bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells
Authors: Fukasawa Kazuya , Lyu Jiajun , Kubo Takuya , Tanaka Yuki , Suzuki Akane , Horie Tetsuhiro , Tomizawa Akane , Osumi Ryoma , Iwahashi Sayuki , Tokumura Kazuya , Murata Misato , Kobayashi Masaki , Todo Tomoki , Hirao Atsushi , Hinoi Eiichi 
Published: January 2023

Glioma stem cells (GSC) promote the malignancy of glioblastoma (GBM), the most lethal brain tumor. ERK5 belongs to the MAPK family. Here, we demonstrated that MAPK kinase 5 (MEK5)-ERK5-STAT3 pathway plays an essential role in maintaining GSC stemness and tumorigenicity by integrating genetic and pharmacologic manipulation and RNA sequencing analysis of clinical specimens. ERK5 was highly expressed and activated in GSCs. ERK5 silencing by short hairpin RNA in GSCs suppressed the self-renewal potential and GBM malignant growth concomitant with downregulation of STAT3 phosphorylation. Conversely, the activation of the MEK5-ERK5 pathway by introducing ERK5 or MEK5 resulted in increased GSC stemness. The introduction of STAT3 counteracted the GSC phenotypes by ERK5 silencing. Moreover, ERK5 expression and signaling are associated with poor prognosis in patients with GBM with high stem cell properties. Finally, pharmacologic inhibition of ERK5 significantly inhibited GSC self-renewal and GBM growth. Collectively, these findings uncover a crucial role of the MEK5-ERK5-STAT3 pathway in maintaining GSC phenotypes and GBM malignant growth, thereby providing a potential target for GSC-directed therapy.Significance:In this study, we demonstrated that MEK5-ERK5-STAT3 axis plays a critical role in maintaining stemness and tumorigenicity in GSCs by using genetic, pharmacologic, and bioinformatics tools, identifying the MEK5-ERK5-STAT3 axis as a potential target for GSC-directed therapy.
Project DESMOS: Development and Evaluation of Self-directed Module in Statistics and Probability
Authors: Sagge Roberto Jr. , Espiritu Evarose E. 
Published: January 2023

Learning is weak not because learning is weak. Learning becomes weak because the modules were not prepared to become self-directed. The goal of this design and development project was to create a self-directed statistics and probability instructional module. Data were gathered from teachers, learners, and experts. The data-gathering instruments were Competency Checklist, Students’ and Experts’ Evaluation Checklist, and Reflection Guide. According on teacher perceptions, a survey of the learners' five least-mastered competencies served as the foundation for the development of the module. This module was pilot tested on a group of Grade 11 learners. Learners utilized the module at home and were asked to answer the exercises. Learners took pictures and short videos while they were answering the module. Afterward, learners evaluated the module. In order to assess the module's level of acceptability, experts were requested to complete the Expert's Evaluation Checklist. Thematic analysis, rank, the mean, and standard deviation were all used as data analysis tools. The results show that the following were the five least-mastered competencies: solving problems involving confidence interval of the population mean, solving problems involving regression analysis, solving problems involving sample size determination, solving problems that require population proportion test of hypothesis, and solving problems involving correlation analysis. Additionally, the experts rated the produced module's acceptability as "highly acceptable." While the learners gave the module a "highly acceptable" rating. As a result, the developed module is appropriate for assisting learners in performing the competencies in the area of Statistics and Probability. It is recommended that teachers should use the Self-directed instructional module for whatever mode of learning their school will have.
Employees Work Engagement: Correlations with Employee Personal Characteristics, Organizational Commitment and Workplace Happiness
Authors: Tugade Guinevere Yvonne G. , Arcinas Myla M. 
Published: January 2023

