bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global burden of multiple sclerosis and its attributable risk factors, 1990–2019
Authors: Safiri Saeid , Ghaffari Jolfayi Amir , Mousavi Seyed Ehsan , Nejadghaderi Seyed Aria , Sullman Mark J. M. , Kolahi Ali-Asghar 
Published: October 2024

BackgroundMultiple sclerosis (MS) is a progressively debilitating disorder that has seen a notable rise in prevalence in recent years. This study examines the burden of MS from 1990 to 2019, providing a detailed analysis by age, sex, and sociodemographic index (SDI) across 204 countries and territories.MethodsData on the prevalence, death and disability-adjusted life years (DALYs) attributable to MS were obtained from the publically available Global Burden of Disease 2019 project. The estimates are reported as numbers, percentages, and age-standardized rates per 100,000, accompanied by 95% uncertainty intervals.ResultsIn 2019, MS accounted for 1.8 million prevalent cases, 22.4 thousand deaths and 1.2 million DALYs worldwide. There were significant declines in the global age-standardized prevalence, mortality and DALY rates of MS over the period 1990–2019. In 2019, females exhibited a higher global point prevalence and a greater total number of prevalent MS cases than males across all age groups. At the regional level, a non-linear relationship was observed between the age-standardized DALY rate of MS and SDI.ConclusionAlthough the global age-standardized DALY rate of MS decreased between 1990 and 2019, MS continues to account for a considerable number of DALYs and prevalent cases. Integrating MS and its associated risk factors into healthcare planning is vital, especially in areas with high levels of socioeconomic development.
Overlapping conditions in Long COVID at a multisite academic center
Authors: Grach Stephanie L. , Dudenkov Daniel V. , Pollack Beth , Fairweather DeLisa , Aakre Chris A. , Munipalli Bala , Croghan Ivana T. , Mueller Michael R. , Overgaard Joshua D. , Bruno Katelyn A. , Collins Nerissa M. , Li Zhuo , Hurt Ryan T. , Tal Michal C. , Ganesh Ravindra , Knight Dacre T. R. 
Published: October 2024

BackgroundMany patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.MethodsPatients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.ResultsIn this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p &lt; 0.001), neurological (92.4% vs. 15.4%, p &lt; 0.001), sleep (82.8% vs. 5.3%, p &lt; 0.001), skin (69.8% vs. 0%, p &lt; 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p &lt; 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p &lt; 0.001). The majority of LC patients with ME/CFS were women (77%).ConclusionWe found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.
Interactions between the human milk oligosaccharide 2′-fucosyllactose and Bifidobacterium longum subspecies infantis in influencing systemic immune development and function in piglets
Authors: Daniels Victoria C. , Monaco Marcia H. , Hirvonen Johanna , Ouwehand Arthur C. , Jensen Henrik Max , Mukerjea Ratna , Christensen Niels , Lehtinen Markus J. , Dilger Ryan N. , Donovan Sharon M. 
Published: October 2024

