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Background: We aimed to compare the analgesic effects of intravenous ibuprofen to ketorolac after open abdominal hysterectomy. Methods: This randomized double-blinded controlled trial included adult women scheduled for elective open abdominal hysterectomy. Participants were randomized to receive either 30 mg ketorolac (n = 50) or 800 mg ibuprofen (n = 50) preoperatively, then every 8 h postoperatively for 24 h. All participants received paracetamol 1 gm/6 h. Rescue analgesic was given if the visual analogue scale (VAS) for pain assessment was > 3. The primary outcome was the mean postoperative dynamic VAS during the first 24 h. Secondary outcomes were static VAS, intraoperative fentanyl consumption, postoperative morphine consumption, time to independent movement, and patient's satisfaction. Results: Forty-six patients in the ibuprofen group and fifty patients in the ketorolac group were analyzed. The 24-h dynamic and static VAS were similar in the two groups. The median (quartiles) dynamic VAS was 1.1 (0.9, 1.9) in the ibuprofen group versus 1.0 (0.7, 1.3) in the ketorolac group, P-value = 0.116; and the median (quartiles) static VAS was 0.9 (0.6, 1.3) in the ibuprofen group versus 0.7 (0.4, 1.1) in the ketorolac group, P-value = 0.113. The intra- and postoperative analgesic requirements were also similar in the two groups. However, patient satisfaction was slightly higher in the ketorolac group than that in the ibuprofen group (median [quartiles]: 6 [5, 7] versus 5 [4, 7], respectively), P-value: 0.009. Conclusion: The two drugs, intravenous ibuprofen and ketorolac produced similar analgesic profile in patients undergoing open abdominal hysterectomy receiving multimodal analgesic regimen. NCT05610384, Date of registration: 09/11/2022 Clinical trial registration: ClinicalTrials.gov Identifier: NCT05610384. https://clinicaltrials.gov/ct2/show/NCT05610384 [ABSTRACT FROM AUTHOR]

Background: There is a lack of quantitative studies that specifically measure the association between the experience of pregnancy and unintended pregnancy. The present study aims to address the prevalence of unintended pregnancy and identify its predictors. Additionally, the study explores whether unintended pregnancy is associated with pregnancy uplifts and hassles. Methods: This cross-sectional study was conducted on 488 pregnant women between 20 to 40 weeks' gestation at the comprehensive health center in Tabriz City from February 2022 to January 2023. A cluster sampling method was used for sampling, and data were collected using socio-demographic questionnaires and the Pregnancy Experience Scale (PES). Descriptive statistics were used to describe the socio-demographic characteristics and the prevalence of unintended pregnancy. Binary logistic regression was employed to identify the predictors of pregnancy desirability. To examine the relationship between unintended pregnancy and pregnancy experience, an independent t-test was used for bivariate analysis, and a general linear model (GLM) was utilized for multivariate analysis, with control for potential confounding variables. Results: The prevalence of unintended pregnancies was 30.7% (24.3% unwanted pregnancies, and 6.4% mistimed pregnancies). The results of the binary logistic regression indicated that the lower age of both the woman and her spouse were significant predictors for unintended pregnancy (P < 0.05). Based on an independent t-test, the mean score for uplifts in women with unintended pregnancy was significantly lower than in women with intended pregnancy (mean difference (MD): -4.99; 95% confidence interval (CI): -5.96 to -4.02; p < 0.001), While the mean score of hassles in women with unintended pregnancy was significantly higher than women with intended pregnancy (MD: 2.92; 95% CI: 2.03 to 3.80; p < 0.001). The results of GLM showed that women who had unintended pregnancies had significantly lower scores for uplifts (B = -4.99; 95% CI: -5.96 to -4.03; P < 0.001) and higher scores for hassles (B = 2.92; 95% CI: 2.06 to 3.78; P < 0.001). Conclusions: The high prevalence of unintended pregnancies in Tabriz highlights the importance of targeted interventions to address this issue, considering the policy framework and unique challenges faced by women. Future studies should focus on developing context-specific interventions that effectively meet the needs of women with unintended pregnancies. Plain Language Summary: An unintended pregnancy is a pregnancy that occurs either when the woman did not intend to get pregnant at all or when she intended to get pregnant but became pregnant at an inappropriate time. This type of pregnancy can have negative effects on the physical and mental health of women during pregnancy and after delivery. So far, no study has investigated the relationship between the experience of pregnancy and unintended pregnancy, and the existing studies, which are qualitative and based on interviews, have examined women's experiences of unintended pregnancy. For the first time, our study examined the relationship between pregnancy experience and unintended pregnancy in 488 women using a valid questionnaire, the Pregnancy Experience Scale, which includes two parts: uplifts and hassles specific to pregnancy. Our findings showed that women who have an unintended pregnancy have a worse pregnancy experience in both uplifts and hassles specific to pregnancy. Also, limited studies have investigated the prevalence of unintended pregnancy in Iran, especially in the city of Tabriz in recent years. Our study, found this prevalence to be 30.7% in Tabriz, with 24.3% of women having no intention of getting pregnant and 6.4% of women experiencing pregnancy at an inappropriate time. The recommendation is to implement strategies to reduce unintended pregnancy rates and improve women's knowledge of fertility, sexuality, and contraception. [ABSTRACT FROM AUTHOR]

Introduction: Sexual risky behaviors, as defined by the World Health Organization, encompass a spectrum of sexual activities that heighten the likelihood of negative outcomes related to sexual and reproductive health. Despite the implementation of various healthcare programs and interventions, youths continue to encounter challenges in accessing reproductive health services. Consequently, they remain vulnerable to engaging in high-risk sexual behaviors; 50.36% of adolescents in Ethiopia. Therefore, this study was aimed to determine the prevalence of risky sexual behavior and associated factors among out-of-school Youths in Addis Ababa, Ethiopia; 2023. Methods: A community based cross sectional mixed methods study was conducted among 701 youths in Addis Ababa from September 1st to 30th, 2023. The quantitative data were collected through face to face interview using a pre-tested structured questionnaire, while qualitative data were gathered through in depth interviews and focus group discussions. For the quantitative study, the study samples were chosen using systematic sampling. Conversely, purposive sampling was employed for the qualitative study. Variables with P-value ≤ 0.25 in the bivariate analysis were considered as candidates for the multivariable analysis. Statistical significance was declared at a P-value less than 0.05. Results: The prevalence of risky sexual behavior among out of school students in Addis Ababa was 40.6% (95%CI: 36.8, 44.1). Age 15–19 years (AOR: 2.52; 95%CI: 1.61, 3.94), being female (AOR: 2.84; 95%CI: 1.93, 4.18), fathers who were unable to read and write (AOR: 4.13; 95%CI: 2.04, 8.37), alcohol consumption (AOR: 2.07; 95%CI: 1.33, 3.19), peer pressure (AOR: 2.59; 95%CI: 1.81, 3.72), live together with either of biological parent (AOR: 2.32; 95%CI: 1.52, 3.55), watching pornography (AOR: 2.10; 95%CI: 1.11, 3.97) and parental monitoring (AOR: 0.59; 95%CI: 0.39, 0.90) were factors associated with risky sexual behavior. Conclusion and recommendations: A lower prevalence of risky sexual behavior compared to prior research efforts. Age, gender, educational level of the husband, alcohol consumption, peer pressure, living arrangements, exposure to pornography, and family monitoring emerged as significant factors associated with risky sexual behavior. Therefore, government should prioritize strategies to reduce substance use, mitigate the impact of watching pornography, and enhance parent-youth connectedness. [ABSTRACT FROM AUTHOR]

