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Purpose: To assess the impact of a retinopathy of prematurity (ROP) mentoring program in four rural regions with 31 neonatal units in Colombia between 2011 and 2019., Methods: Indicators recommended by the national program were used for assessment: screening coverage of eligible preterm newborns, proportion screened with any stage of ROP, and proportion of screened infants treated. Data were also collected on the number of units with ROP services and birth weight (BW) and gestational age (GA) of babies treated. Data on the number of preterm births, BWs of infants screened, and their ROP status (any/none) were extracted from the national health information system. Ophthalmologists in each region provided data on the number screened and treated. A linear-by-linear statistic was used to assess trends in the indicators before and during mentoring., Results: Of the 31 neonatal units, the number providing ROP services increased from 7 (23%) to 26 (84%). The number of eligible infants born in the four regions (total 33,521) was stable over the study period, the proportion screened increased from 14% to 41%, the proportion of those screened who were found to have any ROP tended to decrease overtime, and the proportion of those screened who were treated declined from 9% to 3%, with some regional variation. By year 3 no infant with a BW ≥2000 g or GA of >36 weeks was treated., Conclusions: In our study, mentoring rural providers proved a valuable strategy for inducing new screening programs, increasing coverage, and improving local capacities in neonatal care and ROP services., (Copyright © 2024. Published by Elsevier Inc.)

The electrochemical series is a useful tool in electrochemistry, but its effectiveness in materials chemistry is limited by the fact that the standard electrochemical series is based on a relatively small set of reactions, many of which are measured in aqueous solutions. To address this problem, we have used machine learning to create an electrochemical series for inorganic materials from tens of thousands of entries in the Inorganic Crystal Structure Database. We demonstrate that this series is generally more consistent with oxidation states in solid-state materials than the series based on aqueous ions. The electrochemical series was constructed by developing and parameterizing a physical, human-interpretable model of oxidation states in materials. We show that this model enables the prediction of oxidation states from composition in a way that is more accurate than a state-of-the-art transformer-based neural network model. We present applications of our approach to structure prediction, materials discovery, and materials electrochemistry, and we discuss possible additional applications and areas for improvement. To facilitate the use of our approach, we introduce a freely available website and API., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: Individuals with bipolar disorder (BD) have high rates of suboptimal medication adherence, medical illness, and premature mortality, largely from cardiovascular causes. This analysis examined the association between adherence to antihypertensive and BD medications and clinical symptoms in patients with BD and comorbid hypertension (HTN) from an ongoing trial to optimize adherence., Method: Inclusion criteria were a BD diagnosis, treatment with antihypertensives, adherence challenges, and poorly controlled HTN. Adherence was measured via self-report using the Tablets Routine Questionnaire and using eCAP, an electronic pillcap which captures openings. Average systolic blood pressure (SBP) was calculated from 12 readings over 1 week. The Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Psychiatric Rating Scale (BPRS) assessed BD symptoms., Results: A total of 83 participants with BD and HTN were included. Adherence to BD and antihypertensive medications were positively correlated. eCAP openings showed more missed doses than self-reported antihypertensive adherence. BD medication adherence was positively correlated with BPRS at baseline; antihypertensive adherence was negatively correlated with SBP at screening. Antihypertensive adherence improved and SBP decreased between screening and baseline., Conclusions: Adherence levels fluctuated over time and differed based on measurement method in people with comorbid BD and HTN. Self-reported BD adherence was positively related to global psychiatric symptoms and antihypertensive adherence was related to better SBP control. Monitoring both medication and blood pressure led to change in self-reported adherence. BD symptom severity may indicate poor adherence in patients with BD and should be considered in treatment planning., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Author M.S.: Research grants within past 3 years: Intra-Cellular, Merck, Otsuka, Alkermes, International Society for Bipolar Disorders (ISBD), National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), Patient-Centered Outcomes Research Institute (PCORI). Consultant in the past year: Alkermes, Otsuka, Janssen, Lundbeck, Teva, Neurelis. Royalties: Springer Press, Johns Hopkins University Press, Oxford Press, UpToDate.

Norovirus infection is characterised by a rapid onset of disease and the development of debilitating symptoms including projectile vomiting and diffuse diarrhoea. Vaccines and antivirals are sorely lacking and developments in these areas are hampered by the lack of an adequate cell culture system to investigate human norovirus replication and pathogenesis. Herein, we describe how the model norovirus, Mouse norovirus (MNV), produces a viral protein, NS3, with the functional capacity to attenuate host protein translation which invokes the activation of cell death via apoptosis. We show that this function of NS3 is conserved between human and mouse viruses and map the protein domain attributable to this function. Our study highlights a critical viral protein that mediates crucial activities during replication, potentially identifying NS3 as a worthy target for antiviral drug development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aktepe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah -/- mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease., Competing Interests: Declaration of interests H.A.M. and B.Y.C. consult for Ena Respiratory. A.G.R. received research support from Illumina. P.G.T. is on the SAB of Immunoscape and Cytoagents, consulted for JNJ, received travel support/honoraria from Illumina and 10× Genomics, and has patents related to TCR discovery. J.C.C. and P.G.T. have patents related to treating or reducing severity of viral infections, including SARS-CoV-2., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Qualitative methods are incredibly beneficial to the dissemination and implementation of new digital health interventions; however, these methods can be time intensive and slow down dissemination when timely knowledge from the data sources is needed in ever-changing health systems. Recent advancements in generative artificial intelligence (GenAI) and their underlying large language models (LLMs) may provide a promising opportunity to expedite the qualitative analysis of textual data, but their efficacy and reliability remain unknown., Objective: The primary objectives of our study were to evaluate the consistency in themes, reliability of coding, and time needed for inductive and deductive thematic analyses between GenAI (ie, ChatGPT and Bard) and human coders., Methods: The qualitative data for this study consisted of 40 brief SMS text message reminder prompts used in a digital health intervention for promoting antiretroviral medication adherence among people with HIV who use methamphetamine. Inductive and deductive thematic analyses of these SMS text messages were conducted by 2 independent teams of human coders. An independent human analyst conducted analyses following both approaches using ChatGPT and Bard. The consistency in themes (or the extent to which the themes were the same) and reliability (or agreement in coding of themes) between methods were compared., Results: The themes generated by GenAI (both ChatGPT and Bard) were consistent with 71% (5/7) of the themes identified by human analysts following inductive thematic analysis. The consistency in themes was lower between humans and GenAI following a deductive thematic analysis procedure (ChatGPT: 6/12, 50%; Bard: 7/12, 58%). The percentage agreement (or intercoder reliability) for these congruent themes between human coders and GenAI ranged from fair to moderate (ChatGPT, inductive: 31/66, 47%; ChatGPT, deductive: 22/59, 37%; Bard, inductive: 20/54, 37%; Bard, deductive: 21/58, 36%). In general, ChatGPT and Bard performed similarly to each other across both types of qualitative analyses in terms of consistency of themes (inductive: 6/6, 100%; deductive: 5/6, 83%) and reliability of coding (inductive: 23/62, 37%; deductive: 22/47, 47%). On average, GenAI required significantly less overall time than human coders when conducting qualitative analysis (20, SD 3.5 min vs 567, SD 106.5 min)., Conclusions: The promising consistency in the themes generated by human coders and GenAI suggests that these technologies hold promise in reducing the resource intensiveness of qualitative thematic analysis; however, the relatively lower reliability in coding between them suggests that hybrid approaches are necessary. Human coders appeared to be better than GenAI at identifying nuanced and interpretative themes. Future studies should consider how these powerful technologies can be best used in collaboration with human coders to improve the efficiency of qualitative research in hybrid approaches while also mitigating potential ethical risks that they may pose., (©Maximo R Prescott, Samantha Yeager, Lillian Ham, Carlos D Rivera Saldana, Vanessa Serrano, Joey Narez, Dafna Paltin, Jorge Delgado, David J Moore, Jessica Montoya. Originally published in JMIR AI (https://ai.jmir.org), 02.08.2024.)

