bluuebunny/crossref_metadata_2025_split huggingface dataset:
An osmolarity dependent mechanism partially ameliorates retinal cysts and rescues cone function in a mouse model of X-linked retinoschisis
Authors: Gehrke Ella J. , Thompson Jacob , Kalmanek Emily , Stanley Sarah T. , Laird Joseph , Bhattarai Sajag , Lobeck Brianna , Mayer Sara , Mahoney Angela , Hassan Salma , Hsu Ying , Drack Arlene 
Published: October 2024

IntroductionX-linked retinoschisis (XLRS) is a vitreoretinal dystrophy caused by RS1 gene mutations which disrupt retinoschisin-1 (RS1) function. Vital for retinal architecture, the absence of functional RS1 leads to the development of intraretinal cysts. Intravitreal injection of a gene therapy for treating XLRS caused ocular inflammation in high dose groups in a phase I/II clinical trial. This study investigates a low dose subretinal gene therapy in Rs1 knockout (Rs1-KO) mice compared to injection of buffer alone. Observation of an unexpected therapeutic effect following the subretinal injection of the hypertonic buffer led to novel findings in XLRS.MethodsRs1-KO mice were subretinally injected with an AAV2/4 vector (n = 10) containing the RS1 gene driven by an Ef1α promoter, a hypertonic buffer (n = 15) (180 mM NaCl 0.001% F68/PBS (pH 7.4)), or isotonic buffer (n = 7) (155.2 mM NaCl 0.001% F68/PBS, pH 7.0). A sham puncture group was also included (n = 6). Endpoints included electroretinogram (ERG), optical coherence tomography (OCT), a visually guided swim assay (VGSA), and immunohistochemistry.ResultsUnexpectedly, hypertonic buffer-injected eyes had reduced cyst severity at 1-month post-injection (MPI) (p &lt; 0.0001), higher amplitudes in cone-dominant ERGs persisting to 5 MPI (5 Hz flicker; p &lt; 0.0001; 3.0 flash; p = 0.0033) and a trend for improved navigational vision in the light compared to untreated Rs1-KO eyes. To investigate the role of tonicity on this effect, an isotonic buffer-injected cohort was created (155.2 mM NaCl 0.001% F68/PBS, pH 7.0) (n = 7). Surprisingly, hypertonic buffer-injected eyes exhibited a greater reduction in cyst severity and demonstrated improved cone-dominant ERG metrics over isotonic buffer-injected and sham puncture eyes. An immunohistochemistry assay demonstrated greater cone density in hypertonic buffer-injected eyes than untreated Rs1-KO eyes at 5–6 MPI (p = 0.0198), suggesting a possible cone preservation mechanism. Moreover, our findings reveal a negative correlation between the peak severity of cysts and long-term ERG amplitudes in cone-dominant pathways, implying that effectively managing cysts could yield enduring benefits for cone function.Discussion/conclusionThis study presents evidence that cyst resolution can be triggered through an osmolarity-dependent pathway, and early cyst resolution has long-term effects on cone signaling and survival, offering potential insights for the development of novel treatments for XLRS patients.
The mediating effect of problem-focused coping on the relationship between emotional clarity and mental health among older adults
Authors: Cho Myung Hyun , Choi Kee-Hong 
Published: October 2024

ObjectiveIndividuals who can recognize emotions well are better able to identify and accept their feelings and manage them. This study examined the mediation of problem-focused coping in the pathway through which emotional clarity predicts higher life satisfaction and lower depression in older adults.MethodsIn total, 150 older adults (75 male and 75 female, aged 60–69 years, with a mean of 64.53 [SD = 2.49]) participated in a face-to-face survey, answering questions on emotional clarity, problem-focused coping, life satisfaction, and depression.ResultsEmotional clarity was associated with higher life satisfaction and lower depression in older adults. People who were aware of their emotions well were in better emotional condition. Mediation analysis revealed that problem-focused coping mediated the positive relationship between emotional clarity and life satisfaction and the negative relationship between emotional clarity and depression. Older adults who understand their own emotions tend to deal with emotional events in a problem-focused manner, leading to high life satisfaction and low depression.ConclusionThis study identifies cognitive conditions for increasing life satisfaction and preventing depression in later life and offers suggestions for personal and social efforts to maintain mental health.
Proceedings of a membrane update symposium: advancements, scientific insights, and future trends for dialysis membranes for enhanced clinical outcomes in end stage kidney disease patients
Authors: Wanner Christoph , Vanholder Raymond , Ortiz Alberto , Davenport Andrew , Canaud Bernard , Blankestijn Peter J. , Masereeuw Rosalinde , Kooman Jeroen Peter , Castellano Giuseppe , Stamatialis Dimitrios , Mitra Sandip , Grooteman Muriel , Weber Viktoria , Ebert Thomas , Abdelrasoul Amira , Steppan Sonja , Scheiwe Anna Rebecca , Stenvinkel Peter 
Published: October 2024

