bluuebunny/crossref_metadata_2025 huggingface dataset:
Galectin-1 promotes angiogenesis and chondrogenesis during antler regeneration
Authors: Li Xunsheng , Shi Wanwan , Wei Guanning , Lv Jinpeng , Wang Datao , Xing Baorui , Zhou Jue , Zhao Jianwei , Sun Hongmei
Published: May 2023

Background

Deer antlers are the only known mammalian structure that undergoes full regeneration. In addition, it is peculiar because when growing, it contains vascularized cartilage. The differentiation of antler stem cells (ASCs) into chondrocytes while inducing endochondral extension of blood vessels is necessary to form antler vascularized cartilage. Therefore, antlers provide an unparalleled opportunity to investigate chondrogenesis, angiogenesis, and regenerative medicine. A study found that Galectin-1 (GAL-1), which can be used as a marker in some tumors, is highly expressed in ASCs. This intrigued us to investigate what role GAL-1 could play in antler regeneration.

Methods

We measured the expression level of GAL-1 in antler tissues and cells by immunohistochemistry, WB and QPCR. We constructed antlerogenic periosteal cells (APCs, one cell type of ASCs) with the GAL-1 gene knocked out (APCGAL-1−/−) using CRISPR-CAS9 gene editing system. The effect of GAL-1 on angiogenesis was determined by stimulating human umbilical vein endothelial cells (HUVECs) using APCGAL-1−/− conditioned medium or adding exogenous deer GAL-1 protein. The effect of APCGAL-1−/− on chondrogenic differentiation was evaluated compared with the APCs under micro-mass culture. The gene expression pattern of APCGAL-1−/− was analyzed by transcriptome sequencing.

Results

Immunohistochemistry revealed that GAL-1 was widely expressed in the antlerogenic periosteum (AP), pedicle periosteum (PP) and antler growth center. Western blot and qRT-PCR analysis using deer cell lines further supports this result. The proliferation, migration, and tube formation assays of human umbilical vein endothelial cells (HUVECs) showed that the proangiogenic activity of APCGAL-1−/− medium was significantly decreased (P < 0.05) compared with the APCs medium. The proangiogenic activity of deer GAL-1 protein was further confirmed by adding exogenous deer GAL-1 protein (P < 0.05). The chondrogenic differentiation ability of APCGAL-1−/− was impeded under micro-mass culture. The terms of GO and KEGG enrichment of the differentially expressed genes (DEGs) of APCGAL-1−/− showed that down-regulated expression of pathways associated with deer antler angiogenesis, osteogenesis and stem cell pluripotency, such as the PI3K-AKT signaling pathway, signaling pathways regulating pluripotency of stem cells and TGF-β signaling pathway.

Conclusions

Deer GAL-1, has strong angiogenic activity, is widely and highly expressed in deer antler. The APCs can induce angiogenesis by secreting GAL-1. The knockout of GAL-1 gene of APCs damaged its ability to induce angiogenesis and differentiate into chondrocytes. This ability is crucial to the formation of deer antler vascularized cartilage. Moreover, Deer antlers offer a unique model to explore explore how angiogenesis at high levels of GAL-1 expression can be elegantly regulated without becoming cancerous.

Graphical Abstract
Effects of anesthetic depth on perioperative T lymphocyte subsets in patients undergoing laparoscopic colorectal cancer surgery: a prospective, parallel-controlled randomized trial
Authors: Li Han , Li Jiachi , Hao Conghui , Luan Hengfei , Zhang Xiaobao , Zhao Zhibin
Published: May 2023

Background

During the perioperative period, the surgical stress response induced by surgical trauma tends to cause a decrease in peripheral lymphocytes. Anesthetics could reduce the stress response during surgery and prevent sympathetic nerve overexcitation. The goal of this study was to investigate how BIS-guided anesthetic depth affected peripheral T lymphocytes in patients undergoing laparoscopic colorectal cancer surgery.

Methods

A total of 60 patients having elective laparoscopic colorectal cancer surgery were randomly assigned and analyzed (n = 30 for deep general anesthesia, BIS 35, n = 30 for light general anesthesia, BIS 55). Blood samples were collected immediately before anesthesia induction and immediately after operation, 24 h and 5 days postoperatively. The CD4+/CD8 + ratio, T lymphocyte subsets (including CD3 + T cells, CD4 + T cells, and CD8 + T cells), and natural killer (NK) cells were analyzed by flow cytometry. Serum interleukin-6 (IL-6), interferon -ɣ (IFN-ɣ), and vascular endothelial growth factor-α (VEGF-α) were also measured.

