bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in p53 proficient colon cancer cells
Authors: Slaninová Věra , Heron-Milhavet Lisa , Robin Mathilde , Jeanson Laura , Aissanou Adam , Kantar Diala , Tosi Diego , Bréhélin Laurent , Gongora Céline , Djiane Alexandre
Published: May 2024

YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the p73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using HCT116 cells, we show here that oxaliplatin treatment led to core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of p73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed antagonistic effects with oxaliplatin in co-treatments. Importantly, using several colorectal cell lines, we show that the sensitizing action of TAZ to oxaliplatin is dependent on the p53 status of the cells. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and p53 activity pushes cells towards apoptosis.
Characteristics and spending patterns of high-cost child patients: findings from Fujian in China
Authors: Peng Xiaobo , Guo Ningning
Published: May 2024

Background

The health condition during childhood has been shown to influence an individual’s health and socioeconomic status in adulthood. Understanding the concentration and persistence patterns in children’s healthcare expenditures is crucial for providing risk protection and promoting the well-being of children. Studies regarding the concentration and persistence of health expenditures have focused mainly on elderly individuals in developed regions. To gain insights into factors that contribute to childhood health expenditures, this article examined children with high costs (that is, in the top 10% of the expenditure distribution) and explored the characteristics and spending patterns that distinguished them from other patients in the context of the largest developing economy—China.

Methods

By using a unique individual-level administrative claims dataset over a 5-year observation period, this study identified spending concentrations and the proportion of children whose costs remained high over five years using a linear probability model and logit regression analysis.

Results

Teenagers from 12 to 17 years old were more likely to persist in the high-cost group than any other age groups in the study. Pediatric complex chronic conditions and other severe health ailments were predictive factors for entry into and persistence in the high-cost category. More than half of the total health expenditures were attributed to children in the top 10% expenditure group. In addition, risk protection and healthcare insurance support for high-cost children was found to be inadequate, particularly for children from low-income families.

Conclusions

Healthcare support for children impacts individual development and family financial status. This study described the characteristics and spending patterns of children patients in the largest developing country. The fact that over half of total expenditures are concentrated toward 10% of patients makes it valuable to consider relevant support for this group, especially for families whose medical costs are higher than income.
Self-determined use of provided powered oral hygiene devices leads to improved gingival health after 1 year: a longitudinal clinical trial
Authors: Deeg I. , Wicht M. J. , Barbe A. G. , Derman S. H. M.
Published: May 2024

Purpose

Our study aimed to evaluate the long-term concordance and acceptance when using powered devices for everyday oral hygiene routine and gingival health in patients showing papillary bleeding.

Patients and methods

Thirty-one participants were recruited at the dental clinic of the University Hospital of Cologne, Germany, over a 6-week duration. At baseline, a standard dental check-up was performed, including oral hygiene indices and documentation of oral hygiene devices used. The study consisted of two consecutive phases: the first (motivational trial) was designed to prove the effectiveness and safety of a microdroplet device and a powered toothbrush compared to dental floss and a manual toothbrush over a period of 4 weeks. The second (observational) phase began with all participants receiving the powered oral homecare devices. Participants were able to use their oral hygiene measures of choice over an unsupervised period of 1 year. All participants were then rescheduled for a routine dental check-up, where oral hygiene indices and oral hygiene devices used were reevaluated.

Results

After 1 year, 93.3% of participants stated they performed interdental cleaning on a regular basis (baseline 60.0%). The percentage using a powered toothbrush increased from 41.9% (baseline) to 90.0% after 1 year. Oral hygiene parameters had improved after both the motivational trial and observational phases compared to baseline (papillary bleeding index p = .000; Rustogi Modified Navy Plaque Index p < .05; Quigley-Hein Index p = .000).

Conclusion

In the long term, participants preferred using powered oral hygiene devices over the gold standard dental floss and manual toothbrush. Improved oral hygiene parameters after 1 year may indicate implementation of newly acquired oral-hygiene skills during the 4-week instruction phase.
Optimizing a mentorship program from the perspective of academic medicine leadership – a qualitative study
Authors: Ren Michael , Choi Dorothy , Chan Chloe , Rana Simrit , Najeeb Umberin , Norris Mireille , Singh Simron , Burns Karen E. A. , Straus Sharon E. , Hawker Gillian , Yu Catherine
Published: May 2024

Background

Effective mentorship is an important contributor to academic success. Given the critical role of leadership in fostering mentorship, this study sought to explore the perspectives of departmental leadership regarding 1) current departmental mentorship processes; and 2) crucial components of a mentorship program that would enhance the effectiveness of mentorship.

