Microproteins encoded by noncanonical ORFs are a major source of tumor-specific antigens in a liver cancer patient meta-cohort.

The expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Here, we investigate if microproteins encoded by noncanonical open reading frames (ncORFs) are a relevant source of tumor-specific antigens. We analyze RNA sequencing data from 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue together with ribosome profiling and immunopeptidomics data. Combining human leukocyte antigen-epitope binding predictions and experimental validation experiments, we conclude that around 40% of the tumor-specific antigens in HCC are likely to be derived from ncORFs, including two peptides that can trigger an immune response in humanized mice. We identify a subset of 33 tumor-specific long noncoding RNAs expressing novel cancer antigens shared by more than 10% of the HCC samples analyzed, which, when combined, cover a large proportion of the patients. The results of the study open avenues for extending the range of anticancer vaccines.

Effects of guaranteed basic income interventions on poverty-related outcomes in high-income countries: A systematic review and meta-analysis.

Background: High-income countries offer social assistance (welfare) programs to help alleviate poverty for people with little or no income. These programs have become increasingly conditional and stringent in recent decades based on the premise that transitioning people from government support to paid work will improve their circumstances. However, many people end up with low-paying and precarious jobs that may cause more poverty because they lose benefits such as housing subsidies and health and dental insurance, while incurring job-related expenses. Conditional assistance programs are also expensive to administer and cause stigma. A guaranteed basic income (GBI) has been proposed as a more effective approach for alleviating poverty, and several experiments have been conducted in high-income countries to investigate whether GBI leads to improved outcomes compared to existing social programs. Objectives: The aim of this review was to conduct a synthesis of quantitative evidence on GBI interventions in high-income countries, to compare the effectiveness of various types of GBI versus "usual care" (including existing social assistance programs) in improving poverty-related outcomes. Search Methods: Searches of 16 academic databases were conducted in May 2022, using both keywords and database-specific controlled vocabulary, without limits or restrictions on language or date. Sources of gray literature (conference, governmental, and institutional websites) were searched in September 2022. We also searched reference lists of review articles, citations of included articles, and tables of contents of relevant journals in September 2022. Hand searching for recent publications was conducted until December 2022. Selection Criteria: We included all quantitative study designs except cross-sectional (at one timepoint), with or without control groups. We included studies in high income countries with any population and with interventions meeting our criteria for GBI: unconditional, with regular payments in cash (not in-kind) that were fixed or predictable in amount. Although two primary outcomes of interest were selected a priori (food insecurity, and poverty level assessed using official, national, or international measures), we did not screen studies on the basis of reported outcomes because it was not possible to define all potentially relevant poverty-related outcomes in advance. Data Collection and Analysis: We followed the Campbell Collaboration conduct and reporting guidelines to ensure a rigorous methodology. The risk of bias was assessed across seven domains: confounding, selection, attrition, motivation, implementation, measurement, and analysis/reporting. We conducted meta-analyses where results could be combined; otherwise, we presented the results in tables. We reported effect estimates as standard mean differences (SMDs) if the included studies reported them or provided sufficient data for us to calculate them. To compare the effects of different types of interventions, we developed a GBI typology based on the characteristics of experimental interventions as well as theoretical conceptualizations of GBI. Eligible poverty-related outcomes were classified into categories and sub-categories, to facilitate the synthesis of the individual findings. Because most of the included studies analyzed experiments conducted by other researchers, it was necessary to divide our analysis according to the "experiment" stage (i.e., design, recruitment, intervention, data collection) and the "study" stage (data analysis and reporting of results). Main Results: Our searches yielded 24,476 records from databases and 80 from other sources. After screening by title and abstract, the full texts of 294 potentially eligible articles were retrieved and screened, resulting in 27 included studies on 10 experiments. Eight of the experiments were RCTs, one included both an RCT site and a "saturation" site, and one used a repeated cross-sectional design. The duration ranged from one to 5 years. The control groups in all 10 experiments received "usual care" (i.e., no GBI intervention). The total number of participants was unknown because some of the studies did not report exact sample sizes. Of the studies that did, the smallest had 138 participants and the largest had 8019. The risk of bias assessments found "some concerns" for at least one domain in all 27 studies and "high risk" for at least one domain in 25 studies. The risk of bias was assessed as high in 21 studies due to attrition and in 22 studies due to analysis and reporting bias. To compare the interventions, we developed a classification framework of five GBI types, four of which were implemented in the experiments, and one that is used in new experiments now underway. The included studies reported 176 poverty-related outcomes, including one pre-defined primary outcome: food insecurity. The second primary outcome (poverty level assessed using official, national, or international measures) was not reported in any of the included studies. We classified the reported outcomes into seven categories: food insecurity (as a category), economic/material, physical health, psychological/mental health, social, educational, and individual choice/agency. Food insecurity was reported in two studies, both showing improvements (SMD = -0.57, 95% CI: -0.65 to -0.49, and SMD = -0.41, 95% CI: -0.57 to -0.26) which were not pooled because of different study designs. We conducted meta-analyses on four secondary outcomes that were reported in more than one study: subjective financial well-being, self-rated overall physical health, self-rated life satisfaction, and self-rated mental distress. Improvements were reported, except for overall physical health or if the intervention was similar to existing social assistance. The results for the remaining 170 outcomes, each reported in only one study, were summarized in tables by category and subcategory. Adverse effects were reported in some studies, but only for specific subgroups of participants, and not consistently, so these results may have been due to chance. Authors' Conclusions: The results of the included studies were difficult to synthesize because of the heterogeneity in the reported outcomes. This was due in part to poverty being multidimensional, so outcomes covered various aspects of life (economic, social, psychological, educational, agency, mental and physical health). Evidence from future studies would be easier to assess if outcomes were measured using more common, validated instruments. Based on our analysis of the included studies, a supplemental type of GBI (provided along with existing programs) may be effective in alleviating poverty-related outcomes. This approach may also be safer than a wholesale reform of existing social assistance approaches, which could have unintended consequences.

