bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale for the selection of dual primary endpoints in prevention studies of cognitively unimpaired individuals at genetic risk for developing symptoms of Alzheimer’s disease
Authors: Caputo Angelika , Racine Amy , Paule Ines , Tariot Pierre N. , Langbaum Jessica B. , Coello Neva , Riviere Marie-Emmanuelle , Ryan J. Michael , Lopez Cristina Lopez , Graf Ana 
Published: November 2022

Abstract
Background: There is a critical need for novel primary endpoints designed to detect early and subtle changes in cognition in clinical trials targeting the asymptomatic (preclinical) phase of Alzheimer’s disease (AD). The Alzheimer’s Prevention Initiative (API) Generation Program, conducted in cognitively unimpaired individuals at risk of developing AD (e.g., enriched by the apolipoprotein E (APOE) genotype), used novel dual primary endpoints based on 1) time to event (TTE) – with an event defined as diagnosis of mild cognitive impairment (MCI) due to AD and/or dementia due to AD – and 2) change from baseline to Month 60 in the API preclinical composite cognitive (APCC) test score.
Methods: Historical observational data from three sources were used to fit models to describe the TTE and the longitudinal APCC decline, both in people who do and do not progress to MCI or dementia due to AD. Clinical endpoints were simulated based on the TTE and APCC models to assess the performance of the dual endpoints versus each of the two single endpoints, with the selected treatment effect ranging from a hazard ratio (HR) of 0.60 (40% risk reduction) to 1 (no effect).
Results: A Weibull model was selected for TTE, and power and linear models were selected to describe the APCC score for progressors and non-progressors, respectively. Derived effect sizes in terms of reduction of the APCC change from baseline to Year 5 were low (0.186 for HR=0.67). The power for the APCC alone was consistently lower compared to the power of TTE alone (58% [APCC] vs 84% [TTE] for HR=0.67). Also, the overall power was higher for the 80%/20% distribution (82%) of the family-wise type-1 error rate (alpha) between TTE and APCC compared to 20%/80% (74%).
Conclusions: Dual endpoints including TTE and a measure of cognitive decline perform better than the cognitive decline measure as a single primary endpoint in a cognitively unimpaired population at risk of AD (based on the APOEgenotype). Clinical trials in this population, however, need to be large, include older age, and have a long follow-up period of at least 5 years to be able to detect treatment effects.
Frequent copy number variants in a cohort of Mexican-Mestizo individuals
Authors: Sánchez Silvia , Juárez Ulises , Domínguez Julieta , Molina Bertha , Barrientos Rehotbevely , Martínez-Hernández Angélica , Carnevale Alessandra , Grether-González Patricia , Mayen Dora Gilda , Villarroel Camilo , Lieberman Esther , Yokoyama Emiy , Castillo Victoria Del , Torres Leda , Frias Sara 
Published: November 2022

Abstract
Background. The human genome presents variation at distinct levels, Copy number variants (CNV) are DNA segments of various lengths in bp that are present at a variable number of copies compared to a reference genome. CNV analysis has been done in almost all human populations and most of them have no apparent influence on the phenotype, yet some of them usually long sized, has been associated with pathologies. Recently however, the detection of common and benign CNV within different ethnic populations is becoming increasingly relevant as it helps in discerning real pathological variants and thus avoiding misinterpretations. The aim of this work is to describe four CNV frequently found in a cohort of 147 Mexican-Mestizo individuals.
Results: In this study we found four CNV 2p11.2, 8p11.22, 14q32.33 and 15q11.2, with a high frequency in the Mexican population when contrasted with the HapMap reference (ChAS), while when used an ethnically related population as a reference, the differences are reduced or disappear. The population studied does not show inbreeding or consanguinity.
Conclusion: CNV-type polymorphisms have frequencies that vary according to the ethnic group studied. It highlights the importance of analyzing the CNV of the studied individuals, with a reference group that -as far as possible- share the same ethnicity. These findings should be considered to avoid false associations of CNV with pathological conditions.
Age- and sex-specific trends of HOMA-IR values in adolescents from 2007–2010 to 2019–2020 in Korea
Authors: Kim Sujin , Song Kyungchul , Myeongsub Lee , Suh Junghwan , Chae Hyun Wook , Kim Ho-Seong , Kwon Ahreum 
Published: November 2022

