bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroaxonal damage in natalizumab-treated MS patients: The role of JCV antibody titres
Authors: Dalla Costa Gloria , Leocani Letizia , Pisa Marco , Croese Tommaso , Martinelli Vittorio , Moiola Lucia , Sangalli Francesca , Colombo Bruno , Haghikia Aiden , Gold Ralf , Furlan Roberto , Comi Giancarlo 
Published: June 2024

Background: While John Cunningham virus (JCV) is known to cause neuronal damage in progressive multifocal leukoencephalopathy (PML) among natalizumab-treated MS patients, its association with axonal loss in non-PML conditions remains unclear. Methods: In a cohort of 128 natalizumab-treated MS patients, serum neurofilament (sNfL) levels and JCV antibody titres were measured. Results: Among 128 patients (mean age = 38.4 years, 71.9% female), 51 (40%) were JCV positive. NfL levels increased by 15.3% for JCV index <0.7 (95% confidence interval [CI] = 0.963–1.381), by 18.6% for index 0.7–1.5 (95% CI = 1.009–1.394) and by 21.1% for index >1.5 (95% CI = 1.040–1.409) compared to JCV negative patients. Conclusion: These findings indicate a potential link between JCV burden and neuroaxonal degeneration in natalizumab-treated MS patients.
Flexural behavior of wet joints connecting step-shaped composite slab and steel beam under negative moment
Authors: Shan Yingjie , Gong Yongzhi , Wang Yi 
Published: June 2024

This study proposed an innovative step-shaped composite (SSC) slab system that has a high assembly rate. Experimental and analytical studies were carried out to investigate the flexural behavior of wet joints connecting SSC slabs and H-shaped steel beams under negative moment. The effects of three factors were experimentally examined, including width of the horizontal laminated interface, seated length of precast slabs on steel beam, and type of wet joint materials. The crack development, load–deflection response and strain distribution were monitored during the loading. As found, the SSC slabs showed similar flexural behavior to that of the slab cast-in-situ. The seated length (10-30 mm) had a negligible effect on the flexural behavior of the SSC slabs, while the beneficial effect of using ultra-high performance concrete (UHPC) as the wet joint material was significant. Besides, using a wider horizontal laminated interface, initial cracking load and yield load could be significantly improved, though it had a marginal effect on the bearing capacity. Based on the collected bond test results, a cracking load model for SSC slabs with UHPC wet joint was proposed and validated. Finally, a refined finite element (FE) model was established and calibrated against the test results for parametric analysis.
Adapted Home-Based Exercises in Dementia: An Exploratory Pre-post Pilot and Feasibility Study
Authors: Carrard Sophie , Eyer Stephan , Hilfiker Roger , Mittaz Hager Anne-Gabrielle 
Published: June 2024

The goals of this exploratory pre-post pilot and feasibility study (NCT04916964) were to assess the feasibility and effectiveness of an adapted Test-and-Exercise home-based exercise program on basic functional mobility and executive functions in persons with prodromal or mild Alzheimer’s disease. Participants followed an 8 week exercise program at home, once per week with a physiotherapist and twice per week with their usual caregiver or independently. Functional mobility and executive functions were assessed before and after the intervention. Feasibility criteria were recruitment opportunity, participation agreement rate, cost adequacy, and drop-out rate. Twelve participants aged 80.83 ± 4.65 years took part in the study. All the basic functional mobility measures showed small effect sizes. Concerning executive functions, 5 measures showed small to moderate effect sizes. The 4 feasibility criteria were met. A larger scale study would, however, need adaptations and prior research on the ability of this population to use touch-screen technology.
Factors Associated With Tobacco Cessation Advice Recall and Quit Rates in Vascular Surgery Patients. A Single Center Study
Authors: Peng Yuanzun , Rossi Ryan , Falkenhain Alec , Bose Saideep , Williams Michael , Wittgen Catherine , Han David , Smeds Matthew R. 
Published: June 2024

