bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse
Authors: Suzuki Akiko , Yoshioka Hiroki , Summakia Dima , Desai Neha G. , Jun Goo , Jia Peilin , Loose David S. , Ogata Kenichi , Gajera Mona V. , Zhao Zhongming , Iwata Junichi 
Published: November 2019

AbstractBackgroundCleft lip (CL), one of the most common congenital birth defects, shows considerable geographic and ethnic variation, with contribution of both genetic and environmental factors. Mouse genetic studies have identified several CL-associated genes. However, it remains elusive how these CL-associated genes are regulated and involved in CL. Environmental factors may regulate these genes at the post-transcriptional level through the regulation of non-coding microRNAs (miRNAs). In this study, we sought to identify miRNAs associated with CL in mice.ResultsThrough a systematic literature review and a Mouse Genome Informatics (MGI) database search, we identified 55 genes that were associated with CL in mice. Subsequent bioinformatic analysis of these genes predicted that a total of 33 miRNAs target multiple CL-associated genes, with 20 CL-associated genes being potentially regulated by multiple miRNAs. To experimentally validate miRNA function in cell proliferation, we conducted cell proliferation/viability assays for the selected five candidate miRNAs (miR-124-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7d-5p). Overexpression of miR-124-3p, but not of the others, inhibited cell proliferation through suppression of CL-associated genes in cultured mouse embryonic lip mesenchymal cells (MELM cells) isolated from the developing mouse lip region. By contrast, miR-124-3p knockdown had no effect on MELM cell proliferation. This miRNA-gene regulatory mechanism was mostly conserved in O9–1 cells, an established cranial neural crest cell line. Expression of miR-124-3p was low in the maxillary processes at E10.5, when lip mesenchymal cells proliferate, whereas it was greatly increased at later developmental stages, suggesting that miR-124-3p expression is suppressed during the proliferation phase in normal palate development.ConclusionsOur findings indicate that upregulated miR-124-3p inhibits cell proliferation in cultured lip cells through suppression of CL-associated genes. These results will have a significant impact, not only on our knowledge about lip morphogenesis, but also on the development of clinical approaches for the diagnosis and prevention of CL.
Tuberculosis outbreaks among students in mainland China: a systematic review and meta-analysis
Authors: Bao Hongdan , Liu Kui , Wu Zikang , Wang Xiaomeng , Chai Chengliang , He Tieniu , Wang Wei , Wang Fei , Peng Ying , Chen Bin , Jiang Jianmin 
Published: November 2019

Abstract
Background
In recent years, tuberculosis outbreaks in schools have occurred more frequently in China than in other parts of the world, and have posed a public health threat to students and their families. This systematic review aimed to understand the epidemiological characteristics of tuberculosis (TB) outbreaks and analyze the factors associated with TB outbreaks in schools in China.

Methods
We conducted this systematic review following the standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The meta-analysis was performed with STATA using a random effects model.

Results
We included 107 studies involving 1795 student patients with TB in mainland China. The results of the systematic analysis indicated that TB outbreaks were more frequently reported in senior middle schools and in Eastern China. The outbreaks mainly occurred during the winter and spring, and the median outbreak duration was 4 months. The meta-analysis showed that the total attack rate and the class attack rate of tuberculosis outbreaks among students were 4.60% (95% CI 3.80 to 5.70%) and 22.70% (95% CI 19.20 to 27.00%), respectively. Subgroup analysis showed that outbreaks that occurred at universities or colleges had a relatively higher attack rate than those occurred in senior middle schools. The prevalence of latent tuberculosis infection (LTBI) among close contacts was 23.70% (95% CI 19.50 to 28.90%). The median case-finding interval was 2 months, and 47.40% of the index cases had a case-finding delay.