Results

The CD4+/CD8 + ratio decreased 24 h after surgery in two groups, but the reduction did not differ between the two groups (P > 0.05). The concentration of IL-6 and the numerical rating scale (NRS) score in the BIS 55 group were significantly higher than that in the BIS 35 group 24 h after surgery (P = 0.001). There were no intergroup differences in CD3 + T cells, CD4 + T cells, CD8 + T cells, NK cells, VEGF-α, or the IFN-ɣ. Statistical analyses showed no differences between the two groups in the incidence of fever and surgical site infection during hospitalization.

Conclusions

Despite the fact that patients in deep general anesthesia group had low levels of the IL-6 24 h after surgery, the deep general anesthesia was not associated to a positive effect on patients’ peripheral T lymphocytes during colorectal cancer surgery. We found no evidence that peripheral T lymphocyte subsets and natural killer cells were affected by the targeting a BIS of either 55 or 35 in patients undergoing laparoscopic colorectal cancer surgery in this trial.

Trial registration

ChiCTR2200056624 (www.chictr.org.cn).
Characteristics and key differences between patient populations receiving imaging modalities for coronary artery disease diagnosis in the US
Authors: Pelletier-Galarneau Matthieu , Vandenbroucke Emily , Lu Minyi , Li Olivia
Published: May 2023

Background

There are limited data on the impact of imaging modality selection for the assessment of coronary artery disease (CAD) risk on downstream resource utilisation. This study sought to identify differences between patient populations in the US undergoing stress echocardiography, single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), positron emission tomography (PET) MPI, and coronary computed tomography angiography (cCTA) for the assessment of CAD risk, and associated physician referral patterns.

Methods

Claims and electronic health records data for 2.5 million US patients who received stress echocardiography, cCTA, SPECT MPI or PET MPI between January 2016 and March 2018, from the Decision Resources Group Real-World Evidence US Data Repository, were analysed. Patients were stratified into suspected and existing CAD cohorts, and further stratified by pre-test risk and presence and recency of interventions or acute cardiac events (within 1–2 years pre-index test). Linear and logistic regression were used to compare numeric and categorical variables.

Results

Physicians were more likely to refer patients to standalone SPECT MPI (77%) and stress echocardiography (18%) than PET MPI (3%) and cCTA (2%). Overall, 43% of physicians referred more than 90% of their patients to standalone SPECT MPI. Just 3%, 1% and 1% of physicians referred more than 90% of their patients to stress echocardiography, PET MPI or cCTA. At the aggregated imaging level, patients who underwent stress echocardiography or cCTA had similar comorbidity profiles. Comorbidity profiles were also similar for patients who underwent SPECT MPI and PET MPI.

Conclusion

Most patients underwent SPECT MPI at the index date, with very few undergoing PET MPI or cCTA. Patients who underwent cCTA at the index date were more likely to undergo additional imaging tests compared with those who underwent other imaging modalities. Further evidence is needed to understand factors influencing imaging test selection across patient populations.
The Trial within Cohorts (TwiCs) study design in oncology: experience and methodological reflections
Authors: Kessels Rob , May Anne M. , Koopman Miriam , Roes Kit C. B.
Published: May 2023

A Trial within Cohorts (TwiCs) study design is a trial design that uses the infrastructure of an observational cohort study to initiate a randomized trial. Upon cohort enrollment, the participants provide consent for being randomized in future studies without being informed. Once a new treatment is available, eligible cohort participants are randomly assigned to the treatment or standard of care. Patients randomized to the treatment arm are offered the new treatment, which they can choose to refuse. Patients who refuse will receive standard of care instead. Patients randomized to the standard of care arm receive no information about the trial and continue receiving standard of care as part of the cohort study. Standard cohort measures are used for outcome comparisons. The TwiCs study design aims to overcome some issues encountered in standard Randomized Controlled Trials (RCTs). An example of an issue in standard RCTs is the slow patient accrual. A TwiCs study aims to improve this by selecting patients using a cohort and only offering the intervention to patients in the intervention arm. In oncology, the TwiCs study design has gained increasing interest during the last decade. Despite its potential advantages over RCTs, the TwiCs study design has several methodological challenges that need careful consideration when planning a TwiCs study. In this article, we focus on these challenges and reflect on them using experiences from TwiCs studies initiated in oncology. Important methodological challenges that are discussed are the timing of randomization, the issue of non-compliance (refusal) after randomization in the intervention arm, and the definition of the intention-to-treat effect in a TwiCs study and how this effect is related to its counterpart in standard RCTs.
Exploring barriers to and facilitators of the implementation of home rehabilitation care for older adults with disabilities using the Consolidated Framework for Implementation Research (CFIR)
Authors: Wang Haixia , Zhang Yanyan , Yue Shouwei
Published: May 2023

Background

With global aging on the rise, the number of older adults with disabilities was also increasing exponentially. There has been growing international interest in home rehabilitation care as a new method for older adults with disabilities.

