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Objective: This study aimed to systematically review the relationship between secondary smoking and early childhood caries (ECC) among preschool children. Method: Two independent reviewers systematically searched English publications with keywords in PubMed, Web of Science, Medline, Scopus, and Embase to identify publications reporting on secondary smoking and ECC for children under 71 months. Observational studies, including cohort studies, case-control studies, and cross-sectional surveys, were included. The reviewers screened the titles and abstracts to remove duplicate records, reviews, and irrelevant studies. They performed meta-analyses to investigate the prevalence of ECC in children exposed to secondary smoking. Results: This study identified 1243 publications and included 16 publications. Twelve publications were cross-sectional studies. A meta-analysis of 11 of them revealed that children with secondary smoking exposure had an odds ratio of 1.77 in caries risk (P < .001), whereas one cross-sectional study found no increase in caries risk without data reporting. Two cohort studies with low and very low quality were combined into a meta-analysis, which found children from infancy with secondary smoking exposure had a relative risk of 1.45 in caries incidence (P < .001). Two case-control studies with moderate and low quality were combined into a meta-analysis, which found that children exposed to secondary smoking had an odds ratio of 4.46 in caries prevalence (P < .001). Conclusion: The literature has reported that preschool children with secondary smoking exposure have a higher risk of caries; however, the number and quality of these studies are limited.

Multiparametric magnetic resonance imaging (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, the major limitations are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric magnetic resonance imaging (bpMRI) and advanced, quantitative magnetic resonance imaging (MRI) techniques. One such advanced technique is the Restriction Spectrum Imaging restriction score (RSIrs), an imaging biomarker that has been shown to improve quantitative accuracy of patient-level csPCa detection. Advanced Restriction imaging and reconstruction Technology for Prostate MRI (ART-Pro) is a multisite, multinational trial that aims to evaluate whether IV contrast can be avoided in the setting of standardized, state-of-the-art image acquisition, with or without addition of RSIrs. Additionally, RSIrs will be evaluated as a stand-alone, quantitative, objective biomarker. ART-Pro will be conducted in two stages and will include a total of 500 patients referred for multiparametric prostate MRI with a clinical suspicion of prostate cancer at the participating sites. ART-Pro-1 will evaluate bpMRI, mpMRI, and RSIrs on the accuracy of expert radiologists’ detection of csPCa and will evaluate RSIrs as a stand-alone, quantitative, objective biomarker. ART-Pro-2 will evaluate the same MRI techniques on the accuracy of nonexpert radiologists’ detection of csPCa, and findings will be evaluated against the expertly created dataset from ART-Pro-1. The primary endpoint is to evaluate whether bpMRI is noninferior to mpMRI among expert (ART-Pro-1) and nonexpert (ART-Pro-2) radiologists for the detection of grade group ≥2 csPCa. This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT06579417) at ClinicalTrials.gov. Patient accrual at the first site (UC San Diego) began in December 2023. Initial results are anticipated by the end of 2026.

Abstract: Measurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITDpos) has been hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)–based MRD assay (limit of detection 10−4 to 10−5), we evaluated the prognostic impact of MRD at different time points in 157 patients with FLT3-ITDpos AML who were enrolled in the German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and who were treated with a combination of intensive chemotherapy and midostaurin, followed by midostaurin maintenance. MRD negativity (MRDneg) after 2 cycles of chemotherapy (Cy2), which was observed in 111 of 142 (78%) patients, was predictive of superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR; 26% vs 46%; P = .001) and overall survival (OS) (4y-OS; 70% vs 44%; P = .012). This survival advantage was also seen among patients who underwent allogeneic hematopoietic-cell transplantation during first complete remission (4y-CIR, 14% vs 39%; P = .001; 4y-OS, 71% vs 49%; P = .029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (hazard ratio [HR], 0.29; P = .006) and OS (HR, 0.39; P = .018). During follow-up, conversion from MRDneg to MRD positivity (MRDpos) was a strong, independent factor for inferior CIR (HR, 16.64; P < .001) and OS (HR, 4.05; P < .001). NGS-based FLT3-ITD MRD monitoring identifies patients at high risk for relapse and death following treatment with intensive chemotherapy and midostaurin. Using NGS-based technology.

Osteoid osteomas are benign bone tumors characterized by severe localized pain, often challenging the daily lives of young patients. While these tumors are typically solitary, rare cases of multiple osteoid osteomas have been reported. This research paper presents a case series of 2 young patients with multiple osteoid osteomas, highlighting their clinical presentation, diagnostic workup, treatment with cryoablation, and follow-up. The paper emphasizes the effectiveness of cryoablation as a minimally invasive treatment option for these challenging cases.

