bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic value of clot formation parameters determined by rotational thromboelastometry in 63 patients with congenital dysfibrinogenemia
Authors: Simurda Tomas , Marchi Rita , Casini Alessandro , Neerman-Arbez Marguerite , Drotarova Miroslava , Skornova Ingrid , Zolkova Jana , Kolkova Zuzana , Loderer Dusan , Brunclikova Monika , Belakova Kristina Maria , Stasko Jan 
Published: January 2024

Rotational thromboelastometry (ROTEM) is a global hemostasis assay. The diagnosis added value of ROTEM in congenital dysfibrinogenemia remains to be established.
The aim of this study was to analyze clot formation by ROTEM in a cohort of dysfibrinogenemic patients and to establish correlations with genotype, clinical features, and coagulation parameters.
The study included genetically confirmed congenital dysfibrinogenemia cases (n = 63) and healthy controls (n = 50). EXTEM, INTEM, FIBTEM tests were used to measure ROTEM parameters, that is, clotting time (CT), clot formation time (CFT), maximal clot firmness (MCF) and amplitude 10 min after CT (A10). The ISTH bleeding assessment tool was used to determine bleeding episodes.
CT (INTEM) was statistically significantly shorter in congenital dysfibrinogenemia patients compared to controls while CFT (EXTEM) was prolonged. Patients's MCF in EXTEM, INTEM, and FIBTEM were similar to controls while A10 (FIBTEM) was statistically significantly lower. Fibrinogen activity was positively correlated with fibrinogen antigen, A10 and MCF in all three assays. Bleeding phenotypes were observed in 23 (36.5%) patients. Only CFT in EXTEM and CT in INTEM were statistically different in patients with bleeding phenotype versus controls. Carriers of the FGA mutation p.Arg35His had a CT (EXTEM) slightly prolonged and a reduced A10 (FIBTEM) compared to controls.
Some ROTEM parameters were able to distinguish congenital dysfibrinogenemia patients from controls, and patients with a bleeding phenotype. Prolonged CFT in EXTEM were associated with congenital dysfibrinogenemia and bleeding phenotype. Bleeding episodes in most patients were generally mild and prevalence of thrombosis was very low.
Reflections on Studying Huang Di Nei Jing in the West
Authors: Neal Edward 
Published: January 2024

Abstract

Huang Di Nei Jing (《黄帝内经》The Yellow Emperor’s Inner Classic) has been the source text of Chinese medicine knowledge and innovation for over two thousand years. Despite this key relevance, many of its ideas and practices have proven difficult to understand and implement fully into clinical practice. Cultural and language differences can be compounded with these challenges but may also present new opportunities for advancement and insight when studied by researchers outside of the originating culture. This article introduces the method of Classical-Text Archaeology and delves into the author’s two-decade journey of researching this text, with a discussion on cultural differences and issues of medical scholarship.
The impact of the site of myocardial infarction on in-hospital outcomes for patients with STEMI
Authors: Kwok Chun Shing , Qureshi Adnan I. , Lip Gregory Y.H. 
Published: January 2024

