bluuebunny/crossref_metadata_2025_split huggingface dataset:
A screen of plant-based natural products revealed that quercetin prevents amyloid-β uptake in astrocytes as well as resulting astrogliosis and synaptic dysfunction
Authors: Arndt Helene , Bachurski Mark , Yuanxiang PingAn , Franke Katrin , Wessjohann Ludger A. , Kreutz Michael R. , Grochowska Katarzyna M. 
Published: April 2024

Abstract

Two connected histopathological hallmarks of Alzheimer’s disease (AD) are chronic neuroinflammation and synaptic dysfunction. The accumulation of the most prevalent posttranslationally modified form of Aβ1–42, pyroglutamylated amyloid-β (Aβ3(pE)-42) in astrocytes is directly linked to glial activation and the release of proinflammatory cytokines that in turn contribute to early synaptic dysfunction in AD. At present the mechanisms of Aβ3(pE)-42 uptake to astrocytes are unknown and pharmacological interventions that interfere with this process are not available. Here we developed a simple screening assay to identify substances from a plant extract library that prevent astroglial Aβ3(pE)-42 uptake. We first show that this approach yields valid and reproducible results. Second, we show endocytosis of Aβ3(pE)-42 oligomers by astrocytes and that quercetin, a plant flavonol, is effective to specifically block astrocytic buildup of oligomeric Aβ3(pE)-42. Importantly, quercetin does not induce a general impairment of endocytosis. However, it efficiently protects against early synaptic dysfunction following exogenous Aβ3(pE)-42 application.
CatPred: A comprehensive framework for deep learning in vitro enzyme kinetic parameters kcat, Km and Ki
Authors: Maranas Costas , Boorla Veda Sheersh 
Published: April 2024

Abstract

Quantification of enzymatic activities still heavily relies on experimental assays, which can be expensive and time-consuming. Therefore, methods that enable accurate predictions of enzyme activity can serve as effective digital twins. A few recent studies have shown the possibility of training machine learning (ML) models for predicting the enzyme turnover numbers (kcat) and Michaelis constants (Km) using only features derived from enzyme sequences and substrate chemical topologies by training on in vitro measurements. However, several challenges remain such as lack of standardized training datasets, evaluation of predictive performance on out-of-distribution examples, and model uncertainty quantification. Here, we introduce CatPred, a comprehensive framework for ML prediction of in vitro enzyme kinetics. We explored different learning architectures and feature representations for enzymes including those utilizing pretrained protein language model features and pretrained three-dimensional structural features. We systematically evaluate the performance of trained models for predicting kcat, Km, and inhibition constants (Ki) of enzymatic reactions on held-out test sets with a special emphasis on out-of-distribution test samples (corresponding to enzyme sequences dissimilar from those encountered during training). CatPred assumes a probabilistic regression approach offering query-specific standard deviation and mean value predictions. Results on unseen data confirm that accuracy in enzyme parameter predictions made by CatPred positively correlate with lower predicted variances. Incorporating pre-trained language model features is found to be enabling for achieving robust performance on out-of-distribution samples. Test evaluations on both held-out and out-of-distribution test datasets confirm that CatPred performs at least competitively with existing methods while simultaneously offering robust uncertainty quantification. CatPred offers wider scope and larger data coverage (~ 23k, 41k, 12k data-points respectively for kcat, Km and Ki). A web-resource to use the trained models is made available at: https://tiny.cc/catpred
De novo mutations promote inflammation in children with STAT3 gain-of-function syndrome by affecting IL-1β expression
Authors: Chen Jiyu , Li Yan-Fang , Jiang Xue-Mei , Bi Xin , Yang Mi-Feng , Zhou Zhu , Zhao Bo 
Published: April 2024

