Search

Abstract Integrating diverse types of biological data is essential for a holistic understanding of cancer biology, yet it remains challenging due to data heterogeneity, complexity, and sparsity. Addressing this, our study introduces an unsupervised deep learning model, MOSA (Multi-Omic Synthetic Augmentation), specifically designed to integrate and augment the Cancer Dependency Map (DepMap). Harnessing orthogonal multi-omic information, this model successfully generates molecular and phenotypic profiles, resulting in an increase of 32.7% in the number of multi-omic profiles and thereby generating a complete DepMap for 1523 cancer cell lines. The synthetically enhanced data increases statistical power, uncovering less studied mechanisms associated with drug resistance, and refines the identification of genetic associations and clustering of cancer cell lines. By applying SHapley Additive exPlanations (SHAP) for model interpretation, MOSA reveals multi-omic features essential for cell clustering and biomarker identification related to drug and gene dependencies. This understanding is crucial for developing much-needed effective strategies to prioritize cancer targets.

Abstract Prostate cancer exhibits high prevalence and accounts for a high number of cancer-related deaths. The discovery and characterization of molecular determinants of aggressive prostate cancer represents an active area of research. The Immediate Early Response (IER) family of genes, which regulate Protein Phosphatase 2A (PP2A) activity, has emerged among the factors that influence cancer biology. Here, we show that the less studied member of this family, Immediate Early Response 5 like (IER5L), is upregulated in aggressive prostate cancer. Interestingly, the upregulation of IER5L expression exhibits a robust association with metastatic disease in prostate and is recapitulated in other cancer types. In line with this observation, IER5L silencing reduces foci formation, migration and invasion ability in a variety of human and murine prostate cancer cell lines. In vivo, using zebrafish and immunocompromised mouse models, we demonstrate that IER5L-silencing reduces prostate cancer tumor growth, dissemination, and metastasis. Mechanistically, we characterize the transcriptomic and proteomic landscapes of IER5L-silenced cells. This approach allowed us to identify DNA replication and monomeric G protein regulators as downstream programs of IER5L through a pathway that is consistent with the regulation of PP2A. In sum, we report the alteration of IER5L in prostate cancer and beyond and provide biological and molecular evidence of its contribution to tumor aggressiveness.

Urinary dysfunction encompasses a wide range of syndromes and symptoms and is highly prevalent among the adult population. Urinary issues have been associated with psychosocial sequelae. The interplay between psychosocial comorbidity and symptoms impacts perceived severity and treatment success. While the correlation has been described in the literature, much remains unknown. This article describes the psychosocial impact on conditions such as overactive bladder (OAB), neurogenic lower urinary tract dysfunction (LUTD), recurrent urinary tract infection (UTI), and interstitial cystitis/bladder pain syndrome (IC/BPS). This article also highlights potential interventions for patients afflicted with both urinary disorders and psychosocial comorbidity to improve overall treatment success.

Abstract A better understanding of the relative roles of internal climate variability and external contributions, from both natural (solar, volcanic) and anthropogenic greenhouse gas forcing, is important to better project future hydrologic changes. Changes in the evaporative demand play a central role in this context, particularly in tropical areas characterized by high precipitation seasonality, such as the tropical savannah and semi-desertic biomes. Here we present a set of geochemical proxies in speleothems from a well-ventilated cave located in central-eastern Brazil which shows that the evaporative demand is no longer being met by precipitation, leading to a hydrological deficit. A marked change in the hydrologic balance in central-eastern Brazil, caused by a severe warming trend, can be identified, starting in the 1970s. Our findings show that the current aridity has no analog over the last 720 years. A detection and attribution study indicates that this trend is mostly driven by anthropogenic forcing and cannot be explained by natural factors alone. These results reinforce the premise of a severe long-term drought in the subtropics of eastern South America that will likely be further exacerbated in the future given its apparent connection to increased greenhouse gas emissions.

