bluuebunny/crossref_metadata_2025_split huggingface dataset:
Death for the Minnows: Private Landlords and the Pendulum of Regulation
Authors: Mayfield Ben 
Published: November 2024

Abstract
Recent housing tragedies and scandals such as Grenfell Tower fire, and the death of a child in Rochdale due to mould, cast a long shadow over the provision of housing and have brought several deficiencies of the private rented sector into the light. Security of tenure and rent control in particular have become significant political issues that framed the housing policies of the two major parties at the last general election. This paper examines the history of key legislative interventions in the regulation of this sector to divine lessons for the present. This is a history of pendulum swings between free markets and market failure, with unintended consequences resulting from poorly developed laws that emerged from political overreactions to problems in the private rented sector. The paper notes the relative success of policy compromises and cooperation with private landlords. The tragic history of landlord and tenant law also provides an unrivalled opportunity to test the assertion of R. H Tawney, that ‘freedom for the pike is death for the minnows.’
Painful mycetoma: a study to understand the risk factors in patients visiting the Mycetoma Research Centre (MRC) in Khartoum, Sudan
Authors: El-Amin Saria O , El-Amin Rahba O , El-Sadig Sarah M , Fahal Ahmed Hassan , Musa Ahmed 
Published: November 2024

Abstract

Background
Mycetoma, a neglected tropical disease endemic to Sudan, is traditionally characterized as a painless condition. However, recent studies reporting painful mycetoma lesions have challenged this assumption. With limited reports in the medical literature regarding pain in mycetoma, this study was conducted to investigate the risk factors for painful mycetoma lesions in patients visiting the Mycetoma Research Centre (MRC) in Khartoum, Sudan.

Methods
This cross-sectional study aimed to identify the risk factors for painful mycetoma lesions. The study analyzed electronic records of 481 patients with confirmed mycetoma, seen between 1991 and 2020, using a systematic sampling approach.

Results
The study found that pain was more likely to occur in cases with bone destruction, secondary bacterial infection and actinomycete infection (OR=1.762, 1.815 and 1.259, respectively). Additionally, pain was more frequently observed in patients aged 45 y and older. Smaller mycetoma lesions, measuring less than 5 cm, were less likely to cause pain, and this was identified as a significant risk factor for painful mycetoma lesions (β coefficient=−1.294).

Conclusion
The findings suggested that pain in mycetoma is typically associated with the severity of the condition. Therefore, early initiation of appropriate treatment may help reduce pain. Furthermore, careful differentiation between actinomycetes and eumycetes is essential for the timely and accurate diagnosis of mycetoma.
Infective endocarditis causing recurrent cerebral infarction, cerebral hemorrhage and septic meningitis: A case report
Authors: Wang Huiliang , Fan Lingyan , Li Chenxi , Yu Haining , Han Jilan , Du Yeliang , Xing Guoping 
Published: November 2024

Rationale:
We reported a rare case of recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis, culminating in the diagnosis of a young patient with infective endocarditis who had been treated in 3 hospitals for a long course of illness for 8 months prior to diagnosis. It aims to enhance clinicians’ understanding of the neurological complications caused by infective endocarditis.

Patient concerns:
A 25-year-old male, student, was hospitalized for an 8-hour history of speech impairment and drooling with dysphagia. Magnetic resonance imaging (MRI) showed massive cerebral infarction in the right frontotemporal and insular lobes, and the first diagnosis was “cerebral infarction.” Later, the patient developed recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis.

Diagnoses:
Recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis were confirmed to be caused by infective endocarditis.

Interventions:
The patient was treated with antiplatelet drugs such as aspirin and clopidogrel, mannitol to reduce intracranial pressure, and ceftriaxone and vancomycin to fight infection, and the patient’s condition improved.

Outcomes:
The patient was diagnosed with infective endocarditis after 8 months without a clear diagnosis, and the patient was finally diagnosed with infective endocarditis during the final follow-up.