Gayet-Wernicke encephalopathy (GWE) is a neuropsychiatric syndrome due to Vitamin B1 (thiamine) deficiency, fatal in 30% of cases and preventable if treatment is initiated early, characterized by the classic triad of encephalopathy, ocular involvement: ophthalmoplegia and/or nystagmus and ataxia. GWE is mainly observed in alcoholics, but can also appear in any state of malnutrition. In obstetrics, hyperemesis gravidarum can be complicated by GWE due to low thiamine stores and increased thiamine requirements. We report a case of Gayet-Wernicke encephalopathy complicating incoercible vomiting in a pregnant woman.

Atopobium minutum (A. minutum) has rarely been documented in human infections. However, this report describes a case involving a 52-year-old woman who developed empyema and lung collapse due to A. minutum. She initially presented to the emergency department with nausea, vomiting, diarrhea, and abdominal pain. Her condition quickly declined within the first day of arrival, leading to respiratory failure and requiring intubation and ICU-level care. Despite receiving intensive antibiotic treatment, the patient needed prolonged intubation and a tracheostomy. Initial cultures indicated Streptococcus intermedius and Lactobacillus minutus, but final culture results identified A. minutum as the cause. This case highlights the difficulty in diagnosing A. minutum infections, often necessitating advanced DNA sequencing, and raises concerns about potential multidrug resistance. It highlights the importance of prompt identification of the pathogen by laboratories to allow for effective treatment of these rare infections.

Summary: Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in the hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits. In contrast, abnormal synchronization within the MEC and between HPC and MEC emerged later, by 8 weeks after Pilo-SE, when spatial memory impairment was more severe. Furthermore, a distinct subpopulation of MEC layer 3 excitatory neurons (active at theta troughs) was specifically impaired in epileptic mice. Together, these findings suggest that hippocampal-entorhinal circuit dysfunction accumulates and shifts as cognitive impairment progresses in TLE.

Aim: Standardized evaluation of [18F]PI-2620 tau-PET scans in 4R-tauopathies represents an unmet need in clinical practice. This study aims to investigate the effectiveness of visual evaluation of [18F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility. Methods: A total of 83 individuals with [18F]PI-2620 PET scans were included. Participants were classified as probable 4R-tauopathies (n = 29), Alzheimer's disease (AD) (n = 20), α-synucleinopathies (n = 15), and healthy controls (n = 19) based on clinical criteria. Visual assessment of tau-PET scans (choice: 4R-tauopathy, AD-tauopathy, no-tauopathy) was conducted using either 20–40-minute or 40–60-minute intervals, with raw (common) and cerebellar grey matter scaled standardized reading settings (intensity-scaled). Two readers evaluated scans independently and blinded, with a third reader providing consensus in case of discrepant primary evaluation. A regional analysis was performed using the cortex, basal ganglia, midbrain, and dentate nucleus. Sensitivity, specificity, and interrater agreement were calculated for all settings and compared against the visual reads of parametric images (0–60-minutes, distribution volume ratios, DVR). Results: Patients with 4R-tauopathies in contrast to non-4R-tauopathies were detected at higher sensitivity in the 20–40-minute frame (common: 79%, scaled: 76%) compared to the 40–60-minute frame (common: 55%, scaled: 62%), albeit with reduced specificity in the common setting (20–40-min: 78%, 40–60-min: 95%), which was ameliorated in the intensity-scaled setting (20–40-min: 91%, 40–60-min: 96%). Combined assessment of multiple brain regions did not significantly improve diagnostic sensitivity, compared to assessing the basal ganglia alone (76% each). Evaluation of intensity-scaled parametric images resulted in higher sensitivity compared to intensity-scaled static scans (86% vs. 76%) at similar specificity (89% vs. 91%). Conclusion: Visual reading of [18F]PI-2620 tau-PET scans demonstrated reliable detection of 4R-tauopathies, particularly when standardized processing methods and early imaging windows were employed. Parametric images should be preferred for visual assessment of 4R-tauopathies.

Introduction: Individuals with esophageal and gastroesophageal junction (GEJ) cancers are at especially high risk of malnutrition. However, most patients with malnutrition do not receive adequate nutritional support. We conducted a single-arm trial to test the implementation of Support Through Remote Observation and Nutrition Guidance (STRONG), a multilevel digital intervention to improve nutritional outcomes for patients with locally advanced esophageal and gastroesophageal junction cancer. Methods: Participants received five nutritional counseling sessions with a dietitian, logged daily food intake through the Fitbit app, and completed five study assessments related to patient malnutrition, nutrition-related symptoms, and quality-of-life outcomes. We assessed the feasibility, acceptability, and usability of STRONG against a priori benchmarks. Results: Participants (N = 17) had a median age of 68 years, and 71 % were male. Feasibility benchmarks were met for participants completing the baseline assessment (94 %), completing four out of five assessments (82 %), and participant retention (85 %). Among participants who only received an oral diet during the study period, adherence to dietetic appointments (89 %) and food intake tracking (78 %) were high. Participant recruitment rate (47 %) was slightly below the benchmark (50 %). All participants found the intervention to be acceptable. Usability of the intervention was high, with 69 % and 92 % of participants reporting high satisfaction with tracking food intake through the Fitbit and the dietitian-led nutrition counseling sessions, respectively. Conclusion: Our study demonstrated that STRONG could be implemented with high feasibility, acceptability, and usability for esophageal and GEJ cancer patients. Findings from this study can guide a future efficacy study to assess the impact of STRONG on patient outcomes. Clinical trial registration: The Support Through Remote Observation and Nutrition Guidance Program for Gastroesophageal Cancer Patients (STRONG-GEC) study was registered on clinicaltrials.gov (NCT05438940) in June 2022 prior to participant enrollment.

