bluuebunny/crossref_metadata_2025_split huggingface dataset:
Willingness to pay for social health insurance and its associated factors among public servants in Addis Ababa, Ethiopia: a cross-sectional study
Authors: Kokebie Melkamu Ayalew , Abdo Ziyad Ahmed , Mohamed Shikur , Leulseged Belayneh 
Published: July 2022

Abstract
Background
As a means of establishing a sustained and fair health care financing system, Ethiopia has planned and ratified a legal framework to introduce a social health insurance program for employees of the formal sector to protect them against financial and health burdens. However, the implementation has been delayed due to the resistance of public servants to pay the proposed premium. The aim of this study was to estimate the magnitude of willingness to pay the proposed amount of premium set by the government for the social health insurance program and the factors associated with it among public servants in Addis Ababa, Ethiopia.

Methods
An institution-based cross-sectional study design was used to conduct the study. Multistage sampling was employed to select a total of 503 from 12 randomly selected public sectors. Data were collected using pretested, interviewer-administered structured questionnaires. A contingent valuation method with an iterative bidding game was used to elicit willingness to pay. Finally, logistic regression analysis was used to identify independent predictors of willingness to pay. Statistical significance was considered at P < 0.05 with adjusted odds ratios calculated at 95% CIs.

Results
Only 35.4% were willing to pay the proposed premium (3% of their monthly salary). Those who had children from 6–18 years old (AOR = 3.252; 95% CI: 1.15, 9.22), had a history of unaffordable health service costs during the last 12 months (AOR = 9.631; 95% CI: 4.12, 22.52), and had prior information about the social health insurance program (AOR = 11.011, 95% CI. 3.735–32.462) were more likely to pay for the proposed social health insurance program compared to their counterparts.

Conclusion
The willingness to pay the proposed amount premium for social health insurance among public servants in Addis Ababa was very low that implies the implementation will be challenging. Thus, the government of Ethiopia should consider reviewing the amount of premium contributions expected from employees before implementing the social health insurance scheme.
Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials
Authors: Zhu Haohao , Gao Hui , Ji Yingying , Zhou Qin , Du Zhiqiang , Tian Lin , Jiang Ying , Yao Kun , Zhou Zhenhe 
Published: July 2022

Abstractp53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53–MDM2 negative feedback loop. Abnormal p53 can be observed in almost all tumors, mainly including p53 mutation and functional inactivation. Blocking MDM2 to restore p53 function is a hotspot in the development of anticancer candidates. Till now, nine MDM2 inhibitors with different structural types have entered clinical trials. However, no MDM2 inhibitor has been approved for clinical application. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53–MDM2 interaction.
The gut–liver axis in sepsis: interaction mechanisms and therapeutic potential
Authors: Zhang Xue , Liu Hong , Hashimoto Kenji , Yuan Shiying , Zhang Jiancheng 
Published: July 2022

AbstractSepsis is a potentially fatal condition caused by dysregulation of the body's immune response to an infection. Sepsis-induced liver injury is considered a strong independent prognosticator of death in the critical care unit, and there is anatomic and accumulating epidemiologic evidence that demonstrates intimate cross talk between the gut and the liver. Intestinal barrier disruption and gut microbiota dysbiosis during sepsis result in translocation of intestinal pathogen-associated molecular patterns and damage-associated molecular patterns into the liver and systemic circulation. The liver is essential for regulating immune defense during systemic infections via mechanisms such as bacterial clearance, lipopolysaccharide detoxification, cytokine and acute-phase protein release, and inflammation metabolic regulation. When an inappropriate immune response or overwhelming inflammation occurs in the liver, the impaired capacity for pathogen clearance and hepatic metabolic disturbance can result in further impairment of the intestinal barrier and increased disruption of the composition and diversity of the gut microbiota. Therefore, interaction between the gut and liver is a potential therapeutic target. This review outlines the intimate gut–liver cross talk (gut–liver axis) in sepsis.
Molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae among children in China
Authors: Jin Zhengjiang , Wang Zhenhui , Gong Lin , Yi Lu , Liu Nian , Luo Lan , Gong Wenting 
Published: July 2022