Background: There is a lack of quantitative studies that specifically measure the association between the experience of pregnancy and unintended pregnancy. The present study aims to address the prevalence of unintended pregnancy and identify its predictors. Additionally, the study explores whether unintended pregnancy is associated with pregnancy uplifts and hassles. Methods: This cross-sectional study was conducted on 488 pregnant women between 20 to 40 weeks' gestation at the comprehensive health center in Tabriz City from February 2022 to January 2023. A cluster sampling method was used for sampling, and data were collected using socio-demographic questionnaires and the Pregnancy Experience Scale (PES). Descriptive statistics were used to describe the socio-demographic characteristics and the prevalence of unintended pregnancy. Binary logistic regression was employed to identify the predictors of pregnancy desirability. To examine the relationship between unintended pregnancy and pregnancy experience, an independent t-test was used for bivariate analysis, and a general linear model (GLM) was utilized for multivariate analysis, with control for potential confounding variables. Results: The prevalence of unintended pregnancies was 30.7% (24.3% unwanted pregnancies, and 6.4% mistimed pregnancies). The results of the binary logistic regression indicated that the lower age of both the woman and her spouse were significant predictors for unintended pregnancy (P < 0.05). Based on an independent t-test, the mean score for uplifts in women with unintended pregnancy was significantly lower than in women with intended pregnancy (mean difference (MD): -4.99; 95% confidence interval (CI): -5.96 to -4.02; p < 0.001), While the mean score of hassles in women with unintended pregnancy was significantly higher than women with intended pregnancy (MD: 2.92; 95% CI: 2.03 to 3.80; p < 0.001). The results of GLM showed that women who had unintended pregnancies had significantly lower scores for uplifts (B = -4.99; 95% CI: -5.96 to -4.03; P < 0.001) and higher scores for hassles (B = 2.92; 95% CI: 2.06 to 3.78; P < 0.001). Conclusions: The high prevalence of unintended pregnancies in Tabriz highlights the importance of targeted interventions to address this issue, considering the policy framework and unique challenges faced by women. Future studies should focus on developing context-specific interventions that effectively meet the needs of women with unintended pregnancies. Plain Language Summary: An unintended pregnancy is a pregnancy that occurs either when the woman did not intend to get pregnant at all or when she intended to get pregnant but became pregnant at an inappropriate time. This type of pregnancy can have negative effects on the physical and mental health of women during pregnancy and after delivery. So far, no study has investigated the relationship between the experience of pregnancy and unintended pregnancy, and the existing studies, which are qualitative and based on interviews, have examined women's experiences of unintended pregnancy. For the first time, our study examined the relationship between pregnancy experience and unintended pregnancy in 488 women using a valid questionnaire, the Pregnancy Experience Scale, which includes two parts: uplifts and hassles specific to pregnancy. Our findings showed that women who have an unintended pregnancy have a worse pregnancy experience in both uplifts and hassles specific to pregnancy. Also, limited studies have investigated the prevalence of unintended pregnancy in Iran, especially in the city of Tabriz in recent years. Our study, found this prevalence to be 30.7% in Tabriz, with 24.3% of women having no intention of getting pregnant and 6.4% of women experiencing pregnancy at an inappropriate time. The recommendation is to implement strategies to reduce unintended pregnancy rates and improve women's knowledge of fertility, sexuality, and contraception. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated. Methods: Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups. Results: A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes. Conclusion: The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission. [ABSTRACT FROM AUTHOR]

Describing the structural complexity of seabeds is of primary importance for a number of geomorphological, hydrodynamical and ecological issues. Aiming to bring a decisive insight on the long-term development of a unified view, the present study reports on a comparative multi-site analysis of high resolution topography surveys in rough nearshore environments. The nine study sites have been selected to cover a wide variety of topographical features, including rocky and coral seabeds. The topography data has been processed to separate roughness and bathymetry-related terrain features, allowing to perform a comprehensive spectral and statistical analysis of each site. A series of roughness metrics have been tested to identify the most relevant estimators of the bottom roughness at each site. The spectral analysis highlights the systematic presence of a self-affine range of variable extension and spectral slope. The standard deviation of the seabed elevation varies from 0.04 to 0.77 m. The statistical and multi-scale analysis performed on the whole set of roughness metrics allows to identify connection between metrics and therefore to propose a reduced set of relevant roughness estimators. A more general emphasis is placed on the need to properly define a unified framework when reconstructing roughness statistics and bathymetry from fine seabed topographical data. [ABSTRACT FROM AUTHOR]

Background: Job crafting is defined as a series of proactive behaviors exhibited by employees in order to balance work resources and needs, which has a significant positive impact on the nurses. It is necessary to find the core factors that influence the job crafting, as emergency nurses deal with the most complex tasks, so as to improve their job satisfaction. Objectives: To investigate the core factors of job crafting among emergency nurses. Methods: A cross-sectional design was used in the study. A total of 255 nurses were recruited from two hospitals in Zhengzhou and Shenzhen, China in December 2021. 255 nurses completed an online questionnaire. Hierarchical regression models and fsQCA models were used to explore the factors influencing job crafting among emergency nurses and helped us to identify core factors. Results: The hierarchical regression model and the fsQCA model found that the occupational benefit, psychological empowerment, and research experience were the core factors affecting their job crafting. Job involvement was not significant in the regression model, but the QCA model indicated that it needs to be combined with other factors to impact on job crafting. The QCA model uncovered seven key conditional configurations that led to high and low job crafting among emergency nurses, explaining 80.0% of the results for high job crafting and 82.6% of the results for the low job crafting, respectively. Conclusions: The results of this study provide valuable insights into the job crafting experienced by emergency nurses. Junior emergency nurses should be granted a high level of psychological empowerment without assigning them overly complex tasks, such as research tasks, as these challenges can stop their job crafting. Intermediate and senior emergency nurses, on the other hand, can be assigned research tasks coupled with high psychological empowerment to enhance their job crafting. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the factors influencing glycemic control in patients with type 2 diabetes mellitus (T2DM). Methods: Baseline data, encompassing basic information, lifestyle habits, and treatment of 305 T2DM patients from March 2021 to January 2023, were collected and analyzed using SPSS 26.0 software. Results: Univariate and multivariate logistic regression analyses identified insulin therapy (OR = 2.233; 95%Cl = 1.013–4.520; P = 0.026) and regular clinic visits (OR = 0.567; 95%Cl = 0.330–0.973; P = 0.040) as independent factors influencing glycemic control. No observed interactions between the two variables were noted. Conclusion: History of insulin therapy and regular clinic visits were significantly and independently associated with glycated hemoglobin control in T2DM patients. Tailored interventions based on individual circumstances are recommended to optimize glycemic control. [ABSTRACT FROM AUTHOR]

Objective: There is no study on the relationship between triglyceride-glucose index (TyG index) and skeletal muscle mass in middle-aged and elderly C population. Therefore, the aim of the study is to investigate the relationship between the TyG index and weight-adjusted relative skeletal muscle index (RSMI) in middle-aged and elderly C population. Methods: We retrospectively studied 947 aged ⩾40 years subjects who got a routine medical examination in the Department of Geriatrics of R Hospital from May 2021 to March 2023. The RSMI was designed to evaluate skeletal muscle mass and calculated based on lean mass of the limbs(kg)/body weight(kg) × 100%. Skeletal muscle mass reduction was defined as a RSMI of 1-2 standard deviations (SD) below of healthy adults aged 30-49 years old. Considering the quartile groups of the TyG index, the subjects were assigned to 4 groups: Q1 (less than or equal to 8.171), Q2 (from 8.172 to 8.569), Q3 (from 8.570 to 8.992), and Q4 (greater than or equal to 8.993). Results: With TyG index increased, RSMI levels significantly reduced(P <.001). Spearman's correlation analysis showed that the TyG index was negatively correlated with RSMI in males (r = −0.320) and females (r = −0.240). The TyG index was positively correlated with body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (P <.05). Besides, binary logistic regression analysis showed that the risk of developing reduced skeletal muscle mass in the group Q4 was 2.131 (95%CI:1.118-4.064) in males; and was 2.472 (95%CI:1.581-3.867) in females compared to the Q1 group. Conclusion: TyG index was negatively correlated with relative skeletal muscle index, and a higher TyG index was associated with the development of reduced skeletal muscle mass independently of other influencing factors. Therefore, the TyG index promises to be a predictor of skeletal muscle mass loss. [ABSTRACT FROM AUTHOR]

Background: Ankle fractures are frequent, and despite numerous publications on their treatment and outcome, there is a lack of precise data on the functional results in young, healthy and physically active patients. We hypothesized that patients who underwent open reduction and internal fixation (ORIF) for simple ankle fractures would have similar function compared to a healthy control group, whereas patients with complex fractures will have significant functional deficits. Furthermore, we postulate that there is a discrepancy between the radiological and the functional outcomes. Methods: A set of specific provocation tests was developed to evaluate the postoperative possibility of weight bearing, stop-and-go activities and range of motion. In combination with three questionnaires and a radiographic evaluation, the true functional outcome and the possibility of participating in sporting activities were investigated and compared with those of an age- and sex-matched control group. Results: A significant impairment was found in unilateral and simple ankle fractures. This impairment increased in tests including stop-and-go activities in combination with load bearing and with the complexity of the fractures. Concerning the subjective outcome, there was a significant adverse effect for daily activities without any difference in preoperative or postoperative sporting activity between the groups. No difference was found in the radiological assessment. Conclusions: Both simple and complex ankle fractures treated with ORIF have a significant and long-lasting impact on functional outcome in young and active patients. The radiological result is not associated with a good functional outcome. Trial registration: BASEC-Nr. 2018 − 01124. [ABSTRACT FROM AUTHOR]

Background: There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries. Methods: Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries. Findings: Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class. Conclusions: Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks. [ABSTRACT FROM AUTHOR]

