bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent role of caspases and Bik in augmenting influenza A virus replication in airway epithelial cells and mice
Authors: Soni Sourabh , Walton-Filipczak Stephanie , Nho Richard S. , Tesfaigzi Yohannes , Mebratu Yohannes A. 
Published: April 2023

AbstractCaspases and poly (ADP-ribose) polymerase 1 (PARP1) have been shown to promote influenza A virus (IAV) replication. However, the relative importance and molecular mechanisms of specific caspases and their downstream substrate PARP1 in regulating viral replication in airway epithelial cells (AECs) remains incompletely elucidated. Here, we targeted caspase 2, 3, 6, and PARP1 using specific inhibitors to compare their role in promoting IAV replication. Inhibition of each of these proteins caused significant decline in viral titer, although PARP1 inhibitor led to the most robust reduction of viral replication. We previously showed that the pro-apoptotic protein Bcl-2 interacting killer (Bik) promotes IAV replication in the AECs by activating caspase 3. In this study, we found that as compared with AECs from wild-type mice, bik-deficiency alone resulted in ~ 3 logs reduction in virus titer in the absence of treatment with the pan-caspase inhibitor (Q-VD-Oph). Inhibiting overall caspase activity using Q-VD-Oph caused additional decline in viral titer by ~ 1 log in bik-/- AECs. Similarly, mice treated with Q-VD-Oph were protected from IAV-induced lung inflammation and lethality. Inhibiting caspase activity diminished nucleo-cytoplasmic transport of viral nucleoprotein (NP) and cleavage of viral hemagglutinin and NP in human AECs. These findings suggest that caspases and PARP1 play major roles to independently promote IAV replication and that additional mechanism(s) independent of caspases and PARP1 may be involved in Bik-mediated IAV replication. Further, peptides or inhibitors that target and block multiple caspases or PARP1 may be effective treatment targets for influenza infection.
Globalization and the health and well-being of migrant domestic workers in Malaysia
Authors: Spitzer Denise L. , Thambiah Shanthi , Wong Yut Lin , Kaundan Manimaran Krishnan 
Published: April 2023

Abstract
Background
Neoliberal globalization contributes to the out-migration of labour from sending countries in the global South. Supported by multilateral organizations including the IMF and World Bank, the migration and development nexus holds that nations and households in migrant sending countries can migrate their way out of poverty. Two countries that embrace this paradigm, the Philippines and Indonesia, are major suppliers of migrant labour including domestic workers, and Malaysia is a primary destination country.

Theory and methods
We deployed a multi-scalar and intersectional lens to highlight the impact of global forces and policies, interacting with constructions of gender and national identity, to explore the health and wellbeing of migrant domestic workers in Malaysia. In addition to documentary analysis, we conducted face-to-face interviews with 30 Indonesian and 24 Filipino migrant domestic workers, five representatives from civil society organizations, three government representatives, and four individuals engaged in labour brokerage and the health screening of migrant workers in Kuala Lumpur.

Results
Migrant domestic workers in Malaysia work long hours in private homes and are not protected by labour laws. Workers were generally satisfied with their access to health services; however, their intersectional status, which is both an outcome of, and contextualized by, the lack of opportunities in their own country, prolonged familial separation, low wages, and lack of control in the workplace, contributed to stress and related disorders—which we regard as the embodied manifestation of their migratory experiences. Migrant domestic workers eased these ill effects through self-care, spiritual practices, and the embrace of gendered values of self-sacrifice for the family as a form of solace.

Conclusions
Structural inequities and the mobilization of gendered values of self-abnegation underpin the migration of domestic workers as a development strategy. While individual self-care practices were used to cope with the hardships of their work and family separation, these efforts did not remedy the harms nor redress structural inequities wrought by neoliberal globalization. Improvements in the long-term health and wellbeing of Indonesian and Filipino migrant domestic workers in Malaysia cannot focus solely on the preparation and maintenance of healthy bodies for productive labour, but must attend to workers’ attainment of adequate social determinants of health, which challenges the migration as development paradigm. Neo-liberal policy instruments such as privatization, marketisation and commercialization of migrant labour have led to both host and home countries benefitting, but at the expense of the migrant domestic workers’ well-being.
The efficacy of integrated hepatitis C virus treatment in relieving fatigue in people who inject drugs: a randomized controlled trial
Authors: Vold Jørn Henrik , Chalabianloo Fatemeh , Løberg Else-Marie , Aas Christer F. , Lim Aaron G. , Vickerman Peter , Johansson Kjell Arne , Fadnes Lars Thore 
Published: April 2023