BackgroundThe territory and vessel involved in ST-elevation myocardial infarction (STEMI) is an important and there are limited contemporary studies from the national perspective.MethodsA retrospective cohort study was undertaken of national representative hospital admission in the National Inpatient Sample with a diagnosis of anterior or non-anterior STEMI between 2017 and 2020. Multiple logistic regression and multiple linear regressions were used to determine if there are any differences in in-hospital mortality, length of stay (LOS) and cost for anterior and non-anterior STEMI.ResultsA total of 655 915 admissions with STEMI were included in the analysis (267 920 anterior STEMI, and 387 995 non-anterior STEMI). Non-anterior STEMI was associated with a significant reduction in mortality (OR 0.91 95% CI 0.89–0.99,P = 0.011) and LOS (coefficient −0.15 95% CI −0.22 to −0.08,P < 0.001) compared to anterior STEMI but there was no significant difference in healthcare costs (−297 95% CI −688 to 74). Analyses considering the infarct-related artery showed that the worse outcomes were associated with left main lesions and left-sided lesions had worse outcomes than right coronary artery lesions.ConclusionNon-anterior STEMI is associated with reduced mortality and LOS compared to anterior STEMI. Left-sided coronary lesions had worse outcomes, compared to right coronary lesions. STEMI should be considered in terms of the vessel or territory affected, in relation to outcomes and healthcare costs.
Cerebral Tumefactive Inflammatory Lesion Occurrence During Ixekizumab Treatment in a Patient With Active Psoriatic Arthritis
Authors: Marangi Antonio , Benvenuti Francesco , Mazzai Linda , Riva Giulio , Polo Diana , Franceschetti Ilaria , De Sandre Pierino , Zanusso Mariano Agostino , Scanelli Giovanni , Perini Francesco 
Published: January 2024

Introduction:
Ixekizumab is an anti–interleukin-17A (IL-17A) humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and ankylosing spondylitis. Central nervous system inflammatory manifestations are atypical during therapy with IL-17A inhibitors, with only one case of myelitis described to date.

Case Report:
A 72-year-old man with a medical history of active psoriatic arthritis was admitted to our department owing to the acute onset of left face numbness 1 month after the first ixekizumab administration. Magnetic resonance imaging of the brain displayed a large T2-hyperintense infratentorial lesion involving the root of the fifth and seventh left cranial nerves. A thorough laboratoristic and instrumental work-up did not show elements suggestive of extracerebral neoplasms or infections. Therefore, neuronavigation-assisted brain biopsy was performed, and histologic analysis of the lesion revealed the presence of wide aggregates of foamy histiocytes diffusely infiltrating the brain parenchyma, in the absence of malignant tissue or histologic elements suggestive of central nervous system infections or primary histiocytoses. Steroid treatment (dexamethasone 8 mg/daily) was then administered with subsequent clinical amelioration. One month after hospital discharge, a brain magnetic resonance imaging showed a nearly complete resolution of the lesion.

Conclusion:
This is the first case of a cerebral inflammatory lesion occurring during treatment with ixekizumab. Although very rare, neurological complications may occur during anti–IL-17A therapies, thus leading to the need for careful monitoring of patients exposed to these drugs.
Anticonvulsant Agents for Treatment of Restless Legs Syndrome
Authors: Al-Kassmy Jawad , Alsalmi Mohammed , Kang Woojin , Huot Philippe 
Published: January 2024

Introduction:
Restless Legs Syndrome (RLS) is a neurological disorder primarily treated with pregabalin and gabapentin, followed by dopamine agonists later in the process due to the risk of augmenting RLS symptoms. In addition, clinical reports have disclosed varying degrees of success employing other agents in patients unresponsive to traditional agents. Here, we present a patient who had success in the reduction of RLS symptoms with lamotrigine, a broad-spectrum anticonvulsant. Previously, lamotrigine had been used in 2 trials with successful treatment of RLS.

Case Report:
We present a 58-year-old right-handed lady with long-standing history of smoking, hypertension, dyslipidaemia, prediabetes, gastro-esophageal reflux disease, asthma, strabismus, uterine cancer, severe and debilitating course of RLS accompanied by unexplained deterioration. The patient initially demonstrated abnormal sensation in all her limbs, which worsened with radiotherapy treatment, and was eventually diagnosed with RLS based on the diagnostic criteria. Subsequent examinations were unremarkable and revealed no further explanation for the deterioration of the RLS symptoms. While the complexity of the patient’s medical history had exposed her to a variety of medications, she reported that only lamotrigine, in addition to her original regimen of methadone and pramipexole, offered significant symptomatic relief. It must be noted that no adverse side effects, including impulse-control disorder, were reported by the patient.