The placebo effect occurs when a desired outcome is experienced due to the belief that a treatment is effective, even in the absence of an active ingredient. One explanation for this effect is based on a person's expectations of a drug or supplement. Although caffeine's effects on sports performance have been studied, little is known about how expectations of caffeine affect neuromuscular fatigue during continuous muscle action. The physical working capacity at the fatigue threshold (PWCFT) can be used to assess neuromuscular fatigue noninvasively using surface electromyography. Thus, the purpose of this study was to investigate whether caffeine expectancy influences PWCFT. We hypothesized that regardless of expectancy, caffeine consumption would delay neuromuscular fatigue. The study involved 8 healthy college-aged men (mean ± SEM: age, 25.6 ± 1.0 years) who visited the laboratory on 4 occasions, each separated by 7 days. The subjects completed 4 experimental conditions, in random order, where they were told that they were consuming caffeine or placebo and either received caffeine or placebo. After consuming the drink, the subjects remained in the laboratory for an hour and then performed an incremental exercise test. The results showed that the condition where subjects were told that they were consuming caffeine and received caffeine had significantly higher mean values for maximal power output (F(3, 21) = 11.75; p < 0.001), PWCFT (F(3, 21) = 12.28; p < 0.001), PWCFT (%maximal power output; F(3, 21) = 8.75; p < 0.001), and heart rate at end exercise (%predicted; F(3, 21) = 3.83; p = 0.025) compared with the 2 conditions where placebo was received. However, no statistically significant mean differences were found from the condition where subjects were told that they were consuming placebo but consuming caffeine. This suggests that a person's expectancy and potential somatic response may serve as a cue for how an ergogenic aid or placebo could affect subsequent performance. [ABSTRACT FROM AUTHOR]

Background: High-quality patient care requires nurses with strong clinical competency. Thus, it is essential to examine the factors associated with clinical competency. Purpose: This studywas designed to (a) investigate head nurse leadership, staff nurse demographics, and clinical competency; (b) examine the impact of demographics on the clinical competency of staff nurses; (c) analyze the correlation between head nurse leadership and staff nurse clinical competency; and (d) examine the effects of demographics on clinical competency after controlling for the head nurse leadership. Methods: A cluster sampling method was used to collect data from 200 staff nurses at a national medical center in Taiwan. Questionnaires were used to gather information on head nurse leadership style and staff nurse clinical competency. Descriptive and inferential statistical analyses were conducted, including Mann--Whitney U test, Kruskal--Wallis test, Spearman's rank correlation coefficient, and multivariate analysis of covariance. Results: The average score for transformational leadership style among the head nurses was 2.89, whereas transactional leadership style scored an average of 2.49. The average scores for the components of clinical competency, listed from highest to lowest, were as follows: patient care (3.35), professionalism (3.28), communication skills (3.18), management (2.84), and knowledge (2.73). In addition, statistically significant differences were found in clinical competency based on demographic factors, including age, marital status, educational level, job title, and length of employment. Also, a statistically significant, positive correlation between the head nurse transformational leadership style and nurse clinical competency was found. The main effect of length of employment on the five competency components was statistically significant after controlling for transformational leadership. Furthermore, post hoc analysis of covariance revealed a significant effect of length of employment on patient care, knowledge, communication skills, and management. Conclusions: The findings of this study indicate transformational leadership and employment length impact the clinical competency of staff nurses, particularly in terms of patient care, communication skills, management, and knowledge. Providing education and training in leadership and management to current and prospective head nurses may be expected to enhance clinical competency in staff nurses and create a more nurturing work environment. Moreover, targeted training may help current head nurses gain insight into their leadership styles and acquire skills to promote transformational leadership. In addition, leadership development may help equip prospective head nurses with critical competencies before assuming leadership responsibilities. [ABSTRACT FROM AUTHOR]

Background: Haitian Americans have been disproportionately exposed to risk factors known to play a significant role in the development of mental illness. Yet despite the documented effectiveness of mental health treatment, a high proportion of Haitian Americans with mental health disorders have not received care. Local problem: Internalized stigma of mental illness (ISMI) was reported as one of the primary reasons Haitian Americans do not seek help for mental illnesses, resulting in poor long-term outcomes for individuals and families in this community. This quality improvement project characterized ISMI among Haitian Americans, examined associated demographic factors, and tested the impact of a culturally relevant ISMI educational video intervention on willingness to seek mental health treatment. Methods: Haitian Americans who self-reported mental illness (N = 20) were recruited from a South Florida clinic. Descriptive statistics, correlations, and thematic analyses were completed to analyze the data. Interventions: Participants completed the nine-item ISMI scale, watched an educational video about ISMI, completed a post-intervention survey, and engaged in conversations about mental health and ISMI. Results: Sixty-five percent of participants reported mild levels of ISMI. Sex was significantly correlated with ISMI (r =2 0.458, p = .042); male participants experienced higher levels of ISMI. The educational video improved participants' knowledge of ISMI, and 85% indicated increased willingness to seek treatment. Conclusions: When caring for Haitian Americans with mental illnesses, nurse practitioners should initiate conversations about ISMI, consider gender differences in mental illness beliefs and attitudes, and provide culturally responsive psychoeducational interventions to promote more mental health treatment utilization. [ABSTRACT FROM AUTHOR]

Background: Mental illnesses are leading causes of disability in the United States. Some evidence supports that pharmacogenetic testing may be beneficial in select populations and that lithium is beneficial for treating mood disorders and anxiety in some populations. Purpose: This research aimed to determine whether low-dose lithium effectively decreases depression and anxiety in adults with a risk allele for CACNA1C genotypes. Methodology: The study design was correlational. Fifty patients were treated at a nurse practitioner-owned clinic in Prairie Village, Kansas. Chart review was used. Adults older than 18 years diagnosed with major depressive disorder, bipolar disorder, or generalized anxiety disorder presenting with an abnormality in the CACNA1C gene singlenucleotide polymorphism rs1006737 were included in this research. Assessment tools used were the Patient Health Questionnaire-9 for depression and GAD-7 for anxiety. Results: Low-dose lithium significantly decreased depression by 66% (p < .001) and anxiety by 65% (p = <.001). There was a significant difference in pretest depression levels based on CACNA1C genotype (p = .033). The A allele frequency was 60% higher (48%) in this population than found in general population (30%). Conclusions: Low-dose lithium significantly decreased anxiety and depression compared with baseline. People with different versions of the CACNA1C genotype had responses that differed significantly. The A risk allele was 60% more common than in the general population. [ABSTRACT FROM AUTHOR]

Aim of the study: Participation is an important construct and valuable therapy goal. Due to the lack of validated assessments on the participation level within German-speaking occupational therapy, the possibility to capture a person's participation is still not sufficient. The aim of this study was to test the assessment Activity Card Sort (ACS-DE) developed in Germany - based on the original version - to assess individual participation pattern and activity level. Method: In a cross-sectional study, 74 healthy adults and 53 persons six months after stroke in the 60-85 age group completed the assessment. Comparisons served to examine activity levels between the groups. Regression analyses examined correlations between age, stroke-related limitations, and the activity level. Factor analysis showed whether the data empirically cluster into the four categories proposed by the original version. Results: A large difference between the activity level of healthy adults and persons with stroke and also between the younger and older age groups supports the discriminative validity of the assessment. Factor analysis identified four factors. Results: The results show that the ACS-DE can validly capture the participation pattern and activity level of a person in both groups. [ABSTRACT FROM AUTHOR]