Methods

Department Division Directors (DDDs), Vice-Chairs, and Mentorship Facilitators from the Department of Medicine at the University of Toronto Temerty Faculty of Medicine were interviewed between April and December 2021 using a semi-structured guide. Interviews were audio-recorded and transcribed verbatim, then coded. Analysis occurred in 2 steps: 1) codes were organized to identify emergent themes; then 2) the Social Ecological Model (SEM) was applied to interpret the findings.

Results

Nineteen interviews (14 DDDs, 3 Vice-Chairs, and 2 Mentorship Facilitator) were completed. Analysis revealed three themes: (1) a culture of mentorship permeated the department as evidenced by rigorous mentorship processes, divisional mentorship innovations, and faculty that were keen to mentor; (2) barriers to the establishment of effective mentoring relationships existed at 3 levels: departmental, interpersonal (mentee-mentor relationships), and mentee; and (3) strengthening the culture of mentorship could entail scaling up pre-existing mentorship processes and promoting faculty engagement. Application of SEM highlighted critical program features and determined that two components of interventions (creating tools to measure mentorship outcomes and systems for mentor recognition) were potential enablers of success.

Conclusions

Establishing ‘mentorship outcome measures’ can incentivize and maintain relationships. By tangibly delineating departmental expectations for mentorship and creating systems that recognize mentors, these measures can contribute to a culture of mentorship.
Developing a survey to measure nursing students’ knowledge, attitudes and beliefs, influences, and willingness to be involved in Medical Assistance in Dying (MAiD): a mixed method modified e-Delphi study
Authors: Schroeder Jocelyn , Pesut Barbara , Olsen Lise , Oelke Nelly D. , Sharp Helen
Published: May 2024

Background

Medical Assistance in Dying (MAiD) was legalized in Canada in 2016. Canada’s legislation is the first to permit Nurse Practitioners (NP) to serve as independent MAiD assessors and providers. Registered Nurses’ (RN) also have important roles in MAiD that include MAiD care coordination; client and family teaching and support, MAiD procedural quality; healthcare provider and public education; and bereavement care for family. Nurses have a right under the law to conscientious objection to participating in MAiD. Therefore, it is essential to prepare nurses in their entry-level education for the practice implications and moral complexities inherent in this practice. Knowing what nursing students think about MAiD is a critical first step. Therefore, the purpose of this study was to develop a survey to measure nursing students’ knowledge, attitudes and beliefs, influences, and willingness to be involved in MAiD in the Canadian context.

Methods

The design was a mixed-method, modified e-Delphi method that entailed item generation from the literature, item refinement through a 2 round survey of an expert faculty panel, and item validation through a cognitive focus group interview with nursing students. The settings were a University located in an urban area and a College located in a rural area in Western Canada.

Results

During phase 1, a 56-item survey was developed from existing literature that included demographic items and items designed to measure experience with death and dying (including MAiD), education and preparation, attitudes and beliefs, influences on those beliefs, and anticipated future involvement. During phase 2, an expert faculty panel reviewed, modified, and prioritized the items yielding 51 items. During phase 3, a sample of nursing students further evaluated and modified the language in the survey to aid readability and comprehension. The final survey consists of 45 items including 4 case studies.

Discussion

Systematic evaluation of knowledge-to-date coupled with stakeholder perspectives supports robust survey design. This study yielded a survey to assess nursing students’ attitudes toward MAiD in a Canadian context.

Conclusion

The survey is appropriate for use in education and research to measure knowledge and attitudes about MAiD among nurse trainees and can be a helpful step in preparing nursing students for entry-level practice.
Healthcare workers' attitudes toward and factors influencing their acceptance of an annual COVID-19 booster vaccine: a cross-sectional study in Palestine
Authors: Maraqa Beesan , Nazzal Zaher , Baroud Hassan , Douden Mahmoud , El Hamshary Yousef , Jalamneh Tala
Published: May 2024

Background

The emergence of several SARS-CoV-2 variants may necessitate an annual COVID-19 booster vaccine. This study aimed to evaluate healthcare workers' (HCWs) acceptance of a COVID-19 yearly booster vaccine if recommended and its association with their attitudes and burnout levels.

Methods

We used an online self-administered questionnaire to conduct a cross-sectional study of all HCWs in the West Bank and Gaza Strip of Palestine between August and September 2022. We used the Vaccination Attitudes Examination scale to assess HCWs' vaccination attitudes and the Maslach Burnout Inventory to assess work-related Burnout. In addition, we conducted logistic regression to identify factors independently associated with the acceptance of the booster vaccine.

