bluuebunny/crossref_metadata_2025_split huggingface dataset:
miRNA 548a-3p as biomarker of NEDA-3 at 2 years in multiple sclerosis patients treated with fingolimod
Authors: Gonzalez-Martinez Alicia , Patel Rohit , Healy Brian C. , Lokhande Hrishikesh , Paul Anu , Saxena Shrishti , Polgar-Turcsanyi Mariann , Weiner Howard L. , Chitnis Tanuja 
Published: May 2023

Abstract
Background
Multiple sclerosis (MS) is a disabling autoimmune demyelinating disorder affecting young people and causing significant disability. In the last decade, different microRNA (miRNA) expression patterns have been associated to several treatment response therapies such as interferon and glatiramer acetate. Nowadays, there is increasing interest in the potential role of miRNA as treatment response biomarkers to the most recent oral and intravenous treatments. In this study, we aimed to evaluate serum miRNAs as biomarkers of No Evidence of Disease Activity (NEDA-3) at 2 years in patients with relapsing remitting MS (RRMS) treated with fingolimod.

Main body
A Discovery cohort of 31 RRMS patients treated with fingolimod were identified from the CLIMB study and classified as No Evidence of Disease Activity (NEDA-3) or Evidence of Disease Activity (EDA-3) after 2 years on treatment. Levels of miRNA expression were measured at 6 months using human serum miRNA panels and compared in EDA-3 and NEDA-3 groups using the Wilcoxon rank sum test. A set of differentially expressed miRNA was further validated in an independent cohort of 22 fingolimod-treated patients. We found that 548a-3p serum levels were higher levels in fingolimod-treated patients classified as NEDA-3, compared to the EDA-3 group in both the Discovery (n = 31; p = 0.04) and Validation (n = 22; p = 0.03) cohorts 6 months after treatment initiation; miR-548a-3p provided an AUC of 0.882 discriminating patients with NEDA-3 at 2 years in the Validation cohort.

Conclusion
Our results show differences in miR-548a-3p expression at 6 months after fingolimod start in patients with MS with NEDA-3 at 2 years. These results provide class III evidence of the use of miR-548a-3p as biomarker of NEDA-3 in patients with fingolimod.
Exosomal miR-214-3p from senescent osteoblasts accelerates endothelial cell senescence
Authors: Guo Zhen , Li Jing , Tan Jiyong , Sun Sainan , Yan Qing , Qin Hao 
Published: May 2023

Abstract
Background
Osteoporosis is a common systemic bone disease that leads to bone fragility and increases the risk of fracture. However, the pathogenesis of osteoporosis is considered to be highly complex. The exosomes can regulate the communication between cells. The specific mechanism of information transmission between osteoblasts and endothelial cells is worthy of further study.

Methods
Exosomes were isolated and verified from senescent osteoblasts. The source and properties of exosomes were determined by TEM, particle size analysis and western blot. We established the co-culture model of endothelial cells and senescent osteoblasts. We used qRT-PCR to identify differentially expressed miRNAs. The functional changes of vascular endothelial cells were verified by cell transfection. β-Galactosidase cell senescence assay, Hoechst cell apoptosis assay, Ki67 cell proliferation assay and Transwell migration assay were used to verify cell senescence, apoptosis, proliferation, and migration. The potential target gene of miRNA was detected by bio-informatics pathway and double luciferase report.

Results
We discovered that senescent osteoblasts could promote the senescence and apoptosis of vascular endothelial cells and inhibit their proliferation and migration. miR-214-3p was upregulated in senescent osteoblast-derived exosomes. miR-214-3p could effectively promote senescence and apoptosis of endothelial cells and inhibit proliferation and migration ability. L1CAM is a miR-214-3p direct target gene determined by bio-informatics and double luciferase report.