IntroductionThe oligosaccharide 2′-fucosyllactose (2′-FL) is a predominant component of human milk, serving as a prebiotic for gut microbiota and influencing immune development in infants. Bifidobacterium longum subspecies infantis (B. infantis) is a commensal bacterium found in breastfed infants. Both 2′-FL and a specific strain of B. infantis, Bi-26™, are commercially available. This study investigates the potential synbiotic relationship between 2′-FL and Bi-26™ on immune development.MethodsTwo-day-old piglets (n = 53) were randomized in a 2 × 2 design, receiving either a commercial milk replacer ad libitum without (CON) or with 1.0 g/L 2′-FL (FL). Piglets in each diet were further randomized to receive either glycerol stock alone or Bi-26™ (109 CFU) (BI and FLBI) orally once daily. On postnatal day (PND) 34/35, animals were euthanized, and blood was collected for serum cytokine analysis. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated for ex vivo stimulation and flow cytometry analysis. Serum and ex vivo cytokines were analyzed using a multivariate model. All other outcomes were analyzed using a two-way ANOVA, considering prebiotic and probiotic fixed effects. The significance level was set at a p value &lt;0.05, with trends reported for 0.05 &lt; p &lt; 0.1.ResultsImmune cell populations in PBMCs were unaffected by the experimental treatment. However, serum interleukin (IL)-1RA, IL-1β, IL-12, and IL-18 were all higher (p &lt; 0.05) in the FL group than in the CON group. In isolated PBMCs, lipopolysaccharide (LPS) stimulation resulted in higher IL-1RA and a trend for higher IFN-γ secretion in the FL group vs. the CON group.Conclusion2′-FL stimulates a balanced cytokine profile in healthy piglets without changing immune cell populations. When immune cells are stimulated ex vivo with LPS, 2′-FL primes T-cells for a proinflammatory response, which is moderated by co-administration of Bi-26™.
The prevention and improvement effects of vitamin D on type 2 diabetes mellitus: evidence from an umbrella review on Meta-analyses of cohort studies and randomized controlled trials
Authors: Cheng Le , Lv Chenhui , Xue Lushan , Zhang Cheng , Wang Lili , Wang Xi , Chen Shuangzhi , Li Xuemin , Feng Wenjuan , Xie Haoran , Zhao Haifeng 
Published: October 2024

BackgroundTo clarify whether Vitamin D prevent the occurrence of type 2 diabetes mellitus (T2DM) and improve glucose control in T2DM patients, we conducted this umbrella review, taking into account the inconsistent results of existing Meta-analyses. We aim to reveal the causal relationship between Vitamin D and T2DM through summarizing Meta-analyses of observational studies, and clarify the improvement on glucose control in T2DM patients through summarizing Meta-analyses of RCT studies between Vitamin D supplementation and T2DM patients, especially in T2DM patients with Vitamin D deficiency.MethodsWe collected the Meta-analyses of observational studies and RCTs in PubMed, Scopus, Embase, Web of Science, and Cochrane.Results16 Meta-analyses (6 effect sizes for cohort studies and 10 effect sizes for RCTs) were included in the umbrella Meta-analyses. Random-effects model was carried out to calculate the pooled point estimates and their respective 95% confidence intervals (CI). The results revealed that lower 25(OH)D levels increased the risk of T2DM (Pooled ESRR = 1.34; 95%CI: 1.16, 1.53), Vitamin D supplementation ameliorated FBG (ES = −0.56; 95%CI: −1.00, −0.11), HbA1c (ES = −0.11; 95%CI: −0.20, −0.02), insulin (ES = −0.38; 95%CI: −0.59, −0.18) and HOMA-IR (ES = −0.37; 95%CI: −0.57, −0.16) in T2DM patients, especially in those with Vitamin D deficiency (FBG = −0.98; HbA1c = −0.27; HOMA-IR = −0.52).ConclusionThe present umbrella Meta-analyses demonstrates the potential benefits of higher serum Vitamin D levels and Vitamin D supplementation in reducing the development and symptoms of T2DM.
Plant-based diet and risk of all-cause mortality: a systematic review and meta-analysis
Authors: Tan Junwen , Zhang Shipeng , Jiang Yanjie , Li Jie , Yang Chuan 
Published: October 2024

