bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of orelabrutinib in relapsed/refractory idiopathic multicentric Castleman disease: A single‐centre, retrospective study
Authors: Gao Yu‐Han , Li Si‐Yuan , Dang Yue , Duan Ming‐Hui , Zhang Lu , Li Jian 
Published: October 2024

SummaryIdiopathic multicentric Castleman disease (iMCD) is a rare and heterogeneous lymphoproliferative disorder that lacks standardised treatment options for patients with refractory or relapsed (r/r) disease. Blocking Bruton's tyrosine kinase (BTK) has emerged as a promising therapeutic approach for iMCD without depleting B cells. This single‐centre, retrospective study enrolled 10 patients with r/r iMCD who were treated with orelabrutinib, a novel, next‐generation BTK inhibitor. The median age at orelabrutinib initiation was 48 (range: 31–58) years. The overall response rate was 70% (7/10 patients, 95% CI: 34.8–93.3), with 20% (n = 2) achieving complete response and 50% (n = 5) achieving partial response. The median time to response was 9.8 (range: 5.9–20.5) months. Patients in the non‐responder group also demonstrated a continuous improvement in haemoglobin (91–105 g/L) and albumin (32–38 g/L) levels at month 12 of treatment despite not fulfilling response criteria. No grade 3 or higher adverse events occurred during the median time to the next treatment of 29.0 (range: 15.0–36.2) months. No patient mortality was recorded during the median follow‐up duration of 32.8 (range: 15.0–36.9) months. In conclusion, orelabrutinib is a safe and effective regimen for r/r iMCD.
Analysis of SLC genes alternative splicing identifies the SLC7A6 RI isoform as a therapeutic target for colorectal cancer
Authors: Sun Chao , Zeng Boning , Zhou Jilong , Li Nan , Li Mingwei , Zhu Chaowei , Xie Shouxia , Wang Yifei , Wang Shaoxiang , Wang Xiao 
Published: October 2024

AbstractAlternative splicing (AS), a crucial mechanism in post‐transcriptional regulation, has been implicated in diverse cancer processes. Several splicing variants of solute carrier (SLC) transporters reportedly play pivotal roles in tumorigenesis and tumor development. However, an in‐depth analysis of AS landscapes of SLCs in colon adenocarcinoma (COAD) is lacking. Herein, we analyzed data from The Cancer Genome Atlas and identified 1215 AS events across 243 SLC genes, including 109 differentially expressed AS (DEAS) events involving 62 SLC genes in COAD. Differentially spliced SLCs were enriched in biological processes, including transmembrane transporter activity, transporter activity, ferroptosis, and choline metabolism. In patients with COAD, tumor tissues exhibited higher expression of longer mitochondrial carrier SLC25A16 isoforms than adjacent normal tissues, consistent with bioinformatics analysis. Protein‐coding sequences and transmembrane helices of survival‐related DEAS were predicted, revealing that shifts in splicing sites altered the number and structure of their transmembrane proteins. We developed a prognostic risk model based on the screened 6‐SLC‐AS (SLC7A6_RI_37208 (SLC7A6‐RI), SLC11A2_AP_21724, SLC2A8_ES_87631, SLC35B1_AA_42317, SLC39A11_AD_43204, and SLC7A8_AP_26712). Knockdown of the intronic region of SLC7A6‐RI isoform enhanced colon cancer cell proliferation. In vivo, knockdown of the intronic region of SLC7A6‐RI isoform enhanced tumor growth in colon cancer. Mechanistically, si‐SLC7A6‐RI isoform exerted oncogenic effects by activating the PI3K‐Akt–mTOR signaling pathway and promoting cell proliferation, evidenced by increased expression of key regulators Phosphorylated Mammalian Target of Rapamycin (p‐mTOR) and a cell proliferation marker Proliferating Cell Nuclear Antigen (PCNA) using western blotting. Our study elucidated SLC‐AS in COAD, highlighting its potential as a prognostic and therapeutic target and emphasizing the suppressive influence of SLC7A6‐RI in colon cancer progression.
Family functioning and child internalizing and externalizing problems: A 16‐wave longitudinal study during the COVID‐19 pandemic
Authors: Lee Hyanghee , Fosco Gregory M. , Feinberg Mark E. 
Published: October 2024

