bluuebunny/crossref_metadata_2025 huggingface dataset:
A case report of fungal endocarditis presenting with low back pain as the initial symptom
Authors: Xu Haixia , Zhang Hang , Wu Jiacheng , Jin Libo
Published: December 2024

Rationale:

Fungal endocarditis (FE) is a rare form of infective endocarditis. Compared to bacterial endocarditis, FE develops more slowly and insidiously, with nonspecific clinical manifestations, making diagnosis more challenging. Cases presenting with low back pain as the initial symptom are exceedingly rare, leading to a high risk of misdiagnosis or delayed diagnosis.

Patient concerns:

A 61-year-old male was admitted due to recurrent low back pain accompanied by fever for 2 months. He had no history of invasive procedures or immunosuppressive therapy.

Diagnoses:

The patient was diagnosed with FE.

Interventions:

The patient underwent surgical treatment, during which the excrescence was removed, and mitral valve replacement was performed. Postoperatively, he received a full course of antifungal therapy.

Outcomes:

Postoperatively, the patient experienced relief from low back pain and was afebrile. He was discharged after completing antifungal treatment and, upon follow-up after 1 year, had no recurrence of low back pain.

Lessons:

In this case, the patient initially presented with low back pain, which, despite the presence of fever and other signs of infection, did not readily suggest a cardiac etiology. This case highlights the importance of not being misled by superficial symptoms and underscores the need for comprehensive and accurate physical examinations and targeted investigations for proper diagnosis.
Intravascular large B-cell lymphoma arising in the pituitary gland: A case report
Authors: Jang Kyu Yun , Ahn Ae Ri
Published: December 2024

Rationale:

Primary pituitary lymphoma is defined as a lymphoma that develops only in the pituitary gland without involvement of other areas.

Patient concerns:

We present the case of a 61-year-old female patient who underwent an endonasal transsphenoidal approach for the preoperative diagnosis of a pituitary macroadenoma based on radiological findings.

Diagnoses:

Microscopically, the capillaries were distended by tumor cells. The high-magnification view showed large cells with vesicular nuclei and single or multiple prominent nucleoli, with mitotic figures often observed within the intravascular space.

Interventions:

Immunohistochemical staining showed strong positivity for CD45 and pan-B cell markers such as CD19 and CD20. The postoperative diagnosis was intravascular large B-cell lymphoma of the pituitary gland.

Outcomes:

Next-generation sequencing revealed alterations in 12 genes: ARID5B, BCL2, CD79B, ETV6, HLA-B, LRRC7, MYD88, PIM1, POT1, PTPN11, RASA1, and SRSF2.

Lessons:

To our knowledge, this is the first case report of pituitary intravascular large B-cell lymphoma.
Pediatric Mesenchymal Tumors
Authors: Aljuboori Omar , Saad Ali G.
Published: December 2024

Vascular, fibrous/myofibroblastic, and myogenic tumors account for the majority of mesenchymal tumors in children. These tumors often show significant overlap in morphology and immunophenotype posing diagnostic difficulties and, thus, their classification remains challenging. Recent advances in immunohistochemistry have proved helpful in identifying a specific line of differentiation in some tumors, but other tumors remain difficult to classify. Molecular investigations have provided an existing tool to better understand the pathogenesis of some of these tumors and, in some cases like the EWING family of tumors, expanded the classification resulting in the emergence of previously unknown tumors. Some of these tumors are currently diagnosed according to their underlying molecular abnormality, such as CIC-rearranged sarcoma, BCOR-rearranged sarcoma, etc. This review focuses on the common mesenchymal neoplasms of the pediatric population with emphasis on the salient histologic features, immunoprofile, and molecular characteristics. For practical purposes, the latter are summarized in Supplemental Table 1, Supplemental Digital Content 1, http://links.lww.com/PAP/A46.
A Cross-Disciplinary Study of Facial Asymmetry in a Pre-Hispanic Mesoamerican Sculpture
Authors: Mansilla-Lory Josefina , Sandoval Hugo , Talavera Arturo , Pérez-Neri Iván , Pineda Carlos
Published: December 2024

Background/Historical Perspective

Facial asymmetry has been recognized and represented in Mesoamerican and South American pre-Hispanic cultures.

