bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis reveals alterations in cellular composition and cell-cell communication associated with airway inflammation and remodeling in asthma
Authors: Yu Xiu , Li Lifei , Cai Bicheng , Zhang Wei , Liu Quan , Li Nan , Shi Xing , Yu Li , Chen Rongchang , Qiu Chen 
Published: February 2024

Abstract
Background
Asthma is a heterogeneous disease characterized by airway inflammation and remodeling, whose pathogenetic complexity was associated with abnormal responses of various cell types in the lung. The specific interactions between immune and stromal cells, crucial for asthma pathogenesis, remain unclear. This study aims to determine the key cell types and their pathological mechanisms in asthma through single-cell RNA sequencing (scRNA-seq).

Methods
A 16-week mouse model of house dust mite (HDM) induced asthma (n = 3) and controls (n = 3) were profiled with scRNA-seq. The cellular composition and gene expression profiles were assessed by bioinformatic analyses, including cell enrichment analysis, trajectory analysis, and Gene Set Enrichment Analysis. Cell-cell communication analysis was employed to investigate the ligand-receptor interactions.

Results
The asthma model results in airway inflammation coupled with airway remodeling and hyperresponsiveness. Single-cell analysis revealed notable changes in cell compositions and heterogeneities associated with airway inflammation and remodeling. GdT17 cells were identified to be a primary cellular source of IL-17, related to inflammatory exacerbation, while a subpopulation of alveolar macrophages exhibited numerous significantly up-regulated genes involved in multiple pathways related to neutrophil activities in asthma. A distinct fibroblast subpopulation, marked by elevated expression levels of numerous contractile genes and their regulators, was observed in increased airway smooth muscle layer by immunofluorescence analysis. Asthmatic stromal-immune cell communication significantly strengthened, particularly involving GdT17 cells, and macrophages interacting with fibroblasts. CXCL12/CXCR4 signaling was remarkedly up-regulated in asthma, predominantly bridging the interaction between fibroblasts and immune cell populations. Fibroblasts and macrophages could jointly interact with various immune cell subpopulations via the CCL8/CCR2 signaling. In particular, fibroblast-macrophage cell circuits played a crucial role in the development of airway inflammation and remodeling through IL1B paracrine signaling.

Conclusions
Our study established a mouse model of asthma that recapitulated key pathological features of asthma. ScRNA-seq analysis revealed the cellular landscape, highlighting key pathological cell populations associated with asthma pathogenesis. Cell-cell communication analysis identified the crucial ligand-receptor interactions contributing to airway inflammation and remodeling. Our findings emphasized the significance of cell-cell communication in bridging the possible causality between airway inflammation and remodeling, providing valuable hints for therapeutic strategies for asthma.
Low-frequency ultrasound for pulmonary hypertension therapy
Authors: Ostasevicius Vytautas , Jurenas Vytautas , Venslauskas Mantas , Kizauskiene Laura , Zigmantaite Vilma , Stankevicius Edgaras , Bubulis Algimantas , Vezys Joris , Mikuckyte Sandra 
Published: February 2024

Abstract
Background
Currently, there are no reliable clinical tools that allow non-invasive therapeutic support for patients with pulmonary arterial hypertension. This study aims to propose a low-frequency ultrasound device for pulmonary hypertension therapy and to demonstrate its potential.

Methods
A novel low-frequency ultrasound transducer has been developed. Due to its structural properties, it is excited by higher vibrational modes, which generate a signal capable of deeply penetrating biological tissues. A methodology for the artificial induction of pulmonary hypertension in sheep and for the assessment of lung physiological parameters such as blood oxygen concentration, pulse rate, and pulmonary blood pressure has been proposed.

Results
The results showed that exposure of the lungs to low-frequency ultrasound changed physiological parameters such as blood oxygen concentration, pulse rate and blood pressure. These parameters are most closely related to indicators of pulmonary hypertension (PH). The ultrasound exposure increased blood oxygen concentration over a 7-min period, while pulse rate and pulmonary blood pressure decreased over the same period. In anaesthetised sheep exposed to low-frequency ultrasound, a 10% increase in SpO2, a 10% decrease in pulse rate and an approximate 13% decrease in blood pressure were observed within 7 min.