Conclusions
In conclusion, senescent osteoblast-derived exosomes can accelerate endothelial cell senescence through miR-214-3p/L1CAM pathway. Our experiments reveal the role of exosomes in the skeletal microenvironment.
Perilous medicine in Tigray: a systematic review
Authors: Gesesew Hailay , Kebede Hafte , Berhe Kenfe , Fauk Nelsensius , Ward Paul 
Published: May 2023

AbstractBackgroundThe war in Tigray, North Ethiopia which started in November 2020, has destroyed decades of the region’s healthcare success. There is some emerging published evidence on attacks on health care in the region, and we synthesized the available evidence on ‘perilous medicine’ in Tigray to understand the data source, subjects and content covered, and what gaps exist.MethodsWe employed a systematic review and performed a systematic search of MEDLINE, PubMed, CINHAL, Web of Science and Scopus. We included English written documents published from 4 November 2020 to 18–19 October 2022 and updated the search on 23 January 2023. HG and NF independently performed title, abstract and full-text screening. We used Joanna Briggs Institute (JBI) tools to appraise and extract data, and applied content synthesis to analyze. The PROSPERO registration number is CRD42022364964.ResultsOur systematic review search yielded 8,039 documents, and we finally found 41 documents on conflict and health in Tigray. The areas were: (1) attacks on infrastructure, health or aid workers, patients, ambulances or aid trucks identified in 29 documents—the documents reported targeted attacks on health infrastructure and personnel; (2) interruption of health or social services in 31 documents—the documents reported medical and humanitarian siege; (3) outcomes and direct or indirect impacts in 33 documents—the documents reported increased magnitude of illnesses, and catastrophic humanitarian crises including the use of food, medicine and rape as tools of war; and (4) responses, rebuilding strategies, and recommendations in 21 documents—the documents reported improvisation of services, and calling to seize fire, accountability and allow humanitarian.ConclusionsDespite promising studies on conflict and health in Tigray, the documents lack quality of designs and data sources, and depth and diversity of subjects and contents covered; calling further primary studies on a prioritized future research agenda.
Inferring cell-type-specific causal gene regulatory networks during human neurogenesis
Authors: Aygün Nil , Liang Dan , Crouse Wesley L. , Keele Gregory R. , Love Michael I. , Stein Jason L. 
Published: May 2023

Abstract

Background
Genetic variation influences both chromatin accessibility, assessed in chromatin accessibility quantitative trait loci (caQTL) studies, and gene expression, assessed in expression QTL (eQTL) studies. Genetic variants can impact either nearby genes (cis-eQTLs) or distal genes (trans-eQTLs). Colocalization between caQTL and eQTL, or cis- and trans-eQTLs suggests that they share causal variants. However, pairwise colocalization between these molecular QTLs does not guarantee a causal relationship. Mediation analysis can be applied to assess the evidence supporting causality versus independence between molecular QTLs. Given that the function of QTLs can be cell-type-specific, we performed mediation analyses to find epigenetic and distal regulatory causal pathways for genes within two major cell types of the developing human cortex, progenitors and neurons.

Results
We find that the expression of 168 and 38 genes is mediated by chromatin accessibility in progenitors and neurons, respectively. We also find that the expression of 11 and 12 downstream genes is mediated by upstream genes in progenitors and neurons. Moreover, we discover that a genetic locus associated with inter-individual differences in brain structure shows evidence for mediation of SLC26A7 through chromatin accessibility, identifying molecular mechanisms of a common variant association to a brain trait.