This study aims to describe and contextualize an ancient pre-Hispanic stone face carving from the Early Postclassic Period (1200–1500 AD) discovered during excavations for the construction of what is now the National Rehabilitation Institute in Mexico City. The remarkable facial asymmetry of the artifact, suggesting facial paralysis, is a focal point for an interdisciplinary study combining bioarchaeology, anthropology, paleopathology, and rheumatology.

Conclusions

Although most causes of facial paralysis are idiopathic and pre-Hispanic Mesoamerican populations may have had a higher incidence of infections that could be the leading triggering cause, the potential connection between facial paralysis and rheumatic diseases in pre-Hispanic or pre-Columbian contexts is still a topic of ongoing investigation. This task remains highly relevant for rheumatologists who have traced the history and evolution of rheumatic diseases.

Future Research

To understand the potential causes of disabilities in ancient societies, a comprehensive, holistic, and transdisciplinary approach is needed, including evidence-based reviews to analyze the relationship between facial paralysis and rheumatic diseases.
Impact of Hypothermic Perfusion on Immune Responses and Sterile Inflammation in a Preclinical Model of Pancreatic Transplantation
Authors: Mesnard Benoit , Bruneau Sarah , Le Bas-Bernardet Stéphanie , Ogbemudia Etohan , Kervella Delphine , Masset Christophe , Neel Mélanie , Minault M. David , Hervouet M. Jeremy , Cantarovich Diego , Rigaud Jérôme , Badet Lionel , Friend Peter , Ploeg Rutger , Blancho Gilles , Hunter James , Prudhomme Thomas , Branchereau Julien
Published: December 2024

Background.

In organ transplantation, cold ischemia is associated with sterile inflammation that subsequently conditions adaptive immunity directed against the grafts during revascularization. This inflammation is responsible for venous thrombosis, which is the main postoperative complication affecting graft function. Our aim was to investigate the modulation of immune responses and endothelial function of pancreatic grafts during cold ischemia using different preservation modalities.

Methods.

According to a preclinical porcine model of controlled donation after circulatory death, pancreatic grafts were preserved under hypothermic conditions for 24 h according to 4 modalities: static cold storage, hypothermic machine perfusion, hypothermic oxygenated perfusion at 21%, and 100%. Biopsies of the head and tail of the pancreas were performed during preservation. The first step involved a broad screening of the gene expression profile (84 genes) during preservation on a limited number of grafts. In the second step, a confirmation test was performed in all 4 groups.

Results.

Vascular endothelial growth factor gene expression showed a decrease during preservation in the hypothermic oxygenated perfusion 21% and 100% groups compared with the static cold storage group. In contrast, thrombomodulin gene expression showed an increase during preservation in the hypothermic oxygenated perfusion 21% and 100% groups compared with the static cold storage and hypothermic machine perfusion groups.

Conclusions.

We demonstrated that compared with static cold storage, hypothermic oxygenated perfusion is an effective modality for modulating endothelial function by increasing thrombomodulin expression and decreasing ischemia and vascular endothelial growth factor expression.
Voluntary Swallowing Initiation Difficulty After Dorsomedial Prefrontal Cortex Damage: A Case Report
Authors: Motojima Nanae , Funayama Michitaka , Nakajima Asuka , Nakamura Tomoyuki , Baba Mikoto , Kobayashi Shusuke
Published: December 2024

