bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformer-based framework for multi-class segmentation of skin cancer from histopathology images
Authors: Imran Muhammad , Islam Tiwana Mohsin , Mohsan Mashood Mohammad , Alghamdi Norah Saleh , Akram Muhammad Usman 
Published: April 2024

IntroductionNon-melanoma skin cancer comprising Basal cell carcinoma (BCC), Squamous cell carcinoma (SCC), and Intraepidermal carcinoma (IEC) has the highest incidence rate among skin cancers. Intelligent decision support systems may address the issue of the limited number of subject experts and help in mitigating the parity of health services between urban centers and remote areas.MethodIn this research, we propose a transformer-based model for the segmentation of histopathology images not only into inflammation and cancers such as BCC, SCC, and IEC but also to identify skin tissues and boundaries that are important in decision-making. Accurate segmentation of these tissue types will eventually lead to accurate detection and classification of non-melanoma skin cancer. The segmentation according to tissue types and their visual representation before classification enhances the trust of pathologists and doctors being relatable to how most pathologists approach this problem. The visualization of the confidence of the model in its prediction through uncertainty maps is also what distinguishes this study from most deep learning methods.ResultsThe evaluation of proposed system is carried out using publicly available dataset. The application of our proposed segmentation system demonstrated good performance with an F1 score of 0.908, mean intersection over union (mIoU) of 0.653, and average accuracy of 83.1%, advocating that the system can be used as a decision support system successfully and has the potential of subsequently maturing into a fully automated system.DiscussionThis study is an attempt to automate the segmentation of the most occurring non-melanoma skin cancer using a transformer-based deep learning technique applied to histopathology skin images. Highly accurate segmentation and visual representation of histopathology images according to tissue types by the proposed system implies that the system can be used for skin-related routine pathology tasks including cancer and other anomaly detection, their classification, and measurement of surgical margins in the case of cancer cases.
Revolutionizing orthopedic healthcare: a systematic review unveiling recombinant antimicrobial peptides
Authors: Pennone Vincenzo , Rosini Elena , Mascheroni Elena , Gianola Silvia , Castellini Greta , Bargeri Silvia , Lovati Arianna B. 
Published: April 2024

The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic surgeries carry a risk of infection, especially in patients with comorbidities. The rise of antibiotic resistance exacerbates this issue, necessitating alternatives like in vitro bioengineered antimicrobial peptides (AMPs), offering broad-spectrum activity and multiple action mechanisms. This review aimed to assess the prevalence of antimicrobial potential and the yield after purification among recombinant AMP families. The antimicrobial potential was evaluated using the Minimum Inhibitory Concentration (MIC) values against the most common bacteria involved in clinical infections. This systematic review adhered to PRISMA guidelines, focusing on in vitro studies of recombinant AMPs. The search strategy was run on PubMed, Scopus and Embase up to 30th March 2023. The Population, Exposure and Outcome model was used to extract the data from studies and ToxRTool for the risk of bias analysis. This review included studies providing peptide production yield data and MIC values against pathogenic bacteria. Non-English texts, reviews, conference abstracts, books, studies focusing solely on chemical synthesis, those reporting incomplete data sets, using non-standard MIC assessment methods, or presenting MIC values as ranges rather than precise concentrations, were excluded. From 370 publications, 34 studies on AMPs were analyzed. These covered 46 AMPs across 18 families, with Defensins and Hepcidins being most common. Yields varied from 0.5 to 2,700 mg/L. AMPs were tested against 23 bacterial genera, with MIC values ranging from 0.125 to &gt;1,152 μg/mL. Arenicins showed the highest antimicrobial activity, particularly against common orthopedic infection pathogens. However, AMP production yields varied and some AMPs demonstrated limited effectiveness against certain bacterial strains. This systematic review emphasizes the critical role of bioengineered AMPs to cope infections and antibiotic resistance. It meticulously evaluates recombinant AMPs, focusing on their antimicrobial efficacy and production yields. The review highlights that, despite the variability in AMP yields and effectiveness, Arenicins and Defensins are promising candidates for future research and clinical applications in treating antibiotic-resistant orthopedic infections. This study contributes significantly to the understanding of AMPs in healthcare, underscoring their potential in addressing the growing challenge of antibiotic resistance.Systematic review registration:https://osf.io/2uq4c/.
Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus
Authors: Yang Can , Chen Jing , Zhou Huifen , Zeng Di , Wan Haitong , Yang Jiehong 
Published: April 2024

