bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of GDE2 leads to complex behavioral changes including memory impairment
Authors: Daudelin Daniel , Westerhaus Anna , Zhang Nan , Leyder Erica , Savonenko Alena , Sockanathan Shanthini 
Published: April 2024

Abstract
Background
Alzheimer’s disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized.

Results
Here, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition.

Conclusions
Taken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration.
Attitudes, motivators, and barriers toward influenza vaccination for children: a study from a conflict-ridden country
Authors: Ahmed Wesam S. , Halboup Abdulsalam M. , Alshargabi Arwa , Al-mohamadi Ahmed , Al-Ashbat Yousf K. , Al-Jamei Sayida 
Published: April 2024

AbstractBackgroundDespite the increased recommendations for influenza vaccination, particularly among high-risk groups such as young children, Yemen lacks an influenza vaccination program, and the influenza vaccine is not included in the national immunization regime. This is exacerbated by the country’s fragile infrastructure, as well as the devastating consequences of the ongoing conflict, which include child undernutrition and strained healthcare resources. Thus, the objective of the current study is to assess the public attitudes and perceptions toward vaccinating children against influenza in Yemen.MethodsA cross-sectional study was conducted by distributing a validated survey questionnaire to potential participants using convenience sampling. Descriptive statistics were used to summarize sociodemographic data, knowledge of influenza vaccines, and attitudes and perceptions regarding vaccinating children against influenza. Logistic regression analysis was employed to identify associations between independent variables and the acceptance of vaccines for children.ResultsA total of 853 eligible individuals, parents and non-parents, successfully completed the survey. The uptake of the influenza vaccine among the participants was notably low as the majority (69.2%) had not previously received the vaccine, although the majority expressed a willingness to get vaccinated in the future (59.4%). The majority (68.5%) were willing to vaccinate children. The largest percentage of the participants who expressed hesitancy toward children’s vaccination cited multiple reasons to reject the vaccine (39.7%), with concerns regarding the safety of the vaccine being the predominant barrier to its acceptance for children (29.6%). On the other hand, motivating factors for vaccinating children included the validation of the vaccine’s safety and efficacy, endorsement of the vaccine by the government and physicians, integration of the vaccine into the national immunization program, and the provision of the vaccine free of charge and through schools. Significant predictors for vaccine acceptance in children included male gender, knowledge of the protective effect of the influenza vaccine, previous receipt of the vaccine, and a willingness to receive the vaccine in the future.ConclusionsThe study highlights the need for educational health campaigns to raise awareness and remove misconceptions regarding influenza and the role, benefits, and availability of its vaccine. These findings can serve as a robust foundation for the future design and implementation of an influenza vaccination program for children in Yemen.
ESDM intervention in severe preschool autism: an Italian Case report, psychological and social medicine reflections
Authors: Ferrara Rosaria , Damato Felice , Iovino Leonardo , Marti Flavio , Latina Roberto , Colombi Costanza , Ricci Pasquale 
Published: April 2024

Abstract
Background
The goal of our contribution is to discuss a preschool intervention based on the Early Start Denver Model and the use of the main tools for the detection of adaptive behaviour in cases of autism: Vineland, ABAS. Case presentation: the work is the presentation of a clinical case that has benefited from an intervention with the Early Start Denver Model methodology for the benefit of a child with socio-cultural and economic disadvantages. This early intervention, in a child of 36 months, which followed the diagnosis, was possible thanks to the intervention of many third-sector organizations which allowed this child, with a serious autism profile, to receive an evidence-based intervention for free. At the beginning of the intervention, the child presented a diagnosis of severe autism with absence of gaze, vocalizations and other communicative impairments. The level of motor clumsiness was also quite high, as were stereotypies. Conclusions: Research has shown the usefulness of intervening in this area with an early assessment and/or diagnosis and immediate intervention; however, public health services are not always able to maintain this pace. Our contribution therefore shows on the one hand the evidence of the improvements achieved by the child despite the low intensity of the treatment, and on the other hand, demonstrates the total versatility and adaptability of the Denver Model to the Italian context. In our conclusions, there are also some reflections on the tools used to measure adaptive behavior which seem to have a number of limitations and criticalities.
Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial
Authors: Richter Adrian , Truthmann Julia , Hummers Eva , Pereira Julia Freyer Martins , Gágyor Ildikó , Schuster Franziska , Witte Amelie , Böhm Susanne , Greser Alexandra , Kamin Petra , Stracke Sylvia , Dörr Marcus , Bülow Robin , Engeli Stefan , Chenot Jean François , Ittermann Till 
Published: April 2024

Abstract
Background
To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen.

Study design
This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed.

Statistical analysis plan
N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0–10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients’ global assessment of treatment success are secondary outcomes.

Discussion
The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals.

