bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Spot SCANNER: Colab Notebook for predicting cold spots in protein–protein interfaces
Authors: Gurusinghe Sagara N. S. , Shifman Julia M.
Published: April 2024

Background

Protein–protein interactions (PPIs) are conveyed through binding interfaces or surface patches on proteins that become buried upon binding. Structural and biophysical analysis of many protein–protein interfaces revealed certain unique features of these surfaces that determine the energetics of interactions and play a critical role in protein evolution. One of the significant aspects of binding interfaces is the presence of binding hot spots, where mutations are highly deleterious for binding. Conversely, binding cold spots are positions occupied by suboptimal amino acids and several mutations in such positions could lead to affinity enhancement. While there are many software programs for identification of hot spot positions, there is currently a lack of software for cold spot detection.

Results

In this paper, we present Cold Spot SCANNER, a Colab Notebook, which scans a PPI binding interface and identifies cold spots resulting from cavities, unfavorable charge-charge, and unfavorable charge-hydrophobic interactions. The software offers a Py3DMOL-based interface that allows users to visualize cold spots in the context of the protein structure and generates a zip file containing the results for easy download.

Conclusions

Cold spot identification is of great importance to protein engineering studies and provides a useful insight into protein evolution. Cold Spot SCANNER is open to all users without login requirements and can be accessible at: https://colab.research.google.com/github/sagagugit/Cold-Spot-Scanner/blob/main/Cold_Spot_Scanner.ipynb.
NKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing
Authors: Xie Gengqiang , Toledo Maria Pilar , Hu Xue , Yong Hyo Jeong , Sanchez Pamela Sandoval , Liu Chengyang , Naji Ali , Irianto Jerome , Wang Yue J.
Published: April 2024

Background

Current approaches to profile the single-cell transcriptomics of human pancreatic endocrine cells almost exclusively rely on freshly isolated islets. However, human islets are limited in availability. Furthermore, the extensive processing steps during islet isolation and subsequent single cell dissolution might alter gene expressions. In this work, we report the development of a single-nucleus RNA sequencing (snRNA-seq) approach with targeted islet cell enrichment for endocrine-population focused transcriptomic profiling using frozen archival pancreatic tissues without islet isolation.

Results

We cross-compared five nuclei isolation protocols and selected the citric acid method as the best strategy to isolate nuclei with high RNA integrity and low cytoplasmic contamination from frozen archival human pancreata. We innovated fluorescence-activated nuclei sorting based on the positive signal of NKX2-2 antibody to enrich nuclei of the endocrine population from the entire nuclei pool of the pancreas. Our sample preparation procedure generated high-quality single-nucleus gene-expression libraries while preserving the endocrine population diversity. In comparison with single-cell RNA sequencing (scRNA-seq) library generated with live cells from freshly isolated human islets, the snRNA-seq library displayed comparable endocrine cellular composition and cell type signature gene expression. However, between these two types of libraries, differential enrichments of transcripts belonging to different functional classes could be observed.

Conclusions

Our work fills a technological gap and helps to unleash frozen archival pancreatic tissues for molecular profiling targeting the endocrine population. This study opens doors to retrospective mappings of endocrine cell dynamics in pancreatic tissues of complex histopathology. We expect that our protocol is applicable to enrich nuclei for transcriptomics studies from various populations in different types of frozen archival tissues.
Modified fructan accumulation through overexpression of wheat fructan biosynthesis pathway fusion genes Ta1SST:Ta6SFT
Authors: Chen Tong , Hayes Matthew , Liu Zhiqian , Isenegger Daniel , Mason John , Spangenberg German
Published: April 2024

Background

Fructans are water-soluble carbohydrates that accumulate in wheat and are thought to contribute to a pool of stored carbon reserves used in grain filling and tolerance to abiotic stress.

Results

In this study, transgenic wheat plants were engineered to overexpress a fusion of two fructan biosynthesis pathway genes, wheat sucrose: sucrose 1-fructosyltransferase (Ta1SST) and wheat sucrose: fructan 6-fructosyltransferase (Ta6SFT), regulated by a wheat ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit (TaRbcS) gene promoter. We have shown that T4 generation transgene-homozygous single-copy events accumulated more fructan polymers in leaf, stem and grain when compared in the same tissues from transgene null lines. Under water-deficit (WD) conditions, transgenic wheat plants showed an increased accumulation of fructan polymers with a high degree of polymerisation (DP) when compared to non-transgenic plants. In wheat grain of a transgenic event, increased deposition of particular fructan polymers such as, DP4 was observed.