Objectives: Evidence indicates that people living with HIV (PLHIV) are more impacted by COVID-19. The burden of SARS-CoV-2 infection among PLHIV is unknown in Nigeria. Methods: We conducted repeated cross-sectional SARS-CoV-2 serosurveys in 14 states and the Federal Capital Territory in Nigeria among PLHIV who had an HIV viral load (VL) test during April 2022 to January 2023. Evidence of SARS-CoV-2 immunoglobulin G (IgG) antibodies was assessed using a multiplex bead assay to measure IgG to spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins to identify potential infection and/or vaccination status. Results: Between April 2022 and January 2023, 47,614 remnant VL samples were included and tested for SARS-CoV-2 antibodies. Seroprevalence of SARS-CoV-2 infection, defined as IgG antibodies to spike and RBD591 [S+] and nucleocapsid [N+], (S+N+), ranged between 21.1% (95% confidence intervals [CI]: 11.4-31.8) in Ekiti State in January 2023 to 71.4% (95% CI 71.9-81.9) in Gombe State in November 2022, with overall steady trends within and between states over time, across age and sex. Conclusion: High rates of SARS-CoV-2 antibody seroprevalence among PLHIV in Nigeria were observed. This underscores the need to understand the association between HIV and SARS-CoV-2 to inform strategies to reduce the threat posed by COVID-19.

Background: The adipose tissue may serve as a source of energy supporting cancer growth and metastasis. Our understanding of the adipocytes which compose the adipose tissue in different anatomical locations of the body as well as potential microscopic tumor infiltration in patients with metastatic breast cancer remains limited. This study therefore investigates regional variations in adipocyte size and adipose tissue tumor infiltration in patients with metastatic breast cancer. Methods: Within the UPTIDER rapid autopsy program, (NCT04531696), 94 adipose tissue samples from subcutaneous, visceral, retroperitoneal, and mammary depots of 22 patients with metastatic breast cancer were collected and analyzed. Distant adipocyte size was quantified using digital pathology, and tumor infiltration was assessed histologically. Linear mixed quantile regression analyzed the associations between adipocyte size, fat depot type and major histological subtypes. Results: Distant adipocyte size did not significantly differ across fat depots. A trend towards smaller adipocytes in mammary fat at autopsy versus diagnosis was observed, suggesting potential age and/or treatment effects. Adipocyte size correlated positively with BMI at death, especially in subcutaneous and visceral fat. Visceral fat exhibited higher tumor infiltration, notably in patients with invasive lobular carcinoma (ILC). Conclusion: This study highlights the relatively uniform adipocyte size across fat depots in patients with metastatic breast cancer, with potential changes in mammary adipocytes over the disease course. The microscopic tumor cell infiltration observed in the visceral fat, mainly for ILC, underscores the need to undertake additional research to understanding the contribution of the adipose tissue in breast cancer metastasis.

Immunotherapy has dramatically changed the outcome for patients with advanced melanoma, with significant improvements in overall survival and potential cure for some. The recent approval of nivolumab in combination with relatlimab (nivolumab-relatlimab) added a third immunotherapy option for first-line treatment for advanced melanoma. Nivolumab-relatlimab has shown greater efficacy compared to single-agent nivolumab and has fewer unacceptable side effects compared to the combination of ipilimumab and nivolumab (ipilimumab-nivolumab). However, the lack of both long-term follow-up data and direct comparison with ipilimumab-nivolumab raises uncertainty about where to position nivolumab-relatlimab in clinical practice. Since most patients who respond to combination ipilimumab-nivolumab also respond to nivolumab-relatlimab, and many to single-agent anti-programmed death-1 (PD-1) monotherapy, the challenge is to identify the subgroup of patients who need ipilimumab-nivolumab and would not achieve similar benefits from less toxic alternatives. This review discusses the available data on efficacy of the three approved first-line immunotherapies (single-agent anti-PD-1, nivolumab-relatlimab or ipilimumab-nivolumab) and their value in distinct population groups to help guide clinical decisions.

