bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircRNA circ-ATAD1 suppresses miR-618 maturation to participate in colorectal cancer
Authors: Cao Li , Dong Guanglong , Li Huan 
Published: May 2022

Abstract
Background
CircRNA circ-ATAD1 has been characterized as an oncogenic circRNA in gastric cancer, while its role in colorectal cancer (CRC) is unknown. This study was carried out to explore the role of circ-ATAD1 in CRC.

Methods
Paired CRC and adjacent non-tumor tissue samples collected from 64 CRC patients were subjected to RNA extractions and RT-qPCRs to analyze the expression of circ-ATAD1, premature miR-618, and mature miR-618 in CRC. The effects of circ-ATAD1 overexpression on miR-618 maturation were analyzed by transfecting circ-ATAD1 expression vector into CRC cells, followed by determining the expression of premature miR-618 and mature miR-618 using RT-qPCR. The subcellular location of circ-ATAD1 was analyzed by nuclear fractionation assay, and the interaction between circ-ATAD1 and premature miR-618 was analyzed by RNA pull-down assay. The roles of circ-ATAD1, premature miR-618, and mature miR-618 in regulating CRC cell proliferation were explored by CCK-8 assay.

Results
Circ-ATAD1 was upregulated in CRC and predicted poor survival. In addition, circ-ATAD1 was inversely correlated with mature miR-618 but not premature miR-618. In CRC cells, circ-ATAD1 overexpression decreased the level of mature miR-618 but not premature miR-618. Circ-ATAD1 was detected in both the nucleus and cytoplasm. A direct interaction between circ-ATAD1 and miR-618 was observed. Moreover, circ-ATAD1 overexpression reduced the inhibitory effects of miR-618 overexpression on cell proliferation.

Conclusion
Circ-ATAD1 is overexpressed in CRC and may suppress miR-618 maturation to participate in CRC.
Myasthenia gravis coexisting with HINT1-related motor axonal neuropathy without neuromyotonia: a case report
Authors: Fang Jia , Huang Hui , Lei Qiang , Luo Yingying , Tang Zhengchu , Shi Xiaoliu , Tang Jian Guang 
Published: May 2022

Abstract
Background
HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia.

Case presentation
A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up.

Conclusions
Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.
Biological networks in gestational diabetes mellitus: insights into the mechanism of crosstalk between long non-coding RNA and N6-methyladenine modification
Authors: Du Runyu , Bai Yu , Li Ling 
Published: May 2022

Abstract
Background
Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. The mechanism underlying the crosstalk between long non-coding RNAs (lncRNAs) and N6-methyladenine (m6A) modification in GDM remain unclear.

Methods
We generated a lncRNA-mediated competitive endogenous RNA (ceRNA) network using comprehensive data from the Gene Expression Omnibus database, published data, and our preliminary findings. m6A-related lncRNAs were identified based on Pearson correlation coefficient (PCC) analysis using our previous profiles. An integrated pipeline was established to constructed a m6A-related subnetwork thereby predicting the potential effects of the m6A-related lncRNAs.

Results
The ceRNA network was composed of 16 lncRNAs, 17 microRNAs, 184 mRNAs, and 338 edges. Analysis with the Kyoto Encyclopedia of Genes and Genomes database demonstrated that genes in the ceRNA network were primarily involved in the development and adverse outcomes of GDM, such as those in the fatty acid-metabolism pathway, the peroxisome proliferator-activated receptor signaling pathway, and thyroid hormone signaling pathway. Four m6A-related lncRNAs were involved in the ceRNA network, including LINC00667, LINC01087, AP000350.6, and CARMN. The m6A-related subnetwork was generated based on these four lncRNAs, their ceRNAs, and their related m6A regulators. Genes in the subnetwork were enriched in certain GDM-associated hormone (thyroid hormone and oxytocin) signaling pathways. LINC00667 was positively correlated with an m6A “reader” (YTHDF3; PCC = 0.95) and exhibited the highest node degree in the ceRNA network. RIP assays showed that YTHDF3 directly bind LINC00667. We further found that MYC possessed the highest node degree in a protein–protein interaction network and competed with LINC00667 for miR-33a-5p. qPCR analysis indicated that LINC00667, YTHDF3 and MYC levels were upregulated in the GDM placentas, while miR-33a-5p was downregulated. In a support-vector machine classifier, an m6A-related module composed of LINC00667, YTHDF3, MYC, and miR-33a-5p showed excellent classifying power for GDM in both the training and the testing dataset, with an accuracy of 76.19 and 71.43%, respectively.