Method

The current study is a descriptive qualitative study. Guided by the Consolidated Framework for Implementation Research (CFIR), semistructured face-to-face interviews were performed to collect data. The interview data were analyzed using a qualitative content analysis method.

Result

Sixteen nurses with different characteristics from 16 cities participated in the interviews. The findings highlighted 29 implementation determinants of home-based rehabilitation care for older adults with disabilities, including 16 barriers, and 13 facilitators. These influencing factors aligned with all four CFIR domains that were used to guide the analysis and 15 of the 26 CFIR constructs. More barriers were identified in the CFIR domain of characteristics of individuals, intervention characteristics, and the outer setting, while fewer barriers were identified in the inner setting.

Conclusion

Nurses from the rehabilitation department reported many barriers related to the implementation of home rehabilitation care. They reported facilitators to the implementation of home rehabilitation care despite the barriers, which provided practical recommendations for directions to be explored by researchers in China and elsewhere.
ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer
Authors: Yao Litong , Li Yuwei , Li Siyuan , Wang Mozhi , Cao Hongyi , Xu Ling , Xu Yingying
Published: May 2023

Background

Current studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer.

Methods

ARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan–Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB).

Results

ARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score.

Conclusions

Our findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration.
Post-traumatic stress disorder and its associated factors among survivors of 2015 earthquake in Nepal
Authors: Acharya Pandey Radha , Chalise Pratibha , Khadka Sunita , Chaulagain Bina , Maharjan Binu , Pandey Jyotsna , Nepal Jyoti , Pandey Chandranshu
Published: May 2023

Background

Natural disasters cause long term psychological consequences, especially post-traumatic stress disorders. It has been regarded as the most prevalent of psychiatric disorders after a natural disaster. The purpose of this study is to estimate the prevalence of Post-Traumatic Stress Disorder (PTSD) and determine its associated factors in adult survivors three years after the 2015 Nepal earthquake.

Methods

A cross-sectional descriptive design was used where 1076 adults within the age range of 19–65 were randomly selected and interviewed from four adversely affected districts due to the 2015 earthquake. Instruments included a demographic questionnaire, an earthquake exposure questionnaire, the Oslo Social Support Scale (OSSS), and the Post-traumatic Stress Disorder Checklist-Civilian Version (PCL-C). Descriptive and inferential statistics were applied using Statistical Package for Social Science (SPSS) Version 16 for data analysis.

Results

The prevalence of PTSD among earthquake survivors was 18.9%. The multivariate logistic regression showed that gender, ethnicity, education, occupation, social support and severity of damage to house and property were significantly associated with PTSD. Odds of having PTSD was 1.6 times higher among females (AOR = 1.6, 95% CI: 1.1–2.3) and nearly 2 times higher amongst illiterate survivors (AOR = 1.9, 95% CI: 1.2–2.8). Participants from the Janajati ethnic group and those who had a business occupation had a 50% lower risk of having PTSD. Around 39% of the participants had moderate social support and had 60% lower odds of having PTSD compared to those with poor social support (AOR = 0.4, 95%CI: 0.2–0.5, p < 0.001). Participants with medium and very high-level damage to personal property were more likely to have PTSD.

Conclusion

Post-traumatic stress disorder remained prevalent amongst survivors three years after the 2015 Nepal Earthquake. It is important to provide psychological and social support for survivors to decrease the health burden from PTSD. Socio-demographic characteristics such as females, farmers, those survivors who endured significant personal property damage were at higher risk.
Prevalence of cardiovascular disease among Asian, Pacific Islander and multi-race populations in Hawai’i and California
Authors: Waitzfelder Beth , Palaniappan Latha , Varga Alexandra , Frankland Timothy B. , Li Jiang , Daida Yihe G. , Kaholokula Joseph Keawe’aimoku , Bacong Adrian Matias , Rawlings Andreea M. , Chung Sukyung , Howick Connor , Fortmann Stephen P.
Published: May 2023

Background

Cardiovascular disease (CVD) remains the leading cause of death in the US. CVD incidence is influenced by many demographic, clinical, cultural, and psychosocial factors, including race and ethnicity. Despite recent research, there remain limitations on understanding CVD health among Asians and Pacific Islanders (APIs), particularly some subgroups and multi-racial populations. Combining diverse API populations into one study group and difficulties in defining API subpopulations and multi-race individuals have hampered efforts to identify and address health disparities in these growing populations.