Objectives Smoking is an important modifiable risk factor in all vascular diseases and verbal advice from providers has been shown to increase rates of tobacco cessation. We sought to identify factors that will improve tobacco cessation and recall of receiving verbal cessation advice in vascular surgery patients at a single institution. Methods The study is a retrospective cohort study. Patients seen in outpatient vascular surgery clinic who triggered a tobacco Best Practice Advisory (BPA) during their office visits over a 10-month period were contacted post-clinic and administered surveys detailing smoking status, cessation advice recall, and validated scales for nicotine dependence and willingness to quit smoking. This BPA is a “hard stop” that requires providers to document actions taken. Charts were reviewed for tobacco cessation documentation. Nine-digit zip-codes identified the area deprivation index, a measure of socioeconomic status. Univariate analysis was used to identify factors associated with cessation and advice recall. Results One hundred out of 318 (31.4%) patients responded to the survey. Epic Slicer Dicer found 97 BPA responses. To dismiss the BPA, 89 providers (91.8%) selected “advised tobacco cessation” and “Unable to Advise” otherwise. Of the 318 patients, 115 (36.1%) had cessation intervention documented in their provider notes and 151 (47.5%) received written tobacco cessation advice. Of survey respondents, 70 recalled receiving verbal advice, 27 recalled receiving written advice, 28 reported receiving offers of medication/therapy for cessation. 55 patients reported having tobacco cessation plans, and among those 17 reported having quit tobacco. Recall of receiving written advice (P < .001) and recall of receiving medication/therapy (P = .008) were associated with recall of receiving verbal cessation advice. Conclusions Providing patients with tobacco cessation medication/therapy and written tobacco cessation education during office visits is associated with increased patients’ recall of tobacco cessation advice. Vascular surgeons should continue to provide directed tobacco cessation advice.
Effect of a Whole-Food Plant-Based Diet on Postprandial Sleepiness: A Pilot Study
Authors: Polianovskaia Anastasiia , Sutliffe Jay T. , Lopez Nanette V. , Cheung Joseph 
Published: June 2024

Background Postprandial sleepiness refers to the state of excessive drowsiness that occurs after consuming a meal. This transient phenomenon is experienced by many individuals, often leading to decreased productivity and impaired cognitive performance. This study examined the effect of a whole-food plant-based (WFPB) diet on postprandial sleepiness. Methods Ten participants who had postprandial sleepiness who were on a typical American diet transitioned to a WFPB dietary pattern for 21 days. Postprandial sleepiness was assessed using the Epworth Sleepiness Scale (ESS) questionnaire, focusing on Q7 “sitting quietly after lunch without alcohol” as well as Q5 “lying down to rest in the afternoon when circumstances permit.” Results The participants had a mean age of 44 +/− 15 years, with 30% being male. There was a statistically significant reduction in sleepiness measured by ESS Q7 (median change = −1, P = .012) and ESS Q5 (median change = −1.5, P = .008). Moreover, there was a statistically significant decrease in overall ESS scores (median change = −8.0, P = .006), and weight (median change = −2.9 kg, P = .006). Conclusion Participants demonstrated significant improvement in postprandial sleepiness-related situations. Our findings showed that the WFPB diet may have potential benefits for reducing postprandial and overall daytime sleepiness.
Relationship between carotid web morphology on CT angiography and stroke: A pooled multicenter analysis
Authors: Bala Fouzi , Alhabli Ibrahim , Singh Nishita , Benali Faysal , Coutts Shelagh , Goyal Mayank , Almekhlafi Mohammed , Hill Michael D , Menon Bijoy K 
Published: June 2024