Broncho-esophageal fistulas (BEFs) are a rare but serious complication that can occur after esophagectomy, often resulting in aspiration, respiratory issues, and infection. Management depends on fistula size and location, with options including conservative treatments, surgical closure and stenting. Conventional treatment involves esophageal stents, which may be insufficient for larger or more complex fistulas. This case report describes the first use of a 3D-printed airway stent in combination with an esophageal stent to treat a broncho-esophageal fistula. A 70-year-old patient with distal esophageal adenocarcinoma, treated with neoadjuvant chemoradiation, underwent robot-assisted minimally invasive esophagectomy. The procedure was complicated by a broncho-esophageal fistula, leading to multiple interventions. Despite dual stenting with a custom 3D airway stent, the fistula persisted, and the patient was transitioned to supportive care due to disease progression. This case, the first to use a 3D-printed airway stent for a broncho-esophageal fistula, demonstrates that the stent did not achieve closure, likely due to excessive pressure against the endobronchial wall. This underscores the need for improved 3D stent designs, offering important insights for interventional pulmonologists.

Tropheryma whipplei (T. whipplei) infection can be difficult to diagnose due to its variable clinical manifestations and the limitations of standard diagnostic tests. This case describes a 78-year-old male with blurry vision and floaters in his right eye five months after cataract surgery, along with new onset weight loss and arthralgias. Ophthalmologic examination revealed inflammation and posterior vitritis, and vitreous biopsy identified T. whipplei via broad-range bacterial PCR, despite negative vitreous cultures and unremarkable flow cytometry. Gastrointestinal endoscopic and cerebrospinal fluid studies revealed no pathological or molecular evidence of the disease, complicating the diagnosis. Treatment with intravenous ceftriaxone followed by oral trimethoprim-sulfamethoxazole for 12 months resulted in resolution of symptoms and inflammation, with normalization of laboratory markers. This case underscores the diagnostic utility of broad-range bacterial PCR in atypical infections and highlights Whipple infection as a differential diagnosis in ocular presentations. Comprehensive interdisciplinary evaluation was critical for effective management.

Background and Aims: Patients with type 2 diabetes (T2D) constitute a risk group for presence and severity of metabolic dysfunction–associated steatotic liver disease (MASLD). Yet, there are few published examples of collaborations between endocrinologists and hepatologists in caring for patients with T2D and MASLD. Here, we describe a pathway for screening of liver fibrosis in routine specialist diabetes care at a tertiary care hospital. Methods: Patients with T2D seen at the Endocrinology department at Karolinska University Hospital, Stockholm, Sweden, during a structured intervention for T2D between October 2016 and September 2023 were eligible for inclusion. Liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) as proxies for liver fibrosis and steatosis, respectively, were obtained utilizing vibration-controlled transient elastography (VCTE). An LSM cut-off to exclude advanced fibrosis was set to

Background: Community health workers (CHWs) are vital links between communities and health systems, with CHW models facilitating positive health and life outcomes. However, little is known about CHWs’ experiences serving in these roles or their potential to support the transition to adulthood for adolescents and young adults (AYA). Methods: Semi-structured interviews were conducted with CHWs and their supervisors from five recruitment sites affiliated with Community Health Worker and Mobile Health for Emerging Adults Transitioning Sickle Cell Disease Care (COMETS) Trial. COMETS compared the effectiveness of a CHW intervention, mobile health application, or enhanced usual care on the health-related quality of life of AYA with SCD transitioning from pediatric to adult care. To understand CHW and CHW supervisor experiences during the COMETS trial, interviews were analyzed using an integrated inductive and deductive thematic analytic approach. Results: Three key themes emerged as interviewees described the unique aspects of the CHW role: (1) the supports for transition to adulthood that CHWs provided to patients, (2) the experiences of establishing trusting relationships with patients, and (3) the impact of the role on CHWs themselves. All interviewees reported unique contributions made by CHWs in supporting patients’ transition readiness, and CHWs expressed that participating in COMETS impacted them personally and professionally. Conclusion: This study highlights that the CHW role is unique both in how CHWs connect with AYA and how it impacts CHWs. Health systems should explore paths for sustainable funding and workforce development for CHWs and invest in infrastructure for CHW transition programs.