Methods

The study cohort was comprised of all adult patients at Kaiser Permanente Hawai’i and Palo Alto Medical Foundation in California during 2014–2018 (n = 684,363). EHR-recorded ICD-9 and ICD-10 diagnosis codes were used to indicate coronary heart disease (CHD), stroke, peripheral vascular disease (PVD), and overall CVD. Self-reported race and ethnicity data were used to construct 12 mutually exclusive single and multi-race groups, and a Non-Hispanic White (NHW) comparison group. Logistic regression models were used to derive prevalence estimates, odds ratios, and confidence intervals for the 12 race/ethnicity groups.

Results

The prevalence of CHD and PVD varied 4-fold and stroke and overall CVD prevalence varied 3-fold across API subpopulations. Among Asians, the Filipino subgroup had the highest prevalence of all three CVD conditions and overall CVD. Chinese people had the lowest prevalence of CHD, PVD and overall CVD. In comparison to Native Hawaiians, Other Pacific Islanders had significantly higher prevalence of CHD. For the multi-race groups that included Native Hawaiians and Other Pacific Islanders, the prevalence of overall CVD was significantly higher than that for either single-race Native Hawaiians or Other Pacific Islanders. The multi-race Asian + White group had significantly higher overall CVD prevalence than both the NHW group and the highest Asian subgroup (Filipinos).

Conclusions

Study findings revealed significant differences in overall CVD, CHD, stroke, and PVD among API subgroups. In addition to elevated risk among Filipino, Native Hawaiian, and Other Pacific Islander groups, the study identified particularly elevated risk among multi-race API groups. Differences in disease prevalence are likely mirrored in other cardiometabolic conditions, supporting the need to disaggregate API subgroups in health research.
Research article Individual innovation from the perspective of nursing students: A qualitative study
Authors: Heydari Naval , Rakhshan Mahnaz , Torabizadeh Camellia , Salimi Ghasem
Published: May 2023

Background

One of the necessities of today’s world that prepares nursing students for their future professional roles is the concept of individual innovation. However, there is no clear definition of individual innovation in nursing. This study was designed and implemented with the aim of investigating the concept of individual innovation from the perspective of nursing students using qualitative content analysis.

Methods

This qualitative study was conducted from September 2020 to May 2021 on 11 nursing students of one of the nursing schools in southern Iran. The participants were selected by purposive sampling method. Data were collected through semi-structured individual interviews. Data analysis was done using conventional content analysis and MAXQDA 2018.

Results

Following data analysis, 662 initial codes were extracted forming 9 categories and three main themes. The themes included personal and professional dynamism, professional inventiveness, and the integration of innovation drivers.

Conclusions

The concept of individual innovation in the nursing student included personal and professional dynamics and professional inventiveness. Individual innovation occurred through combination of innovation drivers. Managers and policy makers of nursing education can use the results of this to get acquainted with this concept and develop policies and guidelines to develop nursing students’ individual innovation. Through getting familiar with the concept of individual innovation, nursing students can try to flourish this characteristic in themselves.
Massive expansion of sex-specific SNPs, transposon-related elements, and neocentromere formation shape the young W-chromosome from the mosquitofish Gambusia affinis
Authors: Müller Stefan , Du Kang , Guiguen Yann , Pichler Maria , Nakagawa Shinichi , Stöck Matthias , Schartl Manfred , Lamatsch Dunja K.
Published: May 2023

Background

The Western mosquitofish, Gambusia affinis, is a model for sex chromosome organization and evolution of female heterogamety. We previously identified a G. affinis female-specific marker, orthologous to the aminomethyl transferase (amt) gene of the related platyfish (Xiphophorus maculatus). Here, we have analyzed the structure and differentiation of the G. affinis W-chromosome, using a cytogenomics and bioinformatics approach.

