bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and prognostic features of patients with detailed RAS/BRAF-mutant colorectal cancer in Japan
Authors: Ikoma Tatsuki , Shimokawa Mototsugu , Kotaka Masahito , Matsumoto Toshihiko , Nagai Hiroki , Boku Shogen , Shibata Nobuhiro , Yasui Hisateru , Satake Hironaga 
Published: May 2021

Abstract
Background
RAS/BRAFV600E mutations are the most remarkable oncogenic driver mutations in colorectal cancer (CRC) and play an important role in treatment selection. No data are available regarding the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant metastatic CRC (mCRC) in Japan.

Methods
A total of 152 chemotherapy-naïve patients with mCRC were included in this study between August 2018 and July 2019. Tumor samples were collected, and RAS/BRAFV600E status was investigated. RAS/BRAFV600E status was examined using a MEBGEN RASKET-B kit and polymerase chain reaction reverse sequence-specific oligonucleotide method.

Results
RAS/BRAFV600E mutations were detected in 54% of cases (KRAS codon 12, 26%; KRAS codon 13, 17%; KRAS non-Exon2, 5%; NRAS, 5%; and BRAFV600E, 7%). BRAFV600E-mutant CRC mainly existed in the right colon, whereas KRAS non-Exon2 and NRAS-mutant CRC was predominantly present in the left colon. KRAS non-Exon2 and NRAS-mutant CRC were associated with shorter survival time than RAS wild-type CRC (hazard ratio [HR], 2.26; 95% confidence interval [CI], 0.64–8.03; p = 0.19; HR, 2.42; 95% CI, 0.68–8.61; p = 0.16) and significantly shorter overall survival than KRAS Exon2-mutant CRC (HR, 3.88; 95% CI, 0.92–16.3; p = 0.04; HR, 4.80; 95% CI, 1.14–20.2; p = 0.02).

Conclusions
In our multicenter study, the findings elucidated the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant mCRC in Japan.
Prediction of postoperative refractive astigmatism before toric intraocular lens implantation
Authors: Kawahara Atsushi 
Published: May 2021

Abstract
Background
To determine the preoperative factors influencing refractive astigmatism after cataract surgery for astigmatism correction by toric intraocular lens (IOL) implantation and to evaluate the prediction model using these factors.

Methods
Prospective, observational case series. The right eyes of forty consecutive patients with preoperative corneal astigmatism of the total cornea of 1.5 diopters (D) or more in magnitude and scheduled for implantation of a non-toric IOL during cataract surgery with a 2.4-mm temporal clear corneal incision were examined prospectively. The vertical/horizontal astigmatism component (J0) and oblique astigmatism component (J45) of refractive and corneal astigmatism were converted using power vector analysis. Multivariate regression analysis was performed with refractive astigmatism at three months postoperatively as the dependent variable, and preoperative parameters including age, sex, refractive astigmatism, corneal astigmatism, sphere, spherical equivalent, intraocular pressure, corneal thickness, anterior chamber depth, lens thickness, lens positions (tilt and decentration), axial length, and corneal higher order aberrations as independent variables. The root mean square (RMS) errors were calculated to express the regression model fit.

Results
The regression model for the J0 component was $$ Postoperative\kern0.34em refractive\kern0.2em J0=1.05\times Coneal\kern0.2em J0-0.14 $$
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(R2 = 0.96, P < 0.001). The model for the J45 component was $$ Postoperative\kern0.34em refractive\kern0.2em J45=0.68\times Coneal\kern0.2em J45+0.19\times Preoperative\kern0.34em refractive\kern0.2em J45-0.06 $$
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(R2 = 0.72, P < 0.001). The mean RMS errors for preoperative corneal astigmatism alone and the multivariate model were 0.58 D and 0.46 D, respectively. There was a statistically significant difference between them (P = 0.02).