Results

The study included 919 HCWs; 52.4% were male, 46.5% were physicians, 30.0% were nurses, and 63.1% worked in hospitals. One-third of HCWs (95% CI: 30.5%-36.7%) said they would accept an annual COVID-19 booster vaccine if recommended. HCWs who are suspicious of vaccine benefits [aOR = .70; 95%CI: .65-.75] and those concerned about unforeseeable future effects [aOR = .90; 95%CI: .84-.95] are less likely to accept the booster vaccine if recommended, whereas those who receive annual influenza vaccine are more likely to get it [aOR = 2.9; 95%CI: 1.7–5.0].

Conclusion

Only about a third of HCWs would agree to receive an annual COVID-19 booster vaccine if recommended. Mistrust of the vaccine's efficacy and concerns about side effects continue to drive COVID-19 vaccine reluctance. Health officials need to address HCWs' concerns to increase their acceptance of the annual vaccine if it is to be recommended.
Machine-learning developed an iron, copper, and sulfur-metabolism associated signature predicts lung adenocarcinoma prognosis and therapy response
Authors: Zhang Liangyu , Zhang Xun , Guan Maohao , Zeng Jianshen , Yu Fengqiang , Lai Fancai
Published: May 2024

Background

Previous studies have largely neglected the role of sulfur metabolism in LUAD, and no study has combine iron, copper, and sulfur-metabolism associated genes together to create prognostic signatures.

Methods

This study encompasses 1564 LUAD patients, 1249 NSCLC patients, and over 10,000 patients with various cancer types from diverse cohorts. We employed the R package ConsensusClusterPlus to separate patients into different ICSM (Iron, Copper, and Sulfur-Metabolism) subtypes. Various machine-learning methods were utilized to develop the ICSMI. Enrichment analyses were conducted using ClusterProfiler and GSVA, while IOBR quantified immune cell infiltration. GISTIC2.0 and maftools were utilized for CNV and SNV data analysis. The Oncopredict package predicted drug information based on GDSC1. TIDE algorithm and cohorts GSE91061 and IMvigor210 evaluated patient response to immunotherapy. Single-cell data was processed using the Seurat package, AUCell package calculated cells geneset activity scores, and the Scissor algorithm identified ICSMI-associated cells. In vitro experiments was conducted to explore the role of ICSMRGs in LUAD.

Results

Unsupervised clustering identified two distinct ICSM subtypes of LUAD, each with unique clinical characteristics. The ICSMI, comprising 10 genes, was constructed using integrated machine-learning methods. Its prognostic power was validated in 10 independent datasets, revealing that LUAD patients with higher ICSMI levels had poorer prognoses. Furthermore, ICSMI demonstrated superior predictive abilities compared to 102 previously published signatures. A nomogram incorporating ICSMI and clinical features exhibited high predictive performance. ICSMI positively correlated with patients gene mutations, and integrated analysis of bulk and single-cell transcriptome data revealed its association with TME modulators. Cells representing the high-ICSMI phenotype exhibited more malignant features. LUAD patients with high ICSMI levels exhibited sensitivity to chemotherapy and targeted therapy but displayed resistance to immunotherapy. In a comprehensive analysis across various cancers, ICSMI retained significant prognostic value and emerged as a risk factor for the majority of cancer patients.

Conclusions

ICSMI provides critical prognostic insights for LUAD patients, offering valuable insights into the tumor microenvironment and predicting treatment responsiveness.
Development and application of the Meal and Snack Assessment (MESA) quality scale for children and adolescents using item response theory
Authors: Lemke Stella , de Andrade Dalton Francisco , de Fragas Hinnig Patrícia , da Silva Silvio Aparecido , Vincenzi Silvana Ligia , Roberto Denise Miguel Teixeira , Lobo Adriana Soares , Vieira Francilene Gracieli Kunradi , Di Pietro Patricia Faria , de Assis Maria Alice Altenburg
Published: May 2024

Background

Meals differ in terms of food items and nutritional quality. The aim of the present study was to propose a scale to measure the meals quality of schoolchildren according to food processing degree, perform a preliminary evaluation of the scale's validity and reliability and apply the scale to a representative sample of schoolchildren in a city in southern Brazil.