Background: The Carotid web (CaW) is a cause of stroke, particularly in younger individuals. However, the frequency and the radiological features of the web’s morphology associated with stroke risk are uncertain. We determined the CaW radiological features on computed tomography (CT) angiography associated with ipsilateral stroke. Materials and Methods: Data from six studies of patients with acute ischemic stroke were pooled. Identification and measurement of CaWs were performed by experienced readers using baseline neck CT angiography. We assessed six 2D CaW radiological features on sagittal oblique images, namely, main axis length, thickness, height, base width, distance to wall, and angle between the web main axis and carotid wall, and CaW volume on 3D images. CaWs were divided into symptomatic if acute ischemic stroke was in the ipsilateral internal carotid artery territory and its etiology was undetermined and asymptomatic if one condition was unmet. Univariable and multivariable analyses were conducted to assess the association between each radiological CaW feature and symptomatic CaW. Results: Of the 3442 patients in the pooled data with assessable CTAs, 60 (1.7%) had CaW. In patients with CaW, median age was 59 (interquartile range [IQR]: 50–68) years, 60% were women, and 3 patients had bilateral CaWs. There were 39 (62%) symptomatic and 24 (38%) asymptomatic CaWs. Patients with symptomatic CaW were younger (55 (IQR: 49–61) years versus 69 (IQR: 52–75) years), had lower rates of hypertension (9 (25.0%) versus 12 (57.1%)) and more intracranial large vessel occlusions compared to patients with asymptomatic CaWs. After adjusting for age, hypertension, and occlusion location, CaW length (adjusted odds ratio (aOR) 1.84 (95% confidence interval [CI]: 1.03–3.28)), thickness (aOR: 2.31 (95% CI 1.08–4.97)), volume (aOR: 1.07 per 1 mm3 increment (95% CI: 1.01–1.12)), and angle relative to the carotid wall (aOR: 0.95 (95% CI: 0.91–0.99)) were associated with symptomatic CaW. Conclusion: Radiological assessment of CaW morphology may determine its potential causal role in ischemic stroke etiology. Symptomatic CaWs tend to be longer, larger, and oriented at more acute angles relative to the carotid wall as compared to asymptomatic CaWs.
Prescriptions of opioid-containing drugs in patients with chronic cough
Authors: Weiner Michael , Liu Ziyue , Schelfhout Jonathan , Dexter Paul , Roberts Anna R. , Griffith Ashley , Bali Vishal , Weaver Jessica 
Published: June 2024

Background: Chronic cough (CC) affects about 10% of adults, but opioid use in CC is not well understood. Objectives: To determine the use of opioid-containing cough suppressant (OCCS) prescriptions in patients with CC using electronic health records. Design: Retrospective cohort study. Methods: Through retrospective analysis of Midwestern U.S. electronic health records, diagnoses, prescriptions, and natural language processing identified CC – at least three medical encounters with cough, with 56–120 days between first and last encounter – and a ‘non-chronic cohort’. Student’s t-test, Pearson’s chi-square, and zero-inflated Poisson models were used. Results: About 20% of 23,210 patients with CC were prescribed OCCS; odds of an OCCS prescription were twice as great in CC. In CC, OCCS drugs were ordered in 38% with Medicaid insurance and 15% with commercial insurance. Conclusion: Findings identify an important role for opioids in CC, and opportunity to learn more about the drugs’ effectiveness.
Hetrombopag for the management of chemotherapy-induced thrombocytopenia in patients with advanced solid tumors: a multicenter, randomized, double-blind, placebo-controlled, phase II study
Authors: Qin Shukui , Wang Yusheng , Yao Jun , Liu Yanyan , Yi Tienan , Pan Yueyin , Chen Zhendong , Zhang Xizhi , Lu Jin , Yu Junyan , Zhang Yanjun , Cheng Peng , Mao Yong , Zhang Jian , Fang Meiyu , Zhang Yanming , Lv Jing , Li Runzi , Dou Ning , Tang Qian , Ma Jun 
Published: June 2024

Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis. Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors. Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study. Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 109/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 109/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles. Results: Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, n = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) versus 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0–69.3); odds ratio = 10.44 (95% CI: 2.82–38.65); p value (nominal) based on the Cochran–Mantel–Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) versus 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) versus 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo. Conclusion: Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors. Trial registration: ClinicalTrials.gov identifier: NCT03976882.
Causal Relationships of Ligamentous Injuries in the Knee on Corticospinal Tract Structure: A Mendelian Randomization Analysis
Authors: Yu Le , Tao Weichu , Jin Zhengbiao , Li Yi , Xue Xiao’ao , Wang Ru , Hua Yinghui 
Published: June 2024

