bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world effectiveness and safety of Baloxavir Marboxil or Oseltamivir in outpatients with uncomplicated influenza A: an ambispective, observational, multi-center study
Authors: Cai Jianpeng , Wang Hongyu , Ye Xiaoting , Lu Shengjia , Tan Zhili , Li Zhonghua , Lin Dan , Qian Jiancheng , Lu Xiaoxian , Wan Jiaolong , Wang Jie , Ai Jingwen , Pu Yonglan , Qu Lihong , Wang Sen 
Published: July 2024

IntroductionBaloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce.MethodsWe conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza.ResultsA total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0  h (IQR, 20.0 to 50.0) and 48.0  h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18  h (IQR, 10.0–24.0) and 30.0  h (IQR, 19.0–48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR  =  1.36 [95%CI:1.12–1.64], p =  0.002) and the duration of fever (HR  =  1.93 [95%CI:1.48–2.52], p &lt; 0.001) compared to Oseltamivir. When antiviral drugs were given within 12–48  h after symptom onset, the Baloxavir Marboxil group had a significantly shorter TTAIS compared to the Oseltamivir group. There was no significant difference in the rate of adverse events between the two group (p = 0.555).DiscussionBaloxavir Marboxil was superior to Oseltamivir in alleviating influenza symptoms in outpatients with uncomplicated influenza. Our findings suggested that compared to Oseltamivir, Baloxavir Marboxil might be more appropriate for patients with influenza 12– 48 h after symptom onset.
Defining a clinically meaningful within-patient change threshold for the Cohen-Mansfield Agitation Inventory in Alzheimer’s dementia
Authors: Meunier Juliette , Creel Kristin , Loubert Angély , Larsen Klaus Groes , Aggarwal Jyoti , Hefting Nanco , Oberdhan Dorothee 
Published: July 2024

IntroductionThe Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This post hoc analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer’s disease.MethodsData were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer’s disease (ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584). Change in CMAI Total score (range 29–203; higher scores indicate higher frequency of agitation behaviors) from baseline to Week 12 was the primary endpoint in each trial. MWPC thresholds were estimated from anchor-based mean change analyses and receiver operating characteristic (ROC) curves. The Clinical Global Impression–Severity of illness (CGI-S) and Clinical Global Impression–Improvement (CGI-I) scales, both as related to agitation, were used as anchors. Empirical cumulative distribution functions (eCDFs) and probability density functions (PDFs) were plotted as supportive evidence. Distribution-based methods were also employed.ResultsData from 898 patients were analyzed (mean age, 73.7 years; mean baseline CMAI Total score, 73.8). The mean CMAI Total score change corresponding to a difference of small improvement vs. stable (CGI-S one-point decrease vs. no change), or minimally improved vs. no change (CGI-I rating of 3 vs. 4), ranged from −10.6 to −13.5 points. The mean CMAI Total score change corresponding to a difference of moderate improvement vs. stable (CGI-S two-point decrease vs. no change), or much improved vs. no change (CGI-I rating of 2 vs. 4), ranged from −20.2 to −25.7 points. ROC curve analyses generally produced smaller estimates of meaningful change. eCDFs and PDFs showed good distribution and separation of CMAI Total score change between CGI-S/CGI-I categories. In distribution-based analyses, the minimal detectable change for CMAI Total score (10.5–11.8 points) was generally lower than anchor-suggested thresholds.ConclusionTriangulation of evidence from anchor- and distribution-based analyses supports an MWPC threshold for CMAI Total score of −20 points, with a threshold range of −15 to −25 points, in patients with agitation associated with dementia due to Alzheimer’s disease.
Quantification of morpho-hemodynamic changes in unruptured intracranial aneurysms with irregular pulsation during the cardiac cycle using 4D-CTA
Authors: Chen Shiyao , Zhang Wen , Cheng Yunzhang , Wang Guohui , Lv Nan 
Published: July 2024