AbstractKlebsiella pneumoniae infection and antimicrobial resistance among children are major concerns. The occurrence of hypervirulent K. pneumoniae (hvKp) infections is gradually increasing worldwide, and disinfectant resistance is also being reported. Carbapenem- and disinfectant-resistant hvKp infection has made clinical treatment and nosocomial infection control among children increasingly challenging. In this study, whole-genome sequencing was conducted among 34 Carba NP-positive carbapenem-resistant K. pneumoniae (CRKP) strains, and the distribution of antibiotic resistance genes, virulence genes and disinfectant resistance genes was determined. Eleven distinct STs were identified, and most of them were ST11 (58.8%). Among the carbapenem resistance genes, KPC-2 was predominant (61.8%), followed by NDM-1 (26.5%) and IPM-4 (11.8%), and no other carbapenemase genes were found. Twelve virulence genes were investigated. All 34 CRKP strains carried the following virulence genes: rcsA/B, entA, fimA/H and mrkA/D. The gene iucB was present in only 3 (8.9%) CRKP strains. The positive detection rates of the iroN and ybtA genes were 94.1% and 64.7%, respectively. None of the strains was found to carry the rmpA and iroB genes. Two disinfectant resistance genes were investigated in this study. Twenty-one (61.8%) strains carried both the qacE and cepA disinfectant resistance genes, 13 (38.2%) CRKP strains carried only the cepA gene, and no strains with only the qacE gene was detected. The correlations among virulence, drug resistance and disinfectant tolerance showed that the virulence and disinfectant resistance genes were distinct among several types of carbapenemase-producing CRKP strains.
Lipid metabolism and m6A RNA methylation are altered in lambs supplemented rumen-protected methionine and lysine in a low-protein diet
Authors: Gebeyew Kefyalew , Yang Chao , Mi Hui , Cheng Yan , Zhang Tianxi , Hu Fan , Yan Qiongxian , He Zhixiong , Tang Shaoxun , Tan Zhiliang 
Published: July 2022

Abstract
Background
Methionine or lysine has been reported to influence DNA methylation and fat metabolism, but their combined effects in N6-methyl-adenosine (m6A) RNA methylation remain unclarified. The combined effects of rumen-protected methionine and lysine (RML) in a low-protein (LP) diet on lipid metabolism, m6A RNA methylation, and fatty acid (FA) profiles in the liver and muscle of lambs were investigated. Sixty-three male lambs were divided into three treatment groups, three pens per group and seven lambs per pen. The lambs were fed a 14.5% crude protein (CP) diet (adequate protein [NP]), 12.5% CP diet (LP), and a LP diet plus RML (LP + RML) for 60 d.

Results
The results showed that the addition of RML in a LP diet tended to lower the concentrations of plasma leptin (P = 0.07), triglyceride (P = 0.05), and non-esterified FA (P = 0.08). Feeding a LP diet increased the enzyme activity or mRNA expression of lipogenic enzymes and decreased lipolytic enzymes compared with the NP diet. This effect was reversed by supplementation of RML with a LP diet. The inclusion of RML in a LP diet affected the polyunsaturated fatty acids (PUFA), n-3 PUFA, and n-6 PUFA in the liver but not in the muscle, which might be linked with altered expression of FA desaturase-1 (FADS1) and acetyl-CoA carboxylase (ACC). A LP diet supplemented with RML increased (P < 0.05) total m6A levels in the liver and muscle and were accompanied by decreased expression of fat mass and obesity-associated protein (FTO) and alkB homologue 5 (ALKBH5). The mRNA expressions of methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) in the LP + RML diet group were lower than those in the other two groups. Supplementation of RML with a LP diet affected only liver YTH domain family (YTHDF2) proteins (P < 0.05) and muscle YTHDF3 (P = 0.09), which can be explained by limited m6A-binding proteins that were mediated in mRNA fate.

Conclusions
Our findings showed that the inclusion of RML in a LP diet could alter fat deposition through modulations of lipogenesis and lipolysis in the liver and muscle. These changes in fat metabolism may be associated with the modification of m6A RNA methylation.

