bluuebunny/crossref_metadata_2025_split huggingface dataset:
p.L1795F LRRK2 variant is a common cause of Parkinson’s disease in Central Europe
Authors: Ostrozovicova Miriam , Tamas Gertrud , Dušek Petr , Grofik Milan , Han Vladimir , Holly Petr , Jech Robert , Kalinova Katarina , Klivenyi Peter , Kovacs Norbert , Kulcsarova Kristina , Kurca Egon , Lackova Alexandra , Lee Hamin , Lewis Patrick , Magocova Veronika , Marekova Maria , Murphy David , Necpal Jan , Pinter David , Rabajdova Miroslava , Růžička Evžen , Serranova Tereza , Smilowska Katarzyna , Soos Krisztina , Straka Igor , Svorenova Tatiana , Valkovic Peter , Zarubova Katerina , Gdovinova Zuzana , Houlden Henry , Rizig Mie , Skorvanek Matei 
Published: May 2024

Abstract

Pathogenic variants in LRRK2 are one of the most common genetic risk factors for Parkinson’s disease (PD). Recently, the lesser-known p.L1795F variant was proposed as a strong genetic risk factor for PD, however, further families are currently lacking in literature. A multicentre young onset and familial PD cohort (n = 220) from 9 movement disorder centres across Central Europe within the CEGEMOD consortium was screened for rare LRRK2 variants using whole exome sequencing data. We identified 4 PD cases with heterozygous p.L1795F variant. All 4 cases were characterised by akinetic-rigid PD phenotype with early onset of severe motor fluctuations, 2 receiving LCIG therapy and 2 implanted with STN DBS; all 4 cases showed unsatisfactory effect of advanced therapies on motor fluctuations. Our data also suggest that p.L1795F may represent the most common currently known pathogenic LRRK2 variant in Central Europe compared to the more studied p.G2019S, being present in 1.81% of PD cases within the Central European cohort and 3.23% of familial PD cases. Together with the ongoing clinical trials for LRRK2 inhibitors, this finding emphasises the urgent need for more ethnic diversity in PD genetic research.
Vaping-associated illness: a reassessment
Authors: Schiffman Jonathan S. 
Published: May 2024

Abstract

Background: Recently, there was widespread presentation of respiratory distress as well as other organ system involvement is patients with a history of vaping. There continue to be reports of vaping-associated illness. This has come to be known as e-cigarette and vaping product associated lung injury (EVALI). The mechanism of injury remains unclear. Objectives: This study reexamines the clinical characteristics of patients affected by vaping and suggests that lung injury may not be the primary organ dysfunction but be part of a larger systemic illness.
Methods: This is a retrospective chart review of all patients presenting to one hospital identified as having vaping-associated illness.
Results: 14 patients were identified ranging in age from 15 to 33 years. Patients had a broad range of clinical severity. Respiratory symptoms occurred in 64%, gastrointestinal symptoms in 57%, fever in 78%, neurological symptoms in 15% and other constitutional symptoms in 50%. 35% presented with no respiratory symptoms.
Conclusion: While the lungs are certainly involved in vaping-associated illness, recognizing the extent of involvement of other organ systems may provide insight into the pathophysiology of the disease. Providers should not focus on lung injury exclusively but be aware that vaping-associated illness may present with abdominal pain or headache or even fever without other complaints.
Dietary intake and risk of metabolic syndrome in long-term survivors of pediatric allogeneic hema-topoietic stem cell transplantation
Authors: Müller Klaus , Pedersen Louise , Gerbek Tina , Sorum Maria , Muhic Ena , Christiansen Terkel , Kok Karin , Sørensen Kaspar , Mølgaard Christian 
Published: May 2024

