bluuebunny/crossref_metadata_2025_split huggingface dataset:
A metabolome-wide Mendelian randomization study identifies dysregulated arachidonic acid synthesis as a potential causal risk factor for bipolar disorder
Authors: Stacey David , Benyamin Beben , Lee S Hong , Hyppönen Elina 
Published: December 2024

AbstractBackgroundBipolar disorder (BPD) is a debilitating mood disorder with an unclear aetiology. A better understanding of the underlying pathophysiological mechanisms will help to identify novel targets for improved treatment options and prevention strategies. In this metabolome-wide Mendelian randomization study, we screened for metabolites that may have a causal role in BPD.MethodsWe tested a total of 913 circulating metabolite exposures assessed in 14,296 Europeans using a mass spectrometry-based platform. For the BPD outcome, we used summary data from the largest and most recent genome-wide association study (GWAS) to date, including 41,917 BPD cases.ResultsWe identified 33 metabolites associated with BPD (padj<5.48×10−5). Most of them were lipids, including arachidonic acid (β=−0.154, se=0.023,p=3.30×10−11), a polyunsaturated omega-6 fatty acid, along with several complex lipids containing either an arachidonic or a linoleic fatty acid side chain. These associations did not extend to other closely related psychiatric disorders like schizophrenia or depression, though they may be involved in the regulation of lithium response. These lipid associations were driven by genetic variants within theFADS1/2/3gene cluster, which is a robust BPD risk locus encoding a family of fatty acid desaturase enzymes responsible for catalysing the conversion of linoleic into arachidonic acid. Statistical colocalization analyses indicated that 27 of the 33 metabolites share the same genetic aetiology with BPD at theFADS1/2/3cluster, demonstrating that our findings are not confounded by linkage disequilibrium.ConclusionsOverall, our findings support the notion that ARA and other polyunsaturated fatty acids may represent potential targets for BPD.
Non-invasive Brain Stimulation as Treatment for Motor Impairment in People with Parkinson’s Disease: Protocol for an Umbrella Review
Authors: Harris Dale M , O’Bryan Steven J , Latella Christopher 
Published: December 2024

AbstractIntroductionParkinson’s disease (PD) is a progressive neurodegenerative disorder that predominantly affects movement and currently has no cure. Alongside medication, non-invasive brain stimulation (NIBS) may be used as an adjunct therapy to attenuate the motor symptoms experienced by people with PD. However, there is considerable heterogeneity in the evidence exploring the effects of NIBS for improving aspects of physical function in people with PD. Therefore, this protocol paper will outline the objectives, structure and procedure of a proposed umbrella review which will comprehensively summarise and map the current body evidence on the effectiveness of NIBS for improving physical function in people with PD.Methods and analysisThis study will adhere to the Joanna Briggs Institute (JBI) reviewer’s manual and the PRISMA guidelines for conducting an umbrella review. The protocol is registered in PROSPERO (CRD42022380544). The population, intervention, comparison, and outcomes (PICO) method will be used to guide the search strategies and inclusion/exclusion criteria. Systematic reviews, with or without meta-analyses, based on quantitative or mixed-methods studies, will be searched for, and then critically evaluated by two authors using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) tool. If the data allows, we will run a random effects pooled meta-analysis using standardized mean differences (SMDs), with heterogeneity and publication bias reported using theI2statistic. We will determine the level of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) tool. Overlap in studies across reviews will be assessed using citation matrices and corrected covered areas (CCAs). Lastly, visual bubble plots will display the effects and strength of evidence from each review.Ethics and disseminationEthics approval is not required as data will be searched for and gathered based on the published systematic reviews and meta-analyses. We plan to publish the results of this umbrella review in a peer-reviewed journal and will be presented at a neurology or neurostimulation conference. All the relevant additional data will also be uploaded to the online open access databases.PROSPERO registration numberCRD42022380544
An inflammation-derived and clinical-based model for ischemic stroke recovery
Authors: Luo Jiao , Cai You , Xiao Peng , Cao Changchun , Huang Meiling , Zhang Xiaohua , Guo Jie , Huo Yongyang , Tang Qiaoyan , Zhao Liuyang , Liu Jiabang , Ma Yaqi , Zhou Mingchao , Wang Yulong 
Published: December 2024