Purpose of symposiumFrom September 6 – 8 2022, the Life/2022 Membrane Symposium was held in Frankfurt, Germany, and transmitted live to a worldwide internet audience. The event was part of the Life/Nephrology Campus initiative, a continuous educational platform for the nephrology community to expand knowledge and share expertise on contemporary topics in chronic kidney disease. We describe recent questions and advances in the field, and we underline challenges in the care of dialysis patients and opportunities for integration of new findings into clinical practice to improve patient outcomes in end stage kidney disease patients.TopicsMost patients with kidney failure are on maintenance hemodialysis (MHD). The scientific program of the symposium was developed around topics about the role, functional determinants, technical aspects, limitations, and clinical implications of membranes presently in use. International experts with clinical or technical expertise as well as scientific recognition within the nephrology community were asked to prepare their presentations based on their own experiences, perceptions, opinions, and sources of information. The symposium devoted a major portion to discussing novel approaches for improving membranes and treatment quality, including updates on innovative concepts that may could potentially transform the landscape of kidney replacement therapy for chronic kidney disease patients in the future.ImplicationsThe intent was to provide insights into current attention points for healthcare professionals new to the field of MHD, and to test a unique forum for continuing medical education integrating physician and patient experiences to promote changes in clinical practice. Furthermore, the symposium premiered a specifically developed mixed reality holographic 3D model to demonstrate recent dialyzer innovation diminishing protein fouling on membrane surfaces. As a continuous online educational platform for scientific exchange, this Life/2022 event provided online learning opportunities with on-demand content, with all symposium lectures freely available on nephrologycampus.com.
Incidence of immune effector cell-associated neurotoxicity among patients treated with CAR T-cell therapy for hematologic malignancies: systematic review and meta-analysis
Authors: Han Min Woo , Jeong So Yeong , Suh Chong Hyun , Park Hyesun , Guenette Jeffrey P. , Huang Raymond Y. , Kim Kyung Won , Yoon Dok Hyun 
Published: October 2024

ObjectivesWe aim to assess the pooled incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) in clinical trials and real-world studies of chimeric antigen receptor (CAR) T-cell therapy for hematologic malignancy and compare the incidences among different agents.MethodsThe PubMed, Embase, and Web of Science databases were searched for clinical trials and real-world studies. An inverse-variance weighting model was used to calculate pooled incidences and subgroup analyses. Multivariable analysis was conducted using binomial-normal modeling.ResultsSeventy-five trials comprising 3,184 patients were included. The overall pooled incidence was 26.9% (95% CI, 21.7–32.7%) for all-grade and 10.5% (95% CI, 8.1–13.6%) for high-grade ICANS. In subgroup analysis, cohorts with anti-CD19 drugs had significantly higher ICANS incidences than cohorts with other agents. The multivariable analysis demonstrated higher odds of ICANS in anti-CD19 drug studies for high-grade (OR, 4.6) compared to anti-BCMA drug studies. In 12 real-world studies, studies used axicabtagene ciloleucel with CD28 (54.0% all-grade, 26.4% high-grade) exhibited significantly higher rates of all-grade and high-grade ICANS than studies using tisagenlecleucel with 4-1BB (17.2% all-grade, 6.1% high-grade).ConclusionsThe overall incidences of ICANS with CAR T-cell therapy were 26.9% for all-grade and 10.5% for high-grade. Compared with other agents, patients with anti-CD19 drugs had a significantly increased risk of developing high-grade ICANS. Therefore, careful monitoring of ICANS should be considered for patients undergoing CAR T-cell therapy.
Positron emission tomography neuroimaging of [18F]fluorodeoxyglucose uptake and related behavior in the Pink1−/− rat model of Parkinson disease
Authors: Converse Alexander K. , Krasko Maryann N. , Rudisch Denis Michael , Lunaris Charlie Lenell , Nisbet Alex F. , Slesarev Maxim S. , Szot John C. , Hoerst Andrew G. , Leverson Glen E. , Gallagher Catherine L. , Ciucci Michelle R. 
Published: October 2024

IntroductionParkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The Pink1−/− rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in Pink1−/− and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior.MethodsPink1−/− (n = 12) and WT (n = 14) rats were imaged by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and 6 weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for 18 regions identified a priori for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam.ResultsRelative glucose metabolism was significantly different in Pink1−/− rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, Pink1−/− rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra.ConclusionFDG PET reveals abnormalities in relative regional brain glucose metabolism in Pink1−/− rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the Pink1−/− PD model.
Prevalence of potential risk of eating disorders among young, unprofessional European athletes: results of the ERASMUS+ project SCAED
Authors: Kenđel Jovanović Gordana , Čulina Tatjana 
Published: October 2024

IntroductionAdolescent athletes are at higher risk of developing eating disorders (ED) due to sports environment pressures and developmental characteristics. The ERASMUS+ project Sports Community against Eating Disorders (SCAED) aims to assess the prevalence of the potential risk of eating disorders among young, unprofessional European athletes and to provide them with easier access to professional support and knowledge.MethodsThe online survey included 462 unprofessional athletes from six European countries aged 12–25 (average age 18.49 ± 5.50) on their socio-demographics, sports and lifestyle habits, behaviors, concerns, and perceived pressure from coaches and teammates regarding body weight and shape. The eating disorder potential risk was assessed using the Eating Disorder Examination for Adolescents (EDE-A) and Eating Disorders Screen for Athletes (EDSA).ResultsEvery seventh (14.9%, EDE-A) and fifth (19.9%, EDSA) of young, unprofessional European athletes were at possible risk for developing eating disorders. Overall potential risk (18.7% EDE-A, 26.6% EDSA), dietary restraint (12.9%), and concerns about eating (9.5%), shape (23.7%), and weight (19.6%) were significantly more prevalent among female athletes. Younger athletes showed a slightly higher prevalence and avoidance of food. Athletes training in weight-sensitive sports exhibited more behaviors related to eating disorders. Females (p = 0.003), younger, and those athletes training in less weight-sensitive sports noted higher weight- and shape-related pressure from coaches. Dissatisfaction with their current weight was expressed by 44.6% of athletes, while 46.1% thought that they needed to lose weight to improve performance.ConclusionThe observed prevalence of the potential risk of ED among young, unprofessional European athletes is concerning, particularly due to limited access to support. Efforts to reduce the prevalence should target female and younger athletes in weight-sensitive sports. The SCAED Erasmus+ project aims to decrease ED prevalence among young, unprofessional European athletes, their families, and coaches by supporting them through education and professional consultation.
Retrospective analysis of survival and safety of bevacizumab biosimilar and original drug combination chemotherapy in non-small cell lung cancer
Authors: Zhang Xinyi , Chu Xiaofei , Wang Jun , Gu Wenjing , Fu Xiaoyan , Zhang Jing , Wang Congying , Han Qinghui , Zhou Jing , Zhang Yongjing , Liu Xiaoyan 
Published: October 2024