Abstract

Metabolic syndrome (MetS) is a late effect of stem cell transplantation and has been ascribed to conditioning including total body irradiation (TBI), but the influence of lifestyle factors has not yet been studied. We explored the dietary intake and MetS in 85 long-term survivors (median age 30 years and median follow-up time 20 years). Results: Overall, the distribution of fatty acid deviated from the recommendations with a higher intake of saturated fat and a lower intake of monounsaturated, polyunsaturated fat, and N-3 fatty acids, but was comparable to that of the background population. The prevalence of MetS was 27%, corresponding to that of the elderly background population. Both in the total cohort and within the subgroup treated with TBI we found a higher fat intake in patients with fulfilling MetS criteria (36.8E% [range: 27.2-51.2E%] versus 32.0E% [range: 24.6-42.1E%], (P = 0.013)). This was confirmed in a multivariate analysis adjusted for TBI, sex and age at follow-up (OR 1.20 (1.06–1.39) P = 0.008). Conclusion: Although comparable with the diet in the background population the intake of fat is a key factor for the occurrence of MetS in young TBI treated survivors. This highlights the importance of a reduced fat intake in survivors conditioned with TBI.
Large-scale global retrospective study on the interaction between ancestry and risk of comorbid autoimmune diseases in patients with pemphigus
Authors: Saurabh Rochi , Cani Anikamila , Möller Marius , Busch Hauke 
Published: May 2024

Abstract

The pemphigus family of skin blistering diseases represents a rare yet potentially life-threatening condition characterized by multiple known genetic loci associated with other autoimmune disorders. While several studies have empirically indicated an increased risk of developing additional autoimmune diseases in individuals with pemphigus, the scarcity of data and the rarity of pemphigus have hindered efforts to establish and generalize these associations across diverse populations. In this study, we analyzed a dataset comprising 126 million patients, including 18,000 with pemphigus, to assess the likelihood of developing any of 74 autoimmune diseases following a diagnosis of pemphigus. For a subset of 26 diseases from this list with adequate patient numbers, we conducted further case-control retrospective analyses to quantify the odds and hazard ratios of developing comorbid conditions across various ethnicities. Our findings reveal highly significant and generalizable associations between pemphigus and pemphigoid diseases, discoid lupus erythematosus, lichen planus, and undifferentiated connective tissue disease, among others.
Development and piloting of an online course to improve knowledge, confidence and attitudes towards triaging images of skin lesions submitted online in Primary Care
Authors: Ntessalen Maria , Krasniqi Albana , Murchie Peter 
Published: May 2024

Abstract

Background Melanoma is the 5th commonest cancer in the UK and survivors require frequent and thorough skin checks. During the Achieving Self-directed Integrated Cancer Aftercare (ASICA) trial, melanoma survivors used an app to submit images of concerning lesions for assessment by a dermatology nurse. In the past, online courses have been used to train non-specialist primary care practitioners (PCPs) in this skill.Objectives This study aimed to determine whether an online course could increase knowledge, confidence, and attitudes towards skin image triage in PCPs in the Grampian area.Methods Preliminary discussions were held with PCPs to determine the need for an online course. The course was designed at the University of Aberdeen and included an introduction to the skin, case studies and quizzes on a variety of skin conditions based on melanoma survivors’ submissions via the ASICA app. Two pre- and post-course questionnaires were administered to all participants to 1) assess knowledge gained and 2) assess any improvements in confidence and attitudes towards triaging. All PCPs in the Grampian area were invited to participate. Results were analysed using a paired sample T-test.Results The course was advertised to all GP practices in the Grampian area and 38 PCPs completed all its stages. Undertaking the course improved all PCPs’ confidence and attitudes towards triaging (p < 0.001). It also improved knowledge in all non-GP PCPs (p = 0.01). Most participants found the course useful; thought it was at the right level of difficulty, right format and thought the design was good.Conclusions Our online course in triaging skin lesions submitted digitally to PCPs was able to improve knowledge, confidence, and attitudes towards triaging. The course was acceptable in its design and was deemed useful and applicable to practice. Further research should investigate the effect the course has on secondary care referral numbers.
An Inverted U-shaped Relationship between Neutrophil-to-Lymphocyte Ratio and Hypertension in Overweight and Obese Populations: Evidence from a Large-scale Health Screening Data
Authors: Sun Yongbing , Li Fengli , Zhou Yang , Liu Ao , Lin Xinbei , Zou Zhi , Lv Xue , Zhou Jing , Li Zhonglin , Wu Xiaoling , Dou Shewei , Zhang Michael , Zhu Jiadong , Chen Yalong , Xiao Xinguang , Hu Yangxi , Li Hao , Li Yongli 
Published: May 2024

