bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal Ceroid Lipofuscinosis—Concepts, Classification, and Avenues for Therapy
Authors: Zhang Yuheng , Du Bingying , Zou Miaozhan , Peng Bo , Rao Yanxia 
Published: February 2025

ABSTRACTNeuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative lysosomal storage disorders characterized by excessive accumulation of lysosomal lipofuscin. Thirteen subtypes of NCL have been identified, each associated with distinct genes encoding various transmembrane proteins, secretory proteins, or lysosomal enzymes. Clinically, NCL manifests in infants through vision impairment, motor and cognitive dysfunctions, epilepsy, and premature death. The pathological complexity of NCL has hindered the development of effective clinical protocols. Current treatment modalities, including enzyme replacement therapy, pharmacological approaches, gene therapy, and stem cell therapy, have demonstrated limited efficacy. However, emerging evidence suggests a significant relationship between NCL and microglial cells, highlighting the potential of novel microglial cell replacement therapies. This review comprehensively examines the pathogenic genes associated with various NCL subtypes, elucidating their roles, clinical presentations, and corresponding mouse models. Especially, we thoroughly discuss the advances in the clinical study of potential therapeutics, which crucially calls for early diagnosis and treatment more than ever.
Low‐Frequency Stimulation at the Ventromedial Hypothalamus Exhibits Broad‐Spectrum Efficacy Across Models of Epilepsy
Authors: Zou Shuang , Gong Yiwei , Yan Mengqi , Yuan Zhijian , Sun Minjuan , Zhang Shuo , Yang Yuanzhi , Guo Xiongfeng , Huang Lan , Fei Fan , Wang Yi , Chen Zhong , Xu Cenglin 
Published: February 2025

ABSTRACTAimsThe limited efficacy and very restricted antiseizure range of current deep brain stimulation (DBS) targets highlight the need to find an optimal target for managing various seizure types. Here, we aimed to investigate the efficacy of DBS on the ventromedial hypothalamus (VMH) in the different types of experimental epileptic seizures.MethodsThe efficacy of DBS was examined in various epileptic seizure models, and the potential mechanisms were investigated by using in vivo calcium signal recording and optogenetics.ResultsThe c‐fos expression was significantly increased in the glutamatergic neurons of VMH (VMHglu) following seizures. Then, 1‐Hz low‐frequency stimulation (LFS) at the VMH successfully attenuated the seizure severities across models of epilepsy, including the maximal electroshock, the pentylenetetrazol, the absence seizure, the cortical or hippocampal kainic acid–induced acute seizure, and the hippocampal‐kindling models. The in vivo calcium imaging recordings revealed that LFS could inhibit the activities of the VMHglu. Optogenetic inhibition of VMHglu mirrored LFS's antiseizure impact. Further anterograde viral tracing confirmed the extensive distributed projections of VMHglu, which may compose the circuitry basis of the broad‐spectral efficacy of LFS.ConclusionThese findings demonstrate that VMH‐LFS is a broad‐spectrum treatment approach for different seizure types by decreasing VMHglu activity.
Outcome of Surgical Treatment for Tracheocutaneous Fistula in Paediatric Population: A Meta‐Analysis
Authors: Saniasiaya Jeyasakthy , van der Meer Graeme , Toll Ed , McCaffer Craig , Barber Colin , Neeff Michel , Islam Md Asiful 
Published: February 2025