Introduction: Checkpoint inhibitors (CPI) and targeted therapy (TT) have revolutionised the outcomes for melanoma. Other than the approval of pembrolizumab for resected stage IIB/IIC in February 2023, there were no changes in the Systemic Anti-Cancer Therapy (SACT) treatments available for melanoma in England between 2019 and 2023. The national SACT dataset provides an insight on systemic treatment use during this timeframe. The purpose of this study was to evaluate the patterns of use and costs of SACT for melanoma between 2019 and 2023. Materials and Methods: Data on prescriptions of SACT for adjuvant and metastatic disease between April 2019 to March 2023 were obtained from the SACT dataset and joinpoint regression analyses were used to look for any trends and change in trends. The list prices reported on the British National Formulary (BNF) were used to model drug acquisition costs. Results: Data were available from a total of 71 Hospital Trusts. There was a non significant increasing trend in the adjuvant prescriptions (semestral percentage change = 3.25, 95% confidence interval [CI] -2.15–8.96, p = 0.22) and a non significant negative trend in the metastatic prescriptions (semestral percentage change = -0.59, 95% CI -3.02–1.92, p = 0.64) from April 2019 to March 2023. The estimated costs for SACT in the same timeframe were approximately £ 1.2 billion. Despite an increase in the spending on adjuvant therapy, the total costs in the financial year 2022–2023 decreased compared to 2019–2020 due to a slight reduction in the spending on metastatic treatment. Conclusions: The opposite trends seen for adjuvant and metastatic prescriptions are a potential indicator of the impact of adjuvant treatment on development of distant metastases.

Total antioxidant capacity (TAC) is an important indicator for assessing the merit of natural plants and foods. Herein, a visual TAC assay is developed based on the oxidase-like activity of nitrogen-doped carbon nanotubes loaded with Fe nanoparticles (FeNPs@NCNT), which is prepared via high-temperature pyrolysis of metal-organic framework precursors and can catalyze the oxidation of colorless o-phenylenediamine (OPD) to colored 2,3-diaminophenazine (DAP). The addition of antioxidants (e.g., quercetin) impedes the formation of DAP, diminishing the color change, which can be analyzed via the RGB values obtained with a smartphone color-recognition APP, “Color Picker”. The change of the optical signal can also be analyzed in the fluorescence mode. These two detection modes yield consistent TAC analysis of actual plant samples, in accord with results from the standard ABTS method. Results from this study highlight the unique potential of nanozymes in the development of effective TAC analysis platforms for natural plants and food.

Achieving a decarbonized society requires balancing two critical and seemingly conflicting objectives: reducing energy consumption and ensuring energy demand flexibility to adapt to the variability of renewable energy production. This study introduces ''energy demand science'' as a multidisciplinary field to address these challenges, focusing on the residential sector, which significantly impacts energy use due to occupant behavior and lifestyle. Using a comprehensive review of literature and advanced modeling techniques, this research explores mechanisms driving energy demand. Key results show that energy demand can be reduced by up to 40 % by 2050 through lifestyle adjustments, urbanization, and innovative technologies, aligning with global warming targets below 1.5 °C. Advanced modeling techniques and high-resolution data analyses were employed to explore mechanisms driving energy demand, supported by historical data from 1970 to present, incorporating advancements in IoT and smart metering technologies. The results highlight the importance of integrating technological, human, natural, and socio-economic factors to achieve a sustainable reduction in energy use while maintaining flexibility. Policy implications emphasize the need for holistic, interdisciplinary strategies to enable efficient demand-side management, enhance renewable energy integration, and align energy consumption with decarbonization goals.

The bacterial microbiome of the ant Camponotus floridanus has been well characterized across body regions and maturation levels. However, potential effects of entomopathogens on the gut microbiome, and the fungal communities therein, are yet to be assessed. Additionally, the mycobiome remains often overlooked despite playing a vital role in gut ecology with potential implications for health and infection outcomes. We characterized the effects of two entomopathogens with different infection strategies on the gut micro- and mycobiota of C. floridanus over time; Ophiocordyceps camponoti-floridani and Beauveria bassiana. Specialist, ‘zombie-making’ O. camponoti-floridani fungi hijack the behavior of C. floridanus ants over three weeks, leading them to find an elevated position and fix themselves in place with their mandibles. This summiting behavior is adaptive to Ophiocordyceps as the ant transports the fungus to conditions that favor fruiting body development, spore production, dispersal, and transmission. In contrast, the generalist entomopathogen B. bassiana infects and kills the ant within a few days, without the induction of obvious fungus-adaptive behaviors. By comparing healthy ants with Beauveria- and Ophiocordyceps-infected ants we aimed to 1) describe the dynamics of the micro- and mycobiome of C. floridanus during infection, and 2) determine if the effects on gut microbiota are distinctive between fungi that have different infection strategies. While Beauveria did not measurably affect the ant host micro-and mycobiome, Ophiocordyceps did, especially for the mycobiome. Moreover, ants that were sampled during Ophiocordyceps-adaptive summiting behavior had a significantly different micro- and mycobiome composition compared to healthy controls and those sampled before and after manipulation took place. This suggests that the host microbiome might have a role to play in the manipulation strategy of Ophiocordyceps.