Low health literacy (LHL) significantly impacts patients' ability to participate actively in their healthcare. Registered nurses (RNs) play a crucial role in identifying LHL and addressing patient knowledge gaps and skill deficits. This correlational study examined the relationship between RNs' predictions of patients' health literacy levels (HLL) and the actual HLL of a predominately Hispanic patient population. In addition, personal factors (i.e., demographics) were analyzed to determine their influence on the nurse's predictions and patients' HLL. Data were collected from 84 participant patient–nurse couplets admitted to a medical-surgical unit in a rural setting located on the United States–Mexico border. In addition to demographic information collected via survey, RNs were asked to predict their patient's health literacy abilities while the Newest Vital Sign, a health literacy assessment tool, was deployed to determine the actual HLL of patients participating in the study. Data were analyzed using descriptive statistics, t -tests, and chi-square tests while a Spearman correlational model was used to examine the relationship between predicted HLL and actual HLL. Finally, a logistic regression model was used to analyze the relationship between personal factors and HL data for RNs and patients. Analysis of the data revealed that RNs consistently overestimated patients' abilities, as evidenced by the disparity between patients' actual HLL (mean 1.71) and predicted HLL (mean 4.26) by RNs, with a moderately strong positive relationship (rs =.418). Notably, higher academic preparation and years of experience did not enhance the RNs' ability to identify LHL while the highest level of education completed was the only statistically significant predictor of adequate health literacy in the patient population sampled. These findings emphasize the need to prioritize effective health literacy education in RN academic preparation and clinical practice to support the detection of LHL when a standardized health literacy assessment tool is not utilized in the clinical setting. By recognizing the presence of LHL, healthcare professionals can better support patients' needs and bridge the knowledge gap, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to clarify the interactive combinations of clinical factors associated with knee extension strength 2 yrs after total knee arthroplasty. Design: A retrospective cohort study was conducted on 264 patients who underwent total knee arthroplasty. Knee extension strength was assessed preoperatively, 3 wks, and 2 yrs after total knee arthroplasty. Physical functions were measured with 10-m walking test, Timed Up and Go test, one-leg standing time, isometric knee flexion strength, knee joint stability, knee pain, femora-tibial angle, and passive knee extension and flexion angle before surgery as a baseline and 3 wks after total knee arthroplasty as acute phase. Regression tree analysis was conducted to clarify the interactive combinations that accurately predict the knee extension strength 2 yrs after total knee arthroplasty. Results: Operational side knee extension strength (>1.00 Nm/kg) at acute phase was the primal predictor for the highest knee extension strength at 2 yrs after total knee arthroplasty. Acute phase Timed Up andGo test (=10.13 secs) and baseline 10-m walking test (=11.72 secs) was the second predictor. Acute phase nonoperative side knee extension strength (>0.90 Nm/kg) was also selected as the predictor. Conclusions: This study demonstrated that knee extension strength or Timed Up and Go test in the acute phase and 10-m walking test before total knee arthroplasty are useful for estimating the knee extension strength after total knee arthroplasty. The results will help determine specific postoperative rehabilitation goals and training options. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to compare the surface electromyographic amplitude, activation ratio, and onset latency of the main scapular stabilizing muscles between five typical rehabilitative exercises. Design: Twenty-seven healthy participants performed five scapular exercises (wall slide, wall push-up plus, prone horizontal abduction with external rotation, external rotation in side lying, and lowrow)while simultaneously recording surface electromyographic of serratus anterior, middle trapezius, lower trapezius, and upper trapezius. Surface electromyographic amplitudes, onset latencies, and activation ratios were calculated. Results: Prone horizontal abduction with external rotation showed an excellent upper trapezius/middle trapezius (0.43) and upper trapezius/lower trapezius (0.30) muscle balancewith high (>50% maximum voluntary isometric contraction) middle trapezius and lower trapezius amplitudes, a low (<20% maximum voluntary isometric contraction) upper trapezius amplitude, and an early activation of the scapular stabilizing muscles (-474.7 to 89.9 ms) relative to upper trapezius. External rotation in side lying showed excellent upper trapezius/serratus anterior (0.26), upper trapezius/middle trapezius (0.32), and upper trapezius/lower trapezius (0.21) activation ratios and, along with low row and wall slide, showed early activation of the scapular stabilizing muscles (-378.1 to -26.6 ms). Conclusions: Prone horizontal abduction with external rotation presented optimal scapular neuromuscular control. Although external rotation in side lying, low row, and wall slide did not meet all the criteria associated with optimal scapular neuromuscular control, these exercises could be used in early stages of shoulder rehabilitation because they favor early activation of the scapular stabilizing muscles. [ABSTRACT FROM AUTHOR]

Objective: This study compared the effects of virtual reality-assisted gait adaptation training with the overground gait adaptation training on balance and walking in patients with stroke. Methods: Fifty-four eligible patients were enrolled. All patients were randomly divided into a virtual reality and control group, with 27 patients in each group. The virtual reality group received virtual reality-assisted training on the treadmill, whereas the control group received overground training in a physical therapy room. After the intervention, patients were assessed using walking speed, obstacle avoidance ability, Timed Up and Go test, postural stability, and the Barthel Index. Results: Significant improvements in walking speed, obstacle avoidance ability, Timed Up and Go test, and eye-opening center of pressure speed were observed after the intervention (P < 0.05). No statistically significant differences were found in eye-closing center of pressure speed, tandem center of pressure speed, single-leg center of pressure speed, and Barthel Index (P > 0.05). Conclusions: Stroke patients may benefit fromvirtual reality-assisted gait adaptation training in improving walking and static balance function and reducing the risk of falls. [ABSTRACT FROM AUTHOR]

Foreign military training has become a key component of the United States' security policy. What explains the variation in US training allocation across countries and over time? Past work on security assistance, such as training, focuses on its effectiveness and consequences, largely overlooking questions about which countries receive it in the first place. To understand what drives US military training partnerships, we conducted a global statistical analysis of training from 1999 to 2018, structured around four logics: building relationships through defense diplomacy, deterrence against external, interstate threats, capacity-building in fragile states, and promoting democratic norms to advance democracy around the world. We find that the four logics receive support, with relationship-building and response to interstate and internal threats most consistently so. This analysis demonstrates the different ways the United States has used training in support of the US-led global order and raises questions about how to achieve accountability given these multiple logics. More broadly, the findings also have relevance for understanding how other states allocate training in conjunction with, in emulation of, or in opposition to the United States. [ABSTRACT FROM AUTHOR]

Objective: The mechanism of asymmetric dimethylarginine (ADMA) in thrombosis in patients with nonvalvular atrial fibrillation (NVAF) is still unclear. Our aim was to investigate the relationship between ADMA and indicators of prethrombotic state in NVAF patients and to analyze the predictive role of ADMA in NVAF thrombosis. Methods: A total of 192 NVAF patients were continuously selected from January 2023 to October 2023. Plasma ADMA levels were measured by high‐performance liquid chromatography. P‐selectin (P‐sel), von Willebrand factor (vWF), D‐dimer (D‐D), and plasminogen activator inhibitor‐1 (PAI‐1) levels were measured by enzyme‐linked immunosorbent assay (ELISA). Nitric oxide (NO) levels were measured by the nitrate reductase assay for plasma nitrite/nitrate, then the Griess method (Shanghai Hailian Biotechnology Co., Shanghai, China) was used to calculate plasma NO levels. Results: In our study, ADMA levels were significantly elevated and positively correlated with P‐sel, vWF, D‐D, and PAI‐1, whereas NO levels were significantly negatively correlated with these prethrombotic factors in NVAF. Furthermore, multifactorial logistic regression analysis showed that ADMA and LA diameter were independent predictors of high thrombosis risk (CHA2DS2‐VASc ≥2 score) in patients with NVAF. Conclusions: Our findings suggested that ADMA correlated with the prethrombotic state in NVAF and that reduction of ADMA levels in NVAF patients may be a novel therapeutic strategy for thrombosis risk reduction. [ABSTRACT FROM AUTHOR]

Objective: To assess whether systemic lupus erythematosus (SLE) may be genetically causally associated with migraine, including the two primary subtypes: migraine with aura (MWA) and migraine without aura (MWoA). Background: The association between SLE and migraine has been investigated extensively. Previous studies have shown a higher prevalence of migraine in patients with SLE, although the exact relationship remains unclear. This study investigated the potential causal association between SLE and migraine using the powerful analytical tool of Mendelian randomization (MR). Methods: We performed two‐sample MR analysis of publicly available summary statistic datasets using inverse variance‐weighted (IVW), weighted median, and MR‐Egger methods based on an SLE genome‐wide association study (GWAS; 5201 cases; 9066 controls; the exposure frequency is 36.5%) as an exposure and migraine GWAS (15,905 cases; 264,662 controls) in individuals with European ancestry as outcomes, focusing on the two migraine subtypes MWA (6780 cases; 264,662 controls) and MWoA (5787 cases; 264,662 controls). Thepleiotropy and heterogeneity were performed. Results: We selected 42 single‐nucleotide polymorphisms from SLE GWAS as instrumental variables (IVs) for SLE on migraine, and 41 SNP IVs for SLE on MWA or MWoA. The IVW (odds ratio [OR] = 1.01, 95% confidence interval [CI] = [0.99, 1.03], p = 0.271), weighted median (OR = 1.00, 95% CI = [0.97, 1.03], p = 0.914), and MR‐Egger (OR = 1.04, 95% CI = [0.99, 1.09], p = 0.153) methods showed no causal effect of SLE on migraine. A causal effect of SLE was observed on MWA (IVW: OR = 1.05, 95% CI = [1.02, 1.08], p = 0.001; weighted median: OR = 1.05, 95% CI = [1.01, 1.10], p = 0.018; MR‐Egger: OR = 1.07, 95% CI = [1.01, 1.14], p = 0.035 and pIVW < 0.017 [Bonferroni correction]) but not MWoA (IVW: OR = 0.99, 95% CI = [0.96, 1.02], p = 0.331; weighted median: OR = 0.98, 95% CI = [0.94, 1.03], p = 0.496; MR‐Egger: OR = 1.02, 95% CI = [0.95, 1.09], p = 0.652). The results showed no significant pleiotropy or heterogeneity. Conclusion: Our MR analysis demonstrated the complex relationship between SLE and migraine, suggesting a potential effect of SLE on the risk of MWA but not MWoA. These findings can aid in the development of improved subtype‐specific management of migraine in patients with SLE. Plain Language Summary: Using a method called Mendelian randomization, our study looked into whether there is a genetic relationship between systemic lupus erythematosus (SLE) and migraine. Our findings revealed a complex connection between SLE and migraine. It seems that having SLE could increase the likelihood of having migraine with aura; however, this doesn't seem to be the case for migraine without aura. [ABSTRACT FROM AUTHOR]