Conclusions
Refractive astigmatism after implantation of a toric IOL can be predicted by the regression model more accurately than by corneal astigmatism alone. However, the prediction of oblique astigmatism remains a challenge.
Development and evaluation of a new measure of children’s play: the Children’s Play Scale (CPS)
Authors: Dodd Helen F. , Nesbit Rachel J. , Maratchi Laura R. 
Published: May 2021

Abstract
Background
There is increasing recognition of the importance of children’s play from a public health perspective, given the links between play and children’s physical and mental health. The present research aimed to develop and evaluate a new parent-report questionnaire that measures the time children spend playing across a range of places and includes a supplement to evaluate how adventurously children play.

Methods
The questionnaire was developed with input from a diverse group of parents and experts in children’s play. It was designed to yield a range of metrics including time spent playing per year, time spent playing outside, time spent playing in nature and level of adventurous play. The reliability of the questionnaire was then evaluated with 245 parents (149 mothers, 96 fathers) of 154 children aged 5–11 years. All participants completed the measure at time 1. At time 2, an average of 20 days later, 184 parents (111 mothers and 73 fathers) of 99 children completed the measure again.

Results
Cross-informant agreement, evaluated using Concordance Correlation Coefficients (CCCs), ranged from 0.36 to 0.51. These fall in the poor to moderate range and are largely comparable to cross-informant agreement on other measures. Test-retest reliability for mothers was good (range 0.67–0.76) for time spent playing metrics. For fathers, test-retest reliability was lower (range 0.39–0.63). For both parents the average level of adventurous play variable had relatively poor test retest reliability (mothers = 0.49, fathers = 0.42). This variable also showed a significant increase from time 1 to time 2. This instability over time may be due to the timing of the research in relation to the Covid-19 lockdown and associated shifts in risk perception.

Conclusions
The measure will be of value in future research focusing on the public health benefits and correlates of children’s play as well as researchers interested in children’s outdoor play and play in nature specifically. The development of the measure in collaboration with parents and experts in children’s play is a significant strength. It will be of value for future research to further validate the measure against play diaries or activity monitors.
Associations of midpoint of sleep and night sleep duration with type 2 diabetes mellitus in Chinese rural population: the Henan rural cohort study
Authors: Zhai Zhihan , Liu Xiaotian , Zhang Haiqing , Dong Xiaokang , He Yaling , Niu Miaomiao , Pan Mingming , Wang Chongjian , Wang Xiaoqiong , Li Yuqian 
Published: May 2021

Abstract
Background
The study aimed to investigate the independent and combined effects of midpoint of sleep and night sleep duration on type 2 diabetes mellitus (T2DM) in areas with limited resources.

Methods
A total of 37,276 participants (14,456 men and 22,820 women) were derived from the Henan Rural Cohort Study. Sleep information was assessed based on the Pittsburgh Sleep Quality Index. Logistic regression models and restricted cubic splines were used to estimate the relationship of the midpoint of sleep and night sleep duration with T2DM.

Results
Of the 37,276 included participants, 3580 subjects suffered from T2DM. The mean midpoint of sleep among the Early, Intermediate and Late groups were 1:05 AM ±23 min, 1:56 AM ±14 min, and 2:57 AM ±34 min, respectively. Compared to the Intermediate group, adjusted odds ratios (ORs) and 95% confidence interval (CI) of T2DM were 1.13 (1.04–1.22) and 1.14 (1.03–1.26) in the Early group and the Late group. Adjusted OR (95% CI) for T2DM compared with the reference (7- h) was 1.28 (1.08–1.51) for longer (≥ 10 h) night sleep duration. The combination of late midpoint of sleep and night sleep duration (≥ 9 h) increased 38% (95% CI 10–74%) prevalence of T2DM. These associations were more obvious in women than men.

Conclusions
Late and early midpoint of sleep and long night sleep duration were all associated with higher prevalence of T2DM. Meanwhile, midpoint of sleep and night sleep duration might have combined effects on the prevalence of T2DM, which provided potential health implications for T2DM prevention, especially in rural women.