People with HIV and comorbid substance use problems may be among those who benefit most from long-acting HIV antiretroviral treatment, but they are routinely excluded from Phase 3 clinical trials. Their inclusion would permit an examination of the clinical value of long-acting therapies for people with adherence problems and an exploration of syndemic interactions between HIV, mental health conditions, and substance use problems, which compound into a major challenge in the efforts to end the HIV epidemic., Competing Interests: Competing interest’s statement The authors declare no conflicts of interest.

Reconstructing the global Tree of Life necessitates computational approaches to integrate numerous molecular phylogenies with limited species overlap into a comprehensive supertree. Our survey of published literature shows that individual phylogenies are frequently restricted to specific taxonomic groups due to the expertise of investigators and molecular evolutionary considerations, resulting in any given species present in a minuscule fraction of phylogenies. We present a novel approach, called the chronological supertree algorithm (Chrono-STA), that can build a supertree of species from such data by using node ages in published molecular phylogenies scaled to time. Chrono-STA builds a supertree of organisms by integrating chronological data from molecular timetrees. It fundamentally differs from existing approaches that generate consensus phylogenies from gene trees with missing taxa, as Chrono-STA does not impute nodal distances, use a guide tree as a backbone, or reduce phylogenies to quartets. Analyses of simulated and empirical datasets show that Chrono-STA can combine taxonomically restricted timetrees with extremely limited species overlap. For such data, approaches that impute missing distances or assemble phylogenetic quartets did not perform well. We conclude that integrating phylogenies via temporal dimension enhances the accuracy of reconstructed supertrees that are also scaled to time.

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities., Competing Interests: Declaration of interests E.T., E.C., K.R., J. Button, A.M., M.B., J.A., A.W., M.A., T.K., A.C., S.S.A., D.L.P., and R.J.T. were employees of and stockholders in Illumina, Inc. at the time of this investigation. V.R. is a stockholder in Illumina, Inc. J.O. is a stockholder in Illumina, Inc. and employee of C2N Diagnostics. J. Belmont and T.W. are stockholders in Illumina, Inc. and were compensated as research advisors through Genetics & Genomics Services Inc. C.S. was compensated as a consultant through Genetics & Genomics Services Inc. for statistical analysis. K.M. is an employee of Ambry Genetics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The methamphetamine epidemic threatens progress towards ending the HIV epidemic in the United States. Further characterizing the prevalence and impact of methamphetamine use among people with HIV (PWH) is necessary to inform integrated HIV and methamphetamine treatment strategies., Methods: We conducted a retrospective chart review to characterize methamphetamine use among 3,092 PWH at an urban HIV Medicine clinic between July 1, 2022 and June 30, 2023. The Chi-squared test was utilized to assess for statistically significant differences in demographics and HIV and other health outcomes among PWH who use and do not use methamphetamine., Results: The prevalence of methamphetamine use among PWH in this cohort was 17%. PWH who used methamphetamine were more likely to be < 40 years of age, identify as White race, live in neighborhoods with low Healthy Places Index scores, identify as lesbian, gay, or bisexual, report male sex with men (MSM), MSM and injection drug use (IDU), or IDU as HIV transmission risk factor, miss scheduled HIV primary care visits, and screen positive for hepatitis C virus antibody, gonorrhea, chlamydia, and major depressive disorder. PWH who use methamphetamine were also less likely to be virally suppressed and have a CD4 count ≥ 200 cells/mm3., Conclusion: Methamphetamine use is prevalent among PWH at this urban HIV Medicine Clinic and is associated with worse HIV and other health outcomes which likely increase the risk of HIV transmission. The integration of methamphetamine use disorder treatment into HIV primary care is necessary to work toward ending the syndemics of methamphetamine and HIV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Entertainment-education interventions remain underutilized in sexual and reproductive health (SRH) despite evidence that they can be effective and place a low burden on staff. This study explores perceived facilitators and barriers for implementing an entertainment-education video intervention for 18- to 19-year-old African American and Latina women in SRH clinics., Design: Cross-sectional online survey (n=100) and telephone interviews (n=19) were completed May through August 2018., Setting: SRH clinics were located across 32 US states and 1 Canadian province., Participants: SRH clinic staff were diverse in type of clinic, role, and geography and were recruited using purposive sampling., Methods: Bivariate analyses were used for quantitative data, and thematic analysis was used for qualitative data., Main Outcome Measures: Intervention acceptability, perceived feasibility, and likely uptake were assessed using agreement statements (survey) and open-ended questions (interviews and survey)., Results: Interviewed clinic staff described the intervention as engaging, educational, and promising for improving client SRH knowledge and behaviors. Nearly all (95%) survey respondents said showing the video would be feasible. Most (56%) indicated likely uptake, which was significantly associated with perceived feasibility (P=.000), acceptability (P≤.001), and working at a public health clinic (P=.023). Implementation barriers included the video's potential relevance to only certain clients and the need for additional information or staff and/or management buy-in., Conclusions: This is the first study to assess perceived implementation facilitators and barriers of an entertainment-education video intervention among SRH clinic staff. The intervention was well received, with certain barriers potentially alleviated by offering information about entertainment-education and multiple implementation methods. These findings can help improve dissemination efforts for video-based entertainment-education interventions in clinics serving young women of color., Competing Interests: Conflict of Interest: The authors are affiliated with Sentient Research, which owns the copyright for Plan A. The intervention and its evaluation were supported by grant TP2AH000036 from the Department of Health and Human Services, Office of Population Affairs. Contents are solely the responsibility of the authors and do not represent the official views of the Department of Health and Human Services or the Office of Population Affairs.

Nicotinamide Adenine Dinucleotide (NAD + ) is implicated in bioenergetics, DNA repair, and senescence. Depletion of NAD + is associated with aging and neurodegenerative disease, prompting a growing interest in NAD + supplementation. With rising over-the-counter use of NAD, understanding their impact on perioperative recovery becomes essential. This study investigates the effect of NADH, a common NAD + precursor, on anesthesia in rodents. Baseline and post-anesthesia (1.5% isoflurane) open field and Y-maze activity were recorded in adult male and female C57/BL6 mice (n = 8-10/group). NADH (150 mg/kg, intraperitoneal) or vehicle (0.9% normal saline) were given at baseline or during anesthesia. The NADH-treated group exhibited a significant decrease in open-field activity relative to vehicle-treated. This diminished activity was reflected in reduced distance travelled and average velocity after emergence from anesthesia in the NADH-treated group. NADH treatment did not improve Y-maze performance after anesthesia as the number of visits to the novel arm was significantly decreased. This study demonstrates a potentially adverse impact of NADH on recovery from anesthesia. We revealed a depression in open-field activity and Y-maze performance with NADH supplementation, an indicator of cognitive recovery in rodents. The broad implications of NAD + in aging are likely to shape supplementation trends, highlighting the importance of understanding the potential influence of administering NAD + on anesthetic sensitivity and recovery., Competing Interests: Competing interests There are no conflicts of interests for all authors of this manuscript.