Methods

A methodological study based on the generalized graded unfolding model (GGUM) of item response theory (IRT) with analysis of secondary data was carried out in 6,399 schoolchildren of 6-15y-old attending 2nd to 5th grades of public elementary schools in Florianópolis, Brazil, in 2013–2015 who answered the validated Food Intake and Physical Activities of Schoolchildren (WebCAAFE) questionnaire. Meal quality was the latent trait. The steps for the development of the scale included: latent trait definition; item generation; dimensionality analysis; estimation of item parameters; scale levels definition; assessment of validity and reliability; and assessment of the meal quality of a subsample of schoolchildren aged 7 to 12 years (n = 6,372).

Results

Eleven out of eighteen items had adequate parameters, without differential item functioning for sex or age. Meal quality was categorized into three levels: healthy, mixed, and unhealthy. Higher scores indicate a greater prevalence of ultra-processed foods in daily meals. Most schoolchildren had mixed (40.6%) and unhealthy (41%) meal patterns.

Conclusions

IRT analysis allowed the development of the scale, which measures the quality of meals and snacks based on the degree of food processing. At all snack times, there was a higher frequency of ultra-processed foods consumption, therefore foods consumed as snacks are a potential focus for nutritional interventions.
Magnetically modified-mitoxantrone mesoporous organosilica drugs: an emergent multimodal nanochemotherapy for breast cancer
Authors: Romaní -Cubells Eva , Martínez-Erro Samuel , Morales Victoria , Chocarro-Calvo Ana , García-Martínez José M. , Sanz Raúl , García-Jiménez Custodia , García-Muñoz Rafael A.
Published: May 2024

Background

Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients’ quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge.

Results

In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs.

Conclusions

A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.
Effect of cytoplasmic fragmentation on embryo development, quality, and pregnancy outcome: a systematic review of the literature
Authors: Yazdani Ariella , Halvaei Iman , Boniface Catherine , Esfandiari Navid
Published: May 2024

The role of cytoplasmic fragmentation in human embryo development and reproductive potential is widely recognized, albeit without standard definition nor agreed upon implication. While fragmentation is best understood to be a natural process across species, the origin of fragmentation remains incompletely understood and likely multifactorial. Several factors including embryo culture condition, gamete quality, aneuploidy, and abnormal cytokinesis seem to have important role in the etiology of cytoplasmic fragmentation. Fragmentation reduces the volume of cytoplasm and depletes embryo of essential organelles and regulatory proteins, compromising the developmental potential of the embryo. While it has been shown that degree of fragmentation and embryo implantation potential are inversely proportional, the degree, pattern, and distribution of fragmentation as it relates to pregnancy outcome is debated in the literature. This review highlights some of the challenges in analysis of fragmentation, while revealing trends in our evolving knowledge of how fragmentation may relate to functional development of the human embryos, implantation, and pregnancy outcome.
Research outcomes informing the selection of public health interventions and strategies to implement them: A cross-sectional survey of Australian policy-maker and practitioner preferences
Authors: Wolfenden Luke , Hall Alix , Bauman Adrian , Milat Andrew , Hodder Rebecca , Webb Emily , Mooney Kaitlin , Yoong Serene , Sutherland Rachel , McCrabb Sam
Published: May 2024

Background

A key role of public health policy-makers and practitioners is to ensure beneficial interventions are implemented effectively enough to yield improvements in public health. The use of evidence to guide public health decision-making to achieve this is recommended. However, few studies have examined the relative value, as reported by policy-makers and practitioners, of different broad research outcomes (that is, measures of cost, acceptability, and effectiveness). To guide the conduct of research and better inform public health policy and practice, this study aimed at describing the research outcomes that Australian policy-makers and practitioners consider important for their decision-making when selecting: (a) public health interventions; (b) strategies to support their implementation; and (c) to assess the differences in research outcome preferences between policy-makers and practitioners.

Method

An online value-weighting survey was conducted with Australian public health policy-makers and practitioners working in the field of non-communicable disease prevention. Participants were presented with a list of research outcomes and were asked to select up to five they considered most critical to their decision-making. They then allocated 100 points across these – allocating more points to outcomes perceived as more important. Outcome lists were derived from a review and consolidation of evaluation and outcome frameworks in the fields of public health knowledge translation and implementation. We used descriptive statistics to report relative preferences overall and for policy-makers and practitioners separately.

Results

Of the 186 participants; 90 primarily identified as policy-makers and 96 as public health prevention practitioners. Overall, research outcomes of effectiveness, equity, feasibility, and sustainability were identified as the four most important outcomes when considering either interventions or strategies to implement them. Scores were similar for most outcomes between policy-makers and practitioners.