Abstract Background Carcinoma of unknown primary (CUP) remains an important tumor entity and a disproportionate cause of cancer mortality. Little is known about the contemporary clinical characteristics, treatment patterns, and outcomes of CUP patients based on updated international classification guidelines. We evaluated a contemporary CUP cohort to provide insight into current clinical practice and the impact of tissue of origin assignment, site‐specific and empirical therapy in a real‐world setting. Methods We conducted a retrospective cohort study of CUP patients, as defined by the updated European Society of Medical Oncology (ESMO) 2023 guidelines, across three tertiary referral centers in Australia between 2015 and 2022. We analyzed clinical characteristics, treatment patterns, and survival outcomes using the Kaplan–Meier method and Cox regression proportional hazard model between favorable and unfavorable risk groups. Results We identified a total of 123 CUP patients (n = 86 unfavorable, n = 37 favorable risk as per the 2023 ESMO guidelines). Sixty‐four patients (52%) were assigned a tissue of origin by the treating clinician. Median progression free survival (PFS) was 6.8 (95% confidence interval (CI) 5.1–12.1) months and overall survival (OS) 10.2 (95% CI 6.0–18.5) months. Unfavorable risk (hazard ratio [HR] 2.9, p = 0.006), poor performance status (HR 2.8, p

Aims: Compensatory coping, or maladaptive alterations in behavior with the intention of preventing or managing symptoms, is increasingly being explored as a key factor in how people respond to bladder conditions. Preliminary investigations have identified relations between coping behaviors and psychological distress in urologic conditions, including interstitial cystitis/bladder pain syndrome (IC/BPS). However, previous explorations of coping have not accounted for heterogeneity in coping behaviors or addressed the likelihood that some coping behaviors may be more adaptive than others. This study sought to examine how two specific types of coping behaviors, primary control coping and disengaged coping, are related to distress and symptoms in IC/BPS, and to explore the potential role of pain phenotype in this relationship. Materials and Methods: A secondary data analysis was conducted with a large community data set (N = 677 women with IC/BPS) and employed descriptive and inferential statistics to characterize coping patterns and explore novel predictors of distress. Results: Results indicated that almost all participants engaged in at least one compensatory coping behavior within the last week. Both types of coping behaviors correlated with psychological symptoms, and when controlling for relevant clinical variables (i.e., age and severity of urinary symptoms), disengaged coping behaviors were significantly associated with psychological distress. Further, the addition of pain phenotype to multiple regression models resulted in a more effective predictive model when considering the relation between coping behaviors and depression. Conclusions: By investigating more deeply the relationship between coping and distress, understanding of potential risk factors and mechanisms is increased, offering valuable insights for intervention strategies for IC/BPS patients. [ABSTRACT FROM AUTHOR]

Background: Overactive bladder (OAB) affects one in six adults in Europe and the United States and impairs the quality of life of millions of individuals worldwide. When conservative management fails, third‐line treatments including tibial neuromodulation (TNM) is often pursued. TNM has traditionally been accomplished percutaneously in clinic. Objective: A minimally invasive implantable device activated by a battery‐operated external wearable unit has been developed for the treatment of urgency urinary incontinence (UUI), mitigating the burden of frequent clinic visits and more invasive therapies that are currently commercially available. Methods: A prospective, multicenter, single‐arm, open‐label, pivotal study evaluated the safety and effectiveness of the device in adult females with UUI (i.e., wet OAB) (BlueWind Implantable Tibial Neuromodulation [iTNM] system; IDE number #G200013; NCT03596671). Results with the device were previously published under the name RENOVA iStim, which has been since renamed as the Revi™ System. Approximately 1‐month post‐implantation of the device, participants delivered therapy at their convenience and completed a 7‐day voiding diary before visits 6‐ and 12‐months post‐treatment initiation. The primary efficacy and safety endpoints were the proportion of responders to therapy (≥ 50% improvement on average number of urgency‐related incontinence episodes) and incidence of adverse events from implantation to 12‐month post‐activation. Results: A total of 151 participants, mean age 58.8 (SD: 12.5), were implanted; 144 and 140 completed the 6‐ and 12‐month visits, respectively. The participants demonstrated mean baseline of 4.8 UUI/day (SD 2.9) and 10 voids/day (SD 3.3). Six and 12‐months post‐activation, 76.4% and 78.4% of participants, respectively, were responders to therapy in an intent‐to‐treat analysis. Of the 139 participants with completed 12‐month diaries, 82% were responders, 50% were classified as "dry" (on at least 3 consecutive diary days), and 93.5% of participants reported that their symptoms improved. No implanted participant experienced an SAE related to the procedure or device. Conclusions: iTNM, delivered and powered by a patient‐controlled external wearable communicating with an implant, demonstrated clinically meaningful and statistically significant improvement in UUI symptoms and a high safety profile. This therapy highlights the value of patient‐centric therapy for the treatment of UUI. [ABSTRACT FROM AUTHOR]