Using data collected from 76 employees of a manufacturing company in Manila, Philippines, this study conducted a correlation analysis to determine the relationship between the level of their engagement at work and their personal characteristics, organizational commitment in the workplace, and job satisfaction. A self-administered structured survey questionnaire was use in the survey. The collected data was analyzed using descriptive statistics to determine the mean scores, frequencies, and percentages, and parametric inferential statistics were employed to examine the correlations between variables. The results indicate a high level of employee work engagement and job satisfaction, as well as a moderate level of employee organizational commitment. Employee age, position and monthly salary were significantly correlated with employee work engagement. The level of employee engagement increases with age, position and income. Results also revealed a significant and strong positive correlation between the level of employee engagement and employee happiness at work. Implications for practices are offered.
Health Information System Users in Public Health Facilities: A Descriptive Analytics
Authors: Cortez Joey Ernehst M. , Ishii Jorge Kenneth G. , Ongkiko Angelica Mae R. , Ortega Clinton R. , Malang Bernandino P. , Vigonte Florinda G. 
Published: January 2023

Health Information Systems (HIS) are vital in making or developing the policies of health programs in the Philippines. The HIS is broadly defined as a system that integrates data collection, processing, reporting, and use of the information necessary for improving health service effectiveness and efficiency through better management at all levels of health services. This study is conducted to visualize the current situation of the health information system users in public health facilities in the Province of Bataan. It endeavors to answer on how the health facilities in the Province are described based on their report platform, the number of personnel, trained and untrained per facility, and the needs of the facilities when it comes to the training of the encoders. The researchers used the descriptive method specifically the Dashboarding, Analysis, and Reporting or DAR method for this study. This study focused on the data gathered from the Health Information Systems Assessment Tool. The assessment was conducted with 24 different health facilities in the Province of Bataan. The study revealed that 14 out of 24 (58%) of the Rural Health Units (RHUs) in the Province of Bataan used paper-based reporting while 10 out of 24 (42%) of the RHUs used a health information system. Twenty one out of 48 encoders (44%) are untrained while 27 out of 48 (56%) are trained. Capability training in each health information system used is proposed. In conclusion, the Province of Bataan is supporting the implementation of the use of health information systems (HIS) by designating encoders for every public health facility.
Climate Impacts of Convective Cloud Microphysics in NCAR CAM5
Authors: Lin Lin , Liu Xiaohong , Fu Qiang , Shan Yunpeng 
Published: January 2023

Abstract
We improved the treatments of convective cloud microphysics in the NCAR Community Atmosphere Model version 5.3 (CAM5.3) by 1) implementing new terminal velocity parameterizations for convective ice and snow particles, 2) adding graupel microphysics, 3) considering convective snow detrainment, and 4) enhancing rain initiation and generation rate in warm clouds. We evaluated the impacts of improved microphysics on simulated global climate, focusing on simulated cloud radiative forcing, graupel microphysics, convective cloud ice amount, and tropical precipitation. Compared to CAM5.3 with the default convective microphysics, the too-strong cloud shortwave radiative forcing due primarily to excessive convective cloud liquid is largely alleviated over the tropics and midlatitudes after rain initiation and generation rate is enhanced, in better agreement with the CERES-EBAF estimates. Geographic distributions of graupel occurrence are reasonably simulated over continents; whereas the graupel occurrence remains highly uncertain over the oceanic storm-track regions. When evaluated against the CloudSat–CALIPSO estimates, the overestimation of convective ice mass is alleviated with the improved convective ice microphysics, among which adding graupel microphysics and the accompanying increase in hydrometeor fall speed play the most important role. The probability distribution function (PDF) of rainfall intensity is sensitive to warm rain processes in convective clouds, and enhancement in warm rain production shifts the PDF toward heavier precipitation, which agrees better with the TRMM observations. Common biases of overestimating the light rain frequency and underestimating the heavy rain frequency in GCMs are mitigated.
Efficacy and accuracy of faecal sampling by a digital rectal examination for faecal immunochemical testing
Authors: Maclean William , Benton Sally C , Whyte Martin B , Rockall Timothy , Jourdan Iain 
Published: January 2023