AbstractBackgroundMost people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment.MethodsThis multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores.ResultsAt baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4).ConclusionsFatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue.Trial registrationClinicalTrials.gov.no NCT03155906, 16/05/2017.
Impact of the COVID-19 pandemic on the quality of life and accessing rehabilitation services among patients with spinal cord injury and their fear of COVID-19
Authors: Khadour Fater A. , Khadour Younes A. , Ebrahem Bashar M. , Meng Ling , XinLi Cui , Xu Tao 
Published: April 2023

Abstract
Background
The unanticipated coronavirus disease (COVID-19) had a negative effect on the quality of life (QoL) of patients with spinal cord injury (SCI) and made significant changes in their daily routine. Patients with SCI face additional health risks, especially mental, behavioral, and physical. Without regular physiotherapy sessions, patients' psychological and functional abilities can deteriorate, and complications can occur. There is little information available about the impact of COVID-19 on the quality of life of patients with SCI, and their access to rehabilitation services during the pandemic.

Objective
This study was designed to examine the effects of the COVID-19 pandemic on the quality of life of patients with SCI and also their fear of COVID-19. The pandemic’s impact on the accessibility of rehabilitation services and attendance at physiotherapy sessions in one Chinese hospital were also documented.

Design
An observational study based on an online survey.

Setting
Outpatients clinic at the rehabilitation department of Wuhan's Tongji Hospital.

Participants
People who had been diagnosed with a spinal cord injury (SCI) and who were receiving regular medical monitoring as outpatients at the rehabilitation department were invited to participate in our study (n = 127).

Intervention
Not applicable.

Outcome measures
A 12-Item Short-Form Health Survey (SF-12) designed to measure participants' quality of life before and during the pandemic. Their fear of COVID-19 was quantified using the Fear of COVID-19 Scale (FCV-19S). Demographic and medical status information was extracted from their medical records. Their use of rehabilitation services and attendance at physical therapy sessions was also documented.

Results
Seventy-nine patients with SCI completed the SF-12 and FCV-19 scale. The mental and physical aspects of the participants’ quality of life declined significantly, during the epidemic compared to the pre-epidemic period. More than half of the participants have experienced fear of COVID-19 based on FCV-19S. Most received only irregular physical therapy during routine checkups. Worry about virus transmission was the most common cause cited for not attending regular physical therapy sessions.

Conclusions
The quality of life of these Chinese patients with SCI declined during the pandemic. Most of the participants were shown a high level of fear of COVID-19 and were classified as having an intense fear of COVID-19, in addition to the impact of the pandemic on their access to rehabilitation services and attendance at physical therapy sessions.
Experimental studies from shake flasks to 3 L stirred tank bioreactor of nutrients and oxygen supply conditions to improve the growth of the avian cell line DuckCelt®-T17
Authors: Tingaud Valentine , Bordes Claire , Al Mouazen Eyad , Cogné Claudia , Bolzinger Marie-Alexandrine , Lawton Philippe 
Published: April 2023

Abstract
Background
To produce viral vaccines, avian cell lines are interesting alternatives to replace the egg-derived processes for viruses that do not grow well on mammalian cells. The avian suspension cell line DuckCelt®-T17 was previously studied and investigated to produce a live attenuated metapneumovirus (hMPV)/respiratory syncytial virus (RSV) and influenza virus vaccines. However, a better understanding of its culture process is necessary for an efficient production of viral particles in bioreactors.

Results
The growth and metabolic requirements of the avian cell line DuckCelt®-T17 were investigated to improve its cultivation parameters. Several nutrient supplementation strategies were studied in shake flasks highlighting the interest of (i) replacing L-glutamine by glutamax as main nutrient or (ii) adding these two nutrients in the serum-free growth medium in a fed-batch strategy. The scale-up in a 3 L bioreactor was successful for these types of strategies confirming their efficiencies in improving the cells’ growth and viability. Moreover, a perfusion feasibility test allowed to achieve up to ~ 3 times the maximum number of viable cells obtained with the batch or fed-batch strategies. Finally, a strong oxygen supply – 50% dO2 – had a deleterious effect on DuckCelt®-T17 viability, certainly because of the greater hydrodynamic stress imposed.

