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Multistate modeling is a commonly used method to compute healthy life expectancy. However, there is currently no analytical method to decompose the components of differentials in summary measures calculated from multistate models. In this research note, we propose a derivative-based method to decompose the differentials in population-based health expectancies estimated via a multistate model into two main components: the proportion resulting from differences in initial health structure and the proportion resulting from differences in health transitions. We illustrate the method using data on activities of daily living from the U.S. Health and Retirement Study to decompose the sex differential in disability-free life expectancy (HLE) among older Americans. Our results suggest that the sex gap in HLE results primarily from differences in transition rates between disability states rather than from the initial health distribution of female and male populations. The methods introduced here will enable researchers, including those working in fields other than health, to decompose the relative contribution of initial population structure and transition probabilities to differences in state-specific life expectancies from multistate models., (Copyright © 2023 The Authors.)

Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-approved anti-anginal drug ranolazine (RANO) delays tumour recurrence with acquired BRAFi resistance. Single-cell RNA-sequencing analysis reveals that RANO diminishes the abundance of the therapy-resistant NGFR hi neural crest stem cell subpopulation. Moreover, by rewiring the methionine salvage pathway, RANO enhances melanoma immunogenicity through increased antigen presentation and interferon signalling. Combination of RANO with anti-PD-L1 antibodies strongly improves survival by increasing antitumour immune responses. Altogether, we show that RANO increases the efficacy of targeted melanoma therapy through its effects on FAO and the methionine salvage pathway. Importantly, our study suggests that RANO could sensitize BRAFi-resistant tumours to immunotherapy. Since RANO has very mild side-effects, it might constitute a therapeutic option to improve the two main strategies currently used to treat metastatic melanoma., (© 2023. The Author(s).)

Objectives: To compare characteristics of caregivers of adults with acute traumatic brain injury (TBI) in the U.S. and Latin America (Mexico and Colombia). Design: Secondary data analysis of two cohorts. Cohort 1: English-speaking caregivers of adults with TBI in the U.S. (n = 80). Cohort 2: Spanish-speaking caregivers of adults with TBI in Mexico or Colombia (n = 109). Results: Similarities between the U.S. and Latin American caregiver groups, respectively, were: predominantly women (81.3%, 81.7%, respectively); spouses/domestic partners (45%, 31.2%); and motor vehicle accident (41.5%, 48.6%) followed by fall etiologies (40%, 21.1%). Differences between U.S. and Latin American caregivers were: age (49.5 years, 41.5 years, p < 0.001); employment status ((Χ52 = 59.63, p < 0.001), full-time employment (63.7%, 25.7%), homemaker (2.5%, 31.2%), and retired (17.5%, 1.8%)); violence-related etiology (2.5%, 15.6%); and severity of depressive symptoms (M = 7.9, SD = 5.8; M = 5.8, SD = 5.7; p = 0.014). Conclusions: TBI caregivers in the U.S. were older and employed full-time or retired more often than those in Latin America. Violence-related etiology was nearly five times more common in Latin America, raising concerns for potential implications of post-traumatic stress and family adjustment after injury. Although both groups likely could use mental health support, this was particularly true of the U.S. cohort, maybe due to differential demographics, mechanisms of injury, or family and community support.

ABSTRACT A study was conducted to examine the factor structure of the Neurobehavioral Symptom Inventory (NSI) among a large community sample of 729 Spanish-speakers from the Continental United States ( n  = 174, 23.9%), Latin America ( n  = 465, 63.8%), and Spain (n   = 90, 12.3%) The sample was 62.1% female, had at least 10 years of formal education, and ranged in age from 18 to 65 years ( M  = 36.7, SD   = 12.5). The sample was randomly split into two groups with comparable demographics for a sequential analysis that consisted of an exploratory factor analysis on the first subsample followed by a confirmatory factor analysis within a second validation subsample. Results demonstrated a high internal consistency reliability for the Spanish version of the NSI, and a three-factor solution was supported with somatic, affective, and cognitive factors. Findings were comparable to prior studies with the English version of the NSI providing preliminary support for the construct validity of this measure among a large sample of Spanish-speakers. Further study is needed to determine the criterion-related validity of the individual factors as separate subscales and to examine the appropriateness of this measure for individuals with lower levels of education.