AbstractThis study explored young children's mental health trajectories during the pandemic (May 2020 to April 2021) as well as associations with family functioning (i.e., cohesion, conflict, chaos, and routines) using data reported by 204 parents (children Mage 5.49; 45% girls, 90% White). Children's internalizing problems decreased early on with the onset of the pandemic, but then leveled off, while no change in externalizing problems was found. Family conflict and chaos were significantly associated with internalizing and externalizing problems at the within‐ and between‐family level, when examined independently. When family‐level factors were evaluated simultaneously, family conflict emerged as a robust risk factor. Intervention efforts, specifically for families experiencing increased conflict, may help support the mental health needs of children.
GLS2 reduces the occurrence of epilepsy by affecting mitophagy function in mouse hippocampal neurons
Authors: Gao Yuan , Ma Limin , Yuan Jinxian , Huang Yunyi , Ban Yuenan , Zhang Peng , Tan Dandan , Liang Minxue , Li Zhipeng , Gong Chen , Xu Tao , Yang Xiaolan , Chen Yangmei 
Published: October 2024

AbstractBackgroundAltered mitophagy has been observed in various neurological disorders, such as epilepsy. The role of mitophagy in causing neuronal damage during epileptic episodes is significant, and recent research has indicated that GLS2 plays a crucial role in regulating autophagy. However, exactly how GLS2 affects epilepsy is still unclear.AimsTo investigate the expression and distribution characteristics of GLS2 in epilepsy, and then observed the changes in behavior and electrophysiology caused by overexpression of GLS2 in epileptic mice, and determined whether GLS2 regulated seizure‐like changes in the mouse model through the protective mechanism of mitophagy.ResultsThe expression of GLS2 in a kainic acid (KA)‐induced epileptic mouse model and aglutamate‐inducedneuronal excitatory damage in HT22 cells model was downregulation. In brief, overexpression of GLS2 can alleviate epileptic activity. Subsequently, we demonstrated that GLS2 interacts with mitophagy‐related proteins in a KA‐induced epilepsy mouse model. Mechanistically, overexpression of GLS2 inhibited mitophagy in epileptic mice, downregulating the expression of LC3 and reducing ROS production.ConclusionsThis study proves the GLS2 expression pattern is abnormal in epileptic mice. The function of mitophagy in hippocampal neurons is affected by GLS2, and overexpression of GLS2 can reduce the occurrence of seizure‐like events (SLEs) by altering mitophagy function. Thus, GLS2 might control seizures, and our findings provide a fresh avenue for antiepileptic treatment and offer novel insights into treating and preventing epilepsy.
Strengths and complementarity of systematic conservation planning and Key Biodiversity Area approaches for spatial planning
Authors: Plumptre Andy , Hayes Jack , Baisero Daniele , Rose Rob , Holness S. , von Staden Lize , Smith Robert J. 
Published: October 2024

AbstractDeveloping biodiversity‐inclusive spatial plans at a national level is the focus of Target 1 of the Kunming–Montreal Global Biodiversity Framework (KMGBF). There are 2 general approaches to identifying areas of value for biodiversity plans: criteria‐based, such as the Key Biodiversity Areas (KBA) process, and systematic conservation planning (SCP) approaches, which apply complementarity to efficiently achieve specific quantitative targets. We examined the benefits of both approaches and considered how the KBA approach can best complement SCP. We reviewed 200 papers articles that applied SCP to real‐world data with the Marxan conservation design software. Our review showed that targets for biodiversity elements are poorly selected in many SCP publications, with more than 75% of the studies applying uniform percentage target amounts to planning elements. Uniform targets favor more widespread species and ecosystems that are likely to be more common and less important for conservation. The strengths and complementarities of KBA and SCP approaches were reviewed and we identified the elements from both approaches that should be considered for spatial planning to achieve Target 1 in the KMGBF. In particular, the global approach of KBAs (i.e., identifying sites of global significance for species or ecosystems) better complements SCP, which often has a national or subnational focus. The KMGBF will fail if conservation of globally significant sites is not targeted and these sites are not incorporated in national spatial planning.
Pharmacogenomic augmented machine learning in electronic health record alerts: A health system‐wide usability survey of clinicians
Authors: Grant Caroline W. , Marrero‐Polanco Jean , Joyce Jeremiah B. , Barry Barbara , Stillwell Ashley , Kruger Kellie , Anderson Therese , Talley Heather , Hedges Mary , Valery Jose , White Richard , Sharp Richard R. , Croarkin Paul E. , Dyrbye Liselotte N. , Bobo William V. , Athreya Arjun P. 
Published: October 2024