Aim A digital rectal examination (DRE) during routine assessment for patients with abdominal symptoms provides an opportunity to obtain faeces from the glove for faecal immunochemical testing (FIT). Here, we compared sampling via DRE to the standard faecal sampling by patients. Method Patients were recruited to a prospective observational cohort study between July 2019 and March 2020. Patients provided a sample for the FOB Gold Wide® which was compared to a further sample taken at clinic via DRE. Clinicians reported whether they obtained a ‘good’ sample filling all the grooves, a ‘poor’ sample filling some of the grooves or no faecal sample. Cohen’s kappa was used to compare percentage agreement around a negative threshold of <10 μg haemoglobin/g of faeces. Sensitivity for serious bowel disease (SBD) was calculated. Results Of 596 patients who underwent attempted DRE sampling, there were 258 (43.3%) ‘good’ samples, 117 (19.6%) ‘poor’ samples and 221 (37.1%) with no sample to wipe in the grooves. Cohen’s kappa dropped from 0.70 to 0.30 for the ‘good’ and ‘poor’ samples, respectively. Of those with DRE samples and definitive diagnostic outcomes, the sensitivity for SBD dropped significantly from 76.0% to 41.7% between ‘good’ and ‘poor’ samples, respectively ( p = 0.041). Conclusions A ‘good’ sample obtained by DRE provides comparable results to samples obtained by patients. This creates potential benefit in speed and ease of testing for patients. However, not all DRE sampling attempts are successful, and the clinician must be satisfied that enough faeces is obtained to wipe adequately into all grooves.
Outcomes for Treatment of Capsulolabral Adhesions With a Capsular Spacer During Revision Hip Arthroscopy
Authors: Ruzbarsky Joseph J. , Comfort Spencer M. , Martin Maitland D. , Briggs Karen K. , Philippon Marc J. 
Published: January 2023

Background: The presence of adhesions is a common source of pain and dysfunction after hip arthroscopic surgery and an indication for revision surgery. The placement of a capsular spacer in the capsulolabral recess after lysis of adhesions has been developed to treat and prevent the recurrence of adhesions. Purpose: To evaluate patient-reported outcomes (PROs) and survivorship at a minimum of 2 years after revision hip arthroscopic surgery with capsular spacer placement for capsular adhesions. Study Design: Case series; Level of evidence, 4. Methods: Between January 2013 and June 2018, a total of 95 patients (99 hips) aged ≥18 years underwent revision hip arthroscopic surgery for the treatment of capsular adhesions with the placement of a capsular spacer. Overall, 53 patients (56 hips) met the inclusion criteria and had a minimum 2-year follow-up, forming the cohort of this study. Exclusion criteria included confounding metabolic bone diseases (eg, Legg-Calve-Perthes disease, Marfan syndrome), labral deficiency, or advanced osteoarthritis (Tönnis grade 2 or 3). Preoperative and postoperative outcome scores (modified Harris Hip Score [mHHS], Hip Outcome Score–Activities of Daily Living [HOS-ADL], Hip Outcome Score–Sport-Specific Subscale [HOS-SSS], 12-Item Short Form Health Survey [SF-12], and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were collected and compared in addition to the revision rate, conversion to total hip arthroplasty, and patient satisfaction. Results: The mean age of the cohort was 32 ± 11 years, with 32 female hips (57%) and a median number of previous hip arthroscopic procedures of 1 (range, 1-5). The arthroplasty- and revision-free survivorship rate at 2 years was 91%. Overall, 5 patients (6 hips; 11%) underwent revision surgery at a mean of 2.4 ± 1.4 years after capsular spacer placement, with symptomatic capsular defects being the most common finding. There were 4 patients (7%) who converted to total hip arthroplasty. For hips not requiring subsequent surgery (n = 46), there was a significant improvement in outcome scores except for the SF-12 Mental Component Summary, with rates of achieving the minimal clinically important difference of 70%, 70%, and 65% for the mHHS, HOS-ADL, and HOS-SSS, respectively. Conclusion: Capsular spacers, as part of a systematic approach including lysis of adhesions with early and consistent postoperative physical therapy including circumduction exercises, resulted in improved PROs as well as high arthroplasty– and revision-free survivorship (91%) at a minimum 2-year follow-up. Capsular spacers should be considered in revision hip arthroscopic procedures when an adequate labral volume remains but adhesions continue to be a concern.
Clinical and Second-look Arthroscopic Results for Derotational Distal Femoral Osteotomy With Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation With Increased Femoral Anteversion: A Series of 102 Cases With a Minimum Clinical Follow-up of 2 Years
Authors: Zhang Zhi-Jun , Di Meng Lin Qian , Song Guan-Yang , Li Yue , Cao Yan-Wei , Zheng Tong , Feng Hua , Zhang Hui 
Published: January 2023