Background and purposePrevious studies predicting the rupture risk of intracranial aneurysms (IAs) have predominantly utilized static imaging data, overlooking the dynamic blood flow and biomechanical properties of the aneurysm wall. Irregular pulsation detected by 4D-CTA is a potential predictor of aneurysm rupture, albeit with uncertain clinical significance. This study aimed to analyze the changes in morpho-hemodynamic characteristics of IAs during the cardiac cycle to elucidate the dynamic changes and the associated hemodynamic mechanisms.MethodsA retrospective review was conducted on the 4D-CTA data of IA patients between January 2017 and September 2019. R-R intervals were segmented into 20-time phases, reconstructing 20 CT datasets to identify irregular pulsation and extract 3D aneurysm models. Computational fluid dynamics (CFD) simulations analyzed hemodynamic parameters such as oscillatory shear index (OSI) and relative residence time (RRT). Changes in morpho-hemodynamic characteristics were quantified in terms of the absolute change (parameter*) and relative change rate (parameter%). Rupture risk was assessed using the rupture resemblance model (RRS).ResultsEleven UIAs from 10 patients were finally included, with five aneurysms showing irregular pulsation (45.45%). No significant differences in morpho-hemodynamic characteristics were observed between aneurysms with or without irregular pulsation. More remarkable changes in aneurysm size (size*: 0.59 ± 0.14 mm vs. 0.32 ± 0.12 mm, p = 0.010; size%: 10.49% ± 1.43% vs. 3.95% ± 1.79%, p &lt; 0.001), volume (volume%: 13.72% vs. 6.39%, p = 0.009), OSI (OSI*: 0.02 ± 0.01 vs. 0.004 ± 0.005, p = 0.004; OSI%: 200% vs. 12.50%, p = 0.004) and RRT (RRT%: 97.14% vs. 43.95, p = 0.052) over the cardiac cycle were significantly linked to irregular pulsation. Aneurysms with irregular pulsation demonstrated a more unfavorable hemodynamic environment during the cardiac cycle, irrespective of the predicted rupture risk. Furthermore, irregular pulsation at the aneurysm dome exhibited higher hemodynamic instability than at the sidewall.ConclusionIrregular pulsation may indicate hemodynamic instability within the aneurysm, leading to an increased rupture risk in the area where irregular pulsation occurs. This proof-of-concept study could enhance understanding of dynamic changes in UIAs during the cardiac cycle and the underlying hemodynamic mechanisms.
Polygenic scores and Mendelian randomization identify plasma proteins causally implicated in Alzheimer’s disease
Authors: Cammann Davis B. , Lu Yimei , Rotter Jerome I. , Wood Alexis C. , Chen Jingchun 
Published: July 2024

BackgroundAn increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer’s disease (LOAD) pathology. Due to the increased permeability of the blood–brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.MethodsWe used a genome-wide association study (GWAS) of 90 different plasma proteins (n = 17,747) to create polygenic scores (PGSs) in an independent discovery (cases = 1,852 and controls = 1,990) and replication (cases = 799 and controls = 778) cohort. Multivariate logistic regression was used to associate the plasma protein PGSs with LOAD diagnosis while controlling for age, sex, principal components 1–2, and the number of APOE-e4 alleles as covariates. After meta-analyzing the PGS-LOAD associations between the two cohorts, we then performed a two-sample Mendelian randomization (MR) analysis using the summary statistics of significant plasma protein level PGSs in the meta-analysis as an exposure, and a GWAS of clinically diagnosed LOAD (cases = 21,982, controls = 41,944) as an outcome to explore possible causal relationships between the two.ResultsWe identified four plasma protein level PGSs that were significantly associated (FDR-adjusted p &lt; 0.05) with LOAD in a meta-analysis of the discovery and replication cohorts: CX3CL1, hepatocyte growth factor (HGF), TIE2, and matrix metalloproteinase-3 (MMP-3). When these four plasma proteins were used as exposures in MR with LOAD liability as the outcome, plasma levels of HGF were inferred to have a negative causal relationship with the disease when single-nucleotide polymorphisms (SNPs) used as instrumental variables were not restricted to cis-variants (OR/95%CI = 0.945/0.906–0.984, p = 0.005).ConclusionOur results show that plasma HGF has a negative causal relationship with LOAD liability that is driven by pleiotropic SNPs possibly involved in other pathways. These findings suggest a low transferability between PGS and MR approaches, and future research should explore ways in which LOAD and the plasma proteome may interact.
Influences of noise reduction on speech intelligibility, listening effort, and sound quality among adults with severe to profound hearing loss
Authors: Dong Ruijuan , Liu Pengfei , Tian Xin , Wang Yuan , Chen Younuo , Zhang Jing , Yang Liu , Zhao Shiyang , Guan Jingjing , Wang Shuo 
Published: July 2024

IntroductionNoise reduction (NR) algorithms have been integrated into modern digital hearing aids to reduce noise annoyance and enhance speech intelligibility. This study aimed to evaluate the influences of a novel hearing aid NR algorithm on individuals with severe-to-profound hearing loss.MethodsTwenty-five participants with severe-to-profound bilateral sensorineural hearing loss underwent three tests (speech intelligibility, listening effort, and subjective sound quality in noise) to investigate the influences of NR. All three tests were performed under three NR strength levels (Off, Moderate, and Strong) for both speech in noise program (SpiN) and speech in loud noise program (SpiLN), comprising six different hearing aid conditions.ResultsNR activation significantly reduced listening effort. Subjective sound quality assessments also exhibited benefits of activated NR in terms of noise suppression, listening comfort, satisfaction, and speech clarity.DiscussionIndividuals with severe-to-profound hearing loss still experienced advantages from NR technology in both listening effort measure and subjective sound quality assessments. Importantly, these benefits did not adversely affect speech intelligibility.
Trends in three malnutrition factors in the global burden of disease: iodine deficiency, vitamin A deficiency, and protein-energy malnutrition (1990–2019)
Authors: Ji Shaorong , Zhou Yinglu , Zhao Qilong , Chen Runtong , Su Zhenni 
Published: July 2024