Trial registration
The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-07-06.
Correlates of sun protection behaviors among melanoma survivors
Authors: Heckman Carolyn J. , Manne Sharon L. , Kashy Deborah A. , Bhurosy Trishnee , Ritterband Lee , Coups Elliot J. 
Published: May 2021

Abstract
Background
The study objective was to assess potential correlates of sun protection behaviors among melanoma survivors.

Methods
Participants were 441 melanoma survivors recruited from three health centers and a state cancer registry in the United States. Sun protection behaviors (sunscreen, shade, protective shirts, and hats) were assessed through an online survey, as were potential correlates (demographic, melanoma risk, knowledge and beliefs, psychological and social influence factors). Hierarchical multiple regression analyses were conducted.

Results
Correlates of sun protection behaviors included education, skin cancer risk factors, melanoma knowledge and beliefs, melanoma worry and distress, physician recommendation for sun protection, injunctive norms, and pro-protection beliefs (e.g., perceived barriers, self-efficacy).

Conclusions
Future efforts to improve sun safety among melanoma survivors may benefit from targeting individuals with lower education levels, and addressing sun protection social influence, barriers, and self-efficacy.
Evaluation of anti-stigma social marketing campaigns in Ghana and Kenya: Time to Change Global
Authors: Potts Laura C. , Henderson Claire 
Published: May 2021

AbstractBackgroundLaunched in 2018, Time to Change Global is a new anti-stigma programme to tackle stigma and discrimination towards people with mental health problems in low- and middle-income countries. Our aim was to evaluate pre-post changes in stigma within the target populations for the social marketing campaigns ran in Ghana and Kenya carried out as components of the wider Time to Change Global programme.MethodsUsing data collected before and after each campaign in Accra and Nairobi, we investigated pre-post differences in stigma-related outcome measures: mental health-related knowledge (MAKS), mental health-related attitudes (CAMI), and desire for social distance (RIBS), with regression analyses. Other covariates were included in the models to control for differences in participant demographics.ResultsA significant positive change in a stigma related outcome was found at each site. Reported in standard deviation units, desire for social distance from people with mental health problems in Accra was lower after the launch of the campaign, measured as an increase in intended contact (β = 0.29, 95% CI = 0.14 to 0.43,p < 0.001). In Nairobi, the stigma related knowledge score was higher in the post campaign sample (β = 0.21, 95% CI = 0.07 to 0.34,p = 0.003).ConclusionThe increase in intended contact in the absence of other changes seen in Ghana, is consistent with the early results for Time to Change England. The estimate for the magnitude of this change is the same as Time to Change England for the general population between 2009 and 19, a very promising result for a short term public mental health campaign. The different results observed between sites may be due to campaign as well as population differences.
Spontaneous common bile duct perforation in full term pregnancy: a rare case report and review of literature
Authors: Masroor Matiullah , Sarwari Mohammad Arif 
Published: May 2021

Abstract
Background
Spontaneous biliary system perforation is a rare presentation in clinical practice especially in adults. It is rarely suspected and diagnosed preoperatively due to small number of cases, vague sign and symptoms, and ambiguous presentation.

Case presentation
We describe an interesting case of spontaneous perforation of the common bile duct in a 16 year-old female who presented a week after her first birth to the emergency department with complaints of diffuse abdominal pain, abdominal distention, fever, vomiting, and constipation. She was having generalized peritonitis but the etiology was unclear despite a thorough workup. She underwent exploratory laparotomy, and a perforation in the supra duodenal region of the common bile duct was found intraoperatively. The common bile duct was repaired over T-tube, and cholecystectomy was performed; the patient was recovered uneventfully.