Abstract

Background
STAT3 Gain-of-Function (GOF) syndrome characterized by early onset autoimmunity and primary immune regulatory disorder, the immunological mechanisms remain poorly understood.
Employing whole-genome sequencing within familial trios, our study elucidated the pivotal role of de novo mutations in genetic diseases.
Results
We identified 37 high-risk pathogenic loci affecting 23 genes, notably including the novel STAT3c.508G>A mutation. Furthermore, significant downregulation of pathogenic genes in affected individuals, potentially associated with inflammatory responses regulated by PTPN14 via miR378c, was observed.
Conclusion
These findings not only contribute to our understanding of the pathogenesis but also highlight potential therapeutic strategies. Our study suggests that combined JAK inhibitors and IL-6R antagonists could offer promising avenues for mitigating the severity of these genetic disorders.
The asymmetry of the aquatic macrophyte response to temperature increases with global warming and has to be accounted for in phytoindication
Authors: Zhukov Olexander , Kunakh Olga 
Published: April 2024

Abstract

The study revealed the relationship between geographic and habitat estimates of the optimum of macrophyte species under temperature gradient conditions. How the estimates correlated with the point and habitat scales of the indicators was determined. The results indicate that the abundance of many species decreases sharply under extreme conditions caused by rising temperatures. The Didukh scales, after applying the ideal indicator method, provide a high level of accuracy for temperature estimation. The explanatory power of the Ellenberg scale was somewhat lower, which can be explained by the fact that this scale is "tuned" to optimal values, and under extreme conditions of factor action, the parameters of niche tolerance to which the Didukh scale is "tuned" have a limiting value. In addition, under extreme conditions, species responses to the impact of a factor often or always deviate from a symmetric model that does not take into account traditional Ellenberg scale values. At the landscape level, changes in temperature are associated with changes in oxygen, electrical conductivity and turbidity. Among the morphological characteristics of water bodies, shoreline development has the greatest influence on the temperature regime. The method of the ideal indicator, which takes into account the asymmetric distribution of species responses, has shown a high ability to indicate the temperature regime of water bodies in the Dnipro floodplain.
Explainability of CNN-based Alzheimer’s Disease Detection from Online Handwriting
Authors: Sweidan Jana , El-Yacoubi Mounim A. , Rigaud Anne-Sophie 
Published: April 2024

Abstract

With over 55 million people globally affected by dementia and nearly 10 million new cases reported annually, Alzheimer’s disease is a prevalent and challenging neurodegenerative disorder. Despite significant advancements in machine learning techniques for Alzheimer’s disease detection, the widespread adoption of deep learning models raises concerns about their explainability. The lack of explainability in deep learning models for online handwriting analysis is a critical gap in the literature in the context of Alzheimer’s disease detection. This paper addresses this challenge by interpreting predictions from a Convolutional Neural Network applied to multivariate time series data, generated by online handwriting data associated with continuous loop series handwritten on a graphical tablet. Our explainability methods reveal distinct motor behavior characteristics for healthy individuals and those diagnosed with Alzheimer’s. This emphasizes the critical role of explainability in translating complex models into clinically relevant insights. Our research contributes to the enhancement of early diagnosis, providing significant and reliable insights to stakeholders involved in patient care and intervention strategies. Our work bridges the gap between machine learning predictions and clinical insights, fostering a more effective and understandable application of advanced models for Alzheimer’s disease assessment.
Fusarium equiseti Causes Leaf Rot in Hylotelephium erythrostictum in China
Authors: Yin Fuqiang , jiang jiamin , Song Zhen , Xu Qin , Ma Wanli , Liu Ming , Qi Junseng 
Published: April 2024

Abstract

Colonies with similar molecular characterisation were isolated from rotten leaves of Hylotelephium erythrostictum collected from the Chinese Medicine Herbal Cultural EXPO Garden of Three Gorges, Chongqing, China. In this study, the pathogen that caused these symptoms was identified as Fusarium equiseti using morphological observation, molecular characterisation (ITS, RPB2 and CAMD) and a pathogenicity test. To the best of our knowledge, this is the first report of F. equiseti as a pathogen of H. erythrostictum. The findings of the present study are expected to contribute to the knowledge of H. erythrostictum-associated diseases in China and provide an essential foundation for the development of effective pre-harvest disease management strategies to curb disease spread.
National continuous professional development processes and systems for midwifery educators in low-and-middle-income-countries: a systematic review
Authors: Shikuku Duncan N , Bar-Zeev Sarah , Ameh Charles 
Published: April 2024

