bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic architecture of inter-specific and -generic grass hybrids by network analysis on multi-omics data
Authors: Bornhofen Elesandro , Fè Dario , Nagy Istvan , Lenk Ingo , Greve Morten , Didion Thomas , Jensen Christian S. , Asp Torben , Janss Luc
Published: April 2023

Background

Understanding the mechanisms underlining forage production and its biomass nutritive quality at the omics level is crucial for boosting the output of high-quality dry matter per unit of land. Despite the advent of multiple omics integration for the study of biological systems in major crops, investigations on forage species are still scarce.

Results

Our results identified substantial changes in gene co-expression and metabolite-metabolite network topologies as a result of genetic perturbation by hybridizing L. perenne with another species within the genus (L. multiflorum) relative to across genera (F. pratensis). However, conserved hub genes and hub metabolomic features were detected between pedigree classes, some of which were highly heritable and displayed one or more significant edges with agronomic traits in a weighted omics-phenotype network. In spite of tagging relevant biological molecules as, for example, the light-induced rice 1 (LIR1), hub features were not necessarily better explanatory variables for omics-assisted prediction than features stochastically sampled and all available regressors.

Conclusions

The utilization of computational techniques for the reconstruction of co-expression networks facilitates the identification of key omic features that serve as central nodes and demonstrate correlation with the manifestation of observed traits. Our results also indicate a robust association between early multi-omic traits measured in a greenhouse setting and phenotypic traits evaluated under field conditions.
Antibacterial, antibiofilm, and anti-quorum sensing activities of pyocyanin against methicillin-resistant Staphylococcus aureus: in vitro and in vivo study
Authors: Kamer Amal M. Abo , Abdelaziz Ahmed A. , Al-Monofy Khaled B. , Al-Madboly Lamiaa A.
Published: April 2023

Background

Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered a major public health problem, as the treatment options are restricted. Biofilm formation and the quorum sensing (QS) system play a pivotal role in S. aureus pathogenicity. Hence, this study was performed to explore the antibacterial effect of pyocyanin (PCN) on MRSA as well as its effect on MRSA biofilm and QS.

Results

Data revealed that PCN exhibited strong antibacterial activity against all test MRSA isolates (n = 30) with a MIC value equal to 8 µg/ml. About 88% of MRSA biofilms were eradicated by PCN treatment using the crystal violet assay. The disruption of MRSA biofilm was confirmed using confocal laser scanning microscopy, which showed a reduction in bacterial viability (approximately equal to 82%) and biofilm thickness (approximately equal to 60%). Additionally, the disruption of the formation of microcolonies and the disturbance of the connection between bacterial cells in the MRSA biofilm after PCN treatment were examined by scanning electron microscopy. The 1/2 and 1/4 MICs of PCN exerted promising anti-QS activity without affecting bacterial viability; Agr QS-dependent virulence factors (hemolysin, protease, and motility), and the expression of agrA gene, decreased after PCN treatment. The in silico analysis confirmed the binding of PCN to the AgrA protein active site, which blocked its action. The in vivo study using the rat wound infection model confirmed the ability of PCN to modulate the biofilm and QS of MRSA isolates.

Conclusion

The extracted PCN seems to be a good candidate for treating MRSA infection through biofilm eradication and Agr QS inhibition.
The pan-plastome of tartary buckwheat (fagopyrum tataricum): key insights into genetic diversity and the history of lineage divergence
Authors: Zhou Jiawei , He Wenchuang , Wang Jie , Liao Xuezhu , Xiang Kunli , Ma Mingchuan , Liu Zhang , Li Yongyao , Tembrock Luke R. , Wu Zhiqiang , Liu Longlong
Published: April 2023

Background

Tartary buckwheat (Fagopyrum tataricum) is an important food and medicine crop plant, which has been cultivated for 4000 years. A nuclear genome has been generated for this species, while an intraspecific pan-plastome has yet to be produced. As such a detailed understanding of the maternal genealogy of Tartary buckwheat has not been thoroughly investigated.