Abstract

Background
The Neutrophil-to-Lymphocyte Ratio (NLR) is associated with the development and progression of hypertension, and obesity is a significant risk factor for hypertension. However, the relationship between NLR and overweight and obese hypertension remains unclear.
Methods
This study was a cross-sectional analysis of data from 40,623 participants with body mass index (BMI) ≥ 24 kg/m2 who were health screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were divided into groups with hypertension and those without hypertension, according to hypertension diagnostic criteria. The NLR, our dependent variable, was determined using the equation [neutrophil/ lymphocyte]. We explored the association between NLR and hypertension in overweight and obese individuals through multivariate logistic regression, generalized additive models, smoothed curve fitting, analysis of threshold effects, and subgroup analysis.
Results
After adjusting for other covariates, increased risk of hypertension was still associated with an elevated NLR [OR = 1.27, 95% CI = 1.20–1.36; P < 0.001; P for trend < 0.001, when Q4 was compared with Q1 in model II]. Smoothed curve fitting showed an inverse U-shaped relationship between NLR and risk of hypertension, with a decreased risk of hypertension when NLR was greater than 2.91. In addition, subgroup analyses showed that the relationship between NLR and hypertension was robust across gender, age, BMI, and occupational subgroups.
Conclusion
Our study demonstrated a significant inverted U-shaped association between NLR and hypertension in overweight and obese Chinese adults.
How do temperature and plant resistance shape the colonisation dynamics of wheat plants by Rhopalosiphum padi L. (Hemiptera: Aphididae) and barley yellow dwarf virus (BYDV)?
Authors: Engel Eduardo , Lau Douglas , Zanini Wellington Rogério , Godoy Wesley A. C. 
Published: May 2024

Abstract

This study investigated the colonisation dynamics of wheat plants by Rhopalosiphum padi L. and Barley Yellow Dwarf Virus (BYDV), considering air temperature and host plant genetic resistance as key factors. Bioassays were conducted at different temperatures (5 to 35°C) with two wheat genotypes, partially resistant (BRS Timbaúva) and susceptible (Embrapa 16) to R. padi. Aphid dispersal was assessed every two days, cumulative thermal sum was estimated, and the proportion of plants with R. padi colonies was recorded. After 15 and 30 days, the total aphid population and its age structure on each plant were determined, as well as the viral titres of BYDV-PAV (ELISA). Generalised linear models were used to analyse of colonization data. The optimal temperatures were more explored with a logistic growth model analysis. The effect of genetic resistance was temperature-dependent; at 25°C, R. padi colonised Embrapa 16 more rapidly than BRS Timbaúva. Plant seropositivity differed significantly at the end of the experiment, with a higher percentage of seropositive plants for BRS Timbaúva, especially at temperatures optimal for R. padi development. These results were used to estimate the relationship between aphid populations and indirect damage derived from BYDV transmission, crucial for proper pest management and forming the basis for models estimating aphid focus progression, BYDV dissemination, and grain yield reduction.
Comparison of EfficientNet-B0 and Res2Net Models for Distinguishing Malignant and Benign Pulmonary Nodules
Authors: Shao Meihua , Xu Gang , Chen Xu , Zhang Cui , Tian Fengjuan , Ji Hongli , He Linyang , Yang Dengfa , Shi Hengfeng , Wang Jian 
Published: May 2024

Abstract

To develop and validate two models for convolutional neural networks (CNNs), namely EfficientNet-B0 and Res2Net, constructed from non-contrast CT images for discriminate malignant and benign pulmonary nodules.We recruited 3579 cases of solitary pulmonary nodules, among which 335 cases were benign and 3244 cases were malignant. The EfficientNet-B0 model and Res2Net model were constructed as two-dimensional(2D), and three- dimensional (3D) models, respectively. Furthermore, 4 clinical factors (sex, age, smoking status, and tumor marker) and all clinical factors were combined with Res2Net model to build Res2Net-4F model, and Res2Net-20F model, respectively. The receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficiency and discriminative capability of these models, and ROC curves of these models were compared with Delong test.The diagnostic accuracy of Res2Net, Res2Net-4F, and Res2Net-20F [areas under ROC curves (AUC) = 0.9301, AUC = 0.9811, and AUC = 0.9357, respectively] were higher than that of the EfficientNet B0 (AUC = 0.8801) in the training data set. The results were confirmed by the validation data set (AUC = 0.8282 for the Res2Net; AUC = 0.8299 for Res2Net-4F; AUC = 0.8468 for Res2Net-20F; AUC = 0.7737 for the EfficientNet B0). There was a significant difference between Res2Net model and EfficientNet-B0 model in discriminating malignant and benign pulmonary nodules in both the training data set and validation set (Delong test, both p < 0.05). We developed two novel deep learning models to distinguish malignant and benign pulmonary nodules, and the Res2Net model showed better differentiation accuracy and sensitivity than EfficientNet-B0 model.
Exogenous Hydrogen Sulfide increased Nicotiana tabacum L. resistance against drought by the improved photosynthesis and antioxidant system
Authors: Wang Hang , Moussa Mohamed G. , Huang Wuxing , Han Dan , Dang Bingjun , Hao Haohao , Zhang Li , Xu Zicheng , Jia Wei 
Published: May 2024