High Polymorphism Levels of De Novo ORFs in a Yoruba Human Population.

During evolution, new open reading frames (ORFs) with the potential to give rise to novel proteins continuously emerge. A recent compilation of noncanonical ORFs with translation signatures in humans has identified thousands of cases with a putative de novo origin. However, it is not known which is their distribution in the population. Are they universally translated? Here, we use ribosome profiling data from 65 lymphoblastoid cell lines from individuals of Yoruba origin to investigate this question. We identify 2,587 de novo ORFs translated in at least one of the cell lines. In line with their de novo origin, the encoded proteins tend to be smaller than 100 amino acids and encode positively charged proteins. We observe that the de novo ORFs are more polymorphic in the population than the set of canonical proteins, with a substantial fraction of them being translated in only some of the cell lines. Remarkably, this difference remains significant after controlling for differences in the translation levels. These results suggest that variations in the level translation of de novo ORFs could be a relevant source of intraspecies phenotypic diversity in humans.

Single-pixel imaging through non-homogeneous turbid media with adaptive illumination.

The presence of scattering media limits the quality of images obtained by optical systems. Single-pixel imaging techniques based on structured illumination are highly tolerant to the presence of scattering between the object and the sensor, but very sensitive when the scattering medium is between the light source and the object. This makes it difficult to develop single-pixel imaging techniques for the case of objects immersed in scattering media. We present what we believe to be a new system for imaging objects through inhomogeneous scattering media in an epi-illumination configuration. It works in an adaptive way by combining diffuse optical imaging (DOI) and single pixel imaging (SPI) techniques in two stages. First, the turbid media is characterized by projecting light patterns with an LED array and applying DOI techniques. Second, the LED array is programmed to project light only through the less scattering areas of the media, while simultaneously using a digital micromirror device (DMD) to project light patterns onto the target using Hadamard basis coding functions. With this adaptive technique, we are able to obtain images of targets through two different scattering media with better quality than using conventional illumination. We also show that the system works with fluorescent targets.

Light Scattering by Vitreous of Humans With Vision Degrading Myodesopsia From Floaters.

Purpose: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL. Methods: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission in vitro. Results: All indices of vitreous echodensity in vivo correlated positively with straylight at 0.5° (R = 0.708 to 0.775, P = 0.049 and 0.024, respectively). Straylight mean scatter index correlated with echodensity (R = 0.71, P = 0.04) and VQOL (R = -0.82, P = 0.0075). Dark-field measures in vitro correlated with degraded CS in vivo (R = -0.69, P = 0.04). VQOL correlated with straylight mean scatter index (R = -0.823, P = 0.012). Conclusions: Increased vitreous echodensity in vivo is associated with more straylight scattering in vitro, validating ultrasonography as a clinical surrogate for light scattering. Contrast sensitivity in vivo is more degraded in the presence of dark-field scattering in vitro and VQOL is decreased in patients whose vitreous has increased light scattering. These findings could form the basis for the development of optical corrections for VDM or support new laser treatments, as well as novel pharmacotherapy.