Conclusions

This study demonstrated that the tissue-regulated expression of a gene fusion between Ta1SST and Ta6SFT resulted in modified fructan accumulation in transgenic wheat plants and was influenced by water-deficit stress conditions.
RhMED15a-like, a subunit of the Mediator complex, is involved in the drought stress response in Rosa hybrida
Authors: Xie Nanxin , Shi Haoyang , Shang Xiaoman , Zhao Zixin , Fang Yan , Wu Huimin , Luo Ping , Cui Yongyi , Chen Wen
Published: April 2024

Background

Rose (Rosa hybrida) is a globally recognized ornamental plant whose growth and distribution are strongly limited by drought stress. The role of Mediator, a multiprotein complex crucial for RNA polymerase II-driven transcription, has been elucidated in drought stress responses in plants. However, its physiological function and regulatory mechanism in horticultural crop species remain elusive.

Results

In this study, we identified a Tail module subunit of Mediator, RhMED15a-like, in rose. Drought stress, as well as treatment with methyl jasmonate (MeJA) and abscisic acid (ABA), significantly suppressed the transcript level of RhMED15a-like. Overexpressing RhMED15a-like markedly bolstered the osmotic stress tolerance of Arabidopsis, as evidenced by increased germination rate, root length, and fresh weight. In contrast, the silencing of RhMED15a-like through virus induced gene silencing in rose resulted in elevated malondialdehyde accumulation, exacerbated leaf wilting, reduced survival rate, and downregulated expression of drought-responsive genes during drought stress. Additionally, using RNA-seq, we identified 972 differentially expressed genes (DEGs) between tobacco rattle virus (TRV)-RhMED15a-like plants and TRV controls. Gene Ontology (GO) analysis revealed that some DEGs were predominantly associated with terms related to the oxidative stress response, such as ‘response to reactive oxygen species’ and ‘peroxisome’. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment highlighted pathways related to ‘plant hormone signal transduction’, in which the majority of DEGs in the jasmonate (JA) and ABA signalling pathways were induced in TRV-RhMED15a-like plants.

Conclusion

Our findings underscore the pivotal role of the Mediator subunit RhMED15a-like in the ability of rose to withstand drought stress, probably by controlling the transcript levels of drought-responsive genes and signalling pathway elements of stress-related hormones, providing a solid foundation for future research into the molecular mechanisms underlying drought tolerance in rose.
POSITIVE: experiences of an intervention aiming for reversing and preventing frailty using a home monitoring and communication platform within primary health care
Authors: Timm Linda , Guidetti Susanne , Taloyan Marina
Published: April 2024

Background

Frailty is increasing worldwide as the population ages. Physical activity is one component that has been shown to hinder and even reverse the process. The POSITIVE system (i.e., maintaining and imPrOving the intrinSIc capaciTy Involving primary care and caregiVErs) is a prevention program that consists of home-monitoring equipment and a communication platform to support the initial treatment of frailty symptoms in primary health care. The participants, older aged (+ 70) frail persons and those at risk for frailty, took part in the program that promoted physical activity at home for six months. The aim was to explore and describe older persons’ experiences of participating in a new prevention program using the POSITIVE system including technological tools intended to prevent the development of frailty.

Methods

Nine interviews were conducted about experiences of participating in an intervention including use of technological tools to support physical activity. Qualitative content analysis was applied.

Results

Two themes revealed: (1) Perceptions of being old are seldom positive, and (2) A rewarding and fruitful participation in the project with suggestions for improvement. Becoming older was related to physical pain and tiredness reducing the performance of former meaningful activities as well as an increase in mental stress. There was also a tendency to postpone the start of everyday activities, and in general, fewer activities were planned for one day than at younger ages. Participating in a physical activity intervention, including the use of technical tools, was considered meaningful and added motivation for engaging in other physical activities, this despite some difficulties with technical tools provided by the program. The contact with health care and the research team was appreciated. In addition, contact with other participants was requested and reported to be highly valued if added to the intervention, which could have been an expression of loneliness.