BackgroundVitamin A deficiency, iodine deficiency, and protein-energy malnutrition are prevalent malnutrition issues that disproportionately affect low-income countries and pose significant risks to the health and development of children and adolescents. This study offers a detailed examination of these deficiencies' prevalence trends and gender and regional variations using Global Burden of Disease Study data from 1990 to 2019. It also assesses the specific impact on various age groups, providing essential insights for targeted health interventions and policy-making.MethodsData spanning from 1990 to 2019 on Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition were extracted from the 2019 Global Burden of Disease Study. Age-Standardized Incidence Rates (ASR) were computed by gender, region, and etiology, utilizing the estimated annual percentage change (EAPC) to assess temporal trends.ResultsIn 2019, Central Sub-Saharan Africa had the highest prevalence of Vitamin A deficiency, particularly among males, and iodine deficiency peaked in the same region for both genders. South Asia had the highest incidence of protein-energy malnutrition for both genders. Regions with a low Socio-Demographic Index (SDI) showed lower ASR for these deficiencies. Notably, Cameroon, Equatorial Guinea, and Maldives recorded the highest ASR for vitamin A deficiency, iodine deficiency, and protein-energy malnutrition, respectively. The declining ASR trend for vitamin A deficiency, especially among males, suggests effective interventions. East Asia saw a significant increase in iodine deficiency ASR from 1990 to 2019, particularly among women, requiring targeted interventions. The rising ASR of protein-energy malnutrition in several regions, especially among men, raises concerns. Vitamin A deficiency primarily affected children and adolescents, iodine deficiency predominantly impacted adolescents and young adults, and protein-energy malnutrition was chiefly observed among children under 5 years old. These findings underscore the necessity for tailored interventions considering age-specific nutritional needs and challenges.
Efficacy and safety of radical cystectomy with ileal conduit for muscle-invasive bladder cancer in the elderly: a multicenter retrospective study
Authors: Zhang Heqian , Li Anrui , Wang Wentao , Xu Songlin , Li Changfu , Teng Lichen 
Published: July 2024

ObjectiveRadical cystectomy with ileal conduit is the current mainstay of treatment for muscle-invasive bladder cancer and is also a high-risk procedure. Existing studies have limited targeted assessment of the efficacy and safety of this procedure, and the patient population appropriate for this procedure is still poorly defined. We sought to longitudinally analyze differences in the efficacy and safety of radical cystectomy with ileal conduit by age subgroups to assess whether the age factor should be used as an exclusion criterion when selecting this procedure.Materials and methodsWe retrospectively examined the clinicopathological data of patients with MIBC treated with RC with IC at the Cancer Hospital of Harbin Medical University between February 2014 and October 2023. Additionally, we utilized clinical and pathological data from the SEER database (2000-2020) for external validation of our findings. Patients were categorized into elderly (≥70 years at diagnosis) and non-elderly (&lt;70 years) groups. Statistical analyses included t-tests, non-parametric tests for continuous data, chi-square tests for categorical data, and Kaplan-Meier survival analysis.ResultsIn this study, 152 patients were included: 119 were categorized as non-elderly and 33 as elderly. For external validation, data from 416 patients in the SEER database were analyzed, with 172 classified as non-elderly and 244 as elderly. The results indicated that elderly patients were more likely to require ICU transfer postoperatively but exhibited a lower incidence of stoma inflammation. Additionally, both the data from our center and the external validation from the SEER database showed a concordance in cancer-specific survival (CSS) between the elderly and non-elderly groups. The efficacy of RC with IC was comparable in both elderly and non-elderly patients.ConclusionFor longitudinal age subgroups, RC with IC for both elderly and non-elderly MIBC had good efficacy and safety, and good quality of life after surgery. Although there are surgical and perioperative risks in elderly patients, there is no significant difference compared with non-elderly patients. In elderly patients requiring RC for bladder cancer, IC should remain the preferred mode of urinary diversion, and old age should not be used as an absolute exclusion criterion for IC.
Time budgets and weight shifting as indicators of pain in hospitalized horses
Authors: Nowak Magdalena , Martin-Cirera Albert , Jenner Florien , Auer Ulrike 
Published: July 2024