Conclusions:
We present a case of a woman whose deteriorating symptoms of RLS were successfully alleviated by the administration of lamotrigine. This is only the third case in the literature to have successfully utilized lamotrigine as a treatment option for RLS.
Age-friendly healthcare: integrating the 4Ms to enable age-friendly cancer care
Authors: Hodge Oliver , Rasekaba Tshepo , Blackberry Irene , Steer Christopher B. 
Published: January 2024

Purpose of review
There is a growing movement towards person-centred, age-friendly healthcare in the care of older adults, including those with cancer. The Age-Friendly Health Systems (AFHS) initiative uses the 4Ms framework to enable this change. This review documents the utility and implications of 4Ms implementation across different settings, with a particular focus on cancer care.

Recent findings
The AFHS initiative 4Ms framework uses a set of core, evidence-based guidelines (focussing on What Matters, Medication, Mentation and Mobility) to improve person-centred care. The successful implementation of the 4Ms has been documented in many different healthcare settings including orthopaedics primary care, and cancer care. Implementation of the 4Ms framework into existing workflows complements the use of geriatric assessment to improve care of older adults with cancer. Models for implementation of the 4Ms within a cancer centre are described. Active engagement and education of healthcare providers is integral to success. Solutions to implementing the What Matters component are addressed.

Summary
Cancer centres can successfully implement the 4Ms framework into existing workflows through a complex change management process and development of infrastructure that engages healthcare providers, facilitating cultural change whilst employing quality improvement methodology to gradually adapt the status quo to age-friendly processes.
The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas
Authors: Estrela Tais , Truong Saprina , Garcia Arielle , He Jocelyn , Ying Gui-Shuang , Devakandan Keshini , Reginald Y. Arun , Fisher Michael J. , Liu Grant T. , Ullrich Nicole J. , Avery Robert A. , Heidary Gena 
Published: January 2024

Background:
Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs).

Methods:
Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell–inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations.

Results:
Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05).

Conclusions:
CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.
Clinical impact and public health challenges of a PVL- MRSA bacteraemia outbreak amongst people who inject drugs in South Yorkshire.
Authors: Beaumont Matthew , Subramanian Bala , Agwuh Ken , Ryan Yan , Pichon Bruno 
Published: January 2024

Background: Panton-Valentine leukocidin (PVL) Staphylococcus aureus (SA) is an emergent public health concern. PVL toxin has been mostly associated with methicillin-sensitive Staphylococcus aureus (MSSA) related skin and soft tissue infections occurring in high-risk groups such as people who inject drugs (PWID). The emergence of PVL- methicillin resistant Staphylococcus aureus (MRSA) infection is causing severe and life-threatening disease in PWID.
Clinical cases: we present an outbreak of eight PVL-MRSA bacteraemia cases at a UK teaching hospital between 2018 and 2022. An additional four patients developed bacteraemia cases with PVL-negative MRSA of the same multi-locus sequence type (MLST). All patients were PWID and aged between 33- 51 years old. Four patients developed MRSA bacterial endocarditis. Three patients died. These cases represent the initial cases detected at Doncaster and Bassetlaw Teaching Hospitals of what is an ongoing and developing outbreak.
Management: an outbreak investigation has been undertaken in association with the UK Health Security Agency. Epidemiological factors have been explored, including via direct contact at a local sheltered accommodation and the possibility of a contaminated drug supply. Whole-genome sequencing confirmed that all isolates were closely related and of the same MLST (sequence type 5). A community substance misuse group disseminated health education on the prevention of PVL-MRSA. Preventing infection in PWID presents a major challenge due to the impact of addiction on engagement with services and the significant barriers faced by our patients to observing infection prevention measures.
Conclusion: PVL-MRSA is of major public health concern and outbreak investigation and mapping out local epidemiological patterns plays a vital role in preventing further spread throughout the community. Additionally, this work enables targeted and early treatment in patients in high-risk categories for disease. These cases of PVL-MRSA infection in PWID highlights the transmissibility, pathogenic potential and severe clinical disease spectrum within this population. Further work is required to tackle transmission and infection from this pathogenic strain.
Short-term passive greenspace exposures have little effect on nasal microbiomes: a cross-over exposure study of a Māori cohort
Authors: Brame Joel E. , Warbrick Isaac , Heke Deborah , Liddicoat Craig , Breed Martin F. 
Published: January 2024

