bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhein promotes the proliferation of keratinocytes by targeting oestrogen receptors for skin ulcer treatment
Authors: Xu Ning , Chen Yuanran , Guo Dongjie , Deng Yu , Guo Wanjun , Liu Xin , Wang Yi , Lu Hanzhi , Liu Aijun , Zhu Jianyong , Li Fulun 
Published: August 2022

Abstract
Background
The Sheng-ji Hua-yu (SJHY) formula is a quite effective Traditional Chinese Medicines (TCM) in the treatment of delayed diabetic wounds. Previous research has shown that the SJHY formula has significant anti-inflammatory and wound-healing effects, but the precise mechanism remains unknown. The purpose of this study was to evaluate the effects of rhein, a compound extracted from SJHY formula, in keratinocytes and to investigate the underlying mechanisms.

Methods
Microscale thermophoresis (MST) technology was used to confirm that rhein binds directly to oestrogen receptors (ERs). Rhein was then used to treat keratinocytes in vitro. Cell cycle and proliferation analysis, Real-time polymerase chain reaction (RT-PCR) and Western-blot were conducted.

Results
Rhein increased the proportion of cells in the S phase of the cell cycle and promoted keratinocyte proliferation. ICI 182,780, an ER inhibitor, was also used to treat keratinocytes. The expression of c-myc mRNA and protein induced by rhein was antagonized by ICI 182,780, indicating that this induction is ER dependent. Intervention with ICI 182,780 had no effect on the upregulation of FosB and JunD, indicating that activator protein 1 (AP-1) members (FosB and JunD) are involved in rhein-induced c-myc mRNA and protein expression but does not require the ER.

Conclusion
The present study found that rhein stimulates keratinocyte proliferation by activating the oestrogen signalling pathway via the oestrogen receptor, which induces the expression of c-myc in collaboration with FosB and JunD, thereby accelerating the process of re-epithelialization.
Collaborators as a key to survival: an ethnographic study on newly graduated doctors’ collaboration with colleagues
Authors: Klitgaard Tine Lass , Stentoft Diana , Johansson Nicolaj , Grønkjær Mette , Nøhr Susanne Backman 
Published: August 2022

Abstract
Background
Newly graduated doctors find their first months of practice challenging and overwhelming. As the newly graduated doctors need help to survive this period, collaborators such as peers, senior doctors, registered nurses and other junior doctors are crucial. However, little is known about what characterise these collaborations, and how much is at stake when newly graduated doctors are striving to establish and maintain them. This study aims to describe and explore the collaborations in depth from the newly graduated doctors’ point of view.

Methods
We conducted 135 h of participant observations among newly graduated doctors (n = 11), where the doctors were observed throughout their working hours at various times of the day and the week. Furthermore, six semi-structured interviews (four group interviews and two individual) were carried out. The data was analysed thematically.

Results
Newly graduated doctors consulted different collaborators (peers, senior doctors, registered nurses, and other junior doctors) dependent on the challenge at hand, and they used different strategies to get help and secure good relationships with their collaborators: 1) displaying competence; 2) appearing humble; and 3) playing the game. Their use of different strategies shows how they are committed to engage in these collaborations, and how much is at stake.

Conclusions
Newly graduated doctors rely on building relationships with different collaborators in order to survive their first months of practice. We argue that the collaboration with peer NGDs and registered nurses has not received the attention it deserves when working with the transition from medical school. We highlight how it is important to focus on these and other collaborators and discuss different work-agendas, mutual expectations, and interdependence. This could be addressed in the introduction period and be one way to ensure a better learning environment and a respectful interprofessional culture.
Assessment the effect of diabetes education on self-care behaviors and glycemic control in the Turkey Nursing Diabetes Education Evaluating Project (TURNUDEP): a multi-center study
Authors: Celik Selda , Olgun Nermin , Yilmaz Feride Taskin , Anataca Gulden , Ozsoy Ilksen , Ciftci Nurcan , Aykiz Elif Fidan , Yasa Serap , Karakiraz Ebru , Ulker Yeliz , Demirhan Yeliz Erdem , Celik Sultan Yurtsever , Arpaci Inci , Gunduz Fulya , Temel Derya , Dincturk Cevahir , Sefer Betul Essiz , Bagdemir Elif , Erdem Esin , Sarimehmetoglu Esra , Sahin Fatime , Gulsen Gulay , Kocakgol Nese , Gokmen Sibel , Damar Suna , Celikoz Zekiye , Korkusuz Yesim , Kirlak Senay , Dede Tugce , Kahraman Behice , Sert Arzu , Cetin Nesrin 
Published: August 2022