IntroductionThe advent of bevacizumab has considerably transformed the therapeutic landscape for non-small cell lung cancer (NSCLC) patients devoid of specific genetic mutations. A pivotal milestone has been reached with the recent approval of a bevacizumab biosimilar, following rigorous phase III clinical investigations, poised to augment NSCLC therapeutic strategies.MethodsThis retrospective analysis encompasses a large-scale study conducted between January 2021 and December 2023, involving 1058 NSCLC patients (metastatic or locally advanced stages). The research design entailed a comparative assessment of the safety and efficacy profiles of combined therapies using the original bevacizumab and its biosimilar, adhering to RECIST v1.1 criteria. Adverse event grading was standardized using the National Cancer Institute’s CTCAE v5.0.ResultsNotably, the biosimilar demonstrated an objective response rate (ORR) of 29.79% in 606 patients, closely paralleling the 27.41% ORR observed in 452 patients receiving the original drug, with insignificant risk differences (-0.03) and a risk ratio of 0.987, affirming equivalence. Progression-free survival (PFS) was influenced by radiation status, treatment lines, and regimen combinations, while dosage intensity and genetic factors had negligible impacts. The incidence of treatment-emergent adverse events (TEAEs) was slightly higher in the biosimilar group (75.11%) versus the original drug group (72.78%), with grade 3 or more severe TEAEs occurring in 23.6% and 18.5% of patients, respectively (Detailed criteria for the definition and assessment of TEAEs have been added to the Methods section, including the use of the National Cancer Institute’s CTCAE v5.0 for grading).ConclusionsThe study affirms that bevacizumab biosimilars offer equivalent therapeutic efficacy and a similar safety profile to the originator product in the management of locally advanced or metastatic NSCLC. The tolerability of the toxicity profile, coupled with the absence of unforeseen adverse reactions, underscores the viability of biosimilar bevacizumab as a valuable addition to NSCLC treatment regimens. These findings also imply potential benefits for a broader patient population beyond clinical trial confines through the adoption of biosimilar beta-adrenergic blocking agents.
Robot-assisted Müllerian compartment resection for cervical cancer
Authors: Li Ya , Na Jing , Wang Xinyou , Han Shichao , Wang Jun 
Published: October 2024

ObjectiveRadical hysterectomy has been established as the standard treatment for early stage cervical cancers. Despite numerous efforts to standardize the technique for radical hysterectomy across varying extents of tumor invasion, success has been inconsistent. Total Müllerian Compartment Resection (TMCR), an ontogenetic compartment-based oncologic surgery initially developed for open procedures by Professor Höckel, offers a standardized approach applicable to all patients with locally confined tumors. This method holds promise for achieving thorough oncologic clearance while maintaining acceptable complication rates. Moreover, robotic-assisted surgery may further reduce morbidity compared to open surgery. In this context, we provide a detailed step-by-step description of robotically assisted Total Müllerian Compartment resection (R-TMCR) for cervical cancer and present feasibility data from a cohort of 20 patients.Subjects and methods20 patients with stage IA1-IB2 cervical cancer, robot-assisted resection of the Müllerian embryonic compartment was undertaken. Key metrics such as operative duration, intraoperative blood loss, and postoperative complication rates were meticulously recorded and analyzed.ResultsThe duration of the surgery varied from 185 to 500 minutes, with intraoperative blood loss ranging between 5 mL and 300 mL. Postoperative hemoglobin levels dropped by -15 to 40 g/L from their preoperative values. Notably, there were no instances necessitating conversion to open surgery, and no intraoperative complications occurred. The rate of postoperative complications was 0%. Over the follow-up period, which averaged 18 months, there were no observed locoregional recurrences of cervical cancer, nor were there any deaths attributed to cervical cancer during this time.ConclusionThe application of robotic Müllerian compartment resection in the surgical treatment of cervical cancer is both safe and feasible. Utilizing robotic technology enables more precise and refined surgical outcomes. Combining embryonic compartment-based radical hysterectomy with the principles of membrane anatomy can standardize and optimize the surgical process, helping surgeons master radical hysterectomy more quickly and effectively.
Response of the photosynthetic characteristics and antioxidant system of Suaeda salsa to the changes of underground brine depth
Authors: Wang Ping , Xu Wenjing , Zhang Zehao , Fu Zhanyong , Li Tian , Sun Jingkuan 
Published: October 2024