Conclusions
In this study, we identify cell-type-specific causal gene regulatory networks whereby the impacts of variants on gene expression were mediated by chromatin accessibility or distal gene expression. Identification of these causal paths will enable identifying and prioritizing actionable regulatory targets perturbing these key processes during neurodevelopment.
Genomic and epigenomic determinants of heat stress-induced transcriptional memory in Arabidopsis
Authors: Kappel Christian , Friedrich Thomas , Oberkofler Vicky , Jiang Li , Crawford Tim , Lenhard Michael , Bäurle Isabel 
Published: May 2023

Abstract
Background
Transcriptional regulation is a key aspect of environmental stress responses. Heat stress induces transcriptional memory, i.e., sustained induction or enhanced re-induction of transcription, that allows plants to respond more efficiently to a recurrent HS. In light of more frequent temperature extremes due to climate change, improving heat tolerance in crop plants is an important breeding goal. However, not all heat stress-inducible genes show transcriptional memory, and it is unclear what distinguishes memory from non-memory genes. To address this issue and understand the genome and epigenome architecture of transcriptional memory after heat stress, we identify the global target genes of two key memory heat shock transcription factors, HSFA2 and HSFA3, using time course ChIP-seq.

Results
HSFA2 and HSFA3 show near identical binding patterns. In vitro and in vivo binding strength is highly correlated, indicating the importance of DNA sequence elements. In particular, genes with transcriptional memory are strongly enriched for a tripartite heat shock element, and are hallmarked by several features: low expression levels in the absence of heat stress, accessible chromatin environment, and heat stress-induced enrichment of H3K4 trimethylation. These results are confirmed by an orthogonal transcriptomic data set using both de novo clustering and an established definition of memory genes.

Conclusions
Our findings provide an integrated view of HSF-dependent transcriptional memory and shed light on its sequence and chromatin determinants, enabling the prediction and engineering of genes with transcriptional memory behavior.
Simultaneous acromioclavicular dislocation, proximal humeral fracture, and reverse Hill–Sachs lesion: a case report
Authors: Barati Hasan , Afzal Sina 
Published: May 2023

Abstract
Background
In cases with injuries to the shoulder region, the combination of acromioclavicular joint dislocation, reverse Hill–Sachs lesion, and proximal humeral fracture is a very rare condition.

Case presentation
This study described a 38-year-old male Persian patient with simultaneous acromioclavicular joint dislocation, proximal humeral fracture, and reverse Hill–Sachs lesion due to motor vehicle crash injury who underwent arthroscopic acromioclavicular joint fixation using tight rope technique. In the 7-month follow-up period following the surgical fixation, range of motion was approximately normal. Reduction and hardware were intact, no dislocation or apprehension to dislocation was observed. Patient only had minor shoulder pain at the end of range of motion and a dull pain on the site of incision over the clavicle in deep touch. Our findings showed acceptable arthroscopic outcomes in the management of such complex case.

Conclusion
Our experience on this case showed acceptable outcomes of the arthroscopic treatment of the acromioclavicular joint dislocation in the management of such a complex case with associated injuries to the shoulder region.
Unsupervised deep learning techniques for automatic detection of plant diseases: reducing the need of manual labelling of plant images
Authors: Benfenati Alessandro , Causin Paola , Oberti Roberto , Stefanello Giovanni 
Published: May 2023

AbstractCrop protection from diseases through applications of plant protection products is crucial to secure worldwide food production. Nevertheless, sustainable management of plant diseases is an open challenge with a major role in the economic and environmental impact of agricultural activities. A primary contribution is expected to come from precision crop protection approaches, with treatments tailored to spatial and time-specific needs of the crop, in contrast to the current practice of applying treatments uniformly to fields. In view of this, image-based automatic detection of early disease symptoms is considered a key enabling technology for high throughput scouting of the crop, in order to timely target the treatments on emerging infection spots. Thanks to the unprecedented performance in image-recognition problems, Deep Learning (DL) methods based on Convolutional Neural Networks (CNNs) have recently entered the domain of plant disease detection. This work develops two DL approaches for automatic recognition of powdery mildew disease on cucumber leaves, with a specific focus on exploring unsupervised techniques to overcome the need of large training set of manually labelled images. To this aim, autoencoder networks were implemented for unsupervised detection of disease symptoms through: i) clusterization of features in a compressed space; ii) anomaly detection. The two proposed approaches were applied to multispectral images acquired during in-vivo experiments, and the obtained results were assessed by quantitative indices. The clusterization approach showed only partially capability to provide accurate disease detection, even if it gathered some relevant information. Anomaly detection showed instead to possess a significant potential of discrimination which could be further exploited as a prior step to train more powerful supervised architectures with a very limited number of labelled samples.
Integration and adoption of climate resilient management practices for enhanced productivity of sheep and goats in pastoral communities of Northern Kenya
Authors: Ojango Julie M. K. , Gitau Jennifer , Ndiwa Nicholas , Recha John W. , Gachora Judy , Muigai Anne W. T. 
Published: May 2023