Conclusion

For Australian policy-makers and practitioners working in the field of non-communicable disease prevention, outcomes related to effectiveness, equity, feasibility, and sustainability appear particularly important to their decisions about the interventions they select and the strategies they employ to implement them. The findings suggest researchers should seek to meet these information needs and prioritize the inclusion of such outcomes in their research and dissemination activities. The extent to which these outcomes are critical to informing the decision of policy-makers and practitioners working in other jurisdictions or contexts warrants further investigation.
An overview of the perspectives used in health economic evaluations
Authors: Sittimart Manit , Rattanavipapong Waranya , Mirelman Andrew J. , Hung Trinh Manh , Dabak Saudamini , Downey Laura E. , Jit Mark , Teerawattananon Yot , Turner Hugo C.
Published: May 2024

The term ‘perspective’ in the context of economic evaluations and costing studies in healthcare refers to the viewpoint that an analyst has adopted to define the types of costs and outcomes to consider in their studies. However, there are currently notable variations in terms of methodological recommendations, definitions, and applications of different perspectives, depending on the objective or intended user of the study. This can make it a complex area for stakeholders when interpreting these studies. Consequently, there is a need for a comprehensive overview regarding the different types of perspectives employed in such analyses, along with the corresponding implications of their use. This is particularly important, in the context of low-and-middle-income countries (LMICs), where practical guidelines may be less well-established and infrastructure for conducting economic evaluations may be more limited. This article addresses this gap by summarising the main types of perspectives commonly found in the literature to a broad audience (namely the patient, payer, health care providers, healthcare sector, health system, and societal perspectives), providing their most established definitions and outlining the corresponding implications of their uses in health economic studies, with examples particularly from LMIC settings. We then discuss important considerations when selecting the perspective and present key arguments to consider when deciding whether the societal perspective should be used. We conclude that there is no one-size-fits-all answer to what perspective should be used and the perspective chosen will be influenced by the context, policymakers'/stakeholders’ viewpoints, resource/data availability, and intended use of the analysis. Moving forward, considering the ongoing issues regarding the variation in terminology and practice in this area, we urge that more standardised definitions of the different perspectives and the boundaries between them are further developed to support future studies and guidelines, as well as to improve the interpretation and comparison of health economic evidence.
Single-cell and spatial transcriptomic investigation reveals the spatiotemporal specificity of the beta-defensin gene family during mouse sperm maturation
Authors: Zhang Guoliang , Sun Yuanchao , Guan Minkai , Liu Mengmeng , Sun Shiduo
Published: May 2024

Low sperm motility is a significant contributor to male infertility. beta-defensins have been implicated in host defence and the acquisition of sperm motility; however, the regulatory mechanisms governing their gene expression patterns and functions remain poorly understood. In this study, we performed single-cell RNA and spatial transcriptome sequencing to investigate the cellular composition of testicular and epididymal tissues and examined their gene expression characteristics. In the epididymis, we found that epididymal epithelial cells display a region specificity of gene expression in different epididymal segments, including the beta-defensin family genes. In particular, Defb15, Defb18, Defb20, Defb25 and Defb48 are specific to the caput; Defb22, Defb23 and Defb26 to the corpus; Defb2 and Defb9 to the cauda of the epididymis. To confirm this, we performed mRNA fluorescence in situ hybridisation (FISH) targeting certain exon region of beta-defensin genes, and found some of their expression matched the sequencing results and displayed a close connection with epididimosome marker gene Cd63. In addition, we paid attention to the Sertoli cells and Leydig cells in the testis, along with fibroblasts and smooth muscle cells in the epididymis, by demonstrating their gene expression profile and spatial information. Our study provides a single-cell and spatial landscape for analysing the gene expression characteristics of testicular and epididymal environments and has important implications for the study of spermatogenesis and sperm maturation.
Clinical manifestations, prognostic factors, and outcomes of adenovirus pneumonia after allogeneic hematopoietic stem cell transplantation
Authors: Wang Yuewen , Zhang Xiaohui , Xu Lanping , Wang Yu , Yan Chenhua , Chen Huan , Chen Yuhong , Wei Fangfang , Han Wei , Wang Fengrong , Wang Jingzhi , Huang Xiaojun , Mo Xiaodong
Published: May 2024

Background

Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT.

Methods

Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan–Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses.

Results

The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17–609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia.

Conclusions

We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.
Shikonin reduces M2 macrophage population in ovarian cancer by repressing exosome production and the exosomal galectin 3-mediated β-catenin activation
Authors: Wang Min , Sun Yangyan , Gu Rui , Tang Yan , Han Guorong , Zhao Shaojie
Published: May 2024

Background

Shikonin (SK), a naphthoquinone with anti-tumor effects, has been found to decrease production of tumor-associated exosomes (exo). This study aims to verify the treatment effect of SK on ovarian cancer (OC) cells, especially on the production of exo and their subsequent effect on macrophage polarization.