Results

The long arm of the G. affinis W-chromosome (Wq) is highly enriched in dispersed repetitive sequences, but neither heterochromatic nor epigenetically silenced by hypermethylation. In line with this, Wq sequences are highly transcribed, including an active nucleolus organizing region (NOR). Female-specific SNPs and evolutionary young transposable elements were highly enriched and dispersed along the W-chromosome long arm, suggesting constrained recombination. Wq copy number expanded elements also include female-specific transcribed sequences from the amt locus with homology to TE. Collectively, the G. affinis W-chromosome is actively differentiating by sex-specific copy number expansion of transcribed TE-related elements, but not (yet) by extensive sequence divergence or gene decay.

Conclusions

The G. affinis W-chromosome exhibits characteristic genomic properties of an evolutionary young sex chromosome. Strikingly, the observed sex-specific changes in the genomic landscape are confined to the W long arm, which is separated from the rest of the W-chromosome by a neocentromere acquired during sex chromosome evolution and may thus have become functionally insulated. In contrast, W short arm sequences were apparently shielded from repeat-driven differentiation, retained Z-chromosome like genomic features, and may have preserved pseudo-autosomal properties.
New respiratory syncytial virus immunization products in low- and middle-income countries: potential for cost-effective impact on a high burden of disease in young infants
Authors: Srikantiah Padmini , Klugman Keith P.
Published: May 2023

As new, efficacious respiratory syncytial virus (RSV) immunization products reach the market, affordable pricing as well as improved estimation of disease burden and the full potential and cost effectiveness of RSV prevention in the hardest hit geographies in low- and middle-income countries are critical to inform country adoption and enable maximum impact against infant disease and mortality globally. The data reported in the special issue underscore the enormous burden, and associated cost, of RSV disease in young infants in several LMICs, including Kenya and South Africa, as well as the potential for RSV maternal vaccines or long-acting monoclonal antibodies, to be cost-effective and possibly even cost-saving.
Analysis of the quality, accuracy, and readability of patient information on polycystic ovarian syndrome (PCOS) on the internet available in English: a cross-sectional study
Authors: Vågenes Helene , Pranić Shelly Melissa
Published: May 2023

Background

Online information about PCOS lacks reliability for patients seeking information about the disease. Thus, we aimed to perform an updated analysis of the quality, accuracy, and readability of patient information on PCOS available online.

Methods

We conducted a cross-sectional study using the top five Google Trends search terms in English associated with PCOS, including “symptoms,” “treatment,” “test,” “pregnancy,” and “causes.” Five separate searches in Bing, Yahoo, and Google were performed to obtain the first 10 unique webpages for each term that was categorized as commercial, non-profit organization, scientific resources, or private foundation. We used the 16-item DISCERN with Likert-responses (minimum 1, maximum 5) where the total is 80 and lowest is 16, clarity with the 32-item EQIP, where responses of no = 0 and yes = 1 (minimum 0, maximum 32), and accuracy scores with 1 denoting poor and 5 completely accurate information; low scores of each corresponded to poorly reported information. We assessed readability with Flesch-Kincaid reading ease index, where higher scores correspond to reading ease, and lower grades correspond to easier readability with Flesch-Kincaid grade level, Gunning-Fog, Coleman-Liau index, automated readability index, New Dale-Chall Readability, and simple measure of gobbledygook. We additionally assessed word and sentence characteristics. We used Kruskal-Wallis test to compare scores according to webpage categories.

Results

Out of 150 webpages, most were commercial (n = 85, 57%), followed by non-profit organizations (n = 44, 29%), scientific resources (n = 13, 9%) and private foundations (n = 6, 4%). Google webpages had higher median DISCERN score ([Md] = 47.0) than Bing ([Md] = 42.0) and Yahoo ([Md] = 43.0) webpages; P = 0.023. No difference in EQIP scores according to search engine was found (P = 0.524). Predominantly, webpages from private foundations had higher DISCERN and EQIP scores, although comparisons were not statistically significant (P = 0.456) and P = 0.653.). Accuracy and readability were similar across search engines and webpage categories (P = 0.915, range 5.0–5.0) and (P = 0.208, range 4.0–5.0).