The dorsomedial prefrontal cortex plays a critical role in movement initiation, and damage to this area can impair this function. Here we present the case of an individual who had difficulty with voluntary initiation of liquid swallowing after surgical removal of a glioblastoma from the right dorsomedial prefrontal cortex. This individual had no difficulty swallowing solids, perhaps because of the additional external movement triggers (eg, chewing) involved. Liquid swallowing involves fewer movement triggers and requires a quicker application of force during the oral propulsive phase when liquids are transferred from the oral cavity to the oropharynx. This individual did not have buccofacial apraxia or apraxia of speech, which are often associated with swallowing apraxia linked to damage in the precentral, premotor, and inferior frontal gyri. To our knowledge, few studies have focused on movement initiation impairments affecting the upper extremities and speech, and cases involving swallowing are notably rare.
Exploring interspecies differences in ex vivo models of Pseudomonas aeruginosa keratitis: a comparative study of human, pig and sheep corneas
Authors: Okurowska Katarzyna , MacNeil Sheila , Roy Sanhita , Garg Prashant , Monk Peter N. , Karunakaran Esther
Published: December 2024

Introduction. Interspecies differences in human, pig and sheep corneal thickness may affect the Pseudomonas aeruginosa colonization. Currently, there is no research investigating the impact of these differences, along with variable storage and culture conditions on infection in ex vivo cornea models. These factors could significantly influence utilizing ex vivo models for drug testing research.

Aim. In this study, we aim to compare the relevance of sheep and pig cornea infection models to human.

Methodology. The corneas were stored in McCarey-Kaufman medium or Eagle’s Minimum Essential Medium or Dulbecco’s Modified Eagle’s Medium/Mixture F-12 Ham medium (incubator) and then infected after varying storage durations. The effect of added foetal bovine serum (FBS) to media and continuous shaking mimicking rinsing with tears on infection was also investigated. The infection outcome was evaluated by comparing c.f.u. between conditions.

Results. The study found that storage conditions, culture media, FBS and continuous rinsing of corneas with media had no significant effect on infection progression in ex vivo keratitis models across selected species.

Conclusions. Pig and sheep models yield results comparable to human corneas. These findings support the interchangeability of ex vivo human, pig and sheep keratitis models for P. aeruginosa infection studies, emphasizing their relevance and reliability in research contexts. This interchangeability is particularly useful for research groups where one particular animal model may not be available. The media in this ex vivo keratitis model can be free of animal components by the removal of FBS, which reduces the reliance on animal-derived products, aligning with ethical considerations and promoting more sustainable and humane scientific practices. This study advances the understanding of ex vivo keratitis models, demonstrating their robustness and potential for broader application in ophthalmic research and drug testing.
Common misconceptions held by health researchers when interpreting linear regression assumptions, a cross-sectional study
Authors: Jones Lee , Barnett Adrian , Vagenas Dimitrios
Published: December 2024

Background

Statistical models are powerful tools that can be used to understand complex relationships in health systems. Statistical assumptions are a part of a framework for understanding analysed data, enabling valid inferences and conclusions. When poorly analysed, studies can result in misleading conclusions, which, in turn, may lead to ineffective or even harmful treatments and poorer health outcomes. This study examines researchers’ understanding of the commonly used statistical model of linear regression. It examines understanding around assumptions, identifies common misconceptions, and recommends improvements to practice.

Methods

One hundred papers were randomly sampled from the journal PLOS ONE, which used linear regression in the materials and methods section and were from the health and biomedical field in 2019. Two independent volunteer statisticians rated each paper for the reporting of linear regression assumptions. The prevalence of assumptions reported by authors was described using frequencies, percentages, and 95% confidence intervals. The agreement of statistical raters was assessed using Gwet’s statistic.

Results

Of the 95 papers that met the inclusion and exclusion criteria, only 37% reported checking any linear regression assumptions, 22% reported checking one assumption, and no authors checked all assumptions. The biggest misconception was that the Y variable should be checked for normality, with only 5 of the 28 papers correctly checking the residuals for normality.

Conclusion

The prevalence of reporting linear regression assumptions remains low. When reported, they were often incorrectly checked, with very few authors showing any detail of their checks. To improve reporting of linear regression, a significant change in practice needs to occur across multiple levels of research, from teaching to journal reviewing. The focus should be on understanding results where the underlying statistical theory is viewed through the lens of “everything is a regression” rather than deploying rote-learned statistics.
Electrophysiological Correlates of Dynamic Cycling in Parkinson’s Disease
Authors: Joshi Prajakta , Shigo Lara , Smith Brittany , Kilbane Camilla W. , Guha Aratrik , Loparo Kenneth , Ridgel Angela L. , Shaikh Aasef G.
Published: December 2024

Objective

Physical exercise like dynamic cycling has shown promise in enhancing motor function in Parkinson’s disease (PD). We examined the underlying mechanisms of dynamic cycling in PD, emphasizing its impact on the activity of the subthalamic nucleus (STN), a pivotal region within the basal ganglia.