Abstract
Background
Diabetes education in Turkey is provided by diabetes nurse educators in almost all healthcare organizations. However, the education is not standardized in terms of learning content, duration, and methods. This multi-center study was performed to assess the self-care behaviors and glycemic control following education provided to the patients with type 2 diabetes mellitus by diabetes nurse educators.

Methods
This was a descriptive and cross-sectional study and included 1535 patients admitted to 28 public hospitals for the treatment of type 2 diabetes mellitus. The education was assessed by using a Patient Identification Form and Self-care Scale.

Results
The proportion of individuals who received diabetes education within the last year was 78.5%, with 46.7% of them having received it once. Of the patients, 84.8% reported that they received diabetes education individually. It was found that the proportion of individuals who received education about oral antidiabetics (78.5%) and glucose testing at home (78.5%) was higher than the proportion of individuals who received education about exercise (58.8%) and foot care (61.6%). The status of diabetes education, education intervals, and the correlation of the education method with self-care and glycemic control was evaluated. Self-care and glycemic control levels were better among the patients who received diabetes education thrice or more and in patients who received education both individually and in a group (p < 0.05).

Conclusions
Approximately three-quarters of individuals with type 2 diabetes mellitus received education by diabetes nurse educators in Turkey. Diabetes education is positively correlated with self-care and glycemic control levels among patients with type 2 diabetes mellitus. Efforts for generalization and standardized education for all diabetes patients are necessary.
Facilitators for and barriers to nurses’ work-related health-a qualitative study
Authors: Thapa Dip Raj , Subedi Madhusudan , Ekström-Bergström Anette , Areskoug Josefsson Kristina , Krettek Alexandra 
Published: August 2022

Abstract
Background
Work-related health problems, such as work stress, fatigue, and burnout constitute a global challenge within the nursing profession. Work-related health among nurses is not yet a prioritized phenomenon in Nepal. Health-promoting approaches to maintaining and sustaining nurses’ health are therefore essential. The aim of this study was to explore and thereby gain a deeper understanding of how nurses in Nepal’s hospitals experience their everyday work, with a focus on promoting and sustaining their work-related health.

Methods
A qualitative design with semi-structured individual interviews were used. Nineteen registered nurses working at hospitals in Kathmandu Valley, Nepal, were individually interviewed between October 6 and December 5, 2018. Transcribed interviews were analyzed through thematic analysis.

Results
Four main themes with belonging eight subthemes were constructed from the analysis: (1) “Sense of meaningfulness and belongingness in work culture” with subthemes; “Open environment” and “Sharing attitude and cooperating for the entire team” (2) “Support and rewards from the management team” with subthemes; “Lacking managerial support” and “Fair evaluation and job promotion opportunities”(3) “Workload and protection against work-related hazards” with subthemes; “Stressful and multitasking in workload” and “Lacking equipment for own health and caring”, and (4) “Motivation through opportunities and activities” with subthemes; “Employment benefits that motivate work”, and “Activities outside of work needed to recover”. These main themes and subthemes described nurses’ facilitators for and barriers to their work environment and health.

Conclusion
Our study highlighted nurses’ experiences with facilitators and barriers to their work-related health. Nurses’ work-related health was positively affected by support from colleagues, managers, and the organization. Conversely, less support from managers, lack of equipment, and unfair judgment were barriers to nurses’ work-related health. This study adds new knowledge about nurses’ work-related health from the context of Nepal. Hospital organizations and nursing managers in similar cultural and healthcare settings can apply the results of our study to develop strategies to promote and sustain nurses’ health and prevent work-related illness.
The value of incorporating patient-consulted medication reconciliation in influencing drug-related actions in the outpatient rheumatology setting
Authors: van der Nat Denise J. , Huiskes Victor J. B. , van der Maas Aatke , Derijks-Engwegen Judith Y. M. N. , van Onzenoort Hein A. W. , van den Bemt Bart J. F. 
Published: August 2022

Abstract
Background
Unintentional changes to patients’ medicine regimens and drug non-adherence are discovered by medication reconciliation. High numbers of outpatient visits and medication reconciliation being time-consuming, make it challenging to perform medication reconciliation for all outpatients. Therefore, we aimed to get insight into the proportion of outpatient visits in which information obtained with medication reconciliation led to additional drug-related actions.