AbstractBackgroundNeuroinflammatory responses reflecting disease progression are believed to be closely associated with the severity of prognosis in post-stroke.PurposeThis study developed a combined predicted model of inflammation-derived biomarkers and clinical-based indicators using machine learning algorithms for differentiation of the functional outcome in patients with subacute ischemic stroke.MethodsClinical blood samples and patient data from individuals with subacute ischemic stroke were collected at admission. Based on activities of daily living assessments followed by a 3-month recovery, patients were categorized into two groups: those with little effective recovery (LE) and those with obvious effective recovery (OE). Serum samples underwent proteomic testing for initial candidates. Subsequently, multidimensional validation of candidates in models of ischemia-reperfusion at protein and mRNA levels was performed.T-test, Receiver Operating Characteristic (ROC), and LASSO analysis in an additional cohort were performed to confirm the clinical variables and candidate biomarkers in the discriminatory sensitivity and specificity between the LE and OE groups. Finally, models were developed based on candidates in the training dataset and predicted stroke recovery outcomes in another new dataset using ten standard two-categorical variable algorithms in machine learning.ResultsWe identified higher tissue inhibitor metalloproteinase-1 (TIMP1) and LGALS3 levels were positively correlated with the severity of prognosis after ischemic stroke rehabilitation. TIMP1 (AUC=0.904, 0.873) and LGALS3 (AUC=0.995, 0.794) were confirmed to address superior sensitivity and specificity in distinguishing ischemic stroke from healthy control and LE group from OE group. The TIMP1 and Lgals3 expression exhibited an evident increase in microglia following ischemia-reperfusion. In addition, inflammation-derived biomarkers (TIMP1, LGALS3) coupled with clinical-based indicators (HGB, LDL-c, UA) were built in a combined model with random forest to differentiate OE from LE in 3-month follow-up with high accuracy (AUC = 0.8).ConclusionOur findings provided evidence supporting the critical prognostic potential and risk prediction of inflammation-derived biomarkers after ischemic stroke rehabilitation in complementary to current clinical-based parameters.
RETURN OF VOLUNTARY MOTOR CONTRACTION AFTER COMPLETE SPINAL CORD INJURY: A PILOT HUMAN STUDY ON POLYLAMININ
Authors: Menezes Karla , B. Lima Marco Aurelio , Xerez Denise R. , Menezes João R. L. , Holanda Gustavo S. , Silva Adriana D. , Leite Eliel S. , Franco Olavo B. , Nascimento Marcos A. , Moura de Faria Marco Aurélio Alves , Santana Cíntia F. , Abreu Livia V. , Lichtenberger Renata C. L. , Rosa Maurilio , Graça-Souza Aurélio V. , Côrtes Bruno A. , Jorge Álvaro U. C. , Franzoi Ana Cristina , Louzada Paulo R. , Ferreira Arthur S. , Frajtag Rose M. , Coelho-Sampaio Tatiana 
Published: December 2024

ABSTRACTSpinal cord injury (SCI) is still a major challenge for translational medicine. Polylaminin is a stabilized form of laminin, a natural multifunctional protein, previously shown to promote neuroprotection and axonal growth after SCI in rodents. Here we present the results of a confirmatory preclinical study performed in rats and of a first in human trial of polylaminin to treat acute SCI. The latter was an open-label, single-armed academic study designed to include only patients diagnosed with functional complete SCI, because no more than 15% of these patients recover motor function spontaneously. Eight participants received a single intraspinal injection of polylaminin shortly after trauma (average time = 2.3 days). Two died within the first days of causes related to the gravity of the condition. The six patients that survived to reach the one-month follow-up were evaluated using the International Standards for Neurological Classification of Spinal Cord Injury (6/6) and motor and somatosensory evoked potentials (3/6). All the six patients regained voluntary motor control below the level of the lesion, which is an unprecedented recovery. This preliminary study suggests the efficacy of polylaminin to treat acute SCI, revealing its potential as a new therapy to restore motor function to paralyzed people (UTN: U1111-1144-5390).
Elevated plasma neurofilament light & glial fibrillary acidic protein in epilepsy versus non-epileptic seizures & non-epileptic disorders
Authors: Dobson Hannah , Maawali Said Al , Malpas Charles , Santillo Alexander F , Kang Matthew , Todaro Marian , Watson Rosie , Yassi Nawaf , Blennow Kaj , Zetterberg Henrik , Foster Emma , Neal Andrew , Velakoulis Dennis , O’Brien Terence John , Eratne Dhamidhu , Kwan Patrick 
Published: December 2024