Graphical abstract
A systematic graph illustrates the mechanism of dietary methionine and lysine influence on lipid metabolism and M6A. The green arrow with triangular heads indicates as activation and brown-wine arrows with flat heads indicates as suppression.
A novel E-cadherin/SOX9 axis regulates cancer stem cells in multiple myeloma by activating Akt and MAPK pathways
Authors: Samart Parinya , Rojanasakul Yon , Issaragrisil Surapol , Luanpitpong Sudjit 
Published: July 2022

AbstractCancer stem cells (CSCs) have been identified in multiple myeloma (MM) and are widely regarded as a key driver of MM initiation and progression. E-cadherin, in addition to its established role as a marker for epithelial-mesenchymal transition, also plays critical roles in controlling the aggressive behaviors of various tumor cells. Here, we show that depletion of E-cadherin in MM cells remarkably inhibited cell proliferation and cell cycle progression, in part through the decreased prosurvival CD138 and Bcl-2 and the inactivated Akt and MAPK pathways. CSC features, including the ability of the cells to form clonogenic colonies indicative of self-renewal and side population, were greatly suppressed upon the depletion of E-cadherin and subsequent loss of SOX9 stem-cell factor. We further provide evidence that SOX9 is a downstream target of E-cadherin-mediated CSC growth and self-renewal—ectopic re-expression of SOX9 in E-cadherin-depleted cells rescued its inhibitory effects on CSC-like properties and survival signaling. Collectively, our findings unveil a novel regulatory mechanism of MM CSCs via the E-cadherin/SOX9 axis, which could be important in understanding the long-term cell survival and outgrowth that leads to relapsed/refractory MM.
First descriptions of the seasonal habitat use and residency of scalloped hammerhead (Sphyrna lewini) and Galapagos sharks (Carcharhinus galapagensis) at a coastal seamount off Japan
Authors: Jacoby David M. P. , Watanabe Yuuki Y. , Packard Tre , Healey Mark , Papastamatiou Yannis P. , Gallagher Austin J. 
Published: July 2022

AbstractBackgroundThe Northwestern Pacific is a data-poor region for studies into the movements and habitat use of open ocean and pelagic sharks. However, this region experiences considerable pressure from commercial fishing. Therefore, shark movement data from this region carry significant implications for conservation and management, particularly for threatened species. Here, we provide the first data on seasonal residency and movements of scalloped hammerhead (Sphyrna lewini) and Galapagos sharks (Carcharhinus galapagensis), using acoustic and satellite telemetry, and dive logbooks, off Japan.ResultsEight female sharks, four of each species, were tagged around a coastal seamount off southeastern Japan (Mikomoto Island) in August 2015, and monitored for a period of up to 363 days using an array of six receivers around the island. Analyses of the more abundant scalloped hammerhead acoustic data suggest high seasonal residency predominantly from August to November associated with lower chlorophyll-aconcentrations, before sharks then leave the island and return the following summer. Residency for scalloped hammerhead sharks were highest among those receivers closest to the Kuroshio Current, which produces strong coastal upwelling, however SST was not found to be predictive of occurrence at Mikomoto. Shark presence was corroborated by analysis of dive-log data from a local ecotourism operator. We also produced two unique satellite tracks, whereby a scalloped hammerhead exhibited a 200-km dispersal into a coastal embayment west of the tagging location and a Galapagos shark migrated over 800 km offshore into the high seas.ConclusionThis study provided some of the first behavioral and movement data for scalloped hammerhead and Galapagos sharks in Japan. Our findings suggest varying spatial and temporal visitation of two shark species to a coastal seamount, underscored by some degree of seasonal residency and site fidelity and linked, for scalloped hammerhead sharks at least, to varying productivity. Furthermore, we provided preliminary evidence for long-distance dispersal of these species, and some site fidelity to seamounts in the region. This study highlights the importance of describing shark movements to aid in filling critical data gaps for poorly understood, endemic populations of threatened species.
The voices of incarcerated women at the forefront of parenting program development: a trauma-informed approach to education
Authors: Lovell Belinda J. , Steen Mary P. , Brown Angela E. , Esterman Adrian J. 
Published: July 2022

Abstract
Background
The lives of women experiencing incarceration are complex, impacting many aspects of parenting. Incarceration can present an opportunity for women to access parenting education. However, their specific needs have to be considered. Few parenting programs for women experiencing incarceration have involved the women as part of their development.