ABSTRACTObjectiveThe incidence of persistent tracheocutaneous fistula (TCF) in children has dramatically increased with the increasing number of tracheostomies performed earlier in the paediatric population. Despite the various emerging techniques, two fundamental surgical approaches are primary closure and healing by secondary intention. We aim to compare the surgical outcomes between the two procedures.Data SourcePubMed, EMBASE and Scopus databases were searched from inception to 31 December 2023 with no restrictions on the setting or design of studies.Review MethodsData were pooled using a random effects model to assess the success and complication rates between the two surgical techniques.ResultsA total of 26 studies were identified with a total of 1263 children. Persistent TCF was surgically treated with primary closure in 24 studies (n = 898), whereas healing by secondary intention was reported in 12 studies (n = 366). The success rate following primary closure and healing by secondary intention is 97.3% (95% CI: 95.7%–99.0%) and 94.0% (95% CI: 91.2%–96.7%), respectively. The pooled rate of complications following primary closure was 14.1% (95% CI: 8.9%–19.4%) and 8.4% (95% CI: 3.4%–13.3%) following healing by secondary intention.ConclusionBased on the pooled results, healing by secondary intention is a safer surgical option in children with persistent TCF.
Size‐Sound Iconicity in English‐Like Pseudowords Influences Referent Labeling and Prosody
Authors: Michelini Leonardo , Nygaard Lynne C. 
Published: February 2025

AbstractSpeech sounds can communicate perceptual information through iconicity, or shared resemblance between sound and meaning. Prosody, which encompasses vocal characteristics such as pitch and intensity, can similarly be recruited to communicate meaning by evoking physical features of a referent. This study used English‐like pseudowords to investigate whether iconicity between word form and object properties would affect pronunciation, with the prediction that congruent mappings between label and referent would elicit similarly iconic prosodic modulation. Experiment 1 used size‐sound iconicity to establish perceptual mappings. Participants were presented with three animal figures of varying sizes, small, medium, and big, and asked to assign a label to one of them. The labels were pseudowords designed to be small‐sounding, ambiguous with respect to size, or big‐sounding. We found that small‐sounding pseudowords were more likely to be matched to small referents, and big‐sounding pseudowords to big referents. Participants exhibited no preference when naming medium‐sized animals. Experiment 2 assessed how iconic mappings between labels and referents influenced vocal production. Participants were shown three animals of differing sizes along with a label that was preassigned to a particular referent. Participants were then asked to pronounce aloud the target pseudoword, and responses were recorded. Although the relationship between label and referent did not significantly predict the acoustic form of vocal productions, participants instead produced prosody that reflected the size evoked by the pseudowords themselves, suggesting that not only are language users sensitive to sound to size iconicity in spoken language, but that sensitivity modulates speech production.
Survey of Extracorporeal Life Support Application in Lung Transplantation
Authors: Wilkey Barbara Jeanne , Elliott Tyler , Jones Todd Everett , Vasilopoulos Terrie , Gelzinis Theresa , Bellomy Melissa , Brodt Jessica Louise , Knight Joshua , Geube Mariya Atanassova , Fox John Michael , Racine Christopher Lee , Tawil Justin Nadeem , Kozarek Katharine , Subramani Sudhakar , Siegrist Kara Kimberly , Kothary Pratik , Peng Yong Gang , Miltiades Andrea Nicole , McCartney Sharon Lorraine , Bottiger Brandi Anne , Martin Archer Kilbourne 
Published: February 2025

ABSTRACTIntroductionLung transplantation has been evolving since its inception in 1963. Over recent years, literature has suggested a shift in the perioperative strategy of mechanical support toward extracorporeal membrane oxygenation (ECMO) as the preferred modality of extracorporeal life support (ECLS) in lung transplantation. The Survey of ECLS Application in Lung transplantation (SEAL) was designed to elucidate the current practice patterns of perioperative ECLS within the United States.MethodsIn this cross‐sectional study, a physician from 62 adult lung transplantation centers across the United States of America (USA) was surveyed on their institutional practices regarding the perioperative management of lung transplantation patients, with a focus on mechanical support.ResultsThe survey completion rate was 74% (46/62 eligible institutions). Most transplant centers utilize venoarterial (VA) ECMO (78%, 36/46) and/or venovenous (VV) ECMO (93%, 29/43) as a bridge to lung transplantation. When ECLS is used intraoperatively, 61% of (28/46) responding programs use VA ECMO as their preferred support. All programs use transesophageal echocardiography (TEE) intraoperatively, 85% (33/39) cannulate for ECMO centrally, and 74% (29/39) use a combination of inhaled and intravenous anesthesia while using ECMO intraoperatively. Most programs do not use antifibrinolytic during VA ECMO (62%, 28/45). Anticoagulation management and VA ECMO flows throughout the procedure showed considerable variation.ConclusionData from SEAL illustrates that though there are some practice commonalities within the United States, there is also quite a bit of variability in practice. Multiple dominant practices within the USA are consistent with a recently published International Society of Heart and Lung Transplantation consensus.
Advances and Challenges of Thrombolytic Therapy for Donation After Circulatory Death Organs
Authors: Zhang Peng , Liang Han , Wang Yanfeng 
Published: February 2025