ABSTRACTBackgroundResearch suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood following neuroaxonal damage, and have been hypothesised as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic non-epileptic seizures (PNES), and other non-epileptic disorders.MethodsWe recruited consecutive adults admitted for video-electroencephalography monitoring and formal neuropsychiatric assessment. Plasma samples were collected on admission. NfL and GFAP levels were quantified and compared between patient groups and an age-matched reference cohort (n=1,926), and correlated with clinical variables.Results149 patients were included. 115 were diagnosed with epilepsy, 22 with PNES and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p=0.004, GFAP p=0.004). A significantly higher proportion of patients with epilepsy (26%) had NfL levels above the 95thage-matched percentile compared to the reference cohort (5%; p=0.0265). NfL levels above the 95thpercentile of the reference cohort had a 97% positive predictive value for epilepsy.DiscussionElevated NfL or GFAP levels may support an underlying epilepsy diagnosis and caution against a diagnosis of PNES alone. Further examination of associations between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.
Clot Twist – D-dimer analysis of healthy adults receiving heterologous or homologous booster COVID-19 vaccine after a single prime dose of Ad26.COV2.S in a phase II randomised open-label trial, BaSiS
Authors: Patel Faeezah , Le Roux Jean , Sawry Shobna , Kieser Robert , Dhar Mrinmayee , Gill Katherine , Lazarus Erica , Nana Anusha , Garrett Nigel , Moore Penny L , Sigal Alex , Gray Glenda , Rees Helen V , Jacobson Barry Frank , Fairlie Lee 
Published: December 2024

AbstractBaSiS (BoosterAfterSisonkeStudy) is a prospectively enrolled open-label trial in which healthy adults, with controlled co-morbidities and no prior thrombosis, who received a single Ad26.COV2.S prime vaccination primarily through the Sisonke phase IIIB open label implementation study in South Africa. An exploratory objective evaluated the clotting profiles of participants who were enrolled across 4 sites in South Africa and randomised 1:1:1:1 to receive one of full-dose Ad26.COV2.S, half-dose Ad26.COV2.S, full-dose Comirnaty or half-dose Comirnaty booster. D-dimer testing (INNOVANCE®D-Dimer Assay), as a coagulopathy marker, was conducted pre-booster (baseline) and 2 weeks post-booster. The median age among 285 participants was 42.2 years (IQR:35.5-48.7), 235/285 (82.5%) were female, 269/285 (94.4%) were Black African. Of the 40.4% (115/285) people living with HIV (PLHIV), 79.1% (91/115) were well-controlled on antiretroviral therapy. At baseline, 39.3% (112/285) had elevated d-dimers; all asymptomatic. Females and obese participants were significantly more likely to have elevated baseline d-dimers (OR=4.17; 95% CI:1.88 to 9.26 and OR=2.64; 95% CI:1.57 to 4.43, respectively). Of 169 with normal baseline d-dimers, 29 (17.2%) became elevated 2 weeks post-booster: median increase 0.23µg/ml (IQR:0.15-0.42); those receiving full-dose Comirnaty exhibited lower risk of d-dimer elevation post vaccination, compared to other booster vaccination arms (OR:0.26; 95% CI:0.07 to 0.98). PLHIV experienced significantly higher median increases compared to HIV uninfected participants (0.43 vs 0.17, p=0.004). Elevated d-dimers in asymptomatic, low-risk adults were unexpectedly common but were not associated with thromboembolism, supporting the rationale of using d-dimers only if clinically indicated. Trial Registration: South African Clinical Trails Register number DOH-27-012022-7841.
The safety of antivirals and neutralising monoclonal antibodies used in prehospital treatment of Covid-19
Authors: Bechman Katie , Green Amelia , Russell Mark D , Yang Zijing , Zheng Bang , Norton Sam , Smith Rebecca M , Mehrkar Amir , Bacon Sebastian , Goldacre Ben , MacKenna Brian , Galloway James ,   OpenSAFELY Collaborative
Published: December 2024

