bluuebunny/crossref_metadata_2025_split huggingface dataset:
The overall and smoking-attributable burden of multiple sclerosis among older adults aged 65–89 years from 1990 to 2019 and predictions to 2040
Authors: Su Jiao , Liang Yuanhao , He Xiaofeng 
Published: August 2024

BackgroundThe global prevalence of aging individuals with multiple sclerosis (MS) is increasing. This study aimed to assess the burden and trends of overall and smoking-attributable MS in older adults aged 65–89 years at the global, regional, and national levels.MethodsThe number and rates of years of life lived with disability (YLD) and years of life lost (YLL) due to MS for older adults in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease (GBD) Study 2019. Estimated annual percentage change (EAPC) in the age-standardized YLD and YLL rates were calculated to quantify the temporal trends. The Bayesian age-period-cohort model was used to predict the trends from 2020 to 2040.ResultsIn 2019, there were an estimated 80,040 (95% uncertainty interval 57,534 to 103,608) YLD and 139,132 (107,632 to 161,172) YLL caused by MS among older adults globally. The age-standardized YLD and YLL rates decreased by an average of −0.21% (95% CI –0.26 to −0.16) and − 0.2% (95% CI –0.26 to −0.14) per year for overall MS from 1990 to 2019, respectively. The number of YLL globally in 2019 was 7,891 (5,003 to 10,991) and 15,667 (10,833 to 20,076) due to smoking-attributable MS. The age-standardized YLD and YLL rates decreased by an annual average of −1.14% (95% CI –1.25 to −1.04) and − 1.15% (95% CI –1.27 to −1.03) for MS attributable to smoking. Although the global age-standardized rates of YLD and YLL for MS among older adults declined from 1990 to 2019, many regions showed increases. The largest increase in age-standardized YLD rate of MS was observed in East Asia (average annual change 1.62% [95% CI: 1.56 to 1.68]), while the largest increase in the age-standardized YLL rate occurred in High-income North America (1.74% [1.53 to 1.96]). Nationally, the age-standardized YLD and YLL rates for overall and smoking-attributable MS increased exponentially with increases in SDI level (all model p &lt; 0.001). Furthermore, projections have also indicated an expected decrease in the age-standardized rates of YLD and YLL of MS in the elderly population from 2020 to 2040.ConclusionTracking trends in MS burden among older adults provides insights into the potential shifts in disease patterns over time. The findings lay the groundwork for informed decision-making in public health and healthcare delivery, aiming to ensure that older adults with MS receive appropriate care and support.
Exacerbation of symptoms, nocturnal acid reflux, and impaired autonomic function are associated with sleep disturbance in gastroesophageal reflux disease patients
Authors: Huang Yizhou , Liu Jie , Xu Linsheng , Qi Wu , Dai Jie , Wang Bo , Tian Jiashuang , Fu Xin , Yu Yue 
Published: August 2024

Background and aimGastroesophageal reflux disease (GERD) patients often report sleep disturbance (SD); however, the relationship between GERD and SD is unknown. This study investigated whether SD affects symptoms, acid reflux, and autonomic function in GERD patients.MethodsA total of 257 subjects (126 patients with SD and 99 patients without SD) participated in this survey from January 2020 to August 2022. Participants were required to complete questionnaires including the GERD impact scale (GIS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Esophageal mucosal injury, acid exposure, peristaltic function, and autonomic function were assessed by upper endoscopy, high-resolution esophageal manometry (HRAM), 24-h multichannel intraluminal impedance with pH (24 h-MII-pH), and electrocardiography (ECG).ResultsGastroesophageal reflux disease patients with SD experienced a higher frequency of prolonged reflux (p &lt; 0.001), longest reflux event (p &lt; 0.001), acid exposure time (p &lt; 0.001) during the recumbent period, and a higher incidence of erosive esophagitis (EE) (59.5 vs. 45.5%, p = 0.036) than those without SD. Pearson’s correlation analysis showed that SD was positively correlated with GIS (r = 0.725, p &lt; 0.001), HAMA (r = 0.680, p &lt; 0.001), and HAMD (r = 0.323, p &lt; 0.001) scores, and negatively correlated with parasympathetic or vagal nerve activity (r = −0.770, p &lt; 0.001).ConclusionGastroesophageal reflux disease patients with SD experience more severe reflux symptoms and nocturnal acid reflux, which may be related to autonomic dysfunction.
The impact of physical exercise on neuroinflammation mechanism in Alzheimer’s disease
Authors: Hu Junhui , Huang Baiqing , Chen Kang 
Published: August 2024