ObjectiveIn this study, we examined the therapeutic effects of Yinhuapinggan granules (YHPGs) in influenza-infected mice. We also examined how YHPGs affect the composition of the intestinal flora and associated metabolites.MethodsWe used the nasal drip method to administer the influenza A virus (IAV) H1N1 to ICR mice. Following successful model construction, the mice were injected with 0.9% sterile saline and low (5.5 g/kg), medium (11 g/kg), and high (22 g/kg) doses of YHPGs. The pathological changes in the lungs and intestines were evaluated by gavage for 5 consecutive days. Detection of sIgA, IL-6, TNF-α, INF-γ, and TGF-β cytokine levels in serum by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative polymerase chain reaction and Western blot were used to measure the mRNA and protein expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) in the colon. To assess the influence of YHPGs on the intestinal microbiota, feces were obtained from the mice for 16s rRNA sequencing, and short-chain fatty acids (SCFAs) were measured in the feces.ResultsBy reducing the production of pro-inflammatory cytokines and increasing the relative expression of claudin-1, occludin, and ZO-1 in colon tissues, YHPGs had a protective effect in tissues from the lungs and colon. When YHPGs were administered to mice with IAV infection, the relative abundance of Lactobacillus, Coprobacillus, Akkermansia, Prevotella, Oscillospira, and Ruminococcus increased, whereas the relative abundance of Desulfovibrio decreased.ConclusionThe therapeutic mechanism of YHPGs against IAV infection in mice may be underpinned by modulation of the structural composition of colonic bacteria and regulation of SCFA production.
Tafazzin deficiency causes substantial remodeling in the lipidome of a mouse model of Barth Syndrome cardiomyopathy
Authors: Hachmann Malte , Gülcan Güntas , Rajendran Ranjithkumar , Höring Marcus , Liebisch Gerhard , Bachhuka Akash , Kohlhaas Michael , Maack Christoph , Ergün Süleyman , Dudek Jan , Karnati Srikanth 
Published: April 2024

Barth Syndrome (BTHS) is a rare X-linked disease, characterized clinically by cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the phospholipid acyltransferase tafazzin (Gene: TAFAZZIN, TAZ). Tafazzin catalyzes the final step in the remodeling of cardiolipin (CL), a glycerophospholipid located in the inner mitochondrial membrane. As the phospholipid composition strongly determines membrane properties, correct biosynthesis of CL and other membrane lipids is essential for mitochondrial function. Mitochondria provide 95% of the energy demand in the heart, particularly due to their role in fatty acid oxidation. Alterations in lipid homeostasis in BTHS have an impact on mitochondrial membrane proteins and thereby contribute to cardiomyopathy. We analyzed a transgenic TAFAZZIN-knockdown (TAZ-KD) BTHS mouse model and determined the distribution of 193 individual lipid species in TAZ-KD and WT hearts at 10 and 50 weeks of age, using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Our results revealed significant lipid composition differences between the TAZ-KD and WT groups, indicating genotype-dependent alterations in most analyzed lipid species. Significant changes in the myocardial lipidome were identified in both young animals without cardiomyopathy and older animals with heart failure. Notable alterations were found in phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC) and plasmalogen species. PC species with 2–4 double bonds were significantly increased, while polyunsaturated PC species showed a significant decrease in TAZ-KD mice. Furthermore, Linoleic acid (LA, 18:2) containing PC and PE species, as well as arachidonic acid (AA, 20:4) containing PE 38:4 species are increased in TAZ-KD. We found higher levels of AA containing LPE and PE-based plasmalogens (PE P-). Furthermore, we are the first to show significant changes in sphingomyelin (SM) and ceramide (Cer) lipid species Very long-chained SM species are accumulating in TAZ-KD hearts, whereas long-chained Cer and several hexosyl ceramides (HexCer) species accumulate only in 50-week-old TAZ-KD hearts These findings offer potential avenues for the diagnosis and treatment of BTHS, presenting new possibilities for therapeutic approaches.
Association between loneliness and cognitive function, and brain volume in community-dwelling elderly
Authors: Lee Hunju , Yong Sang Yeol , Choi Hyowon , Yoon Ga Young , Koh Sangbaek 
Published: April 2024

