additional experiments, may open a whole new field to study the impact of compound exocytosis on biphasic secretion of insulin. Identifying targets to increase the compound exocytosis process can help potentiate insulin secretion in diabetics.
Targeting GSK‐3β for adipose dysfunction and cardiovascular complications of metabolic disease: An entangled WNT/β‐catenin question
Authors: Alotaiq Nasser , Khalifa Ahmed S. , Youssef Amr , El‐Nagar Esraa G. , Elwali Nasr Eldin , Habib Hosam M. , AlZaim Ibrahim , Eid Ali H. , Bakkar Nour‐Mounira Z. , El‐Yazbi Ahmed F. 
Published: December 2024

AbstractIndividuals with metabolic syndrome have a high risk of developing cardiovascular disorders that is closely tied to visceral adipose tissue dysfunction, as well as an altered interaction between adipose tissue and the cardiovascular system. In metabolic syndrome, adipose tissue dysfunction is associated with increased hypertrophy, reduced vascularization, and hypoxia of adipocytes, leading to a pro‐oxidative and pro‐inflammatory environment. Among the pathways regulating adipose tissue homeostasis is the wingless‐type mammary tumor virus integration site family (Wnt) signaling pathway, with both its canonical and non‐canonical arms. Various modulators of the Wnt signaling have been identified to contribute to the development of metabolic diseases and their cardiovascular complications, with a particularly significant role played by Glycogen Synthase Kinase‐3β (GSK‐3β). GSK‐3β levels and activities have various and often contrasting roles in obesity and related metabolic disorders, as well as their cardiovascular sequelae. Here, we explore the possibility that altered Wnt signaling and GSK‐3β activities could serve as a connection between adipose tissue dysfunction and the development of cardiovascular disease in individuals with metabolic syndrome. We attempt to define a context‐specific approach for intervention, which could possibly serve as a novel disease modifying therapy for the mitigation of such complications.
Outcomes of Growth-Friendly Surgical Treatment of Early Onset Scoliosis in Children With Prune Belly Syndrome: A Preliminary Report
Authors: Ashebo Leta , Sponseller Paul , Hedequist Daniel , Ramirez Norman , Oetgen Matthew , Li Ying ,   Pediatric Spine Study Group
Published: December 2024

Background:
Prune belly syndrome (PBS) is a rare condition characterized by absence of abdominal musculature, cryptorchidism, and obstructive uropathy. The most common orthopaedic problem is scoliosis, yet no reports on growth-friendly surgical treatment of early-onset scoliosis (EOS) exist. Our purpose was to evaluate outcomes of distraction-based implants in children with PBS.

Methods:
This was a multicenter retrospective review. Children with PBS treated with TGR, MCGR, or VEPTR with a minimum 2-year follow-up were identified. Demographics, radiographic/surgical data, complications, and unplanned returns to the operating room (UPROR) were collected. Quality of life was measured using EOSQ-24.

Results:
Seven patients (100% male) were identified. The mean age at index surgery was 5.6 years. The mean length of follow-up was 4 years (range: 2 to 11 y). Implant types included MCGR (4 patients), TGR (2 patients), and VEPTR (1 patient). Two patients had pelvic fixation. The mean major curve magnitude was 87 degrees preindex, 47 degrees postindex, and 53 degrees at the last follow-up. Mean kyphosis was 55 degrees preindex, 25 degrees postindex, and 42 degrees at the most recent follow-up. Mean T1-T12 and T1-S1 lengths increased 4.4 and 4.8 cm, respectively, between preindex and last follow-up.
Complications occurred in 3 patients. One patient had 3 TGR breakages resulting in 3 UPRORs to revise the rods and 1 superficial wound infection treated with antibiotics. Another patient was readmitted for respiratory failure after TGR lengthening and a third patient had a superficial infection manifested by incisional swelling after MCGR insertion that resolved with antibiotics. Two patients have undergone definitive fusion and 1 patient has retained his TGR definitively. The other patients are still undergoing rod lengthening.

Conclusions:
Children with PBS can develop severe scoliosis at a young age. Distraction-based implants can successfully control scoliosis while allowing spinal growth. The complication rate is comparable to patients with idiopathic EOS treated with growth-friendly implants.