IntroductionAlzheimer’s disease (AD), a major cause of dementia globally, imposes significant societal and personal costs. This review explores the efficacy of physical exercise as a non-pharmacological intervention to mitigate the impacts of AD.MethodsThis review draws on recent studies that investigate the effects of physical exercise on neuroinflammation and neuronal enhancement in individuals with AD.ResultsConsistent physical exercise alters neuroinflammatory pathways, enhances cognitive functions, and bolsters brain health among AD patients. It favorably influences the activation states of microglia and astrocytes, fortifies the integrity of the blood-brain barrier, and attenuates gut inflammation associated with AD. These changes are associated with substantial improvements in cognitive performance and brain health indicators.DiscussionThe findings underscore the potential of integrating physical exercise into comprehensive AD management strategies. Emphasizing the necessity for further research, this review advocates for the refinement of exercise regimens to maximize their enduring benefits in decelerating the progression of AD.
Lectin-type oxidized LDL receptor-1 as a potential therapeutic target for cerebral cavernous malformations treatment
Authors: Ashok Karthik , Martinez Tyra , Sesen Julie , Nasim Sana , Lang Shih-Shan , Heuer Gregory , Tucker Alexander , Lopez-Ramirez Miguel Alejandro , Smith Edward R. , Ghalali Aram 
Published: August 2024

IntroductionCerebral cavernous malformations (CCMs) are pathologic lesions comprised of clusters of thin-walled capillaries characterized by abnormal proliferation, angiogenesis, and bleeding secondary to somatic or germline mutations in endothelial cells. CCMs can cause headaches, seizures and/or neurological defects. There is a clinical need to develop better tools to detect CCMs and follow their progression in conjunction with the current use of neuroimaging techniques. Here we present data supporting the utility of LOX-1 (lectin-type oxidized LDL receptor 1), a 50 kDa transmembrane protein implicated in endothelial cell dysfunction and ischemia, as a putative biomarker for CCM.MethodsCCM urine samples (n = 23) were collected from pediatric CCM patients. Matched healthy controls (n = 24) were collected from pediatric patients with either Chiari I malformation or fatty filum terminale, and otherwise normal findings. All samples were collected with patient/family consent and institutional review board approval.Samples were analyzed with Olink Proteomic Proximity Extension Assay (PEA). Differences in expression for 2,925 unique proteins were quantified between healthy control urine samples and CCM urine samples. The results were normalized, validated, and analyzed for demographic bias. In addition to urine samples, CCM tissue from patients was harvested and used to create primary cell lines for in vitro analysis of LOX-1 expression, in addition to immunofluorescence of lesional tissue excised at surgery.ResultsANOVA analysis of the CCM urine samples showed a statistically significant increase in LOX-1 compared to the control samples, with CCM patients exhibiting a &gt; 5-fold increase in urinary expression. Corroborating these elevated levels of circulating marker, analysis of source tissue from surgically resected CCMs revealed that LOX-1 is increased in both CCM patient cavernoma primary cell lines and operative specimens.ConclusionLOX-1 is involved with pathways implicated in CCM pathogenesis and our data here reveals that LOX-1 expression is significantly elevated in CCM patients as compared to matched healthy control individuals, including both source tissue from surgically excised CCMs and in analysis of samples collected from outside of the central nervous system, particularly urine. This proof-of-principle data suggests that LOX-1 may have potential utility as a target for CCM treatment and supports further investigation related to its potential mechanistic impact on CCM pathogenesis.
Prevalence and determinants of overweight or obesity among medical students over a 2-year observation
Authors: Szemik Szymon , Zieleń-Zynek Iwona , Szklarek Ewa , Kowalska Małgorzata 
Published: August 2024