ObjectiveA systematic analysis was conducted to determine the relationship between a plant-based diet and all-cause mortality.MethodsThe PubMed, Embase and Web of Science databases were searched. Two authors selected English documents from the database. Then the other two authors extracted the data and evaluated the Newcastle–Ottawa Scale (NOS). This study adhered to the guidelines of the Preferred Reporting Project (PRISMA) and the PROSPERO Registry protocols. A mixed-effects model combined maximum adjusted estimates, with heterogeneity measured using the I2 statistic. The sensitivity analysis validated the analysis’s robustness, while publication bias was assessed.ResultsThe results of the meta-analysis of 14 articles revealed that a plant-based diet (PDI) can reduce cancer mortality (RR = 0.88, [95% CI 0.79–0.98], τ2: 0.02, I2: 84.71%), cardiovascular disease (CVD) mortality (RR = 0.81, [95% CI 0.76–0.86], τ2: 0.00, I2: 49.25%) and mortality (RR = 0.84, [95% CI 0.79–0.89], τ2: 0.01, I2: 81.99%) risk. Adherence to a healthy plant-based diet (hPDI) was negatively correlated with cancer mortality (RR = 0.91, [95% CI 0.83–0.99], τ2:0.01, I2:85.61%), CVD mortality (RR = 0.85, [95% CI 0.77–0.94], τ2: 0.02, I2: 85.13%) and mortality (RR = 0.85, [95% CI 0.80–0.90], τ2: 0.01, I2: 89.83%). An unhealthy plant-based diet (uPDI) was positively correlated with CVD mortality (RR = 1.19, [95% CI 1.07–1.32], τ2: 0.02, I2: 80.03%) and mortality (RR = 1.18, [95% CI 1.09–1.27], τ2: 0.01, I2: 89.97%) and had a certain correlation with cancer mortality (RR = 1.10, [95% CI 0.97–1.26], τ2: 0.03, I2: 93.11%). Sensitivity analysis showed no contradictory results.ConclusionThe hPDI was negatively associated with all-cause mortality, and the uPDI was positively associated with all-cause mortality.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#loginpage.
Endoscopic far-lateral supracerebellar infratentorial approach for resection of clival chordoma: case report
Authors: Han Song , Bai Yang , Sun Xiaoyu , Chen Ligang , Gao Yang , Liu Hongzhe , Li Huanhuan , Lai Jieyu , Feng Sizhe 
Published: October 2024

IntroductionThe surgery of clival chordoma remains one of the most formidable challenges for neurosurgeons because of its location at great depth in the cranium and proximity to critical neurovascular structures. Here, we describe the technique and feasibility of the purely endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) for resection of an intradural clival chordoma.Case descriptionA 68-year-old women presented with sudden ptosis on the left side for two weeks. Imaging examinations revealed an upper-middle clival lesion that transgressed dural confines towards the posterior fossa, which was separated from the sphenoid cavity by an intact thin layer of membrane structure in front. For surgery, the EF-SCITA approach via suboccipital craniotomy was attempted for protecting surrounding neurovascular tissue and the membrane barrier under direct vision. The patients were placed in a “head-up” lateral park-bench position. With the endoscopic holder, endoscopic procedures were performed using standard two-hand microsurgical techniques by one surgeon. Tentorium incision allowed a working corridor toward the clival bulge through the crural cistern, without brain traction seen in traditional retrosigmoid approach. Efficient tumor debulking facilitated the exposure of surrounding critical structures, including ipsilateral CN III and superior cerebellar artery above, the brainstem and basilar artery posteriorly, as well as ipsilateral CN VI displaced laterally, and subsequent tumor separation from them. Step-wise tumor resection was performed within dural and bone confines. After significant tumor removal, the pituitary stalk could be visualized anteriorly, together with contralateral internal carotid artery and CN III. Postoperative MRI depicted gross total excision of the lesion. The patient on follow-up at one year had complete recovery of cranial nerve functions, without signs of cerebrospinal fluid rhinorrhea.DiscussionThis technique combines advantages of the posterolateral approach and endoscopy, allowing access to the upper-middle clivus with seemingly low risks of postoperative morbidity. It would be a safe and effective alternative for resection of this rare entity.
Telehealth based parental support over 6 months improves physical activity and sleep quality in children with autism: a randomized controlled trial
Authors: Shen Xin , Huang Peiying , Liu Qian , Guo Yin , Zheng Lan 
Published: October 2024