Conclusions

Quality and clarity of the data were fair according to search engine and category. Accuracy of information was high, showing that the public may encounter accurate information about PCOS. However, the readability of the information was high, reflecting a need for more readable resources about PCOS.
Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases
Authors: Kakavandi Sareh , Zare Iman , VaezJalali Maryam , Dadashi Masoud , Azarian Maryam , Akbari Abdullatif , Ramezani Farani Marzieh , Zalpoor Hamidreza , Hajikhani Bahareh
Published: May 2023

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases.
Bacillus cereus extracellular vesicles act as shuttles for biologically active multicomponent enterotoxins
Authors: Buchacher Tanja , Digruber Astrid , Kranzler Markus , Del Favero Giorgia , Ehling-Schulz Monika
Published: May 2023

Background

Extracellular vesicles (EVs) from Gram-positive bacteria have gained considerable importance as a novel transport system of virulence factors in host–pathogen interactions. Bacillus cereus is a Gram-positive human pathogen, causing gastrointestinal toxemia as well as local and systemic infections. The pathogenicity of enteropathogenic B. cereus has been linked to a collection of virulence factors and exotoxins. Nevertheless, the exact mechanism of virulence factor secretion and delivery to target cells is poorly understood.

Results

Here, we investigate the production and characterization of enterotoxin-associated EVs from the enteropathogenic B. cereus strain NVH0075-95 by using a proteomics approach and studied their interaction with human host cells in vitro. For the first time, comprehensive analyses of B. cereus EV proteins revealed virulence-associated factors, such as sphingomyelinase, phospholipase C, and the three-component enterotoxin Nhe. The detection of Nhe subunits was confirmed by immunoblotting, showing that the low abundant subunit NheC was exclusively detected in EVs as compared to vesicle-free supernatant. Cholesterol-dependent fusion and predominantly dynamin-mediated endocytosis of B. cereus EVs with the plasma membrane of intestinal epithelial Caco2 cells represent entry routes for delivery of Nhe components to host cells, which was assessed by confocal microscopy and finally led to delayed cytotoxicity. Furthermore, we could show that B. cereus EVs elicit an inflammatory response in human monocytes and contribute to erythrocyte lysis via a cooperative interaction of enterotoxin Nhe and sphingomyelinase.

Conclusion

Our results provide insights into the interaction of EVs from B. cereus with human host cells and add a new layer of complexity to our understanding of multicomponent enterotoxin assembly, offering new opportunities to decipher molecular processes involved in disease development.
MiR-146a rs2910164 (G/C) polymorphism is associated with the development and prognosis of acute coronary syndromes: an observational study including case control and validation cohort
Authors: Qiao Xiang-Rui , Zheng Tao , Xie Yifei , yao Xinyi , Yuan Zuyi , Wu Yue , Zhou Dong , Chen Tao
Published: May 2023

Background

Polymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms.

Methods

A case–control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining.

Results

The miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000–1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017–1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018–1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele.

Conclusion

The variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3′UTR of IKBA and activating NF-κB inflammatory pathways.
Sexual and reproductive health services access and provision in Cambodia during the COVID-19 pandemic: a mixed-method study of urban–rural differences
Authors: Ung Mengieng , Lam Sze Tung , Tuot Sovannary , Chhoun Pheak , Prum Virak , Nagashima-Hayashi Michiko , Neo Pearlyn , Marzouk Manar , Durrance-Bagale Anna , De Beni Davide , Yi Siyan , Howard Natasha
Published: May 2023

Background

The COVID-19 pandemic pushed governments worldwide to implement unprecedented mitigation measures, including safe-distancing, lockdowns, disruption of non-essential services, border closures and travel restrictions, with both potential to affect rural and urban service-users differently and unintended consequences including reductions in sexual and reproductive health (SRH) services. We aimed to explore rural–urban differences in progress and challenges in SRH services provision in Cambodia, particularly during initial months of the COVID-19 pandemic.

Methods

We used a mixed-methods study design, including a household survey of 423 adolescents and women aged 18–49 and semi-structured interviews with 21 healthcare providers. We analysed survey data using multivariable logistic regression to identify associations between rural–urban setting and contraceptive perceptions or access. We analysed interview data thematically.

Results

Rural–urban residence was significantly associated with reported perceptions about and access to contraceptives. Rural participants had higher odds of stating it was possible to change contraceptive methods early in the COVID-19 pandemic, compared with urban participants. Qualitative data showed that although SRH services continued, health-workers faced differential challenges in rural and urban areas, e.g. service-users not attending due to job losses in urban areas and not complying with safe-distancing and mask-wearing requests in rural areas.

Conclusions

COVID-19 and inadequate mitigation responses differentially affected rural and urban SRH service providers and service-users, exacerbating existing socioeconomic stressors while adding new fears of infection, transport constraints, and reduced livelihoods. Added financial support could help mitigate challenges in both rural and urban areas.
Improving multi-scale detection layers in the deep learning network for wheat spike detection based on interpretive analysis
Authors: Yan Jiawei , Zhao Jianqing , Cai Yucheng , Wang Suwan , Qiu Xiaolei , Yao Xia , Tian Yongchao , Zhu Yan , Cao Weixing , Zhang Xiaohu
Published: May 2023

Background

Detecting and counting wheat spikes is essential for predicting and measuring wheat yield. However, current wheat spike detection researches often directly apply the new network structure. There are few studies that can combine the prior knowledge of wheat spike size characteristics to design a suitable wheat spike detection model. It remains unclear whether the complex detection layers of the network play their intended role.