Background: The association between ligamentous knee injuries and corticospinal tract (CST) structure has attracted attention; however, any causal relationship remains uncertain. We performed Mendelian randomization (MR) analysis to identify the causal effects of ligamentous knee injuries on the CST. Hypothesis: Ligamentous knee injuries impair CST microstructure (ie, by reducing fractional anisotropy [FA] and increasing mean diffusivity [MD]). Study Design: MR analysis. Level of Evidence: Level 2. Methods: MR uses genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. Summary data for ligamentous injuries in knee and CST structure were obtained from genome-wide association study datasets. Significant and independent (5 × 10−6; r2 < 0.001; 10,000 kb) single-nucleotide polymorphisms were extracted for MR analysis. Three methods for MR analysis were used (hypothesis-driven 1-tailed inverse variance weighted, MR-Egger, and weighted median), and sensitivity analyses were conducted to test reliability and stability. Results: Results from 3 MR methods consistently demonstrated that ligamentous knee injuries increased MD of the right CST (β, 0.063; 90% CI, 0.003-0.123; P = 0.04), and weak statistical significance suggested increased MD of the left CST (β, 0.060; 90% CI, -0.002 to -0.121; P = 0.05). However, no significant causal relationships were observed in CST FA, and no significant pleiotropy or heterogeneity was observed. Sensitivity analysis utilizing 2-tailed tests had no significant associations between ligamentous knee injuries and changes in CST structure. Conclusion: There is statistically weak genetic evidence that corticospinal pathway abnormalities may evolve after ligamentous knee injuries, which manifests as abnormally organized neurites. Clinical Relevance: Ligamentous knee injuries require attention not only to damage to the structure of the knee joint itself but also to the process of maladaptive neuroplasticity that leads to structural and functional changes of the CST; novel interventions that target the corticospinal pathway may provide subsequent treatment of ligamentous knee injuries.
Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine
Authors: Zeidan Amer M. , Bewersdorf Jan Philipp , Hasle Vanessa , Shallis Rory M. , Thompson Ethan , de Menezes Daniel Lopes , Rose Shelonidta , Boss Isaac , Halene Stephanie , Haferlach Torsten , Fox Brian A. 
Published: June 2024

Background: TP53 mutations are associated with an adverse prognosis in acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS). However, the integrated genetic, epigenetic, and immunologic landscape of TP53-mutated AML/HR-MDS is not well defined. Objectives: To define the genetic, epigenetic, and immunologic landscape of TP53-mutant and TP53 wild-type AML and HR-MDS patients. Design: Post hoc analysis of TP53-mutant and TP53 wild-type patients treated on the randomized FUSION trial with azacitidine ± the anti-PD-L1 antibody durvalumab. Methods: We performed extensive molecular, epigenetic, and immunologic assays on a well-annotated clinical trial dataset of 61 patients with TP53-mutated disease (37 AML, 24 MDS) and 144 TP53 wild-type (89 AML, 55 MDS) patients, all of whom received azacitidine-based therapy. A 38 gene-targeted myeloid mutation analysis from screening bone marrow (BM) was performed. DNA methylation arrays, immunophenotyping and immune checkpoint expression by flow cytometry, and gene expression profiles by bulk RNA sequencing were assessed at baseline and serially during the trial. Results: Global DNA methylation from peripheral blood was independent of TP53 mutation and allelic status. AZA therapy led to a statistically significant decrease in global DNA methylation scores independent of TP53 mutation status. In BM from TP53-mutant patients, we found both a higher T-cell population and upregulation of inhibitory immune checkpoint proteins such as PD-L1 compared to TP53 wild-type. RNA sequencing analyses revealed higher expression of the myeloid immune checkpoint gene LILRB3 in TP53-mutant samples suggesting a novel therapeutic target. Conclusion: This integrated analysis of the genetic, epigenetic, and immunophenotypic landscape of TP53 mutant AML/HR-MDS suggests that differences in the immune landscape resulting in an immunosuppressive microenvironment rather than epigenetic differences contribute to the poor prognosis of TP53-mutant AML/HR-MDS with mono- or multihit TP53 mutation status. Trial registration: FUSION trial (NCT02775903).
Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study
Authors: Baez-Polan J. , Danciu T.E. , Sweier D. , González-Cabezas C. , Fontana M. , Tenuta L.M.A. 
Published: June 2024