Conclusions
Our results shed insights into the potential role of m6A-related lncRNAs in GDM and have implications in terms of novel therapeutic targets for GDM.
Associations of keratinocyte cancers with snp variants in the sonic hedgehog pathway
Authors: Rodriguez-Acevedo Astrid J. , Antonsson Annika , Liyanage Upekha E. , Hughes Maria Celia , Gordon Scott , van der Pols Jolieke , Green Adele C. 
Published: May 2022

Abstract
Background
Sonic Hedgehog (SHH) pathway dysregulation is implicated in basal cell carcinoma (BCC) development. To evaluate the possible wider role of SHH gene variants in skin carcinogenesis, we assessed associations of genes in the SHH pathway with lifetime development of any keratinocyte cancer (KC), and with developing either BCCs or squamous cell carcinomas (SCCs) exclusively, in a 25-year prospective, population-based study of 1,621 Australians.

Methods
We genotyped 795 unrelated adults with available blood samples: 311 cases with any KC (186 developing BCCs-only, 55 SCCs-only, 70 BCCs and SCCs) and 484 controls. We compared allele frequencies of 158 independent SNPs across 43 SHH genes between cases and controls, and performed a gene-based analysis.

Results
We found associations between SNP rs4848627 (GLI2) (related to DNA synthesis in keratinocytes) and development of any KC (OR = 1.53; 95% CI = 1.06–2.13, P < 0.01) and SCCs exclusively (OR = 2.12; 95%CI = 1.39–3.23, P < 0.01). SNP rs3217882 located in CCND2 was associated with exclusive BCC development (OR = 1.43, CI = 1.12–1.82, P < 0.01). The gene-based analysis suggested an association of PRKACG (protein kinase cAMP-activated catalytic subunit gamma) with any KC (P = 0.013).

Conclusion
We conclude that variants located in genes in the SHH pathway may are involved in SCC as well as BCC development.
Thoracic kyphosis in light of lumbosacral alignment in thoracic adolescent idiopathic scoliosis: recognition of thoracic hypokyphosis and therapeutic implications
Authors: Iimura Takuya , Ueda Haruki , Inami Satoshi , Moridaira Hiroshi , Takeuchi Daisaku , Aoki Hiromichi , Taneichi Hiroshi 
Published: May 2022

Abstract
Background
The uniqueness of spinal sagittal alignment in thoracic adolescent idiopathic scoliosis (AIS), for example, the drastically smaller thoracic kyphosis seen in some patients, has been recognized but not yet fully understood. The purpose of this study was to clarify the characteristics of sagittal alignment of thoracic AIS and to determine the contributing factors.

Methods
Whole spine radiographs of 83 thoracic AIS patients (73 females) were analyzed. The measured radiographic parameters were the Cobb angle of thoracic scoliosis, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (C7 SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Additionally, max-LL, which was defined as the maximum lordosis angle from the S1 endplate, the inflection point between thoracic kyphosis and lumbar lordosis, and the SVA of the inflection point (IP SVA) were measured. The factors significantly related to a decrease in TK were assessed by stepwise logistic regression analysis. In addition, cluster analysis was performed to classify the global sagittal alignment.

Results
The significant factors for a decrease in TK were an increase in SS (p = 0.0003, [OR]: 1.16) and a decrease in max-LL (p = 0.0005, [OR]: 0.89). According to the cluster analysis, the global sagittal alignment was categorized into the following three types: Type 1 (low SS, low max-LL, n = 28); Type 2 (high SS, low max-LL, n = 22); and Type 3 (high SS, high max-LL, n = 33).

Conclusions
In thoracic AIS, a decreased TK corresponded to an increased SS or a decreased max-LL. The sagittal alignment of thoracic AIS patients could be classified into three types based on SS and max-LL. One of these three types includes the unique sagittal profile of very small TK.
Student characteristics associated with interpersonal skills in medical consultations
Authors: Bellier Alexandre , Chaffanjon Philippe , Morand Patrice , Palombi Olivier , Francois Patrice , Labarère José 
Published: May 2022

Abstract
Background
The quality of medical care depends on effective physician–patient communication. Interpersonal skills can be improved through teaching, but the determinants are poorly understood. We therefore assessed the factors associated with the interpersonal skills of medical students during simulated medical consultations.

Methods
We conducted a cross-sectional study of fourth-year medical students participating in simulated consultations with standardized patients. Each video-recorded medical consultation was independently assessed by two raters, using a cross-cultural adaptation of the Four Habits Coding Scheme (4-HCS) into French. We then collected information on demographics and education-related characteristics. The relationship between the overall 4-HCS score and student characteristics was modeled using univariable and multivariable linear regression.