Abstract
Background/Objectives: Changes in the percentile value of the homeostasis model assessment of insulin resistance (HOMA-IR) value in adolescents in Korea are yet to be elucidated. This study aimed to investigate the age- and sex-specific trends in insulin resistance (IR) according to the HOMA-IR in Korean adolescents, using data from the Korean National Health and Nutrition Examination Survey IV, VI, and VIII conducted between 2007–2010 and 2019–2020.
Subjects/Methods: Overall, 4621 adolescents (2484 boys and 2137 girls) aged 10–18 years were evaluated. Among them, 3473 subjects (1855 boys and 1618 girls) were from the 2007–2010 dataset, and 1148 subjects (629 boys and 519 girls) were from the 2019–2020 dataset. The subjects were grouped according to body mass index (BMI) and evaluated according to age and sex. Percentile curves of HOMA-IR were calculated as a function of age and stratified by sex and BMI group.
Results: In the normal weight group, HOMA-IR values peaked at age 12–14 years in boys and at age 10–12 years in girls. In the overweight/obese group, HOMA-IR values did not show a specific pattern according to age. In the normal-weight group, there was no difference in the mean HOMA-IR values between 2007–2010 and 2019–2020, but the distribution range was wider in 2019–2020 than in 2007–2010. Meanwhile, in the overweight/obese group, HOMA-IR values were significantly higher in 2019–2020 than in 2007–2010.
Conclusions: Percentiles of HOMA-IR vary significantly according to age, sex, and BMI among Korean adolescents. Therefore, because the value of HOMA-IR in adolescents is affected by several factors, including age, sex, weight status, and race, these factors should be considered when clinically utilizing HOMA-IR. In addition, active intervention for IR, especially during the growth spurt period, is needed.
Post-fumigation sub-lethal activities of phosphine and ethyl formate on survivorship, fertility and female sex pheromone production of Callosobruchus chinensis (L.)
Authors: Chiluwal Kashinath , Lee Byung Ho , Kwon Tae Hyung , Kim Junheon , Park Chung Gyoo 
Published: November 2022

Abstract
Phosphine (PH3) and ethyl formate (EF), the two popular fumigant disinfectants of stored product insect pests, are primarily evaluated for their knock down effects without considering their post-fumigation sub-lethal activities. The sub-lethal activities (adult survivorship, fecundity, sterility and female sex pheromone production) of the fumigants were evaluated on a field-to-storage insect pest adzuki bean beetle, Callosobruchus chinensis (L.). The adults’ survivorship and female fecundity, both were dose-dependently affected by sub-lethal PH3 and EF fumigation exposures. Hatchability of the eggs laid by fumigated female adults were also significantly affected. Gas-chromatography mass-spectrometry analysis of solid-phase micro-extraction from virgin fumigated C. cinensis females revealed that the PH3 LC25 (the lethal concentration required to kill the 25% of the population) fumigated female C. chinensis released significantly less amount of the pheromone components. In contrast, EF LC25 exposure did not affect the pheromone release. This study unveils the facts that the EF and PH3 fumigation have detrimental bioactivities against C. chinensis. Notably, this suggests to consider the sub-lethal EF and PH3 fumigation rather than the dose required to instantly kill all the C. chinensis individuals for disinfestation of stored adzuki bean.
The Relationship Between Fear of Surgery and Affecting Factors in Surgical Patients
Authors: Akutay Seda , Ceyhan Özlem 
Published: November 2022