Although the presence of female contact sex pheromones in P . vannamei has been hypothesized, to date its existence has not been proven. To gather more evidence of their existence, cuticular liposoluble extracts were obtained from the following samples of adult females to be used as the experimental treatments: (1) ventral exoskeleton of immature female (VI), (2) dorsolateral exoskeleton of immature female (DI), (3) ventral exoskeleton of mature female (VM), and (4) dorsolateral exoskeleton of mature female (DM). Polyvinyl chloride tubes (artificial females; AF) were coated with each extract and the behavior displayed by sexually mature males in contact with the AF was recorded and classified as follows: 0 = no response; 1 = contact; 2 = pushing; and 3 = prolonged contact (≥10 s). To test the hypothesis that the extracts collected from the ventral portion of the abdomen exoskeleton have a higher effect on the behavior of males than the extracts collected from the dorsolateral portion of the abdomen exoskeleton, the experiment was divided into two bioassays: Bioassay I (VI vs. DI) and Bioassay II (VM vs. DM). In each bioassay, all experimental treatments were significantly different ( p > 0.05) from the CTL group (AF coated with hexane). Notably, the pushing behavior was significantly higher ( p < 0.05) in the VI treatment compared to the CTL and DI treatment. These results provide evidence of the existence of contact female sex pheromones with sexual recognition function located primarily in the ventral portion of the abdomen exoskeleton of P . vannamei .

The germ cell-less gene is crucial for gonad development in various organisms. Early interventions in its expression suggested a regulatory role at the mitotic stages of spermatogenesis, and its early knockout resulted in complete sterility in Drosophila. Genomic and transcriptomic data available for the catadromous giant prawn Macrobrachium rosenbergii enabled the identification of a germ cell-less homolog for this species, which we termed MroGCL (mRNA accession number OQ533056). An open reading frame containing 494 amino acids and a typical evolutionarily conserved BTB/POZ domain suggests possible protein-protein interaction functions in keeping with the Drosophila germ cell-less protein. Genomic mapping of MroGCL showed a full length of 120 896 bases. Analysis of the temporal expression of MroGCL showed constant expression in early prawn embryonic and larval stages, but a significant increase 10 days after metamorphosis when crucial sexual differentiation processes occur in prawns. In adult animals, high expression was detected in the gonads compared to the somatic tissues. RNAi-based knock-down experiments showed that both the silenced and control groups reached advanced spermatogenic stages, but that there was a significant decrease in the yield of spermatozoa in about half of the silenced animals. This finding supports our hypothesis that MroGCL is crucial for mitosis during early stage spermatogenesis. In conclusion, this study contributes to the understanding of crustacean gonad development and provides a stepping stone in the development of environmentally valuable sterile crustacean populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαβ+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αβ T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei., (© 2024 Guérin et al.)

There is strong evidence that social context plays a role in the processing of acoustic signals. Yet, the circuits and mechanisms that govern this process are still not fully understood. The insectivorous big brown bat, Eptesicus fuscus , emits a wide array of communication calls, including food-claiming calls, aggressive calls, and appeasement calls. We implemented a competitive foraging task to explore the influence of behavioral context on auditory midbrain responses to conspecific social calls. We recorded neural population responses from the inferior colliculus (IC) of freely interacting bats and analyzed data with respect to social context. Analysis of our neural recordings from the IC shows stronger population responses to individual calls during social events. For the first time, neural recordings from the IC of a copulating bat were obtained. Our results indicate that social context enhances neuronal population responses to social vocalizations in the bat IC., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations., Results: We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change., Conclusions: With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance., (© 2024. The Author(s).)

This review paper presents the practical development of imaging biomarkers in the scope of the PRIMAGE (PRedictive In silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers) project, as a noninvasive and reliable way to improve the diagnosis and prognosis in pediatric oncology. The PRIMAGE project is a European multi-center research initiative that focuses on developing medical imaging-derived artificial intelligence (AI) solutions designed to enhance overall management and decision-making for two types of pediatric cancer: neuroblastoma and diffuse intrinsic pontine glioma. To allow this, the PRIMAGE project has created an open-cloud platform that combines imaging, clinical, and molecular data together with AI models developed from this data, creating a comprehensive decision support environment for clinicians managing patients with these two cancers. In order to achieve this, a standardized data processing and analysis workflow was implemented to generate robust and reliable predictions for different clinical endpoints. Magnetic resonance (MR) image harmonization and registration was performed as part of the workflow. Subsequently, an automated tool for the detection and segmentation of tumors was trained and internally validated. The Dice similarity coefficient obtained for the independent validation dataset was 0.997, indicating compatibility with the manual segmentation variability. Following this, radiomics and deep features were extracted and correlated with clinical endpoints. Finally, reproducible and relevant imaging quantitative features were integrated with clinical and molecular data to enrich both the predictive models and a set of visual analytics tools, making the PRIMAGE platform a complete clinical decision aid system. In order to ensure the advancement of research in this field and to foster engagement with the wider research community, the PRIMAGE data repository and platform are currently being integrated into the European Federation for Cancer Images (EUCAIM), which is the largest European cancer imaging research infrastructure created to date., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Patients with diffuse large B-cell lymphoma (DLBCL) are typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, a standard of care for managing adolescents and young adults (AYAs) with DLBCL is lacking. We examine treatment approaches and outcomes of this population. Methods: We included 90 AYAs (15-39 years) diagnosed with DLBCL between 2008 and 2018 in three tertiary centers in Peru. Overall response rates (ORR) were available for all patients. Overall survival (OS) and progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. Results: The median age at diagnosis was 33 years, 57% were males, 57% had good performance status (Lansky/Karnofsky ≥90), and 61% were diagnosed with early-stage disease (Ann Arbor stages I-II). R-CHOP ( n  = 69, 77%) was the most frequently used first-line regimen, with an ORR of 91%. With a median follow-up of 83 months, the 5-year OS and PFS among all patients were 79% and 67%, respectively. Among the patients who received R-CHOP, the 5-year OS and PFS were 77% and 66%, respectively. Of the 29 (32%) patients with relapsed/refractory (R/R) disease, 83% received second-line treatment and only 14% underwent consolidation therapy with autologous transplantation. The 3-year OS for R/R DLBCL was 36%. Conclusion: Our data show that AYAs with DLBCL who received conventional therapy had comparable outcomes to those observed in studies conducted among the adult population. However, the prognosis for AYAs with R/R disease was dismal, indicating the unmet need for developing and increasing access to novel treatment modalities in AYAs.

Introduction: The purpose of this study was to determine the prevalence of congestive heart failure (CHF) among patients admitted with preeclampsia as well as to analyze the independent association of CHF with in-hospital outcomes among women with preeclampsia., Methods: Data were obtained from the National (Nationwide) Inpatient Sample (NIS) from January 2016 to December 2019. We assessed the independent association of CHF with outcomes in patients admitted with preeclampsia. Predictors of mortality in patients admitted with preeclampsia were also analyzed., Results: Women with preeclampsia in the United States between 2016 and 2019 were included in our analysis. A total of 256,010 cases were isolated, comprising 1150 patients with preeclampsia and CHF (0.45%). Multivariate analysis demonstrated that CHF in patients with preeclampsia was independently associated with several outcomes, among them cardiac arrest (adjusted OR (aOR) 4.635, p=0.004), ventricular tachycardia (aOR 17.487, p<0.001), pulmonary embolism (aOR 6.987, p<0.001), and eclampsia (aOR 2.503, p=0.011). Conversely, we found CHF to be protective against postpartum hemorrhage (aOR 0.665, p=0.003). Among the predictors of mortality in preeclampsia are age (aOR 1.062, p=0.022), Asian or Pacific Islander race (aOR 4.695, p=0.001), and CHF (aOR 25.457, p<0.001).  Conclusions: In a large cohort of patients admitted with preeclampsia, we found the prevalence of CHF to be 0.45%. CHF was associated with several adverse outcomes as well as increased length of stay., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Elkattawy et al.)