Methods
In October and November 2018, we performed a cross-sectional observational study at the rheumatology outpatient clinic. Based on a standardized data collection form, outpatient visits were observed by a pharmacy technician trained to observe and report all drug-related actions made by the rheumatologist. Afterwards, the nine observed rheumatologists and an expert panel, consisting of two rheumatologists and two pharmacists, were individually asked which drug information reported on the drug list composed by medication reconciliation was required to perform the drug-related actions. The four members of the expert panel discussed until consensus was reached about their assessment of the required information. Subsequently, a researcher determined if the required information was available in digital sources: electronic medical record (electronic prescribing system plus physician’s medical notes) or Dutch Nationwide Medication Record System.

Results
Of the 114 selected patients, 83 (73%) patients were included. If both digital drug sources were available, patient’s input during medication reconciliation resulted in additional information to perform drug-related actions according to the rheumatologist in 0% of the visits and according to the expert panel in 14%. If there was only access to the electronic medical record, the proportions were 8 and 29%, respectively. Patient’s input was especially required for starting a new drug and discussing drug-related problems.

Conclusions
If rheumatologists only had access to the electronic medical record, in 1 out of 3 visits the patient provided additional information during medication reconciliation which was required to perform a drug-related action. When rheumatologists had access to two digital sources, patient’s additional input during medication reconciliation was at most 14%. As the added value of patient’s input was highest when rheumatologists prescribe a new drug and/or discuss a drug-related problem, it may be considered that rheumatologists only perform medication reconciliation during the visit when performing one of these actions.
Association of IKZF1 and CDKN2A gene polymorphisms with childhood acute lymphoblastic leukemia: a high-resolution melting analysis
Authors: Sattarzadeh Bardsiri Mahla , Zehtab Shahrzad , Karami Najibe , Farsinejad Alireza , Ehsan Mohsen , Fatemi Ahmad 
Published: August 2022

Abstract
Background
Acute lymphoblastic leukemia is the most prevailing pediatric hematologic malignancy, and various factors such as environmental exposures and genetic variation affect ALL susceptibility and patients outcome. According to genome-wide association studies, several single nucleotide polymorphisms (SNPs) in IKZF1 (rs4132601) and CDKN2A (rs3731249 and rs3731217) genes are associated with ALL susceptibility. Hereupon, this study aimed to discover the association between these SNPs and the risk of childhood ALL among a sample of the Iranian population.

Methods
A total of fifty children with ALL were included in this case–control study, along with an additional fifty healthy children, matched for age and gender. High-resolution melting (HRM) analysis was employed to genotyping rs4132601, rs3731249, and rs3731217.

Results
In the patient group, the CT genotype and T allele frequency of rs3731249 were significantly greater than controls (p = 0.01 and p = 0.005, respectively). Moreover, the positive association of CT and dominant model (CT + TT) genotypes and T allele at rs3731249 with the risk of ALL was confirmed (OR = 9.56, OR = 10.76 and OR = 11.00, respectively). There was no significant relation between rs4132601 (IKZF1), rs3731217 (CDKN2A), and childhood ALL.

Conclusion
The present study indicates that CT genotype and T allele at rs3731249 (CDKN2A) can significantly increase the risk of ALL among children.
Recent advances in conventional and unconventional vesicular secretion pathways in the tumor microenvironment
Authors: Kuo I.-Ying , Hsieh Chih-Hsiung , Kuo Wan-Ting , Chang Chih-Peng , Wang Yi-Ching 
Published: August 2022