IntroductionWater and salt conditions are key factors influencing vegetation growth on shell island in the Yellow River Delta. However, the effects of the depth of underground brine on the photosynthetic characteristics and antioxidant system of halophytes remain unclear.MethodsThe laboratory simulation experiment was carried out to investigate the effect of the changes of underground brine depth on Suaeda salsa using four levels of groundwater: 0 cm, 15 cm, 30 cm and 45 cm.ResultsThe results showed that different underground brine depths had significant impacts on the photosynthetic characteristics and antioxidant system of S. salsa, and 0-30 cm underground brine depth was suitable for S. salsa growth. The net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), light utilization efficiency (LUE) and carboxylation efficiency (CE) of S. salsa increased first and then decreased with increasing depth of underground brine. The stomatal limitation value (Ls) and WUE of S. salsa reached the peak value at the groundwater depth of 0 cm, and water use efficiency was reduced by 19.4%, 8.0% and 8.6% at 15 cm, 30 cm, and 45 cm, respectively, compared to the 0 cm treatment. With the deepening of underground brine depth, the value of LUE and CE firstly increased and then decreased, and reached the peak value when the depth was 30 cm. The antioxidant enzyme (SOD, POD and CAT) activities of S. salsa decreased and then increased with the increase of underground brine depth. The enzyme activities were the lowest when the underground brine depth was 30 cm. As the groundwater depth increased, MDA content decreased and then increased. The highest degree of membrane peroxidation in S. salsa leaves was observed at the depth of 45 cm.DiscussionOur study reveals that the antioxidant capacity of S. salsa was weakened at the underground brine depth of 45 cm and the growth of S. salsa was inhibited.
Prevenção da Pneumonia associada à ventilação mecânica com o uso de antibióticos aerossolizados: uma revisão sistemática
Authors: Rodrigues Lucas Vicente , Costa André Falcão Pedrosa 
Published: October 2024

A Pneumonia Associada à Ventilação Mecânica (PAV) é reconhecida como a segunda infecção mais comum em UTIs, associada a taxas significativas de mortalidade. Diversas abordagens são propostas para sua profilaxia. Entre elas o uso de antibióticos aerossolizados. Para observar a pertinência do uso de antibióticos administrados sob forma de aerossol, para a prevenção da Pneumonia Associada à Ventilação Mecânica, foi realizada uma revisão sistemática seguindo todo protocolo clássico. Foram incluídos e analisados estudos que investigam a eficácia e segurança desta abordagem. Os resultados são divergentes: enquanto alguns estudos indicam redução na incidência de PAV com antibióticos aerossolizados, outros não encontram diferenças significativas. A eficácia depende de fatores como a anatomia das vias aéreas e a técnica de administração, além de preocupações com a deposição ineficiente de drogas e o aumento da resistência bacteriana. Conclui-se que pesquisas de melhor qualidade são necessárias para confirmar a eficácia dos antibióticos aerossolizados para este intuito para que se obtenha evidências que indiquem sua aplicabilidade clínica.
Incidência das manifestações cutâneas e suas repercussões em pacientes com Coronavírus em Alagoas
Authors: Lisboa Camyla de Oliveira , Moura Aline Coelho , Pol-Fachin Laércio , Malta Pedro Henrique Oliveira , Costa Alessa Moísa Barros , Costa Gisele Vasconcelos Calheiros de Oliveira , Ferreira Brunna Karolyne Aguiar , Costa Maria Eduarda Lisboa 
Published: October 2024

A pandemia do vírus SARS COV, afetou socialmente, economicamente o mundo todo. Além do acometimento das vias aéreas típico, percebeu-se também a presença de manifestações dermatológicas nesse quadro viral, bem como: lesões urticariformes, maculopapulares, bolhosas, maculopapulares, urticariformes, isquêmicas. O foco principal do estudo foi quantificar a frequência com que surgem as manifestações cutâneas do coronavírus e avaliar suas repercussões em pacientes com Coronavírus. Foi realizado um estudo observacional analítico transversal, por meio da aplicação de um questionário online. O perfil predominante da amostra foram mulheres totalizando 71,2%, sendo a sua maioria 63,5% com idade entre 18-29 anos. Todos afirmaram residir em Alagoas. Desses, cerca de 99% das respostas afirmam ter sentido algum dos sintomas característicos, em sua maioria diagnosticados pelo exame RT-PCR positivo. Diante dos dados analisados, constatou-se que a presença das manifestações cutâneas não foi percebida na grande maioria dos entrevistados e dentre as que foram notadas, destacam-se as lesões descritas como avermelhadas isoladas ou em placas que coçavam. Dentre os locais do corpo mais afetados, as pernas se destacaram nas respostas, mostrando, assim, um achado relevante para diagnóstico.