Towards a common European ethical and legal framework for conducting clinical research: the GATEKEEPER experience.

This paper examines the ethical and legal challenges encountered during the GATEKEEPER Project and how these challenges informed the development of a comprehensive framework for future Large-Scale Pilot (LSP) projects. GATEKEEPER is a LSP Project with 48 partners conducting 30 implementation studies across Europe with 50,000 target participants grouped into 9 Reference Use Cases. The project underscored the complexity of obtaining ethical approval across various jurisdictions with divergent regulations and procedures. Through a detailed analysis of the issues faced and the strategies employed to navigate these challenges, this study proposes an ethical and legal framework. This framework, derived from a comparative analysis of ethical application forms and regulations, aims to streamline the ethical approval process for future LSP research projects. By addressing the hurdles encountered in GATEKEEPER, the proposed framework offers a roadmap for more efficient and effective project management, ensuring smoother implementation of similar projects in the future.

KIS counteracts PTBP2 and regulates alternative exon usage in neurons.

Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.

Non-clinical toxicity and immunogenicity evaluation of a Plasmodium vivax malaria vaccine using Poly-ICLC (Hiltonol®) as adjuvant.

Malaria caused byPlasmodium vivaxis a pressing public health problem in tropical and subtropical areas.However, little progress has been made toward developing a P. vivaxvaccine, with only three candidates being tested in clinical studies. We previously reported that one chimeric recombinant protein (PvCSP-All epitopes) containing the conserved C-terminus of the P. vivax Circumsporozoite Protein (PvCSP), the three variant repeat domains, and aToll-like receptor-3 agonist,Poly(I:C), as an adjuvant (polyinosinic-polycytidylic acid, a dsRNA analog mimicking viral RNA), elicits strong antibody-mediated immune responses in mice to each of the three allelic forms of PvCSP. In the present study, a pre-clinical safety evaluation was performed to identify potential local and systemic toxic effects of the PvCSP-All epitopes combined with the Poly-ICLC (Poly I:C plus poly-L-lysine, Hiltonol®) or Poly-ICLC when subcutaneously injected into C57BL/6 mice and New Zealand White Rabbits followed by a 21-day recovery period. Overall, all observations were considered non-adverse and were consistent with the expected inflammatory response and immune stimulation following vaccine administration. High levels of vaccine-induced specific antibodies were detected both in mice and rabbits. Furthermore, mice that received the vaccine formulation were protected after the challenge with Plasmodium berghei sporozoites expressing CSP repeats from P. vivax sporozoites (Pb/Pv-VK210). In conclusion, in these non-clinical models, repeated dose administrations of the PvCSP-All epitopes vaccine adjuvanted with a Poly-ICLC were immunogenic, safe, and well tolerated.

Racial and Ethnic Minorities Underrepresented in Pain Management Guidelines for Total Joint Arthroplasty: A Meta-analysis.