Conclusions
The research findings demonstrate the therapeutic efficiency of low-frequency ultrasound on hypertensive lungs, while also revealing insights into the physiological aspects of gas exchange within the pulmonary system.
Integrated approach for detection of SARS-CoV-2 and its variant by utilizing LAMP and ARMS-PCR
Authors: Nawab Maryam , Riaz Syeda Kiran , Ismail Eiman , Ahamed Alfar , Tariq Aaysha , Malik Muhammad Faraz Arshad , Qusty Naeem F. , Bantun Farkad , Slama Petr , Umair Massab , Haque Shafiul , Bonilla-Aldana D. Katterine , Rodriguez-Morales Alfonso J. 
Published: February 2024

AbstractGlobal impact of COVID-19 pandemic has heightened the urgency for efficient virus detection and identification of variants such as the Q57H mutation. Early and efficient detection of SARS-CoV-2 among densely populated developing countries is paramount objective. Although RT-PCR assays offer accuracy, however, dependence on expansive kits and availability of allied health resources pose an immense challenge for developing countries. In the current study, RT-LAMP based detection of SARS-Cov-2 with subsequent confirmation of Q57H variant through ARMS-PCR was performed. Among the 212 collected samples, 134 yielded positive results, while 78 tested negative using RT-LAMP. Oropharyngeal swabs of suspected individuals were collected and processed for viral RNA isolation. Isolated viral RNA was processed further by using either commercially available WarmStart Master Mix or our in house developed LAMP master mix separately. Subsequently, the end results of each specimen were evaluated by colorimetry. For LAMP assays, primers targeting three genes (ORF1ab, N and S) were designed using PrimerExplorer software. Interestingly, pooling of these three genes in single reaction tube increased sensitivity (95.5%) and specificity (93.5%) of LAMP assay. SARS-CoV-2 positive specimens were screened further for Q57H mutation using ARMS-PCR. Based on amplicon size variation, later confirmed by sequencing, our data showed 18.5% samples positive for Q57H mutation. Hence, these findings strongly advocate use of RT-LAMP-based assay for SARS-CoV-2 screening within suspected general population. Furthermore, ARMS-PCR also provides an efficient mean to detect prevalent mutations against SARS-Cov-2.
Preference for hotline versus mobile application/countdown-based mobile overdose response services: a qualitative study
Authors: Rioux William , Teare Adrian , Rider Nathan , Jones Stephanie , Ghosh S. Monty 
Published: February 2024

Abstract
Background
In response to the exacerbated rates of morbidity and mortality associated with the overlapping overdose and COVID-19 epidemics, novel strategies have been developed, implemented, operationalized and scaled to reduce the harms resulting from this crisis. Since the emergence of mobile overdose response services (MORS), two strategies have aimed to help reduce the mortality associated with acute overdose including staffed hotline-based services and unstaffed timer-based services. In this article, we aim to gather the perspectives of various key interest groups on these technologies to determine which might best support service users.

Methods
Forty-seven participants from various interested groups including people who use substances who have and have not used MORS, healthcare workers, family members, harm reduction employees and MORS operators participated in semi-structured interviews. Transcripts were coded and analyzed using a thematic analysis approach.

Results
Four major themes emerged regarding participant perspectives on the differences between services, namely differences in connection, perceived safety, privacy and accessibility, alongside features that are recommended for MORS in the future.

Conclusions
Overall, participants noted that individuals who use substances vary in their desire for connection during a substance use session offered by hotline and timer-based service modalities. Participants perceived hotline-based approaches to be more reliable and thus potentially safer than their timer-based counterparts but noted that access to technology is a limitation of both approaches.
The siRNA-mediated knockdown of AP-1 restores the function of the pulmonary artery and the right ventricle by reducing perivascular and interstitial fibrosis and key molecular players in cardiopulmonary disease
Authors: Comarița Ioana Karla , Tanko Gabriela , Anghelache Iliuță Laurențiu , Georgescu Adriana 
Published: February 2024

Abstract
Background
Pulmonary hypertension (PH) is a complex multifactorial vascular pathology characterized by an increased pulmonary arterial pressure, vasoconstriction, remodelling of the pulmonary vasculature, thrombosis in situ and inflammation associated with right-side heart failure. Herein, we explored the potential beneficial effects of treatment with siRNA AP-1 on pulmonary arterial hypertension (PAH), right ventricular dysfunction along with perivascular and interstitial fibrosis in pulmonary artery-PA, right ventricle-RV and lung in an experimental animal model of monocrotaline (MCT)-induced PAH.

Methods
Golden Syrian hamsters were divided into: (1) C group-healthy animals taken as control; (2) MCT group obtained by a single subcutaneous injection of 60 mg/kg MCT at the beginning of the experiment; (3) MCT-siRNA AP-1 group received a one-time subcutaneous dose of MCT and subcutaneous injections containing 100 nM siRNA AP-1, every two weeks. All animal groups received water and standard chow ad libitum for 12 weeks.