Conclusion
The results of our review indicated that school TB outbreaks were reported most frequently in senior middle schools in China. The attack rates of outbreaks at universities or colleges were higher than those in senior middle schools. The TB outbreaks in schools usually occurred over prolonged periods. The case-finding delay in the index cases must be reduced to prevent transmission in classes and schools. Effective surveillance and screening of presumptive TB cases in schools should be strengthened to reduce outbreaks in schools.
Lapatinib sensitivity in nasopharyngeal carcinoma is modulated by SIRT2-mediated FOXO3 deacetylation
Authors: Aimjongjun Sathid , Mahmud Zimam , Jiramongkol Yannasittha , Alasiri Glowi , Yao Shang , Yagüe Ernesto , Janvilisri Tavan , Lam Eric W.-F. 
Published: November 2019

Abstract
Background
Chemoresistance is an obstacle to the successful treatment of nasopharyngeal carcinoma (NPC). Lapatinib is a targeted tyrosine kinase inhibitor therapeutic drug also used to treat NPC, but high doses are often required to achieve a result. To investigate the mechanism for the development of Lapatinib resistance, we characterised a number of NPC cell lines to determine the role of FOXO3 and sirtuins in regulating NPC resistance.

Methods
Sulforhodamine B (SRB) assays, Clonogenic assays, Protein extraction, quantification and western blotting, RT qPCR, Co-immunoprecipitation assay.

Results
To explore novel treatment strategies, we first characterized the Lapatinib-sensitivity of a panel of NPC cell lines by SRB and clonogenic cytotoxic assays and found that the metastatic NPC (C666–1 and 5-8F) cells are highly resistant whereas the poorly metastatic lines (6-10B, TW01 and HK-1) are sensitive to Lapatinib. Western blot analysis of the Lapatinib-sensitive 6-10B and resistant 5-8F NPC cells showed that the expression of phosphorylated/inactive FOXO3 (P-FOXO3;T32), its target FOXM1 and its regulator SIRT2 correlate negatively with Lapatinib response and sensitivity, suggesting that SIRT2 mediates FOXO3 deacetylation to promote Lapatinib resistance. In agreement, clonogenic cytotoxic assays using wild-type and foxo1/3/4−/− mouse embryonic fibroblasts (MEFs) showed that FOXO1/3/4-deletion significantly attenuates Lapatinib-induced cytotoxicity, confirming that FOXO proteins are essential for mediating Lapatinib response. SRB cell viability assays using chemical SIRT inhibitors (i.e. sirtinol, Ex527, AGK2 and AK1) revealed that all SIRT inhibitors can reduce NPC cell viability, but only the SIRT2-specific inhibitors AK1 and AGK2 further enhance the Lapatinib cytotoxicity. Consistently, clonogenic assays demonstrated that the SIRT2 inhibitors AK1 and AGK2 as well as SIRT2-knockdown increase Lapatinib cytotoxicity further in both the sensitive and resistant NPC cells. Co-immunoprecipitation studies showed that besides Lapatinib treatment, SIRT2-pharmaceutical inhibition and silencing also led to an increase in FOXO3 acetylation. Importantly, SIRT2 inhibition and depletion further enhanced Lapatinib-mediated FOXO3-acetylation in NPC cells.

Conclusion
Collectively, our results suggest the involvement of SIRT2-mediated FOXO3 deacetylation in Lapatinib response and sensitivity, and that SIRT2 can specifically antagonise the cytotoxicity of Lapatinib through mediating FOXO3 deacetylation in both sensitive and resistant NPC cells. The present findings also propose that SIRT2 can be an important biomarker for metastatic and Lapatinib resistant NPC and that targeting the SIRT2-FOXO3 axis may provide novel strategies for treating NPC and for overcoming chemoresistance.
Circulating tumour DNA (ctDNA) as a biomarker in metachronous melanoma and colorectal cancer- a case report
Authors: Calapre Leslie , Warburton Lydia , Millward Michael , Gray Elin S. 
Published: November 2019

Abstract
Background
Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker for monitoring disease status of patients with advanced cancers. The presence of ctDNA in the blood is a result of biological processes, namely tumour cell apoptosis and/or necrosis, and can be used to monitor different cancers by targeting cancer-specific mutation.

