bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple stressors, allostasis and metabolic scaling in developing zebrafish
Authors: Hunt von Herbing Ione , Pan Francis T. C. 
Published: September 2022

ABSTRACTDeoxygenation and warming affect adult fish physiology in all aquatic ecosystems, but how these stressors impact the energetics of sensitive developing stages is largely unknown. Addressing this knowledge gap, we investigated chronic and acute effects of two stressors (high temperature and hypoxia) in yolk-sac larval (48–168 hpf) zebrafish (Danio rerio) energy budgets measuring, oxygen consumption rate, growth rate (absolute and specific), % net conversion efficiency, net cost of growth and scaling relationships. Embryos and larvae were raised under four chronic treatments: (1) control (28°C and PO2 21 kPa, T28O21), (2) high temperature (31°C and PO2 21 kPa, T31O21), (3) hypoxia (28°C and PO2 11 kPa, T28TO11) and (4) high temperature and hypoxia (31°C and PO2 11 kPa, T31O11). From each chronic treatment, larvae were acutely exposed to the same combinations of stressors for 1 h in a respirometer. At hatching, larvae from chronic high temperature (T31O21 and T31O11) treatments were larger (higher dry mass and standard length) than controls (T28O21 and T28O11), but by the end of the yolk-sac stage, increased metabolic demands diverted energy away from growth, increasing net cost of growth and lowering % net conversion efficiency. Control metabolic scaling relationships were significant and differed from 0.75, but metabolic levels were lower in acute hypoxia and high temperature/hypoxia. Thus, high temperature dominated larval energetics, acting synergistically with hypoxia to increase cumulative energetic costs and making allostasis difficult compared with older stages.
The flavonoid kaempferol protects the fruit fly Drosophila melanogaster against the motor impairment produced by exposure to the insecticide fipronil
Authors: Ramírez-Moreno Daniela M. , Lubinus Klaus F. , Riveros Andre J. 
Published: September 2022

ABSTRACT
Exposure to pesticides across species has been associated with cognitive and motor impairments. As the problem impacts ecosystem stability, food production and public health, it is urgent to develop multifactorial solutions, from regulatory legislation to pharmacological alternatives that ameliorate the impairments. Fipronil, a commonly used insecticide, acts as a GABAA receptor (GABAAR) antagonist and induces motor impairments in vertebrates and invertebrates. Here, we hypothesized that kaempferol, a secondary metabolite derived from plants, acting as an allosteric modulator of GABAARs, would protect against the negative effects induced by the administration of fipronil in adults of the fruit fly Drosophila melanogaster. We further evaluated our hypothesis via co-administration of flumazenil, a competitive antagonist on the GABAAR, and through in silico analyses. We administered kaempferol prophylactically at three concentrations (10, 30 and 50 µmol l−1) and evaluated its protective effects against motor impairments induced by fipronil. We then used a single dose of kaempferol (50 µmol l−1) to evaluate its protective effect while administering flumazenil. We found that oral administration of fipronil impaired motor control and walking ability. In contrast, kaempferol was innocuous and protected flies from developing the motor-impaired phenotype, whereas the co-administration of flumazenil counteracted these protective effects. These results are supported by the binding of the ligands with the receptor. Together, our results suggest that kaempferol exerts a protective effect against fipronil via positive allosteric modulation of GABAARs, probably within brain areas such as the central complex and the mushroom bodies. These findings further support current attempts to use metabolites derived from plants as protectors against impairments produced by pesticides.
Identification of the Minimum Combination of Serum microRNAs to Predict the Recurrence of Colorectal Cancer Cases
Authors: Yoshikawa Yukihiro , Fukunaga Mitsuko , Takahashi Junichi , Shimizu Dai , Masuda Takaaki , Mizushima Tsunekazu , Yamada Kazutaka , Mori Masaki , Eguchi Hidetoshi , Doki Yuichiro , Ochiya Takahiro , Mimori Koshi 
Published: September 2022

Abstract
Background
Serum microRNAs (miRNAs) have been recognized as potential stable biomarkers for various types of cancer. Considering the clinical applications, there are certain critical requirements, such as minimizing the number of miRNAs, reproducibility in a longitudinal clinical course, and superiority to conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9. This study aimed to identify serum miRNAs that indicate the recurrence of colorectal cancer (CRC), surpassing inter-tumor heterogeneity.