Results

In this study, we de novo assembled 513 complete plastomes of Fagopyrum and compared with 8 complete plastomes of Fagopyrum downloaded from the NCBI database to construct a pan-plastome for F. tartaricum and resolve genomic variation. The complete plastomes of the 513 newly assembled Fagopyrum plastome sizes ranged from 159,253 bp to 159,576 bp with total GC contents ranged from 37.76 to 37.97%. These plastomes all maintained the typical quadripartite structure, consisting of a pair of inverted repeat regions (IRA and IRB) separated by a large single copy region (LSC) and a small single copy region (SSC). Although the structure and gene content of the Fagopyrum plastomes are conserved, numerous nucleotide variations were detected from which population structure could be resolved. The nucleotide variants were most abundant in the non-coding regions of the genome and of those the intergenic regions had the most. Mutational hotspots were primarily found in the LSC regions. The complete 521 Fagopyrum plastomes were divided into five genetic clusters, among which 509 Tartary buckwheat plastomes were divided into three genetic clusters (Ft-I/Ft-II/Ft-III). The genetic diversity in the Tartary buckwheat genetic clusters was the greatest in Ft-III, and the genetic distance between Ft-I and Ft-II was the largest. Based on the results of population structure and genetic diversity analysis, Ft-III was further subdivided into three subgroups Ft-IIIa, Ft-IIIb, and Ft-IIIc. Divergence time estimation indicated that the genera Fagopyrum and Rheum (rhubarb) shared a common ancestor about 48 million years ago (mya) and that intraspecies divergence in Tartary buckwheat began around 0.42 mya.

Conclusions

The resolution of pan-plastome diversity in Tartary buckwheat provides an important resource for future projects such as marker-assisted breeding and germplasm preservation.
“Because it eases my Childbirth Plan”: a qualitative study on factors contributing to preferences for caesarean section in Thailand
Authors: Nuampa Sasitara , Ratinthorn Ameporn , Lumbiganon Pisake , Rungreangkulkij Somporn , Rujiraprasert Nilubon , Buaboon Natthapat , Jampathong Nampet , Dumont Alexandre , Hanson Claudia , de Loenzien Myriam , Bohren Meghan A. , Betrán Ana Pilar
Published: April 2023

Background

Although caesarean section (CS) rates have increased rapidly in Thailand, the upward trend is not supported by significant maternal or perinatal health benefits. The appropriate use of CS through QUALIty DECision-making by women and providers (QUALI-DEC project) aims to design and implement a strategy to optimize the use of CS through non-clinical interventions. This study aimed to explore the factors influencing women’s and health professionals’ preferences for CS delivery in Thailand.

Methods

We conducted a formative qualitative study by using semi-structured in-depth interviews with pregnant and postpartum women, and healthcare staff. Purposive sampling was used to recruit participants from eight hospitals across four regions of Thailand. Content analysis was used to develop the main themes.

Results

There were 78 participants, including 27 pregnant and 25 postpartum women, 8 administrators, 13 obstetricians, and 5 interns. We identified three main themes and seven sub-themes of women and healthcare providers’ perceptions on CS: (1) avoiding the negative experiences from vaginal birth (the pain of labor and childbirth, uncertainty during the labor period); (2) CS is a safer mode of birth (guarantees the baby’s safety, a protective shield for doctors); and (3) CS facilitates time management (baby’s destiny at an auspicious time, family’s management, manage my work/time).

Conclusions

Women mentioned negative experiences and beliefs about vaginal delivery, labor pain, and uncertain delivery outcomes as important factors influencing CS preferences. On the other hand, CS is safer for babies and facilitates multiple tasks in women’s lives. From health professionals’ perspectives, CS is the easier and safer method for patients and them. Interventions to reduce unnecessary CS, including QUALI-DEC, should be designed and implemented, taking into consideration the perceptions of both women and healthcare providers.
Challenges of being a maternity service leader during the COVID-19 pandemic: a descriptive analysis of the journey
Authors: Tan Annie , Wilson Alyce N. , Bucknall Tracey , Digby Robin , Vogel Joshua P. , Homer Caroline SE.
Published: April 2023

Background

In Australia, maternity care services provide care for pregnant and postpartum women and their newborns. The COVID-19 pandemic forced these services to quickly adapt and develop policies and procedures for dealing with transmission in health care facilities, as well as work under public health measures to counter its spread within the community. Despite well-documented responses and adaptations by healthcare systems, no studies have examined the experiences of maternity service leaders through the pandemic. This study aimed to explore the experiences of maternity service leaders, to understand their perspectives on what happened in health services and what was required of a leader during the COVID-19 pandemic in one Australian state.