Background: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders. This study aims to determine the effect of oral Melatonin 5 mg immediate release (IR) nightly for five nights on the severity of delirium in older (≥65 years) medical inpatients. Methods: This was a double‐blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital. Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 h of admission or onset of in‐hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS). A previous pilot trial showed 120 participants randomized 1:1 to Melatonin or Placebo would provide 90% power to demonstrate a 3‐point reduction in the MDAS. Results: One hundred and twenty participants were randomized, 61 to Melatonin 5 mg and 59 to Placebo. The medication was well tolerated. The mean MDAS improvement was 4.9 (SD 7.6) in the Melatonin group and 5.4 (SD 7.2) in the Placebo group, p‐value 0.42, a non‐significant difference. A post‐hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [Interquartile Range (IQR) 4, 12] vs. Placebo group 10 [IQR 6, 16] p‐value = 0.033, Wilcoxon Rank Sum test). Conclusions: This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, an effect not captured on a multidimensional delirium assessment scale, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied. [ABSTRACT FROM AUTHOR]

The 2015 Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Statement was published to improve reporting transparency for prediction modeling studies. The objective of this review is to highlight methodologic challenges that aging‐focused researchers will encounter when designing and reporting studies involving prediction models for older adults and provide guidance for addressing these challenges. In following the 22‐item TRIPOD checklist, researchers must consider the representativeness of cohorts used (e.g., whether older adults with frailty, cognitive impairment, and social isolation were included), strategies for incorporating common geriatric predictors (e.g., age, comorbidities, functional status, and frailty), methods for handling missing data and competing risk of death, and assessment of model performance heterogeneity across important subgroups (e.g., age, sex, race, and ethnicity). We provide guidance to help aging‐focused researchers develop, validate, and report models that can inform and improve patient care, which we label "TRIPOD‐65." [ABSTRACT FROM AUTHOR]

Measuring success plays a central role in justifying and advocating for a statistical or data science consulting or collaboration program (SDSP) within an academic institution. We present several specific metrics to report to targeted audiences to tell the story for success of a robust and sustainable program. While gathering such metrics includes challenges, we discuss potential data sources and possible practices for SDSPs to inform their own approaches. Emphasizing essential metrics for reporting, we also share the metric gathering and reporting practices of two programs in greater detail. New or existing SDSPs should evaluate their local environments and tailor their practice to gathering, analysing and reporting success metrics accordingly. This approach provides a strong foundation to use success metrics to tell compelling stories about the SDSP and enhance program sustainability. The area of success metrics provides ample opportunity for future research projects that leverage qualitative methods and consider mechanisms for adapting to the changing landscape of data science. [ABSTRACT FROM AUTHOR]

Objective: To investigate the performance of human papilloma virus (HPV) typing as a triage tool in the management of patients with postcoital bleeding (PCB). Methods: All patients referred for colposcopy at a cervical pathology clinic of a nationwide health insurance organization, due to PCB and had a preceding high-risk HPV (hrHPV) test between 2018 and 2020, were retrospectively located. Demographic and pathologic data were collected from electronic medical files. Sensitivity, specificity, and negative and positive predictive value of hrHPV test according to final pathology were calculated. Results: Three hundred ninety patients referred for colposcopy due to PCB with a preceding hrHPV test were located. HrHPV-positive patients were significantly younger (33.7 ± 10 vs. 37.2 ± 9, p < 0.006) with a higher proportion of nulliparous, nonmarried, and smokers compared with hrHPV-negative patients (75% vs. 47%, p < 0.001; 75.4% vs. 45.1%, p < 0.001; and 24.6% vs. 12.8%, p < 0.028, respectively). No case of high-grade cervical intraepithelial neoplasia (CIN2/3) was identified among hrHPV-negative patients. The sensitivity and NPV of the hrHPV test for high-grade cervical lesions were both 100%, decreasing to 36% and 95%, respectively, for any cervical dysplasia (CIN1/CIN2/CIN3). Adding cytology to HPV typing had a negligible effect on test performance. At univariate analysis, age, HPV vaccine status, nulliparity, and positive HPV typing were independently associated with cervical dysplasia. At multivariate analysis, only positive HPV typing remained significantly associated with cervical dysplasia (hazard ratio 2.75, confidence interval 1.1–6.5, p = 0.023). Conclusion: A negative HPV test even in the presence of PCB may rule out cervical dysplasia with extremely high accuracy and may save unnecessary colposcopies. [ABSTRACT FROM AUTHOR]

Background: Tubal sterilization is more commonly utilized by racial/ethnic minority groups and has been implicated in underscreening for cervical cancer. The objective is to determine if prior tubal sterilization is a risk factor for cervical cancer underscreening. Methods: National Survey of Family Growth dataset from 2015 to 2019 used for analysis; data were weighted to represent the 72 million women in the U.S. population aged 22–49. Chi-square tests, Fisher exact tests, and logistic regression were used for analysis. The primary predictor variable was tubal sterilization which was categorized into no previous sterilization, sterilization completed <5 years ago, and sterilization completed ≥5 years ago. The outcome variable was underscreened versus not underscreened. Other predictor variables included age, household income as a percent of federal poverty level, previous live birth, primary care provider, and insurance status. Results: Prevalence of tubal sterilization completed 5 or more years ago was 12.5% and varied by most measured characteristics in univariate analyses. Approximately 8% of women were underscreened for cervical cancer. In multivariable analyses, women with a tubal sterilization 5 or more years ago had 2.64 times the odds (95% confidence interval = 1.75–4.00) of being underscreened for cervical cancer compared with women who did not have a tubal sterilization. Conclusions: Approximately 4.3 million women ages 22–49 in the United States are potentially underscreened for cervical cancer and women with previous tubal ligation ≥5 years ago are more likely to be underscreened. These results may inform the need for culturally sensitive public health messages informing people who have had these procedures about the need for continued screening. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is a highly impairing condition with important public health impacts. Despite the availability of treatment options for AUD, research shows that few people receive treatment, and even fewer can maintain abstinence/low‐drinking levels. This study investigated the role of personality traits in past‐year alcohol use among individuals with severe AUD who ever attended Alcoholics Anonymous (AA), a widespread and easily accessible self‐help group for alcohol problems. Methods: Univariable and multivariable regressions were performed separately in females and males with alcohol consumption as an outcome. Socioeconomic factors, genetic liability, and psychopathology were included as covariates in the analyses. Results: Results from the multivariable model indicated that in females who attended AA, greater alcohol use was related to both positive and negative urgency and low sensation seeking, while in males, greater alcohol use was related to positive urgency. Results also showed that, in both sexes, younger age and lower educational levels were associated with greater alcohol use. Moreover, single males and individuals with lower AUD severity were at higher risk of using alcohol in the past year. Conclusions: These findings highlight sex‐specific correlates of drinking in individuals with AUD who engaged in self‐help groups. These findings may help to improve treatment options, as personality encompasses modifiable traits that can be targeted in psychological interventions. [ABSTRACT FROM AUTHOR]

Background: Chronic alcohol consumption is a major public health issue. The primary organ damaged by alcohol abuse is the liver, leading to alcohol‐associated liver disease (ALD). ALD begins with hepatic steatosis and can progress to fibrosis and cirrhosis; however, we have an incomplete understanding of ALD pathogenesis. Interestingly, the liver is also the major organ for vitamin A metabolism and storage, and ALD has previously been linked with altered hepatic vitamin A homeostasis. We hypothesize that alcohol‐induced vitamin A depletion disrupts its normal function in the liver, contributing to the pathogenesis of ALD. To test this hypothesis, we postulated that adding copious vitamin A to the diet might alleviate ALD, and conversely, that a vitamin A deficient diet would worsen ALD. Methods: We conducted two dietary intervention studies in mice comparing deficient (0 IU/g diet) and copious (25 IU/g diet) dietary vitamin A intake versus control (4 IU/g diet), using the NIAAA chronic‐binge model of ALD. Hepatic steatosis was assessed using histopathological and biochemical approaches. Tissue Vitamin A levels were measured using high‐performance liquid chromatography. Markers of ALD, hepatic inflammation and lipid metabolism were analyzed by the quantitative polymerase chain reaction and western blotting. Results: As expected, a 0 IU/g Vitamin A diet decreased, and a 25 IU/g Vitamin A diet increased hepatic Vitamin A stores. However, alcohol induced changes in hepatic triglyceride levels, markers of hepatic lipid metabolism, inflammation and fibrosis were not significantly different in mice consuming a copious or deficient vitamin A diet compared to control. Conclusions: Altered vitamin A intake and hepatic vitamin A storage have a minor effect on the pathogenesis of ALD. Thus, given the known link between altered retinoic acid signaling and ALD, future studies that further explore this linkage are warranted. [ABSTRACT FROM AUTHOR]