Level of Evidence:
Therapeutic level IV.
Developmental Coaching for Clinician Educators: Just What the Doctor Ordered
Authors: Branzetti Jeremy 
Published: December 2024

Abstract:
Despite intensive attempts to create scholarship equity at academic medical centers, clinician educators continue to face a challenging professional promotion environment that puts them at risk for burnout, stalled career advancement, and abandonment of academic medicine altogether. Coaching, which has a wealth of supportive evidence from outside of medicine, is distinguished by (1) being driven by the agentic coachee that is inherently capable, creative, and resourceful, (2) not requiring the coach and coachee to have shared content expertise, and (3) not being centered around transfer of expertise from the more knowledgeable or experienced party to the recipient. Initial evidence from within medicine indicates that coaching reduces burnout and improves learner self-reflection, teaching effectiveness, goal setting, reflective capacity, professional identity formation, career planning, and development of adaptive expertise. In this article, faculty coaching is presented as a powerful means to help clinician educators overcome the myriad challenges to professional advancement and career fulfillment. The current evidence in support of coaching—both within and outside of medicine—is reviewed. Finally, a conceptual model is provided, as are guidelines demonstrating specific roles, behaviors, and responsibilities for faculty coaches and coachees.
Secondary Hemophagocytic Lymphohistiocytosis Syndrome Developing in a Patient With Chronic Lymphocytic Leukemia Under a Long-term Ibrutinib Therapy: A Case Report and Literature Review
Authors: Gao Liang , Wang Lihong , Wang Bingjie , Wang Qian , Cen Xinan , Dong Yujun 
Published: December 2024

Secondary hemophagocytic lymphohistiocytosis (HLH) syndrome, a fatal disorder characterized by NK/T-cell deficiency, cytokine storm, and organ damage, is rare in chronic lymphocytic leukemia (CLL). Ibrutinib, the first generation of irreversible Bruton’s tyrosine kinase inhibitor, has been the first-line therapy for CLL. As an off-target effect, it can also block IL-2 inducible T-cell kinase (ITK), which is essential in maintaining normal NK and T-cell functions. Up to now, 4 cases reported secondary HLH developed in CLL patients shortly after ibrutinib therapy, which indicated ibrutinib might be associated with HLH via NK/T cell damage as a result of ITK inhibition. We herein report the first case describing EBV-driven HLH developed in a CLL patient under long-term ibrutinib monotherapy (4 year﻿), also showing concurrent NK and T cell deficiency. Therefore, the relationship between the long-term use of ibrutinib and the pathophysiology of HLH, as well as the mediating role of NK/T cell disorder caused by ITK blockade therein, deserves attention and further studies.
Impact of eicosapentaenoic acid on cardiovascular outcomes after acute coronary syndrome: a systematic review and meta-analysis of randomized clinical trials
Authors: Fallahtafti Parisa , Nayebirad Sepehr , Karimi Elaheh , Hassanzadeh Ali , Habibzadeh Amirhossein , Safaee Ehsan , Ebrahimi Rasoul , Tajdini Masih , Najafi Kimia , Askari Mani K. , Harrison Anil , Nelson John R. , Hosseini Kaveh 
Published: December 2024

Background and purpose:
Studies show that individuals recovering from acute coronary syndrome (ACS) benefit from intensive lipid-lowering treatment, which offers better protection against cardiovascular events than standard regimens. While the benefits of polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA), in coronary artery disease are well-established, their use in ACS patients remains debated. This systematic review and meta-analysis aimed to evaluate the effects of EPA supplementation on cardiovascular outcomes in ACS patients.

Methods:
A systematic search was conducted in PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov from inception to March 22, 2024, focusing on randomized clinical trials (RCTs) and post hoc analyses of adults with ACS examining the effects of adding EPA to statin therapy. The risk of bias was assessed using the Cochrane risk of bias-2 tool. Data synthesis included calculating relative risks (RR) and assessing heterogeneity with I² and Cochran’s Q test, using fixed or random-effects models as appropriate. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke.