Methods

A longitudinal qualitative study collected data from 11 maternity care leaders during the pandemic in the state of Victoria. Leaders participated in a series of interviews over the 16-month study period, with a total of 57 interviews conducted. An inductive approach to developing codes allowed for semantic coding of the data, then a thematic analysis was conducted to explore patterned meaning across the dataset.

Results

One overarching theme, ‘challenges of being a maternity service leader during the pandemic’, encompassed participant’s experiences. Four sub-themes described the experiences of these leaders: (1) needing to be a rapid decision-maker, (2) needing to adapt and alter services, (3) needing to filter and translate information, and (4) the need to support people. At the beginning of the pandemic, the challenges were most acute with slow guideline development, rapid communications from the government and an urgent need to keep patients and staff safe. Over time, with knowledge and experience, leaders were able to quickly adjust and respond to policy change.

Conclusion

Maternity service leaders played an important role in preparing and adapting services in accordance with government directives and guidelines while also developing strategies tailored to their own health service requirements. These experiences will be invaluable in designing high quality and responsive systems for maternity care in future crises.
Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia
Authors: Cai Yiqing , Chen Xiaomin , Lu Tiange , Yu Zhuoya , Hu Shunfeng , Liu Jiarui , Zhou Xiangxiang , Wang Xin
Published: April 2023

Background

As an essential regulator of type I interferon (IFN) response, TMEM173 participates in immune regulation and cell death induction. In recent studies, activation of TMEM173 has been regarded as a promising strategy for cancer immunotherapy. However, transcriptomic features of TMEM173 in B-cell acute lymphoblastic leukemia (B-ALL) remain elusive.

Methods

Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were applied to determine the mRNA and protein levels of TMEM173 in peripheral blood mononuclear cells (PBMCs). TMEM173 mutation status was assessed by Sanger sequencing. Single-cell RNA sequencing (scRNA-seq) analysis was performed to explore the expression of TMEM173 in different types of bone marrow (BM) cells.

Results

The mRNA and protein levels of TMEM173 were increased in PBMCs from B-ALL patients. Besides, frameshift mutation was presented in TMEM173 sequences of 2 B-ALL patients. ScRNA-seq analysis identified the specific transcriptome profiles of TMEM173 in the BM of high-risk B-ALL patients. Specifically, expression levels of TMEM173 in granulocytes, progenitor cells, mast cells, and plasmacytoid dendritic cells (pDCs) were higher than that in B cells, T cells, natural killer (NK) cells, and dendritic cells (DCs). Subset analysis further revealed that TMEM173 and pyroptosis effector gasdermin D (GSDMD) restrained in precursor-B (pre-B) cells with proliferative features, which expressed nuclear factor kappa-B (NF-κB), CD19, and Bruton’s tyrosine kinase (BTK) during the progression of B-ALL. In addition, TMEM173 was associated with the functional activation of NK cells and DCs in B-ALL.

Conclusions

Our findings provide insights into the transcriptomic features of TMEM173 in the BM of high-risk B-ALL patients. Targeted activation of TMEM173 in specific cells might provide new therapeutic strategies for B-ALL patients.
Expression characteristics and their functional role of IGFBP gene family in pan-cancer
Authors: Liu Yingnan , Shen Shixuan , Yan Ziwei , Yan Lirong , Ding Hanxi , Wang Ang , Xu Qian , Sun Liping , Yuan Yuan
Published: April 2023

Background

Insulin-like growth factor binding proteins (IGFBPs) are critical regulators of the biological activities of insulin-like growth factors. The IGFBP family plays diverse roles in different types of cancer, which we still lack comprehensive and pleiotropic understandings so far.

Methods

Multi-source and multi-dimensional data, extracted from The Cancer Genome Atlas (TCGA), Oncomine, Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA) was used for bioinformatics analysis by R language. Immunohistochemistry and qRT-PCR were performed to validate the results of the database analysis results. Bibliometrics and literature review were used for summarizing the research progress of IGFBPs in the field of tumor.