Background: Derotational distal femoral osteotomy (DDFO) has been used to treat patients with recurrent patellar dislocation (RPD) with increased femoral anteversion. However, no study has reported second-look arthroscopic findings in the patellofemoral joint after DDFO. Purpose: To report clinical and second-look arthroscopic outcomes for DDFO with combined medial patellofemoral ligament reconstruction (MPFL-R) in treating RPD with increased femoral anteversion. Study Design: Case series; Level of evidence, 4. Methods: From 2015 to 2019, 131 consecutive patients (144 knees) with RPD were treated with combined MPFL-R and DDFO. Patients with a femoral anteversion angle >30° and a minimum 2-year clinical follow-up period were included in the study. Three-dimensional computed tomography was performed to evaluate rotational deformities of the lower leg. Radiographic parameters presenting bony abnormalities associated with RPD were measured. Second-look arthroscopic evaluations were available for 86 knees to assess patellar tracking and chondral lesion changes. Moreover, clinical and radiologic outcomes were assessed pre- and postoperatively at a minimum 2 years. Results: A total of 102 knees in 92 patients were included in the present study with a mean clinical follow-up of 4.1 years (range, 2.0-5.6 years). Mean ± SD femoral anteversion changed significantly from 34.7°± 7.5° preoperatively to 11.3°± 0.2° postoperatively ( P < .001), and mean tibial tubercle–trochlear groove distance decreased significantly from 19.6 ± 3.5 mm preoperatively to 17.4 ± 3.2 mm postoperatively ( P < .001). In the majority of knees, at the time of second-look arthroscopic assessment, chondral lesion status remained unchanged at the lateral patellar facet (96%) and trochlear groove (95%); in contrast, chondral damage at the medial patellar facet was aggravated in 9 cases (10%). All functional scores (Tegner, Lysholm, visual analog scale, and Kujala scores) improved significantly at final follow-up. None of the patients experienced redislocation or subluxation after surgery. Conclusion: Chondral lesions in the patellofemoral joint remained unchanged in the majority of cases in second-look arthroscopy after combined MPFL-R and DDFO. Moreover, high-grade trochlear dysplasia and arthroscopic residual patellar maltracking might be associated with cartilaginous deterioration at the medial patellar facet after surgery.
Minimum sample size for developing a multivariable prediction model using multinomial logistic regression
Authors: Pate Alexander , Riley Richard D , Collins Gary S , van Smeden Maarten , Van Calster Ben , Ensor Joie , Martin Glen P 
Published: January 2023