Conclusion

Participation in a prevention program motivated activities and social interaction. Adding opportunities for participants to meet each other is suggested for improving the intervention in terms of increasing the social dimensions. Our findings conclude that despite difficulties with handling the technical tools for the home-monitoring and communication platform, participation in the POSITIVE intervention was in general a positive experience.
Longitudinal changes in body mass index, height, and weight in children with acute myeloid leukemia
Authors: Wen Xiaojia , He Hongbo , Zhang Ruidong , Wu Ying , Zhang Yuanyuan , Lin Wei , Yu Jiaole , Fan Jia , Huang Pengli , Chen Jiajia , Li Wenjing , Gong Chunxiu , Zheng Huyong
Published: April 2024

Background

This study reported height prediction and longitudinal growth changes in Chinese pediatric patients with acute myeloid leukemia (AML) during and after treatment and their associations with outcomes.

Methods

Changes in 88 children with AML in percentages according to the growth percentile curve for Chinese boys/girls aged 2–18/0–2 years for body mass index (BMI), height, and weight from the time of diagnosis to 2 years off therapy were evaluated. The outcomes of AML were compared among patients with different BMI levels.

Results

The proportion of underweight children (weight < 5th percentile) increased significantly from the initial diagnosis to the end of consolidation treatment. The proportion of patients with low BMI (BMI < 5th percentile) was highest (23.08%) during the consolidation phase, and no children were underweight, but 20% were overweight (BMI > 75th percentile) after 2 years of drug withdrawal. Unhealthy BMI at the initial diagnosis and during intensive chemotherapy leads to poorer outcomes. For height, all patients were in the range of genetic height predicted based on their parents’ height at final follow-up.

Conclusions

Physicians should pay more attention to the changes in height and weight of children with AML at these crucial treatment stages and intervene in time.
Survival status and its predictors among undernourished children on antiretroviral therapy in Bahir Dar city, Northwest Ethiopia, 2010 – 2020, a multicenter retrospective cohort study
Authors: Moga Lencha Fikre , Mekonnen Workie Hailemariam , Tadesse Mequanint Fikir , Jebero Zaza Zenebe
Published: April 2024

Background

In environments with limited resources, undernutrition is a serious public health risk. Its dual relationship to human immunodeficiency virus infection (HIV) leads to crises in a child's physical, emotional, social, and economic spheres of life. Nevertheless, little research has been done on the survival rate and risk factors that lead to poor survival outcomes in undernourished children receiving antiretroviral therapy. This study sought to evaluate survival status and its predictors among undernourished children on antiretroviral therapy (ART) in public health facilities, Bahir Dar city, September 1, 2010 – December 31, 2020.

Methods

An institution-based retrospective cohort study design was used among 414 study participants from September 1, 2010 – December 31, 2020. A simple random sampling method was applied to select study participants. All collected data were entered into epi data version 4.6 and exported to STATA version 14.0 for analysis. Each independent predictor variable with ap-value < 0.05 in the multivariable Cox proportional hazard regression was considered statistically significant.

Results

The overall incidence of mortality was 11.6 deaths per 1000 child year observation (95%CI: 7.7- 17.5). Baseline weight for age < -3 Z score (adjusted hazard ratio (AHR) = 4.9, 95% CI: 1.30–18.98), height for age < -3 Z score (AHR = 4.34, 95%CI 1.13–16.6), cotrimoxazole prophylaxis given (AHR = 0.27, 95%CI 0.08–0.87), hemoglobin level < 10 g/dl (AHR = 3.7, 95%CI 1.1–12.7), CD4 cells < threshold (AHR = 4.86, 95%CI 1.9–12.7), and WHO clinical disease stage III and IV (AHR = 8.1, 95%CI 1.97–33) were found independent predictors of mortality.

Conclusion and recommendation

The incidence of mortality was determined in the study to be 11.6 per 1000 child years. Mortality was predicted by severe stunting, severe underweight, a low hemoglobin level, a low CD4 count, and WHO clinical stages III and IV. But the risk of death is reduced by starting cotrimoxazole preventative therapy early. The risk factors that result in a low survival status should be the primary focus of all concerned bodies, and early cotrimoxazole preventive treatment initiation is strongly recommended.
Patient adherence as a predictor of acute and long-term outcomes in concentrated exposure treatment for difficult-to-treat obsessive-compulsive disorder
Authors: Tjelle Kristian , Opstad Håvard Berg , Solem Stian , Kvale Gerd , Wheaton Michael G. , Björgvinsson Thröstur , Hansen Bjarne , Hagen Kristen
Published: April 2024

Background

Exposure and response prevention (ERP) is considered the first-line psychotherapy for obsessive-compulsive disorder (OCD). Substantial research supports the effectiveness of ERP, yet a notable portion of patients do not fully respond while others experience relapse. Understanding poor outcomes such as these necessitates further research. This study investigated the role of patient adherence to ERP tasks in concentrated exposure treatment (cET) in a sample who had previously not responded to treatment or relapsed.