Objective: Despite advances in artificial intelligence (AI) in glaucoma prediction, most works lack multicenter focus and do not consider fairness concerning sex, race, or ethnicity. This study aims to examine the impact of these sensitive attributes on developing fair AI models that predict glaucoma progression to necessitating incisional glaucoma surgery. Design: Database study. Participants: Thirty-nine thousand ninety patients with glaucoma, as identified by International Classification of Disease codes from 7 academic eye centers participating in the Sight OUtcomes Research Collaborative. Methods: We developed XGBoost models using 3 approaches: (1) excluding sensitive attributes as input features, (2) including them explicitly as input features, and (3) training separate models for each group. Model input features included demographic details, diagnosis codes, medications, and clinical information (intraocular pressure, visual acuity, etc.), from electronic health records. The models were trained on patients from 5 sites (N = 27 999) and evaluated on a held-out internal test set (N = 3499) and 2 external test sets consisting of N = 1550 and N = 2542 patients. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUROC) and equalized odds on the test set and external sites. Results: Six thousand six hundred eighty-two (17.1%) of 39 090 patients underwent glaucoma surgery with a mean age of 70.1 (standard deviation 14.6) years, 54.5% female, 62.3% White, 22.1% Black, and 4.7% Latinx/Hispanic. We found that not including the sensitive attributes led to better classification performance (AUROC: 0.77–0.82) but worsened fairness when evaluated on the internal test set. However, on external test sites, the opposite was true: including sensitive attributes resulted in better classification performance (AUROC: external #1 - [0.73–0.81], external #2 - [0.67–0.70]), but varying degrees of fairness for sex and race as measured by equalized odds. Conclusions: Artificial intelligence models predicting whether patients with glaucoma progress to surgery demonstrated bias with respect to sex, race, and ethnicity. The effect of sensitive attribute inclusion and exclusion on fairness and performance varied based on internal versus external test sets. Prior to deployment, AI models should be evaluated for fairness on the target population. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Summary: Polygenic scores (PGSs) are a promising tool for estimating individual-level genetic risk of disease based on the results of genome-wide association studies (GWASs). However, their promise has yet to be fully realized because most currently available PGSs were built with genetic data from predominantly European-ancestry populations, and PGS performance declines when scores are applied to target populations different from the populations from which they were derived. Thus, there is a great need to improve PGS performance in currently under-studied populations. In this work we leverage data from two large and diverse cohorts the Million Veterans Program (MVP) and All of Us (AoU), providing us the unique opportunity to compare methods for building PGSs for multi-ancestry populations across multiple traits. We build PGSs for five continuous traits and five binary traits using both multi-ancestry and single-ancestry approaches with popular Bayesian PGS methods and both MVP META GWAS results and population-specific GWAS results from the respective African, European, and Hispanic MVP populations. We evaluate these scores in three AoU populations genetically similar to the respective African, Admixed American, and European 1000 Genomes Project superpopulations. Using correlation-based tests, we make formal comparisons of the PGS performance across the multiple AoU populations. We conclude that approaches that combine GWAS data from multiple populations produce PGSs that perform better than approaches that utilize smaller single-population GWAS results matched to the target population, and specifically that multi-ancestry scores built with PRS-CSx outperform the other approaches in the three AoU populations.

Purpose: To bring awareness on how the false eyelash beauty trend can impact routine glaucoma evaluations. Observation: False eyelashes have the ability to induce pseudoptosis and visual disturbance complaints from patients. This translates to the patient care setting by inhibiting proper administration of Humphrey Visual Field analysis and portraying gross overestimations on patients’ glaucoma progression. Conclusions: Patients should be asked to remove false eyelashes prior to administering Humphrey Visual Field analysis or have their eyelids taped up to prevent obstruction of view during examination. Importance: Making medical management decisions based on a Humphrey Visual Field analysis completed on a patient wearing false eyelashes could lead to overly aggressive treatment on an otherwise healthy patient.

Background: Pre-clinical and clinical studies propose that statins may have chemopreventive effects against cancer, suggesting their possible roles as adjunctive therapies for melanoma. Objective: To investigate the association between regular statin use and disease recurrence in patients with resected Stage I-III melanoma. Methods: We conducted a retrospective analysis of patients enrolled in the multi-center Melanoma Research Victoria cohort with a histologically confirmed, resected American Joint Committee on Cancer Stage I-III cutaneous melanoma. Patients with uveal melanoma, melanoma of unknown primary site, or mucosal melanoma were excluded. Melanoma recurrence outcomes were compared between statin users and statin non-users, with statin use determined by linkage to the Pharmaceutical Benefits Scheme (Australia) prescription database. Results: 624 patients with resected Stage I-III melanoma at diagnosis were eligible for the study. 193 patients were classified as statin users and 431 patients as statin non-users. In all, 45 statin users experienced disease recurrence compared to 140 (23.3 vs 32.5%, p = 0.05) statin non-users with similar durations of follow-up (median 2.2 and 2.4 years, respectively). After adjustment, statin users had a lower risk melanoma recurrence than statin non-users (HR 0.66, 95%CI 0.44–0.99, p = 0.04). A lower risk of recurrence was also observed in subset analyzes of statin users on high-dose therapy (HR 0.50, 95%CI 0.25–0.99, p = 0.05) and patients who were adherent to statin therapy (HR 0.60, 95%CI 0.39–0.92, p = 0.02). Conclusion: Our study supports the possibility that an association exists between statin use and reduced disease recurrence in resected cutaneous melanoma.