Methods

The investigation involved 100 dynamic cycling sessions conducted among nine PD individuals. Each participant underwent a maximum of 12 sessions over a four-week period. Local field potentials (LFPs) originating from the STN were recorded before and after cycling, utilizing DBS electrodes positioned within the nucleus. We evaluated both immediate and sustained impacts of dynamic cycling on LFP. The periodic LFP activity was assessed by determining the dominant spectral frequency and the power associated with that frequency. Aperiodic LFP activity was analyzed by calculating the 1/f exponent of the power spectrum.

Results

Immediate and sustained effects of dynamic cycling on LFPs were evaluated. While immediate changes were insignificant, long-term effects showed an increasing trend in power and the 1/f exponent of the power spectrum, a measure of fluctuation in the signal, in the dorsolateral region of the STN. Ventral region of the STN did not show a significant response to the exercise intervention.

Conclusion

These results highlight the impact of dynamic cycling on STN neuronal activity in PD. Prolonged interventions, even without immediate changes, bring about significant modifications, emphasizing the role of extended exercise in PD management and neuroplasticity.

Significance

These results highlight the impact of dynamic cycling showing changing in the STN neurophysiology in PD.

Highlights

Long-term exercise intervention affects the dorsal STN, without any immediate change, while the ventral STN shows no response.

Aperiodic exponent increases with exercise, mimicking the effect of dopamine

Periodic power also increases, behaving oppositely to its response to dopamine medication.
Cross Border Population Movement Patterns, Kenya, Uganda, and Rwanda, November 2022
Authors: King Patrick , Wanyana Mercy Wendy , Mayinja Harriet , Simbwa Brenda Nakafeero , Zalwango Marie Gorreti , Kobusinge Joyce Owens , Migisha Richard , Kadobera Daniel , Kwesiga Benon , Bulage Lilian , Gonahasa Doreen , Ahabwe Peter Babigumira , Nchoko Serah , Salat Edna , Weithaka Freshia , Gunya Oscar , Odhiambo Fredrick , Mutabazi Vincent , Habimana Metuschelah , Twagirimana Gabriel , Ndabarinze Ezechiel , Manishimwe Alexis , Itiakorit Harriet , Kadivani Samuel , Seib Katy , Whitney Ellen , Ario Alex Riolexus
Published: December 2024

Background

The frequent population movement across the five East African Countries poses risk of disease spread in the region. A clear understanding of population movement patterns is critical for informing cross-border disease control interventions.

We assessed population mobility patterns across the borders of the East African states of Kenya, Uganda, and Rwanda.

Methods

In November 2022, we conducted Focus Group Discussions (FGDs), Key Informant Interviews (KIIs), and participatory mapping. Participants were selected using purposive sampling and a topic guide used during interviews. Key informants included border districts (Uganda and Rwanda) and county health officials (Kenya). FGD participants were identified from border communities and travellers and these included truck drivers, commercial motorcyclists, and businesspersons. During KIIs and FGDs, we conducted participatory mapping using Population Connectivity Across Borders toolkits. Data were analysed using grounded theory approach using Atlas ti 7 software.