BACKGROUND: Total joint arthroplasty aims to improve quality of life and functional outcomes for all patients, primarily by reducing their pain. This goal requires clinical practice guidelines (CPGs) that equitably represent and enroll patients from all racial/ethnic groups. To our knowledge, there has been no formal evaluation of the racial/ethnic composition of the patient population in the studies that informed the leading CPGs on the topic of pain management after arthroplasty surgery. QUESTIONS/PURPOSES: Using papers included in the 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines and comparing them with US National census data, we asked: (1) What is the representation of racial/ethnic groups in randomized controlled trials compared with their representation in the US national population? (2) Is there a relationship between the reporting of racial/ethnic groups and year of data collection/publication, location of study, funding source, or guideline section? METHODS: Participant demographic data (study year published, study type, guideline section, year of data collection, study site, study funding, study size, gender, age, and race/ethnicity) were collected from articles cited by this guideline. Studies were included if they were full text, were primary research articles conducted primarily within the United States, and if they reported racial and ethnic characteristics of the participants. The exclusion criteria included duplicate articles, articles that included the same participant population (only the latest dated article was included), and the following article types: systematic reviews, nonsystematic reviews, terminology reports, professional guidelines, expert opinions, population-based studies, surgical trials, retrospective cohort observational studies, prospective cohort observational studies, cost-effectiveness studies, and meta-analyses. Eighty-two percent (223 of 271) of articles met inclusion criteria. Our original literature search yielded 27 papers reporting the race/ethnicity of participants, including 24 US-based studies and three studies conducted in other countries; only US-based studies were utilized as the focus of this study. We defined race/ethnicity reporting as the listing of participants' race or ethnicity in the body, tables, figures, or supplemental data of a study. National census information from 2000 to 2019 was then used to generate a representation quotient (RQ), which compared the representation of racial/ethnic groups within study populations to their respective demographic representation in the national population. An RQ value greater than 1 indicates an overrepresented group and an RQ value less than 1 indicates an underrepresented group, relative to the US population. Primary outcome measures of RQ value versus time of publication for each racial/ethnic group were evaluated with linear regression analysis, and race reporting and manuscript parameters were analyzed with chi-square analyses. RESULTS: Two US-based studies reported race and ethnicity independently. Among the 24 US-based studies reporting race/ethnicity, the overall RQ was 0.70 for Black participants, 0.09 for Hispanic participants, 0.1 for American Indian/Alaska Natives, 0 for Native Hawaiian/Pacific Islanders, 0.08 for Asian participants, and 1.37 for White participants, meaning White participants were overrepresented by 37%, Black participants were underrepresented by 30%, Hispanic participants were underrepresented by 91%, Asian participants were underrepresented by 92%, American Indian/Alaska Natives were 90% underrepresented, and Native Hawaiian Pacific Islanders were virtually not represented compared with the US national population. On chi-square analysis, there were differences between race/ethnicity reporting among studies with academic, industry, and dual-supported funding sources (χ2 = 7.449; p = 0.02). Differences were also found between race/ethnicity reporting among US-based and non-US-based studies (χ2 = 36.506; p < 0.001), with 93% (25 of 27) of US-based studies reporting race as opposed to only 7% (2 of 27) of non-US-based studies. Finally, there was no relationship between race/ethnicity reporting and the year of data collection or guideline section referenced. CONCLUSION: The 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines provide evidence-based recommendations that reflect the current standards in orthopaedic surgery, but the studies upon which they are based overwhelmingly underenroll and underreport racial/ethnic minorities relative to their proportions in the US population. As these factors impact analgesic administration, their continued neglect may perpetuate inequities in outcomes after TJA. CLINICAL RELEVANCE: Our study demonstrates that all non-White racial/ethnic groups were underrepresented relative to their proportion of the US population in the 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines, underscoring a weakness in the orthopaedic surgery evidence base and questioning the overall external validity and generalizability of these combined CPGs. An effort should be made to equitably enroll and report outcomes for all racial/ethnic groups in any updated CPGs.

Anesthetic management of pulmonary artery banding in adult patient with single ventricle and uncorrected transposition of the great arteries.

Pulmonary artery banding (PAB) is a procedure mainly performed during the neonatal period as an initial stage to definitive palliative reconstruction, a scenario in which the criteria for banding adjustment are well defined. However, the indication for BAP in the adult is extraordinarily rare, even more in patients with single ventricle and unrepaired transposition of the great arteries (TGA), and there are no established criteria for banding adjustment. Due to the small number of these procedures, there is limited experience in their anesthetic management and complications. We describe a case of a 29-year-old patient diagnosed with a cyanotic congenital heart disease of double-inlet left ventricle with TGA and unrepaired mitral stenosis, who underwent to a hybrid procedure of PAB and enlargement of the communication between the two atria.

Head-mounted adaptive optics visual simulator.