Results

This study proposes an interpretive analysis method for quantitatively evaluating the role of three-scale detection layers in a deep learning-based wheat spike detection model. The attention scores in each detection layer of the YOLOv5 network are calculated using the Gradient-weighted Class Activation Mapping (Grad-CAM) algorithm, which compares the prior labeled wheat spike bounding boxes with the attention areas of the network. By refining the multi-scale detection layers using the attention scores, a better wheat spike detection network is obtained. The experiments on the Global Wheat Head Detection (GWHD) dataset show that the large-scale detection layer performs poorly, while the medium-scale detection layer performs best among the three-scale detection layers. Consequently, the large-scale detection layer is removed, a micro-scale detection layer is added, and the feature extraction ability in the medium-scale detection layer is enhanced. The refined model increases the detection accuracy and reduces the network complexity by decreasing the network parameters.

Conclusion

The proposed interpretive analysis method to evaluate the contribution of different detection layers in the wheat spike detection network and provide a correct network improvement scheme. The findings of this study will offer a useful reference for future applications of deep network refinement in this field.
Mapping the forage nitrogen, phosphorus, and potassium contents of alpine grasslands by integrating Sentinel-2 and Tiangong-2 data
Authors: Zhang Xuanfan , Liang Tiangang , Gao Jinlong , Zhang Dongmei , Liu Jie , Feng Qisheng , Wu Caixia , Wang Zhiwei
Published: May 2023

Nitrogen (N), phosphorus (P), and potassium (K) contents are crucial quality indicators for forage in alpine natural grasslands and are closely related to plant growth and reproduction. One of the greatest challenges for the sustainable utilization of grassland resources and the development of high-quality animal husbandry is to efficiently and accurately obtain information about the distribution and dynamic changes in N, P, and K contents in alpine grasslands. A new generation of multispectral sensors, the Sentinel-2 multispectral instrument (MSI) and Tiangong-2 moderate-resolution wide-wavelength imager (MWI), is equipped with several spectral bands suitable for specific applications, showing great potential for mapping forage nutrients at the regional scale. This study aims to achieve high-accuracy spatial mapping of the N, P, and K contents in alpine grasslands at the regional scale on the eastern Qinghai-Tibet Plateau. The Sentinel-2 MSI and Tiangong-2 MWI data, coupled with multiple feature selection algorithms and machine learning models, are applied to develop forage N, P, and K estimation models from data collected at 92 sample sites ranging from the vigorous growth stage to the senescent stage. The results show that the spectral bands of both the Sentinel-2 MSI and Tiangong-2 MWI have an excellent performance in estimating the forage N, P, and K contents (the R2values are 0.68–0.76, 0.54–0.73, and 0.74–0.82 for forage N, P, and K estimations, respectively). Moreover, the model integrating the spectral bands of these two sensors explains 78%, 74%, and 84% of the variations in the forage N, P, and K contents, respectively. These results indicate that the estimation ability of forage nutrients can be further improved by integrating Tiangong-2 MWI and Sentinel-2 MSI data. In conclusion, integration of the spectral bands of multiple sensors is a promising approach to map the forage N, P, and K contents in alpine grasslands with high accuracy at the regional scale. This study offers valuable information for growth monitoring and real-time determination of forage quality in alpine grasslands.
Perceived benefit of yoga among adults who have practiced yoga for a long time: a qualitative study
Authors: Akdeniz Şengül , Kaştan Özlem
Published: May 2023

Background

Previous quantitative studies have shown many of the perceived benefits of yoga practice on the mind and body. Although there are many quantitative studies in the international literature on yoga, the number of qualitative studies showing the experience of yoga practice is insufficient. An accurate demonstration of yoga participents experiences, opinions, and judgments on this subject requires a qualitative, rather than a quantitative approach.

Purpose

This study was to explore the benefit perceived by adults who have practiced yoga for a long time.

Design and method

This qualitative study is based on a hermeneutic–phenomenological approach. The research sample consisted of 18 adults who volunteered to participate in the research and regularly joined yoga practice. The study data were collected through individual and focus group interviews with the participants who practise yoga and analyzed by content analysis method.