Methods
We conducted an analysis of 434 serum samples from 91 patients with CRC and 71 healthy subjects. miRNAs were obtained from Toray Co., Ltd, and miRNA profiles were analyzed using a three-step approach. miRNAs that were highly expressed in patients with CRC than in the healthy controls in the screening phase, and those that were highly expressed in the preoperative samples than in the 1-month postoperative samples in the discovery phase, were extracted. In the validation phase, the extracted miRNAs were evaluated in 323 perioperative samples, in chronological order.

Results
A total of 12 miRNAs (miR-25-3p, miR-451a, miR-1246, miR-1268b, miR-2392, miR-4480, miR-4648, miR-4732-5p, miR-4736, miR-6131, miR-6776-5p, and miR-6851-5p) were significantly concordant with the clinical findings of tumor recurrence, however their ability to function as biomarkers was comparable with CEA. In contrast, the combination of miR-1246, miR-1268b, and miR-4648 demonstrated a higher area under the curve (AUC) than CEA. These three miRNAs were upregulated in primary CRC tissues.

Conclusion
We identified ideal combinatorial miRNAs to predict CRC recurrence.
Approaches to integrating online videos into health professions curricula: educators’ perspectives from multiple institutions
Authors: Aluri Kelly , Sow Mohamed , Amieva Manuel , Chen Sharon 
Published: September 2022

Background: The COVID-19 pandemic has accelerated a transition from lecture-based classes to blended and online learning, increasing the need to integrate publicly available online educational videos. Although online videos are widely available, it is challenging for educators to effectively integrate them into a curriculum. Years before the pandemic, educators from different institutions integrated videos from a library of microbiology and immunology resources into different curricula. Their experiences may inform current educators on the approach to incorporating external resources into their unique curricula. Methods: We interviewed US health professions instructors or course directors who had previously requested access to online microbiology and immunology videos. Using thematic analysis, we organized prominent themes into an existing framework for curriculum development. We then reflected on the meaning of the themes using the same conceptual framework. Results: We found that educators from different schools were able to integrate the same publicly available videos into varying contexts. Most used them as preparation for interactive sessions. For integrating videos, educators felt success when the following actions occurred. 1) Educators integrated videos as a tool to enhance active-learning activities. 2) Educators created activities that focused on clinical applications of knowledge, taught critical thinking, and developed enthusiasm for the subject. 3) They tested students on knowledge application and major concepts rather than solely on content for high-stakes exams. 4) Educators worked with administrators who understood the goals of integrating external videos and supported educators with time and resources to develop effective blended learning. Conclusion: Our study suggests that educators integrating external resources into their curricula may benefit from first establishing their goals and aspirations for their students. These goals then become the anchor for other curricular elements, including external videos, in-class activities, and assessments. Our study highlights the need for dedicated time to develop experienced and enthusiastic educators.
Analytical Solution to a Partially Observable Machine Maintenance Problem with Obvious Failures
Authors: Zhang Hao , Zhang Weihua 
Published: September 2022

We study the maintenance of a machine that deteriorates according to a Markov process until it fails. When failure occurs (which is observable), corrective replacement is made. Otherwise, the machine can be in one of two unobservable working states, and the decision maker can choose production, inspection, or preventive replacement. The state is revealed upon inspection and is reset by corrective or preventive replacement. The objective is to minimize the expected total discounted cost over an infinite horizon. We derive an exact, analytical solution to this problem via a dual framework for partially observable Markov decision processes. The solution can be easily computed without value iteration. We identify six possible structures of the optimal solution, which are represented as graphs. Each graph contains an absorbing, cyclic subgraph that governs the steady-state behavior of the machine. The exact analytical solution facilitates comparative statics analysis, comprehensive numerical studies, and the generation of insights. This paper was accepted by Chung Piaw Teo, optimization. Funding: This work was supported by the Natural Sciences and Engineering Research Council of Canada [Grant RGPIN-2014-04979]. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4547 .
Disclosure Substitution
Authors: Heinle Mirko , Samuels Delphine , Taylor Daniel 
Published: September 2022

This study develops and tests a simple model of voluntary disclosure in which managers can choose to withhold (i.e., redact) certain elements from mandatory disclosure. We consider a setting in which mandatory disclosure is a disaggregated disclosure (e.g., a financial statement), voluntary disclosure is an aggregate disclosure (e.g., an earnings forecast), and the costs of each type of disclosure are distinct. In this setting, we show that managers endogenously substitute between the two types of disclosure; managers that choose to withhold information from mandatory disclosure are more likely to provide voluntary disclosure. We test our predictions using a comprehensive sample of mandatory disclosures in which the SEC allows the firm to redact information that would otherwise jeopardize its competitive position. Consistent with our predictions, we find strong evidence that redacted mandatory disclosure is associated with greater voluntary disclosure. This paper was accepted by Suraj Srinivasan, accounting. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4549 .
Health related quality of life among adult hypertensive patients on treatment in Dessie City, Northeast Ethiopia
Authors: Adamu Kidist , Feleke Amsalu , Muche Amare , Yasin Toyeb , Mekonen Asnakew Molla , Chane Muluken Genetu , Eshete Sisay , Mohammed Anisa , Endawkie Abel , Fentaw Zinabu 
Published: September 2022