AbstractObjectiveThis proof-of-principle pharmacovigilance study used Electronic Health Record (EHR) data to examine the safety of sotrovimab, paxlovid and molnupiravir in prehospital treatment of Covid-19.MethodWith NHS England approval, we conducted an observational cohort study using OpenSAFELY-TPP, a secure software-platform which executes analyses across EHRs for 24 million people in England. High-risk individuals with Covid-19 eligible for prehospital treatment were included. Adverse events (AEs) were categorised into events in the drug’s Summary of Product Characteristics (SmPC), drug-reactions and immune-mediated. Cox models compared risk across treatments. A pre-pandemic record analysis was performed for comparative purposes.ResultsBetween 2021-2023, 37,449 patients received sotrovimab, paxlovid or molnupiravir whilst 109,647 patients made up an eligible-but-untreated population. The 29-day rates of AEs were low: SmPC 0.34 per 1000 patient-years (95%CI 0.32-0.36); drug-reactions 0.01(95% CI0.01-0.02) and immune-mediated 0.03(95%CI 0.03-0.04), and similar or lower than the pre-pandemic period. Compared with the eligible but untreated population, sotrovimab and paxlovid associated with a risk of SmPC AE [adjHR 1.36(95%CI 1.15-1.62) and 1.28(95%CI 1.05-1.55), respectively], whilst sotrovimab associated with a risk of drug-reactions [adjHR 2.95(95%CI 1.56-5.55)] and immune-mediated events [adjHR 3.22(95%CI 1.86-5.57)].ConclusionSotrovimab, paxlovid and molnupiravir demonstrate acceptable safety profiles. Although the risk of AEs was greatest with sotrovimab, event rates were lower than comparative pre-pandemic period.
Efficacy of Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease Patients with Exercise Pulmonary Hypertension
Authors: Naka Yutaro , Inami Takumi , Takeuchi Kaori , Kikuchi Hanako , Goda Ayumi , Kataoka Masaharu , Kohno Takashi , Soejima Kyoko , Satoh Toru 
Published: December 2024

ABSTRACTBackgroundThe efficacy of balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary disease (CTEPD) with or mild pulmonary hypertension (PH) or without PH remains unknown. Exercise pulmonary hypertension (Ex-PH) is associated with impaired exercise capacity and ventilatory efficiency, even under normalized pulmonary hemodynamics at rest. We hypothesized that patients with Ex-PH and/or hypoxemia would be candidates for BPA. We aimed to verify the prevalence and clinical profiles of Ex-PH and the effect of BPA on oxygenation and Ex-PH in patients with CTEPD with mean pulmonary arterial pressure (mPAP) < 25 mmHg.MethodsWe retrospectively reviewed 29 patients with CTEPD and mPAP < 25 mmHg at rest, who had undergone a cardiopulmonary exercise test with right heart catheterization (median age, 65 years; 38% male). Patients were divided into two groups: Ex-PH, defined as a cardiac output slope (mPAP/CO slope) > 3.0, and non-Ex-PH.ResultsOverall, six patients had mild PH (mPAP: 21–24 mmHg), and 16 and 13 were assigned to the Ex-PH and Non-Ex-PH groups, respectively. There were no significant differences in the clinical parameters, including hemodynamics at rest, blood gas analysis, and 6-minute walk distance, between the Ex-PH and Non-Ex-PH groups. Among the 16 patients with Ex-PH and/or long-term oxygen therapy (LTOT), BPA improved the World Health Organization-functional class (WHO-FC) and PaO2in association with a decrease in the mPAP/CO slope. All nine patients discontinued LTOT after BPA. No significant complications were observed during each BPA session.ConclusionsEx-PH was common among patients with CTEPD and mPAP < 25 mmHg. BPA can improve symptoms, oxygenation, and exercise hemodynamics in patients with CTEPD and Ex-PH and/or hypoxemia.What is Known?BPA has been recommended for patients with non-operable CTEPH.Although there is still a small body of evidence, BPA for patients with CTEPD with mild PH (mPAP < 25 mmHg) or without PH can safely improve symptoms.The prevalence of Ex-PH in CTEPD patients with or without PH is unknown.What the Study Adds?Approximately 50% of CTEPD patients with mild PH or without PH had Ex-PH.In patients with CTEPD with mPAP < 25 mmHg, BPA improves exercising hemodynamics, such as the mPAP/CO slope, which could be a parameter to determine the indication for BPA.Graphical Abstract.The distribution of exercise pulmonary hypertension (Ex-PH) in patients with chronic thromboembolic pulmonary disease (CTEPD) with mild pulmonary hypertension (PH) or without PH, and efficacy of balloon pulmonary angioplasty (BPA) for CTEPD with Ex-PH and/or hypoxemia. Blue person symbols mean Ex-PH, and white person symbols mean non-Ex-PH.
Superior long-term patency of no-touch vein graft compared to conventional vein grafts in over 1500 consecutive patients
Authors: Ferrari Gabriele , Loayza Richard , Azari Ava , Geijer Håkan , Cao Yang , Carlsson Roland , Bojö Leif , Samano Ninos , Souza Domingos 
Published: December 2024