AbstractInterventions to improve productivity in pastoral livestock systems of northern Kenya focus on the management of the rangeland resources and grazing areas with few initiatives on changes related to the livestock assets. However, changing climatic conditions with high frequencies of droughts have increased the vulnerability of pastoral communities and necessitate prompt interventions in animal management practices. In 2018, the Ministry of Agriculture, Livestock, Fisheries and Irrigation in collaboration with the International Livestock Research Institute commenced a programme to build the resilience of pastoral holdings using their animal assets rather than depending on humanitarian emergency responses. Interventions necessitated changes in management practices related to sheep and goat production. Core innovation groups (CIG) each comprising 30 pastoral households in select communities were established to model new practices for wider adoption using participatory processes in Isiolo, Marsabit and Turkana Counties. CIG members went through a 3-year phased training programme on animal management practices for more efficient, resilient and productive animals. The adoption of new practices in CIG flocks was monitored by extension personnel. Data were analysed using logistic regression techniques to assess household-level adoption of livestock breed improvement, feeding and disease control interventions. The 3 years of the programme (2018–2021) were relatively satisfactory in terms of pasture availability; hence, communities pursued strategies to enhance their flocks. All CIG adopted more than one of the introduced technologies concurrently. Prevention of diseases was the most readily adopted, followed by crossbreeding using indigenous breeds of sheep and goats from other arid areas of Kenya. Turkana County had the lowest probability of adopting any of the technologies as previous devastating droughts have resulted in an increased emphasis on animals for survival rather than productivity. The study shows that pastoral communities are open to technological interventions for animal productivity. Adoption of the technologies was enhanced by the experiential capacity development activities adapted to the education level of the different communities.
Separate and joint associations of chronic pain, multisite pain and mental health with sickness absence among younger employees: a register based longitudinal study
Authors: Fagerlund Pi , Shiri Rahman , Suur-Uski Johanna , Kaartinen Sara , Rahkonen Ossi , Lallukka Tea 
Published: May 2023

Abstract
Background
Pain conditions and poorer mental health are associated with work disability. However, few studies have examined the association of concurrent pain and poorer mental health with sickness absence among younger employees. We examined separate and joint associations of chronic pain, multisite pain, and mental health with total and long-term all-cause sickness absence days among younger Finnish municipal employees.

Methods
The Young Helsinki Health-study data were collected in 2017 from 19–39-year-old employees of the City of Helsinki, Finland. Chronic (≥ 3 months) and multisite (≥ 2 body sites) pain and mental health (RAND-36 emotional wellbeing subscale dichotomized by median score) were self-reported (n = 3911). Chronic pain, multisite pain and mental health were analyzed separately and combined. Register data on total (≥ 1 workdays) and long-term (≥ 11 workdays) sickness absence days during the following year were obtained. Negative binomial regression analyses were performed with sociodemographic, socioeconomic, and health-related factors as confounders. Gender interaction and synergistic indices were examined.

Results
Chronic multisite pain was associated with long-term sickness absence days (rate ratio [RR] 2.51, 95% CI 1.17–5.42). Chronic pain (RR 5.04, 95% CI 2.14–11.87) and multisite pain (RR 4.88, 95% CI 2.30–10.33) were associated with long-term sickness absence days among employees with poorer mental health. There was a synergistic interaction between gender and multisite pain for total sickness absence days (synergy index 1.80, 95% CI 1.27–2.54), with stronger associations among women.