Results
In comparison with the MCT group, siRNA AP-1 treatment had significant beneficial effects on investigated tissues contributing to: (1) a reduction in TGF-β1/ET-1/IL-1β/TNF-α plasma concentrations; (2) a reduced level of cytosolic ROS production in PA, RV and lung and notable improvements regarding the ultrastructure of these tissues; a decrease of inflammatory and fibrotic marker expressions in PA (COL1A/Fibronectin/Vimentin/α-SMA/CTGF/Calponin/MMP-9), RV and lung (COL1A/CTGF/Fibronectin/α-SMA/F-actin/OB-cadherin) and an increase of endothelial marker expressions (CD31/VE-cadherin) in PA; (4) structural and functional recoveries of the PA [reduced Vel, restored vascular reactivity (NA contraction, ACh relaxation)] and RV (enlarged internal cavity diameter in diastole, increased TAPSE and PRVOFs) associated with a decrease in systolic and diastolic blood pressure, and heart rate; (5) a reduced protein expression profile of AP-1S3/ pFAK/FAK/pERK/ERK and a significant decrease in the expression levels of miRNA-145, miRNA-210, miRNA-21, and miRNA-214 along with an increase of miRNA-124 and miRNA-204.

Conclusions
The siRNA AP-1-based therapy led to an improvement of pulmonary arterial and right ventricular function accompanied by a regression of perivascular and interstitial fibrosis in PA, RV and lung and a down-regulation of key inflammatory and fibrotic markers in MCT-treated hamsters.
SeptoSympto: a precise image analysis of Septoria tritici blotch disease symptoms using deep learning methods on scanned images
Authors: Mathieu Laura , Reder Maxime , Siah Ali , Ducasse Aurélie , Langlands-Perry Camilla , Marcel Thierry C. , Morel Jean-Benoît , Saintenac Cyrille , Ballini Elsa 
Published: February 2024

Abstract
Background
Investigations on plant-pathogen interactions require quantitative, accurate, and rapid phenotyping of crop diseases. However, visual assessment of disease symptoms is preferred over available numerical tools due to transferability challenges. These assessments are laborious, time-consuming, require expertise, and are rater dependent. More recently, deep learning has produced interesting results for evaluating plant diseases. Nevertheless, it has yet to be used to quantify the severity of Septoria tritici blotch (STB) caused by Zymoseptoria tritici—a frequently occurring and damaging disease on wheat crops.

Results
We developed an image analysis script in Python, called SeptoSympto. This script uses deep learning models based on the U-Net and YOLO architectures to quantify necrosis and pycnidia on detached, flattened and scanned leaves of wheat seedlings. Datasets of different sizes (containing 50, 100, 200, and 300 leaves) were annotated to train Convolutional Neural Networks models. Five different datasets were tested to develop a robust tool for the accurate analysis of STB symptoms and facilitate its transferability. The results show that (i) the amount of annotated data does not influence the performances of models, (ii) the outputs of SeptoSympto are highly correlated with those of the experts, with a similar magnitude to the correlations between experts, and (iii) the accuracy of SeptoSympto allows precise and rapid quantification of necrosis and pycnidia on both durum and bread wheat leaves inoculated with different strains of the pathogen, scanned with different scanners and grown under different conditions.

Conclusions
SeptoSympto takes the same amount of time as a visual assessment to evaluate STB symptoms. However, unlike visual assessments, it allows for data to be stored and evaluated by experts and non-experts in a more accurate and unbiased manner. The methods used in SeptoSympto make it a transferable, highly accurate, computationally inexpensive, easy-to-use, and adaptable tool. This study demonstrates the potential of using deep learning to assess complex plant disease symptoms such as STB.
Young children’s development after forced displacement: a systematic review
Authors: Bernhardt Katharina , Le Beherec Saskia , Uppendahl Jana R. , Fleischmann Melia , Klosinski Matthias , Rivera Luisa M. , Samaras Georgia , Kenney Martha , Müller Ruth , Nehring Ina , Mall Volker , Hahnefeld Andrea 
Published: February 2024

Abstract
Objectives
To examine the impact of displacement experiences on 0- to 6-year-old children’s social-emotional and cognitive development, as well as influencing factors on reported outcomes.

Study design
We systematically searched MEDline, Psyndex, Cochrane Library, Web of Science, Elsevier, TandF, Oxford Journal of Refugee Studies, Journal of Immigrant & Refugee Studies, and Canada’s Journal on Refugees for existing literature regarding social-emotional and cognitive outcomes in children directly exposed to forced displacement due to political violence. Results were synthesized in the discussion and displayed using harvest plots.