Background: We previously reported that binge ethanol induces atrophy of the spleen, a key immune organ, in adolescent male F344 rats. Because there are significant sex effects in immune function, we investigated whether binge ethanol exerts sex‐dependent effects on the spleen, including producing splenic atrophy. Methods: We gave F344 rats ethanol (4.8 g/kg/day; 52% w/v; i.g.) on postnatal days [PND] 36 ~ 38 and sacrificed them on PND 39 for spleen collection. We performed immunophenotyping analysis of splenic cells and examined the expression of 158 genes related to alcohol metabolism, epigenetic modification, and immune regulation in the spleens of adolescent (PND 39) male and female rats. Results: Following a 3‐day ethanol exposure, a loss of body weight, and absolute and relative spleen weight, was seen only in male adolescent rats. Ethanol altered the relative proportions of lymphocyte subtypes in both sexes with different patterns. We also found that 3‐day ethanol exposure induced sex‐dependent gene expression changes in spleen. Among the 158 genes studied, the expression of only three genes was significantly increased in female rats. However, the expression of 30 genes was significantly increased/decreased in male rats. Female rats had greater expression of alcohol metabolizing enzyme genes in the spleen under physiological conditions and when stimulated by binge ethanol. The genes are involved in epigenetic modification were differentially expressed in a sex‐dependent manner. Conclusion: We found that male adolescent rats were more sensitive to binge ethanol than female rats. Differential expression of the genes related to alcohol metabolism and epigenetic modification (of DNA methyltransferase and histone deacetylases) between the sexes could account for the observed sex‐dependent responses to binge ethanol in adolescent rats. [ABSTRACT FROM AUTHOR]

Background: Enhanced liver fibrosis (ELF) score is an accurate, noninvasive test for assessing the severity of liver fibrosis in chronic liver disease, including alcohol‐related liver disease. However, whether the ELF score changes during alcohol withdrawal is unknown. This pilot study assessed changes in the ELF score during withdrawal in patients with a history of excessive alcohol intake. Methods: In this prospective study, ELF was performed on day 0 (D0, at the beginning of hospitalization), at day 7 (D7, on discharge from hospital), and at follow‐up visits on days 30 (D30) and 90 (D90). Transient elastography (TE) was also assessed on days 4 (D4) and D30. Results: The study included 35 patients (71% male) with a mean alcohol intake of 139 g/day. On D30 and D90, 8 and 13 patients had resumed alcohol consumption (mean intake of 90 and 80 g/day, respectively). In patients who remained abstinent, the mean ELF score was 8.93 on D0, 9.14 on D30 (p = 0.32), and 9.27 on D90 (p = 0.14). In patients who resumed alcohol, mean ELF score was 9.7 on D0, 10.05 on D30 (p = 0.09), and 9.71 on D90 (p = 0.12). ELF score was comparable over the first months after withdrawal, although there was a slight increase in the first week (mean ELF score increased from 9.24 on D0 to 9.74 on D7, p < 0.001). Mean TE value was 7.9 kPa on D4 and 8.1 kPa on D30 (p = 0.84) in patients who resumed alcohol consumption, and 8.3 and 7.5 kPa (p = 0.03) on D4 and D30, respectively, in abstinent patients. Conclusion: The ELF score is stable during the first months after withdrawal and thus appears to be a useful tool to assess liver fibrosis or cirrhosis in this setting. Nevertheless, because in the first week there is a transient increase in ELF score, caution in interpretation is warranted. [ABSTRACT FROM AUTHOR]

Aims: To assess the association between experiences of discrimination and mental health among the Sámi population in Sweden. Methods: Cross-sectional study among the self-identified Sámi population living in Sweden in 2021, registered in the electoral roll of the Sámi Parliament, the reindeer mark register and the 'Labour statistics based on administrative sources'. The analysis was based on a final sample of 3658 respondents aged between 18 and 84 years. Adjusted prevalence ratios aPRs for psychological distress (Kessler scale), self-reported anxiety and depression were estimated for four different forms of discrimination (direct experience of discrimination, offended because of ethnicity, historical trauma, and combined discrimination). Results: Higher aPRs of psychological distress, anxiety and depression were observed in women experiencing direct discrimination because of their ethnicity, having been offended because of their ethnicity, and those with a family history of discrimination. Among men, higher aPRs for psychological distress were observed in those experiencing the four different forms of discrimination, but not for anxiety. Depression was only detected in the case of having been offended. Adding experiences of discrimination was associated with a higher prevalence of negative outcomes for all the indicators in women and for psychological distress in men. Conclusions: The observed association between experiences of discrimination and mental health problems would support a gender approach when considering ethnic discrimination in public health policies concerning the Sámi in Sweden. [ABSTRACT FROM AUTHOR]

Adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) post-stroke is often problematic, despite potential benefits. This study aimed to evaluate CPAP adherence in patients with OSA post-stroke based on the Andersen behavioral model of health services utilization. A total of 227 eligible participants were recruited from a Chinese hospital. After baseline assessment, participants were followed for 6 months to determine short-term CPAP adherence. Those with good short-term adherence were followed for an additional 6 months to explore long-term adherence and influencing factors. Short-term CPAP adherence rate was 33%. Being married or living with a partner, having an associate degree or baccalaureate degree or higher, and stronger health beliefs independently predicted short-term CPAP adherence. Only 25% of participants from the adherent group showed good long-term adherence. The factor associated with long-term CPAP adherence was participants not using alcohol. Adherence to CPAP is suboptimal among patients having OSA post-stroke. Addressing unfavorable predisposing factors and modifying health beliefs are suggested. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effect of fluid management, symptom control, and quality of life on education based on the Roy Adaptation Model. This randomized controlled study was conducted with the participation of 107 patients (53 intervention, 54 control). Data were collected using the "Patient Data Collection Form," "Fluid Control in Hemodialysis Patients Scale," "Dialysis Symptom Index," and "Nottingham Health Profile." The forms were filled out through face-to-face interviews with the patients in the intervention and control groups at the 0th (onset), 1st, and 3rd months. The patients in the intervention group were trained with an education booklet based on the Roy Adaptation Model. The results revealed that the education given according to the Roy Adaptation Model improved the compliance with fluid control, quality of life, and symptom control of hemodialysis patients. It is recommended that education based on the Roy Adaptation Model be systematically used by hemodialysis nurses. The results are limited to the population included in the study, and further research on hemodialysis populations is needed. [ABSTRACT FROM AUTHOR]

Active migration and globalization have led to increased opportunities for critical care nurses to care for patients from diverse racial and cultural backgrounds. This study thus aimed to identify the individual, interpersonal, and organizational factors affecting cultural competence levels among neonatal intensive care unit (NICU) nurses based on an ecological model. This was a cross-sectional descriptive study that included 135 NICU nurses in South Korea. A hierarchical multiple linear regression analysis was conducted using the proposed ecological model, and a regression model for each of the four subdomains of cultural competence was constructed and compared. NICU nurses' cultural competencies were influenced not only by the "necessity of multicultural education" and "ethnocultural empathy" at the individual level but by the "hospital's readiness and support for cultural competencies" at the organizational level. To promote the cultural competence of nurses in critical care settings, environmental and organizational support should be improved, along with developing strategies that focus on nurses' individual characteristics. It is also necessary to investigate the "intersectionality" of the effects of individual and environmental factors on cultural competence. [ABSTRACT FROM AUTHOR]