ABSTRACTObjectivesTo evaluate the long-term angiographic patency of saphenous vein grafts (SVG) harvested using the no-touch technique compared to the conventional technique.MethodsThis was a single-center, retrospective, cohort study. The inclusion criteria were individuals who underwent a CABG (coronary artery bypass grafting) between January 1995 and July 2020, and who successively needed a clinically-driven angiography. The primary endpoint was long-term patency. The secondary endpoints were differences in patency based on sub-group analysis (single vs. sequential graft, divided by target vessel).ResultsThe study included 1520 individuals (618 no-touch, 825 conventional and 77 arterial grafts). The mean clinical follow-up time was 8.4 years ± 5.5 years. The patency per patient was 70.7% in the no-touch grafts vs. 46.7% in the conventional grafts (p < 0.001, OR = 2.8). The graft patency was 75.9% in the no-touch grafts vs. 62.8% in the conventional grafts (p < 0.001, OR= 1.8).ConclusionsThe no-touch vein grafts were associated with statistically significantly higher patency at long-term compared to the conventional grafts.Clinical Trial RegistrationNCT04656366, 7 December 2020Clinical Perspective-What is new?➣The largest follow-up of the patency of no-touch vein grafts in the international literature.➣Patients with a no-touch vein graft had significantly better patency (p < 0.001) at mean follow-up of more than 8 years.-What are the clinical implications?➣Consequent reduction in cardiovascular events after no-touch vein graft.➣Benefits at individual level due to fewer episodes of re-angina and myocardial infarction, and fewer coronary interventions.➣Benefits at community level due to fewer re-hospitalizations and a reduction in healthcare costs.
Are abnormalities in lipid metabolism, together with adverse childhood experiences, the silent causes of immune-linked neurotoxicity in major depression?
Authors: Maes Michael , Jirakran Ketsupar , Vasupanrajit Asara , Zhou Bo , Tunvirachaisakul Chavit , St. Stoyanov Drozdstoj , Almulla Abbas F. 
Published: December 2024

AbstractBackgroundSevere or recurring major depression is associated with increased adverse childhood experiences (ACEs), heightened atherogenicity, and immune-linked neurotoxicity (INT). Nevertheless, the interconnections among these variables in outpatient of major depression (OMDD) have yet to be determined.ObjectivesDetermine the correlations among INT, atherogenicity, and ACEs in 66 OMDD patients (of whom thirty-three had metabolic syndrome, MetS) and sixty-seven controls (31 of whom had MetS).ResultsThe free cholesterol/reverse cholesterol transport ratio, apolipoprotein (Apo) B and E, and a comprehensive atherogenicity index were all significantly associated with increased INT in OMDD subjects without MetS. ACEs were substantially correlated with INT in patients with MetS. INT (only in MetS) and atherogenicity indices (only in people without MetS) were significantly associated with the clinical phenome features of OMDD, including the recurrence of illness (ROI, including lifetime suicidal behaviors), the lifetime phenome (neuroticism + lifetime anxiety disorders and dysthymia), and the current phenome (including current suicidal behaviors). A significant proportion of the variability (58.3%) in the lifetime + current phenome could be accounted for by INT, interactions between INT and atherogenicity (labeled "atherommune index"), ApoE, three ACE subtypes (all positively correlated), and age (inversely correlated). A single validated latent construct could be extracted from ROI, lifetime phenome, current phenome, INT, and atherommune index. 36.1% of this factor’s variance was accounted for by three ACE subtypes.DiscussionWe have developed a novel OMDD model, namely a pathway phenotype, labeled the "atherommune-phenome," which demonstrates that the interplay between INT and atherogenicity is essential to OMDD.