Adaptive optics visual simulation is a powerful tool for vision testing and evaluation. However, the existing instruments either have fixed tabletop configurations or, being wearable, only offer the correction of defocus. This paper proposes a novel head-mounted adaptive optics visual simulator that can measure and modify complex ocular aberrations in real-time. The prototype is composed of two optical modules, one for the objective assessment of aberrations and the second for wavefront modulation, all of which are integrated into a wearable headset. The device incorporates a microdisplay for stimulus generation, a liquid crystal on silicon (LCoS) spatial light modulator for wavefront manipulation, and a Hartmann-Shack wavefront sensor. Miniature optical components and optical path folding structures, together with in-house 3D printed mounts and housing, were adapted to realize the compact size. The system was calibrated by characterizing and compensating the internal aberrations of the visual relay. The performance of the prototype was analyzed by evaluating the measurement and compensation of low-order and higher-order aberrations induced through trial lenses and phase masks in an artificial eye. The defocus curves for a simulated bifocal diffractive lens were evaluated in real eyes. The results show high accuracy while measuring and compensating for the induced defocus, astigmatism, and higher-order aberrations, whereas the MTF analysis shows post-correction resolution of up to 37.5 cycles/degree (VA 1.25). Moreover, the subjective test results show the defocus curves closely matched to a commercial desktop visual simulator.

Miastenia gravis y enfermedad de Alzheimer: una asociación a estudio / Association between myasthenia gravis and Alzheimer’s disease

Introducción La miastenia gravis (MG) y la enfermedad de Alzheimer (EA) son dos de las enfermedades neurológicas en cuya fisiopatología interviene la acetilcolina en distintos niveles. En la primera, la alteración de este neurotransmisor se produce en la unión neuromuscular, y en la segunda, en el sistema nervioso central. Objetivo Analizar la posible relación entre dichas patologías estudiando la prevalencia y la odds ratio de la EA dentro de los pacientes diagnosticados de MG con respecto a la prevalencia de EA en la población general. Pacientes y métodos Se han examinado datos de las historias clínicas electrónicas del sistema de salud de Castilla-La Mancha utilizando el procesamiento de lenguaje natural a través de la plataforma clínica de inteligencia artificial Savana Manager?. Resultados Se ha identificado a 970.503 pacientes mayores de 60 años, de los que 1.028 tenían diagnóstico de MG. La proporción de pacientes con diagnóstico de EA dentro de este grupo (4,28%) es mayor que en el resto de la población (2,82%; p = 0,0047), con una odds ratio de 1,54 (intervalo de confianza al 95%: 1,13-2,08; p = 0,0051), sin que se encuentren diferencias significativas en el análisis bivariante del resto de los factores de riesgo para EA más importantes conocidos hasta ahora. Conclusiones Nuestros resultados sugieren que podría existir un aumento de la prevalencia de EA en pacientes con MG. (AU)

INTRODUCTION Myasthenia gravis (MG) and Alzheimer’s disease (AD) are two of the most important diseases where the dysregulation of acetylcholine activity plays a crucial role. In the first, this dysregulation happens at the level of the neu­romuscular junction and in the second, in the central nervous system (CNS). AIM To analyze the possible relationship between these two pathologies, analyzing the prevalence and the odds ratio of AD within patients previously diagnosed with MG. We will compare these data with respect to the prevalence of AD in the general population. PATIENTS AND METHODS We examined the data obtained by the electronic medical records of patients in the health care system of Castilla La Mancha using the Natural Language Process provided by a clinical platform of artificial intelligence known as the Savana Manager?. RESULTS We identified 970,503 patients over the age of 60 years, of which 1,028 were diagnosed with MG. The proportion of the patients diagnosed with AD within this group (4.28%) was greater than the rest of the population (2.82%) (p = 0,0047) with an odds ratio of 1.54 (confidence interval at 95% 1.13-2.08; p = 0.0051) without finding significant differences in the bivariate analysis for the rest of the most important actual known risk factors for AD. CONCLUSION. Our results suggest that there might be an increase in the prevalence of AD in patients previously diagnosed with MG. (AU)

Chromosome ends and the theory of marginotomy: implications for reproduction.

Telomeres are the protective structures located at the ends of linear chromosomes. They were first described in the 1930s, but their biology remained unexplored until the early 70s, when Alexey M. Olovnikov, a theoretical biologist, suggested that telomeres cannot be fully copied during DNA replication. He proposed a theory that linked this phenomenon with the limit of cell proliferation capacity and the "duration of life" (theory of marginotomy), and suggested a potential of telomere lenghthening for the prevention of aging (anti-marginotomy). The impact of proliferative telomere shortening on life expectancy was later confirmed. In humans, telomere shortening is counteracted by telomerase, an enzyme that is undetectable in most adult somatic cells, but present in cancer cells and adult and embryonic stem and germ cells. Although telomere length dynamics are different in male and female gametes during gametogenesis, telomere lengths are reset at the blastocyst stage, setting the initial length of the species. The role of the telomere pathway in reproduction has been explored for years, mainly because of increased infertility resulting from delayed childbearing. Short telomere length in ovarian somatic cells is associated to decreased fertility and higher aneuploidy rates in embryos. Consequently, there is a growing interest in telomere lengthening strategies, aimed at improving fertility. It has also been observed that lifestyle factors can affect telomere length and improve fertility outcomes. In this review, we discuss the implications of telomere theory in fertility, especially in oocytes, spermatozoa, and embryos, as well as therapies to enhance reproductive success.