IntroductionUniversity students are a special population group characterized by changes in BMI values over the subsequent years of education, with an upward tendency to BMI. The presented study aims to evaluate the prevalence of overweight and obesity and their determinants in medical students during the 2-year follow-up observation.Materials and methodsWe analyzed data collected from the first follow-up of the cohort study named “POLLEK” conducted among medical students at the Medical University of Silesia in Katowice. Students were followed at two points of time: in their inaugural year of studies (the academic year 2021/2022, T1, N = 427), and subsequently in their second year (the academic year 2022/2023, T2, N = 335).ResultsIn the initial year of evaluation, 371 individuals (86.9%) exhibited normal body weight, 47 (11.0%) were overweight, and 9 (2.1%) were classified as obese. Subsequent assessments during the second year revealed the following distribution: 277 students (84.2%) with normal body weight, 40 (12.2%) classified as overweight, and 12 (3.6%) identified as obese. In summary, regardless of the academic year, an increased risk of being overweight or obese was significantly associated with dissatisfaction with personal health, financial strain, and a diet abundant in animal products.ConclusionThe results of our study confirmed an increase in the prevalence of overweight or obesity among medical students during the 2-year follow-up observation. Significant determinants of overweight or obesity among medical students were: dissatisfaction with individual health status, male sex, financial deficiencies, and a diet abundant in meat consumption.
Case Report: Methylphenidate and venlafaxine improved abdominal nociplastic pain in an adult patient with attention deficit hyperactivity disorder, autism spectrum disorder, and comorbid major depression
Authors: Kasahara Satoshi , Takahashi Miwako , Takahashi Kaori , Morita Taito , Matsudaira Ko , Sato Naoko , Momose Toshimitsu , Niwa Shin-Ichi , Uchida Kanji 
Published: August 2024

IntroductionNociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression.Case presentationHerein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved.ConclusionThe treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP.
Pharmacokinetics and safety profiles of beinaglutide injection, a recombinant human GLP-1, in adults with overweight/obesity: results from a phase I clinical trial
Authors: Lin Pingping , Li Chengqian , Liu Yanping , Sun Feifei , Hsieh Tsung-Han , Lin Zhang  , Ma Yaping , Gao Xiaomeng , Yu Qing , Cao Yu 
Published: August 2024

BackgroundBeinaglutide, whose active ingredient is rhGLP-1, has been widely used as a pharmacological therapy for T2DM. We explored the safety and pharmacokinetics of beinaglutide in Chinese overweight/obese volunteers to lay a foundation for clinical applications of beinaglutide as an anti-obesity drug.MethodsAn open-label, single center, multiple ascending dose phase I clinical trial was conducted in 16 overweight/obese Chinese volunteers. The plasma concentrations of beinaglutide were determined by a validated ELISA method and the pharmacokinetic parameters were estimated via non-compartmental analysis methods. Adverse events were also recorded.ResultsBeinaglutide sequentially multiple dosing (three times daily) at different doses were generally well tolerated, without serious AEs leading to discontinuation of the trial. After multiple subcutaneous injections of different doses (0.1, 0.14 and 0.2 mg), the average blood concentration of beinaglutide with or without baseline correction showed a similar trend among different dose groups on different study days. After reaching the peak concentration around 15 min, it began to decrease, and the median of Tmax and Tmax,adj was 10–15 min. The exposure in vivo increased in proportion to the dosage increment, demonstrating linear pharmacokinetic characteristics. There were no statistically significant differences in the main PK parameters and no accumulation of beinaglutide after multiple dosing. After multiple subcutaneous injections, a gender difference was observed, while no differences in BMI were found under the grouping conditions.ConclusionThe safety profile and pharmacokinetic properties support further development and clinical applications of beinaglutide as an anti-obesity drug.Systematic Review Registration[https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BPEI&amp;selectaction=Edit&amp;uid=U00050YQ&amp;ts=2&amp;cx=wy0ioj].
CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017–2023)
Authors: Shi Jing , Liu Xinya , Jiang Yun , Gao Mengjiao , Yu Jian , Zhang Yuanming , Wu Li 
Published: August 2024