IntroductionPain assessment in horses presents a significant challenge due to their nonverbal nature and their tendency to conceal signs of discomfort in the presence of potential threats, including humans. Therefore, this study aimed to identify pain-associated behaviors amenable to automated AI-based detection in video recordings. Additionally, it sought to determine correlations between pain intensity and behavioral and postural parameters by analyzing factors such as time budgets, weight shifting, and unstable resting. The ultimate goal is to facilitate the development of AI-based quantitative tools for pain assessment in horses.Materials and methodsA cohort of 20 horses (mean age 15 ± 8) admitted to a university equine hospital underwent 24-h video recording. Behaviors were manually scored and retrospectively analyzed using Loopy® software. Three pain groups were established based on the Pain Score Vetmeduni Vienna : pain-free (P0), mild to moderate pain (P1), and severe pain (P2).ResultsWeight shifting emerged as a reliable indicator for discriminating between painful and pain-free horses, with significant differences observed between pain groups (p &lt; 0.001) and before and after administration of analgesia. Additionally, severely painful horses (P2 group) exhibited lower frequencies of feeding and resting standing per hour compared to pain-free horses, while displaying a higher frequency of unstable resting per hour.DiscussionThe significant differences observed in these parameters between pain groups offer promising prospects for AI-based analysis and automated pain assessment in equine medicine. Further investigation is imperative to establish precise thresholds. Leveraging such technology has the potential to enable more effective pain detection and management in horses, ultimately enhancing welfare and informing clinical decision-making in equine medicine.
Pleomorphic xanthoastrocytoma with NTRK fusion presenting as spontaneous intracranial hemorrhage—case report and literature review
Authors: Wu Yilong , Aw Sze Jet , Jain Swati , Ooi Li Yin , Tan Enrica E. K. , Chang Kenneth T. E. , Teo Harvey J. , Seow Wan Tew , Low Sharon Y. Y. 
Published: July 2024

BackgroundPleomorphic xanthoastrocytoma (PXA) is a rare brain tumor that accounts for &lt;1% of all gliomas. An in-depth understanding of PXA's molecular makeup remains a work in progress due to its limited numbers globally. Separately, spontaneous intracranial hemorrhage (pICH) is an uncommon but potentially devastating emergency in young children, often caused by vascular malformations or underlying hematological conditions. We describe an interesting case of a toddler who presented with pICH, later found to have a PXA as the underlying cause of hemorrhage. Further molecular interrogation of the tumor revealed a neurotrophic tyrosine receptor kinase (NTRK) gene fusion and CDKN2A deletion more commonly seen in infantile high-grade gliomas. The unusual clinicopathological features of this case are discussed in corroboration with published literature.Case presentationA previously well 2-year-old male presented with acute drowsiness and symptoms of increased intracranial pressure secondary to a large right frontoparietal intracerebral hematoma. He underwent an emergency craniotomy and partial evacuation of the hematoma for lifesaving measures. Follow-up neuroimaging reported a likely right intra-axial tumor with hemorrhagic components. Histology confirmed the tumor to be a PXA (WHO 2). Additional molecular investigations showed it was negative for BRAFV600E mutation but was positive for CDKN2A homozygous deletion and a unique neurotrophic tyrosine receptor kinase (NTRK) gene fusion. The patient subsequently underwent second-stage surgery to proceed with maximal safe resection of the remnant tumor, followed by the commencement of adjuvant chemotherapy.ConclusionTo date, there are very few pediatric cases of PXA that present with spontaneous pICH and whose tumors have undergone thorough molecular testing. Our patient's journey highlights the role of a dedicated multidisciplinary neuro-oncology team to guide optimal treatment.
Prevalence of scoliosis in children and adolescents: a systematic review and meta-analysis
Authors: Li Mingyang , Nie Qilong , Liu Jiaying , Jiang Zeping 
Published: July 2024

BackgroundThe understanding of the prevalence and early predictive factors of scoliosis in children and adolescents is limited, which poses challenges to developing preventative strategies. This systematic review and meta-analysis aimed to clarify the prevalence and predictors of scoliosis among children and adolescents.MethodsWe conducted a comprehensive search in PubMed, Cochrane, Embase, and Web of Science through October 2023. The quality of included studies was evaluated using the Joanna Briggs Institute scale or the Newcastle-Ottawa Scale. Subgroup analyses were performed to examine different types of scoliosis and specific demographic groups.ResultsFrom 32 studies encompassing 55,635,351 children and adolescents, we identified 284,114 cases of scoliosis, resulting in a prevalence rate of 3.1% (95% CI: 1.5%–5.2%). This rate varied by gender, degrees of scoliosis severity, and between idiopathic vs. congenital forms. Notable predictors included gender, age, Body Mass Index (BMI), race, environmental factors, and lifestyle choices.ConclusionScoliosis is a significant condition affecting a minority of children and adolescents, particularly adolescent girls and individuals who are overweight. It is recommended that guardians and schools enhance educational efforts towards its prevention.Systematic Review Registrationhttps://www.crd.york.ac.uk/, Identifier CRD42023476498.