Optimization of a rapid method for screening drugs in blood by liquid chromatography tandem mass spectrometry.

Objectives: In the recent years, liquid chromatography with tandem mass spectrometry has gained popularity in laboratories. This technique has a higher specificity, detects different analytes from a single specimen, measures analytes in distinct matrices, and substantially reduce analytical interference, with respect to immunoassay. The processing and preparation of biological samples are crucial in chromatography. Interferences in blood testing are usually caused by the presence of phospholipids and proteins. The main objective of this study was to improve analytical processes for drug screening by LC-MS/MS using a novel blood sample preparation method based on protein precipitation and removal of phospholipids. Methods: An evaluation was performed of a new method for the preparation of blood samples based on protein precipitation and removal of phospholipids by LC-Q-q-LIT. Results: Limit of detection, limit of quantification and measurement range were determined for 56 molecules. The results of 11 cases were compared with those obtained using standard blood collection methods and instruments. Conclusions: The novel blood preparation and testing method based on LC-Q-q-LIT, a more sensitive technique, has demonstrated to yield comparable results to traditional methods. In addition, this new technique reduces turnaround time and costs.

Dietary Diversity and Its Association with Diet Quality and Health Status of European Children, Adolescents, and Adults: Results from the I.Family Study.

Dietary diversity (DD) plays a crucial role in fostering high-quality diets, but its association with health outcomes, particularly body adiposity and non-communicable diseases (NCDs), is inconsistent. This may be due to a lack of a standardized method for estimating DD. Our study investigates the association between two DD indices, namely the dietary diversity score (DDS) and food variety score (FVS), and anthropometric measures, biochemical parameters, and diet quality in a large population sample from the I.Family study across research centers in eight European countries. In our cross-sectional analysis of 3035 participants, DDSs varied among countries, with a higher prevalence in the third DDS tertile among those with higher education. DDS showed a positive association with diet quality across all age groups. Higher DDS tertile individuals showed increased fiber, fruit, and vegetable intake, greater meal frequency, and lower ultra-processed food consumption. No relevant biochemical differences were observed across DDS tertiles, and a higher DDS was associated with lower overweight/obesity prevalence only in adults. No significant associations were found with FVS. Our findings emphasize the need to consider food groups for a more accurate estimation of diet quality. This aligns with studies suggesting DDS alone is not an independent risk factor for obesity in children and adolescents. Public health programs should prioritize food diversity to promote improved nutrition and overall well-being in communities.

Predictors of Preexposure Prophylaxis Eligibility among Pregnant People with Opioid Use Disorder.