Conclusions
The culture process using glutamax supplementation with a batch or a fed-batch strategy was successfully scaled-up to 3 L bioreactor. In addition, perfusion appeared as a very promising culture process for subsequent continuous virus harvesting.
The rationale and study design of two phase II trials examining the effects of BI 685509, a soluble guanylyl cyclase activator, on clinically significant portal hypertension in patients with compensated cirrhosis
Authors: Reiberger Thomas , Berzigotti Annalisa , Trebicka Jonel , Ertle Judith , Gashaw Isabella , Swallow Ros , Tomisser Andrea 
Published: April 2023

Abstract
Background
Clinically significant portal hypertension (CSPH) drives cirrhosis-related complications (i.e. hepatic decompensation). Impaired nitric oxide (NO) bioavailability promotes sinusoidal vasoconstriction, which is the initial pathomechanism of CSPH development. Activation of soluble guanylyl cyclase (sGC), a key downstream effector of NO, facilitates sinusoidal vasodilation, which in turn may improve CSPH. Two phase II studies are being conducted to assess the efficacy of the NO-independent sGC activator BI 685509 in patients with CSPH due to various cirrhosis aetiologies.

Methods
The 1366.0021 trial (NCT05161481) is a randomised, placebo-controlled, exploratory study that will assess BI 685509 (moderate or high dose) for 24 weeks in patients with CSPH due to alcohol-related liver disease. The 1366.0029 trial (NCT05282121) is a randomised, open-label, parallel-group, exploratory study that will assess BI 685509 (high dose) alone in patients with hepatitis B or C virus infection or non-alcoholic steatohepatitis (NASH) and in combination with 10 mg empagliflozin in patients with NASH and type 2 diabetes mellitus for 8 weeks. The 1366.0021 trial will enrol 105 patients, and the 1366.0029 trial will enrol 80 patients. In both studies, the primary endpoint is the change from baseline in hepatic venous pressure gradient (HVPG) until the end of treatment (24 or 8 weeks, respectively). Secondary endpoints include the proportion of patients with an HVPG reduction of >10% from baseline, the development of decompensation events and the change from baseline in HVPG after 8 weeks in the 1366.0021 trial. In addition, the trials will assess changes in liver and spleen stiffness by transient elastography, changes in hepatic and renal function and the tolerability of BI 685509.

Discussion
These trials will enable assessment of the short-term (8 weeks) and longer-term (24 weeks) safety of BI 685509, and the effect of sGC activation by BI 685509 on CSPH due to various cirrhosis aetiologies. The trials will use central readings of the diagnostic gold standard HVPG for the primary endpoint, and changes in established non-invasive biomarkers, such as liver and spleen stiffness. Ultimately, these trials will provide key information for developing future phase III trials.

Trial registration
1366.0021: EudraCT no. 2021–001285-38; ClinicalTrials.gov NCT05161481. Registered on 17 December 2021, https://www.clinicaltrials.gov/ct2/show/NCT05161481.
1366.0029: EudraCT no. 2021–005171-40; ClinicalTrials.gov NCT05282121. Registered on 16 March 2022, https://www.clinicaltrials.gov/ct2/show/NCT05282121.
Distribution of ticks in the Western Palearctic: an updated systematic review (2015–2021)
Authors: Noll Madeleine , Wall Richard , Makepeace Benjamin L. , Vineer Hannah Rose 
Published: April 2023

Abstract
Background
The distributions of ticks and tick-borne pathogens are thought to have changed rapidly over the last two decades, with their ranges expanding into new regions. This expansion has been driven by a range of environmental and socio-economic factors, including climate change. Spatial modelling is being increasingly used to track the current and future distributions of ticks and tick-borne pathogens and to assess the associated disease risk. However, such analysis is dependent on high-resolution occurrence data for each species. To facilitate such analysis, in this review we have compiled georeferenced tick locations in the Western Palearctic, with a resolution accuracy under 10 km, that were reported between 2015 and 2021

Methods
The PubMed and Web of Science databases were searched for peer-reviewed papers documenting the distribution of ticks that were published between 2015 and 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The papers were then screened and excluded in accordance with the PRISMA flow chart. Coordinate-referenced tick locations along with information on identification and collection methods were extracted from each eligible publication. Spatial analysis was conducted using R software (version 4.1.2).

Results
From the 1491 papers identified during the initial search, 124 met the inclusion criteria, and from these, 2267 coordinate-referenced tick records from 33 tick species were included in the final dataset. Over 30% of articles did not record the tick location adequately to meet inclusion criteria, only providing a location name or general location. Among the tick records, Ixodes ricinus had the highest representation (55%), followed by Dermacentor reticulatus (22.1%) and Ixodes frontalis (4.8%). The majority of ticks were collected from vegetation, with only 19.1% collected from hosts.