There continues to be considerable research on the adverse effect of photovoltaic (PV) panel temperature on its power production. Aside from attempting to minimize heating up of the panel by providing heat sinks and the like, several studies looked into using the unconverted heat as an input to a Thermoelectric generator residing below the PV panel and questionably generating additional power. Using simple steady energy balances, simplified steady thermal models of PV panels, individually or thermally-in-series coupled to heat engines are studied. The nodal energy equations are solved to ascertain resulting temperatures and efficiencies under different insolations. After establishing a simplified model for a lone PV panel, a PV panel with an added thermoelectric generator attached to its back side is studied. Solving the associated steady energy equations, the photovoltaic-thermoelectric system is found to have a smaller than expected advantage in net power, no more than 4.15 %, over the lone PV panel and then only at high insolation's and concentrations. The implication of this work is that hybridizing a PV panel by bottoming it with a thermoelectric generator is not quite attractive except possibly at higher solar concentrations. The margin to Increase the overall efficiency of a photovoltaic-thermoelectric hybrid by improving the thermoelectric-figure-of-merit does not appear to be significant although further consideration of thermoelectric materials may be required. [ABSTRACT FROM AUTHOR]

The newest generation of psychologists in the United States will serve the most diverse public in recorded history. Although some health service psychology training programs have systematically integrated antiracist initiatives into their training curriculums and supervision, many have not. There is an urgent call to increase antiracist training in health psychology as the field navigates the dismantling of oppressive systems. This article details how an American Psychological Association (APA)-accredited pediatric psychology internship training program has intentionally addressed pipeline problems related to the recruitment and retention of diverse trainees over 10 years. It outlines the steps taken to create a diversity mission and vision statement, cultivate a training culture that elevates contributions of individuals from traditionally underrepresented groups, emphasize antiracism in recruitment materials, and develop an experiential, intersectional, and antiracist cultural humility curriculum for predoctoral interns. Quantitative ratings and qualitative feedback from trainees about the experiential curriculum and outcomes related to recent recruitment and retention are described. This article clearly demonstrates how an investment of multiple antiracist training resources within a training program across several years can result in the recruitment and retention of diverse trainees, a more inclusive and protective training culture, and the advancement of antiracism within the field of health service psychology. Public Significance Statement: Predoctoral internship training program leadership report wanting strategies to improve the recruitment and retention of diverse trainees, innovative approaches to cultivating more inclusive training cultures, and the advancement of antiracist action within the field of health service psychology. This article outlines multiple antiracist and cultural humility training initiatives within a predoctoral internship training program across several years, associated trainee-related outcomes, and recommendations for implementation. [ABSTRACT FROM AUTHOR]

Urinary dysfunction encompasses a wide range of syndromes and symptoms and is highly prevalent among the adult population. Urinary issues have been associated with psychosocial sequelae. The interplay between psychosocial comorbidity and symptoms impacts perceived severity and treatment success. While the correlation has been described in the literature, much remains unknown. This article describes the psychosocial impact on conditions such as overactive bladder (OAB), neurogenic lower urinary tract dysfunction (LUTD), recurrent urinary tract infection (UTI), and interstitial cystitis/bladder pain syndrome (IC/BPS). This article also highlights potential interventions for patients afflicted with both urinary disorders and psychosocial comorbidity to improve overall treatment success. [ABSTRACT FROM AUTHOR]