AbstractAll cells in the changing tumor microenvironment (TME) need a class of checkpoints to regulate the balance among exocytosis, endocytosis, recycling and degradation. The vesicular trafficking and secretion pathways regulated by the small Rab GTPases and their effectors convey cell growth and migration signals and function as meditators of intercellular communication and molecular transfer. Recent advances suggest that Rab proteins govern conventional and unconventional vesicular secretion pathways by trafficking widely diverse cargoes and substrates in remodeling TME. The mechanisms underlying the regulation of conventional and unconventional vesicular secretion pathways, their action modes and impacts on the cancer and stromal cells have been the focus of much attention for the past two decades. In this review, we discuss the current understanding of vesicular secretion pathways in TME. We begin with an overview of the structure, regulation, substrate recognition and subcellular localization of vesicular secretion pathways. We then systematically discuss how the three fundamental vesicular secretion processes respond to extracellular cues in TME. These processes are the conventional protein secretion via the endoplasmic reticulum-Golgi apparatus route and two types of unconventional protein secretion via extracellular vesicles and secretory autophagy. The latest advances and future directions in vesicular secretion-involved interplays between tumor cells, stromal cell and host immunity are also described.
Population knowledge, attitudes and practices towards malaria prevention in the locality of Makenene, Centre-Cameroon
Authors: Djoufounna Joel , Bamou Roland , Mayi Marie Paul Audrey , Kala-Chouakeu Nelly Armanda , Tabue Raymond , Awono-Ambene Parfait , Achu-Fosah Dorothy , Antonio-Nkondjio Christophe , Tchuinkam Timoléon 
Published: August 2022

Abstract
Background
To contribute to the mission of the National Malaria Control Programme (NMCP) and guide future interventions in Cameroon in general, and in Makenene in particular, this study assessed the knowledge, attitudes and practices of the population of Makenene towards the fight against malaria.

Methods
Using a semi-structured questionnaire, a descriptive cross-sectional household community survey was carried out in randomly selected households in Makenene, a locality situated between forest and savannah ecotypes.

Results
Out of the 413 households surveyed, all (100%) claimed to have heard of malaria with over 94% (n = 391) associating disease transmission with mosquito bites. The main mosquito control tools used in the area were mosquito nets (92.25%). The majority of participants had good knowledge (55.93%; n = 231), good practices (71.67%, n = 296) but moderate attitudes (47.94%; n = 198) towards malaria control and fight. Good knowledge and practices were recorded mostly in educated persons including public servants and students. Good attitudes were adopted mostly by public servants and students of secondary and higher levels of education.

Conclusion
In Makenene, the population exhibits good knowledge and practices towards malaria and its control. However, despite high LLINs ownership and use, people still complain about malaria in the area. Control tools should be monitored, repaired or replaced when necessary to support the achievement of the NMCP mission.
Risk predictive model based on three immune-related gene pairs to assess prognosis and therapeutic sensitivity for hepatocellular carcinoma
Authors: Qian Baifeng , Lin Haozhong , Lan Tian , Li Muqi , Wu Xiwen , Lin Shuirong , Song Zimin , Shen Shunli , Peng Baogang 
Published: August 2022

Abstract
Background
Hepatocellular carcinoma (HCC) as a common tumor has a poor prognosis. Recently, a combination of atezolizumab and bevacizumab has been recommended as the preferred regimen for advanced HCC. However, the overall response rate of this therapy is low. There is an urgent need to identify sensitive individuals for this precise therapy among HCC patients.

Methods
The Wilcox test was used to screen the differentially expressed immune-related genes by combining the TCGA cohort and the Immunology Database. Univariate and multivariate Cox regression analysis were used to screen the immune gene pairs concerning prognosis. A predictive model was constructed using LASSO Cox regression analysis, and correlation analysis was conducted between the signature and clinical characteristics. ICGC cohort and GSE14520 were applied for external validations of the predictive risk model. The relationship between immune cell infiltration, TMB, MSI, therapeutic sensitivity of immune checkpoint inhibitors, targeted drugs, and the risk model were assessed by bioinformatics analysis in HCC patients.

Results
A risk predictive model consisting of 3 immune-related gene pairs was constructed and the risk score was proved as an independent prognostic factor for HCC patients combining the TCGA cohort. This predictive model exhibited a positive correlation with tumor size (p < 0.01) and tumor stage (TNM) (p < 0.001) in the chi-square test. The predictive power was verified by external validations (ICGC and GSE14520). The risk score clearly correlated with immune cell infiltration, MSI, immune checkpoints, and markers of angiogenesis.