Lessons:
Febrile patients should be aware of infective endocarditis, particularly if the fever is persistent of unknown origin or structural changes in the heart with neurologic lesions. Cardiogenic neurological diseases are relatively more severe, have a worse prognosis, and have a higher recurrence rate than primary neurological diseases, so early diagnosis and treatment are more urgently needed.
Multitissue Multiomics Integration Reveals Tissue-Specific Pathways, Gene Networks, and Drug Candidates for Type 1 Diabetes
Authors: Blencowe Montgomery , Saleem Zara , Liu Ruoshui , Tseng I-Hsin , Wier Julian , Yang Xia 
Published: November 2024

ABSTRACTAims/hypothesisAlthough genome-wide association studies (GWAS) have identified loci associated with Type 1 diabetes (T1D), the specific pathways and regulatory networks linking these loci to disease pathology remain largely unknown. We hypothesized that T1D genetic risk factors disrupt tissue-specific biological pathways and gene networks that ultimately lead to beta cell loss.MethodsWe conducted a multitissue multiomics analysis that integrates human GWAS data for T1D with tissue-specific regulatory data on gene expression and gene network models across relevant tissues to highlight key pathways and key driver genes contributing to T1D pathogenesis. Key driver genes were validated using islet-specific gene expression and protein data from non-obese diabetic (NOD) mice compared to non-T1D mouse models. Drug repositioning predictions were generated using the L1000 and PharmOmics platforms.ResultsOur integrative genomics approach identified known immune pathways across multiple tissues, such as adaptive immune responses, cytokine-mediated inflammation, primary immunodeficiency, and interactions between lymphoid and non-lymphoid cells. Tissue-specific signals included genes related to type 2 diabetes in lymphocytes, viral response pathways in macrophages and monocytes, and Notch signaling in adipose and immune cells. In pancreatic islet analysis, we observed significant enrichment for T1D and type 2 diabetes gene sets alongside immune-related pathways, including antigen processing, systemic lupus erythematosus, and interferon signaling. Removing HLA genes from the analysis revealed additional immune pathways, such as RIG-I/MDA5 induction of interferons, along with melanogenesis, steroid hormone synthesis, and iron transport. Network modeling highlighted the autoimmune basis of disease with key drivers such as FYN, TAP1, WAS, and HLA-B/C/G, as well as further immunomodulatory genes such as LCK, LCP2, EMR1, and GC. These key drivers were further supported by gene and protein expression data from NOD mice. We additionally highlight various drug classes that target the T1D genetic networks and may be useful to delay T1D development.Conclusions/interpretationOur multitissue multiomics approach provides a detailed landscape of the tissue-specific genetic networks and regulators underlying T1D. This analysis confirms the roles of known immune pathways while uncovering additional regulatory elements and disease-associated networks, thus expanding our understanding of T1D pathogenesis. The identification of potential drug candidates through network analysis offers potential therapeutic strategies for targeting disease pathways and holds promise for delaying or preventing T1D progression.
DuckDerm: An Improved Water Infiltration Prevention Product for Long-Term Intravenous Therapy Patients
Authors: Fantini Dalia , Fisk Abigail , Leon-Vargas Andres , Lynch Emma , Scarlett Christine , Stafford Devon , Zegarra Marcos , Bielewicz Brady John 
Published: November 2024

AbstractWe propose an alternative to the widely implemented intravenous (IV) shower guard solution, AnchorDry, which we have coined DuckDerm. The AnchorDry is a rigid square of plastic with an adhesive border on the outer edge. This design does not adhere to the arm during the bathing period as it cannot withstand the range of motion (ROM) patients exert, leaving the Tegaderm and IV site vulnerable to water intrusion. Significant water intrusion compromises the IV site, leaving it susceptible to infection. By interviewing seasoned clinicians, nursing faculty, students, and patient care technicians (PCTs) we ascertained ineffective shower guard fit is an issue rooted in design and material selections. We have found that nurses and PCTs are often getting creative to modify or make their own IV shower guards.After several design iterations and consultations with several University of Pittsburgh nursing faculty, we mass-manufactured our design. The DuckDerm body is composed of 1 mil polyethylene plastic, which is biocompatible and able to move with the skin, a hypoallergenic adhesive, and a foam barrier to envelop the Tegaderm. Based on this initial testing, we formulated our design specifications: (1) maintaining the patient’s ROM, (2) ease of use for both patients and clinicians, and (3) preventing water infiltration. We provided our manufactured design and interviewed nursing students and faculty (n=21) to address the following criteria: (1) the DuckDerm must be simple for clinicians to apply to not take away time from more essential tasks and to encourage patient self-application; (2) the DuckDerm must retain functionality without providing discomfort to the patient during use and removal. We also conducted functionality testing using our manufactured design to address the following criteria on volunteers (n=11): the DuckDerm must (1) contain all the IV components within the foam barrier, (2) not place unnecessary pressure on components to dislodge, and (3) fit securely on the patient’s arm. Additionally, the Duckderm must adhere to the skin while subjected to running water and movement, and the DuckDerm must be able to provide a sufficient range of motion about the antecubital space to allow for arm movements required while showering. The Duckderm outperformed the currently utilized solution in both verbal feedback and assessment by potential users (nurses and PCTs) and in functionality testing; therefore, we propose our novel design as an alternative to the currently employed AnchorDry.
Shared Clinical and Immunologic Features of mRNA Vaccines: Preliminary Results from a Comparative Clinical Study
Authors: Fierro Carlos , Sanchez-Crespo Nelia , Makrinos Daniel , Zhang Weijie , Sun Yanbo , Rohilla Poonam , Girard Bethany , Adeniji Abidemi , DiPiazza Anthony , Paris Robert 
Published: November 2024