Abstract

Hydrogen sulfide (H2S) has emerged as a potential regulator of plant responses to abiotic stress. In this study, we investigated the effects of exogenous sodium hydrosulfide (NaHS) on tobacco seedlings subjected to polyethylene glycol (PEG)-induced drought stress. Compared to control conditions, drought stress significantly reduced several parameters in tobacco seedlings, including shoot dry weight (22.83%), net photosynthesis (37.55%), stomatal conductance (33.56%), maximum quantum yield of PSII (Fv/Fm) (11.31%), photochemical quantum yield of PSII (ΦPSⅡ) (25.51%), and photochemical quenching (qP) (18.17%). However, applying NaHS, an H2S donor, mitigated these effects, ultimately enhancing photosynthetic performance in tobacco seedlings. Furthermore, optimal NaHS concentration (0.4 mmol/L) effectively increased leaf relative water content (RWC) and root activity while promoting the accumulation of soluble sugars and proline content to maintain osmotic pressure balance under drought stress. NaHS pretreatment also bolstered the antioxidant defense system in leaves, leading to a reduction in hydrogen peroxide (H2O2) and malondialdehyde (MDA) content and an increase in the activities of antioxidant enzymes such as ascorbate peroxidase (APX), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Consequently, NaHS protected chloroplast structure and attenuated chlorophyll degradation, thus mitigating severe oxidative damage. Overall, our findings provide valuable insights into exogenous NaHS's role in enhancing tobacco drought tolerance. These results lay the foundation for further research utilizing H2S-based treatments to improve crop resilience to water deficit conditions.
Assessing the Impact of COVID-19 on the Epidemiology of Acinetobacter baumannii: A Longitudinal Study Spanning from 2014 to 2023
Authors: Zhang Wei , Lei Chunmei , Liu Jianhua , Yang Wenhang , Zhao Jianqing , Zhan Changwen , Liu Ziye , Wang Xinsheng , Zhang Zhihua 
Published: May 2024

Abstract

Background
Understanding the changes in the epidemiological characteristics of Acinetobacter baumannii before and after the COVID-19 pandemic may provide a scientific basis for clinical treatment and public health management.
Methods
Over a 10-year span from 2014 to 2023, a tertiary hospital in China separated A. baumannii isolated from patients according to whether it was carbapenem-resistant or carbapenem-sensitive. Information, such as sample type, drug sensitivities, MIC50, seasonal differences, and variances in patient sex, age, department, and outpatient and inpatient status, was examined.
Results
A total of 3,498 isolates of A. baumannii were assessed, including 1909 (54.6%) carbapenem-resistant A. baumannii (CRAB), 1501 (42.9%) carbapenem-sensitive A. baumannii (CSAB) isolates, and 88 (2.5%) carbapenem-intermediate A. baumannii isolates. Since the COVID-19 pandemic outbreak, the isolation rate of A. baumannii in outpatients had sharply decreased to 6.4%, while it had surged to 110% in inpatients. Simultaneously, the proportion of CRAB isolates had decreased to 67.3%, whereas that of CSAB isolates had increased to 150.8%. Notably, overall, the resistance rate of A. baumannii to 17 antibiotics decreased, with the most significant decreases in the combined sulfamethoxazole and amikacin, with decreases to 51.1% and 53.9%, respectively (p < 0.05). However there was an increase in the usage rate of moxifloxacin to 146.9%. The distribution proportion of CSAB in the third quarter was 0.6 times higher than that in the other three quarters, while the distribution of CRAB throughout the year was relatively balanced.
Conclusions
During the COVID-19 pandemic, significant changes occurred in people’s lifestyle. The notable decrease in the CRAB isolation rate highlights the effectiveness of strict isolation measures for controlling the transmission of drug-resistant bacteria in hospitals.
Adenosine stress myocardial contrast echocardiography combined with myocardial work function in patients with ischemia and nonobstructive coronary artery disease
Authors: ZHANG Xuemei , LI Yuhan , LI Fengsheng , DOU Shuixiu , ZHANG Feifei , LOU Ping , JIN Jing , ZHAO Ying , ZHAO Xin 
Published: May 2024