Lower extremity injuries are prevalent in military trainees, especially in female and older trainees. Modifiable factors that lead to higher injury risk in these subgroups are not clear. The purpose of this study was to identify whether external loading variables during military‐relevant tasks differ by age and sex in U.S. Army trainees. Data was collected on 915 trainees in the first week of Basic Combat Training. Participants performed running and ruck marching (walking with 18.1 kg pack) on a treadmill, as well as double‐/single‐leg drop landings. Variables included: vertical force loading rates, vertical stiffness, first peak vertical forces, peak vertical and resultant tibial accelerations. Comparisons were made between sexes and age groups (young, ≤19 years; middle, 20–24 years; older, ≥25 years). Significant main effects of sex were found, with females showing higher vertical loading rates during ruck marching, and peak tibial accelerations during running and ruck marching (p ≤ 0.03). Males showed higher vertical stiffness during running and peak vertical tibial accelerations during drop landings (p < 0.01). A main effect of age was found for vertical loading rates during running (p = 0.03), however no significant pairwise differences were found between age groups. These findings suggest that higher external loading may contribute to higher overall injury rates in female trainees. Further, higher stiffness during running may contribute to specific injuries, such as Achilles Tendinopathy, that are more prevalent in males. The lack of differences between age groups suggests that other factors contribute more to higher injury rates in older trainees. Highlights: Female trainees showed higher lower extremity loading during running and ruck marching that may predispose them to higher rates of musculoskeletal injury during initial‐entry training.Male trainees showed higher stiffness during running, which may relate to an increased risk of specific musculoskeletal injuries that are more prevalent in males, such as Achilles tendinopathy.Overall, older trainees did not show different lower extremity loading patterns compared to younger, suggesting that these factors are not related to the increased risk for musculoskeletal injury in older trainees. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy‐induced peripheral neuropathy (CIPN) is a debilitating disturbance among patients who received chemotherapy, with no effective treatment available. Scrambler therapy (ST) is a noninvasive treatment capable of improving multiple quality‐of‐life symptoms beyond pain. We aimed to evaluate the efficacy of ST for pain and nonpain symptoms related to CIPN. Methods: Ten patients with moderate to severe CIPN symptoms for >3 months were enrolled in a single‐arm trial of ST for 10 daily sessions. CIPN‐related symptoms were measured throughout the treatment period and up to 6 months thereafter. Results: The worst pain was reduced by 6 months (p = 0.0039). QST demonstrated the greatest improvement in pressure of 60 g (p = 0.308, Cohen's d = 0.42) and cold temperature threshold of 2.5°C (p = 0.9375, Cohen's d = 0.51) in the gastrocnemius area. Symptoms of numbness, tingling, trouble walking, and disturbed sleep had significant improvements at 6 months. Pain medication use decreased by 70% at the end of treatment and by 42% at 6 months. Patient satisfaction was high (82%) and no adverse events with ST treatment were reported. Conclusions: The results of this pilot trial support the use of ST by demonstrating improvement in multiple domains of quality of life for CIPN patients during an extended follow‐up of 6 months. However, further large‐scale studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Quality-of-life metrics are increasingly important for oncological patients alongside traditional endpoints like mortality and disease progression. Statistical tools such as Win Ratio, Win Odds, and Net Benefit prioritize clinically significant outcomes using composite endpoints. In randomized trials, Win Statistics provide fair comparisons between treatment and control groups. However, their use in observational studies is complicated by confounding variables. Propensity score (PS) matching mitigates confounding variables but may reduce the sample size, affecting the power of win statistics analyses. Alternatively, PS matching can stratify samples, preserving the sample size. This study aims to assess the long-term impact of these methods on decision making, particularly in colorectal cancer patients. Methods: A motivating example involves a cohort of patients from the ReSARCh observational study (2016–2021) with locally advanced adenocarcinoma of the rectum, situated up to 12 cm from the anal verge. These patients underwent either a watch-and-wait approach (WW) or trans-anal local excision (LE). Win statistics compared the effects of WW and LE on a composite outcome (overall survival, recurrence, presence of ostomy, and rectum excision). For matched win statistics, we used robust inference techniques proposed by Matsouaka et al. (2022), and for stratified win statistics, we applied the method proposed by Dong et al. (2018). A simulation study assessed the coverage probability of matched and stratified win statistics in balanced and unbalanced groups, calculating how often the confidence intervals included the true values of WR, NB, and WO across 1000 simulations. Results: The results suggest a better efficacy of the LE approach when considering efficacy outcomes alone (WR: 0.47 (0.01 to 1.14); NB: −0.16 (−0.34 to 0.02); and WO: 0.73 (0.5 to 1.05)). However, when QoL outcomes are included in the analyses, the estimates are closer to 1 (WR: 0.87 (0.06 to 2.06); WO: 0.93 (0.61 to 1.4)) and to 0 (NB: −0.04 (−0.25 to 0.17)), indicating a negative impact of the treatment effect of LE regarding the presence of ostomy and the excision of the rectum. Moreover, based on the simulation study, our findings underscore the superior performance of matched compared to stratified win statistics in terms of coverage probability (matched WR: 97% vs. stratified WR: 33.3% in a high-imbalance setting; matched WR: 98% vs. stratified WR: 34.4% in a medium-imbalance setting; and matched WR: 99.2% vs. stratified WR: 37.4% in a low-imbalance setting). Conclusions: In conclusion, our study sheds light on the interpretation of the results of win statistics in terms of statistical significance, providing insights into the application of pairwise comparison in observational settings, promoting its use to improve outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiparametric MRI with radiomics features derived from T2WI and ADC maps distinguished non-tumor regions from significant cancer and predicted the Gleason score using support vector machine (SVM) and random forest (RF) classification methods with tuned hyperparameters, as well as recursive feature elimination (RFE) and the least absolute shrinkage and selection operator (LASSO) feature selection methods. Successful application of a novel approach to machine learning incorporating recursive feature elimination combined with random forest and support vector classifiers allowed stratification of Gleeson scores in clinical cohorts at a sensitivity greater than 0.91. We developed a novel machine-learning algorithm to augment the clinical diagnosis of prostate cancer utilizing first and second-order texture analysis metrics in a novel application of machine-learning radiomics analysis. We successfully discriminated between significant prostate cancers versus non-tumor regions and provided accurate prediction between Gleason score cohorts with statistical sensitivity of 0.82, 0.81 and 0.91 in three separate pathology classifications. Tumor heterogeneity and prediction of the Gleason score were quantified using two feature selection approaches and two separate classifiers with tuned hyperparameters. There was a total of 71 patients analyzed in this study. Multiparametric MRI, incorporating T2WI and ADC maps, were used to derive radiomics features. Recursive feature elimination (RFE), the least absolute shrinkage and selection operator (LASSO), and two classification approaches, incorporating a support vector machine (SVM) (with randomized search) and random forest (RF) (with grid search), were utilized to differentiate between non-tumor regions and significant cancer while also predicting the Gleason score. In T2WI images, the RFE feature selection approach combined with RF and SVM classifiers outperformed LASSO with SVM and RF classifiers. The best performance was achieved by combining LASSO and SVM into a model that used both T2WI and ADC images. This model had an area under the curve (AUC) of 0.91. Radiomic features computed from ADC and T2WI images were used to predict three groups of Gleason score using two kinds of feature selection methods (RFE and LASSO), RF and SVM classifier models with tuned hyperparameters. Using combined sequences (T2WI and ADC map images) and combined radiomics (1st and GLCM features), LASSO, with a feature selection method with RF, was able to predict G3 with the highest sensitivity at a level AUC of 0.92. To predict G3 for single sequence (T2WI images) using GLCM features, LASSO with SVM achieved the highest sensitivity with an AUC of 0.92. [ABSTRACT FROM AUTHOR]

Simple Summary: Our findings confirm the role of developmental aspects in extracranial germ cell tumors (eGCTs). Strong associations between syndromes or congenital anomalies and eGCTs may hint at the need for research to identify potential causes and mechanisms. Strong effects were observed for Swyer and Currarino syndrome. The strengths of the associations emphasize the need for further elaboration on presently discussed pathophysiological mechanisms. For other suggested risk factors such as Klinefelter, Turner, and Down syndrome, the strength of risk appears to be substantially low and may be missed because of diagnostic bias for the first two or lack of power for the latter. A number of further syndromes were identified in single cases. Most of these pertain to girls. GCTs are developmental tumors and are likely to reflect ontogenetic and teratogenetic determinants. The objective of this study was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were included. According to Teilum's holistic concept, malignant and benign teratomas were registered. We used a case–control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher's exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7–2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2–88.6). We additionally found 16 isolated cases of eGCT with a wide range of syndromes. However, these were not found to be significantly associated following Bonferroni correction. Most of these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study, we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of PCa at diagnosis is assessed by classification systems that aim to group homogenous sets of patients. However, great heterogeneity exists within these risk groups, in terms of prognostic factors and treatment options. The aim of this study was to assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy at a high-volume tertiary referral center. Objectives: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox's proportional hazards and logistic regression model. Results: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840–10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057–5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease. Conclusions: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: It is generally reported that the prognostic factors for ampulla of Vater cancer include T stage, N stage, and lymphovascular invasion and subtype, and the meaning of MUC stain is controversial. This retrospective study by the authors evaluated the significance of various MUC stains in AoV cancer using single-center clinicopathological data. The results showed that MUC5AC was significant for lymph node metastasis and was furthermore valuable as a prognostic factor for predicting overall survival. If this is evaluated in addition to the hematoxylin and eosin stain, which is commonly performed in preoperative biopsy, it is expected to be a method to select groups that require more extensive LN dissection and further prevent locoregional recurrence. Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods: Using samples from 68 patients with AoV cancer, we performed immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 using a tissue microarray. Subsequently, we analyzed their expression patterns in relation to clinicopathological parameters and patient outcomes. Results: Of the patients, 98.5% exhibited positive expression for MUC1, while MUC2, MUC5AC, and MUC6 were expressed in 44.1%, 47.1%, and 41.2% of the patients, respectively. Correlation analyses between mucin expression and clinicopathological factors revealed no significant associations, except between MUC5AC expression and N stage. Univariate analysis demonstrated significant associations between MUC5AC expression and overall survival (OS). Multivariate analysis further confirmed that MUC5AC expression was a significant predictor of OS, along with the N stage. However, MUC5AC expression was not meaningfully associated with recurrence-free survival (RFS). The patients positive for MUC5AC expression had a considerably shorter OS than those with negative expression. Conclusions: Our study provides insights into the clinical impact of mucins on AoV cancer, regardless of the histological subtype. Although MUC1 expression is universal, MUC5AC expression is a significant prognostic indicator that correlates with lymph node metastasis and poor OS. These results emphasize the possible utility of MUC5AC as a biomarker for extensive lymph node dissection and the prognostic evaluation of patients with AoV cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral squamous cell carcinoma is a global health concern, particularly affecting the South Asian population. The South Asian community is among Canada's largest and most rapidly expanding minority groups. This study compared the outcomes of South Asian patients with oral squamous cell carcinoma to the general population at a Canadian cancer center. In total, 697 patients who underwent surgery for oral squamous cell carcinoma between 2009 and 2022 were evaluated, with South Asian patients constituting 9% of the cohort. Despite similar tumor characteristics and treatments, South Asian patients had double the risk of cancer recurrence and significantly worse survival compared to non-South Asian patients. Understanding the association between South Asian ethnicity and outcomes in OSCC is crucial for informing public health initiatives to meet the distinctive needs of this population, thus fostering a more inclusive and supportive environment. (1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/− adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan–Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28–3.14), DSS: HR 1.79 (1.12–2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to elucidate whether osteopenia predicts clinicopathological findings in patients with hepatocellular carcinoma. Bone mineral density was assessed using computed tomography scan images taken within 3 months before surgery. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. The overall survival of osteopenia patients was shorter than that of non-osteopenia patients, regardless of gender. Osteopenia was an independent risk factor for overall survival and recurrence-free survival. The pathological factor associated with osteopenia was microvascular portal vein invasion. Background: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival. Methods: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan–Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox's proportional hazard model. Results: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion. Conclusion: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion. [ABSTRACT FROM AUTHOR]