Abstract
Background: This study aimed to explain the fear of surgery in surgical patients, the affecting factors, and their relationship.
Methods:This study was conducted as a descriptive and cross-sectional study. The study population consists of 300 patients undergoing surgical intervention. Data were collected using the "Patient Information Form" and "Surgical Fear Questionnaire". Parametric and nonparametric tests were used to evaluate the data. The relationship between the fear questionnaireand age, number of previous surgeries, and pre-operative pain were evaluated using Spearman correlation analysis. The relationship with emotional stress was evaluated with multiple linear regression analysis.
Results: In this study, it was determined that the predictors of the surgical fear level of the patients were age, gender, anesthesia type, and pre-operative pain experience. There was a negative correlation between the age of the patients and the fear of surgery score and a positive correlation between the pre-operative pain severity and the fear of surgery score. It was determined that the factors most associated with pre-operative fear levels were the patients' pre-operative sense of inadequacy (p <0.001), feeling anxious and unhappy, and confusion about the surgery decision (p <0.005).
Conclusion: According to the results of this study, it has been determined that the emotional states and fears of the patients before the surgery have significant effects on the fear of surgery. For this, it is recommended to determine the emotional states and fears of the patients before the surgery and to make appropriate interventions, as it will facilitate compliance with the surgical process.
Impact of the mental health reform in Israel on health care and mortality among people with severe mental illness
Authors: Gal Gilad , Levav Itzhak , Kodesh Arad 
Published: November 2022

Abstract
Objective
Reports show disparities in the health care of people with severe mental illness (SMI). Yet, the moderating effect of mental health reforms on the health care disparities remain unexplored. The current study aimed to investigate the outcomes of the mental health reform in Israel on the use of health services among people with SMI.
Method
A case-control epidemiological study comparing the use of health services 3.5 years before and after the mental health reform for service users diagnosed with schizophrenia, schizoaffective disorder, and bipolar disorder. Data on health services included: blood cholesterol test (LDL), hemogalobin-A1C test, and visits to GPs and specialists. Mortality was recorded.
Results
Following the reform the number of visits to GPs was decreased among service users of the three SMI groups, as well as visits to specialists among service users with a schizoaffective or bipolar disorder. Following the reform service users of the three SMI groups showed no-change in the performance of LDL test. Complex findings were noted with regard to the performance of Hemoglobin-A1C test. Mortality rates were higher among service users with SMI and did not change following the reform.
Conclusions
Users of the three SMI groups showed no benefits of the mental health reform in terms of use of health services. Improved health care can be attained by a closer collaboration between the primary physicians and community mental health services.
Disparities in Postoperative Opioid Prescribing by Race and Ethnicity: An Electronic Health Records-Based Observational Study
Authors: Romanelli Robert J. , Shenoy Rivfka , Martinez Meghan C. , Mudiganti Satish , Mariano Louis T. , Zanocco Kyle A. , Wagner Zachary , Kirkegaard Allison , Watkins Katherine E. 
Published: November 2022