Conclusion
Spontaneous biliary perforation is a rare cause of acute abdomen in adults and extremely rare in pregnancy. Its delayed diagnoses and management can lead to a high morbidity and mortality. All physicians, especially surgeons, should be aware of this possibility and consider it a cause of peritonitis on differential diagnosis particularly when there is no apparent etiology available for presentation.
A plant-based medicinal food inhibits the growth of human gastric carcinoma by reversing epithelial–mesenchymal transition via the canonical Wnt/β-catenin signaling pathway
Authors: Chen Xuxi , Yue Wuyang , Tian Lin , Li Na , Chen Yiyi , Zhang Lishi , Chen Jinyao 
Published: May 2021

Abstract
Background
Natural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. In this study, the effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo.

Methods
A subcutaneous xenograft model of gastric cancer was successfully established in nude mice inoculated with SGC-7901 cells. The tumor-bearing mice were separately underwent with particular diets supplemented with three doses of PBMF (43.22, 86.44, and 172.88 g/kg diet) for 30 days. Tumor volumes were recorded. Histopathological changes in and apoptosis of the xenografts were evaluated by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, respectively. Serum levels of TNF-α, MMP-2, and MMP-9 were detected by enzyme-linked immunosorbent assay. The mRNA expression levels of β-catenin, GSK-3β, E-cadherin, N-cadherin, MMP-2/9, Snail, Bax, Bcl-2, Caspase-3/9, and Cyclin D1 were evaluated via real-time quantitative polymerase chain reaction. The protein expression levels of GSK-3β, E-cadherin, N-cadherin, and Ki-67 were determined by immunohistochemistry staining.

Results
PBMF treatment efficiently suppressed neoplastic growth, induced apoptosis, and aggravated necrosis in the xenografts of SGC-7901 cells. PBMF treatment significantly decreased the serum levels of MMP-2 and MMP-9 and significantly increased that of TNF-α. Furthermore, PBMF treatment notably upregulated the mRNA expression levels of GSK-3β, E-cadherin, Bax, Caspase-3, and Caspase-9 but substantially downregulated those of β-catenin, N-cadherin, MMP-2, MMP-9, Snail, and Cyclin D1 in tumor tissues. The Bax/Bcl-2 ratio was upregulated at the mRNA level. Moreover, PBMF treatment remarkably increased the protein expression levels of GSK-3β and E-cadherin but notably reduced those of Ki-67 and N-cadherin in tumor tissues.

Conclusions
The PBMF concocted herein exerts anti-gastric cancer activities via epithelial–mesenchymal transition reversal, apoptosis induction, and proliferation inhibition. The underlying molecular mechanisms likely rely on suppressing the Wnt/β-catenin signaling pathway.
A Q-method approach to perceptions of professional reasoning in occupational therapy undergraduates
Authors: Márquez-Álvarez Luis-Javier , Calvo-Arenillas José-Ignacio , Jiménez-Arberas Estíbaliz , Talavera-Valverde Miguel-Ángel , Souto-Gómez Ana-Isabel , Moruno-Miralles Pedro 
Published: May 2021

Abstract
Background
Professional reasoning provides a firm basis for the development of teaching and assessment strategies to support the acquisition of skills by healthcare students. Nevertheless, occupational therapy educators should use diverse methods of learning assessment to examine student learning outcomes more fully with an evaluation that supports the overall complexity of the process, particularly learners’ subjective experience. The aim of this article is to identify the range of perspectives among occupational therapy undergraduates regarding terms or concepts that are key for improving their professional reasoning.

Methods
Q-methodology was used to address the aim of the study. A concourse relating to a series of ideas, phrases, terminology, and concepts associated with various studies on professional reasoning in occupational therapy, specifically on students in this field, was generated. The terms that had the clearest evidence, the most relevance or the greatest number of citations in the literature were collected (n = 37). The P-set was assembled by non-probabilistic sampling for convenience. It comprised undergraduate university students in occupational therapy. Factor analysis was conducted using Ken-Q Analysis v.1.0.6, reducing the number of Q-sets to smaller groups of factors representing a common perspective.

Results
Through statistical analysis of the Q-sorts of 37 occupational therapy students, 8 default factors were identified. The four factors in accordance with the selection criteria were rotated by varimax rotation to identify variables that could be grouped together. Each viewpoint was interpreted, discussed and liked to different aspects of professional reasoning in occupational therapy.

