Exploring the Relationship Between Anticipated Stigma and Community Shared Concerns about HIV on Defaulting from HIV Care in Rural South Africa.

Although stigma has been associated with people living with HIV defaulting from care, there is a gap in understanding the specific impact of individual stigma and community-level concern about HIV on defaulting. Methods: This is a secondary analysis of a unique dataset that links health facility-based medical records to a population-representative community survey conducted in 2018 in rural Mpumalanga province, South Africa. We used the parametric g-formula to estimate associations among individual anticipated stigma, low perceived community and local leader concern about HIV, and defaulting from care in the prior year. In addition, we estimated the population-level effects of intervening to reduce stigma and increase concern on defaulting. Results: Among 319 participants on treatment, 42 (13.2%) defaulted from care during the prior year. Anticipated stigma (risk ratio [RR] 1.22, 95% confidence interval [CI]: 0.72, 2.74), low perceived concern about HIV/AIDS from community leadership (RR 1.12, 95% CI 0.76, 3.38), and low shared concerns about HIV/AIDS in the community (RR 1.37; 95% CI 0.79, 3.07) were not significantly associated with default. Hypothetical population intervention effects to remove individual anticipated stigma and low community concerns yielded small reductions in default (~1% reduction). Conclusions: In this sample, we found limited impact of reducing anticipated stigma and increasing shared concern about HIV on retention in care. Future studies should consider the limitations of this study by examining the influence of other sources of stigma in more detail and assessing how perceptions of stigma and concern impact the full HIV testing and care cascade.

Large Language Models Diagnose Facial Deformity.

Purpose: This study examines the application of Large Language Models (LLMs) in diagnosing jaw deformities, aiming to overcome the limitations of various diagnostic methods by harnessing the advanced capabilities of LLMs for enhanced data interpretation. The goal is to provide tools that simplify complex data analysis and make diagnostic processes more accessible and intuitive for clinical practitioners. Methods: An experiment involving patients with jaw deformities was conducted, where cephalometric measurements (SNB Angle, Facial Angle, Mandibular Unit Length) were converted into text for LLM analysis. Multiple LLMs, including LLAMA-2 variants, GPT models, and the Gemini-Pro model, were evaluated against various methods (Threshold-based, Machine Learning Models) using balanced accuracy and F1-score. Results: Our research demonstrates that larger LLMs efficiently adapt to diagnostic tasks, showing rapid performance saturation with minimal training examples and reducing ambiguous classification, which highlights their robust in-context learning abilities. The conversion of complex cephalometric measurements into intuitive text formats not only broadens the accessibility of the information but also enhances the interpretability, providing clinicians with clear and actionable insights. Conclusion: Integrating LLMs into the diagnosis of jaw deformities marks a significant advancement in making diagnostic processes more accessible and reducing reliance on specialized training. These models serve as valuable auxiliary tools, offering clear, understandable outputs that facilitate easier decision-making for clinicians, particularly those with less experience or in settings with limited access to specialized expertise. Future refinements and adaptations to include more comprehensive and medically specific datasets are expected to enhance the precision and utility of LLMs, potentially transforming the landscape of medical diagnostics.

Spontaneous recovery from amblyopia following fellow eye vision loss: a systematic review and narrative synthesis.

BACKGROUND: The effectiveness of traditional amblyopia therapies is largely restricted to childhood. However, spontaneous recovery in adulthood is possible following vision loss in the fellow eye due to enucleation, injury, or disease. The twofold purpose of this study was (1) to define the incidence of recovery and (2) to elucidate the clinical features associated with greater amblyopic eye gains. METHODS: A systematic review of three databases yielded 24 reports containing 110 cases of patients ≥18 years old with unilateral amblyopia and vision-limiting fellow eye pathology. RESULTS: Our analysis revealed that 25 of 42 of adult patients (59.5%) gained ≥2 logMAR lines in the amblyopic eye after fellow eye vision loss. The degree of improvement is clinically meaningful (median, 2.6 logMAR lines). Recovery occurs within 12 months of initial loss of fellow eye vision. Regression analysis demonstrated that younger age, worse baseline visual acuity in the amblyopic eye, and worse vision in the fellow eye independently conferred greater gains in amblyopic eye visual acuity. Recovery occurs across amblyopia types and fellow eye pathologies, although disease entities affecting fellow eye retinal ganglion cells demonstrate shorter latencies to recovery. CONCLUSIONS: Amblyopia recovery after fellow eye injury demonstrates that the adult brain harbors the neuroplastic capacity for clinically meaningful recovery, which could potentially be harnessed by novel approaches to treat adults with amblyopia.