Abstract
Background: Prior studies on disparities in postoperative opioid prescribing have focused primarily on in-hospital opioid administration or long-term opioid use, with fewer studies examining discharge opioid prescribing for adults, and no studies looking across different surgical subspecialties or service lines. We sought to examine racial and ethnic disparities in postoperative opioid prescribing to test the hypothesis that racial and ethnic minority groups receive opioid prescriptions at postoperative discharge with lower morphine milligram equivalents (MME) than non-Hispanic whites (NHW).
Methods: We utilized electronic health records (EHR) data across 24 hospitals from a healthcare delivery system in northern California from January 1, 2015 to February 2, 2020 (study period). The sample included adult patients undergoing a procedure during the study period, discharged to home with an opioid prescription. Cross-sectional, secondary data analyses were conducted to examine differences by race and ethnicity in opioid prescribing, measured as MME, among patients who underwent select, but commonly performed, surgical procedures. Linear regression models included adjustment for factors that would likely influence prescribing decisions and race and ethnicity-specific propensity weights. Opioid prescribing, overall and by race and ethnicity, was also compared to postoperative opioid guidelines.
Results: Among 61,564 patients, on adjusted regression analysis, non-Hispanic Black (NHB) patients received prescriptions with higher mean MME than NHW patients (+6.4% [95% confidence interval: 4.4%, 8.3%]), whereas Hispanic and non-Hispanic Asian patients received lower mean MME (-4.2% [-5.1%, -3.2%] and -3.6% [-4.8%, -2.3%], respectively). Nevertheless, 72.8% of all patients received prescriptions above guidelines, ranging from 71.0% to 80.3% by race and ethnicity. Disparities in prescribing were eliminated among Hispanic and NHB patients versus NHW patients when prescriptions were written within guideline recommendations.
Conclusions: Racial and ethnic disparities in opioid prescribing exist in the postoperative setting, yet all groups received prescriptions above guideline recommendations. Policies encouraging guideline-based postoperative prescribing can reduce disparities and overall excess prescribing.
The differentiation status of luminal-type breast cancer–derived organoids can be altered in vitro through the activation of NOTCH signaling
Authors: Uematsu Hiroyuki , Saito Chieko , Kondo Jumpei , Onuma Kunishige , Coppo Roberto , Mori Yukiko , Mutou Manabu , Kikawa Yuichiro , Tada Manami , Sugie Tomoharu , Inoue Masahiro 
Published: November 2022

AbstractBackground Drug therapy of luminal-type breast cancer has advanced remarkably; however, its effectiveness continues to be limited by primary and acquired treatment resistance. To identify the means of overcoming such resistance,in vitrodisease models that faithfully reproduce the characteristics of original patient tumors must be developed. Although the three-dimensional culturing of breast cancer cells has been improved, the changes in differentiation status and underlying mechanisms require further elucidation. Methods The organoids from 33 luminal-type breast cancers were prepared using a method developed by us. Using immunohistochemistry and gene expression profiling, the levels and time courses of estrogen receptor, progesterone receptor, Ki67, and differentiation marker expression were monitored during culture as well as the variation among the patients and individual organoids. Furthermore, we examined the effect of NOTCH inhibitor treatment on differentiation status. Results We successfully prepared organoids from samples obtained from 33 patients with luminal-type breast cancer and studied their ER expression. The expression status was well maintained in primary organoids, whereas it decreased after passaging in most of the cases. In fact, the studied organoid lines were classified into those that retained a high level of ER expression (9%), those that completely lost it (9%), and those that repressed it to varying degrees (82%). In some cases, the ER expression was suddenly and drastically decreased after passaging. Marker protein immunohistochemistry revealed that after passaging, the differentiation status shifted from a luminal- to a basal-like status. Differentially expressed genes suggested the activation of NOTCH signaling in the passaged organoids, wherein a NOTCH inhibitor was able to substantially rescue the decreased ER expression and alter the differentiation status. Conclusions Our findings suggest that the differentiation status of luminal-type cancer cells is quite flexible, and that by inhibiting the NOTCH signaling we can preserve the differentiation status of luminal-type breast cancer organoids.
Machine Learning Algorithms Predict Successful Weaning from Mechanical Ventilation Before Intubation
Authors: Kim Hyung-Jun , Kim Jinchul , Kim Yun Kwan , Kim Hyeyeon , Jung Hyojung , Koh Soonjeong , Kim Yujeong , Yoon Dukyong , Yi Hahn 
Published: November 2022