Results
Our analytical sample included 165 medical students for analysis. The factors significantly associated with 4-HCS score were gender (β = − 4.8, p = 0.011) and completion of an international clinical placement (β = 6.2, p = 0.002) or a research laboratory clerkship (β = 6.5, p = 0.005). Education-related characteristics, multiple-choice examinations in the first to third preclinical years, and number of medicine or surgery clerkships were not significantly associated with 4-HCS score.

Conclusions
Undergraduate students with higher level of interpersonal skills during video-recorded medical consultations with standardized patients are more likely to be female, to have completed international clinical placement as part of the ERASMUS exchange program or research laboratory clerkship.
Experiences of simulated patients in providing feedback in communication skills teaching for undergraduate medical students
Authors: George Riya Elizabeth , Wells Harvey , Cushing Annie 
Published: May 2022

Abstract
Background
Simulated Patients (SPs) are commonplace in the teaching of communication skills in medical education and can provide immediate feedback to students from the patient’s perspective. The experiences of SPs and their perspective on providing feedback is an under-studied area. This study aims to explore SP experiences and views on feedback, factors influencing their feedback and implications for training.

Methods
Using a constructivist grounded theory approach, we conducted six focus groups with 30 SPs. Participants included experienced simulated patients from a London-based actor agency, used in undergraduate teaching programmes of communication skills. Consistent with the principles of grounded theory, data was collected and analysed in an iterative process to identify themes.

Results
Five over-arching themes were identified: 1.) Feedback processes, 2.) Challenges in providing feedback, 3.) Cumulative experiences, 4.) Web of interpersonal relationships and dynamics and 5.) Portraying the character and patient representations.

Discussion
These SPs regarded the sharing of the emotions they experienced during the consultation as the focus of their feedback. Their preference was for giving a ‘sandwich style’ of feedback and ‘out-of-role’ approach. The relationship with facilitators and students and politeness conventions emerged as significant factors when providing feedback. Sensitivity to the social dynamics of groups and implicit facilitator expectations were challenges they experienced as was divergence in views of student performance.

Conclusion
This study explored SP experiences and perspectives on providing feedback. Findings reveal complex social and structural dynamics at play in providing feedback which have not been reported so far in the literature. It is recommended that these issues should be addressed in training of both SPs and facilitators, in addition to feedback guidelines.
Electronic health record implementation and healthcare workers’ work characteristics and autonomous motivation—a before-and-after study
Authors: Veenstra Gepke L. , Rietzschel Eric F. , Molleman Eric , Heineman Erik , Pols Jan , Welker Gera A. 
Published: May 2022

Abstract
Background
Technological innovation in healthcare is often assumed to contribute to the quality of care. However, the question how technology implementation impacts healthcare workers has received little empirical attention. This study investigates the consequences of Electronic Health Record (EHR) implementation for healthcare workers’ autonomous work motivation. These effects are further hypothesized to be mediated by changes in perceived work characteristics (job autonomy and interdependence). Additionally, a moderating effect of profession on the relationship between EHR implementation and work characteristics is explored.

Methods
A quantitative uncontrolled before-and-after study was performed among employees from a large university medical centre in the Netherlands. Data were analysed following the component approach for testing a first stage moderated mediation model, using Generalized Estimating Equations (GEE).

Results
A total of 456 healthcare workers (75 physicians, 154 nurses, 145 allied healthcare professionals, and 82 administrative workers) finished both the baseline and the follow-up survey. After EHR implementation, perceived job autonomy decreased, whereas interdependence increased. In line with our hypothesis, job autonomy was positively associated with autonomous motivation. In contrast to our expectations, interdependence also showed a positive association with autonomous motivation. Autonomous motivation was stable over the course of EHR implementation. This study did not provide support for a moderating effect of profession: no differences were observed between the various professions regarding the changes in their experienced job autonomy and interdependence after EHR implementation.