Aim: To assess the effectiveness of Clinical Decision Support Tools (CDSTs) in enhancing the quality of care outcomes in primary cardiovascular disease (CVD) prevention. Methods: A systematic review was undertaken in accordance with PRISMA guidelines, and included searches in Ovid Medline, Ovid Embase, CINAHL, and Scopus. Eligible studies were randomized controlled trials of CDSTs comprising digital notifications in electronic health systems (EHS/EHR) in various primary healthcare settings, published post-2013, in patients with CVD risks and without established CVD. Two reviewers independently assessed risk of bias using the Cochrane RoB-2 tool. Attainment of clinical targets was analysed using a Restricted Maximum Likelihood random effects meta-analysis. Other relevant outcomes were narratively synthesised due to heterogeneity of studies and outcome metrics. Results: Meta-analysis revealed CDSTs showed improvement in systolic (Mean Standardised Difference (MSD)=0.39, 95 %CI=-0.31, -1.10) and diastolic blood pressure target achievement (MSD=0.34, 95 %CI=-0.24, -0.92), but had no significant impact on lipid (MSD=0.01; 95 %CI=-0.10, 0.11) or glucose target attainment (MSD=-0.19, 95 %CI=-0.66, 0.28). The CDSTs with active prompts increased statin initiation and improved patients’ adherence to clinical appointments but had minimal effect on other medications and on enhancing adherence to medication. Conclusion: CDSTs were found to be effective in improving blood pressure clinical target attainments. However, the presence of multi-layered barriers affecting the uptake, longer-term use and active engagement from both clinicians and patients may hinder the full potential for achieving other quality of care outcomes. Lay Summary: The study aimed to evaluate how Clinical Decision Support Tools (CDSTs) impact the quality of care for primary cardiovascular disease (CVD) management. CDSTs are tools designed to support healthcare professionals in delivering the best possible care to patients by providing timely and relevant information at the point of care (ie. digital notifications in electronic health systems). Although CDST are designed to improve the quality of healthcare outcomes, the current evidence of their effectiveness is inconsistent. Therefore, we conducted a systematic review with meta-analysis, to quantify the effectiveness of CDSTs. The eligibility criteria targeted patients with CVD risk factors, but without diagnosed CVD. The meta-analysis found that CDSTs showed improvement in systolic and diastolic blood pressure target achievement but did not significantly impact lipid or glucose target attainment. Specifically, CDSTs showed effectiveness in increasing statin prescribing but not antihypertensives or antidiabetics prescribing. Interventions with CDSTs aimed at increasing screening programmes were effective for patients with kidney diseases and high-risk patients, but not for patients with diabetes or teenage patients with hypertension. Alerts were effective in improving patients' adherence to clinical appointments but not in medication adherence. This study suggests CDSTs are effective in enhancing a limited number of quality of care outcomes in primary CVD prevention, but there is need for future research to explore the mechanisms and context of multiple barriers that may hinder the full potential for cardiovascular health outcomes to be achieved.

Background: Statins have been shown to reduce atherosclerotic cardiovascular disease (ASCVD). In the United States, statins are underutilized, and the literature suggests women and Latine individuals received even fewer prescriptions than men even when eligible. No study has shown how statins are prescribed when looking at language, ethnicity, and considering sex. Methods: Data were analyzed from a multistate EHR network across the US from 2014 to 2020. We included patients aged 40+ that were non-Hispanic White, English speaking Latine, and Spanish speaking Latine and further disaggregated by sex with the aim to examine statin prescription prevalence and rates between groups. GEE logistic and negative binomial regression models were used determine the outcomes adjusted by appropriate covariates. Results: We found compared to non-Hispanic White men, only Spanish speaking Latinos had higher odds of receiving a statin prescription, but once one statin was prescribed, non-Hispanic White women were the only group with higher rates. We found a higher percent of Spanish speaking Latine patients regardless of sex had a statin prescription. Prevalence of having a statin prescription was 59.3 % and 59.7 % for Spanish speaking Latinos and Latinas respectively compared to 55.5 % 57.0 % for non-Hispanic White men and women respectively. Conclusions: Overall, we found ethnicity, language, and sex differences. Clinicians in CHCs play an important role in the process to eliminate the sex gap in preventive health. The attention to statin prescribing in Spanish speaking Latine patients indicates more conscious care is being implemented in these vulnerable populations.