Case presentation
We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer. The kinetics of ctDNA derived from each cancer type were monitored targeting BRAF V600R (melanoma) and KRAS G13D (colon cancer), specifically reflected the status of the patient’s tumours. In fact, the discordant pattern of BRAF and KRAS ctDNA was significantly correlated with the clinical response of melanoma to pembrolizumab treatment and progression of colorectal cancer noted by PET and/or CT scan. Based on these results, ctDNA can be used to specifically clarify disease status of patients with metachronous cancers.

Conclusions
Using cancer-specific mutational targets, we report here for the first time the efficacy of ctDNA to accurately provide a comprehensive outlook of the tumour status of two different cancers within one patient. Thus, ctDNA analysis has a potential clinical utility to delineate clinical information in patients with multiple cancer types.
Comparability of three intraocular pressure measurement: iCare pro rebound, non-contact and Goldmann applanation tonometry in different IOP group
Authors: Chen Min , Zhang Lina , Xu Jia , Chen Xinyi , Gu Yuxiang , Ren Yuping , Wang Kaijun 
Published: November 2019

Abstract
Background
Measurement of intraocular pressure (IOP) is essential for glaucoma patients. Many factors such as central corneal thickness (CCT) can affect the accuracy of IOP measurement. The purpose of this study was to evaluate the agreement of IOP measured by non-contact tonometer (NCT), iCare pro rebound tonometer (iCare), and Goldmann applanation tonometer (GAT) in different IOP group.

Methods
This was a Hospital-based cross-sectional study. Two hundred subjects were enrolled in this study. All subjects underwent IOP measurement using an NCT–iCare–GAT sequence. Bland-Altman, Pearson correlation and intraclass correlation analysis were performed using SPSS 17.0 software. The influence of CCT on each IOP measurement methods was evaluated by linear regression analysis.

Results
The mean difference (Δ) of NCT–GAT did not differ from (Δ) iCare–GAT in IOP < 10 and 10–21 mmHg group. However, (Δ) NCT–GAT was significantly higher than (Δ) iCare–GAT in IOP 22–30 and > 30 mmHg group (P < 0.05). Bland–Altman analysis showed significant agreement between the three devices (P < 0.01). IOP measurements of the three methods were significantly correlated with CCT (P < 0.01).

Conclusions
ICare pro shows a higher agreement with GAT over a wide range of IOP compared with NCT. The consistency between the three tonometers was similar in a low and normal IOP range. However, NCT shows a greater overestimate of IOP in moderate and higher IOP group. The variability of IOP measurement affected by CCT is NCT > iCare pro > GAT.
Study protocol: a clinical trial for improving mental health screening for Aboriginal and Torres Strait Islander pregnant women and mothers of young children using the Kimberley Mum's Mood Scale
Authors: Carlin Emma , Blondell Sarah J. , Cadet-James Yvonne , Campbell Sandra , Williams Melissa , Engelke Catherine , Taverner Des , Marriott Rhonda , Edmonds Karen , Atkinson David , Marley Julia V. 
Published: November 2019

Abstract
Background
Improving the rates of, and instruments used in, screening for perinatal depression and anxiety among Aboriginal and Torres Strait Islander women are important public health priorities. The Kimberley Mum’s Mood Scale (KMMS) was developed and later validated as an effective and acceptable perinatal depression and anxiety screening tool for the Kimberley region under research conditions. Other regions have expressed interest in using the KMMS with perinatal Aboriginal and Torres Strait Islander women. It is, however, important to re-evaluate the KMMS in a larger Kimberley sample via a real world implementation study, and to test for applicability in other remote and regional environments before recommendations for wider use can be made. This paper outlines the protocol for evaluating the process of implementation and establishing the ‘real world’ validity and acceptability of the KMMS in the Kimberley, Pilbara and Far North Queensland in northern Australia.