Results

Different age groups travelled across borders for various reasons. Younger age groups travelled across the border for education, trade, social reasons, employment opportunities, agriculture and mining. While older age groups mainly travelled for healthcare and social reasons. Other common reasons for crossing the borders included religious and cultural matters. Respondents reported seasonal variations in the volume of travellers. Respondents reported using both official (4 Kenya-Uganda, 5 Rwanda-Uganda borders) and unofficial Points of Entry (PoEs) (14 Kenya-Uganda, 20 Uganda-Rwanda) for exit and entry movements on borders. Unofficial PoEs were preferred because they had fewer restrictions like the absence of health screening, and immigration and customs checks. Key destination points (points of interest) included: markets, health facilities, places of worship, education institutions, recreational facilities and business towns. Twenty-eight health facilities (10- Lwakhakha, Uganda, 10- Lwakhakha, Kenya, and 8- Cyanika, Uganda) along the borders were the most commonly visited by the travellers and border communities.

Conclusion

Complex population movement and connectivity patterns were identified along the borders. These were used to guide cross-border disease surveillance and other border health strategies in the three countries. Findings were used to revise district response and preparedness plans by strengthening community-based surveillance in border communities.
A Drift-Oriented Adaptive Framework for Concept Drift Detection in Large-Scale Internet-of-Medical-Things Data Streams
Authors: Maheshwari Vikash , Bt. Osman Nurul Aida , Daud Hanita , Kurniati Angelina Prima , Bt. Wan Yusoff Wan Nur Syahidah
Published: December 2024

Background

The rise of the Internet-of-Medical-Things (IoMT) and smart devices has led to a substantial increase in extensive data streams in the healthcare domain. The interconnected nature of medical devices introduces dynamic and evolving data patterns. However, this dynamism poses a significant challenge known as Concept Drift, particularly crucial in the medical field. Concept Drift reflects the inherent instability in data patterns over time. In medical applications, this challenge intensifies as sensors must seamlessly transition from general healthcare monitoring to handling critical situations like emergency ICU operations. The complexity deepens due to imbalanced data distributions inherent in e-health scenarios.

Methods

The study introduces an Adaptive Ensemble Framework (AEF-CDA) designed to detect and adapt to concept drift in large-scale medical data streams from IoMT. The framework incorporates adaptive data preprocessing, a novel drift-centric adaptive feature selection approach, the learning of base models, and the selection of models adapted to concept drift. Additionally, an online ensemble model is integrated to enhance concept drift adaptation.

Results

The proposed AEF-CDA framework is evaluated using three public IoMT and IoT datasets. The experimental results demonstrate its superiority over contemporary methods, achieving a remarkable accuracy of 99.64% with a precision of 99.39%. These metrics surpass the performance of other approaches in the simulation.

Conclusion

In conclusion, the research presents a robust solution in the form of the adaptive ensemble framework (AEF-CDA) to effectively address the challenges posed by concept drift in IoMT data streams. The demonstrated high accuracy and precision underscore the framework’s efficacy, highlighting its potential significance in the dynamic landscape of medical data analysis.
Acute Intermittent Hypoxia Induces Motor and Cognitive Plasticity in Persons with Relapsing Remitting Multiple Sclerosis
Authors: Sandhu Milap S. , Motl Robert W. , Rymer William Z. , LaVela Sherri L.
Published: December 2024

Background

MS significantly impacts motor and cognitive function, yet therapies to effectively address these impairments remain limited. This study explores acute intermittent hypoxia (AIH) as a novel intervention for enhancing neuroplasticity and functional improvement in individuals with MS.

Objective

To examine the efficacy of a single AIH session in improving spinal motor output and cognitive performance in MS.

Methods

A randomized, blinded, placebo-controlled and crossover study was done in 10 individuals with relapsing-remitting MS. Participants underwent both AIH and sham AIH on separate days. AIH consisted of 15 brief exposures of low oxygen (9% O2) alternating with normoxia (i.e., room air). Sham AIH comprised of normoxic episodes. Pre- and post-intervention evaluations included isometric ankle torque to assess motor strength and standardized tests to evaluate cognitive function.

Results

Participants showed a significant increase in both plantarflexion and dorsiflexion ankle torque (p < .05), alongside significant enhancements in cognitive processing speeds as measured by the Symbol Digit Modalities Test (p < .01) after AIH. No changes were observed in auditory/verbal memory, and no adverse events were reported.