Addressing the unmet needs of women with breast cancer in Mexico: a non-randomised pilot study of the digital ePRO intervention.

OBJECTIVES: This study aimed to explore the acceptability, feasibility, usability, and preliminary effect of an electronic patient-reported outcome (ePRO) intervention for patients with breast cancer in Mexico. DESIGN: We conducted a multimethod non-randomised pilot study. We used a pre-test/post-test design for quantitative assessment of the intervention's effect on patients' supportive care needs and quality of life. We conducted in-depth interviews (IDIs) with participants and healthcare workers to explore the intervention's benefits and barriers and understand its feasibility. PARTICIPANTS: 50 women aged 20-75 diagnosed with stage I-III breast cancer were enrolled within 2 weeks of starting neoadjuvant or adjuvant treatment with chemotherapy or radiotherapy. We excluded illiterate women and those with visual impairment, cognitive disability or severe depression. IDIs were conducted with 18 participants and 10 healthcare providers. SETTING: Oncology services in three public hospitals of the Mexican Social Security Institute. INTERVENTION: The ePRO intervention consisted of a responsive web application for weekly symptom reporting combined with proactive follow-up by nurses guided by predefined clinical algorithms for 6 weeks. RESULTS: 50 women were enrolled out of 66 eligible patients approached (75.8%). All 50 completed the 4-week follow-up assessment (100% retention). Completion of the symptom registry declined from 100% in week 1 to 66% in week 6. Participants experienced decreases in supportive care needs and increased quality of life. The ePRO application was rated highly usable. Participants and health professionals both perceived intervention benefits. Drawbacks included poor fit for women receiving radiotherapy and challenges using the application for women with low digital literacy or experiencing severe symptoms. CONCLUSIONS: This pilot study provided evidence of the high usability and potential efficacy of a web-based ePRO intervention. We revised recruitment during the pilot to include multiple facilities, and we will further revise for the randomised trial to address barriers to successful ePRO implementation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT05925257.

Adapting and testing measures of organizational context in primary care clinics in KwaZulu-Natal, South Africa.

BACKGROUND: Implementation science frameworks situate intervention implementation and sustainment within the context of the implementing organization and system. Aspects of organizational context such as leadership have been defined and measured largely within US health care settings characterized by decentralization and individual autonomy. The relevance of these constructs in other settings may be limited by differences like collectivist orientation, resource constraints, and hierarchical power structures. We aimed to adapt measures of organizational context in South African primary care clinics. METHODS: We convened a panel of South African experts in social science and HIV care delivery and presented implementation domains informed by existing frameworks and prior work in South Africa. Based on panel input, we selected contextual domains and adapted candidate items. We conducted cognitive interviews with 25 providers in KwaZulu-Natal Province to refine measures. We then conducted a cross-sectional survey of 16 clinics with 5-20 providers per clinic (N = 186). We assessed reliability using Cronbach's alpha and calculated interrater agreement (awg) and intraclass correlation coefficient (ICC) at the clinic level. Within clinics with moderate agreement, we calculated correlation of clinic-level measures with each other and with hypothesized predictors - staff continuity and infrastructure - and a clinical outcome, patient retention on antiretroviral therapy. RESULTS: Panelists emphasized contextual factors; we therefore focused on elements of clinic leadership, stress, cohesion, and collective problem solving (critical consciousness). Cognitive interviews confirmed salience of the domains and improved item clarity. After excluding items related to leaders' coordination abilities due to missingness and low agreement, all other scales demonstrated individual-level reliability and at least moderate interrater agreement in most facilities. ICC was low for most leadership measures and moderate for others. Measures tended to correlate within facility, and higher stress was significantly correlated with lower staff continuity. Organizational context was generally more positively rated in facilities that showed consistent agreement. CONCLUSIONS: As theorized, organizational context is important in understanding program implementation within the South African health system. Most adapted measures show good reliability at individual and clinic levels. Additional revision of existing frameworks to suit this context and further testing in high and low performing clinics is warranted.