Results

We created five themes. Themes coded by researchers: meaning of the concept of yoga (theme 1), physical, mental, and social state before starting yoga (theme 2), reasons for practising yoga (theme 3), the participants' experiences related to their physical and mental health and social relationships (theme 4), and difficulties of doing yoga (theme 5). In addition, individuals in the study reported their perceptions of the concept of "yoga" through the creation of metaphors that completed the following sentence “yoga is like ……”. These metaphors were used to give insight into the participants deep feelings about yoga.

Conclusions

Both in their individual and focus group interviews, almost all of the participants described that doing yoga has positive benefits on the mind and body. The positive experiences of the participants in the study included decrease in pain and flexibility, increase in sleep quality, development of positive personality traits, increase in self-esteem, and coping with anxiety and stress more effectively. Because the study was qualitative and long-term, it was able to evaluate the beliefs, attitudes and behaviors of individuals in a realistic, systematic, and detailed manner.
Implementation of a batched stepped wedge trial evaluating a quality improvement intervention for surgical teams to reduce anastomotic leak after right colectomy
Authors: Venn Mary L. , Knowles Charles H. , Li Elizabeth , Glasbey James , Morton Dion G. , Hooper Richard ,   ESCP EAGLE Safe Anastomosis Collaborative
Published: May 2023

Background

Large-scale quality improvement interventions demand robust trial designs with flexibility for delivery in different contexts, particularly during a pandemic. We describe innovative features of a batched stepped wedge trial, ESCP sAfe Anastomosis proGramme in CoLorectal SurgEry (EAGLE), intended to reduce anastomotic leak following right colectomy, and reflect on lessons learned about the implementation of quality improvement programmes on an international scale.

Methods

Surgical units were recruited and randomised in batches to receive a hospital-level education intervention designed to reduce anastomotic leak, either before, during, or following data collection. All consecutive patients undergoing right colectomy were included. Online learning, patient risk stratification and an in-theatre checklist constituted the intervention. The study was powered to detect an absolute risk reduction of anastomotic leak from 8.1 to 5.6%. Statistical efficiency was optimised using an incomplete stepped wedge trial design and study batches analysed separately then meta-analysed to calculate the intervention effect. An established collaborative group helped nurture strong working relationships between units/countries and a prospectively designed process evaluation will enable evaluation of both the intervention and its implementation.

Results

The batched trial design allowed sequential entry of clusters, targeted research training and proved to be robust to pandemic interruptions. Staggered start times in the incomplete stepped wedge design with long lead-in times can reduce motivation and engagement and require careful administration.

Conclusion

EAGLE’s robust but flexible study design allowed completion of the study across globally distributed geographical locations in spite of the pandemic. The primary outcome analysed in conjunction with the process evaluation will ensure a rich understanding of the intervention and the effects of the study design.

Trial registration

National Institute of Health Research Clinical Research Network portfolio IRAS ID: 272,250. Health Research Authority approval 18 October 2019. ClinicalTrials.gov, identifier NCT04270721, protocol ID RG_19196.
Concept and study protocol of the process evaluation of a pragmatic randomized controlled trial to promote physical activity in outpatients with heterogeneous mental disorders—the ImPuls study
Authors: Fiedler David Victor , Rosenstiel Stephanie , Zeibig Johanna-Marie , Seiffer Britta , Welkerling Jana , Frei Anna Katharina , Studnitz Thomas , Baur Julia , Helmhold Florian , Ray Andreas , Herzog Eva , Takano Keisuke , Nakagawa Tristan , Kropp Saskia , Franke Sebastian , Peters Stefan , Flagmeier Anna Lena , Zwanzleitner Lena , Sundmacher Leonie , Ramos-Murguialday Ander , Hautzinger Martin , Ehring Thomas , Sudeck Gorden , Wolf Sebastian
Published: May 2023

Background

Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial.

Methods

The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis.

Discussion

The results of our process evaluation will complement the evaluation of effectiveness and cost-effectiveness and will, for example, provide important information about mechanisms of impact, structural prerequisites, or provider qualification that may support the decision-making process of health policy stakeholders. It might contribute to paving the way for exercise programs like ImPuls to be made successively available for patients with heterogeneous mental disorders in the German outpatient mental health care system.

Trial registration

The parent clinical study was registered in the German Clinical Trials Register (ID: DRKS00024152, registered 05/02/2021, https://drks.de/search/en/trial/DRKS00024152).