Method

The present study included 163 adults with difficult-to-treat OCD. All patients received cET delivered during four consecutive days. Patients’ treatment adherence was assessed using the Patient EX/RP Adherence Scale (PEAS-P) after the second and third day of treatment. OCD severity was evaluated at post-treatment, 3-month follow-up, and 1-year follow-up by independent evaluators.

Results

PEAS-P scores during concentrated treatment were associated with OCD-severity at post-treatment, 3-month follow-up, and 1-year follow-up. Moreover, PEAS-P scores predicted 12-month OCD severity adjusting for relevant covariates. Adherence also predicted work- and social functioning at 1-year follow-up.

Conclusions

These results indicate that ERP adherence during the brief period of cET robustly relates to improvement in OCD symptoms and functioning in both the short and long term. Assessing adherence might identify patients at risk of poor outcomes, while improving adherence may enhance ERP for treatment resistant patients.

Trial Registration

ClinicalTrials.gov identifier: NCT02656342.
Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial
Authors: Lammi Matthew R. , Mukherjee Monica , Saketkoo Lesley Ann , Carey Kyle , Hummers Laura , Hsu Steven , Krishnan Amita , Sandi Marie , Shah Ami A. , Zimmerman Stefan L. , Hassoun Paul M. , Mathai Steven C.
Published: April 2024

Background

Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21–24 mmHg).

Methods

The SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks.

Discussion

The SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP.

Trial registration

ClinicalTrials.gov Identifier NCT04797286.
High prevalence of erectile dysfunction in men with hyperthyroidism: a meta-analysis
Authors: Liu Xiaowen , Wang Yanling , Ma Li , Wang Danhui , Peng Zhihong , Mao Zenghui
Published: April 2024

Objective

The objective of this study was to evaluate the association between hyperthyroidism and the risk of developing erectile dysfunction (ED).

Methods

A comprehensive search of multiple databases, including PubMed, Embase, Cochrane, and Web of Science, was conducted to identify relevant studies investigating the relationship between hyperthyroidism and ED in men. The quality of the included studies was assessed using the Newcastle‒Ottawa Quality Rating Scale, and a meta-analysis was performed using Stata 16.0 and RevMan 5.3 software.

Results

A total of four papers encompassing 25,519 study subjects were included in the analysis. Among these, 6,429 individuals had hyperthyroidism, while 19,090 served as controls. The overall prevalence of ED in patients with hyperthyroidism was determined to be 31.1% (95% CI 0.06–0.56). In patients with uncomplicated hyperthyroidism, the incidence of ED was 21.9% (95% CI 0.05–0.38). The combined odds ratio (OR) for the four studies was 1.73 (OR: 1.73; 95% CI [1.46–2.04]; p < .00001).

Conclusion

Our findings demonstrate a higher incidence of ED in patients with hyperthyroidism. These results provide valuable information for healthcare professionals and can facilitate discussions surrounding appropriate treatment options for ED in patients with hyperthyroidism.
Risky sexual behavior and associated factors among reproductive age women in eastern African countries: a multilevel analysis of the recent demographic and health survey
Authors: Workneh Belayneh Shetie , Zegeye Alebachew Ferede , Tamir Tadesse Tarik , Mekonen Enyew Getaneh
Published: April 2024

Introduction

Risky sexual behavior exposes an individual to the risk of contracting sexually transmitted infections including human immunodeficiency virus (HIV). Even though risky sexual behavior is a devastating problem in low- and middle-income countries, studies on risky sexual behavior and associated factors among reproductive-age women in Eastern African countries are limited. Therefore, this study aimed to assess the magnitude of risky sexual behavior and associated factors among reproductive-age women in Eastern African countries that help to target high-risk groups and set appropriate intervention.