Influenza A virus (IAV) is one of the major global public health concerns but the emerging resistance of IAV to currently available antivirals requires the need to identify potential alternatives. Polyphenol rich sugarcane extract (PRSE) is an extract prepared from the sugarcane plant Saccharum Officinarum. Herein we aimed to determine if PRSE had antiviral activity against IAV. We showed that treatment of IAV-infected cells with PRSE results in a dose-dependent inhibition of virus infection at concentrations that were non-cytotoxic. PRSE treatment limited the early stages of infection, reducing viral genome replication, mRNA transcription and viral protein expression. PRSE did not affect the ability of IAV to bind sialic acid or change the morphology of viral particles. Additionally, PRSE treatment attenuated the replication of multiple IAV strains of the H3N2 and H1N1 subtype. In conclusion, we show that PRSE displays antiviral activity against a broad range of IAV strains, in vitro., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This research was supported by funding from The Product Makers. M.F. is employed by The Product Makers. All other co-authors have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mitochondrial ATAD3A is an ATPase Associated with diverse cellular Activities (AAA) domain containing enzyme, involved in the structural organization of the inner mitochondrial membrane and of increasing importance in childhood disease. In humans, two ATAD3A paralogs arose by gene duplication during evolution: ATAD3B and ATAD3C. Here we investigate the cellular activities of the ATAD3C paralog that has been considered a pseudogene. We detected unique ATAD3C peptides in HEK 293T cells, with expression similar to that in human tissues, and showed that it is an integral membrane protein that exposes its carboxy-terminus to the intermembrane space. Overexpression of ATAD3C, but not of ATAD3A, in fibroblasts caused a decrease in cell proliferation and oxygen consumption rate, and an increase of cellular ROS. This was due to the incorporation of ATAD3C monomers in ATAD3A complex in the mitochondrial membrane reducing its size. Consistent with a negative regulation of ATAD3A function in mitochondrial membrane organization, ATAD3C expression led to increased accumulation of respiratory chain dimeric CIII in the inner membrane, to the detriment to that assembled in respiratory supercomplexes. Our results demonstrate a negative dominant role of the ATAD3C paralog with implications for mitochondrial OXPHOS function and suggest that its expression regulates ATAD3A in the cell., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The escalating industrial and artisanal extraction of natural resources in the Amazon Basin has centered it into the spotlight of global environmental concern. This study deals with the environmental problems of heavy metals pollution and biomagnification, which stem from mining, agricultural, petrochemical, and industrial discharges. We conducted an extensive investigation, analyzing 360 fish specimens representing 58 species, to assess the concentrations of 11 metals (Al, As, Cd, Cr, Cu, He, Mn, Ni, Pb, Zn, and Hg) along the Ecuadorian sections of the Napo and Pastaza watersheds. Stable isotope analyses (δ 15 N and δ 13 C) were employed to determine their trophic positions and potential biomagnification risks. Sampling was carried out during two distinct hydrological seasons to capture seasonal variations in metal concentrations. Furthermore, we estimated species-specific daily heavy metal intake levels. The results of our study revealed that 15 fish species and 53 individual specimens exhibited heavy metal concentrations surpassing recommended standards, with elevated levels of Al, As, and Hg posing significant risks to human consumers with daily intakes of 0.46 kg/day. Notably, our investigation unveiled concerning trends, including increased metal concentrations, Hg biomagnification within fish populations from the Pastaza watershed, and an association between smaller fish size and higher metal content. This study provides a crucial baseline for monitoring future environmental changes and understanding the persistent impacts of heavy metal pollution in the Ecuadorian Amazon region and the broader Western Amazon. It underscores the urgent need for sustainable environmental management practices to mitigate the escalating threat to these vital ecosystems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: José Montoya, Blanca Ríos-Touma and Francisco Cuesta report financial support was provided by the Belgian Development Cooperation (DGD), the World Wildlife Fund Inc.(WWF), and UDLA through grants EC14507, EC11553, and FGE.JMC.21.01., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The primate infraorder Simiiformes, comprising Old and New World monkeys and apes, includes the most well-studied species on earth. Their most comprehensive molecular timetree, assembled from thousands of published studies, is found in the TimeTree database and contains 268 simiiform species. It is, however, missing 38 out of 306 named species in the NCBI taxonomy for which at least one molecular sequence exists in the NCBI GenBank. We developed a three-pronged approach to expanding the timetree of Simiiformes to contain 306 species. First, molecular divergence times were searched and found for 21 missing species in timetrees published across 15 studies. Second, untimed molecular phylogenies were searched and scaled to time using relaxed clocks to add four more species. Third, we reconstructed ten new timetrees from genetic data in GenBank, allowing us to incorporate 13 more species. Finally, we assembled the most comprehensive molecular timetree of Simiiformes containing all 306 species for which any molecular data exists. We compared the species divergence times with those previously imputed using statistical approaches in the absence of molecular data. The latter data-less imputed times were not significantly correlated with those derived from the molecular data. Also, using phylogenies containing imputed times produced different trends of evolutionary distinctiveness and speciation rates over time than those produced using the molecular timetree. These results demonstrate that more complete clade-specific timetrees can be produced by analyzing existing information, which we hope will encourage future efforts to fill in the missing taxa in the global timetree of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Craig, Bamba, Barba-Montoya, Hedges and Kumar.)

This topic review aims to present a global vision of multilevel analysis models’ applicability to health research, explaining its theoretical, methodological, and statistical foundations. We describe the basic steps to build these models and examples of their application according to the data hierarchical structure. It ir worth noticing that before using these models, researchers must have a rationale for needing them, and a statistical evaluation accounting for the variance percentage explained by the observations grouping effect. The requirements to conduct this type of analysis depends on special conditions such as the type of variables, the number of units per level, or the type of hierarchical structure. We conclude that multilevel analysis models are a useful tool to integrate information, considering the complexity of the relationships and interactions involved in most health conditions, including the loss of independence between observation units.

Purpose: Pregnancy is a period in a woman's life that has important consequences on oral health, particularly for gingival health. Present study aims to identify women at higher risk of developing periodontal disease (gingivitis and periodontitis) during late pregnancy and evaluate how this condition evolves during this period., Methods: Prospective cohort study was designed with pregnant women who were assessed during the first and third trimesters of gestation in a southern Spanish public hospital. Data regarding gingival and periodontal health, oral hygiene, and overall health status (obesity and diabetes mellitus) were collected. Reporting followed STROBE checklist., Results: Significantly higher number of women had the periodontal and gingival disease in the third trimester of gestation compared with in early pregnancy. In the third trimester of gestation, 42 (28.6%) and 63 (42.9%) of women presented symptoms of periodontal disease and gingival disease, respectively. Obesity (OR 2.834; 95%CI 0.919-8.741), worse oral hygiene during the first trimester of gestation (OR: 4.031; 95%CI 2.12-7.65), and periodontal disease during early pregnancy (OR: 15.104; 95%CI 3.60-63.36) most effectively predicted periodontal disease during late pregnancy., Conclusions: Pregnancy is associated with exacerbated periodontal and gingival disease symptoms throughout the different trimesters of gestation. Obesity and oral hygiene during early pregnancy were the risk factors that most contributed to the aforementioned changes in periodontal disease., (© 2022. The Author(s).)