Methods
Six focus groups were conducted in a prison setting involving thirty-one women to explore and understand their parenting education needs.

Results
Four main themes were identified to reflect the complex lives of the women and their parenting education needs. These themes were: working towards a positive self, communication as a lifeline, supporting and nurturing their children and hopefulness and reconnecting. The trauma women experienced in their lives was apparent during discussions.

Conclusion
Women requested a non-judgmental parenting program to be developed to meet their specific needs and circumstances. The program needed to be designed to enable them to share stories with women in similar situations. Women gave insights into some of the specific content and topics they would like included in a parenting program. The women revealed experiences of trauma in their lives, demonstrating the importance of the need for a trauma informed approach to parenting education.
Goal setting with young people for anxiety and depression: What works for whom in therapeutic relationships? A literature review and insight analysis
Authors: Jacob Jenna , Stankovic Milos , Spuerck Inga , Shokraneh Farhad 
Published: July 2022

AbstractBackgroundGoal setting and goal-focused work is widely used in young people’s mental health settings. However, little is known about how, why or for whom this is helpful. This study aims to explore the mechanisms of collaborative goal setting as part of therapeutic relationships: is it helpful for young people experiencing anxiety and/or depression, how and why/not, for whom, and under what circumstances?MethodsOnline database searches generated 10,907 records. Seven unique studies are included, combined with insight analysis from directed discussions with international advisors with lived experience of anxiety and/or depression and therapy (N = 8; mean age = 20.8), and mental health academics/clinicians (N = 6).ResultsFindings are presented as a narrative synthesis and suggest that goal setting is helpful to young people experiencing anxiety and/or depression because it helps build good therapeutic relationships through open communication and building trust. Goal setting helps make things more manageable, enabling young people to feel supported and have ownership of their care. Individual preferences, or high levels of distress, trauma, low confidence, hopelessness, negative past experiences of goal setting, perfectionism, and rumination are considered limiting factors to goal setting. Additionally, contextual factors including country and long-term therapy are explored.ConclusionWhilst the resultant sample is small, emphasis on the voices of young people in the research is both prominent and of paramount importance. Several key literature gaps are identified, including evidenced links to the reduction in symptoms. Priority must be given to researching unhelpful mechanisms of goal setting for young people experiencing anxiety and/or depression, to avoid any potential iatrogenic effects.
Examine the relationships between health-related quality of life, achievement motivation and job performance: the case of Taiwan hospitality industry
Authors: Ni Wei-Ya , Ng Eric , Chiang Yi-Te , LePage Ben A. , Yang Feng-Hua , Fang Wei-Ta 
Published: July 2022

Abstract
Background
Employees are considered as one of the most important assets in many organizations, and their health well-being is critical to help achieve a sustainable and motivated workforce that is committed to delivering quality hospitality services through enhanced performance and productivity. Given the extent of the challenges and impact presented by the COVID-19 pandemic to the hospitality industry, it is timely to gain further insights on employees’ health well-being. The key purpose of this study is to examine the relationships between health-related quality of life, achievement motivation and job performance in the Taiwan hospitality industry, to acquire a better understanding of their relationships through the job performance pathway models.

Methods
This study has used a purposeful sampling technique to select the 10 highest-earning hospitality companies in Taiwan. A total of 292 questionnaires were collected from the employees of these hospitality companies. Based on the multi-dimensional concept of health-related quality of life (HRQoL), the relationships between the five key dimensions (i.e. psychological health, physical health, social health, achievement motivation, and job performance) were examined. To measure these dimensions, the survey questions were adapted from previous research such as the World Health Organization’s WHOQOL-BREF scale, Minnesota Satisfaction Questionnaire. Partial least squares - Structural Equation Modeling method was used to explore these dimensions, and two job performance pathway models (for manager and staff) were subsequently developed.