Introduction
Hypertension is one global public health emergency disease, and is one of the most critical factors for chronic diseases such as cardiovascular disease, stroke, arrhythmias, heart failure, and renal diseases. Hypertension affects quality of life of patients, however there is limited evidence on the factors that affect health related quality of life among hypertensive patients. As a result, the purpose of this study is to look into factors that affect the health-related quality of life of adult hypertensive patients.

Methods
An institutional based cross-sectional study was conducted in Dessie City public health facilities from March to April 2021 with the total samples size of 376 hypertensive patients. Simple random sampling technique was employed to select study participants. World health organization health related quality of life 26 items were used to measure outcome variable. Simple linear regression analysis was done and forwarded to multivariable linear regression analysis at p-value<0.2. In multivariable linear regression analysis variables whose p-value less than 0.05 at 95% confidence interval with unstandardized β-coefficient were declared as statistically significant.

Results
A total of 360 hypertensive patients were included in the study. The mean scores of physical, psychological, social and environmental domains were 42.93, SD (18.86), 51.78, SD (20.40), 57.31, SD (20.20) and 48.15, SD (16.26), respectively. Age, duration of antihypertensive treatment, low social support, physical inactivity, co-morbidity, being widow, khat chewing, and being single had a significant association with lower health related quality of life.

Conclusion and recommendations
The health-related quality of life of hypertensive patients were found low in all domains. The findings indicate the necessity for health professionals, government, non-governmental organizations and community to pay more attention to patients’ quality of life, seeking changes in the therapeutic approach in general.
Cost-utility analysis of robotic-assisted radical cystectomy for bladder cancer compared to open radical cystectomy in the United Kingdom
Authors: Machleid Felix , Ho-Wrigley Jenessa , Chowdhury Ameera , Paliah Anita , Poon Ho Lam , Pizzo Elena 
Published: September 2022

Background
Bladder cancer is the tenth most common cancer in the United Kingdom. Currently, open radical cystectomy (ORC) is the gold standard. Due to the risk of complications and a 2.3-8% mortality rate1, there is growing interest in the use of robot-assisted radical cystectomy (RARC). The aim of this study is to perform a cost-utility analysis, comparing RARC to ORC for bladder cancer patients from the perspective of the National Health Service England.

Methods
A three-stage decision tree: surgery, post-surgery transfusions and complications, in a 90-day time horizon, was produced to simulate possible pathways of patients. The incremental cost-effectiveness ratio (ICER) was calculated based on data derived from current literature. Multiple univariate sensitivity analysis was carried out to evaluate influences of varying costs of RARC and ORC on the ICER.

Results
The ICER for RARC compared to ORC resulted in £25,536/QALY. At the lower threshold of £20,000/QALY, RARC resulted in a negative NMB (£-4,843.32) and at the upper threshold of £30,000/QALY, a positive NMB (£624.61) compared to ORC. Threshold analysis showed that the intervention costs of £13,497 and £14,403 are met at the lower and upper threshold respectively. The univariate sensitivity analysis showed that the intervention costs of RARC or ORC, and the probabilities of complications, had the greatest impact on the ICER.

Conclusion
As the resultant ICER did not fall below the £20,000/QALY threshold, our study did not provide a definitive recommendation for RARC for bladder cancer. Negative values for the NMB at the lower threshold indicated the intervention was not feasible from a cost perspective. At the upper threshold of £30,000/QALY, this situation was reversed. The intervention became cost-effective. Therefore, further research is needed to justify the intervention.
Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis
Authors: Di Stefano Leon , Ogburn Elizabeth L. , Ram Malathi , Scharfstein Daniel O. , Li Tianjing , Khanal Preeti , Baksh Sheriza N. , McBee Nichol , Gruber Joshua , Gildea Marianne R. , Clark Megan R. , Goldenberg Neil A. , Bennani Yussef , Brown Samuel M. , Buckel Whitney R. , Clement Meredith E. , Mulligan Mark J. , O’Halloran Jane A. , Rauseo Adriana M. , Self Wesley H. , Semler Matthew W. , Seto Todd , Stout Jason E. , Ulrich Robert J. , Victory Jennifer , Bierer Barbara E. , Hanley Daniel F. , Freilich Daniel ,   on behalf of the Pandemic Response COVID-19 Research Collaboration Platform for HCQ/CQ Pooled Analyses
Published: September 2022

Background
Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.