Conclusion

AIH presents a promising intervention for inducing neuroplasticity and improving rehabilitation outcomes in MS, suggesting the need for further exploration into its long-term impacts and mechanisms.
A computationally efficient method for dimensionality reduction in multi-channel spectral CT
Authors: Sandvold Olivia F. , Proksa Roland , Daerr Heiner , Perkins Amy E. , Brown Kevin M. , Koehler Thomas , Manjeshwar Ravindra M. , Noël Peter B.
Published: December 2024

Objective

Multi-channel spectral CT technology holds the promise of measuring incoming X-rays across various energy spectrums, significantly enhancing iodine imaging performance. Nonetheless, it necessitates the reduction of data dimensions, such as condensing multiple energy bins, to ensure processing times remain within clinically acceptable limits and to maintain compatibility with traditional two-dimensional material decomposition methodologies. This study presents an optimization strategy designed to efficiently integrate multi-channel spectral CT data, aiming to minimize the anticipated noise in the iodine domain across different system parameters influencing channel content.

Approach

The Cramer-Rao lower bound of variance (CRLB) was used to estimate the iodine domain noise for four two-input weighting schemes including kVp-switching compared to a four-input material decomposition noise estimate. Two of the four weighting schemes were optimized to contain weights that minimized the expected CRLB noise. A model of rapid kVp-switching x-ray tube and dual-layer detector were used to simulate acquisitions of a hybrid, combined technology multi-channel spectral CT system. The impact of the duty cycle ratio, or proportion of high kVp to low kVp, and the phantom size ranging from adult to pediatric were investigated.

Main Results

The two-input weighting schemes with varying amounts of each spectral channel, optimized for low iodine noise, showed consistent low estimated noise performance within 0.27% difference to the ideal, four-input material decomposition results for all tested duty cycles in a standard adult-sized 300 mm water phantom. These schemes were always superior to kVp-switching regardless of duty cycle or phantom size. In the pediatric (150 mm) and large adult (400 mm) phantom cases, the two-input weighted schemes were within 1% difference to the ideal four-input noise estimator results on average, across all tested duty cycles.

Significance

Advanced dimensionality reduction techniques, such as those presented in this work, that merge multi-channel spectral CT data illustrate a potential in improvement the accuracy of iodine contrast material measurement, while filling clinical specifications. This study also indicates the significant role that hybird spectral CT technologies could play in elevating the reliability of quantitative CT.
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

Background

Bipolar 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.

Methods

We 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.

Results

We 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.

Conclusions

Overall, 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

Introduction

Parkinson’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 analysis

This 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 dissemination

Ethics 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 number

CRD42022380544
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

Background

Neuroinflammatory responses reflecting disease progression are believed to be closely associated with the severity of prognosis in post-stroke.

Purpose

This 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.

Methods

Clinical 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.

Results

We 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).

Conclusion

Our 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

Spinal 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

Background

Research 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.

Methods

We 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.

Results

149 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.

Discussion

Elevated 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

BaSiS (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

Objective

This 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.

Method

With 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.

Results

Between 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)].

Conclusion

Sotrovimab, 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

Background

The 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.

Methods

We 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.

Results

Overall, 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.

Conclusions

Ex-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

Objectives

To evaluate the long-term angiographic patency of saphenous vein grafts (SVG) harvested using the no-touch technique compared to the conventional technique.

Methods

This 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).

Results

The 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).

Conclusions

The no-touch vein grafts were associated with statistically significantly higher patency at long-term compared to the conventional grafts.

Clinical Trial Registration

NCT04656366, 7 December 2020

Clinical Perspective

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What is new?

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The largest follow-up of the patency of no-touch vein grafts in the international literature.

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Patients with a no-touch vein graft had significantly better patency (p < 0.001) at mean follow-up of more than 8 years.

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What are the clinical implications?

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Consequent reduction in cardiovascular events after no-touch vein graft.

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Benefits at individual level due to fewer episodes of re-angina and myocardial infarction, and fewer coronary interventions.

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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

Background

Severe 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.

Objectives

Determine 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).

Results

The 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.

Discussion

We 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.