AbstractPharmacogenomic (PGx) biomarkers integrated using machine learning can be embedded within the electronic health record (EHR) to provide clinicians with individualized predictions of drug treatment outcomes. Currently, however, drug alerts in the EHR are largely generic (not patient‐specific) and contribute to increased clinician stress and burnout. Improving the usability of PGx alerts is an urgent need. Therefore, this work aimed to identify principles for optimal PGx alert design through a health‐system‐wide, mixed‐methods study. Clinicians representing multiple practices and care settings (N = 1062) in urban, rural, and underserved regions were invited to complete an electronic survey comparing the usability of three drug alerts for citalopram, as a case study. Alert 1 contained a generic warning of pharmacogenomic effects on citalopram metabolism. Alerts 2 and 3 provided patient‐specific predictions of citalopram efficacy with varying depth of information. Primary outcomes included the System's Usability Scale score (0–100 points) of each alert, the perceived impact of each alert on stress and decision‐making, and clinicians' suggestions for alert improvement. Secondary outcomes included the assessment of alert preference by clinician age, practice type, and geographic setting. Qualitative information was captured to provide context to quantitative information. The final cohort comprised 305 geographically and clinically diverse clinicians. A simplified, individualized alert (Alert 2) was perceived as beneficial for decision‐making and stress compared with a more detailed version (Alert 3) and the generic alert (Alert 1) regardless of age, practice type, or geographic setting. Findings emphasize the need for clinician‐guided design of PGx alerts in the era of digital medicine.
Multisystem ALK‐Positive Histiocytosis With DCTN1::ALK Fusion in an Adult, Responsive to Alectinib: Case Report and Literature Review
Authors: Phillips Gregory S. , Knapp Maxwell , Olsen Keith C. , Martin William , Hayes‐Lattin Brandon , Chung Jina 
Published: October 2024

ABSTRACTAnaplastic lymphoma kinase (ALK)‐positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK‐positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK‐positive histiocytosis with xanthogranuloma‐like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK‐positive histiocytoses with cutaneous involvement reported in the literature. A 56‐year‐old male developed a widespread eruption of red‐brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well‐circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next‐generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow‐up. This case adds to the spectrum of ALK‐positive histiocytoses and further demonstrates the positive response with targeted therapy.
PFO Device Complications: Literature Review and Possible Implications for Echocardiographic Follow‐Up
Authors: Foreman Kaitlyn , Lyman Elizabeth , Conroy Sara , Salavitabar Arash , Cua Clifford L. 
Published: October 2024