Trial registration
ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).
Clavicle fracture and triathlon performance: a case report
Authors: Gerdesmeyer Lennart , Burgkart Rainer , Saxena Amol 
Published: April 2024

Abstract
Background
Collarbone fracture is a common injury, particularly among athletes involved in contact sports and participating in endurance activities. Conventional treatment requires surgery and postoperative immobilization, resulting in an average return-to-sport timeframe of approximately 13 weeks. This case challenges the established treatment protocols, aiming to expedite recovery and enable a quicker resumption of high-intensity athletic activities.

Case presentation
A 24-year-old Caucasian athlete completed a Half-Ironman Triathlon (70.3) merely three weeks post-collarbone fracture. Utilizing Extracorporeal Magneto-Transduction Therapy (EMTT) alongside surgical intervention, the patient achieved accelerated healing and remarkable performance outcomes without encountering any adverse effects.

Conclusions
The integration of EMTT into the treatment paradigm for bone fractures alters the traditional understanding of recovery timelines and rehabilitation strategies. This case highlights the potential benefits of electromagnetic wave therapy in expediting the healing process and enabling athletes to resume high-level sports activities at an earlier stage.
Using test-time augmentation to investigate explainable AI: inconsistencies between method, model and human intuition
Authors: Hartog Peter B. R. , Krüger Fabian , Genheden Samuel , Tetko Igor V. 
Published: April 2024

Abstract
Stakeholders of machine learning models desire explainable artificial intelligence (XAI) to produce human-understandable and consistent interpretations. In computational toxicity, augmentation of text-based molecular representations has been used successfully for transfer learning on downstream tasks. Augmentations of molecular representations can also be used at inference to compare differences between multiple representations of the same ground-truth. In this study, we investigate the robustness of eight XAI methods using test-time augmentation for a molecular-representation model in the field of computational toxicity prediction. We report significant differences between explanations for different representations of the same ground-truth, and show that randomized models have similar variance. We hypothesize that text-based molecular representations in this and past research reflect tokenization more than learned parameters. Furthermore, we see a greater variance between in-domain predictions than out-of-domain predictions, indicating XAI measures something other than learned parameters. Finally, we investigate the relative importance given to expert-derived structural alerts and find similar importance given irregardless of applicability domain, randomization and varying training procedures. We therefore caution future research to validate their methods using a similar comparison to human intuition without further investigation.

Scientific contribution
In this research we critically investigate XAI through test-time augmentation, contrasting previous assumptions about using expert validation and showing inconsistencies within models for identical representations. SMILES augmentation has been used to increase model accuracy, but was here adapted from the field of image test-time augmentation to be used as an independent indication of the consistency within SMILES-based molecular representation models.

Graphical Abstract
Analysis and prediction of virtual machine boot time on virtualized computing environments
Authors: Auliya Ridlo Sayyidina , Lee Yen-Lin , Chen Chia-Ching , Liang Deron , Wang Wei-Jen 
Published: April 2024

AbstractStarting a virtual machine (VM) is a common operation in cloud computing platforms. In order to achieve better management of resource provisioning, a cloud platform needs to accurately estimate the VM boot time. In this paper, we have conducted several experiments to analyze the factors that could affect VM boot time in a computer cluster with shared storage. We also implemented four models for VM boot time prediction and evaluated the performance of the four models based on the datasets of four hosts and seven hosts in our environment, where the four models are the rule-based model, the regression tree model, the random forest regression model, and the linear regression model. According to our analysis, we found that host capability and maximal network bandwidth are two main factors that can influence VM boot time. We also found that VM boot time becomes harder to predict when booting VMs at different hosts concurrently due to competition between hosts to obtain resources. According to the experimental results, the proposed random forest regression is the best model for VM boot time prediction with an average accuracy of 94.76$$\%$$
%
and 96.59$$\%$$
%
in predicting VM boot time in two clusters with four and seven compute hosts, respectively.
Board gender diversity and corporate social responsibility
Authors: Chang Yuan , Wu Kun-Tsung , Lin Shu-Hui , Lin Chia-Jung 
Published: April 2024

AbstractBased on a total of 1,590 listed non-financial firms on the Taiwan Stock Exchange and the Taipei Exchange (formerly the Over The Counter securities market) covering the period of 2007~2020, this study examines whether firm's performance on Corporate Social Responsibility (CSR) is affected by corporate board gender diversity. Based on the Upper Echelons Theory, the Agency Theory and the Resource Dependence Theory, increasing the number of female director to achieve higher level of gender diversity brings forth traits such as compassion, kindness, helpfulness, empathy, interpersonal sensitivity, a willingness to nurture, and a greater concern for others' well-being. These traits help firms form policies that prioritize stakeholders' welfare. Moreover, board gender diversity corresponds to a more diverse and broad background, understanding and experience of business operations, enabling firms to better understand where the key interest groups they face are and what they value. This allows firms to make more effective and better-performing decision in CSR. Through correlation analysis and multiple regression estimation, the principal outcome shows that greater degree of board gender diversity is associated with better CSR performance, confirming the hypothesis that a more gender diversified board enhances the efficiency of monitoring and advising function of board and then forming corporate strategies and implementations toward a better stakeholders’ management.
A novel practical method to predict anterior cruciate ligament hamstring graft size using preoperative MRI
Authors: Liau Zi Qiang Glen , Ng Matthew Song Peng , Low Shawn Shao En , Chin Brian Zhaojie , Hui James Hoi Po , Kagda Fareed Husain Yusuf 
Published: April 2024