Results:
A total of 1,333 subjects with recent ACS were included across five RCTs, with 653 receiving standard statin therapy and 680 receiving statins plus EPA. EPA supplementation trended toward reduced all-cause and cardiac death. Meta-analysis revealed a significant reduction in composite outcomes for the EPA group compared to controls (RR: 0.67, 95% confidential interval: 0.45–1.00, P = 0.04). No significant differences were found in re-infarction, coronary revascularization, or atherosclerotic plaque characteristics between the groups.

Conclusions:
Our study shows that adding EPA to statins after recent ACS reduces cardiovascular events. Despite limitations, our findings support early EPA use in ACS patients.
Recent Advances in the Diagnosis and Management of Limbal Stem Cell Deficiency
Authors: Kittipibul Thanachaporn , Dalin Chea Piseth , Masoudi Ali , Zheng Jie , Deng Sophie X. 
Published: December 2024

Abstract:
This concise review focuses on the latest advancements in the diagnosis and management of limbal stem cell deficiency (LSCD). Ensuring the standard of care for individuals affected by LSCD involves the crucial task for physicians to meticulously and accurately diagnose the condition and determine its specific stage. A standardized diagnostic approach forms the foundation for formulating and delivering customized therapeutic interventions to maximize treatment outcomes for each patient. In this review, we introduce a systematic diagnostic algorithm to guide the assessment of LSCD. In addition, the current management algorithm and emerging therapies for LSCD are summarized.
Digital Interventions for Promoting Skin Self-Examination Behaviors of Melanoma Survivors
Authors: Li Leilei , Qu Hui , Fu Chaohong , Niu Jianpei , Yang Changyong 
Published: December 2024

Background
Regular and thorough skin self-examination (SSE) is an important strategy to reduce mortality among melanoma survivors. However, less than a quarter of melanoma survivors participate in skin self-examination.

Objective
The aim of this study was to systematically review the effectiveness of digital interventions on SSE-related practices in melanoma survivors.

Methods
Cochrane Library, Web of Science, PubMed, and EBSCO were used to identify literature with a search period from January 1, 2000, to June 11, 2024. Two researchers conducted the quality evaluation and summarized and analyzed the included literature.

Results
Twelve articles were included, with a quality score of 5-9 and an average score of 7.67 for the included studies. The digital intervention methods are web based (n = 5), mobile applications (n = 5), videos (n = 1), and interactive multimedia (n = 1). Eleven studies used at least 1 theoretical framework to guide their intervention design. Ten studies reported SSE rates, 2 studies reported SSE areas, and 2 studies reported SSE frequencies and other practical effects. Compared with the control group, the increase in SSE rate ranged from 26.2% to 78.9%; 90% of participants had a frequency of SSE ≥ 2 times per month, with an average of 5.14 areas of SSE; the usage rate of mirrors ranged from 67% to 88%.

Conclusions
Digital intervention can effectively improve the rates, frequency, and number of areas of SSE for melanoma survivors.

Implications for Practice
Digital intervention can be used in clinical practice to provide efficient and effective SSE for melanoma survivors in the short to medium term.
A Scoping Review of Chemotherapy-induced Peripheral Neuropathy-Related Gait Abnormalities in Children With Cancer
Authors: Washist Regan , Steventon Dan , Samuelson Paige , Anderson Brittany , Berg-Poppe Patti , Milanovich Samuel 
Published: December 2024

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) with associated weakness, areflexia, neuropathic pain, and sensory loss, is a common occurrence in children treated for cancer. However, accurate, quantifiable descriptions of gait deviations due to CIPN are lacking. This scoping review explores common gait abnormalities in children with CIPN.

Methods:
Using extensive database and manual literature reviews, 3 relevant studies were identified that assessed CIPN-related gait changes in children.

Results:
Though each study used different methods to analyze gait patterns, decreased ankle dorsiflexion with slower and shorter gait were common findings across the studies. Changes to ankle dorsiflexion range of motion can lead to slower walking speeds and compensatory changes that can cause developmental effects on a child’s gait.

Conclusions:
Relevant research on the topic of CIPN-related gait abnormalities in children with cancer identifies knowledge gaps and the need for more studies on the effects of CIPN on children.