Results and conclusions
Findings showed that psychological health directly affected the manager’s job performance and physical health had a similar effect through social health. While psychological health had not affected the staff’s job performance, but it could affect achievement motivation through both direct and indirect effects of social health. The pathway models that were developed indicated that the manager’s job performance was mainly affected by psychological health and social health, whereas the key dimension that had affected the staff’s job performance was achievement motivation.
circCYP24A1 promotes Docetaxel resistance in prostate Cancer by Upregulating ALDH1A3
Authors: Yin Haoli , Qin Haixiang , Yang Lei , Chen Mengxia , Yang Yang , Zhang Wenlong , Hao Jiange , Lu Qun , Shi Jingyan , Zhuang Junlong , Qiu Xuefeng , Guo Hongqian 
Published: July 2022

Abstract
Background
Docetaxel (DTX) is the most widely prescribed first-line chemotherapy for advanced prostate cancer (PCa). Unfortunately, DTX resistance invariably emerges, leading to worse prognosis of PCa. Growing evidence has shown that circRNAs had complex spatiotemporal specificity during the tumor development and oncogenesis. This study was designed to investigate the biological functions and possible molecular mechanisms of circRNAs in DTX resistance of PCa.

Methods
circRNAs in established DTX-resistant DU145 cell line were identified by RNA sequencing. Biological function of circCYP24A1 was verified in vitro and in vivo. The potential role of circCYP24A1 in the development of DTX-resistant PCa was investigated via dual-luciferase reporter assays, RIP assays and RNA pull-down assays. Univariate and multivariate logistic regression analyses was used to predict DTX-chemotherapy response based on patients’ clinical and biological information.

Results
CircCYP24A1 was identified to be upregulated in DTX-resistant DU145 cells. Upregulated circCYP24A1 was found to suppress the DTX chemosensitivity in vitro and in vivo. Furthermore, we found that circCYP24A1 promoted DTX resistance in PCa via regulating ALDH1A3 expression by sponging miR-1301-3p and activating PI3K/AKT/mTOR signaling pathway. Statistical analyses elucidated that circCYP24A1 was an independent risk factor to predict DTX response (OR = 0.165; 95% CI: 0.038–0.723; P = 0.017).

Conclusions
This study demonstrated that circCYP24A played an essential role in DTX resistance in PCa, suggesting that circCYP24A1 could be a promising biomarker to predict DTX response and a potential therapeutic target in PCa patients resistant to DTX chemotherapy.
IGSF11 and VISTA: a pair of promising immune checkpoints in tumor immunotherapy
Authors: Tang Xi-Yang , Xiong Yan-Lu , Shi Xian-Gui , Zhao Ya-Bo , Shi An-Ping , Zheng Kai-Fu , Liu Yu-Jian , Jiang Tao , Ma Nan , Zhao Jin-Bo 
Published: July 2022

AbstractImmunotherapy has become the major treatment for tumors in clinical practice, but some intractable problems such as the low response rate and high rates of immune-related adverse events still hinder the progress of tumor immunotherapy. Hence, it is essential to explore additional immunotherapy treatment targets. In this review, we focus on the structure, expression and expression-related mechanisms, interactions, biological functions and the progress in preclinical/clinical research of IGSF11 and VISTA in tumors. We cover the progress in recent research with this pair of immune checkpoints in tumor immune regulation, proliferation, immune resistance and predictive prognosis. Both IGSF11 and VISTA are highly expressed in tumors and are modulated by various factors. They co-participate in the functional regulation of immune cells and the inhibition of cytokine production. Besides, in the downregulation of IGSF11 and VISTA, both inhibit the growth of some tumors. Preclinical and clinical trials all emphasize the predictive role of IGSF11 and VISTA in the prognosis of tumors, and that the predictive role of the same gene varies from tumor to tumor. At present, further research is proving the enormous potential of IGSF11 and VISTA in tumors, and especially the role of VISTA in tumor immune resistance. This may prove to be a breakthrough to solve the current clinical immune resistance, and most importantly, since research has focused on VISTA but less on IGSF11, IGSF11 may be the next candidate for tumor immunotherapy.