Purpose: Urgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice., Methods: BRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation., Results: A total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0-360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0-2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0-60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam., Conclusion: IV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: V. Villanueva has received honoraria and/or research funds from Angelini Pharma, Bial, Eisai, Jazz Pharmaceuticals, Neuraxpharm, Novartis, Nutricia, Takeda, UCB Pharma, and Xenon. X. Rodríguez-Osorio has received honoraria and/or research funds from Angelini Pharma, Bial, Eisai, Jazz Pharmaceuticals, Neuraxpharm, UCB Pharma, and LivaNova. A Juiz-Fernández declares research funding and speaking fees from Bial Pharmaceutical, Jazz Pharmaceuticals, Eisai Inc., and UCB Pharma. M. Garcés has received consultant and/or speaker honoraria from Angelini-Pharma, Bial, Eisai, and UCB Pharma. E Rubio-Nazábal has received honoraria from BIAL, Eisai, and UCB Pharma for speaking. E Santamarina reports grants and personal fees from UCB Pharma, Eisai, and Bial; personal fees from Angelini Pharma, Esteve, and Ferrer outside the submitted work. M Falip has received speaker honoraria from UCB. I Garcia-Morales has received honoraria consultant and/or speaker honoraria from UCB, EISAI, Neuraxpharm, and Angelini. Ana Belén Martínez has received consultant and/or speaker honoraria from Angelini-Pharma, Eisai, and UCB Pharma. B Chavarria has received travel support from UCB. Rodrigo Rocamora has received travel support and honoraria as advisor from UCB, EISAI, Angelini, and Jazz Pharmaceutical. D Sayas, K Hampel, A Castillo, J Montoya, D Campos, A Fernández-Cabrera, A Gifreu, G Hernández Pérez, B Parejo-Carbonell, M Massot, M Asensio, J Giménez, V Guillen, J Ruiz-Giménez, R Rocamora, and I Escalza have no conflicts of interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the Cure All framework, which can be replicated in low- and middle-income countries., Methods: A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services., Results: Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology., Conclusions: The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

A common practice in molecular systematics is to infer phylogeny and then scale it to time by using a relaxed clock method and calibrations. This sequential analysis practice ignores the effect of phylogenetic uncertainty on divergence time estimates and their confidence/credibility intervals. An alternative is to infer phylogeny and times jointly to incorporate phylogenetic errors into molecular dating. We compared the performance of these two alternatives in reconstructing evolutionary timetrees using computer-simulated and empirical datasets. We found sequential and joint analyses to produce similar divergence times and phylogenetic relationships, except for some nodes in particular cases. The joint inference performed better when the phylogeny was not well resolved, situations in which the joint inference should be preferred. However, joint inference can be infeasible for large datasets because available Bayesian methods are computationally burdensome. We present an alternative approach for joint inference that combines the bag of little bootstraps, maximum likelihood, and RelTime approaches for simultaneously inferring evolutionary relationships, divergence times, and confidence intervals, incorporating phylogeny uncertainty. The new method alleviates the high computational burden imposed by Bayesian methods while achieving a similar result., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barba-Montoya, Sharma and Kumar.)

Introduction: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders., Purpose: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology., Methods: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology., Results: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence., Conclusions: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Falip has received honoraria for advisory boards/consultancy and speaking fees from Angelini, BIAL, ESAI, Esteve, GW Pharmaceuticals/Jazz Pharmaceuticals, UCB Pharma/Zogenix; J. López has participated in advisory boards and industry-sponsored symposia by Angelini, BIAL, Cyberonics, ESAI, Esteve, GSK, Jazz Pharmaceuticals, Pfizer, UCB Pharma; I. Rey Gómez-Serranillos has received fees for his participation in the study from Angelini; V. Merino-Bohórquez has received fees for his participation in the study from Angelini; J. Montoya has received research grants or honoraria for advisory boards/consultancy from Angelini, EISAI, BIAL, Esteve, Exeltis, Neuraxpharm, UCB Pharma; J Uranga has received honoraria as speaker or participant in advisory boards from Angelini, BIAL, EISAI, Glaxo-SmithKline, GW Pharma, Livanova, Lumdbeck, Medtronic, Pfizer, UCB Pharma; E. Ruiz has received fees for his participation in the study from Angelini; A Sancho-López has received fees for her participation in the study from Angelini; J.L. Trillo has received fees for his participation in the study from Angelini; J.A. Vallès has received fees for his participation in the study from Angelini. E. Álvarez-Barón and J. Sabaniego are employees of Angelini; S. Subías-Labazuy and A. Gil are employees of Omakase Consulting which received funding from Angelini to develop and conduct this study., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Introduction: obesity in the pediatric population is a public health problem. The correlation of uric acid and carotid intima media thickness in adults has been demonstrated. Objective: to identify the correlation of uric acid and carotid intima media thickness in adolescents with obesity. Material and methods: an observational, cross-sectional study was carried out. Patients aged ten to 16 years with a diagnosis of obesity were included. Uric acid, lipid profile and carotid intima media thickness were determined. In relation to the statistical analysis, carotid intima media thickness was correlated with uric acid levels through Spearman's correlation coefficient. Results: one hundred and sixty-nine adolescents were included with a median age of 13 years, without predominance of sex. A positive correlation of uric acid with carotid intima media thickness was identified (r = 0.242, p = 0.001). When stratified according to sex, there was no correlation in women (r = -0.187, p = 0.074), while in men it increased (r = 0.36, p = 0.001) and by pubertal stage, pubertal male adolescents had a positive correlation (p = 0.384, p = 0.002). Conclusion: a weak positive correlation was identified between carotid intimal thickness and uric acid in obese adolescents.

The development of virus-like particle (VLP) based vaccines for human papillomavirus, hepatitis B and hepatitis E viruses represented a breakthrough in vaccine development. However, for dengue and COVID-19, technical complications, such as an incomplete understanding of the requirements for protective immunity, but also limitations in processes to manufacture VLP vaccines for enveloped viruses to large scale, have hampered VLP vaccine development. Selecting the right adjuvant is also an important consideration to ensure that a VLP vaccine induces protective antibody and T cell responses. For diseases like COVID-19 and dengue fever caused by RNA viruses that exist as families of viral variants with the potential to escape vaccine-induced immunity, the development of more efficacious vaccines is also necessary. Here, we describe the development and characterisation of novel VLP vaccine candidates using SARS-CoV-2 and dengue virus (DENV), containing the major viral structural proteins, as protypes for a novel approach to produce VLP vaccines. The VLPs were characterised by Western immunoblot, enzyme immunoassay, electron and atomic force microscopy, and in vitro and in vivo immunogenicity studies. Microscopy techniques showed proteins self-assemble to form VLPs authentic to native viruses. The inclusion of the glycolipid adjuvant, α-galactosylceramide (α-GalCer) in the vaccine formulation led to high levels of natural killer T (NKT) cell stimulation in vitro , and strong antibody and memory CD8 + T cell responses in vivo , demonstrated with SARS-CoV-2, hepatitis C virus (HCV) and DEN VLPs. This study shows our unique vaccine formulation presents a promising, and much needed, new vaccine platform in the fight against infections caused by enveloped RNA viruses., Competing Interests: VL, VP, and SM are employees of Sanofi-Pasteur. Part of the dengue VLP work was performed under an unrestricted research agreement between JT, University of Melbourne and Sanofi-Pasteur. There are two patents (PCT 35580344 and PCT 35580347) and three provisional patents (Patent Specification – 35541073, Patent Specification, SARS-CoV-2 VLP – 35555578, and Patent Specification, SARS-CoV-2 VLP – 35549058) covering this work. DG is a member of the Scientific Advisory Board of Avalia Immunotherapies. SG is a Director of Avalia Immunotherapies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Collett, Earnest, Carrera Montoya, Edeling, Yap, Wong, Christiansen, Roberts, Mumford, Lecouturier, Pavot, Marco, Loi, Simmons, Gulab, Mackenzie, Elbourne, Ramsland, Cameron, Hans, Godfrey and Torresi.)