ABSTRACTIntroductionTransthoracic (TTE) follow up guidelines after PFO device closure are vague. The primary goal of this study was to perform a literature search to characterize the timing of complications that occur after PFO device placement to determine the utility of long‐term routine TTE.MethodsA search was performed in Medline (PubMed) with English language and publication date (2000–2023) filters were applied. Studies were included if they reported on patients who underwent a PFO device closure. Studies were excluded if they only reported on ASD device closure patients, were meta‐analysis or review papers, or did not report any outcomes for the PFO device procedure.ResultsA total of 305 articles met the criteria (observational cohort study, n = 196; case study, n = 99; and randomized control study, n = 10). Age at the time of PFO device closure was 47.5 ± 9.3 years. The incidence of complications was 6.9% (3358/48 348). Maximum range of follow‐up was 0–17 years. The plurality of complications was due to arrhythmias (46.3%, 1554/3358), followed by residual shunts (29.7%, 999/3358). The majority of complications occurred ≤6 months post‐device placement (57.8%, 1941/3358). Only 0.8% (27/3358) of complications took place >5 years. All patients with complications >5 years of device placement were presented with clinical symptoms related to their complications.ConclusionThe incidence of patients presenting with PFO‐reported complications beyond 5 years post‐procedure diminished. The utility of routine TTE beyond 5 years post‐PFO after device placement should be further assessed.
Associations Between Echocardiographic Right Heart Measurements With Short‐Term Prognosis in Heart Failure: A Prospective Study
Authors: Dinç Asarcıklı Lale , İnan Duygu , Murat Selda , Çöllüoğlu İnci Tuğçe , Bakhshaliyev Nijat , Ulutaş Zeynep , Çabuk Gizem , Hasırcı Senem , Naser Abdulrahman , Ünal Dayı Şennur , Çelik Ahmet , Güvenç Tolga Sinan 
Published: October 2024

ABSTRACTBackgroundEchocardiographic right ventricular (RV) dysfunction is a strong risk determinant for prognosis in patients with heart failure (HF). Although parameters of RV systolic function are widely used to define RV dysfunction, there is scarce data to suggest these parameters are best suited to predict HF‐related outcomes.AimsWe aimed to understand which morphologic or functional parameters are most closely associated with short‐term mortality and HF‐related hospitalization in patients with HF.MethodsA total of 191 patients from eight study centers were included to this study. A detailed echocardiographic examination was done at enrollment, and patients were followed up for 6 months via direct interviews or phone calls.ResultsAll right‐sided echocardiographic parameters other than tricuspid annular plane systolic excursion were associated with outcomes. In a proportional hazards model that included right‐heart parameters, RV longitudinal diameter (HR: 1.07, 95%CI: 1.04–1.10, p < 0.001), wall thickness (HR: 1.3, 95%CI: 1.13–1.50, p < 0.001), and tricuspid annular systolic velocity (HR: 0.90, 95%CI: 0.82–0.96, p = 0.02) were found as the independent predictors. However, only RV longitudinal dimension (HR: 1.04, 95%CI: 1.01–1.08, p = 0.01) and RV wall thickness (HR: 1.32, 95%CI: 1.10–1.60, p = 0.004) were associated with short‐term outcomes after adjusting for other clinical and left‐sided echocardiographic variables. On a Bayesian logistic regression model that included right‐sided echocardiography variables, there was strong evidence for including either RV longitudinal diameter (BF10: 190.4) or wall thickness (BF10: 30.7) to the final model.ConclusionParameters of RV morphology were better predictors of short‐term outcomes in HF patients.
Comparing Echocardiographic Strain Imaging in Cardiac Amyloid and End‐Stage Renal Disease Patients
Authors: Ferris Taylor , Yohannan Ethan , Daniel Kurt , Richardson Karl M. 
Published: October 2024

ABSTRACTPurposeDiagnosing cardiac amyloidosis (CA) is difficult due to nonspecific clinical symptoms and echocardiographic findings. Prior studies have suggested that apical sparing strain patterns may be diagnostically useful. With increasing strain usage, it remains unclear how specific this pattern is to diagnose CA. We analyzed strain patterns between CA and end‐stage renal disease (ESRD) patient populations.MethodsPatients with ESRD proven negative for CA (n = 19) were compared to CA patients with CKD stage 3 or less (n = 25). The ESRD cohort was stratified based on time on dialysis. Echocardiographic longitudinal strain (LS) parameters were collected, including regional and global LS, echocardiographic, and demographic parameters. Relative apical LS was calculated using the following equation: average apical LS/(average mid LS + average basal LS).ResultsNo significant differences were found regarding regional strain or relative apical strain. Our study showed a sensitivity of 80% and specificity of 42% when using a relative apical strain ratio of >1. All groups demonstrated an apical sparing strain pattern visually on the bulls‐eye plot.ConclusionESRD demonstrates significant overlapping findings across various imaging modalities compared to CA. We demonstrated that relative apical sparing strain is nonspecific for CA among patients with ESRD. Our study calls into question the clinical value of relative apical‐sparing stain patterns in identifying CA in an ESRD population and suggests that diagnostic evaluation should be driven by strong clinical suspicion and other imaging and demographic variables.
Clinical presentation and treatment of a bronchocutaneous fistula with intrathoracic abscessation in a yearling
Authors: Garcia‐Collao M. R. , Curtiss A. L. , Mendez‐Angulo J. L. 
Published: October 2024