Conclusions
The data presented provides a collection of recent high-resolution, coordinate-referenced tick locations for use in spatial analyses, which in turn can be used in combination with previously collated datasets to analyse the changes in tick distribution and research in the Western Palearctic. In the future it is recommended that, where data privacy rules allow, high-resolution methods are routinely used by researchers to geolocate tick samples and ensure their work can be used to its full potential.

Graphical Abstract
ATG5 as biomarker for early detection of malignant mesothelioma
Authors: Tomasetti Marco , Monaco Federica , Strogovets Olga , Volpini Luca , Valentino Matteo , Amati Monica , Neuzil Jiri , Santarelli Lory 
Published: April 2023

Abstract
Objectives
Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups.

Results
The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.
Multi-channel deep learning model-based myocardial spatial–temporal morphology feature on cardiac MRI cine images diagnoses the cause of LVH
Authors: Diao Kaiyue , Liang Hong-qing , Yin Hong-kun , Yuan Ming-jing , Gu Min , Yu Peng-xin , He Sen , Sun Jiayu , Song Bin , Li Kang , He Yong 
Published: April 2023

Abstract
Background
To develop a fully automatic framework for the diagnosis of cause for left ventricular hypertrophy (LVH) via cardiac cine images.

Methods
A total of 302 LVH patients with cine MRI images were recruited as the primary cohort. Another 53 LVH patients prospectively collected or from multi-centers were used as the external test dataset. Different models based on the cardiac regions (Model 1), segmented ventricle (Model 2) and ventricle mask (Model 3) were constructed. The diagnostic performance was accessed by the confusion matrix with respect to overall accuracy. The capability of the predictive models for binary classification of cardiac amyloidosis (CA), hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) were also evaluated. Additionally, the diagnostic performance of best Model was compared with that of 7 radiologists/cardiologists.

Results
Model 3 showed the best performance with an overall classification accuracy up to 77.4% in the external test datasets. On the subtasks for identifying CA, HCM or HHD only, Model 3 also achieved the best performance with AUCs yielding 0.895–0.980, 0.879–0.984 and 0.848–0.983 in the validation, internal test and external test datasets, respectively. The deep learning model showed non-inferior diagnostic capability to the cardiovascular imaging expert and outperformed other radiologists/cardiologists.

Conclusion
The combined model based on the mask of left ventricular segmented from multi-sequences cine MR images shows favorable and robust performance in diagnosing the cause of left ventricular hypertrophy, which could be served as a noninvasive tool and help clinical decision.
Further improvement of finite-time boundedness based nonfragile state feedback control for generalized neural networks with mixed interval time-varying delays via a new integral inequality
Authors: Zamart Chantapish , Botmart Thongchai 
Published: April 2023

AbstractThis article investigates new delay-dependent finite-time boundedness for generalized neural networks (GNNs) with mixed-interval time-varying delays based on nonfragile feedback control to achieve the improved stability criterion. We also propose a new integral inequality with an exponential function to estimate the derivative of the Lyapunov–Krasovskii functional (LKF). Furthermore, the well-known Wirtinger’s inequality is a particular case of the new integral inequality. Using a toolbox optimization in MATLAB, we derive and solve new delay-dependent conditions in terms of linear matrix inequalities (LMIs). Additionally, we give three numerical examples to show the advantages of our obtained methods. The examples can apply the continuous time-varying delays that do not need to be differentiable. One of them presents the benchmark problem’s real-world application, which is a four-tank system.
Global classical solutions to the viscous two-phase flow model with slip boundary conditions in 3D exterior domains
Authors: Li Zilai , Liu Hao , Wang Huaqiao , Zhou Daoguo 
Published: April 2023

AbstractWe consider the two-phase flow model in 3D exterior domains with slip boundary conditions. We establish the global existence of classical solutions of this system, provided that the initial energy is suitably small. Furthermore, we prove that the pressure has large oscillations and contains vacuum states when the initial pressure allows large oscillations and a vacuum. Finally, we also obtain the large-time behavior of the classical solutions.
Solvability and Volterra property of nonlocal problems for mixed fractional-order diffusion-wave equation
Authors: Adil Nauryzbay , Berdyshev Abdumauvlen S. , Eshmatov B. E. , Baishemirov Zharasbek D. 
Published: April 2023

AbstractThe paper is devoted to the study of one class of problems with nonlocal conditions for a mixed diffusion-wave equation with two independent variables. The main results of the work are the proof of regular and strong solvability, as well as the Volterra property of three problems with conditions pointwise connecting the values of the tangent derivative of the desired solution on one of the characteristics with derivatives in various directions of the solution on an arbitrary curve lying inside the characteristic triangle for a fractional-order diffusion-hyperbolic equation.