Hispanics are more likely to be diagnosed with skin cancer at a later stage and experience worse overall survival than Whites. The objective of this cross-sectional study was to assess the skin cancer knowledge, attitudes, perceived risk, and sun protection practices among an underserved population in the Phoenix area. We recruited participants from the greater Phoenix area to undergo skin examination and complete a questionnaire. 208 participants were included. The majority were Hispanic (64.9%). Of this Hispanic group, most were from Mexico (87.9%). The Hispanic cohort had an overall mean skin cancer knowledge score of 3.68/6, the lowest of any other racial/ethnic group, but had the highest desire to learn more about skin cancer (64.6%, "strongly agree"). They were the most concerned about developing skin cancer (50.4%, "very concerned") but had relatively lower rates of sun protection practices (7.9% "always use" sunscreen, 22.0% "always use" sun-protective clothing). Limitations of this study include a small sample size, lack of validation for the skin cancer knowledge score, lack of season as a covariate in the multivariate analysis, lack of follow-up, and lack of robust skin cancer risk assessment. In conclusion, despite poorer skin cancer knowledge and sun protection practices, the Hispanic population had the highest concern for developing skin cancer and desire to learn more about skin cancer. Targeted and culturally relevant skin cancer and sun protection education for this group is needed., (© 2022. W. Montague Cobb-NMA Health Institute.)

Rationale and Objectives: We previously reported a novel manual method for measuring bone mineral density (BMD) in coronary artery calcium (CAC) scans and validated our method against Dual X-Ray Absorptiometry (DEXA). Furthermore, we have developed and validated an artificial intelligence (AI) based automated BMD (AutoBMD) measurement as an opportunistic add-on to CAC scans that recently received FDA approval. In this report, we present evidence of equivalency between AutoBMD measurements in cardiac vs lung CT scans., Materials and Methods: AI models were trained using 132 cases with 7649 (3 mm) slices for CAC, and 37 cases with 21918 (0.5 mm) slices for lung scans. To validate AutoBMD against manual measurements, we used 6776 cases of BMD measured manually on CAC scans in the Multi-Ethnic Study of Atherosclerosis (MESA). We then used 165 additional cases from Harbor UCLA Lundquist Institute to compare AutoBMD in patients who underwent both cardiac and lung scans on the same day., Results: Mean±SD for age was 69 ± 9.4 years with 52.4% male. AutoBMD in lung and cardiac scans, and manual BMD in cardiac scans were 153.7 ± 43.9, 155.1 ± 44.4, and 163.6 ± 45.3 g/cm 3 , respectively (p = 0.09). Bland-Altman agreement analysis between AutoBMD lung and cardiac scans resulted in 1.37 g/cm 3 mean differences. Pearson correlation coefficient between lung and cardiac AutoBMD was R 2 = 0.95 (p < 0.0001)., Conclusion: Opportunistic BMD measurement using AutoBMD in CAC and lung cancer screening scans is promising and yields similar results. No extra radiation plus the high prevalence of asymptomatic osteoporosis makes AutoBMD an ideal screening tool for osteopenia and osteoporosis in CT scans done for other reasons., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Morteza Naghavi reports financial support was provided by American Technologies LLC and HeartLung.AI. Morteza Naghavi reports a relationship with American Technologies LLC and HeartLung.AI that includes: board membership, consulting or advisory, employment, and equity or stocks. Song Shou Mao reports a relationship with The Lundquist Institute that includes: consulting or advisory. Venkat Manubolu reports a relationship with HeartLung.AI that includes: consulting or advisory. Dong Li reports a relationship with HeartLung.AI that includes: consulting or advisory. Thomas Atlas reports a relationship with HeartLung.AI that includes: consulting or advisory. Anthony Reeves reports a relationship with HeartLung.AI that includes: consulting or advisory. Claudia Henschke reports no financial relationship with HeartLung.AI or American Heart Technologies LLC. David Yankelevitz reports a relationship with HeartLung.AI that includes: consulting or advisory. Matthew Budoff reports a relationship with HeartLung.AI that includes: consulting or advisory. Amirhossein Jaberzadeh reports a relationship with HeartLung.AI that includes: employment. Chenyu Zhang reports a relationship with HeartLung.AI that includes: employment. Marlon Montes reports a relationship with HeartLung.AI that includes: employment. Mathew Budoff has patent #US 9119,590 B2 issued to Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA. Mathew Budoff has patent #US 10,695,022,B2 issued to Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA., (© 2023 Published by Elsevier Ltd.)

What, how and why people eat has long been understood to be important for human health, but until recently, has not been recognised as an essential facet of climate change and its effects on planetary health. The global climate change and diet-related health crises occurring are connected to food systems, food environments and consumer food choices. Calls to transform food systems for human and planetary health highlight the importance of understanding individual food choice. Understanding what, how and why people eat the way they do is crucial to successful food systems transformations that achieve both human and planetary health goals. Little is known about how food choice relates to climate. To clarify potential paths for action, we propose that individual food choice relates to climate change through three key mechanisms. First, the sum of individual food choices influences the supply and demand of foods produced and sold in the marketplace. Second, individual food decisions affect type and quantity of food waste at the retail and household level. Third, individual food choices serve as a symbolic expression of concern for human and planetary health, which can individually and collectively stimulate social movements and behaviour change. To meet the dietary needs of the 2050 global population projection of 10 billion, food systems must transform. Understanding what, how and why people eat the way they do, as well as the mechanisms by which these choices affect climate change, is essential for designing actions conducive to the protection of both human and planetary health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Youth who have experienced trauma often face challenges with self-regulation and can have diminished health outcomes, including those related to sexual and reproductive health. We developed a 12-session blended e-learning intervention for youth involved in juvenile justice systems to encourage healthy sexual decision-making by improving self-regulation skills. This paper describes the development of the program, e-Practice Self-Regulation, as well as an assessment of program acceptability and perceived effectiveness among youth participants. Data were collected using a feedback survey from youth who both completed (n = 95) and did not complete (n = 80) the intervention. Program acceptability was high among all participants, and over 70 % of both completers and non-completers would recommend e-Practice Self-Regulation to peers. Youth reported positive interactions with facilitators and described sessions as helpful, interesting, and educational. The most common criticism was online session length. A majority in both groups reported perceived effectiveness related to sexual health and self-regulation, which increased with more sessions completed. Results suggest e-Practice Self-Regulation is acceptable to youth participants, who reported learning skills necessary for self-regulation and sexual health and intended to use these skills to avoid unplanned pregnancy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aaron Plant reports a relationship with Sentient Research that includes: employment. Jorge Montoya reports a relationship with Sentient Research that includes: employment. Deborah Neffa-Creech reports a relationship with Sentient Research that includes: employment. Joann Schladale reports a relationship with Resources for Resolving Violence, Inc. that includes: employment. While Sentient Research and Resources for Resolving Violence authors have the right to distribute the e-PS-R intervention, the study presented was conducted independently by The Policy & Research Group (which has no financial interest in e-PS-R)., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Adipokines are associated with cardiovascular disease; in chronic kidney disease (CKD) patients adipokines could be useful prognostic factors., Objectives: To explore whether leptin and adiponectin in kidney replacement therapy (KRT) children could have a role on their cardiac function, in the long-term., Design: Prospective cohort study was performed with pediatric KRT patients, aged 8 to 17 years who were undergoing hemodialysis or peritoneal dialysis. At enrollment, lipid profile, adipokines (leptin, leptin receptor, free leptin, and adiponectin), anthropometric measurements and cardiological evaluation were determined. At two-year follow-up, a new cardiological evaluation was performed. Statistical analysis : Quantitative data are presented as median and interquartile range (IQR). Mann-Whitney U test and Chi-squared were used for the between-group comparison. Multivariate analyzes were performed to determine the association of adipokines levels with ventricular ejection fraction (LEVF)., Results: We included 56 patients, with a median age of 12.5 years. In the first cardiological evaluation, median LVEF was 70.0% (IQR 61%, 76%), 20 patients (35.7%) had some cardiovascular condition, and 10 (17.8%) altered LVEF. At 24-month follow-up, the median LVEF was 70.5% (IQR 65.1%, 77%), while the delta-LVEF values was 3% (IQR -6.5%, 7%). Delta-LVEF were correlated with baseline adipokines serum levels, and the only positive correlation found was with free leptin (r=0.303, p=0.025). In multivariate analysis, levels of free leptin (Coef. 0.12, p<0.036) and leptin (coef. 1.72, p=0.049), as well as baseline LVEF (Coef. -0.65, p<0.001) were associated with delta-LVEF., Conclusions: Free leptin, leptin and LVEF at the beginning of follow-up were associated with the LVEF decrease at the 24-month follow-up in KRT children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Villasis-Keever, Zurita-Cruz, Zepeda-Martinez, Alegria-Torres, Serret-Montoya, Estrada-Loza, Hernández-Hernández, Alonso-Flores and Zavala-Serret.)