Results
Our search generated 9,791 articles of which 32 were selected for review and evaluation according to NICE criteria. Included studies provided results for 6,878 forcibly displaced children. Measured outcomes were diverse and included areas such as peer relations, prosocial behavior, family functioning, play, intelligence, learning performance, and language development. Repeated exposure to adverse experiences, separation from parents, parental distress, as well as duration and quality of resettlement in the host country were reported as influencing factors in the reviewed studies.

Conclusion
As protective factors like secure and stable living conditions help to promote children’s development, we call for policies that enhance participation in the welcoming society for refugee families. Early integration with low-threshold access to health and educational facilities can help to mitigate the wide-ranging negative consequences of forced displacement on young children’s development.
Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study
Authors: Petit Matthieu , Bidar Frank , Fosse Quentin , Lefevre Lucie , Paul Marine , Urbina Tomas , Masi Paul , Bavozet Florent , Lemarié Jérémie , de Montmollin Etienne , Andriamifidy-Berti Chloé , Dessajan Julien , Zuber Benjamin , Zafrani Lara , Peju Edwige , Meng Paris , Charrier Liliane , Le Guennec Loic , Simon Marie , Luyt Charles-Edouard , Haudebourg Luc , Geri Guillaume 
Published: February 2024

Abstract
Background
Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged.

Methods
Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death.

Results
From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21–42), 40% (95% CI 26–55) and 21% (95% CI 15–28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92–61.91)].

Conclusion
Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.
Simple but powerful interactive data analysis in R with R/LinkedCharts
Authors: Ovchinnikova Svetlana , Anders Simon 
Published: February 2024

AbstractIn research involving data-rich assays, exploratory data analysis is a crucial step. Typically, this involves jumping back and forth between visualizations that provide overview of the whole data and others that dive into details. For example, it might be helpful to have one chart showing a summary statistic for all samples, while a second chart provides details for points selected in the first chart. We present R/LinkedCharts, a framework that renders this task radically simple, requiring very few lines of code to obtain complex and general visualization, which later can be polished to provide interactive data access of publication quality.
The ROCK trial—a multidisciplinary Rehabilitation intervention for sudden Out-of-hospital Cardiac arrest survivors focusing on return-to-worK: a pragmatic randomized controlled trial protocol
Authors: Christensen Jan , Winkel Bo Gregers , Kirkeskov Lilli , Folke Fredrik , Winther-Jensen Matilde , Eckhardt-Bentsen Christine , Kjærgaard Jesper , Hassager Christian , Wagner Mette Kirstine 
Published: February 2024

Abstract
Introduction
Most cardiac arrest survivors are classified with mild to moderate cognitive impairment; roughly, 50% experience long-term neurocognitive impairment. Postarrest challenges complicate participation in society and are associated with social issues such as failure to resume social activities and impaired return to work. The effectiveness of rehabilitation interventions for out-of-hospital cardiac arrest survivors are sparsely described, but the body of evidence describes high probabilities of survivors not returning to work, returning to jobs with modified job descriptions, returning to part-time employment, and often in combination with extensive unmet rehabilitation needs. Hence, there is a need to develop and test a pragmatic individual targeted intervention to facilitate return to work (RTW) in survivors of OHCA. The overall aim of the ROCK trial is to evaluate the effectiveness of a comprehensive individually tailored multidisciplinary rehabilitation intervention for survivors of OHCA on RTW compared to usual care.

Methods and analysis
The ROCK trial is a two-arm parallel group multicentre investigator-initiated pragmatic randomized controlled superiority trial with primary endpoint measured 12 months after the cardiac arrest. Adult survivors who were part of the labour force prior to the OCHA and had at least 2 years until they are qualified to receive retirement state pensions are eligible for inclusion. Survivors will be randomized 1:1 to usual care group or usual care plus a comprehensive tailored rehabilitation intervention focusing on supporting RTW. After comprehensive assessment of individual rehabilitation needs, the intervention is ongoingly coordinated within a multidisciplinary rehabilitation team, and the intervention can be delivered for up until 12 months. Data for the primary outcome will be obtained from the national register on social transfer payments. The primary outcome will be analysed using logistic regression assessing RTW status at 12 months adjusting for the intervention and age at OHCA, sex, marital status, and occupation prior to OHCA.

Discussion
The ROCK trial is the first RCT to investigate the effectiveness of a rehabilitation intervention focusing on return to work after cardiac arrest.

Trial registration
ClinicalTrials.gov NCT05173740. Registered on May 2018