Abstract

Objective To evaluate the abnormal myocardial perfusion in patients with INOCA using adenosine-stressed myocardial contrast echocardiography (AS-MCE) combined with myocardial work (MW).
Methods A total of 102 patients who underwent coronary angiography (CAG) or Coronary Artery CT Angiography (CCTA) for chest pain in Shaanxi Provincial People's Hospital from January 2022 to January 2024 were enrolled, those with normal results were then examined by AS-MCE, and 42 patients with INOCA results were classified as the INOCA group, while 30 normal results were classified as the control group. Conventional parameters were measured by two-dimensional echocardiography, left ventricular ejection fraction (Simpson's method) was measured, and the global longitudinal strain (GLS) and MW parameters of the left ventricle were analyzed by the Echo PAC (version 203) workstation. The myocardial perfusion parameters: peak signal intensity (A-value), curve upward slope (β value) and A×β value (reflecting myocardial blood volume) were obtained by analyzing the perfusion parameters of each group of all subjects under rest and stress states using QLab software, and the differences between the above two groups were compared.
Results The INOCA group and the control group did not show significant differences in gender, age, heart rate, weight, height, body surface area, prevalence of hypertension and diabetes, hyperlipidemia, alcohol history, smoking history, and conventional ultrasound parameters such as left atrial diameter, left ventricular end-systolic and end-diastolic diameters and volumes, LVEF, diastolic mitral valve velocity, E/A, e, EDT, E/e, MW parameters, and A-value, β-value, and A-× β value at rest (P>0.05, Table 1). However, after hypertension medication, the parameters in the INOCA group decreased significantly compared to those in the control group, and the β-value in the INOCA group was significantly lower than that in the control group at rest (P<0.05).
Conclusion Compared to myocardial work, adenosine-stressed myocardial echocardiography is more suitable for the clinical diagnosis of ischemia with non-obstructive coronary artery disease and its application is worthy of clinical practice promotion.
Analysis of Intracellular Communication Reveals Consistent Gene Changes Associated with Early-Stage Acne Skin
Authors: Deng Min , Odhiambo Woodvine O. , Qin Min , To Thao Tam , Brewer Gregory M. , Kheshvadjian Alexander R. , Cheng Carol , Agak George W. 
Published: May 2024

Abstract

A comprehensive understanding of the intricate cellular and molecular changes governing the complex interactions between cells within acne lesions is currently lacking. Herein, we analyzed early papules from six subjects with active acne vulgaris, utilizing single-cell and high-resolution spatial RNA sequencing. We observed significant changes in signaling pathways across seven different cell types when comparing lesional skin samples (LSS) to healthy skin samples (HSS). Using CellChat, we constructed an atlas of signaling pathways for the HSS, identifying key signal distributions and cell-specific genes within individual clusters. Further, our comparative analysis revealed changes in 49 signaling pathways across all cell clusters in the LSS— 4 exhibited decreased activity, whereas 45 were upregulated, suggesting that acne significantly alters cellular dynamics. We identified ten molecules, including GRN, IL-13RA1 and SDC1 that were consistently altered in all donors. Subsequently, we focused on the function of GRN and IL-13RA1 in TREM2 macrophages and keratinocytes as these cells participate in inflammation and hyperkeratinization in the early stages of acne development. We evaluated their function in TREM2 macrophages and the HaCaT cell line. We found that GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5, and CXCL2 in TREM2 macrophages. Additionally, the activation of IL-13RA1 by IL-13 in HaCaT cells promoted the dysregulation of genes associated with hyperkeratinization, including KRT17, KRT16, and FLG. These findings suggest that modulating the GRN-SORT1 and IL-13-IL-13RA1 signaling pathways could be a promising approach for developing new acne treatments.