Background: The United States currently faces a public health crisis with regarding to antibiotic‐resistant bacteria, and new urinary tract infection (UTI) diagnostics are needed. Women with recurrent UTI (rUTI) and complicated UTI (cUTI) are at particular risk given their complexity and the paucity of adequate testing modalities. The standard urine culture (SUC) is the cornerstone for diagnosis, but it has many shortcomings. These pitfalls lead to dissatisfaction and frustration among women afflicted with rUTI and cUTI, as well as overuse of antibiotics. One innovation is PCR UTI testing, which has been shown to outperform SUC among symptomatic women. Aims: This article discusses UTI PCR testing, as well as a possible role in clinical practice. Materials and Methods: Published literature was reviewed and summarized. Results: Management of rUTI and cUTI is complex, and providers should have all diagnostics available to facilitate providing optimal care. Urine PCR testing faces reimbursement issues despite fulfilling clinical indication parameters as described by insurance companies. Discussion: The role of UTI PCR testing remains unclear. Reimbursement issues have led to underuse and limited real‐world outcomes reinforcing benefit. Conclusion: This study proposes an algorithm for PCR testing among women with rUTI and cUTI. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to investigate the impact of reduction of salt content (from 1.5 to 0.75%), the technique of mixing half of the salt content with animal fat, and the salt particle size on the instrumental texture, cooking losses, diameter reduction, overall liking, and sensory characteristics of burgers. The results showed that regardless of the types of micronized salt (MS

El objetivo fue evaluar la mejora en la gestión de la calidad e inocuidad en la empresa América Alimentos S.R.L., a partir de la implementación del esquema FSSC 22000+Quality en la producción de arroz fortificado destinado a programas sociales. En primera instancia, se formó un equipo de trabajo multidisciplinario comprometido con la mejora continua, luego se definieron los objetivos y alcance del sistema. A partir del análisis situacional inicial, se plantearon los escenarios estratégicos para la empresa. Asimismo, se identificaron los riesgos y establecieron acciones de mitigación, con foco en la actualización de los programas pre requisitos y establecimiento del plan HACCP. Resultado de la implementación, se verifica una reducción del 40% en productos no conformes, un incremento del 25% en eficiencia de producción y una disminución del 15% en microorganismos patógenos. Además, se logró un análisis costo-beneficio favorable con un retorno de S/ 2,88 y un VAN de S/ 121 065,26. El esquema FSSC 22000+Quality representa un paso significativo hacia la mejora de la gestión de calidad e inocuidad, puesto que, es una estrategia efectiva para obtener productos seguros y de calidad.

Abstract The red-legged partridge (Alectoris rufa) is a popular game bird species that is in decline in several regions of southwestern Europe. The introduction of farm-reared individuals of a distinct genetic make-up in hunting reserves can result in genetic swamping of wild populations. Here we present a de novo genome assembly for the red-legged partridge based on long-read sequencing technology. The assembled genome size is 1.14 Gb, with scaffold N50 of 37.6 Mb and contig N50 of 29.5 Mb. Our genome is highly contiguous and contains 97.06% of complete avian core genes. Overall, the quality of this genome assembly is equivalent to those available for other close relatives such as the Japanese quail or the chicken. This genome assembly will contribute to the understanding of genetic dynamics of wild populations of red-legged partridges with releases of farm-reared reinforcements and to appropriate management decisions of such populations.