Simple Summary: Mutation of the SMARCB1 gene can cause one of the most aggressive and lethal cancers of early childhood and infancy, malignant rhabdoid tumor (MRT). Despite the standard multimodal therapy (resection, conventional chemotherapy, and radiotherapy), the outlook for young children with MRT is poor. For infants, the disease can also preclude the use of radiotherapy. Numerous experimental treatments explore epigenetic mechanisms, but the DNA damage response has not yet been extensively evaluated as a therapeutic approach for MRT. We report a new therapeutic strategy for SMARCB1-deficient MRTs, combining PARP1 inhibition and DNA damage induction. The observed synergy between the PEGylated PARP1 inhibitor talazoparib (PEG~TLZ) and the DNA alkylating agent temozolomide (TMZ) may lead to improved therapeutic strategies for patients with this challenging cancer. We identified a new potential biomarker of response to PEG~TLZ+TMZ, O6-methylguanine methyltransferase (MGMT), and uncovered dysregulated signaling pathways involved in the response. Additionally, we elucidated the pro-survival role of SMARCB1 loss in MRT cells. Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the SMARCB1 gene (occasionally SMARCA4)—a pivotal component of the SWI/SNF chromatin remodeling complex—is homozygously deleted, although the precise etiology of these tumors remains unknown. While young patients with localized MRT generally show improved outcomes, especially those who are older and have early-stage disease, the overall prognosis remains poor despite optimal standard treatments. This highlights the urgent need for more effective treatment strategies. We investigated the antitumor activity of a PARP1 inhibitor (talazoparib, TLZ) combined with a DNA alkylating agent (temozolomide, TMZ) in MRT xenograft models. PARP1 is a widely targeted molecule in cancer treatment and, beyond its role in DNA repair, it participates in transcriptional regulation by recruiting chromatin remodeling complexes to modulate DNA accessibility for RNA polymerases. To widen the therapeutic window of the drug combination, we employed PEGylated TLZ (PEG~TLZ), which has been reported to reduce systemic toxicity through slow drug release. Remarkably, our findings indicate that five out of six MRT xenografts exhibited an objective response to PEG~TLZ+TMZ therapy. Significantly, the loss of SMARCB1 was found to confer a protective effect, correlating with higher expression levels of DNA damage and repair proteins in SMARCB1-deficient MRT cells. Additionally, we identified MGMT as a potential biomarker indicative of in vivo MRT response to PEG~TLZ+TMZ therapy. Moreover, our analysis revealed alterations in signaling pathways associated with the observed antitumor efficacy. This study presents a novel and efficacious therapeutic approach for MRT, along with a promising candidate biomarker for predicting tumor response. [ABSTRACT FROM AUTHOR]

Simple Summary: Telomerase reverse transcriptase promoter (TERTp) mutation is commonly observed in brain tumors and are known to contribute to the acquisition of immortality in tumors via maintaining telomere length. In this study, we aimed to investigate the prognostic impact of several known prognostic factors, including TERTp mutations, in 528 adult-type diffuse gliomas classified according to the 2021 WHO criteria. Our data showed that TERTp mutation status had a significant impact on prognosis in the combined group of glioblastoma, IDH-wildtype and astrocytoma, IDH-mutant, but was not a predictor of prognosis within any individual tumor groups. We also showed that several known clinicopathologic factors have different prognostic significance depending on the type of tumor. This supports the need for systematic tumor diagnosis based on molecular pathology classification and indicates that multiple factors, not just TERTp mutation status, should be considered in the prognosis of tumors. Mutation in the telomerase reverse transcriptase promoter (TERTp)is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan–Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Spatial characteristics, including cell morphology and spatial distribution patterns, hold potential prognostic value in melanoma. This study builds on existing research by exploring these spatial factors through a computational pipeline, including both univariate and multivariate Cox proportional hazards models, supplemented by rigorous cross-validation techniques. Our findings reveal that spatial and morphological features can potentially enhance the prognostication of melanoma, supporting their integration into standard prognostic models. We also discuss potential limitations and outline directions for future research. In this study, the prognostic value of cellular morphology and spatial configurations in melanoma has been examined, aiming to complement traditional prognostic indicators like mitotic activity and tumor thickness. Through a computational pipeline using machine learning and deep learning methods, we quantified nuclei sizes within different spatial regions and analyzed their prognostic significance using univariate and multivariate Cox models. Nuclei sizes in the invasive band demonstrated a significant hazard ratio (HR) of 1.1 (95% CI: 1.03, 1.18). Similarly, the nuclei sizes of tumor cells and Ki67 S100 co-positive cells in the invasive band achieved HRs of 1.07 (95% CI: 1.02, 1.13) and 1.09 (95% CI: 1.04, 1.16), respectively. Our findings reveal that nuclei sizes, particularly in the invasive band, are potentially prognostic factors. Correlation analyses further demonstrated a meaningful relationship between cellular morphology and tumor progression, notably showing that nuclei size within the invasive band correlates substantially with tumor thickness. These results suggest the potential of integrating spatial and morphological analyses into melanoma prognostication. [ABSTRACT FROM AUTHOR]

Simple Summary: Different immunotherapy combinations improved prognosis for advanced non-oncogene driven NSCLC, but they were not directly compared. The aim of our study is to present the real-world data for 122 patients treated at the Institute of Oncology in Cluj-Napoca with three different consecutive immunotherapy combinations (dual immunotherapy—18 patients, dual immunotherapy plus short course chemotherapy—33 patients, mono-immunotherapy plus full course chemotherapy—71 patients). Efficacy results using different immunotherapy combination strategies were in line with those from the registration trials, with 22.2 months median overall survival and 49% actuarial 2-year survival. Results were not significantly different between the three protocols. Older age, impaired performance status, corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate survival analysis. Long-term data are available for the dual immunotherapy cohorts, with 30.5% and 18.8% of patients alive at 5 years. Purpose. Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. Methods. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. RESULTS. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0–1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Conclusions. Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite instability (MSI) is a hallmark of colorectal cancer (CRC) that is present in 10–15% of all patients with this condition. MSI results from the inactivation of the mismatch repair (MMR) pathway in tumors due to germline MMR mutations, known as Lynch syndrome or sporadic epigenetic gene silencing, leading to an increased mutation rate and genomic instability. In this study, we assessed the utility of the polymerase chain reaction (PCR)-based molecular method as an alternative to immunohistochemistry for determining MSI status in formalin-fixed paraffin-embedded tissues and investigated the clinicopathological significance and prognostic value of MSI in CRC. We found that patients with MSI-high (i.e., high MSI) had better overall and disease-free survival than those with microsatellite stability, and this result was significant in patients with right-sided CRC. Our results demonstrate that PCR-based MSI detection may serve as a useful prognostic predictor in patients with CRC and may have clinical value in the management of these patients. Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen's kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan–Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026–0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001–1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC. [ABSTRACT FROM AUTHOR]