Conclusions
Our study showed that healthcare professionals’ perceptions of their work characteristics, but not their autonomous motivation, were changed after EHR implementation, and that these experiences were relatively similar for physicians, nurses, and allied healthcare professionals. The stability of healthcare workers’ autonomous motivation may be explained by the opposite effects of decreased job autonomy and increased interdependence, and by the EHR being in line with healthcare workers’ values. The changes in job autonomy and interdependence may have consequences beyond motivation, for example by affecting clinical decision-making, proactive behaviour, and the quality of teamwork. These potential consequences of EHR implementation warrant further research.
Electronic prescribing systems as tools to improve patient care: a learning health systems approach to increase guideline concordant prescribing for venous thromboembolism prevention
Authors: Gallier S. , Topham A. , Nightingale P. , Garrick M. , Woolhouse I. , Berry M. A. , Pankhurst T. , Sapey E. , Ball S. 
Published: May 2022

Abstract
Background
Venous thromboembolism (VTE) causes significant mortality and morbidity in hospitalised patients. Risk factors for VTE are well known and there are validated risk assessment tools to support the use of prophylactic therapies. In England, reporting the percentage of patients with a completed VTE risk assessment is mandated, but this does not include whether that risk assessment resulted in appropriate prescribing. Full guideline compliance, defined as an assessment which led to an appropriate action—here prescribing prophylactic low molecular weight heparin where indicated, is rarely reported. Education, audit and feedback enhance guideline compliance but electronic prescribing systems (EPS) can mandate guideline-compliant actions. We hypothesised that a systems-based EPS intervention (prescribing rules which mandate approval or rejection of a proposed prescription of prophylactic low molecular weight heparin based on the mandated VTE assessment) would increase full VTE guideline compliance more than interventions which focused on targeting individual prescribers.

Methods
All admitted patients within University Hospitals Birmingham NHS Foundation Trust were included for analysis between 2011 and 2020. The proportion of patients who received a fully compliant risk assessment and action was assessed over time. Interventions included teaching sessions and face-to-face feedback based on measured performance (an approach targeting individual prescribers) and mandatory risk assessment and prescribing rules into an EPS (a systems approach).

Results
Data from all 235,005 admissions and all 5503 prescribers were included in the analysis. Risk assessments were completed in > 90–95% of all patients at all times, but full guideline compliance was lower (70% at the start of this study). Face-to-face feedback improved full VTE guideline compliance from 70 to 77% (p ≤ 0.001). Changes to the EPS to mandate assessment with prescribing rules increased full VTE compliance to 95% (p ≤ 0.001). Further amendments to the EPS system to reduce erroneous VTE assessments slightly reduced full compliance to 92% (p < 0.001), but this was then maintained including during changes to the low molecular weight heparin used for VTE prophylaxis.

Discussion
An EPS-systems approach was more effective in improving sustained guideline-compliant VTE prevention over time. Non-compliance remained at 8–5% despite this mandated system. Further research is needed to assess the potential reasons for this.
An exploratory study of client and provider experience and perceptions of facility-based childbirth care in Quiché, Guatemala
Authors: Sethi Reena , Hill Kathleen , Stalls Suzanne , Moffson Susan , de Tejada Sandra Saenz , Gomez Leonel , Marroquin Miguel Angel 
Published: May 2022

Abstract
Introduction
Respectful maternity care (RMC) is fundamental to women’s and families’ experience of care and their decision about where to give birth. Studies from multiple countries describe the mistreatment of women during facility-based childbirth, though only a small number of studies from Guatemala have been published. Less information is available on women’s negative and positive experiences of childbirth care and health workers’ perceptions and experiences of providing maternity care.

Methods
As part of a program implemented in the Western Highlands of Guatemala to improve quality of reproductive maternal newborn and child health care, a mixed methods assessment was conducted in three hospitals and surrounding areas to understand women’s and health workers’ experience and perceptions of maternity care. The quantitative component included a survey of 31 maternity health workers and 140 women who had recently given birth in these hospitals. The qualitative component included in-depth interviews (IDIs) and focus group discussions (FGDs) with women and maternity health workers and managers.

Results
Women reported a mix of positive and negative experiences of childbirth care related to interpersonal and health system factors. 81% of surveyed women reported that health workers had treated them with respect while 21.4% of women reported verbal abuse. Fifty-five percent and 12% of women, respectively, reported not having access to a private toilet and bath or shower. During IDIs and FGDs, many women described higher rates of verbal abuse directed at women who do not speak Spanish. A regression analysis of survey results indicated that speaking Ixil or K’iche at home was associated with a higher likelihood of women being treated negatively during childbirth in a facility. Health worker survey results corroborated negative aspects of care described by women and also reported mistreatment of health workers by clients and families (70.9%) and colleagues (48.2%).

Conclusions
This study adds to the literature on women’s experience of institutional childbirth and factors that influence this experience by triangulating experience and perceptions of both women and health workers. This assessment highlights opportunities to address mistreatment of both women and health workers and to build on positive care attributes to strengthen RMC for all women.