Results

The members of IGFBP gene family are differentially expressed in various cancer types. IGFBPs expression can affect prognosis of different cancers. The expression of IGFBPs expression is associated with multiple signal transduction pathways. The expression of IGFBPs is significantly correlated with tumor mutational burden, microsatellite instability, tumor stemness and tumor immune microenvironment. The qRT-PCR experiments verified the lower expression of IGFBP2 and IGFBP6 in gastric cancer and the lower expression of IGFBP6 in colorectal cancer. Immunohistochemistry validated a marked downregulation of IGFBP2 protein in gastric cancer tissues. The keywords co-occurrence analysis of IGFBP related publications in cancer showed relative research have been more concentrating on the potential of IGFBPs as tumor diagnostic and prognostic markers and developing cancer therapies.

Conclusions

These findings provide frontier trend of IGFBPs related research and new clues for identifying novel therapeutic targets for various cancers.
Transcriptome profiling of a synergistic volumetric muscle loss repair strategy
Authors: Roberts Kevin , Kim John Taehwan , Huynh Tai , Schluns Jacob , Dunlap Grady , Hestekin Jamie , Wolchok Jeffrey C
Published: April 2023

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in severe functional deficits that have defied clinical repair strategies. In this manuscript we pair the early in vivo functional response induced by differing volumetric muscle loss tissue engineering repair strategies that are broadly representative of those explored by the field (scaffold alone, cells alone, or scaffold + cells) to the transcriptomic response induced by each intervention. We demonstrate that an implant strategy comprising allogeneic decellularized skeletal muscle scaffolds seeded with autologous minced muscle cellular paste (scaffold + cells) mediates a pattern of increased expression for several genes known to play roles in axon guidance and peripheral neuroregeneration, as well as several other key genes related to inflammation, phagocytosis, and extracellular matrix regulation. The upregulation of several key genes in the presence of both implant components suggests a unique synergy between scaffolding and cells in the early period following intervention that is not seen when either scaffolds or cells are used in isolation; a finding that invites further exploration of the interactions that could have a positive impact on the treatment of volumetric muscle loss.
Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder
Authors: Dmochowski Roger R. , Rovner Eric S. , Kennelly Michael J. , Newman Diane K. , Abedinzadeh Laleh , Snyder Daniel , Thomas Elizabeth , Haag-Molkenteller Cornelia , Rosenberg Matt T.
Published: April 2023

Background

Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective β3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence.

Methods

This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence.

Discussion

OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting.

Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.
Protocol for developing a dashboard for interactive cohort analysis of oral health-related data
Authors: Sharma Vinay , Cassetti Oscar , Winning Lewis , O’Sullivan Michael , Crowe Michael
Published: April 2023

Introduction

A working knowledge of data analytics is becoming increasingly important in the digital health era. Interactive dashboards are a useful, accessible format for presenting and disseminating health-related information to a wide audience. However, many oral health researchers receive minimal data visualisation and programming skills.

Objectives

The objective of this protocols paper is to demonstrate the development of an analytical, interactive dashboard, using oral health-related data from multiple national cohort surveys.

Methods

The package was used within the R Studio framework to create the structure-elements of the dashboard and interactivity was added with the package. Data sources derived from the national longitudinal study of children in Ireland and the national children’s food survey. Variables for input were selected based on their known associations with oral health. The data were aggregated using tidyverse packages such as and summarised using and with specific functions created to generate bar-plots and tables.

Results

The dashboard layout is structured by the YAML (YAML Ain’t Markup Language) metadata in the R Markdown document and the syntax from Flexdashboard. Survey type, wave of survey and variable selector were set as filter options. Shiny’s render functions were used to change input to automatically render code and update output. The deployed dashboard is openly accessible at https://dduh.shinyapps.io/dduh/. Examples of how to interact with the dashboard for selected oral health variables are illustrated.