IntroductionWe investigated the relationship between loneliness, cognitive impairment, and regional brain volume among elderly individuals residing in the Korean community.MethodsData from the ARIRANG aging-cognition sub-cohort, collected between 2020 and 2022, were utilized for the present study. Loneliness was assessed using the UCLA-Loneliness Scale (UCLA-LS) questionnaire and the relevant item from Center for Epidemiologic Studies Depression Scale Korean version (CES-D-K). Cognitive impairment was measured through Mini-Mental State Examination (K-MMSE-2) and Seoul Neuropsychological Screening Battery (SNSB-C), with five sub-categories: attention, memory, visuospatial function, language, and executive function. Logistic regression was employed for prevalence ratios related to cognitive impairment, while linear regression was used for regional brain volume including white matter hyperintensity (WMH) and cortical thickness.ResultsOur analysis involved 785 participants (292 men and 493 women). We observed increased cognitive impairment assessed by K-MMSE-2 [UCLA-LS: odds ratio (OR) 3.133, 95% confidence interval (CI) 1.536–6.393; loneliness from CES-D: OR 2.823, 95% CI 1.426–5.590] and SNSB-C total score (UCLA-LS: OR 2.145, 95% CI 1.304–3.529) in the lonely group compared to the non-lonely group. Specifically, the lonely group identified by UCLA-LS showed an association with declined visuospatial (OR 1.591, 95% CI 1.029–2.460) and executive function (OR 1.971, 95% CI 1.036–3.750). The lonely group identified by CES-D-K was associated with impaired memory (OR 1.577, 95% CI 1.009–2.466) and executive function (OR 1.863, 95% CI 1.036–3.350). In the regional brain volume analysis, loneliness was linked to reduced brain volume in frontal white matter (left: −1.24, 95% CI −2.37 ∼−0.12; right: −1.16, 95% CI −2.31 ∼ −0.00), putamen (left: −0.07, 95% CI −0.12 ∼−0.02; right: −0.06, 95% CI −0.11 ∼−0.01), and globus pallidus (−15.53, 95% CI −30.13 ∼−0.93). There was no observed association in WMH and cortical thickness.ConclusionLoneliness is associated with cognitive decline and volumetric reduction in the frontal white matter, putamen, and globus pallidus.
Rate of atrial fibrillation by Holter-Stroke Risk Analysis in undetermined TIA/rapidly improving stroke symptoms patients
Authors: Cannizzaro F , Izquierdo A , Cocho D 
Published: April 2024

IntroductionHolter-SRA (Stroke Risk Analysis) is an automated analysis of ECG monitoring for Atrial Fibrillation (AF) detection. The aim of this study was to evaluate the rate of AF in undetermined TIA/Rapidly improving stroke symptoms (RISS) patients.MethodsProspective study of undetermined TIA/RISS patients who presented to the emergency department. Early vascular studies (angio CT, transthoracic echocardiography and ECG) were performed in emergency department. The Holter-SRA device was placed for 2 h and the patients were classified into: confirmed AF, high risk of AF or low risk of AF. Prolonged ambulatory monitoring (7 days) was carried out every month for patients with a high-risk pattern. The results were evaluated until definitive detection of AF or low-risk pattern. The endpoints were rate of AF and vascular recurrence at 90 days.ResultsOver a period of 24 months, 83 undetermined TIA/RISS patients were enrolled. The mean age was 70 ± 10 years and 61% were men. The median ABCD2 score was 4 points (1–7). After 2 h of monitoring in the emergency department, AF was detected in one patient (1.2%), 51 patients with a low-risk pattern and 31 patients (37.3%) showed a high-risk pattern of AF. During the ambulatory monitoring, of the 31 patients high risk pattern patients, AF was diagnosed to 17 cases and of the 51 patients with a low-risk pattern, one case experienced a recurrent vascular due to undetected AF (1.9% false negative). Three patients (3.6%) suffered a vascular recurrence within the first 90 days, before AF diagnosis.ConclusionsIn our study, AF was detected in 22.9% of the 83 patients with indeterminate TIA/RISS. Holter-SRA has allowed us to increase the detection of AF, especially those patients with a high-risk pattern in the first 3 months.
Causal effects of immune cells in glioblastoma: a Bayesian Mendelian Randomization study
Authors: Huang Mingsheng , Liu Yiheng , Peng Jie , Cheng Yuan 
Published: April 2024

BackgroundGlioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined.MethodIn this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis.ResultsAfter conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515–0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L– HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004–2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031–1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma.ConclusionOur study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.
Safety considerations in the treatment with anti-CGRP(R) monoclonal antibodies in patients with migraine
Authors: Van Der Arend Britt W. H. , Van Veelen Nancy , De Ruijter Joëlle E. T. , Olsen Michael H. , MaassenVanDenBrink Antoinette , Terwindt Gisela M. 
Published: April 2024