Users' perception of quality as a driver of private healthcare use in Mexico: Insights from the People's Voice Survey.

OBJECTIVE: The Mexican government has pursued multiple initiatives to improve healthcare coverage and financial protection. Yet, out-of-pocket health spending and use of private sector providers in Mexico remains high. In this paper, we sought to describe the characteristics of public and private healthcare users, describe recent visit quality across provider types, and to assess whether perceiving the public healthcare sector as poor quality is associated with private health sector use. METHODS AND FINDINGS: We analyzed the cross-sectional People's Voice Survey conducted from December 2022 to January 2023. We used Chi-square tests to compare contextual, individual, and need-for-care factors and ratings of most recent visits between users of public (social security and other public providers) and private sector providers (stand-alone private providers and providers adjacent to pharmacies). We used a multivariable Poisson regression model to assess associations between low ratings of public healthcare sources and the use of private care. Among the 811 respondents with a healthcare visit in the past year, 31.2% used private sources. Private healthcare users were more educated and had higher incomes than public healthcare users. Quality of most recent visit was rated more highly in private providers (70.2% rating the visit as excellent or very good for stand-alone private providers and 54.3% for pharmacy-adjacent doctors) compared to social security (41.6%) and other public providers (46.6%). Those who perceived public health institutions as low quality had a higher probability of seeking private healthcare. CONCLUSION: Users rated public care visits poorly relative to private care; at the population level, perceptions of poor quality care may drive private care use and hence out-of-pocket costs. Improving public healthcare quality is necessary to ensure universal health coverage.

Patient-specific reference model estimation for orthognathic surgical planning.

PURPOSE: Accurate estimation of reference bony shape models is fundamental for orthognathic surgical planning. Existing methods to derive this model are of two types: one determines the reference model by estimating the deformation field to correct the patient's deformed jaw, often introducing distortions in the predicted reference model; The other derives the reference model using a linear combination of their landmarks/vertices but overlooks the intricate nonlinear relationship between the subjects, compromising the model's precision and quality. METHODS: We have created a self-supervised learning framework to estimate the reference model. The core of this framework is a deep query network, which estimates the similarity scores between the patient's midface and those of the normal subjects in a high-dimensional space. Subsequently, it aggregates high-dimensional features of these subjects and projects these features back to 3D structures, ultimately achieving a patient-specific reference model. RESULTS: Our approach was trained using a dataset of 51 normal subjects and tested on 30 patient subjects to estimate their reference models. Performance assessment against the actual post-operative bone revealed a mean Chamfer distance error of 2.25 mm and an average surface distance error of 2.30 mm across the patient subjects. CONCLUSION: Our proposed method emphasizes the correlation between the patients and the normal subjects in a high-dimensional space, facilitating the generation of the patient-specific reference model. Both qualitative and quantitative results demonstrate its superiority over current state-of-the-art methods in reference model estimation.

Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.

Neonatal and Maternal Ichthyosiform Dermopathy in Association with Kava Use during Pregnancy.

INTRODUCTION: Kava, a substance derived from the Piper methysticum plant, is enjoying a surge in popularity in the United States due to its purported anxiolytic and analgesic effects. Though ichthyosiform dermopathy is a known adverse effect associated with chronic kava exposure in adults, dermopathy in a newborn due to maternal kava use has not yet been described. CASE REPORT: This is a case of a 41-year-old woman who was taking a combination kava/kratom product throughout her pregnancy. She developed an ichthyosiform dermopathy that resolved after she stopped using the product postpartum. Her male infant had a neonatal course complicated by both neonatal opioid withdrawal syndrome, attributed to maternal kratom and buprenorphine use, as well as a diffuse ichthyosiform rash similar to descriptions of kava ichthyosiform dermopathy in adults. His neonatal course was complicated by Group B streptococcus and Serratia marscecens bacteremia (treated with antibiotics) and seizures (treated with lorazepam and phenobarbital). His rash resolved completely by day of life 22. At 9-month outpatient follow-up, he had no dermatologic abnormalities or rash recurrence. DISCUSSION: Maternal kava use during pregnancy may cause fetal dermopathy presenting as an acquired ichthyosis. More public education is needed about the potential consequences of kava use, particularly during pregnancy.