Methods

OC cells SKOV3 and A2780 were treated with SK. The exo were isolated from OC cells with or without SK treatment, termed OC exo and SK OC exo, respectively. These exo were used to treat PMA-induced THP-1 cells (M0 macrophages). M2 polarization of macrophages was determined by measuring the M2 specific cell surface markers CD163 and CD206 as well as the secretion of M2 cytokine IL-10. The functions of galectin 3 (LGALS3/GAL3) and β-catenin in macrophage polarization were determined by gain- or loss-of-function assays. CB-17 SCID mice were subcutaneously injected with SKOV3 cells to generate xenograft tumors, followed by OC exo or SK OC exo treatment for in vivo experiments.

Results

SK suppressed viability, migration and invasion, and apoptosis resistance of OC cells in vitro. Compared to OC exo, SK OC exo reduced the M2 polarization of macrophages. Regarding the mechanism, SK reduced exo production in cancer cells, and it decreased the protein level of GAL3 in exo and recipient macrophages, leading to decreased β-catenin activation. M2 polarization of macrophages was restored by LGALS3 overexpression but decreased again by the β-catenin inhibitor FH535. Compared to OC exo, the SK OC exo treatment reduced the xenograft tumor growth in mice, and it decreased the M2 macrophage infiltration within tumor tissues.

Conclusion

This study suggests that SK reduces M2 macrophage population in OC by repressing exo production and blocking exosomal GAL3-mediated β-catenin activation.
The landscape of rare genetic variation associated with inflammatory bowel disease and Parkinson’s disease comorbidity
Authors: Kars Meltem Ece , Wu Yiming , Stenson Peter D. , Cooper David N. , Burisch Johan , Peter Inga , Itan Yuval
Published: May 2024

Background

Inflammatory bowel disease (IBD) and Parkinson’s disease (PD) are chronic disorders that have been suggested to share common pathophysiological processes. LRRK2 has been implicated as playing a role in both diseases. Exploring the genetic basis of the IBD-PD comorbidity through studying high-impact rare genetic variants can facilitate the identification of the novel shared genetic factors underlying this comorbidity.

Methods

We analyzed whole exomes from the BioMe BioBank and UK Biobank, and whole genomes from a cohort of 67 European patients diagnosed with both IBD and PD to examine the effects of LRRK2 missense variants on IBD, PD and their co-occurrence (IBD-PD). We performed optimized sequence kernel association test (SKAT-O) and network-based heterogeneity clustering (NHC) analyses using high-impact rare variants in the IBD-PD cohort to identify novel candidate genes, which we further prioritized by biological relatedness approaches. We conducted phenome-wide association studies (PheWAS) employing BioMe BioBank and UK Biobank whole exomes to estimate the genetic relevance of the 14 prioritized genes to IBD-PD.

Results

The analysis of LRRK2 missense variants revealed significant associations of the G2019S and N2081D variants with IBD-PD in addition to several other variants as potential contributors to increased or decreased IBD-PD risk. SKAT-O identified two significant genes, LRRK2 and IL10RA, and NHC identified 6 significant gene clusters that are biologically relevant to IBD-PD. We observed prominent overlaps between the enriched pathways in the known IBD, PD, and candidate IBD-PD gene sets. Additionally, we detected significantly enriched pathways unique to the IBD-PD, including MAPK signaling, LPS/IL-1 mediated inhibition of RXR function, and NAD signaling. Fourteen final candidate IBD-PD genes were prioritized by biological relatedness methods. The biological importance scores estimated by protein–protein interaction networks and pathway and ontology enrichment analyses indicated the involvement of genes related to immunity, inflammation, and autophagy in IBD-PD. Additionally, PheWAS provided support for the associations of candidate genes with IBD and PD.

Conclusions

Our study confirms and uncovers new LRRK2 associations in IBD-PD. The identification of novel inflammation and autophagy-related genes supports and expands previous findings related to IBD-PD pathogenesis, and underscores the significance of therapeutic interventions for reducing systemic inflammation.
The role of M1/M2 macrophage polarization in primary Sjogren’s syndrome
Authors: Chen Xiaochan , Zhu Linjiang , Wu Huaxiang
Published: May 2024

Background

The purpose of this study was to investigate the role of macrophage polarization in the pathogenesis of primary Sjogren’s syndrome (pSS).