BackgroundAnti-CGRP-(receptor-)monoclonal antibodies (anti-CGRP(R)-mAbs) represent a novel class of drugs for migraine treatment, but their long-term cerebrovascular and cardiovascular (CV) safety warrants further examination.MethodsIn this observational cohort study we assessed the CV safety for erenumab and fremanezumab in a real-world setting during a follow-up period of at least 1 year. Patients with hypertension or CV history were excluded. We conducted ECGs and collected clinical data at treatment initiation and thereafter every 3 months, including liver and kidney function, lipid-, electrolyte-and glucose levels.ResultsAmong patients receiving erenumab (n = 101) or fremanezumab (n = 92), 3.1% (6/193) developed abnormal ECGs or CV adverse events. Of these, three (1.6%) experienced moderate to severe CV adverse events (cerebellar stroke, spontaneous coronary artery dissection, and pericarditis) and discontinued treatment. The remaining three (1.6%) developed non-threatening ECG abnormalities without physical complaints. No significant changes were observed in liver and kidney function, lipid-, electrolyte-, or glucose levels.DiscussionWe observed CV events in 1.6% of patients with 1.5-year follow-up of anti-CGRP(R)-mAbs treatment. We advise awareness regarding CV events in patients with migraine undergoing CGRP-targeted treatment, not as a confirmation of increased risk but as a proactive measure to address potential multifactorial influences.
Activation and functional connectivity of cerebellum during reading and during arithmetic in children with combined reading and math disabilities
Authors: Ashburn Sikoya M. , Matejko Anna A. , Eden Guinevere F. 
Published: April 2024

BackgroundReading and math constitute important academic skills, and as such, reading disability (RD or developmental dyslexia) and math disability (MD or developmental dyscalculia) can have negative consequences for children’s educational progress. Although RD and MD are different learning disabilities, they frequently co-occur. Separate theories have implicated the cerebellum and its cortical connections in RD and in MD, suggesting that children with combined reading and math disability (RD + MD) may have altered cerebellar function and disrupted functional connectivity between the cerebellum and cortex during reading and during arithmetic processing.MethodsHere we compared Control and RD + MD groups during a reading task as well as during an arithmetic task on (i) activation of the cerebellum, (ii) background functional connectivity, and (iii) task-dependent functional connectivity between the cerebellum and the cortex.ResultsThe two groups (Control, RD + MD) did not differ for either task (reading, arithmetic) on any of the three measures (activation, background functional connectivity, task-dependent functional connectivity).ConclusionThese results do not support theories that children’s deficits in reading and math originate in the cerebellum.
Design of urban road fault detection system based on artificial neural network and deep learning
Authors: Lin Ying 
Published: April 2024

IntroductionIn urban traffic management, the timely detection of road faults plays a crucial role in improving traffic efficiency and safety. However, conventional methods often fail to fully leverage the information from road topology and traffic data.MethodsTo address this issue, we propose an innovative detection system that combines Artificial Neural Networks (ANNs), specifically Graph Convolutional Networks (GCN), Bidirectional Gated Recurrent Units (BiGRU), and self-attention mechanisms. Our approach begins by representing the road topology as a graph and utilizing GCN to model it. This allows us to learn the relationships between roads and capture their structural dependencies. By doing so, we can effectively incorporate the spatial information provided by the road network. Next, we employ BiGRU to model the historical traffic data, enabling us to capture the temporal dynamics and patterns in the traffic flow. The BiGRU architecture allows for bidirectional processing, which aids in understanding the traffic conditions based on both past and future information. This temporal modeling enhances our system's ability to handle time-varying traffic patterns. To further enhance the feature representations, we leverage self-attention mechanisms. By combining the hidden states of the BiGRU with self-attention, we can assign importance weights to different temporal features, focusing on the most relevant information. This attention mechanism helps to extract salient features from the traffic data. Subsequently, we merge the features learned by GCN from the road topology and BiGRU from the traffic data. This fusion of spatial and temporal information provides a comprehensive representation of the road status.Results and discussionsBy employing a Multilayer Perceptron (MLP) as a classifier, we can effectively determine whether a road is experiencing a fault. The MLP model is trained using labeled road fault data through supervised learning, optimizing its performance for fault detection. Experimental evaluations of our system demonstrate excellent performance in road fault detection. Compared to traditional methods, our system achieves more accurate fault detection, thereby improving the efficiency of urban traffic management. This is of significant importance for city administrators, as they can promptly identify road faults and take appropriate measures for repair and traffic diversion.