Self-assembly of a supramolecular spin-crossover tetrahedron.

A new mononuclear iron(II) SCO compound featuring H-bonding donor and acceptor units has been synthesized and exploited to produce a purely supramolecular switchable [Fe4] tetrahedron. Magnetic and crystallographic measurements evidence a singular magnetic behavior for each of the four Fe(II) centers of the generated architecture and underscore the potential of this strategy to develop novel SCO materials.

Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients with Early Coronavirus Disease 2019 Infection.

Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; P = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (P = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P = .021), CD3+CD4+ cell (95% CI, -105.35 to -11.59; P = .042), CD3+CD8+ cell (95% CI, -324.55 to -57.13; P = .038), and CD3-CD56+ cell (95% CI, -193.51 to -47.31; P = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation.

Relative predation intensity of an intertidal gastropod on artificial coastal defense structures.

Despite seawalls becoming ubiquitous coastal features, and having some physical similarities to natural rocky shores, it remains unclear how these urban habitats influence predator-prey interactions. Predators can affect intertidal mobile prey densities through two pathways: (1) successful predation directly influences prey mortality rates, and (2) direct and indirect effects of predation can scare and induce motile prey to seek safer areas. In this study, we investigated whether intertidal predators affect the density of the marine gastropod, Nerita undata, at four seawall sites in Singapore. Using a tethering method that we developed, we monitored the mortality and other evidence of predation (shell state) of tethered N. undata. Field experiments revealed high (22.5%-82.5%) predation potential of N. undata across the four sites, with significantly higher predation risk at lower shore heights and for snails with mixed shell coloration. Observations and analysis of the shell state after 3 days showed that predation on seawalls was primarily by crushing predators such as fish. Other predators of N. undata include predatory snails, with various feeding methods that left behind different predator signatures. Our results add substantially to the limited knowledge on predator-prey interactions on seawalls, particularly for Nerita undata, and suggest that seawall systems are more dynamic than previously thought. This further highlights the role of these artificial structures as important habitats and feeding grounds in urban coastal ecosystems.

Model-Based Approaches to Investigating Mismatch Responses in Schizophrenia.

Alterations of mismatch responses (ie, neural activity evoked by unexpected stimuli) are often considered a potential biomarker of schizophrenia. Going beyond establishing the type of observed alterations found in diagnosed patients and related cohorts, computational methods can yield valuable insights into the underlying disruptions of neural mechanisms and cognitive function. Here, we adopt a typology of model-based approaches from computational cognitive neuroscience, providing an overview of the study of mismatch responses and their alterations in schizophrenia from four complementary perspectives: (a) connectivity models, (b) decoding models, (c) neural network models, and (d) cognitive models. Connectivity models aim at inferring the effective connectivity patterns between brain regions that may underlie mismatch responses measured at the sensor level. Decoding models use multivariate spatiotemporal mismatch response patterns to infer the type of sensory violations or to classify participants based on their diagnosis. Neural network models such as deep convolutional neural networks can be used for improved classification performance as well as for a systematic study of various aspects of empirical data. Finally, cognitive models quantify mismatch responses in terms of signaling and updating perceptual predictions over time. In addition to describing the available methodology and reviewing the results of recent computational psychiatry studies, we offer suggestions for future work applying model-based techniques to advance the study of mismatch responses in schizophrenia.

Circular food system approaches can support current European protein intake levels while reducing land use and greenhouse gas emissions.