PurposeSleep disturbances are prevalent in autistic children. The emergence of telehealth offers new possibilities for remote professional intervention. By combining telehealth with parental support, this study aims to explore a novel family-based model to enhance moderate-to-vigorous physical activity (MVPA) and improve sleep quality in children with autism.MethodsThirty-four autistic children (mean age = 15.7 years) were randomly assigned to either a 6-month intervention group or a control group. Both groups received standard physical education classes at school. The intervention group received additional after-school telehealth support. MVPA and sleep quality were assessed 1 week before the intervention and at the 6-month follow-up.ResultsAfter 6 months, children in the intervention group nearly doubled their daily MVPA compared to the control group (Cohen's d = 8.34, CI95% = 6.17–10.52). Actigraphy-assessed sleep efficiency was notably higher (d = 2.35, CI95% = 1.44–3.26), and there were reductions in wake time (d = 1.65, CI95% = 0.84–2.46), sleep fragmentation (d = 0.80, CI95% = 0.07–1.52), and sleep latency (d = 0.82, CI95% = 0.09–1.54) were all reduced. These improvements in objective sleep metrics were corroborated by subjective assessments using the Sleep Disturbance Scale for Children (d = 0.86, CI95% = 0.13–1.59).ConclusionsTelehealth combined with parental support addresses barriers to enhancing health behaviors at home. This innovative model not only improves after-school MVPA and sleep quality in autistic children but also holds significant potential for benefiting other populations requiring remote support.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT06444659?id=NCT06444659&amp;rank=1 (NCT06444659).
Dopamine internalization via Uptake2 and stimulation of intracellular D5-receptor-dependent calcium mobilization and CDP-diacylglycerol signaling
Authors: Kang Wenfei , Siewe Arlette Deukam , Oluigbo Chizurum C. , Arijesudade Mercy O. , Brailoiu Eugen , Undieh Ashiwel S. 
Published: October 2024

Dopamine stimulates CDP-diacylglycerol biosynthesis through D1-like receptors, particularly the D5 subtype most of which is intracellularly localized. CDP-diacylglycerol regulates phosphatidylinositol-4,5-bisphosphate-dependent signaling cascades by serving as obligatory substrate for phosphatidylinositol biosynthesis. Here, we used acute and organotypic brain tissues and cultured cells to explore the mechanism by which extracellular dopamine acts to modulate intracellular CDP-diacylglycerol. Dopamine stimulated CDP-diacylglycerol in organotypic and neural cells lacking the presynaptic dopamine transporter, and this action was selectively mimicked by D1-like receptor agonists SKF38393 and SKF83959. Dopaminergic CDP-diacylglycerol stimulation was blocked by decynium-22 which blocks Uptake2-like transporters and by anti-microtubule disrupters of cytoskeletal transport, suggesting transmembrane uptake and guided transport of the ligands to intracellular sites of CDP-diacylglycerol regulation. Fluorescent or radiolabeled dopamine was saturably transported into primary neurons or B35 neuroblastoma cells expressing the plasmamembrane monoamine transporter, PMAT. Microinjection of 10-nM final concentration of dopamine into human D5-receptor-transfected U2-OS cells rapidly and transiently increased cytosolic calcium concentrations by 316%, whereas non-D5-receptor-expressing U2-OS cells showed no response. Given that U2-OS cells natively express PMAT, bath application of 10 μM dopamine slowly increased cytosolic calcium in D5-expressing cells. These observations indicate that dopamine is actively transported by a PMAT-implicated Uptake2-like mechanism into postsynaptic-type dopaminoceptive cells where the monoamine stimulates its intracellular D5-type receptors to mobilize cytosolic calcium and promote CDP-diacylglycerol biosynthesis. This is probably the first demonstration of functional intracellular dopamine receptor coupling in neural tissue, thus challenging the conventional paradigm that postsynaptic dopamine uptake serves merely as a mechanism for deactivating spent or excessive synaptic transmitter.
Efficacy and safety of Shenmai injection in the treatment of viral myocarditis: a systematic review and meta-analysis
Authors: Yang Qianhe , Qin Jie , Li Ziyue , He Yue , Zhou Yabin 
Published: October 2024