Methods

Peripheral venous blood samples were collected from 30 patients with pSS and 30 healthy controls. Minor salivary gland samples were abtainted from 10 of these patients and 10 non-pSS controls whose minor salivary gland didn’t fulfill the classification criteria for pSS. Enzyme-linked immuno sorbent assay was used to examine the serum concentration of M1/M2 macrophage related cytokines (TNF-a, IL-6, IL-23, IL-4, IL-10 and TGF-β). Flow cytometry was used to examine the numbers of CD86+ M1 macrophages and CD206+ M2 macrophages in peripheral blood mononuclear cells (PBMCs). Immunofluorescence was used to test the infiltration of macrophages in minor salivary glands.

Results

This study observed a significant increase in pSS patients both in the numbers of M1 macrophages in peripheral blood and serum levels of M1-related pro-inflammatory cytokines (IL-6, IL-23 and TNF-α). Conversely, M2 macrophages were downregulated in the peripheral blood of pSS patients. Similarly, in the minor salivary glands of pSS patients, the expression of M1 macrophages was increased, and that of M2 macrophages was decreased. Furthermore, a significantly positive correlation was found between the proportions of M1 macrophages in PBMCs and serum levels of IgG and RF.

Conclusions

This study reveals the presence of an significant imbalance in M1/M2 macrophages in pSS patients. The M1 polarization of macrophages may play an central role in the pathogenesis of pSS.
Unveiling a foreign body masquerading as periarticular calcification: a case report
Authors: Kamalinia Amirhossein , Seifaei Asal , Moein Seyed Arman , Namazi Hamid
Published: May 2024

Introduction

Evaluating isolated extremity discomfort can be challenging when initial imaging and exams provide limited information. Though subtle patient history hints often underlie occult pathologies, benign symptoms are frequently miscategorized as idiopathic.

Case presentation

We present a case of retained glass obscuring as acute calcific periarthritis on imaging. A 48-year-old White male with vague fifth metacarpophalangeal joint pain had unrevealing exams, but radiographs showed periarticular calcification concerning inflammation. Surgical exploration unexpectedly revealed an encapsulated glass fragment eroding bone. Further history uncovered a forgotten glass laceration decade prior. The foreign body was removed, resolving symptoms.

Discussion

This case reveals two imperative diagnostic principles for nonspecific extremity pain: (1) advanced imaging lacks specificity to differentiate inflammatory arthropathies from alternate intra-articular processes such as foreign bodies, and (2) obscure patient history questions unearth causal subtleties that direct accurate diagnosis. Though initial scans suggested acute calcific periarthritis, exhaustive revisiting of the patient’s subtle decade-old glass cut proved pivotal in illuminating the underlying driver of symptoms.

Conclusion

Our findings underscore the critical limitations of imaging and the vital role that meticulous history-taking plays in clarifying ambiguous chronic limb presentations. They spotlight the imperative of probing even distant trauma when symptoms seem disconnected from causative events. This case reinforces the comprehensive evaluation of all subtle patient clues as key in illuminating elusive extremity pain etiologies.
Effect of slip boundary conditions on unsteady pulsatile nanofluid flow through a sinusoidal channel: an analytical study
Authors: Dawood A. S. , Kroush Faisal A. , Abumandour Ramzy M. , Eldesoky Islam M.
Published: May 2024

A novel analysis of the pulsatile nano-blood flow through a sinusoidal wavy channel, emphasizing the significance of diverse influences in the modelling, is investigated in this paper. This study examines the collective effects of slip boundary conditions, magnetic field, porosity, channel waviness, nanoparticle concentration, and heat source on nano-blood flow in a two-dimensional wavy channel. In contrast to prior research that assumed a constant pulsatile pressure gradient during channel waviness, this innovative study introduces a variable pressure gradient that significantly influences several associated parameters. The mathematical model characterising nano-blood flow in a horizontally wavy channel is solved using the perturbation technique. Analytical solutions for fundamental variables such as stream function, velocity, wall shear stress, pressure gradient, and temperature are visually depicted across different physical parameter values. The findings obtained for various parameter values in the given problem demonstrate a significant influence of the amplitude ratio parameter of channel waviness, Hartmann number of the magnetic field, permeability parameter of the porous medium, Knudsen number due to the slip boundary, volume fraction of nanoparticles, radiation parameter, Prandtl number, and heat source parameters on the flow dynamics. The simulations provide valuable insights into the decrease in velocity with increasing magnetic field and its increase with increasing permeability and slip parameters. Additionally, the temperature increases with increasing nanoparticle volume fraction and radiation parameter, while it decreases with increasing Prandtl number.
STAM-LSGRU: a spatiotemporal radar echo extrapolation algorithm with edge computing for short-term forecasting
Authors: Cheng Hailang , Cui Mengmeng , Shi Yuzhe
Published: May 2024