Protein transition and circular food system transition are two proposed strategies for supporting food system sustainability. Here we model animal-sourced protein to plant-sourced protein ratios within a European circular food system, finding that maintaining the current animal-plant protein share while redesigning the system with circular principles resulted in the largest relative reduction of 44% in land use and 70% in greenhouse gas (GHG) emissions compared with the current food system. Shifting from a 60:40 to a 40:60 ratio of animal-sourced proteins to plant-sourced proteins yielded a 60% reduction in land use and an 81% GHG emission reduction, while supporting nutritionally adequate diets. Differences between current and recommended total protein intake did not substantially impact minimal land use and GHG emissions. Micronutrient inadequacies occurred with less than 18 g animal protein per capita per day. Redesigning the food system varied depending on whether land use or GHG emissions were reduced-highlighting the need for a food system approach when designing policies to enhance human and planetary health.

Deviations in RSV epidemiological patterns and population structures in the United States following the COVID-19 pandemic.

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with the greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially in the United States (US) following the implementation of COVID-19-related non-pharmaceutical interventions but later rebounded with abnormal seasonality. The biological and epidemiological factors underlying this altered behavior remain poorly defined. In this retrospective cohort study from 2009 to 2023 in Chicago, Illinois, US, we examined RSV epidemiology, clinical severity, and genetic diversity. We found that changes in RSV diagnostic platforms drove increased detections in outpatient settings post-2020 and that hospitalized adults infected with RSV-A were at higher risk of intensive care admission than those with RSV-B. While population structures of RSV-A remained unchanged, RSV-B exhibited a genetic shift into geographically distinct clusters. Mutations in the antigenic regions of the fusion protein suggest convergent evolution with potential implications for vaccine and therapeutic development.

Improving Image Segmentation with Contextual and Structural Similarity.

Deep learning models for medical image segmentation are usually trained with voxel-wise losses, e.g., cross-entropy loss, focusing on unary supervision without considering inter-voxel relationships. This oversight potentially leads to semantically inconsistent predictions. Here, we propose a contextual similarity loss (CSL) and a structural similarity loss (SSL) to explicitly and efficiently incorporate inter-voxel relationships for improved performance. The CSL promotes consistency in predicted object categories for each image sub-region compared to ground truth. The SSL enforces compatibility between the predictions of voxel pairs by computing pair-wise distances between them, ensuring that voxels of the same class are close together whereas those from different classes are separated by a wide margin in the distribution space. The effectiveness of the CSL and SSL is evaluated using a clinical cone-beam computed tomography (CBCT) dataset of patients with various craniomaxillofacial (CMF) deformities and a public pancreas dataset. Experimental results show that the CSL and SSL outperform state-of-the-art regional loss functions in preserving segmentation semantics.

Availability of basic infection control items and personal protection equipment in 7948 health facilities in eight low- and middle-income countries: Evidence from national health system surveys.

Background: Hundreds of millions of people become infected globally every year while seeking care in health facilities that lack basic needs like infection control measures and personal protective equipment (PPE). We aimed to evaluate the availability of infection control items and PPE in eight low- and middle-income countries and identify disparities in the availability of those items. Methods: In this study, we combined publicly available nationally representative cross-sectional health system surveys (Service Provision Assessments by the Demographic and Health Survey Programme) conducted in eight countries between 2013 and 2018: Afghanistan, Bangladesh, the Democratic Republic of the Congo, Haiti, Malawi, Nepal, Senegal, and Tanzania. The availability of infection control items was evaluated using a list of six items (a waste receptacle, a sharps container, disinfectant, single-use disposable or auto-disposable syringes, soap and running water, or an alcohol-based hand rub, and guidelines for standard precautions). PPE includes four items: gloves, medical masks, gowns, and eye protection. We considered these items available in a facility if they were observed in general outpatient areas or any service-specific area (i.e. delivery room). Results: We analysed data from 7948 health facilities (694 hospitals and 7254 health centres/clinics). Overall, among the infection control items and PPE, most surveyed facilities had high availability of single-use disposable or auto-disposable syringes (91.40%) and latex gloves (92.56%). Of infection control measures, guidelines for infection control were the least available during the survey, with the lowest (6.15%) in Nepal and the highest (68.18%) in Malawi. Of the PPE items, eye protection was the least available during the survey, with the lowest (5.4% in Senegal) and the highest (28.17%) in Haiti. Only 1567 (19.71%) facilities looked to have all the basic infection control materials, and 1023 (12.87%) of the analysed facilities possessed all of the PPE. Within the same country, the availability of items varied more between hospitals and health centres/clinics than between them. Conclusions: All eight of our study countries experience shortages of the most fundamental standard precaution items to avert infection. Steps must be taken in each of these countries to reduce inadequacies and disparities and enhance efficiency in the conversion of health-system inputs into the facility's availability of standard precaution items for infection control - to curb the risk of infectious disease transmission.