Method

The appended and recent Demographic and Health Survey dataset of 10 Eastern African countries from 2012 to 2022 was used for data analysis. A total of 111,895 participants were included in this study as a weighted sample. Associated factors were determined using a multilevel mixed-effects logistic regression model. Significant factors in the multilevel mixed-effect logistic regression model were declared significant at p-values < 0.05. The adjusted odds ratio (AOR) and confidence interval (CI) were used to interpret the results.

Result

The overall magnitude of risky sexual behavior among reproductive-age women in Eastern African countries was 28.16% (95% CI 27.90%, 28.43%), which ranged from 3.80% in Ethiopia to 67.13% in Kenya. In the multivariable analysis, being a younger woman, being an educated woman, being tested for human immunodeficiency virus, having work, drinking alcohol, and being an urban dweller were factors that were significantly associated with higher odds of risky sexual behavior.

Conclusion

The overall magnitude of risky sexual behavior among reproductive-age women in Eastern African countries was high. Individual-level (being a younger woman, being an educated woman, being tested for human immunodeficiency virus, having work, and drinking alcohol) and community-level (being an urban dweller) variables were associated with higher odds of risky sexual behavior. Therefore, policymakers and other stakeholders should give special consideration to urban dwellers, educated, worker and younger women. Better to improve the healthy behavior of women by minimizing alcohol consumption and strengthening HIV testing and counseling services to reduce the magnitude of risky sexual behavior.
Psychological impact and associated factors of the COVID-19 pandemic among pregnant women in Fafan Zone health institutions, Somali Region, Eastern Ethiopia, 2021
Authors: Jibril Meka Kedir , Yimam Ahmed Adem , Abdu Neima Ridwan , Ali Seid Yimam
Published: April 2024

Background

Despite pregnant women's vulnerability to respiratory illnesses and pregnancy complications during the COVID-19 pandemic, research on its psychological impact in the study area, is limited.

Objective

This study aims to fill this gap by examining the prevalence and factors linked to the psychological impact among pregnant women in the Fafan zone, Somali region of Ethiopia.

Methods

A cross-sectional study conducted from April 1st to April 30th, 2021, randomly selected health facilities for inclusion. The Impact of Event Scale-Revised (IES-R) assessed psychological impact, and data were analyzed using SPSS V 22. Variables with a p-value ≤ 0.25 in bivariate analysis were considered for multivariate analysis via multiple logistic regressions with the backward elimination method.

Results

The study involved 294 pregnant women, constituting 73% of the respondents. The prevalence of psychological impact attributed to the COVID-19 pandemic was 27.2%. Factors such as being in the first trimester of pregnancy (AOR: 5.32), travel history to infected areas (AOR: 3.71), obtaining COVID-19 information from television (AOR: 4.81), and using social media for 1 to 2 hours daily for updates (AOR: 1.35) were significantly associated with this impact.

Conclusion

While the psychological impact among pregnant women in this study was relatively lower compared to other research, factors such as gestational age, TV media exposure, travel history, and social media usage for COVID-19 updates were strongly linked to this impact, highlighting the necessity for psychological support services for pregnant women during challenging times.
Designing, implementation and evaluation of story reading: a solution to increase general empathy in medical students
Authors: Mahmoudi Masoumeh , Ghorbani Ali Asghar , Pourasghar Mehdi , Balaghafari Azita , Charati Jamshid Yazdani , Ghahrani Nassim , Amini Farzaneh
Published: April 2024

Background

Communication and mutual understanding among healthcare providers is a significant concern within the healthcare system, and enhancing empathy is one way to foster effective communication and mutual understanding. The aim of this research is to evaluate and compare the impact of story reading on the level of empathy in medical students at Mazandaran University of Medical Sciences.

Methods

The study employed an intervention educational design (a quasi-experimental), with a convenience sample of 51 medical students selected as the statistical population. The process of story reading was conducted over six two-hour virtual sessions in the students' classroom, spanning six weeks. Selected stories were discussed in an online virtual class under the supervision of an instructor, focusing on story elements. To assess students' empathy in this educational program, the Davis General Empathy Questionnaire was administered before each of the six sessions, after, and one week later at the end of the course. Statistical analysis of the collected data was performed using repeated measures analysis of variance and Bonferroni's post hoc test through SPSS version 28 software, with a significance level set at 0.05.