Conclusion

Visualisation of national child cohort data in an interactive dashboard allows viewers to dynamically explore oral health data without requiring multiple plots and tables and sharing of extensive documentation. Dashboard development requires minimal non-standard R coding and can be quickly created with open-source software.
There’s no time for no stress! Exploring the relationship between pharmacy student stress and time use
Authors: Minshew Lana M. , Bensky Hannah P. , Zeeman Jacqueline M.
Published: April 2023

Background

Health professions students experience significantly more stress than students 20 years ago. While prior studies have explored student time use and other studies have begun to explore factors influencing student stress, little is known about the relationship between student time use and stress. As more efforts are employed to promote student wellness and better understand student stress, it is imperative to recognize the implications of time as a finite resource. Thus, it is important to understand if and how time use relates to student stress so the two can be better managed.

Methods

A mixed methods approach exploring the challenge-hindrance stressor framework was used to collect and analyze student stress and time use. First, second, and third year pharmacy students were invited to participate. Participants completed the Perceived Stress Scale (PSS10), a week-long daily time logging activity, and daily stress questionnaire. After the week-long daily time logging, students participated in a semi-structured focus group. Descriptive statistics were used to analyze quantitative data, and inductive coding along with creation of summary reports were created for the qualitative data.

Results

Students reported moderate stress on the PSS10, and spending the majority of their time on activities of daily life and academic activities. Students shared that academics, co-curriculars, and working for pay increased their stress, whereas discretionary activities such as socializing and exercising alleviated stress. Finally, students reported feeling overwhelmed due to too little time to complete all necessary activities daily, including limited time to invest in discretionary activities to support their wellbeing.

Conclusions

Increased stress levels among students is a concerning trend that affects students’ mental health and therefore limits their ability to perform to their greatest potential. Better understanding of the relationship between time use and stress is critical to improve the quality of life of students in the health professions. These findings provide critical insight into factors contributing towards student stress that can inform curricular strategies that support wellness within health professions education.
Submersion and hypoxia inhibit alveolar epithelial Na+ transport through ERK/NF-κB signaling pathway
Authors: Zhou Wei , Hou Yapeng , Yu Tong , Wang Tingyu , Ding Yan , Nie Hongguang
Published: April 2023

Background

Hypoxia is associated with many respiratory diseases, partly due to the accumulation of edema fluid and mucus on the surface of alveolar epithelial cell (AEC), which forms oxygen delivery barriers and is responsible for the disruption of ion transport. Epithelial sodium channel (ENaC) on the apical side of AEC plays a crucial role to maintain the electrochemical gradient of Na+ and water reabsorption, thus becomes the key point for edema fluid removal under hypoxia. Here we sought to explore the effects of hypoxia on ENaC expression and the further mechanism related, which may provide a possible treatment strategy in edema related pulmonary diseases.

Methods

Excess volume of culture medium was added on the surface of AEC to simulate the hypoxic environment of alveoli in the state of pulmonary edema, supported by the evidence of increased hypoxia-inducible factor-1 expression. The protein/mRNA expressions of ENaC were detected, and extracellular signal-regulated kinase (ERK)/nuclear factor κB (NF-κB) inhibitor was applied to explore the detailed mechanism about the effects of hypoxia on epithelial ion transport in AEC. Meanwhile, mice were placed in chambers with normoxic or hypoxic (8%) condition for 24 h, respectively. The effects of hypoxia and NF-κB were assessed through alveolar fluid clearance and ENaC function by Ussing chamber assay.

Results

Hypoxia (submersion culture mode) induced the reduction of protein/mRNA expression of ENaC, whereas increased the activation of ERK/NF-κB signaling pathway in parallel experiments using human A549 and mouse alveolar type 2 cells, respectively. Moreover, the inhibition of ERK (PD98059, 10 µM) alleviated the phosphorylation of IκB and p65, implying NF-κB as a downstream pathway involved with ERK regulation. Intriguingly, the expression of α-ENaC could be reversed by either ERK or NF-κB inhibitor (QNZ, 100 nM) under hypoxia. The alleviation of pulmonary edema was evidenced by the administration of NF-κB inhibitor, and enhancement of ENaC function was supported by recording amiloride-sensitive short-circuit currents.