ABSTRACTThe demand for organ transplantation has exceeded the global supply of available organs. Donation after circulatory death (DCD) is considered an effective method to solve the disparity between the supply and demand of organs, by expanding the donor pool. However, DCD organs experience long‐term damage caused by warm ischemia (WI) and microthrombosis caused by diffuse intravascular coagulation. Unfortunately, because of concerns about post‐transplantation complications, most organs considered high‐risk are discarded, resulting in wasted medical resources and economic losses. However, thrombolytic therapy before transplantation may dissolve microthrombosis in DCD organs, improve organ microcirculation, and increase organ use. Herein, we review the current status and potential value of thrombolytic therapy before DCD organ transplantation, summarize the progress of thrombolytic therapy for DCD organ transplantation according to preclinical and clinical research, and emphasize the heterogeneity and limitations of studies that have caused some controversies associated with this therapy. Overall, the role of thrombolytic therapy should not be overlooked. We anticipate that thrombolytic therapy combined with machine perfusion will provide an opportunity to improve inferior‐quality DCD grafts, resulting in their becoming more widely available and safer for transplantation, thus solving the urgent problem of organ shortage.
Functional Status Trajectory and Survival for Adult Patients Undergoing Heart Transplantation
Authors: Wittenberg Rachel E. , Mostofsky Elizabeth , Mittleman Murray A. 
Published: February 2025

ABSTRACTBackgroundTransplantation is a critical treatment for end‐stage heart disease and improves length and quality of life. We investigated predictors of functional status improvement following transplant and the association between functional status trajectory and survival.MethodsWe conducted a retrospective cohort study using Scientific Registry of Transplant Recipients data on 34 009 US adults who underwent heart transplant 2006–2021. Functional status was measured using the Karnofsky Performance Scale (KPS; 0%–100%). Linear regression with stepwise selection was used to identify predictors of KPS trajectories. Kaplan–Meier curves and adjusted Cox proportional hazard models were used to compare survival.ResultsMean KPS was low at listing (47.9%) and transplant (45.6%) and increased to 85.7% and 89.2% at 1‐ and 5‐years posttransplant. Independent predictors of KPS trajectory in the first year included hypertension, diabetes, BMI, prior tobacco, previous malignancy, age, sex, education level, insurance type, etiology of heart disease, prior cardiac surgery, “1A” waitlist priority, and hospitalization status. KPS trajectory during the waitlist period and the first year posttransplant predicted survival, independent of baseline KPS. Decrease in KPS > −30% and −30% to < 0% in the first year were associated with 5.74 (3.45–9.56) and 2.09 (1.69–2.59) times higher mortality than stable KPS after adjusting for baseline KPS and other factors. Poor KPS trajectory in the waitlist period was similarly associated with higher mortality.ConclusionsFunctional status improvement is an important outcome following heart transplantation, and KPS trajectory predicts survival. Most patients achieve high KPS, but clinical and social interventions may optimize KPS trajectory for high‐risk patients.
Bayesian Population Pharmacokinetic Modeling of Ondansetron for Neonatal Opioid Withdrawal Syndrome
Authors: Lam Kevin , Mondick John T. , Peltz Gary , Wu Manhong , Kraft Walter K. 
Published: February 2025