AbstractIntroductionClinical trials do not typically assess underlying molecular mechanisms of vaccine immunogenicity or reactogenicity. We evaluated the reactogenicity and immunogenicity of 4 mRNA vaccines and potential contributing mechanisms and identified shared and unique clinical and immunologic features.MethodsThis ongoing open-label, phase 1 trial randomized healthy adults (18-75 years) to receive a single dose of mRNA-1273.222 (bivalent COVID-19), mRNA-1345 (RSV), mRNA-1010 (influenza), and FLUAD (active influenza comparator) or 2 or 3 doses of mRNA-1647 (CMV). The primary objective was to assess the safety and reactogenicity of each study vaccine, with humoral immunogenicity (neutralizing antibody [nAb] responses) as the secondary objective. This interim analysis reports safety and reactogenicity in all study vaccines and humoral immunogenicity in single-dose vaccines (mRNA-1273.222, mRNA-1345, mRNA-1010, and FLUAD). Exploratory objectives included antigen-specific T-cell responses after single-dose mRNA-1345 or mRNA-1273.222, and soluble mediators of inflammation and innate immunity following vaccination in single-dose vaccine groups and two doses of mRNA-1647.ResultsAt the interim analysis data cutoff (February 1, 2023), 302 participants received 1 dose of the study vaccines. Reactogenicity exhibited a consistent trend across vaccine groups; most solicited local and systemic adverse reactions within 7 days were mild or moderate in severity. There were no deaths or serious, severe, or treatment-related adverse events leading to study discontinuation. At Day 29, nAb titers against vaccine-specific antigens increased 2- to 8-fold versus baseline for all single-dose vaccine groups. In an exploratory analysis, mRNA-1273.222 and mRNA-1345 induced antigen-specific Th1-biased CD4+and CD8+T-cell responses at Day 29. The cytokine response analysis showed increased levels of IFN-γ, IL-6, IL-2Ra, CXCL9, IP-10, MCP-2, and MIP-1β on Day 2 following vaccination, with generally greater increases observed with mRNA vaccines versus FLUAD. Regardless of age and across mRNA vaccine groups, peak serum levels of IL-1Ra and MCP-1/MCP-2 on Day 2 weakly correlated with systemic reactogenicity scores (correlation coefficient range: 0.15-0.27).ConclusionsThe 4 mRNA vaccines had acceptable reactogenicity, demonstrated changes in serum biomarkers of innate immune activation, and were immunogenic. This suggests that the observed reactogenicity of mRNA vaccines may be related to shared features of the mRNA platform (LNP platform).Clinical Trial RegistrationClinicalTrials.govNCT05397223
H-MpoxNet: A Hybrid Deep Learning Framework for Mpox Detection from Image Data
Authors: Chakroborty Sajal 
Published: November 2024