ABSTRACTIndigenous health interventions have emerged in New Zealand aimed at increasing human interactions with and exposure to macro and microbial diversity. Urban greenspaces provide opportunities for people to gain such exposures. However, the dynamics and pathways of microbial transfer from natural environments onto a person remain poorly understood. Here, we analysed bacterial 16S rRNA amplicons in air samples (n= 7) and pre- and post-exposure nasal samples (n= 238) from 35 participants who had 30-minute exposures in an outdoor park. The participants were organised into two groups: over eight days each group had two outdoor park exposures and two indoor office exposures, with a cross-over study design and washout days between exposure days. We investigated the effects of participant group, location (outdoor park vs. indoor office), and exposures (pre vs. post) on the nasal bacterial community composition and three key suspected health-associated bacterial indicators (alpha diversity, generic diversity of Gammaproteobacteria, and read abundances of butyrate-producing bacteria). The participants had distinct nasal bacterial communities, but these communities did not display notable shifts in composition following exposures. The community composition and key health bacterial indicators were stable throughout the trial period, with no clear or consistent effects of group, location, or exposure. We conclude that 30-minute exposure periods to urban greenspaces are unlikely to create notable changes in the nasal microbiome of visitors, which contrasts with previous research. Our results suggest that longer exposures or activities that involves closer interaction with microbial rich ecological components (e.g., soil) are required for greenspace exposures to result in noteworthy changes in the nasal microbiome.
A video-rate hyperspectral camera for monitoring plant health and biodiversity
Authors: Brooks Laura J. , Pearce Daniel , Kwok Kenton , Jawade Nikhil , Qi Man , Fenollosa Erola , Beker Deniz , Whicker James , Davis Katrina , Salguero-Gómez Roberto , Wang Robin , Chappell Steve 
Published: January 2024

ABSTRACTHyperspectral cameras are a key enabling technology in precision agriculture, biodiversity monitoring, and ecological research. Consequently, these applications are fuelling a growing demand for devices that are suited to widespread deployment in such environments. Current hyperspectral cameras, however, require significant investment in post-processing, and rarely allow for live-capture assessments. Here, we introduce a novel hyperspectral camera that combines live spectral data and high-resolution imagery. This camera is suitable for integration with robotics and automated monitoring systems. We explore the utility of this camera for applications including chlorophyll detection and live display of spectral indices relating to plant health. We discuss the performance of this novel technology and associated hyperspectral analysis methods to support an ecological study of grassland habitats at Wytham Woods, UK.
Cell type and regulatory analysis in amphioxus illuminates evolutionary origin of the vertebrate head
Authors: Markos Anna , Kubovciak Jan , Mrstakova Simona Mikula , Zitova Anna , Paces Jan , Machacova Simona , Kozmik Zbynek , Kozmik Zbynek , Kozmikova Iryna 
Published: January 2024

AbstractTo shed light on the enigmatic origin of the vertebrate head, our study employs an integrated approach that combines single-cell transcriptomics, perturbations in signalling pathways, and cis-regulatory analysis in amphioxus, a close relative of chordate common ancestor. Through cell type characterization, we identified the presence of a prechordal plate, pre-migratory and migratory neural crest-like cell populations in the developing amphioxus embryo. Functional analysis established conserved roles of the Nodal and Hedgehog signalling pathways in prechordal plate, and of Wnt signalling pathway in neural crest development. Furthermore, the trans-species transgenic experiments provided evidence of cis-regulatory level homology within the chordate lineage. Our findings provide evidence that the key features of vertebrate head development can be traced back to the common ancestor of all chordates.One Sentence SummaryCell populations forming the vertebrate head are present in the close relative of chordate common ancestor.
The integration of network biology and pharmacophore modeling suggests repurposing Clindamycin as an inhibitor of pyroptosis via Caspase-1 blockage in tumor-associated macrophages
Authors: Weich Adrian , Flamann Cindy , Berges Johannes , Singh Krishna Pal , Chambers David , Lai Xin , Wolkenhauer Olaf , Berking Carola , Krönke Gerhard , Gupta Shailendra , Bruns Heiko , Vera Julio 
Published: January 2024