ABSTRACTOndansetron is an anti‐emetic 5‐HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double‐blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two‐compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis‐Hastings Markov‐chain Monte Carlo estimation algorithm in NONMEM. The updated Bayesian model indicated a slower absorption rate (KA) but no differences in model parameters (CL, V, V2, Q) after including body weight and postmenstrual age. Sensitivity analyses on CL prior revealed statistical improvement favoring larger body weights, but not changes in postmenstrual age. However, further model development using larger body weights did not illustrate superior performance through visual inspection of diagnostic plots. Overall, a cumulative AUC of at least 1000 ng*h/mL appears to be the threshold for reductions in symptom severity. Exposure‐response analyses suggest the total number of doses to be the primary driver for efficacy with respect to AUC, which reasonably aligns with the literature. Overall, it is suggested that at least three doses of the current oral ondansetron regimen are required to reduce symptom severity in neonates.
Unmet treatment need: The size of the gap for alcohol and other drugs in Australia
Authors: Ritter Alison , O'Reilly Keelin 
Published: February 2025

AbstractIntroductionAssessing unmet demand for alcohol and other drug (AOD) treatment requires accurately counting those in treatment and determining those in need of treatment. Using updated epidemiological and treatment data, this study sought to provide an updated estimate of the unmet demand for AOD treatment in Australia.MethodsAustralian prevalence rates for alcohol, cannabis, methamphetamine and opioid use disorders were obtained from the Global Burden of Disease and research studies. The estimated proportion of people who would likely not seek or need treatment were subtracted from the diagnosed population. The number of people receiving treatment was estimated using AOD treatment databases and previous research.ResultsAn estimated 752,812 to 1,291,119 people met criteria for a substance use disorder in Australia in 2023. Removing the proportion of people who would not need or seek treatment resulted in between 406,697 and 668,497 people as the potential treatment population. The number of people who received treatment in Australia was estimated at 198,731 people. The unmet demand for AOD treatment was estimated to be between 207,966 and 469,767 in 2023.Discussion and ConclusionsIn Australia, we only treat between 30% and 48% of the population who would seek and benefit from AOD treatment. This is a conservative analysis that assumes only 40% of the alcohol and cannabis use disorder population would seek treatment. The findings from this analysis highlight the continued significant unmet treatment needs of people with substance use disorders. Treatment resources need to be doubled in order to address this unmet treatment population.
Attunement and the Sense of Significance in Dianthropocene Life
Authors: Lybke Steen Hjul 
Published: February 2025

ABSTRACTThe concept of the Anthropocene rightly points to the damaging effects of human agency on ecosystems and the climate. In this article, I argue that the agency of nature nonetheless continues to play a central role on the human sense of significance. For this purpose, I introduce and discuss the Danish philosopher‐theologian K.E. Løgstrup's concept of attunement and show how attunement constitutes a relationship between humans and nature through which a sense of fellowship, rather than hostility, springs. This section is divided into two parts. The first part outlines the elementary features to Løgstrup's argument in his philosophy of sensation, while the second part elaborates on his concept of attunement. It is argued that Løgstrup's philosophy of sensation and attunement describes what I call sovereign conditions of life that are continuously at work in midst of the Anthropocene. Subsequently, two empirical cases are applied to illustrate how attunement is operative in experiences of agency in nature. In conclusion, I propose the concept of the Dianthropocene as a tool for rediscovering the mutual ‘throughput’ circulations between human and more‐than‐human agency.
Familial High‐Risk for Psychosis and Bipolar Disorder Amongst Youth in an Academic Healthcare System: A Real‐World Assessment of Clinical Characteristics and Implications for Clinical Care
Authors: Türközer Halide Bilge , Guvenek‐Cokol Perihan Esra , Millman Zachary B. , Dickstein Daniel , Öngür Dost 
Published: February 2025