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients’ T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported.MethodsUsing SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs).ResultsThe FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%).ConclusionThis study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers.
Initial dosage optimization of olanzapine in patients with bipolar disorder based on model-informed precision dosing: a study from the real world
Authors: Chen Xiao , Hu Ke , Shi Hao-Zhe , Chen Liang , Zhang Yi-Jia , He Su-Mei , Zhang Cun , Wang Dong-Dong 
Published: August 2024

ObjectivesOlanzapine is used for treating bipolar disorder (BPD); however, the optimal initial dosing regimen is unclear. The present study aimed to investigate the optimal olanzapine initial dosage in patients with BPD via model-informed precision dosing (MIPD) based on a real-world study.MethodsThirty-nine patients with BPD from the real-world study were collected to construct the MIPD model.ResultsWeight, combined used quetiapine influenced olanzapine clearances in patients with BPD, where the clearance rates were 0.152:1 in patients with or without quetiapine under the same weight. We simulated olanzapine doses once a day or twice a day, of which twice a day was optimal. Without quetiapine, for twice-a-day olanzapine doses, 0.80, 0.70, and 0.60 mg/kg/day were suitable for 40- to 56-kg BPD patients, 56- to 74-kg BPD patients, and 74- to 100-kg BPD patients, respectively. With quetiapine, for twice-a-day olanzapine doses, 0.05 mg/kg/day was suitable for 40- to 100-kg BPD patients.ConclusionThis study was the first to investigate the optimal olanzapine initial dosage in patients with BPD via MIPD based on a real-world study, providing clinical reference for the precision medication of olanzapine in BPD patients.
Requirement analysis in medical phantom development: a survey tool approach with an illustrative example of a multimodal deformable pelvic phantom
Authors: Wegner Marie , Schmiech Jonte , Sobirey Eve , Krause Dieter , Gargioni Elisabetta 
Published: August 2024

IntroductionMedical phantoms play a crucial role in medical imaging and therapy. However, the successful development of these phantoms heavily relies on a comprehensive understanding of the requirements specific to each application.MethodsIn this paper, we emphasize the significance of requirement analysis in medical phantom development and develop a novel approach for gathering and classifying requirements specific for phantom development.ResultsThe implemented survey tool is designed to accommodate the diverse needs of stakeholders involved in phantom development, including medical staff, physicists, engineers, and product developers. To validate the effectiveness of the approach, we conduct the development of a multimodal deformable pelvic phantom, providing insights into the process and its applicability.DiscussionThe results demonstrate the utility and reliability of our approach in systematically gathering, categorizing, and prioritizing requirements, thus facilitating the streamlined and efficient development of medical phantoms.
Autonomy support, peer relations, and teacher-student interactions: implications for psychological well-being in language learning
Authors: Wu Di , Dong Xin 
Published: August 2024

IntroductionThis research explores the intricate interplay among teacher-student relationships, perceived autonomy support, peer relationships, and their collective impact on the psychological well-being of 387 university students enrolled in French language courses across diverse academic institutions in China.MethodsEmploying Confirmatory Factor Analysis (CFA) and Structural Equation Modeling (SEM), this study aims to establish the validity and robustness of the proposed model. Data collection involved online surveys utilizing Likert scales and standardized measures to assess variables concerning educational relationships and psychological well-being.ResultsThe findings reveal significant associations between teacher-student relationships, autonomy support, positive peer relationships, and psychological well-being. Importantly, analyses demonstrate the influential role of positive peer relationships in mediating the effects of teacher-student relationships and autonomy support on students’ psychological well-being.DiscussionThese outcomes emphasize the crucial significance of educational relationships in shaping students’ psychological well-being within academic settings. The findings contribute to understanding the nuanced dynamics of educational interactions and their profound implications for student well-being. This highlights the necessity of cultivating positive educational environments for enhanced student mental health.