Results

The findings revealed that 27 participants (58.7%) were female students, with the remaining being male students, having an average age of 19.5 ± 0.86 years. The level of general empathy among the students significantly increased after the intervention compared to before the intervention (P<0.001). Furthermore, the analysis of variance with repeated measures indicated a significant effect of the story reading program on enhancing empathy in terms of emotional and cognitive transfer among students in the intervention group (P<0.001).

Conclusions

The research findings suggest that the story reading program effectively enhances the overall sense of empathy among medical students at the University of Medical Sciences. Therefore, implementing this method in universities, higher education centers, libraries, and psychology centers for teaching empathy can be valuable in fostering empathy skills and improving healthcare.
Sociocultural and perceived public image of nurses among nursing students: the mediating role of self-concept
Authors: Sacgaca Lailani , an Eddieson Pasay , Alqarni Aida Sanad , Pangket Petelyne , Alshammari Salman Amish , Ramadan Magda Yousif , Alonezei Ameera Khaled , Alamoudi Fatmah Ahmed , Mohammed Insaf Hassan Ahmed , Cabansag Dolores , Benjamin Lizy Sonia
Published: April 2024

Background

Studying the public perception of nurses among nursing students is vital in establishing strategic solutions to recruit and retain more students in nursing programs and to contain nurses in the health care system.

Aim

This study aimed to determine the mediating role of self-concept in the relationship between sociocultural and perceived public image of nurses.

Methods

This study employed a correlational approach using convenience sampling of 1390 participants. This study was conducted at six large universities in three regions of Saudi Arabia (central, northern, and eastern). Student nurses in their second to fourth years of study were included as participants, with an 89.7% response rate. Data were collected from January to April 2023.

Results

A significant positive relationship was observed between sociocultural factors and self-concept (r = .685, p = .0001). In addition, there was a significant positive relationship between self-concept and public image (PI) (r = .352, p value = 0.0001). Furthermore, there was a significant positive relationship between sociocultural and public image (r = .456, p = .0001); sociocultural had a direct effect on self-concept (β = 0.324, SE = 0.098, t = 9.429, p < .0001) and public image (β = 0.605, SE = 0.038, t = 22.617, p < .0001). Furthermore, sociocultural had an indirect effect on public image through self-concept (H6) (β = 0.389, SE = 0.123, t = 12.766, p < .0001).

Discussion

The study findings suggest that nursing school programs should take measures to foster a supportive environment that promotes self-concept and public image, while also being mindful of the sociocultural background. This would also open the scope for further research on the matter involving multiple centers.

Conclusions

This study suggests the need for programs to boost self-concept and public image that consider sociocultural influences. These ’findings have crucial implications for student nurses’ social and psychological wellbeing as they improve the understanding of how sociocultural affects self-concept and public image.
Arginine and its metabolites stimulate proliferation, differentiation, and physiological function of porcine trophoblast cells through β-catenin and mTOR pathways
Authors: Li Shuai , Ye Xiangyang , Wen Xiaolu , Yang Xuefen , Wang Li , Gao Kaiguo , Xiao Hao , Jiang Zongyong
Published: April 2024

Arginine, which is metabolized into ornithine, proline, and nitric oxide, plays an important role in embryonic development. The present study was conducted to investigate the molecular mechanism of arginine in proliferation, differentiation, and physiological function of porcine trophoblast cells (pTr2) through metabolic pathways. The results showed that arginine significantly increased cell viability (P < 0.05). The addition of arginine had a quadratic tendency to increase the content of progesterone (P = 0.06) and protein synthesis rate (P = 0.03), in which the maximum protein synthesis rate was observed at 0.4 mM arginine. Arginine quadratically increased (P < 0.05) the intracellular contents of spermine, spermidine and putrescine, as well as linearly increased (P < 0.05) the intracellular content of NO in a dose-dependent manner. Arginine showed a quadratic tendency to increase the content of putrescine (P = 0.07) and a linear tendency to increase NO content (P = 0.09) in cell supernatant. Moreover, increasing arginine activated (P < 0.05) the mRNA expressions for ARG, ODC, iNOS and PCNA. Furthermore, inhibitors of arginine metabolism (L-NMMA and DFMO) both inhibited cell proliferation, while addition of its metabolites (NO and putrescine) promoted the cell proliferation and cell cycle, the mRNA expressions of PCNA, EGF and IGF-1, and increased (P < 0.05) cellular protein synthesis rate, as well as estradiol and hCG secretion (P < 0.05). In conclusion, our results suggested that arginine could promote cell proliferation and physiological function by regulating the metabolic pathway. Further studies showed that arginine and its metabolites modulate cell function mainly through β-catenin and mTOR pathways.
Exploring the role of spending on malaria incidence in Uganda using the auto-regressive distributed lag approach
Authors: Katushabe Jemimah , Nnyanzi John Bosco , Muwanga Gertrude Sebunya
Published: April 2024