AbstractBackgroundUveal melanoma (UM) is a highly malignant intraocular tumor with a poor prognosis and response to therapy, including immune checkpoint inhibitors (ICIs), after the onset of liver metastasis. The metastatic microenvironment contains high levels of tumor-associated macrophages (TAMs) that correlate positively with a worse patient prognosis. We hypothesized that one could increase the efficacy of ICIs in UM metastases by immunomodulating UM-associated macrophages.MethodsTo identify potential targets for the immunomodulation, we created a network-based representation of the biology of TAMs and employed (bulk and single-cell) differential gene expression analysis to obtain a regulatory core of UM macrophages-associated genes. We utilized selected targets for pharmacophore-based virtual screening against a library of FDA-approved chemical compounds, followed by refined flexible docking analysis. Finally, we ranked the interactions and selected one novel drug-target combination forin vitrovalidation.ResultsBased on the generated TAM-specific interaction network (3863 nodes, 9073 edges), we derived a UM macrophages-associated regulatory core (74 nodes, 286 edges). From the regulatory core genes, we selected eight potential targets for pharmacophore-based virtual screening (YBX1, GSTP1, NLRP3, ISG15, MYC, PTGS2, NFKB1, CASP1). Of 266 drug-target interactions screened, we identified the interaction between the antibiotic Clindamycin and Caspase-1 as a priority for experimental validation. Ourin vitrovalidation experiments showed that Clindamycin specifically interferes with activated Caspase-1 and inhibits the secretion of IL-1β, IL-18, and lactate dehydrogenase (LDH) in macrophages after stimulation. Our results suggest that repurposed Clindamycin could reduce pyroptosis in TAMs, a pro-inflammatory form of programmed immune cell death favouring tumor progression.ConclusionWe were able to predict a novel Clindamycin-Caspase-1 interaction that effectively blocks Caspase-1-mediated inflammasome activity and pyroptosis in vitro in macrophages. This interaction is a promising clinical immunomodulator of the tumor microenvironment for improving ICI responsivenss. This work demonstrates the power of combining network-based transcriptomic analysis with pharmacophore-guided screening forde novodrug-target repurposing.Graphical Abstract
Antibody targeting of surface PSGL-1 glycoprotein leads to lymphoma apoptosis and tumorigenesis inhibition
Authors: Pereira João L. , Ferreira Francisca , dos Santos Nuno R. 
Published: January 2024

AbstractLymphomas are a heterogeneous group of diseases that originate from T, B or natural killer (NK) cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P-selectin glycoprotein ligand 1 (PSGL-1) is expressed at the surface of hematological malignant cells and has been shown to have a pro-oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL-1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL-1 was expressed in both T and B cell-derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell-derived lymphoma cell lines,in vitrotargeting with the PL1 mAb, which recognizes the PSGL-1 N-terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro-apoptotic activity was shown to be dose-dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti-PSGL-1 treatment of mice xenografted with the HUT-78 cutaneous T-cell lymphoma (CTCL) cell line resulted in decreased tumor growth, had no effect onin vivoproliferation, but increased the levels of apoptosis in tumors. Anti-PSGL-1 treatment of mice xenografted with a Burkitt lymphoma (BL) cell line that was resistant to anti-PSGL-1 treatmentin vitro, had no impact on tumorigenesis. These findings show that PSGL-1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL-1 as a potential target for lymphoma therapy.