Purpose: To analyze the influence of Caucasian mitochondrial haplogroups on controlled ovarian stimulation outcome (COS), embryo (E), and pregnancy success., Methods: In a Caucasian population (n = 517) undergoing COS, mitochondrial haplogroups and physiological parameters were determined. Patients were classified, according to Bologna criteria, as good (>3)/poor ≤3) responder, on dependence of recruited oocytes (RO), and in pregnancy/non-pregnancy groups. Haplogroups were determined by sequencing mitochondrial hypervariable sequence I and confirmed by polymerase chain reaction (PCR), followed by restriction fragment length polymorphisms (RFLP)., Results: The rank of total dose of FSH (TD FSH) was similar in all clusters/haplogroups, except in JT, which is narrower (950-3,650 IU), particularly in T (1,350-3,650 IU). The statistical analysis showed higher RO and E in JT when compared to U, although it was only Uk which accumulated significantly in pregnancy respect to JT. Pearson's correlations between TD FSH and RO showed negative statistical significance in all population (P = 0.001), H (P = 0.03), JT (P = 0.01), and T (P = 0.03). The percentage of contribution of TD FSH on RO was almost nine times in the JT cluster as compared to all population one., Conclusions: JT cluster shows a different influence of TD FSH on RO. JT cluster shows higher RO and E than U, but it is Uk which exhibits a significant higher pregnancy rate than JT. The negative influence of the JT cluster on pregnancy success strongly suggests that the m.4216 T > C polymorphism could be responsible., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A progressive volitional cycling test is useful in determining exercise prescription in populations with cardiovascular and metabolic diseases. However, little is known about the association between heart rate during this test and endothelial dysfunction (EDys) parameters in hypertensive (HTN) patients., Objective: To investigate the association between EDys markers (flow-mediated dilation [FMD], pulse wave velocity of the brachial artery [PWVba], and carotid-intima media thickness [cIMT]) and heart rate during a cycling test in HTN adults. A secondary aim was to characterize cardiovascular, anthropometric, and body composition outcomes in this population., Methods: This was a descriptive clinical study in which adults (men and women) were assigned to one of three groups: HTN, elevated blood pressure (Ele), or a normotensive control group (CG), and completed a progressive cycling test. The primary outcomes were FMD, PWVba, cIMT, and heart rate (HR) at 25-50 watts (HR 25-50 ), 50-100 watts (HR 50-100 ), and 75-150 watts (HR 75-150 ) of the Astrand test. Secondary outcomes included body mass index (BMI), waist circumference, body fat percentage (BF%), skeletal muscle mass (SMM), resting metabolic rate (RMR), and estimated body age, as measured by a bio-impedance digital scale., Results: Analyses of the associations between FMD, PWV, and HR 25-50 , HR 50-100 , and HR 75-150 watts revealed no significant association in the HTN, Ele, and CG groups. However, a significant association was found between cIMT and HR 75-150 watts in the HTN group (R 2 47.1, β -0.650, p = 0.038). There was also a significant trend ( p = 0.047) towards increasing PWVba in the CG, Ele, and HTN groups., Conclusion: Heart rate during a progressive cycling test is associated with the EDys parameters cIMT in HTN patients, with particularly strong predictive capacity for vascular parameters in the second and third stages of the Astrand exercise test compared to normotensive control.

Introduction: There is evidence that the percentage of adolescents that practice testicular self-examination is low., Objective: To assess the short-term and long-term (6 months) impact in male adolescents of an educational intervention on the knowledge of testicular self-examination and attitude toward it., Methods: We conducted a quasi-experimental pre-test post-test study in male adolescents. A questionnaire was validated to assess knowledge on testicular self-examination and attitudes towards it (awareness, intentions, and behaviour). The educational intervention was group-based and consisted in an instructional talk with the aid of diagrams and brochures. The questionnaire was administered before and after the intervention. A follow-up was scheduled 6 months later, and the talk was delivered again, with administration of the questionnaire before and after., Results: The study included 139 adolescents with a median age of 14 years. We found an improvement in knowledge (18.3% vs 78.9%; P = 0.02) and attitude (5.6% vs 53.5%; P = 0.02) after the initial intervention. At the 6-month follow-up (n=98), there was no change in knowledge (87.0% vs 93.0%; P = 0.671), but attitude improved after the second intervention (58.0% vs 78.0%; P = 0.009)., Conclusion: An educational intervention on testicular self-examination improved the proportion of adolescents with an adequate attitude (5.6% vs 53.5%) and adequate knowledge (18.3% vs 78.9%). The repetition of the intervention at 6 months increased the proportion of adolescents with an adequate attitude (53.5% vs 86.4%)., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Heredity of familial hypercholesterolemia (FH) can present as a dominant monogenic disorder of polygenic origin or with no known genetic cause. In addition, the variability of the symptoms among individuals or within the same families evidence the potential contribution of additional factors than monogenic mutations that could modulate the development and severity of the disease. In addition, statins, the lipid-lowering drugs which constitute the first-line therapy for the disease, cause associated muscular symptoms in a certain number of individuals. Here, we analyze the evidence of the mitochondrial genetic variation with a special emphasis on the role of CoQ 10 to explain this variability found in both disease symptoms and statins side effects. We propose to use mtDNA variants and copy numbers as markers for the cardiovascular disease development of FH patients and to predict potential statin secondary effects and explore new mechanisms to identify new markers of disease or implement personalized medicine strategies for FH therapy.

The study aimed to evaluate the effects of ensiling length, storage temperature, and its interaction with crude protein (CP) levels in sorghum−soybean forage mixtures on in vitro rumen fermentation and post-ruminal digestibility of nutrients. The dietary treatments consisted of fresh forages (d 0) and silages of sorghum and soybean stored indoors or outdoors for 75 and 180 d with additional ingredients to make two dietary CP levels, 90 and 130 g/kg dry matter (DM) and a forage-to-concentrate ratio of 80 to 20. An in vitro procedure was conducted using the ANKOM RF technique to study rumen fermentation. The dietary treatments were incubated in duplicate for 8 and 24 h in three runs. After each incubation time, in vitro rumen fermentation parameters were measured, and the protozoa population was counted using a microscope. Post-ruminal digestibility was determined using the pepsin and pancreatic solubility procedure. Cumulative gas production (GP) increased quadratically with ensiling length (8 h, p < 0.01; 24 h, p = 0.02), and the GP differed between CP levels at both incubation times (p < 0.01). However, total short-chain fatty acid (SCFA) concentrations in rumen inoculum increased quadratically with ensiling length (p < 0.01; for both incubation times), and interaction between ensiling length and CP levels was observed in proportions of acetate and propionate after 24 h of incubation (p < 0.01; for both incubation times). Similarly, an interaction between ensiling length and CP levels was found in the proportion of valerate after 24 h of incubation (p < 0.01). There was a quadratic response to ensiling length in the NH4−N concentration after 8 h (p < 0.01) and 24 h (p < 0.05), and the CP level also differed (p < 0.01) at both incubation times. The ciliate protozoa count after 24 h was higher in low CP diets than in high CP diets (p = 0.04). The amount of CP in the undegraded substrate at both incubation times differed between CP levels (p < 0.01; for both incubation times). An interaction effect between ensiling length and storage temperature after 8 h (p = 0.02) and 24 h (p < 0.01) was observed for intestinal CP digestibility. The effect of CP levels on intestinal CP digestibility differed after 8 h (p < 0.01) and 24 h (p < 0.01). In conclusion, increasing ensiling length beyond 75 d reduced CP digestibility, and additional CP inclusion did not ameliorate this.