OBJECTIVE: We seek to evaluate risk factors for eligibility for preexposure prophylaxis (PrEP) among pregnant people with opioid use disorder (OUD). STUDY DESIGN: This is a single-site retrospective cohort study of pregnant people admitted for management of OUD at an urban, tertiary care center from 2013 to 2022. PrEP eligibility was defined based on (1) modified American College of Obstetricians and Gynecologists' (ACOG) 2014 criteria: diagnosis of a sexually transmitted infection (STI), engagement in transactional sex work, intravenous drug use (IVDU), or incarceration and (2) modified 2021 Centers for Disease Control (CDC) criteria: diagnosis of bacterial STI (e.g., gonorrhea or syphilis) or transactional sex work. Risk factors associated with PrEP eligibility were evaluated using chi- square or Fischer's exact tests for categorical variables and t-tests or Wilcoxon rank-sum tests for continuous variables. Multivariable regression was used to control for confounding covariates, defined as p < 0.10 on bivariate analysis. p < 0.05 was used to indicate statistical significance. RESULTS: A total of 132 individuals met inclusion criteria, of whom 101 (76.5%) were deemed eligible for PrEP by meeting one or more modified 2014 ACOG criteria: 42 (31.8%) were incarcerated or had one or more STIs, while 30 (22.7%) endorsed engaging in transactional sex work and 68 (58.6%) endorsed IVDU. Using modified 2021 CDC criteria, 37 (28%) met PrEP eligibility, with 12 (9.1%) diagnosed specifically with a bacterial STI and 30 (22.7%) engaging in transactional sex work. Only comorbid psychiatric illness was associated with an increased risk for PrEP eligibility based on 2014 criteria, which persisted after controlling for maternal race/ethnicity (aRR 1.52, 95% confidence interval [CI] 1.24-1.86), and 2021 criteria, which persisted after controlling for nulliparity (aRR 2.12, 95% CI 1.30-3.57). CONCLUSION: A significant number of pregnant people with OUD meet one or more criteria for PrEP, with comorbid psychiatric conditions increasing the risk of meeting criteria. KEY POINTS: · Comorbid psychiatric illness is significantly associated with high risk of PrEP eligibility.. · A large proportion of pregnant individuals with active OUD meet criteria for PrEP prescribing.. · Risk-based screening algorithms for PrEP eligibility have limitations..

Comparing Mitochondrial Activity, Oxidative Stress Tolerance, and Longevity of Thirteen Ascomycota Yeast Species.

Aging is characterized by a number of hallmarks including loss of mitochondrial homeostasis and decay in stress tolerance, among others. Unicellular eukaryotes have been widely used to study chronological aging. As a general trait, calorie restriction and activation of mitochondrial respiration has been proposed to contribute to an elongated lifespan. Most aging-related studies have been conducted with the Crabtree-positive yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and with deletion collections deriving from these conventional yeast models. We have performed an unbiased characterization of longevity using thirteen fungi species, including S. cerevisiae and S. pombe, covering a wide range of the Ascomycota clade. We have determined their mitochondrial activity by oxygen consumption, complex IV activity, and mitochondrial redox potential, and the results derived from these three methodologies are highly overlapping. We have phenotypically compared the lifespans of the thirteen species and their capacity to tolerate oxidative stress. Longevity and elevated tolerance to hydrogen peroxide are correlated in some but not all yeasts. Mitochondrial activity per se cannot anticipate the length of the lifespan. We have classified the strains in four groups, with members of group 1 (Kluyveromyces lactis, Saccharomyces bayanus and Lodderomyces elongisporus) displaying high mitochondrial activity, elevated resistance to oxidative stress, and elongated lifespan.

Upscaling the effect of traits in response to drought: The relative importance of safety-efficiency and acquisitive-conservation functional axes.

We tested the idea that functional trade-offs that underlie species tolerance to drought-driven shifts in community composition via their effects on demographic processes and subsequently on shifts in species' abundance. Using data from 298 tree species from tropical dry forests during the extreme ENSO-2015, we scaled-up the effects of trait trade-offs from individuals to communities. Conservative wood and leaf traits favoured slow tree growth, increased tree survival and positively impacted species abundance and dominance at the community-level. Safe hydraulic traits, on the other hand, were related to demography but did not affect species abundance and communities. The persistent effects of the conservative-acquisitive trade-off across organizational levels is promising for generalization and predictability of tree communities. However, the safety-efficient trade-off showed more intricate effects on performance. Our results demonstrated the complex pathways in which traits scale up to communities, highlighting the importance of considering a wide range of traits and performance processes.

The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer.

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment and can result in complete remissions even at advanced stages of the disease. However, only a small fraction of patients respond to the treatment. To better understand which factors drive clinical benefit, we have generated whole exome and RNA sequencing data from 27 advanced urothelial carcinoma patients treated with anti-PD-(L)1 monoclonal antibodies. We assessed the influence on the response of non-synonymous mutations (tumor mutational burden or TMB), clonal and subclonal mutations, neoantigen load and various gene expression markers. We found that although TMB is significantly associated with response, this effect can be mostly explained by clonal mutations, present in all cancer cells. This trend was validated in an additional cohort. Additionally, we found that responders with few clonal mutations had abnormally high levels of T and B cell immune markers, suggesting that a high immune cell infiltration signature could be a better predictive biomarker for this subset of patients. Our results support the idea that highly clonal cancers are more likely to respond to ICI and suggest that non-additive effects of different signatures should be considered for predictive models.