Abstract
Background
Predicting hamstring graft size preoperatively for anterior cruciate ligament (ACL) reconstruction is important for preempting an insufficient diameter in graft size intraoperatively, possibly leading to graft failure. While there are multiple published methods using magnetic resonance imaging (MRI) picture archiving and communication systems (PACS), most are not feasible and practical. Our study aims to (1) practically predict the ACL hamstring graft size in a numerically continuous manner using the preoperative MRI from any native MRI PACS system, (2) determine the degree of correlation between the predicted and actual graft size, and (3) determine the performance of our prediction method if we define an adequate actual graft size as ≥ 8 mm.

Methods
A retrospective review of 112 patients who underwent primary ACL reconstruction with quadrupled hamstring semitendinosus-gracilis grafts at a tertiary institution was conducted between January 2018 and December 2018. Graft diameter can be predicted in a numerically continuous manner as √[2*(AB + CD)], where A and B are the semitendinosus cross-sectional length and breath, respectively, and C and D are the gracilis cross-sectional length and breath, respectively.

Results
A moderately positive correlation exists between the predicted and actual graft diameter (r = 0.661 and p < .001). Our method yields a high specificity of 92.6% and a moderate sensitivity of 67.2% if we define an adequate actual graft size as ≥ 8 mm. An area under receiver-operating characteristic curve shows good discrimination (AUC = 0.856).

Conclusions
We present a practical method to predict the ACL hamstring graft size with high specificity using preoperative MRI measurements.
MC4R Variants Modulate α-MSH and Setmelanotide Induced Cellular Signaling at Multiple Levels
Authors: Rodríguez Rondón Alejandra V , Welling Mila S , van den Akker Erica L T , van Rossum Elisabeth F C , Boon Elles M J , van Haelst Mieke M , Delhanty Patric J D , Visser Jenny A 
Published: April 2024

Abstract

Context
The melanocortin-4 receptor (MC4R) plays an important role in body weight regulation. Pathogenic MC4R variants are the most common cause of monogenic obesity.

Objective
We have identified 17 MC4R variants in adult and pediatric patients with obesity. Here we aimed to functionally characterize these variants by analyzing 4 different aspects of MC4R signaling. In addition, we aimed to analyze the effect of setmelanotide, a potent MC4R agonist, on these MC4R variants.

Materials and Methods
Cell surface expression and α-melanocyte stimulating hormone (α-MSH)- or setmelanotide-induced cAMP response, β-arrestin-2 recruitment, and ERK activation were measured in cells expressing either wild type or variant MC4R.

Results
We found a large heterogeneity in the function of these variants. We identified variants with a loss of response for all studied MC4R signaling, variants with no cAMP accumulation or ERK activation but normal β-arrestin-2 recruitment, and variants with normal cAMP accumulation and ERK activation but decreased β-arrestin-2 recruitment, indicating disrupted desensitization and signaling mechanisms. Setmelanotide displayed a greater potency and similar efficacy as α-MSH and induced significantly increased maximal cAMP responses of several variants compared to α-MSH. Despite the heterogeneity in functional response, there was no apparent difference in the obesity phenotype in our patients.

Conclusion
We show that these obesity-associated MC4R variants affect MC4R signaling differently yet lead to a comparable clinical phenotype. Our results demonstrate the clinical importance of assessing the effect of MC4R variants on a range of molecular signaling mechanisms to determine their association with obesity, which may aid in improving personalized treatment.
Survival Outcome and Optimal Candidates of Primary Tumor Resection for Patients With Metastatic Medullary Thyroid Cancer
Authors: Liu Chu-Qiao , Shen Cen-Kai , Du Yu-Xin , Li Zi-Meng , Shi Xiao , Wang Yu , Wei Wen-Jun 
Published: April 2024

Abstract

Context
Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival.

Objective
The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy.

Materials and Methods
Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests.

Results
A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung, and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (P = .007) and cancer-specific survival (P = .0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality and cancer-specific mortality (all P &lt; .05). When analyzing different metastatic patterns, PTR significantly lowered the risk of overall mortality and cancer-specific mortality for patients with bone, lung, liver, or distant lymph node involvement (all P &lt; .05). Additionally, among patients with 1 or 2 metastases, those undergoing surgical resection were significantly associated with favorable overall survival (P = .008) and cancer-specific survival (P = .0247).

Conclusion
PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.