Conclusions
Chronic and multisite pain are associated with long-term sickness absence among younger employees, particularly among women and employees with concurrent poorer mental health. Consideration of this knowledge at workplaces and in healthcare could help to identify and support employees at increased risk of later sickness absence.
Enablers and inhibitors of digital startup evolution: a multi-case study of Swedish business incubators
Authors: Page Andrew , Holmström Jonny 
Published: May 2023

AbstractGlobal advances in digital technology are facilitating corresponding rises in digital entrepreneurship and its startup manifestation. There are many uncertainties on the road to digital startup evolution, some of which may be successfully navigated with the assistance of business incubators. While these organisations provide valuable guidance and support to the startup community, their efforts are at least partly constrained by the lack of a consistent, coherent roadmap to guide both them and their incubatees. T0 help efforts to develop such a map, this paper seeks to identify factors that influence digital startup evolution within an incubator setting through a multiple-case study focusing on digital startups under the umbrella of three business incubators in the Swedish city Umeå. Sets of enabling and inhibitory factors are identified through literature searches and the case studies. The latter may include inertia and possibly attitudes towards failure. In addition, present the Ideation Dynamics Model as a guide for both incubators and digital startups is proposed.
APSIC guide for prevention of catheter associated urinary tract infections (CAUTIs)
Authors: Ling Moi Lin , Ching P. , Apisarnthanarak A. , Jaggi N. , Harrington G. , Fong S. M. 
Published: May 2023

Abstract
Background
The Asia Pacific Society of Infection Control launched the APSIC guide for prevention of catheter associated urinary tract infections in July 2022. It aims to highlight practical recommendations in a concise format designed to assist healthcare facilities in the Asia Pacific region to achieve high standards in infection prevention and control practices during the management and care of patients with a urinary catheter.

Methods
The guidelines were developed by an appointed workgroup comprising experts in the Asia Pacific region, following reviews of previously published guidelines and recommendations relevant to each section.

Results
It recommends that healthcare institutions have a catheter associated urinary tract infection prevention program that includes surveillance and the use of the insertion and maintenance bundles. Implementation of the bundles is best done using a quality improvement approach with a multidisciplinary team.

Conclusions
Healthcare facilities should aim for excellence in care of patients with urinary catheters. It is recommended that healthcare facilities have a catheter associated urinary tract infection prevention program as part of their Infection Prevention and Control program.
Utility of indium-111 platelet scintigraphy for understanding the mechanism of thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia
Authors: Durand Pauline , Pottier Valérie , Mesguich Charles , Debordeaux Frédéric , Lazaro Estibaliz , Viallard Jean-François , Rivière Etienne 
Published: May 2023

Abstract
Background
Thrombocytopenia occurs in 60% of patients with myelodysplastic syndromes (MDS), increasing the risk of life-threatening haemorrhage in this population of mainly old patients with comorbidities. However, data are scare regarding immune thrombocytopenia (ITP) secondary to MDS.

Aim
We analyzed the utility of indium-111 platelet scintigraphy (IPS) to better characterize the mechanisms of thrombocytopenia in 21 adult patients with MDS.

Methods
Adult patients with a definite diagnosis of MDS according to the international criteria who underwent IPS between 2009 and 2018 because of an increased bleeding risk were retrospectively selected. Autologous 111Indium platelet labelling was performed with a technique similar to that described previously using a standardized method.

Results
Platelet lifespan ≤ 6 days identified patients with peripheral platelet destruction. Taking into account the response to ITP-directed therapies after IPS, the sensitivity, specificity, and positive and negative predictive values of IPS were 100%, 84.6%, 80%, and 100%, respectively.

Conclusion
We show that IPS can be a useful tool to identify the mechanism and guide treatment of a chronic thrombocytopenia increasing the bleeding risk in patients with MDS.