Methods
The study will use a range of quantitative and qualitative methods across all sites. KMMS validation/revalidation internal consistency of Part 1 will be determined using Cronbach’s alpha. Equivalence for identifying risk of depression and anxiety compared to a standard reference assessment will be determined from receiver operating characteristic curves. Sensitivity and specificity will be determined based on these cut-points. Qualitative methods of phenomenology will be used to explore concepts of KMMS user acceptability (women and health professionals). Additional process evaluation methods will collate, assess and report on KMMS quality review data, consultations with health service administrators and management, field notes, and other documentation from the research team. This information will be reported on using the Dynamic Sustainability Framework.

Discussion
This project is contributing to the important public health priority of screening Aboriginal and Torres Strait Islander women for perinatal depression and anxiety with tools that are meaningful and responsive to cultural and clinical needs. Identifying and addressing barriers to implementation contributes to our understanding of the complexity of improving routine clinical practie.

Trial registration
The study was registered retrospectively on 15/05/2019 with the Australian and New Zealand Clinical Trial registry (ACTRN12619000580178).
Delay in treatment seeking and associated factors among suspected pulmonary tuberculosis patients in public health facilities of Adama town, eastern Ethiopia
Authors: Wondawek Tirusew Maru , Ali Musa Mohammed 
Published: November 2019

Abstract
Background
In low-income countries, delays in treatment seeking among tuberculosis patients contribute to easy transmission and high prevalence of tuberculosis.

Objective
The aim of this study was to determine the magnitude of delays in treatment-seeking and risk factors among pulmonary tuberculosis suspected patients in health facilities located in Adama, Ethiopia.

Method
A health-facility based cross-sectional study was conducted at Adama from December 20, 2015, to March 1, 2016, among 598 tuberculosis suspected patients. Data was collected from all study participants on the same day of tuberculosis diagnosis using a structured questionnaire. Epi-Info 3.5.3 and Statistical package for the social sciences (SPSS) version 16.0 were used for data entry and analysis respectively. A bivariate and multivariable regression model was used to investigate the association between delay in seeking-treatment and various factors. Odds ratio with 95% CI and P-value < 0.05 were considered as cut off point to measure the strength and significance of the association.

Results
Among 598 pulmonary tuberculosis suspected patients, 79 (13.2%) were smear-positive. Among smear-positive participants, 61(77.2%) delayed seeking treatment and 275 (46%) patients delayed seeking treatment for > 30 days. The following factors were significantly associated with a delay in seeking treatment: female sex OR = 1.57, 95% CI (1.14, 2.18), low monthly income OR = 1.45, 95% CI (1.05, 2.01), lack of knowledge regarding tuberculosis OR = 1.67, 95% CI (1.13, 2.48), and cure rate of tuberculosis OR = 1.836, 95% CI (1.25, 2.69).

Conclusion
Nearly half of pulmonary tuberculosis suspected patients delayed seeking treatment in our study area. Female sex, low income, family size of five and greater, no knowledge about tuberculosis and cure rate were factors contributing to delay in treatment-seeking among suspected tuberculosis patients.
Autotransplantation of mature impacted tooth to a fresh molar socket using a 3D replica and guided bone regeneration: two years retrospective case series
Authors: Wu Ye , Chen Jiaming , Xie Fuping , Liu Huanhuan , Niu Gang , Zhou Lin 
Published: November 2019

Abstract
Background
The aim of this study was to evaluate the clinical outcome of autotransplantation of mature third molars to fresh molar extraction sockets using 3D replicas.

Methods
Ten patients underwent teeth autotransplantation with or without GBR. We observed the mobility, percussion, radiography examination, the probing depth and the masticatory function of the transplanted teeth during 2 years following up, which were transplanted into fresh molar sockets by using 3D replicas, and GBR when it is necessary.

Results
The average extra-oral time of donor tooth had been shortened to 1.65 min when used the 3D replica. Some probing depth of the transplanted tooth were deeper than 3 mm at 4 or 5 weeks temporarily. And one patient felt slight sensitive when chewing with soft food at 4 weeks, then disappeared. The clinical examination of the autotransplantation teeth during 1 year follow-up showed no sign of failure.