Methods
We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions.

Results
Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76–1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively).

Conclusions
The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.
Factors influencing the practice of Smoking Cessation Assessment and Management among Primary Care Doctors (SCAAM-DOC) in three districts of Malaysia
Authors: Ngee Ling Beatrice Jee , Cheong Ai Theng , Manap Abdul Hadi Abdul 
Published: September 2022

BackgroundSmoking prevalence remains high in Malaysia. Primary care doctors have a good opportunity to motivate the smokers to quit smoking in view of the accessibility of primary healthcare clinics to the public. The objective of this study was to determine the practice of smoking cessation management among primary care doctors and its associated factors.MethodsA cross-sectional online survey was carried out among 383 medical officers and interns in all government primary healthcare clinics in the district of Petaling, Klang and Hulu Langat from June to August 2020. All doctors were involved in the care of patients for smoking cessation. The knowledge, attitude and practice of smoking cessation management were assessed using a 17-items validated questionnaire which covered the components of 5As (Ask, advise, assess, assist, arrange) and 5Rs (Relevance, risk, reward, roadblocks, repetition). The management of pre-contemplation phase included the components of ask, advise, assess and 5Rs. The management of the contemplation phase included the components of assist and arrange.ResultThe majority of the respondents had poor score of knowledge (62.4%); attitude (58%) and practice (pre-contemplation management:50.9%; contemplation management:75.7%). Using multivariate logistic regression analysis, the significant factors associated with the poor practice of smoking cessation management in the pre-contemplation phase were poor (OR = 2.14, 95% CI 1.11–4.12, p <0.01) or moderate knowledge (OR = 2.50, 95% CI 1.19–5.26, p<0.01), poor attitude (OR = 2.16, 95% CI 1.39–3.37, p<0.01), lacks smoking cessation banners, brochures and leaflets in the clinic (OR = 2.01, 95%CI 1.26–3.19, p<0.01) and lack of nicotine replacement medications (OR = 2.27. 95%CI 1.27–4.06, p<0.01). No significant factors were shown associated with the practice of the contemplation phase.ConclusionThe majority of primary care doctors had poor knowledge, attitude and practice of smoking cessation management. Factors that had increased the odds of the poor practice of smoking management at the pre-contemplation phase were poor knowledge, poor attitude, and insufficient organizational support for health promotion materials and nicotine replacement medication.
Recovery of neuropsychological function following abstinence from alcohol in adults diagnosed with an alcohol use disorder: Protocol for a systematic review of longitudinal studies
Authors: Powell Anna , Sumnall Harry , Smith Jessica , Kuiper Rebecca , Montgomery Catharine 
Published: September 2022

Background
Alcohol use disorders (AUD) associate with structural and functional brain differences, including impairments in neuropsychological functions; however, review level research (largely cross-sectional) is inconsistent with regards to recovery of such functions following abstinence. Such recovery is important, as these impairments associate with treatment outcomes and quality of life.

Objective(s)
To assess neuropsychological function recovery following abstinence in individuals with a clinical AUD diagnosis. The secondary objective is to assess predictors of neuropsychological recovery in AUD.

Methods
Four electronic databases (APA PsycInfo, EBSCO MEDLINE, CINAHL, Web of Science Core Collection) will be searched between 1999–2022, with search strategies adapted for each source. Study reporting will follow the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis, study quality will be assessed using the JBI Checklist for Cohort Studies. Eligible studies are those with a longitudinal design that assessed neuropsychological recovery following abstinence from alcohol in adults with a clinical diagnosis of AUD. Studies will be excluded if participant group is defined by another or co-morbid condition/injury, or by relapse.

Results
This is an ongoing review. As of July 2022, the review protocol is registered on PROSPERO (CRD42022308686), searches have been conducted, and screening is in progress. Results are predicted to be complete by October 2022.

Conclusions
Comparing data on neuropsychological recovery from AUD will improve understanding of the impact of alcohol on the brain, and the relationship between AUD recovery and quality of life/treatment outcomes. It may provide information that could one day inform aspects of treatment and aftercare (e.g., options for cognitive training of functions that do not improve on their own).