Abstract

Background
Strengthening the capacity of midwifery educators through continuous professional development (CPD) is a critical component of improving quality midwifery care provision and thus reducing maternal and newborn mortality. Variation in the quality and standards of midwifery educator training, scope of practice, weak regulation, and lack of opportunities for educators to update their knowledge or skills competencies are known barriers to midwifery educator development in low- and middle-income countries (LMICs). Most CPD programmes specific for midwifery educators have been implemented in high income settings and little is known about the availability, content and effectiveness of such programmes in LMICs that experience the greatest burden of maternal and newborn mortality and mobidity. This review appraises the current approaches, content and effectiveness of midwifery educator CPD programmes in LMICs.
Methods
An in-depth literature search across five databases was undertaken between 2000–2021. Quality appraisal based on internal and external validity was conducted and a combined numerical summary and categorical description were undertaken. A narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for reporting. The protocol was registered in PROSPERO (CRD42021283273).
Results
Twenty-two papers met inclusion criteria although many did not report on CPD directly but focused on midwifery educator development initiatives. All the studies included were of good quality. Main CPD approaches identified was twinning (international collaborations employing the train-the-trainer approach). Others were greenfield, directed by regulators and formal program guided by an international midwifery/medical body. No formal CPD program managed by a national nursing/midwifery regulator or international midwifery body was identified. Content covered included: educational approaches in curriculum design and teaching; research; leadership and management in health; and project management & evaluation. Immediate outputs and outcomes of these programmes contributed to personal/professional development/promotions, institutional improvements in midwifery teaching and learning, and maternal newborn health systems. Few studies measured effectiveness of the CPD programmes.
Conclusion
There is low evidence of midwifery educator specific CPD programmes to maintain competence in LMICs. There is need for clear guidance from national regulatory bodies to inform the design of regulator accredited midwifery educator CPD programmes at country level. Robust evaluation of existing CPD programmes to measure effectiveness/impact is required.
Research on the Interaction Mechanism between Landslides and Tunnels: A Case Study of the Walibie Tunnel in Southwest China
Authors: Zhou Wenjiao , Fan Jiawei , Qiu Shumao , Zhang Yufang 
Published: April 2024

Abstract

The construction of tunnels can easily trigger the reactivation of old landslide bodies, posing a threat to the transportation safety. In this study, using methods such as engineering geological investigation, slope deformation monitoring, deep displacement monitoring, and numerical simulation, the interaction between landslides and tunnels was investigated from the perspective of landslide deformation and failure characteristics. The Walibie Tunnel (WLBT) of Shangri-La to Lijiang (XL) Expressway was taken as an example. The results showed that there were two unstable slopes developed in the upper part of the tunnel, with the new active landslides. Shallow and deep creeping deformation zones also exist within the landslide area. Combining the position of the deformation zones of the unstable slopes and the actual tunnel damage observed, it was determined that the failure mode of the tunnel was longitudinal tensile fracture in the traction section-tunnel. Numerical simulation and field investigation revealed the mechanism of interaction between the WLBT and landslides: the traction section of the tunnel passed through the unstable slope parallelly, and during the continuous opening and expansion process at the rear edge of the unstable slope, a significant tensile force was exerted on the tunnel, resulting in initial tensile fracture damage.
A Lophomonas infection mimicking Angina: An extremely rare case report
Authors: Hadid Noura , Ahmad Heya Ahmad , Tawashi Kenana , Al-Ghotani Basel , Kassem Ali , Assaf Amal 
Published: April 2024