Conclusions
The tooth autotransplantation using 3D replica with or without GBR is an effective method which can reduce the extra-oral time of the donor teeth and may result in less failure.
Specialty choice determinants among Mexican medical students: a cross-sectional study
Authors: Gutiérrez-Cirlos Carlos , Naveja J. Jesús , García-Minjares Manuel , Martínez-González Adrián , Sánchez-Mendiola Melchor 
Published: November 2019

Abstract
Background
The choice of medical specialty is related to multiple factors, students’ values, and specialty perceptions. Research in this area is needed in low- and middle-income countries, where the alignment of specialty training with national healthcare needs has a complex local interdependency. The study aimed to identify factors that influence specialty choice among medical students.

Methods
Senior students at the National Autonomous University of Mexico (UNAM) Faculty of Medicine answered a questionnaire covering demographics, personal experiences, vocational features, and other factors related to specialty choice. Chi-square tests and factor analyses were performed.

Results
The questionnaire was applied to 714 fifth-year students, and 697 provided complete responses (response rate 81%). The instrument Cronbach’s alpha was 0.8. The mean age was 24 ± 1 years; 65% were women. Eighty percent of the students wanted to specialize, and 60% had participated in congresses related to the specialty of interest. Only 5% wanted to remain as general practitioners. The majority (80%) wanted to enter a core specialty: internal medicine (29%), general surgery (24%), pediatrics (11%), gynecology and obstetrics (11%) and family medicine (4%). The relevant variables for specialty choice were grouped in three dimensions: personal values that develop and change during undergraduate training, career needs to be satisfied, and perception of specialty characteristics.

Conclusions
Specialty choice of medical students in a middle-income country public university is influenced by the undergraduate experience, the desire to study a subspecialty and other factors (including having skills related to the specialty and type of patients).
Intern preparedness for the CanMEDS roles and the Dunning-Kruger effect: a survey
Authors: Prozesky Detlef Richard , Molwantwa Mmoloki Cornelius , Nkomazana Oathokwa , Kebaetse Masego Baitseng 
Published: November 2019

Abstract
Background
The purpose of this study was to determine whether the first cohort of graduates from a new undergraduate medical programme in Botswana were adequately prepared for internship.

Methods
The authors surveyed 27 interns and 13 intern supervisors on site, who rated intern preparedness for 44 tasks using a previously validated instrument. Tasks were grouped according to the seven roles of the physician in the CanMEDS framework and Cronbach α values confirmed internal consistency. To determine the direction of differences between intern and supervisor ratings for tasks Likert scale ratings were treated as interval data and mean scores calculated. Rating frequencies for each role were compared using the χ2 statistic. Reasons for differences between intern and supervisor ratings were explored by determining correlations between scores using the Spearman ρ statistic, and analysing qualitative data generated by the questionnaire.

Results
Preparedness for all seven roles and the majority of tasks was found to be between ‘Fairly well prepared’ and ‘Well prepared’. The ratings for four roles (Medical expert, Communicator, Collaborator, Professional) differed statistically, but not for the three others (Leader, Health advocate, Scholar). Interns rated their proficiency higher than their supervisors for the tasks in six roles; for the ‘Professional’ role intern ratings were mostly lower. Correlations between intern and supervisors scores were only significant for three roles (Medical expert, Communicator, Collaborator). Qualitative data provided further insights into the reasons for these associations.

Conclusions
Intern preparedness for tasks and roles varied but was generally satisfactory. Based on the analysis of the data seeming discrepancies in between interns and supervisor ratings were investigated and explanations are offered. For three roles the data indicate that their component tasks are understood in the same way by interns and supervisors, but not for the other roles. The Dunning-Kruger effect offers a plausible explanation for higher intern scores for tasks in six of the roles. For the ‘Professional’ role differences between interns’ internal, individual understanding and supervisors’ external, group understanding may explain lower intern scores. The fact that respondents may understand the tasks they rate differently has implications for all research of this nature.