PurposeTo evaluate the efficacy and safety of Shenmai injection for the treatment of viral myocarditis (VMS) through systematic evaluation and meta-analysis.MethodsSeven databases were searched to identify randomized controlled trials that examined the use of Shenmai injection for the treatment of VMS. The databases were searched from inception to 20 January 2024. The quality of the included studies was evaluated via the Cochrane risk of bias tool (RoB 2) version 2. Data analysis was performed using Review Manager 5.4 and Stata 16.ResultsIn total, 18 randomized controlled trials were included. The trials were conducted in 2006–2024 and included 1,661 patients with VMS. The results reveal that Shenmai injection combined with conventional treatment was superior to conventional treatment alone in terms of the following outcomes: total effective rate [RR = 1.22, 95% CI (1.16, 1.28)], CKMB [SMD = −3.33, 95% CI (−4.85, −1.81)], electrocardiogram (ECG) efficacy [RR = 1.30, 95% CI (1.20, 1.40)], AST [SMD = -0.70, 95% CI (−1.28, −0.11)], LDH [SMD = −1.17, 95% CI (−1.37, −0.97], p &lt; 0.00001], CK [SMD = −1.74, 95% CI (−2.34, −1.13)], TNF-α [SMD = −1.35, 95% CI (−1.85, −0.84)], and IL-6 [SMD = −1.40, 95% CI (−1.76, −1.05)]. There were no significant differences in the incidence of adverse reactions [RR = 1.56, 95% CI (0.73, 3.33), p = 0.25] or cTnI levels [SMD = −3.35, 95% CI (−6.81, 0.11)] between the groups.ConclusionShenmai injection with conventional treatment can reduce the degree of myocardial injury in patients with VMS, weaken the inflammatory response and improve the clinical efficacy of the conventional treatment. This approach was found to be safe. However, additional high-quality studies are necessary to confirm the reliability of this treatment method.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/logout.php, identifier PROSPERO (CRD42024518665).
Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic/pharmacodynamic assessment in Chinese patients with community-acquired bacterial pneumonia
Authors: Bian Xingchen , Li Nanyang , Li Yi , Zhu Xu , Yu Jicheng , Hu Yingying , Yang Haijing , Wei Qiong , Wu Xiaojie , Wang Jingjing , Cao Guoying , Wu Jufang , Wang Yang , Zhang Jing 
Published: October 2024

PurposeLefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against Streptococcus pneumoniae and Staphylococcus aureus via PK/PD analysis.MethodsThe population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK/PD analysis was conducted for the intravenous administration of 150 mg q12 h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600 mg q12 h were assessed, considering original and higher plasma protein binding.ResultsLefamulin displayed similar PK characteristics in both Chinese and Western populations. The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150 mg q12 h via intravenous infusion for 1/1.5/2 h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% S. pneumoniae and S. aureus, considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1/1.5 h–2 h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600 mg q12 h lefamulin via oral administration proved comparable to those for intravenous administration.ConclusionThis study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of S. pneumoniae and S. aureus. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.
Safety assessment of sapropterin dihydrochloride: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS)
Authors: Zhong Jiahong , Yu Xihui , Lin Zhuomiao 
Published: October 2024

ObjectiveSapropterin dihydrochloride is the first drug for the therapy of phenylketonuria, which is a rare disease that occurs one of 10,000–15,000 newborns. As a result, detailed and comprehensive reports on the safety of sapropterin in large, real-world populations are required. The purpose of this study is to undertake a complete analysis of sapropterin’s adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) database.MethodsWe retrieved reports of adverse events with sapropterin as the principal suspect from FAERS between the first quarter of 2008 and the first quarter of 2024. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals.ResultsThe study collected 4,953 suspected AE cases from the FAERS database, with sapropterin as the major suspect. A total of 130 positive signals were obtained utilizing the ROR, PRP, and BCPNN. The FAERS database revealed that common clinical AEs of sapropterin included vomiting, upper respiratory infection, rhinorrhea, and a reduction in amino acid concentrations. Furthermore, we detected probable unexpected adverse events (AEs) using disproportionality analysis, including gastroesophageal reflux disease, flatulence, influenza, ear infection, viral infection, pharyngitis streptococcal, spontaneous abortion, and nephrolithiasis.ConclusionBy analyzing huge amounts of real-world data from the FAERS database, we found potential novel AEs of sapropterin using disproportionate analysis. It is advantageous for healthcare professionals and pharmacists to focus on efficiently managing sapropterin’s high-risk adverse events, improving drug levels in clinical settings, and ensuring patient medication safety.