ABSTRACTObjectiveFamily history is amongst the most significant risk factors for psychotic and bipolar disorders. Despite being clearly defined, easily and early identifiable, familial high‐risk status is minimally accounted for in mainstream prevention paradigms. This study reports on the demographics and clinical characteristics of youth with a first‐degree relative affected by psychotic or bipolar disorders within a large academic healthcare system.MethodIn this quality improvement study, using electronic medical records, the authors examined demographics, psychiatric and medical diagnoses, substance use, service utilisation, and psychotropic medication use in children, adolescents and young adults (age 24 or younger) with and without a family history of psychotic or bipolar disorders within the Mass General Brigham (MGB) healthcare system.ResultsFamily history‐positive (FHP) youth demonstrated markedly higher rates of psychiatric problems (57.8%) compared to family history‐negative (FHN) youth (8.5%), including higher rates of psychotic and bipolar disorders, as well as anxiety disorders and depression. FHP youth also had more frequent psychotropic medication use and medical problems. Additionally, FHP youth reported higher cannabis and alcohol use, along with higher rates of suicidal ideation and trauma. Despite this, only 4% of FHP youth visited an MGB psychiatry or psychology department within the six months preceding the analysis.ConclusionFHP youth constitute a distinct and practically identifiable risk cohort within a large academic healthcare system. Increased psychiatric and medical problems coupled with more prevalent risk factors amongst familial high‐risk youth highlight the need for tailored clinical programmes to achieve both primary and secondary prevention.
The Impact of Social Entrepreneurship Education on Students' Social Entrepreneurial Intention: The Mediating Role of Social Entrepreneurial Competence
Authors: Mao Di , Yao Wei 
Published: February 2025

ABSTRACTWhile extensive research has been conducted on social entrepreneurship education and its potential to enhance university students' social entrepreneurial intentions, questions persist in relation to whether social entrepreneurial competence plays a relevant role in this context. This paper presents the findings from a Chinese study that aims to investigate the impact of social entrepreneurship education in universities on students' social entrepreneurial competence and their intentions toward social entrepreneurship. Our findings highlight the importance of competence‐based education in fostering social entrepreneurial intentions. Social entrepreneurship education increases university students' emotional competence and functional competence, which are crucial for developing social entrepreneurial intentions. This paper contributes to social entrepreneurship education literature by emphasising the need to integrate a competence‐based view into social entrepreneurship education programs. Some implications and suggestions for further practice and research are also put forward based on the result analysis.
Beyond the Classroom: How Socioeconomic Status, Parental Involvement and Home Environment Impact on Students' Science Academic Performance at Secondary Schools
Authors: Zafeer Hafiz Muhammad Ihsan , Maqbool Samra , Rong Yu , Maqbool Sufyan 
Published: February 2025

ABSTRACTScience education is crucial for students as it fosters critical thinking, problem‐solving skills and a deeper understanding of the natural world. The present study explored factors beyond the classroom that impact students' science academic performance (SSAP) at secondary schools. Based on research questions and literature, three hypotheses were formulated using factors beyond the classroom such as socioeconomic status (SES), parents' involvement (PI) and home environment (HE) that impact SSAP at secondary schools. A quantitative survey approach was employed. Data were collected from 430 participants who were science teachers and currently teaching science courses at secondary schools in Lahore, Punjab, Pakistan. The data collection process included using a survey questionnaire to collect data on SES, PI, HE and SSAP. In order to analyse the given data, two statistical software were used, namely SPSS and AMOS 24. Several statistical methods were used to analyse the collected data, such as exploratory factor analysis (EFA) to uncover the underlying structure of a relatively large set of variables and confirmatory factor analysis (CFA) to test whether the data fit a hypothesised measurement model. Moreover, correlation analysis was conducted to discover the relationship among variables, while regression analysis was conducted to determine the impact of independent variables on the dependent variable. The findings revealed factors beyond the classroom (SES, PI and HE) statistically positive impact SSAP. Based on the results, the study recommends that schools organise workshops and training sessions for parents to support their children's science learning, offer flexible parental involvement opportunities and provide educational resources like books and kits to help the academic environment at home. Policymakers and other stakeholders should ensure equitable resource distribution across schools, mainly targeting low‐SES areas and providing additional funding for science programmes and extracurricular activities.