Abstract
Prediction of successful weaning from mechanical ventilation in advance to intubation can facilitate discussions regarding end-of-life care before unnecessary intubation. In this context, we aimed to develop a machine-learning-based model that predicts successful weaning from ventilator support based on routine clinical and laboratory data taken before or immediately after intubation. We used the Medical Information Mart for Intensive Care-IV database, including adult patients who underwent mechanical ventilation in intensive care at the Beth Israel Deaconess Medical Center, USA. Clinical and laboratory variables collected before or within 24 hours of intubation were used to develop machine-learning models that predict the probability of successful weaning within 14 days of ventilator support. Of 23,242 patients, 19,025 (81.9%) patients were successfully weaned from mechanical ventilation within 14 days. We selected 46 clinical and laboratory variables to create machine-learning models. The machine-learning-based ensemble voting classifier revealed the area under the receiver operating characteristic curve of 0.863 (95% confidence interval 0.855–0.870), which was significantly better than that of Sequential Organ Failure Assessment (0.588 [0.566–0.609]) and Simplified Acute Physiology Score II (0.749 [0.742–0.756]). The top features included lactate, anion gap, and prothrombin time. The model’s performance achieved a plateau with approximately the top 21 variables. We developed machine learning algorithms that can predict successful weaning from mechanical ventilation in advance to intubation in the intensive care unit. Our models can aid in appropriate management for patients who hesitate to decide on ventilator support or meaningless end-of-life care.
Association between eating alone and depression by income level
Authors: Min Ju-Hong , Jung Hye-Sun 
Published: November 2022

Abstract
Background
In Korea, the number of single-person households is increasing annually, with increases from 23.9% in 2010 to 27.9% in 2016, and 31.7% in 2020. As the number of single-person household increases, the number of people eating alone also increases. As a result, mental health problems such as depression and stress have occurred. This phenomenon may show a different tendency depending on socioeconomic levels.
Methods
Frequency analysis was conducted to understand the general characteristics of the study subjects. In addition, a chi-squared test was conducted to verify the difference in income levels according to the characteristics of the study subjects. To verify the differences between the characteristics and depression in the study subjects by income level, a chi-squared test was conducted. Multiple logistic regression analysis was conducted to confirm the factors affecting depression by income level.
Results
In the case of commensality, 75.7% of the group with high-income levels were higher than 67.4% of the group with low-income levels. In the case of depression, 18.6% of the low-income group was higher than 11.3% of the high-income group. When divided according to income level, in the low-income group, the group that eats alone had 1.46-times (95% confidence interval (CI): 1.077~2.066) higher depression than the group that does not eat with others. In contrast, in the high-income group, eating alone did not have a significant effect on depression.
Conclusion
The effect of eating alone on depression varies depending on the income level. Thus, other factors may have affected depression in the high-income group rather than eating alone. In the low-income group, it is necessary to improve the environment so that they can eat together for healthy eating and mental health, and promotion or education should be provided.
Nonlinear Feedback Synthesis and Control of Periodic, Quasiperiodic, Chaotic and Hyper-Chaotic Oscillations in Mechanical Systems
Authors: Kundu Prasanjit Kumar , Chatterjee Shyamal 
Published: November 2022

Abstract
Self-excited periodic, quasiperiodic and chaotic oscillations have many significant applications in engineering devices and processes. In the present paper a centralized nonlinear controller is proposed to artificially generate and control self-excited periodic, quasiperiodic, chaotic and hyper-chaotic oscillations of required characteristics in a fully-actuated n-DOF spring-mass-damper mechanical system. The analytical relations among the amplitude, frequency and controller parameters for minimum control energy have been obtained using the method of two-time scale. It is shown that the proposed control can generate modal and nonmodal self-excited periodic and quasiperiodic oscillations of desired amplitude and frequency for minimum control energy. The analytical results have been verified numerically with MATLAB SIMULINK. Bifurcation analysis and extensive numerical simulations reveal a region of multistability in the plane of control parameters, where system responses may be periodic, quasiperiodic, chaotic and hyper-chaotic depending on initial conditions. However, it has been shown that the probability of obtaining chaotic and hyper-chaotic oscillations are very high for a wide range of controller parameters. The procedures of controlling the amplitude, frequency and characteristics of chaotic oscillations are also discussed. The results of the present paper is expected to find applications in various macro and micro mechanical systems and applications.