Background

Malaria has remained a persistent global health problem. Despite multiple government and donor initiatives to eradicate malaria and its detrimental effects on Uganda's health outcomes, the incidence of malaria is worrying as it appears higher than the average of 219 cases per 1000 for sub-Saharan Africa for the period 2017–2018. This study investigated the effect of public and private healthcare spending on the incidence of malaria in Uganda.

Methods

Employing time series data spanning over 20 years from the first quarter of 2000 to the last quarter of 2019, the study builds a model based on the Grossman framework for analysing demand for health. The estimation technique used was the ARDL approach that takes into account reverse causality and incidental relationships. Prior to the adoption of the technique, a bounds test was performed to determine whether the variables contained in the model have a long-term relationship. Several diagnostic tests for serial correlation, functional normality, and heteroskedastic specification error were carried out to verify the ARDL model's goodness of fit. Additionally, the cumulative sum of recursive (CUSUM) and cumulative sum of squares of recursive residuals (CUSUMSQ) were used to test model stability.

Results

The results indicate that in the long run, an increase in public spending of one percent significantly reduces malaria incidence by 0.196 at the 10 percent level of significance. On the other hand, there is no significant evidence of private health expenditure's effect on malaria incidence. However, in the short run, public spending reduces malaria incidence by a smaller magnitude of 0.158 percent relative to the long-run. Still, private expenditure is found to exhibit no significant effect. Additional findings point to the importance of GDP per capita and urban population growth in reducing malaria incidence, whereas female unemployment, income inequality, as well as female-headed household. In the short run, however, the female-headed households and urban population growth are found to significantly reduce malaria incidence while an improvement in regulatory quality decreases malaria incidence by 0.129 percent.

Conclusions

There is need for further government interventions to reduce malaria incidence in the country via budget allocation, as well as the strengthening of programmes to raise household income to support private health spending, in addition to the development of strategies to promote well-planned and organized urban centres.
Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice
Authors: Gao Weihang , Li Jiao Jiao , Shi Jingyu , Lan Hongbing , Guo Yuanyuan , Fu Dehao
Published: April 2024

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.
Biomimetic nanodrug blocks CD73 to inhibit adenosine and boosts antitumor immune response synergically with photothermal stimulation
Authors: Li Tan , Zhang Xingyu , Shi Chengyu , Liu Qiao , Zhao Yuetao
Published: April 2024

Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, β-Methyleneadenosine 5′-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.
Loss of tumor-derived SMAD4 enhances primary tumor growth but not metastasis following BMP4 signalling
Authors: Chi Lap Hing , Redfern Andrew D. , Roslan Suraya , Street Ian P. , Burrows Allan D. , Anderson Robin L.
Published: April 2024

Background

Bone morphogenetic protein 4 (BMP4) is a potent inhibitor of breast cancer metastasis. However, a tumor-promoting effect of BMP4 is reported in other tumor types, especially when SMAD4 is inactive.

Methods

To assess the requirement for SMAD4 in BMP4-mediated suppression of metastasis, we knocked down SMAD4 in two different breast tumors and enforced SMAD4 expression in a third line with endogenous SMAD4 deletion. In addition, we assessed the requirement for SMAD4 in tumor cell-specific BMP signalling by expression of a constitutively active BMP receptor. Delineation of genes regulated by BMP4 in the presence or absence of SMAD4 was assessed by RNA sequencing and a BMP4-induced gene, MYO1F was assessed for its role in metastasis. Genes regulated by BMP4 and/or SMAD4 were assessed in a publicly available database of gene expression profiles of breast cancer patients.