With the advent of Mobile Edge Computing (MEC), shifting data processing from cloud centers to the network edge presents an advanced computational paradigm for addressing latency-sensitive applications. Specifically, in radar systems, the real-time processing and prediction of radar echo data pose significant challenges in dynamic and resource-constrained environments. MEC, by processing data near its source, not only significantly reduces communication latency and enhances bandwidth utilization but also diminishes the necessity of transmitting large volumes of data to the cloud, which is crucial for improving the timeliness and efficiency of radar data processing. To meet this demand, this paper proposes a model that integrates a spatiotemporal Attention Module (STAM) with a Long Short-Term Memory Gated Recurrent Unit (ST-ConvLSGRU) to enhance the accuracy of radar echo prediction while leveraging the advantages of MEC. STAM, by extending the spatiotemporal receptive field of the prediction units, effectively captures key inter-frame motion information, while optimizations to the convolutional structure and loss function further boost the model’s predictive performance. Experimental results demonstrate that our approach significantly improves the accuracy of short-term weather forecasting in a mobile edge computing environment, showcasing an efficient and practical solution for processing radar echo data under dynamic, resource-limited conditions.
Durability of Japanese-earth cob walls subjected to accelerated rain simulation
Authors: Reynolds Emily K. , Muramoto Makoto
Published: May 2024

Earthen materials are increasingly being recognized in architecture for their low embodied energy, recyclability, and hygrothermal properties. However, the common use of manufactured stabilizers, while enhancing weathering resistance, compromises these merits. Japan, known for its typhoons, has used unstabilized earth in construction for centuries, suggesting the viability of this construction material. While architecture around the world attests to its resilience, in-depth research into unstabilized earthen material is limited. This study examines unstabilized earth durability through 90-min accelerated rain simulation tests, totaling over 6500 mm of “rain” exposure on each of twelve test surfaces (eight representing rural Japanese cob-ball construction and four, monolithic cob walls). Surface changes were monitored by 3D scans performed at seven intervals. The test walls were built using two common materials in Japanese earthen wall craft, sourced from the areas of Kashiba and Fukakusa. It was clear from 3D-scan analysis that the base-layer material, Kashiba, is remarkably resistant to weathering. The four monolithic Kashiba test surfaces, constructed on four different foundation types, respectively eroded just 1 mm, 2.6 mm, 3.8 mm, and 3.9 mm. These results corroborate traditional building practices. Thus, our study also underscores the value of incorporating knowledge from vernacular earthen architecture professionals in expediting academic research. Additionally, our results suggest the potential of hose-showerhead tool use for research, and for on-site testing of earthen material erosion levels for material adequacy.
Role of Bacillus subtilis exopolymeric genes in modulating rhizosphere microbiome assembly
Authors: Nishisaka Caroline Sayuri , Ventura João Paulo , Bais Harsh P. , Mendes Rodrigo
Published: May 2024

Background

Bacillus subtilis is well known for promoting plant growth and reducing abiotic and biotic stresses. Mutant gene-defective models can be created to understand important traits associated with rhizosphere fitness. This study aimed to analyze the role of exopolymeric genes in modulating tomato rhizosphere microbiome assembly under a gradient of soil microbiome diversities using the B. subtilis wild-type strain UD1022 and its corresponding mutant strain UD1022eps−TasA, which is defective in exopolysaccharide (EPS) and TasA protein production.

Results

qPCR revealed that the B. subtilis UD1022eps−TasA− strain has a diminished capacity to colonize tomato roots in soils with diluted microbial diversity. The analysis of bacterial β-diversity revealed significant differences in bacterial and fungal community structures following inoculation with either the wild-type or mutant B. subtilis strains. The Verrucomicrobiota, Patescibacteria, and Nitrospirota phyla were more enriched with the wild-type strain inoculation than with the mutant inoculation. Co-occurrence analysis revealed that when the mutant was inoculated in tomato, the rhizosphere microbial community exhibited a lower level of modularity, fewer nodes, and fewer communities compared to communities inoculated with wild-type B. subtilis.

Conclusion

This study advances our understanding of the EPS and TasA genes, which are not only important for root colonization but also play a significant role in shaping rhizosphere microbiome assembly. Future research should concentrate on specific microbiome genetic traits and their implications for rhizosphere colonization, coupled with rhizosphere microbiome modulation. These efforts will be crucial for optimizing PGPR-based approaches in agriculture.