Purpose: To evaluate cardiac function in mechanically ventilated patients with COVID-19., Materials and Methods: Prospective, cross-sectional multicenter study in four university-affiliated hospitals in Chile. All consecutive patients with COVID-19 ARDS requiring mechanical ventilation admitted between April and July 2020 were included. We performed systematic transthoracic echocardiography assessing right and left ventricular function within 24 h of intubation., Results: 140 patients aged 57 ± 11, 29% female were included. Cardiac output was 5.1 L/min [IQR 4.5-6.2] and 86% of the patients required norepinephrine. ICU mortality was 29% (40 patients). Fifty-four patients (39%) exhibited right ventricle dilation out of whom 20 patients (14%) exhibited acute cor pulmonale (ACP). Eight out of the twenty patients with ACP exhibited pulmonary embolism (40%). Thirteen patients (9%) exhibited left ventricular systolic dysfunction (ejection fraction <45%). In the multivariate analysis acute cor pulmonale and PaO 2 /FiO 2 ratio were independent predictors of ICU mortality., Conclusions: Right ventricular dilation is highly prevalent in mechanically ventilated patients with COVID-19 ARDS. Acute cor pulmonale was associated with reduced pulmonary function and, in only 40% of patients, with co-existing pulmonary embolism. Acute cor pulmonale is an independent risk factor for ICU mortality., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The Hitnü indigenous people live in precarious sanitary conditions, with food insecurity and being victims of sociopolitical violence in Arauca, Colombia. In addition, it is possible that they may be affected by exposure to hydrocarbons found in oil. Objective: To identify the health outcomes of morbidity and mortality profiles of the Hitnü people that could be associated with the exposure to crude oil. Materials and methods: A cross-sectional study was carried out with Hitnü indigenous people, during February and March, 2021, time of drought. A household questionnaire was applied, and one individual to collect data from the environment around the house, occupations and other activities, as well as data from sociodemographic, signs, symptoms, and findings of a medical examination. The potential association with hydrocarbons was explored considering three groups: inhabitants in Arauca city, Aspejaná reserve (not exposed), and San José del Lipa and La Vorágine reserves (exposed by the Ele river and tributaries). With free listings, causes of death were explored. The study incorporated a rigorous intercultural management in all its components. Results: A total of 576 indigenous people from 16 settlements participated. The water consumed could serve as means of exposure to hydrocarbons. Health problems were very varied, including infectious and chronic diseases, malnutrition, and trauma. The masses on the neck were associated with residing in the ancestral reserves (PR = 3.86; CI95% 1.77-8.39), territories with potential exposure to crude-oil. The most relevant causes of death were homicide, tumors, and tuberculosis. Conclusion: For its possible association with exposure to hydrocarbons, it is a priority to start the intercultural study of lymphadenopathies in indigenous communities potentially exposed to crude oil.

Purpose: Critical care echocardiography is a fundamental tool in the hemodynamic evaluation of critically ill patients and prone position ventilation might limit its application. We aim to evaluate the feasibility of transthoracic echocardiography to assess different measurements performed in prone vs supine position in patients during COVID-19 pandemic to answer our research question: What is the feasibility of classic echocardiographic measurements in COVID-19 patients in prone position ventilation?, Methods: Patients with covid-19 admitted to ICUs in four academic hospitals with respiratory failure and on mechanical ventilation were evaluated with critical care echocardiography. The first ultrasound assessment was compared between prone and supine patients recording feasibility of several echocardiographic measurements, using Fisher's exact test complementing with Crombach's Alpha., Results: 139 patients were included. Sixty-eight (49%) were evaluated in prone position and seventy one (51%) in supine position. Most variables were highly feasible, left ventricular volumes and ejection fraction were more possible to obtain in prone position, while cardiac output was in supine position. Tricuspid regurgitation was the least feasible overall measurement., Conclusion: Prone position ultrasound achieved a high feasibility of measurements compared with supine ultrasound in critically ill patients with COVID-19 respiratory failure and on mechanical ventilation., Registration: Post hoc analysis of Echo-COVID study (NTC04628195, registered November 13, 2020, retrospectively registered)., (© 2022. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Background: Prone positioning is currently applied in time-limited daily sessions up to 24 h which determines that most patients require several sessions. Although longer prone sessions have been reported, there is scarce evidence about the feasibility and safety of such approach. We analyzed feasibility and safety of a continuous prolonged prone positioning strategy implemented nationwide, in a large cohort of COVID-19 patients in Chile., Methods: Retrospective cohort study of mechanically ventilated COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS), conducted in 15 Intensive Care Units, which adhered to a national protocol of continuous prone sessions  ≥ 48 h and until PaO 2 :FiO 2 increased above 200 mm Hg. The number and extension of prone sessions were registered, along with relevant physiologic data and adverse events related to prone positioning. The cohort was stratified according to the first prone session duration: Group A, 2-3 days; Group B, 4-5 days; and Group C, > 5 days. Multivariable regression analyses were performed to assess whether the duration of prone sessions could impact safety., Results: We included 417 patients who required a first prone session of 4 (3-5) days, of whom 318 (76.3%) received only one session. During the first prone session the main adverse event was grade 1-2 pressure sores in 97 (23.9%) patients; severe adverse events were infrequent with 17 non-scheduled extubations (4.2%). 90-day mortality was 36.2%. Ninety-eight patients (24%) were classified as group C; they exhibited a more severe ARDS at baseline, as reflected by lower PaO 2 :FiO 2 ratio and higher ventilatory ratio, and had a higher rate of pressure sores (44%) and higher 90-day mortality (48%). However, after adjustment for severity and several relevant confounders, prone session duration was not associated with mortality or pressure sores., Conclusions: Nationwide implementation of a continuous prolonged prone positioning strategy for COVID-19 ARDS patients was feasible. Minor pressure sores were frequent but within the ranges previously described, while severe adverse events were infrequent. The duration of prone session did not have an adverse effect on safety., (© 2022. The Author(s).)

We developed and standardized an efficient and cost-effective in-house RT-PCR method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, and other statistical parameters by different RT-qPCR methods including triplex, duplex, and simplex assays adapted from the initial World Health Organization- (WHO) recommended protocol. This protocol included the identification of the E envelope gene (E gene; specific to the Sarvecovirus genus), RdRp gene of the RNA-dependent RNA polymerase (specific for SARS-CoV-2), and RNase P gene as endogenous control. The detection limit of the E and the RdRp genes were 3.8 copies and 33.8 copies per 1 µL of RNA, respectively, in both triplex and duplex reactions. The sensitivity for the RdRp gene in the triplex and duplex RT-qPCR tests were 98.3% and 83.1%, respectively. We showed a decrease in sensitivity for the RdRp gene by 60% when the E gene acquired Ct values > 31 in the diagnostic tests. This is associated with the specific detection limit of each gene and possible interferences in the protocol. Hence, developing efficient and cost-effective methodologies that can be adapted to various health emergency scenarios is important, especially in developing countries or settings where resources are limited.