Abstract The red-legged partridge Alectoris rufa plays a crucial role in the ecosystem of southwestern Europe, and understanding its genetics is vital for conservation and management. Here we sequence, assemble, and annotate a highly contiguous and nearly complete version of its genome. This assembly encompasses 96.9% of the avian genes flagged as essential in the BUSCO aves_odb10 dataset. Moreover, we pinpointed RNA and protein-coding genes, 95% of which had functional annotations. Notably, we observed significant chromosome rearrangements in comparison to quail (Coturnix japonica) and chicken (Gallus gallus). In addition, a comparative phylogenetic analysis of these genomes suggests that A. rufa and C. japonica diverged roughly 20 million years ago and that their common ancestor diverged from G. gallus 35 million years ago. Our assembly represents a significant advancement towards a complete reference genome for A. rufa, facilitating comparative avian genomics, and providing a valuable resource for future research and conservation efforts for the red-legged partridge.

Abstract The quest for low-carbon alternatives to fossil fuels and the carbon emissions associated with the natural degradation of biomass have accelerated the development of biomass processing technologies. Microwave catalytic pyrolysis is emerging as a technology for efficient conversion of biomass into energy, fuels and chemicals. However, due to the inherent poor dielectric properties and complex composition of biomass, two main technical challenges faced by microwave catalytic pyrolysis of biomass are efficient heating of biomass and improving the selectivity of target products. Potential solutions involve the use of microwave absorbents and catalysts, respectively. This review begins by addressing the difficulty in balancing energy efficiency and conversion efficiency by introducing microwave absorbents that play a positive role in improving heating efficiency. The principle of microwave absorbents in assisting biomass heating is revealed, and the impacts of the microwave absorbent type (related to microwave properties and physical properties) and the additive amount on the heating effect and biomass pyrolysis product distribution are discussed. Subsequently, the search for catalysts applied in biomass microwave pyrolysis for modulation of product distribution is explored. Special attention has been paid to the catalysts with microwave absorption properties, including activated carbon, zeolites, some metal oxides and metal salts. In addition, the energy efficiency, economic feasibility, and environmental impacts of this processing technology utilizing microwave absorbents and catalysts are examined based on energy analysis, techno-economic assessment, and life cycle assessment. The current scale-up challenges of microwave catalytic pyrolysis of biomass and some potential solutions to enhance the commercial feasibility of this technology are also discussed. Finally, the review provides some future development directions of this technology.

Controlling postprandial hyperglycemia is considered as a viable prophylactic treatment for type 2 diabetes mellitus. A major strategy in decreasing postprandial glucose involves inhibition of the carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase. The aim of this study was to evaluate the hypoglycemic potential of almond hull extract in vitro and in vivo. The in vitro results showed that, among the 0 %, 30 %, 50 % and 80 % ethanol extracts of almond hull, the 50 % ethanol extracts demonstrated the most significant inhibition of digestive enzymes. With in vivo tests, the blood glucose concentration in the control rats increased sharply near the peak glucose level in 15 min, while the peak glucose level of rats loading the almond hull extract occurred in 30 min. Therefore, almond hull extract can reduce postprandial blood glucose levels and delay the time to peak by about 15 min, providing a sustained and gradual release of energy.

Costa Rica prohibits abortion except under narrow circumstances to save the pregnant person’s life. The country boasts historically strong support for social policy and human rights, while also presenting a complex and restrictive abortion access landscape. From September 2021 to March 2022, we conducted 23 interviews with obstetrician-gynecologist (OB/GYN) physicians, OB/GYN medical residents, and policy stakeholders to explore the socio-ecological influences on abortion access in Costa Rica. We sampled clinicians and policy stakeholders from the Universidad de Ciencias Médicas listserv through snowball sampling and conducted semi-structured in-depth interviews in Spanish. We identified limited access to comprehensive sexual health education, lack of support from interpersonal networks, inadequate provider knowledge and training, financial and migratory status, and both provider and community stigma as substantial barriers to abortion access. This study addresses a gap in published research around the social determinants of abortion in Costa Rica and sheds light on the attitudes and opinions of the medical and policy stakeholder communities about abortion access. The results highlight the need for expanded access to comprehensive sexual health education, abortion-related training for healthcare providers, and increased programming efforts, such as funding, outreach, and implementation, to ensure comprehensive reproductive health services are available and accessible, especially for vulnerable populations in Costa Rica.