SummaryThis case report describes the clinical presentation, surgical treatment, post‐operative management and outcome of a bronchocutaneous fistula with intrathoracic abscessation in a yearling horse. The animal was presented with a history of several months of persistent coughing and a cutaneous fistula located over the right ventral hemithorax. The yearling had purulent discharge similar in character from both nares and draining out of the fistula. A bronchocutaneous fistula with intrathoracic abscessation was diagnosed by endoscopic examination of the cutaneous fistula. The treatment initially consisted of cyanoacrylate applied topically to the affected bronchi under endoscopic guidance, which was not successful. The fistula was successfully sealed with a diode laser used to create local inflammation at the site. One week after the second intervention, the patient's clinical signs resolved and the fistula was completely sealed 10 weeks following intervention. Follow‐up at 16 months revealed that the patient was doing well and clinically normal.
The role of training and medication reminder wristwatch in adherence to treatment in geriatric patients diagnosed with hypertension: A randomized controlled trial
Authors: Solmaz Tuğba , Altay Birsen 
Published: October 2024

AimThe purpose of this study was to determine the effects of the training and medication reminder wristwatch on treatment adherence in geriatric patients diagnosed with hypertension.MethodsIn this study, which was conducted as a randomized clinical trial with a pretest‐posttest design, 90 patients were randomly divided into the training and medication reminder wristwatch (W) group (n = 30) group, the training (T) group (n = 30), and the control (C) group (n = 30). All patients answered the data collection forms before and after the interventions.ResultsBy the end of the 12th week, the mean knowledge scores of the groups significantly differed from each other (t = −13.207, P < 0.001). The mean Hypertension Compliance Assessment Scale score of the W group was found to be significantly lower (t = 22.732, P < 0.001). The highest mean Medication Adherence Self‐Efficacy Scale–Short Form score was found in the W group (t = −13.560, P < 0.001). In the posttest, the mean systolic blood pressure values of the patients were 142.7 ± 11.1 in the C group, 126.0 ± 13.0 mm Hg in the T group, and 120.0 ± 9.5 mm Hg in the W group (Kruskal–Wallis test = 38.065, P < 0.05).ConclusionsThis study demonstrates that 12 weeks of a training program and the use of medication reminder wristwatches were effective in adherence to treatment. Geriatr Gerontol Int 2024; 24: 1189–1195.
Where Did the Global Elite Go to School? Hierarchy, Harvard, Home and Hegemony
Authors: Salas‐Díaz Ricardo , Young Kevin L. 
Published: October 2024

ABSTRACTWe examine the educational backgrounds of the global elite, using new data on a diversity of organizational leadership roles as well as the population of the super‐rich across the world. Four trends emerge when examining the university education of the global elite. First, we find a small number of globally prestigious universities to take on super prominent roles, suggesting a strongly hierarchical distribution of credentials among the global elite. Second, we find a consistent and unique place for Harvard University within this system. Third, we find evidence for a significant yet variable ‘home‐bias’ in the education of the global elite. This is moderated by the fourth regularity, the hegemony of Anglo‐American credentials. These four global regularities can enhance ongoing research on global elite populations. Our findings are robust to both the removal of all American elites in the sample, to dynamic stratified sampling of the network boundary and to disaggregating the sample into different elite roles. The analysis of this article is the first of its kind to offer a large‐scale descriptive mapping of central tendencies in global elite university education.