Conclusions

The expression of ENaC was downregulated under hypoxia induced by submersion culture, which may be mediated by ERK/NF-κB signaling pathway.
Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis
Authors: Runge Manuela , Stahlfeld Anne , Ambrose Monique , Toh Kok Ben , Rahman Semiu , Omoniwa Omowunmi F. , Bever Caitlin A. , Oresanya Olusola , Uhomoibhi Perpetua , Galatas Beatriz , Tibenderana James K. , Gerardin Jaline
Published: April 2023

Background

A recent WHO recommendation for perennial malaria chemoprevention (PMC) encourages countries to adapt dose timing and number to local conditions. However, knowledge gaps on the epidemiological impact of PMC and possible combination with the malaria vaccine RTS,S hinder informed policy decisions in countries where malaria burden in young children remains high.

Methods

The EMOD malaria model was used to predict the impact of PMC with and without RTS,S on clinical and severe malaria cases in children under the age of two years (U2). PMC and RTS,S effect sizes were fit to trial data. PMC was simulated with three to seven doses (PMC-3-7) before the age of eighteen months and RTS,S with three doses, shown to be effective at nine months. Simulations were run for transmission intensities of one to 128 infectious bites per person per year, corresponding to incidences of < 1 to 5500 cases per 1000 population U2. Intervention coverage was either set to 80% or based on 2018 household survey data for Southern Nigeria as a sample use case. The protective efficacy (PE) for clinical and severe cases in children U2 was calculated in comparison to no PMC and no RTS,S.

Results

The projected impact of PMC or RTS,S was greater at moderate to high transmission than at low or very high transmission. Across the simulated transmission levels, PE estimates of PMC-3 at 80% coverage ranged from 5.7 to 8.8% for clinical, and from 6.1 to 13.6% for severe malaria (PE of RTS,S 10–32% and 24.6–27.5% for clinical and severe malaria, respectively. In children U2, PMC with seven doses nearly averted as many cases as RTS,S, while the combination of both was more impactful than either intervention alone. When operational coverage, as seen in Southern Nigeria, increased to a hypothetical target of 80%, cases were reduced beyond the relative increase in coverage.

Conclusions

PMC can substantially reduce clinical and severe cases in the first two years of life in areas with high malaria burden and perennial transmission. A better understanding of the malaria risk profile by age in early childhood and on feasible coverage by age, is needed for selecting an appropriate PMC schedule in a given setting.
Sublobar resection versus lobectomy in the treatment of synchronous multiple primary lung cancer
Authors: Niu Niu , Zhou Liang , Zhao Junjie , Ma Xingjie , Yang Fan , Qi Weibo
Published: April 2023

Objective

Although synchronous multiple primary lung cancers (sMPLCs) are common in clinical practice, the choice of surgical modalities for the main lesion is still at the stage of exploration. This study is designed to analyze the prognosis of sMPLCs and single primary lung cancers with similar tumor stages and to explore whether sublobar resection has a similar prognosis as lobectomy for sMPLCs.

Methods

One-hundred forty-one cases of sMPLCs were selected, including the following: 65 cases underwent lobectomy for main lesions, and 76 cases underwent sublobar resection for main lesions. One thousand one hundred forty-four cases of single primary lung cancer were matched at 1:1 by propensity score matching. Then, the patients with sMPLCs were divided into a lobectomy group and a sublobar group according to the first tumor stage. Ninety-eight cases of patients with sMPLCs were matched. The short-term perioperative effect, 5-year disease-free survival (DFS) rate, and 5-year overall survival (OS) rate between the two groups were compared.

Results

There was no significant difference in OS between sMPLCs and single primary lung cancer after lobectomy (77.1% vs. 77.2%, P = 0.157) and sublobar resection (98.7% vs. 90.7%, P = 0.309). There was no significant difference in OS (86.7% vs. 83.9%, P = 0.482) or DFS (67.6 vs. 87.7%, P = 0.324) between the lobectomy group and sublobar group with sMPLCs. The sublobar resection group obtained a lower incidence of postoperative complications (40.8% vs. 16.3%, P = 0.007) and shorter postoperative hospital stay (11.22 vs. 9.27, P = 0.049).

Conclusion

The prognosis of patients with sMPLCs generally depends on the main tumor state, which has no statistical difference regardless of sublobar resection or lobectomy, and the perioperative period of sublobar resection is safer than that of lobectomy.
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

Caspases 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

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

Background

Most 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.

Methods

This 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.

Results

At 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).

Conclusions

Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue.

Trial registration

ClinicalTrials.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

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

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

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.