Results

In the absence of SMAD4, BMP4 promotes primary tumor growth that is accompanied by increased expression of genes associated with DNA replication, cell cycle, and MYC signalling pathways. Despite increased primary tumor growth, BMP4 suppresses metastasis in the absence of tumor cell expression of SMAD4. Consistent with the anti-metastatic activity of BMP4, enforced signalling through the constitutively active receptor in SMAD4 positive tumors that lacked BMP4 expression still suppressed metastasis, but in the absence of SMAD4, the suppression of metastasis was largely prevented. Thus BMP4 is required for suppression of metastasis regardless of tumor SMAD4 status. The BMP4 upregulated gene, MYO1F, was shown to be a potent suppressor of breast cancer metastasis. Gene signature upregulated by BMP4 in the absence of SMAD4 was associated with poor prognosis in breast cancer patients, whereas gene signature upregulated by BMP4 in the presence of SMAD4 was associated with improved prognosis.

Conclusions

BMP4 expression is required for suppression of metastasis regardless of the SMAD4 status of the tumor cells. Since BMP4 is a secreted protein, we conclude that it can act both in an autocrine manner in SMAD4-expressing tumor cells and in a paracrine manner on stromal cells to suppress metastasis. Deletion of SMAD4 from tumor cells does not prevent BMP4 from suppressing metastasis via a paracrine mechanism.
Developing and validating a clinlabomics-based machine-learning model for early detection of retinal detachment in patients with high myopia
Authors: Li Shengjie , Li Meiyan , Wu Jianing , Li Yingzhu , Han Jianping , Song Yunxiao , Cao Wenjun , Zhou Xingtao
Published: April 2024

Background

Retinal detachment (RD) is a vision-threatening disorder of significant severity. Individuals with high myopia (HM) face a 2 to 6 times higher risk of developing RD compared to non-myopes. The timely identification of high myopia-related retinal detachment (HMRD) is crucial for effective treatment and prevention of additional vision impairment. Consequently, our objective was to streamline and validate a machine-learning model based on clinical laboratory omics (clinlabomics) for the early detection of RD in HM patients.

Methods

We extracted clinlabomics data from the electronic health records for 24,440 HM and 5607 HMRD between 2015 and 2022. Lasso regression analysis assessed fifty-nine variables, excluding collinear variables (variance inflation factor > 10). Four models based on random forest, gradient boosting machine (GBM), generalized linear model, and Deep Learning Model were trained for HMRD diagnosis and employed for internal validation. An external test of the models was done. Three random data sets were further processed to validate the performance of the diagnostic model. The primary outcomes were the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) to diagnose HMRD.

Results

Nine variables were selected by all models. Given the AUC and AUCPR values across the different sets, the GBM model was chosen as the final diagnostic model. The GBM model had an AUC of 0.8550 (95%CI = 0.8322–0.8967) and an AUCPR of 0.5584 (95%CI = 0.5250–0.5879) in the training set. The AUC and AUCPR in the internal validation were 0.8405 (95%CI = 0.8060–0.8966) and 0.5355 (95%CI = 0.4988–0.5732). During the external test evaluation, it reached an AUC of 0.7579 (95%CI = 0.7340–0.7840) and an AUCPR of 0.5587 (95%CI = 0.5345–0.5880). A similar discriminative capacity was observed in the three random data sets. The GBM model was well-calibrated across all the sets. The GBM-RD model was implemented into a web application that provides risk prediction for HM individuals.

Conclusion

GBM algorithms based on nine features successfully predicted the diagnosis of RD in patients with HM, which will help ophthalmologists to establish a preliminary diagnosis and to improve diagnostic accuracy in the clinic.
Fusobacterium periodonticum BCT protein targeting glucose metabolism to promote the epithelial-mesenchymal transition of esophageal cancer cells by lactic acid
Authors: Guo Xinxin , Wan Ping , Shen Weitao , Sun Mingjun , Peng Zhenyan , Liao Yinghao , Huang Yang , Liu Ran
Published: April 2024

Background

The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC.

Methods

We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes.

Results

Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and β-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells.

Conclusion

Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/β-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.
Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis
Authors: Dadgar Neda , Sherry Christopher , Zimmerman Jenna , Park Hyun , Lewis Catherine , Donnenberg Albert , Zaidi Ali H. , Fan Yong , Xiao Kunhong , Bartlett David , Donnenberg Vera , Wagner Patrick L.
Published: April 2024

Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.