Conclusions
Our research established a risk predictive model based on 3 immune-related gene pairs and explored its relationship with immune characteristics, which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of HCC patients.
A national prevalence and profile of single and multiple developmental delays among children aged from 1 year up to 12 years: an Egyptian community-based study
Authors: Metwally Ammal M. , Abdallah Ali M. , Salah El-Din Ebtissam M. , Khadr Zeinab , Raouf Ehab R. Abdel , Elghareeb Nahed A. , Saleh Rehan M. , Abuelela Manal H. , Amer Hala A. , Hasanin Hasanin M. , Mawla Mohamed A. Abdel , Sallam Sara F. , El-Alameey Inas R. , Sami Samia M. , Abdel-Latif Ghada A. , Abdelrahman Mohamed , Shehata Manal A. 
Published: August 2022

Abstract
Objective
This study aimed at providing a national prevalence of single and multiple developmental delays (DDs) among 41,640 Egyptian children aged 1 to 12 years and exploring DDs’ associated risk and protective factors.

Methods
A national household survey from eight governorates of Egypt representing the four major subdivisions of Egypt was conducted through systematic probability proportionate to size. All enrolled children were assessed according to Vineland Adaptive Behavior Scales, (VABS) as a reliable screening questionnaire for identifying categories of DDs that were verified by pediatrics’ specialists.

Results
The overall prevalence of children with DDs was 6.7%. The prevalence of a single DD was 3.9% versus 2.8% multiple DDs. Communication deficit was the most prevalent type (5.3%). Lower prevalence was identified for fine motor delay (1.0%), gross motor delay, and socialization deficit (1.5% each). Whereas deficits in daily life skills (self-help and adaptive behavior delay) amounted to 2.3%. Living without mothers and/or fathers in homes was associated with increased odds of having DDs by one and a half times (OR = 1.72 and OR = 1.34 respectively). Multiple logistic regression analysis revealed the most predictors for DDs including children who suffer from convulsions after birth (OR = 3.10), low birth weight babies (OR = 1.94), male sex (OR = 1.75), mothers having health problems during pregnancy (OR = 1.70) and belonging to middle socioeconomic status (OR = 1.41). Children who suffered from cyanosis after birth was found to be at risk for any or multiple DDs. Difficult labor was significantly associated with increased odds for multiple DDs (OR = 1.55). Higher paternal and maternal education was associated with decreased odds to have any DDs by 40% (OR = 0.60 and OR = 0.58 respectively).

Conclusions
The detected prevalence of DDs is within the estimated range of prevalence of DDs for the pediatric population. The majority of the detected risk factors are preventable. Developmental screening is recommended to be implemented in all primary care settings as a routine practice.
Interstitial deletion 4p15.32p16.1 and complex chromoplexy in a female proband with severe neurodevelopmental delay, growth failure and dysmorphism
Authors: Li Dong , Strong Alanna , Hou Cuiping , Downes Helen , Pritchard Amanda Barone , Mazzeo Pamela , Zackai Elaine H. , Conlin Laura K. , Hakonarson Hakon 
Published: August 2022

AbstractComplex chromosomal rearrangements involve the restructuring of genetic material within a single chromosome or across multiple chromosomes. These events can cause serious human disease by disrupting coding DNA and gene regulatory elements via deletions, duplications, and structural rearrangements. Here we describe a 5-year-old female with severe developmental delay, dysmorphic features, multi-suture craniosynostosis, and growth failure found to have a complex series of balanced intra- and inter-chromosomal rearrangements involving chromosomes 4, 11, 13, and X. Initial clinical studies were performed by karyotype, chromosomal microarray, and FISH with research-based short-read genome sequencing coupled with sanger sequencing to precisely map her breakpoints to the base pair resolution to understand the molecular basis of her phenotype. Genome analysis revealed two pathogenic deletions at 4p16.1-p15.32 and 4q31.1, accounting for her developmental delay and dysmorphism. We identified over 60 breakpoints, many with blunt ends and limited homology, supporting a role for non-homologous end joining in restructuring and resolution of the seminal chromoplexy event. We propose that the complexity of our patient’s genomic rearrangements with a high number of breakpoints causes dysregulation of gene expression by three-dimensional chromatin interactions or topologically associating domains leading to growth failure and craniosynostosis. Our work supports an important role for genome sequencing in understanding the molecular basis of complex chromosomal rearrangements in human disease.