Conclusions
The observed perceptions were linked to the various aspects of professional reasoning that have been widely discussed in the occupational therapy literature. For most of the students, there was a strong correspondence between the narrative, interactive and conditional aspects of the various components.
Swedish snuff (snus) and risk of cardiovascular disease and mortality: prospective cohort study of middle-aged and older individuals
Authors: Titova Olga E. , Baron John A. , Michaëlsson Karl , Larsson Susanna C. 
Published: May 2021

Abstract
Background
Cigarette smoking is a well-known risk factor for cardiovascular disease (CVD), but whether smokeless tobacco such as snuff is associated with the risk of CVD is still unclear. We investigated the association of the use of Swedish oral moist snuff (snus) with a broad range of CVDs and CVD mortality.

Methods
We used data from a population-based cohort of 41,162 Swedish adults with a mean baseline age of 70 (56–94) years who completed questionnaires regarding snus use and other lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular outcomes and death over 8 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios (HR) were estimated by Cox proportional hazards regression. We conducted analyses among all subjects as well as among never smokers to reduce residual confounding from smoking.

Results
After adjustment for smoking and other confounders, snus use was not associated with myocardial infarction, heart failure, atrial fibrillation, aortic valve stenosis, abdominal aortic aneurysm, stroke, or CVD mortality. However, in never smokers, snus use was associated with a statistically significant increased risk of total and ischemic stroke (HRs [95% confidence intervals] = 1.52 [1.01–2.30] and 1.63 [1.05–2.54], respectively) and non-significantly positively associated with some other CVDs.

Conclusions
In this middle-aged and elderly Swedish population, current Swedish snus use was not associated with the risk of major heart and valvular diseases, abdominal aortic aneurysm, or CVD mortality in the entire study population, but was linked to an increased risk of stroke in never smokers.
NEDD4 regulates ubiquitination and stability of the cell adhesion molecule IGPR-1 via lysosomal pathway
Authors: Sun Linzi , Amraei Razie , Rahimi Nader 
Published: May 2021

Abstract
Background
The cell adhesion molecule IGPR-1 regulates various critical cellular processes including, cell–cell adhesion, mechanosensing and autophagy and plays important roles in angiogenesis and tumor growth; however, the molecular mechanism governing the cell surface levels of IGPR-1 remains unknown.

Results
In the present study, we used an in vitro ubiquitination assay and identified ubiquitin E3 ligase NEDD4 and the ubiquitin conjugating enzyme UbcH6 involved in the ubiquitination of IGPR-1. In vitro GST-pulldown and in vivo co-immunoprecipitation assays demonstrated that NEDD4 binds to IGPR-1. Over-expression of wild-type NEDD4 downregulated IGPR-1 and deletion of WW domains (1–4) of NEDD4 revoked its effects on IGPR-1. Knockdown of NEDD4 increased IGPR-1 levels in A375 melanoma cells. Deletion of 57 amino acids encompassing the polyproline rich (PPR) motifs on the C-terminus of IGPR-1 nullified its binding with NEDD4. Furthermore, we demonstrate that NEDD4 promotes K48- and K63-dependent polyubiquitination of IGPR-1. The NEDD4-mediated polyubiquitination of IGPR-1 stimulates lysosomal-dependent degradation of IGPR-1 as the treatment of cells with the lysosomal inhibitors, bafilomycine or ammonium chloride increased IGPR-1 levels ectopically expressed in HEK-293 cells and in multiple endogenously IGPR-1 expressing human skin melanoma cell lines.

Conclusions
NEDD4 ubiquitin E3 ligase binds to and mediates polyubiquitination of IGPR-1 leading to its lysosomal-dependent degradation. NEDD4 is a key regulator of IGPR-1 expression with implication in the therapeutic targeting of IGPR-1 in human cancers.