Aims Multinomial logistic regression models allow one to predict the risk of a categorical outcome with > 2 categories. When developing such a model, researchers should ensure the number of participants ([Formula: see text]) is appropriate relative to the number of events ([Formula: see text]) and the number of predictor parameters ([Formula: see text]) for each category k. We propose three criteria to determine the minimum n required in light of existing criteria developed for binary outcomes. Proposed criteria The first criterion aims to minimise the model overfitting. The second aims to minimise the difference between the observed and adjusted [Formula: see text] Nagelkerke. The third criterion aims to ensure the overall risk is estimated precisely. For criterion (i), we show the sample size must be based on the anticipated Cox-snell [Formula: see text] of distinct ‘one-to-one’ logistic regression models corresponding to the sub-models of the multinomial logistic regression, rather than on the overall Cox-snell [Formula: see text] of the multinomial logistic regression. Evaluation of criteria We tested the performance of the proposed criteria (i) through a simulation study and found that it resulted in the desired level of overfitting. Criterion (ii) and (iii) were natural extensions from previously proposed criteria for binary outcomes and did not require evaluation through simulation. Summary We illustrated how to implement the sample size criteria through a worked example considering the development of a multinomial risk prediction model for tumour type when presented with an ovarian mass. Code is provided for the simulation and worked example. We will embed our proposed criteria within the pmsampsize R library and Stata modules.
Impact of Age at Diagnosis of Bladder Cancer on Survival: A Surveillance, Epidemiology, and End Results-Based Study 2004-2015
Authors: Lin Wu , Pan Xuming , Zhang Chun , Ye Bochun , Song Jia 
Published: January 2023

Background An older age contributes to the development of bladder cancer. However, the relationship between advanced age at the diagnosis and prognosis of bladder cancer has been few reported. This study aimed to determine the effect of age on survival in bladder cancer with different subgroups. Methods 117,275 patients with bladder cancer, identified from the Surveillance, Epidemiology, and End Results database during 2004-2015 in America, were divided into 4 age groups (≤54, 55 to 64, 65 to 74, and ≥75 years). Multivariable Cox proportional-hazards model and competing risk model were conducted according to different age groups. Heat maps were plotted to show the impact of age on survival in subgroups classified by other clinicopathological variables. Moreover, restricted cubic spline was used to model the association between age and the risk of death. Results Patients aged ≥75 years had shorter overall survival in comparison with those aged ≤54 years (hazard ratio [HR] = 5.36, 95% confidence interval [CI] = 5.13-5.59). Compared with patients aged ≤54 years, patients older than 75 years experienced a decreased rate of bladder cancer-specific survival (subdistribution HR = 2.15, 95% CI = 2.04-2.25). Heat maps also showed that older ages were associated with worse overall cumulative mortality and bladder cancer-specific cumulative mortality. Similarly, restricted cubic spline verified the impact of age on survival of bladder cancer. Conclusions Age at diagnosis of bladder cancer was found to be a significant predictor for the worse overall survival and bladder cancer-specific survival even in an era with more effective therapies. Exploring the reasons why older age contributes to poor outcomes for bladder cancer will be the focus of future research.
Residual contamination in antineoplastic drug packaging
Authors: e Silva Luciana Stein , Machado Cibele da Silva Barbosa , Linden Rafael , Antunes Marina Venzon , da Silva Laura Cé , Wayhs Carlos Alberto Yasin , Capp Edison , Ness Sandro Luís Ribeiro 
Published: January 2023

Introduction The handling of antineoplastic drugs should follow strict supervision and safety rules to minimize the occupational exposure risks to professionals involved. The external surface contamination of drug vials is recognized as a health risk. So, our goal was to determine if there is residual contamination on the vials and containers surface of the antineoplastic drugs doxorubicin (DOX) and cyclophosphamide (CP). Methods A cross-sectional study was conducted. Samples were collected using a uniform sampling procedure on the inner surfaces of the packages/boxes and the outer surfaces of the vials. The analyzes were executed by high-performance liquid chromatography/mass spectrometry (UHPLC-MS/MS). Results A total of 209 samples were analyzed, 66 of CP and 143 of DOX. CP levels were detected in nine samples (13.63%), three were below the lower limit of quantification (LLQ) and the other six had contamination levels ranging from 1.24 to 28.04 ng/filter. DOX levels were detected in 36 samples (25.17%), two were below the LLQ and the others had levels between 1.32 and 664.84 ng/filter. The majority of samples with residual contamination were in vials (80.0%), however, boxes also showed contamination. Conclusions The results revealed the presence of residual contamination in the vials and packages of CP and DOX drugs. Although the residues found in each sample are small, special care should be taken in the handling and disposal of the antineoplastic drugs. The use of personal protective equipment is fundamental while handling the vials and packaging of cytotoxic drugs.