Amino acids (AAs) play an important role in the modern health industry as key synthetic precursors for pharmaceuticals, biomaterials, biosensors, and drug delivery systems. Currently, over 30% of small-molecule drugs contain residues of tailor-made AAs or derived from them amino-alcohols and di-amines. In this review article, we profile 12 AA-derived new pharmaceuticals approved by the FDA in 2020. These newly introduced drugs include Tazverik (epithelioid sarcoma), Gemtesa (overactive bladder), Zeposia (multiple sclerosis), Byfavo (induction and maintenance of procedural sedation), Cu 64 dotatate, and Gallium 68 PSMA-11 (both PET imaging), Rimegepant (acute migraine), Zepzelca (lung cancer), Remdesivir (COVID-19), Amisulpride (nausea and vomiting), Setmelanotide (obesity), and Lonafarnib (progeria syndrome). For each compound, we describe the spectrum of biological activity, medicinal chemistry discovery, and synthetic preparation., (© 2021 Wiley Periodicals LLC.)

Background: With structured interviews being an established method for assessing one's exposure to traumatic brain injury across their lifetime, effective assessment tools are needed to serve the large population of Spanish speakers in the U.S. and abroad., Objective: To obtain preliminary evidence of validity for a Spanish version of a web-based, structured interview designed to assess lifetime exposure to TBI., Methods: A sample of 720 Spanish-speaking individuals between the ages of 18 through 65 from the continental U.S. (34.3%), South America (30.8%), the Caribbean (12.6%), Spain (12.4%), and Mexico and Central America (9.9%) completed an online survey containing the Ohio State University Traumatic Brain Injury Identification Method (Self-Administered-Brief; OSU TBI-ID SAB), Neurobehavioral Symptom Inventory, and PROMIS Cognitive Concerns Scale., Results: Indices of severity of worst TBI, time since most recent TBI, and multiple injuries demonstrated expected relationships with neurobehavioral symptoms such that greater symptom reporting was observed among those who had more severe injuries, more recent injuries, and multiple injuries over a period of time., Conclusions: Findings provide preliminary evidence of validity for three of the indices derived from OSU TBI-ID SAB among Spanish-speaking individuals. Further study is needed to assess other aspects of this instrument to pave the way for further epidemiological studies involving lifetime exposure to TBI among Spanish-speaking individuals across the U.S., Spain, and Latin America.

Over the last two decades, fluorine substitution has become one of the essential structural traits in modern pharmaceuticals. Thus, about half of the most successful drugs (blockbuster drugs) contain fluorine atoms. In this review, we profile 17 fluorine-containing drugs approved by the food and drug administration (FDA) in 2018. The newly approved pharmaceuticals feature several types of aromatic F and CF 3 , as well as aliphatic (CF 2 ) substitution, offering advances in the treatment of various diseases, including cancer, HIV, malarial and smallpox infections., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Using computational algorithms to design tailored drug cocktails for highly active antiretroviral therapy (HAART) on specific populations is a goal of major importance for both pharmaceutical industry and public health policy institutions. New combinations of compounds need to be predicted in order to design HAART cocktails. On the one hand, there are the biomolecular factors related to the drugs in the cocktail (experimental measure, chemical structure, drug target, assay organisms, etc.); on the other hand, there are the socioeconomic factors of the specific population (income inequalities, employment levels, fiscal pressure, education, migration, population structure, etc.) to study the relationship between the socioeconomic status and the disease. In this context, machine learning algorithms, able to seek models for problems with multi-source data, have to be used. In this work, the first artificial neural network (ANN) model is proposed for the prediction of HAART cocktails, to halt AIDS on epidemic networks of U.S. counties using information indices that codify both biomolecular and several socioeconomic factors. The data was obtained from at least three major sources. The first dataset included assays of anti-HIV chemical compounds released to ChEMBL. The second dataset is the AIDSVu database of Emory University. AIDSVu compiled AIDS prevalence for >2300 U.S. counties. The third data set included socioeconomic data from the U.S. Census Bureau. Three scales or levels were employed to group the counties according to the location or population structure codes: state, rural urban continuum code (RUCC) and urban influence code (UIC). An analysis of >130,000 pairs (network links) was performed, corresponding to AIDS prevalence in 2310 counties in U.S. vs. drug cocktails made up of combinations of ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4856 protocols, and 10 possible experimental measures. The best model found with the original data was a linear neural network (LNN) with AUROC>0.80 and accuracy, specificity, and sensitivity≈77% in training and external validation series. The change of the spatial and population structure scale (State, UIC, or RUCC codes) does not affect the quality of the model. Unbalance was detected in all the models found comparing positive/negative cases and linear/non-linear model accuracy ratios. Using synthetic minority over-sampling technique (SMOTE), data pre-processing and machine-learning algorithms implemented into the WEKA software, more balanced models were found. In particular, a multilayer perceptron (MLP) with AUROC=97.4% and precision, recall, and F-measure >90% was found., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The purpose of the current study was to evaluate the relative contribution of acculturation to two tests of nonverbal test performance in Hispanics., Method: This study compared 40 Hispanic and 20 non-Hispanic whites on Digit Symbol-Coding (DSC) and the Wisconsin Card Sorting Test (WCST) and evaluated the relative contribution of the various acculturation components to cognitive test performance in the Hispanic group., Results: Hispanics performed significantly worse on DSC and WCST relative to non-Hispanic whites. Multiple regressions conducted within the Hispanic group revealed that language use uniquely accounted for 11.0% of the variance on the DSC, 18.8% of the variance on WCST categories completed, and 13.0% of the variance in perseverative errors on the WCST. Additionally, years of education in the United States uniquely accounted for 14.9% of the variance in DSC., Conclusions: The significant impact of acculturation on DSC and WCST lends support that nonverbal cognitive tests are not necessarily culture free. The differential contribution of acculturation proxies highlights the importance of considering these separate components when interpreting performance on neuropsychological tests in clinical and research settings. Factors, such as the country where education was received, may in fact be more meaningful information than the years of education of education attained. Thus, acculturation should be considered an important factor in any cognitive evaluation of culturally diverse individuals.