Abstract

Background: Lophomonas is a non-aerobic protozoan parasite. This parasite has the ability to invade the respiratory tract. It presents with non-specific clinical manifestations. The gold standard for diagnosis is microscopic examination. The drug of choice for the treatment is Metronidazole. We report a rare case of Lophomonas infection that manifested with a dry cough and chest tightness, which was not reported in the medical literature previously.
Case presentation: We report the case of a 45-year-old asian male who experienced episodes of chest tightness and cough. He showed elevated numbers of Eosinophils and IGE. A bronchoscopy was performed to investigate the presence of elevated Eosinophils in the bronchoalveolar lavage (BAL). The microscopic examination of BAL detected a parasite with flagella. The Giemsa staining procedure confirmed the diagnosis of Lophomonas. He was cured with Metronidazole. Now the patient is in good condition.
Conclusions: Even if Lophomonas is a rare and unexpected diagnosis, we should keep it in mind as a probable cause in patients with unspecific manifestations and radiological and laboratory investigations. In addition, biosecurity procedures should be taken especially in endemic regions and workplaces.
Evaluation of a targeted congenital cytomegalovirus testing strategy: utilizing cytomegalovirus IgM antibody screening followed by DNA diagnosis
Authors: Li Dongming , Zhuo Weiyuan , Liang Zhikun , Feng Yuanyuan , Pan Minzhu , Fu Chunyun , Hu Xuehua 
Published: April 2024

Abstract

Background: Congenital cytomegalovirus (cCMV) infection is a prominent global public health concern due to its association with enduring neurological sequelae and sensorineural hearing impairments. Despite the recommendation for universal cCMV screening, its implementation remains limited. Consequently, alternative targeted testing strategies have been explored to augment detection rates. This study aimed to assess the efficacy of a targeted strategy for screening for cCMV utilizing CMV-IgM antibody screening followed by DNA diagnosis.
Methods: A retrospective analysis was conducted, utilizing data collected between January 2013 and December 2022, encompassing all infants who underwent early cCMV testing. The testing protocol entailed an initial screening of CMV-IgM antibodies, subsequently confirmed through the detection of CMV-DNA in urine, blood, or both, to ascertain cCMV infection. Comprehensive data pertaining to infant presentation, test modalities, and outcomes were recorded for subsequent analysis.
Results: Of the total 60,950 infants subjected to CMV-IgM testing, 816 progressed to CMV-DNA diagnostic testing. Indications for CMV-DNA testing encompassed clinical symptoms (84.31%), maternal HIV infection (8.09%), maternal CMV infection (7.23%), and fetal CMV infection (0.37%). Among the tested population, 95 infants received a diagnosis of cCMV infection, accounting for 0.16% of all screened infants, 11.64% of those who underwent CMV-DNA testing, and 94.74% of symptomatic infants. Fifteen different symptoms were identified, with the highest detection rates for cCMV being hepatitis (38.46%, 5/13), intestinal intussusception (33.33%, 2/6), abnormal CNS imaging (25%, 3/12), jaundice (16.24%, 57/351), sepsis (16.13%, 15/95), and pneumonitis (14.29%, 37/259). The sensitivity and specificity of CMV-IgM screening for cCMV, based on CMV-DNA diagnosis, were determined to be 69.47% and 94.59%, respectively.
Conclusions: The targeted testing strategy utilizing CMV-IgM antibody screening followed by DNA diagnosis exhibits promising potential in substantially enhancing the detection rate of infants affected by cCMV who might otherwise remain undiagnosed. Further investigation is warranted to validate and optimize this approach, as well as assess its feasibility, implementation, and cost-effectiveness in diverse clinical settings.
Work from home, time allocations, and wellbeing: The impact of lockdowns
Authors: Giménez-Nadal José Ignacio , Velilla Jorge 
Published: April 2024