Environmental assessment of diets: overview and guidance on indicator choice.

Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.

The burden of RSV, hMPV, and PIV amongst hospitalized adults in the United States from 2016 to 2019.

BACKGROUND: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus (PIV) hospitalize many people yearly. Though severe lower respiratory tract disease has been described in children, the elderly, and the immunocompromised, there is a gap in our understanding of RSV, hMPV, and PIV in hospitalized adults. We sought to evaluate the association of RSV, hMPV, and PIV with severe respiratory disease requiring noninvasive or mechanical ventilation and death in hospitalized adults in the United States. METHODS: We conducted a retrospective, pooled, cross-sectional study of general medicine hospitalizations in the United States from 2016 to 2019 using the National Inpatient Sample published by the Agency for Healthcare Quality and Research. We used multivariable Poisson regression to estimate the likelihood of severe respiratory disease or death. We used linear regression to estimate the mean difference in length of stay for those hospitalized with and without a respiratory virus. RESULTS: We found that RSV (incidence rate ratio [IRR]: 1.68, 95% confidence interval [CI]: 1.61-1.74, p < .001), hMPV (IRR: 1.82, 95% CI: 1.71-1.93, p < .001), and PIV (IRR: 1.81, 95% CI: 1.68-1.94, p < .001) were independently associated with severe respiratory disease, even after adjustment. Additionally, we found the presence of a respiratory virus prolonged hospitalizations by (0.79 ± 0.27 days, p < .003) for RSV, (0.88 ± 0.28 days, p < .002) for hMPV, and (1.43 ± 0.30 days, p < .001) for PIV. CONCLUSIONS: RSV, hMPV, and PIV have a significant burden on hospitalized adults, even without classic risk factors.

A Compound That Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer.

Metastatic castration-resistant prostate cancer remains incurable regardless of recent therapeutic advances. Prostate cancer tumors display highly glycolytic phenotypes as the cancer progresses. Nonspecific inhibitors of glycolysis have not been utilized successfully for chemotherapy, because of their penchant to cause systemic toxicity. This study reports the preclinical activity, safety, and pharmacokinetics of a novel small-molecule preclinical candidate, BKIDC-1553, with antiglycolytic activity. We tested a large battery of prostate cancer cell lines for inhibition of cell proliferation, in vitro. Cell-cycle, metabolic, and enzymatic assays were used to demonstrate their mechanism of action. A human patient-derived xenograft model implanted in mice and a human organoid were studied for sensitivity to our BKIDC preclinical candidate. A battery of pharmacokinetic experiments, absorption, distribution, metabolism, and excretion experiments, and in vitro and in vivo toxicology experiments were carried out to assess readiness for clinical trials. We demonstrate a new class of small-molecule inhibitors where antiglycolytic activity in prostate cancer cell lines is mediated through inhibition of hexokinase 2. These compounds display selective growth inhibition across multiple prostate cancer models. We describe a lead BKIDC-1553 that demonstrates promising activity in a preclinical xenograft model of advanced prostate cancer, equivalent to that of enzalutamide. BKIDC-1553 demonstrates safety and pharmacologic properties consistent with a compound that can be taken into human studies with expectations of a good safety margin and predicted dosing for efficacy. This work supports testing BKIDC-1553 and its derivatives in clinical trials for patients with advanced prostate cancer.