Objective: To determine whether racial/ethnic disparities occur in depression, anxiety, and satisfaction with life at 1 and 2 years postdischarge., Design: A prospective, longitudinal, multicenter study of individuals with traumatic brain injury (TBI) participating in the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems project. Medical, demographic, and outcome data were obtained from the Model Systems database at baseline, as well as 1 and 2 years postdischarge., Setting: A total of 16 TBI Model Systems hospitals in the United States., Participants: Individuals with moderate or severe TBI (N=1662) aged 16 years or older consecutively discharged between January 2008 and June 2011 from acute care and comprehensive inpatient rehabilitation at a Model Systems hospital., Intervention: Not applicable., Main Outcome Measures: The Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, and Satisfaction with Life Scale assessed depression, anxiety, and satisfaction with life at 1 and 2-year follow-ups., Results: After controlling for all possible covariates, hierarchal linear models found that black individuals had elevated depression across the 2 time points relative to white individuals. Asian/Pacific Islanders' depression increased over time in comparison to the decreasing depression in those of Hispanic origin, which was a greater decrease than in white individuals. Black individuals had lower life satisfaction than did white and Hispanic individuals, but only marginally greater anxiety over time than did white individuals and similar levels of anxiety as did Asian/Pacific Islanders and Hispanic individuals., Conclusions: Mental health trajectories of individuals with TBI differed as a function of race/ethnicity across the first 2 years postdischarge, providing the first longitudinal evidence of racial/ethnic disparities in mental health after TBI during this time period. Further research will be required to understand the complex factors underlying these differences., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Approximately 25% of working-aged Americans with disabilities work full or part time, yet still face discrimination despite the passing of the American's with Disabilities Act (ADA) over 20 years ago., Objectives: To determine if the proportion of allegations of ADA Title I workplace discrimination with merit closed at any year between 1993 and 2008 differs among Whites, African Americans, Hispanics, and Asians; to determine if there was a change over time from 1993 to 2008 in merit closure rate within each race/ethnicity group; and to determine whether changes over time between 1993 and 2008 in the merit closure rate differ among the race/ethnicity groups., Methods: Logistic regression was used for this cross-sectional panel study to model the merit closure rate for each ethnic group from 1993 to 2008 using 318,587 charging parties from the EEOC database., Results: All ethnic groups exhibited significant changes over time in the merit closure rate. There were significant differences in the closure rates among the race/ethnicity groups specifically at closure years 1995-2000, 2002, 2003, and 2006. Finally, there was evidence that the trends in merit closure rates over time differed significantly among the race/ethnicity groups., Conclusions: There was significant evidence that the proportion of claims closed with merit was significantly different among the racial/ethnicity groups.