Abstract

During the COVID-19 pandemic, the incidence of WFH skyrocketed as business closed and distancing standards were mandated, exposing many workers to a remote work arrangement. How working from home (WFH) affects worker time management, activity timing, and enjoyment, considering gender differences and pandemic phases, is explored in the current study. The study uses real-time data from the UK Click-and-Drag Diary covering pre-pandemic, lockdown, and post-pandemic periods. Findings show no significant overall impact on time allocations, but reveal gender disparities: pre-pandemic, WFH involved less paid work and more leisure among women, but during lockdowns, patterns converged. No notable differences in instant enjoyment were found between WFH and non-WFH employees, though pre-pandemic negative correlations in women's WFH leisure time vanished during and post-pandemic. The economic implications span across labor productivity, gender dynamics in employment, business model adaptation, and work-life balance. These findings could impact corporate policies, human resource strategies, and the design of governmental policies related to the labor market and gender equality.
JEL classification: J16, J22.
Assessing the phytoextraction of Cd, Pb, and Zn from a slag-contaminated soil by legume species inoculated with rhizobial strains
Authors: Silva Jessyca Adriana Gomes Florêncio , Freitas Ana Dolores Santiago , Silva Vinicius Santos Gomes , Rosália Carolina Etienne , Fernandes Paulo Ivan , Melo Aline Fernandes , Souza Pablo Acácio Santos , Oliveira Andressa Silva , Santos Nielson Machado , Nascimento Clistenes Williams Araújo 
Published: April 2024

Abstract

Metal-polluted soils can pose a severe threat to the environment and need remediation. We assessed the potential of jack bean and mucuna inoculated with rhizobial strains on the phytoremediation of soils contaminated by lead (Pb) smelting activities in Santo Amaro, Bahia state, the most severe case of Pb contamination in Brazil. Plants were grown in pots containing soils with three contamination levels for Pb, cadmium (Cd), and zinc (Zn) based on the distance from the chimney of the abandoned Pb smelter plant. Legumes and inoculated strains were tolerant to soil contamination. The BR 2811 strain is potentially indicated to increase jack bean biomass. The Cd, Pb, and Zn concentrations in plants were highest when grown on the soil with the highest contamination level. We found significant interactions between strains and soil contamination levels for phytoextraction efficiency. However, soil's very high metal contents can make phytoextraction unfeasible due to the time required to bring the metals to regulatory concentrations. The Cd, Pb, and Zn net removal from soil was proportional to increased contamination levels. The legumes did not show potential for Pb phytoextraction, but they have the potential for Zn phytoextraction and Cd phytostabilization. The BR 2811, BR 3501, and BR 7606 strains were the most promising to increase the phytoremediation potential of jack bean and mucuna.
Real-time Monitoring of Urban Roadway Health: Utilizing GPR Techniques for Early Detection and Classification of Subsurface Cavity Diseases
Authors: Shrestha Rohit , Zhang Zhihou 
Published: April 2024

Abstract

The effectiveness of ground penetrating radar (GPR) in identifying and categorizing diseases that occur underground beneath the surfaces of urban roads is investigated in this study. Both 2D and 3D forward modeling use simulation with the GprMax program to show the response characteristics of common cavity illnesses, which facilitates interpretation in practical situations. The cavity morphology classification accuracy is improved to 90.5% by using convolutional neural networks (CNNs), specifically transfer learning with AlexNet. This method outperforms existing approaches even with minimal data. Four primary types are identified from an analysis of 1965 subsurface cavity data: hollow bodies, empty bodies, loose bodies, and water-rich bodies. These categories are important for evaluating road risks such as voids and subsidence. However, it is still difficult to interpret picture features linked to cavity diseases accurately because of a variety of elements, such as anthropogenic, environmental, and geological influences. However, the accurate interpretation and recognition of image features related to cavity diseases remain challenging. Moreover, there are various factors involved in the formation of underground diseases and cavities, including geological and environmental factors, physical and chemical properties of the geotechnical materials, anthropogenic engineering activity and social population or commercial effects.