ABSTRACTInfectious diseases can create significant global threats to public health and economic stability by creating pandemics. SARS-CoV-2 is a recent example. Early detection of infectious diseases is crucial to prevent global outbreaks. Mpox, a contagious viral disease first detected in humans in 1970, has experienced multiple outbreaks in recent decades, which emphasizes the development of tools for its early detection. In this paper, we develop a hybrid deep learning framework for Mpox detection. This framework allows us to construct hybrid deep learning models combining deep learning architectures as a feature extraction tool with Machine Learning classifiers and perform a comprehensive analysis of Mpox detection from image data. Our best-performing model consists of MobileNetV2 with LightGBM classifier, which achieves an accuracy of 91.49%, 91.87% weighted precision, 91.49% weighted recall, 91.51% weighted F1-score and Matthews Correlation Coefficient score of 0.83.
CRL4DCAF12regulation of MCMBP ensures optimal licensing of DNA replication
Authors: Yadav Anoop Kumar , Abdirov Alikhan , Ondruskova Katarina , Negi Simran , Kolarova Karolina , Dibus Nikol , Krejci Jana , Polasek-Sedlackova Hana , Cermak Lukas 
Published: November 2024

ABSTRACTThe minichromosome maintenance (MCM2-7) protein complexes are central drivers of genome duplication. Distinct protein pools, parental and nascent MCMs, and their precise equilibrium are essential to sustain error-free DNA replication1. However, the mechanism responsible for generating these pools and maintaining their equilibrium remains largely unexplored. Here, we identified CRL4DCAF12as a new factor controlling the assembly of nascent MCM complexes. During MCM biogenesis, MCMBP facilitates the assembly and transport of newly synthesized MCM3-7 subcomplexes into the nucleus2,3. Once in the nucleus, the MCM2 subunit must be incorporated into the MCM3-7 subcomplex, while MCMBP needs to be removed. CRL4DCAF12facilitates the degradation of MCMBP and thereby regulates the assembly of MCM2-7 complexes. The absence of CRL4DCAF12adversely affects the level of chromatin-bound nascent MCMs, resulting in accelerated replication forks and genome instability. Collectively, our findings uncovered the molecular mechanism underlying nascent MCM production essential to counteract genome instability and tumor formation.
Decoding substrate specificity determining factors in glycosyltransferase-B enzymes – Insights from machine learning models
Authors: Hennen Samantha G. , Bomble Yannick J. , Urbanowicz Breanna R. , Bharadwaj Vivek S. 
Published: November 2024

AbstractSubstrate specificity is an essential characteristic of any enzyme’s function and an understanding of the factors that determine this specificity is crucial for enzyme engineering. Unlike the structure of an enzyme which is directly impacted by its sequence, substrate specificity as an enzyme attribute involves a rather indirect relationship with sequence as it also depends on structural aspects that dictate substrate accessibility and active site dynamics. In this study, we explore the performance of classifier-based machine learning models trained on curated sequence and structural data for a class of glycosyltransferases (GTs), namely GT-Bs, to understand their substrate specificity determining factors. GTs enable the transfer of sugar moieties to other biomolecules such as oligosaccharides or proteins and are found in all kingdoms of life. In plants, GTs participate in the biosynthesis of plant cell wall biopolymers (eg: hemicelluloses and pectins) and are an integral part of the enzymatic machinery that enables the storage of carbon and energy as plant biomass. To elucidate the substrate specificity of uncharacterized GT-Bs, we constructed multi-label machine learning models (Support Vector Classifier, K-Nearest Neighbors, Gaussian Naïve-Bayes, Random Forest) that incorporate both sequence and structural features. These models achieve good predictive accuracies on test datasets. However, despite our use of structural information, we highlight that there is further scope for improvement in training these models to draw interpretable relationships between sequence, structure and substrate specificity determining motifs in GT-Bs.
The Role of Health Professionals in Managing Type 2 Diabetes Mellitus in Community: A Scoping Review
Authors: Pasambo Yourisna , Pandin Moses Glorino Rumambo , Efendi Ferry 
Published: November 2024