Introduction: Previous studies have shown that a calcium prerinse can increase intraoral fluoride retention from a fluoride rinse. To explore the potential of this approach to control root caries, we assessed intraoral fluoride bioavailability after a calcium prerinse in older adults with normal to low salivary flow rates. Methods: In a 2-period crossover trial (NCT04239872), 20 participants (65–80 y old), with low or normal salivary flow rate, rinsed for 1 min with a 0.05% NaF mouth rinse (226 ppm F, F only) or with this rinse immediately after a 1-min rinse with 150 mM calcium lactate (Ca→F). Dental biofilm and saliva samples were collected before and up to 2 h after the rinse(s). Fluoride concentrations in saliva (whole and clarified) and dental biofilm (fluid and solid phases) were blindly determined. Data were statistically analyzed by a mixed-effects model for the effect of treatment, time, and their interaction ( α = 5%). Results: The Ca→F group resulted in significantly higher fluoride concentrations in all variables analyzed, for almost all of the collection time points. The effect was greater in the biofilm solids and whole saliva (compatible with the formation of calcium fluoride deposits) and still significant ( P < 0.001) after 2 h in the biofilm fluid and clarified saliva, suggesting that fluoride stored in insoluble particles was released, increasing free fluoride. Conclusion: The use of a calcium prerinse before a fluoride rinse was able to prolong intraoral fluoride bioavailability in older adults. Knowledge Transfer Statement: A calcium prerinse increased intraoral fluoride bioavailability in older individuals. This approach could be used to improve root caries control without the need to increase the fluoride concentration in dental products.
Triple Jeopardy in Oral Health: Additive Effects of Immigrant Status, Education, and Neighborhood
Authors: Soares G.H. , Haag D. , Bastos J.L. , Mejia G. , Jamieson L. 
Published: June 2024

Purpose: To estimate the additive effects of parent’s nativity status/language spoken at country of birth, education, and area-level socioeconomic status (SES) on untreated dental caries among children aged 5 to 9 y in Australia. Methods: Cross-sectional population-based data were obtained from the 2014 National Child Oral Health Study (N = 12,140). Indicators of social position used to explore additive effects on dental caries included nativity status, language, university degree, and neighborhood socioeconomic level. Multiple-way interactions were examined, and departure from additivity resulting from 2- and 3-way interactions were estimated as relative excess risk due to interaction (RERI). Results: Children marginalized across multiple layers of disadvantage had substantially higher frequencies of dental caries compared with children in the most advantaged category. RERI for the 3-way interaction between immigrant status, education, and neighborhood SES was negative (RERI3: −0.14; 95% confidence interval [CI]: −1.68, 1.40). When operationalizing language, education, and neighborhood SES, the joint effect of the 3 marginalized positions was additive (RERI3: 0.43; 95% CI: −2.08, 2.95). Conclusion: Children marginalized across multiple intersecting axes of disadvantage bear the greatest burden of dental caries, with frequencies surpassing the cumulative effect of each social position alone. Findings emphasize the need to account for intersecting inequities and their oral health effects among children with immigrant backgrounds. Knowledge Transfer Statement: Our analysis underscores the necessity for policies and public health strategies targeting dental caries–related inequities to comprehensively account for various indicators of social disadvantage, particularly encompassing language proficiency, educational attainment, and neighborhood socioeconomic status. Within the intricate interplay of these factors, we identify a vulnerable subgroup comprising children with the highest prevalence of dental decay. Therefore, prioritizing this specific demographic should be the focal point of policies and public health initiatives aimed at fostering equitable oral health outcomes.