AbstractBackgroundDiabetes Mellitus Type 2 (T2DM) is a global health problem that continues to increase. Suboptimal treatment can worsen the patient’s condition, cause more serious complications, and increase the death rate. The role of various health professionals in the management of T2DM in the community is increasingly recognized as an important element for achieving better outcomes. Objective of this review is to identify and analyze the role of each health professional and their challenges in treating T2DM.MethodReview of the scope of the main research that discusses it the role of the role of each health professional health professional in treating T2DM in the community. Various databases were searched via Web of Science, Scopus, PubMed, and ProQuest. Four databases were searched and 462 articles were retrieved. After screening articles and abstracts, 51 full texts were assessed for eligibility, and finally 9 studies were further analyzed and synthesized.Resultsseven quantitative studies and two qualitative studies met the inclusion criteria. Four themes emerged: (1) the role of each health professional, (2) Determining factors for the success of T2DM treatment, (3) Challenges in treating T2DM, and (4) Health policy and support systems.Conclusionfound unclear role definitions for healthcare professionals managing T2DM, leading to overlapping responsibilities and inefficiencies in patient care. This study highlights the importance of a clear and standardized treatment protocol and guideline, containing clear roles for each health professional for the management of people with T2DM in the community. Governments need to promote IPC and provide the necessary resources and infrastructure to support collaborative practice resulting in better outcomes for T2DM patients.
Effect of Acipimox on skeletal muscle biochemistry, structure and function in older people with probable sarcopenia: an experimental medicine study
Authors: McDonald Claire , Alderson Craig , Birkbeck Matthew G , Din Silvia Del , Gorman Grainne G , Hollingsworth Kieren G , Kirk Cameron , Massarella Clare , Rochester Lynn , Tuppen Helen AL , Warren Charlotte , Sayer Avan A , Witham Miles D 
Published: November 2024

AbstractBackgroundSkeletal muscle Nicotinamide Adenine Dinucleotide (NAD) concentrations are low in people with sarcopenia. Increasing NAD concentrations may offer a novel therapy. This study tested if Acipimox (a NAD precursor) improves skeletal muscle NAD concentration and function in people with probable sarcopenia.MethodsParticipants aged 65 and over with low walk speed (<0.8m/s) and low muscle strength (by 2019 European Working Group criteria) were recruited to this before and after, proof-of-concept study. Participants received acipimox 250mg orally (twice or thrice daily according to creatinine clearance) + aspirin 75mg daily (to prevent facial flushing) for 4 weeks.Muscle biopsy of the vastus lateralis,31P magnetic resonance spectroscopy, and a 7-digital mobility assessment were performed before starting acipimox and after 3 weeks of treatment. The primary outcome was change in skeletal muscle NAD concentration. Secondary outcomes included change in phosphocreatine recovery rate and measures of physical performance.ResultsEleven participants (8 women), mean age 78.9 years (SD 4.3), were recruited. Mean walk speed at baseline was 0.69m/s (SD 0.07). All completed baseline and follow-up visits. Median medication adherence was 95% (range 91–104%). There was no statistically significant difference in the primary outcome of change in NAD concentrations in skeletal muscle between baseline and follow-up [median difference: −0.003umol/g (IQR −0.058 to 0.210); P=0.26] or secondary outcomes. Nineteen adverse events were reported, none serious.ConclusionsAlthough the study protocol was feasible and well tolerated, acipimox did not improve skeletal muscle NAD concentration, biochemical markers or physical function in people with probable sarcopenia.
Targeted Proteomic Biomarker Profiling Using NULISA in a cohort enriched with risk for Alzheimer’s Disease and Related Dementias
Authors: Reyes Ramiro Eduardo Rea , Wilson Rachael E. , Langhough Rebecca E. , Studer Rachel L. , Jonaitis Erin M. , Oomens Julie E. , Planalp Elizabeth M. , Bendlin Barbara B. , Chin Nathaniel A. , Asthana Sanjay , Zetterberg Henrik , Johnson Sterling C 
Published: November 2024

Structured AbstractINTRODUCTIONTargeted proteomic assays may be useful for diagnosing and staging Alzheimer’s disease and related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning the AD spectrum.METHODSCross-sectional plasma samples (n=252) were analyzed using Alamar’s NULISAseq CNS panel. ROC analyses demonstrated NULISAseq-pTau217 accuracy in detecting amyloid (A) and tau (T) PET positivity. Differentially expressed proteins were identified using volcano plots.RESULTSNULISAseq-pTau217 accurately classified A/T PET status with ROC AUCs of 0.92/0.86. pTau217 was upregulated in A+, T+, and impaired groups with log2-fold changes of 1.21, 0.57 and 4.63, respectively, compared to A-. Interestingly, pTDP43-409 was also upregulated in the impaired group and correlated with declining hippocampal volume and cognitive trajectories.DISCUSSIONThis study shows the potential of a targeted proteomics panel for characterizing brain changes pertinent to ADRD. The promising pTDP43-409 findings require further replication.