Summary: Neural representations for visual stimuli typically emerge with a bilateral distribution across occipitotemporal cortex (OTC). Pediatric patients undergoing unilateral OTC resection offer an opportunity to evaluate whether representations for visual stimulus individuation can sufficiently develop in a single OTC. Here, we assessed the non-resected hemisphere of patients with pediatric resection within (n = 9) and outside (n = 12) OTC, as well as healthy controls’ two hemispheres (n = 21). Using functional magnetic resonance imaging, we mapped category selectivity (CS), and representations for visual stimulus individuation (for faces, objects, and words) with repetition suppression (RS). There were no group differences in CS or RS. However, OTC resection patients’ accuracy on face and object (but not word) recognition was lower than controls’. The neuroimaging results highlight neural resilience following damage to the contralateral homologue. Critically, however, a single OTC does not suffice for typical behavior, and, thereby, implicates the necessary contributions of bilateral OTC for visual recognition.

Conflict of interest: No Introduction and Objectives: Hepatic involvement as an extraintestinal manifestation of inflammatory bowel disease (IBD) has been widely described; however, there is limited information on the presence of non-alcoholic steatosis and hepatic fibrosis, as well as the recent definition of metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of our study is to describe the frequency of non-alcoholic hepatic fibrosis and steatosis, as well as MASLD, and to describe the associated factors for these conditions. Patients / Materials and Methods: This is a cross-sectional and analytical study. Patients diagnosed with IBD were included, and transient hepatic elastography (THE) with iLivTouchFT100® /UAP was performed to obtain values of steatosis and hepatic fibrosis. Additionally, the presence of metabolic syndrome criteria was evaluated to diagnose MASLD. Demographic and clinical variables of the disease were recorded. For the statistical analysis, R Commander software and R Studio Desktop application were used. Results and Discussion: A total of 136 patients diagnosed with IBD were included, of which 80 (58.82%) were women and 56 (41.18%) were men. The mean age was 44.83 years (SD ±15.78). Regarding the type of IBD, 106 (77.9%) patients were diagnosed with UC, while CD was diagnosed in 30 (22.1%) patients; the majority, 90 participants (66.18%), presented some degree of hepatic steatosis, with mild being the most common in 34 patients (25%). Regarding fibrosis, 33 (24.26%) patients presented some degree of fibrosis. 76 (55.8%) patients were diagnosed with MASLD, while 14 (10.29%) patients with hepatic steatosis did not meet any criteria for metabolic syndrome. No significant differences were observed regarding disease activity, but differences were seen in nutritional variables such as BMI, weight, and waist circumference. Conclusions: In patients with IBD, the presence of non-alcoholic hepatic steatosis is significant, with 66.18% (n=90) of patients showing some degree of steatosis. More than half of the patients [n=76 (55.8%)] met the criteria for MASLD.

Conflict of interest: No Introduction and Objectives: Non-invasive methods for screening metabolic dysfunction-associated steatotic liver disease (MASLD) are gaining attention. A recent advancement in non-invasive screening is the MAFLD-S score, a tool that exclusively uses clinical data to predict the risk of MASLD.The aim is to evaluate the performance of the MAFLD-S score to identify individuals with MASLD in a cohort of apparently healthy individuals. Patients / Materials and Methods: A cross-sectional study was conducted including adults with unknown MASLD. A transient elastography was performed and hepatic steatosis was defined by a controlled attenuation parameter (CAP) > 248 dB/m. The MASLD criteria were assessed, and the MAFLD-S score, Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) were calculated in each member of the cohort. The classification accuracy of these scores was evaluated through their areas under the receiver-operating characteristic (AUROC) curves and their calibration to predict the risk of MASLD was assessed graphically. Results and Discussion: A total of 521 participants were included, being 61% women, and the mean age was 41 years. The frequency of MASLD in the study population was 44.1%. The area under the ROC curve for MAFLD-S was 0.823 (95% CI, 0.788-0.858), for FLI was 0.841 (95% CI, 0.807-0.875) and for HSI was 0.822 (95% CI, 0.787-0.858). The calculated sensitivity for MAFLD-S score using the recommended threshold was 61% (95% CI 0.55-0.68) and specificity of 81% (95% CI 0.77-0.86), for FLI sensitivity was 62% (95% CI 0.56-0.68) and specificity was 82% (95% CI 0.78-0.87) and for HSI sensitivity was 85% (95% CI 0.80-.89) and specificity was 61% (95% CI 0.56-0.67). Conclusions: The MAFLD-S score, a tool that only uses clinical variables, confirmed to be a very good tool for screening MASLD in apparently healthy individuals in Mexico.

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Monitoring wildlife populations at scale is fraught with logistical and resource constraints. Despite this, estimating wildlife population state variables and vital rates remains crucial for science, and to assess conservation investment and effort. The veracity and transparency of results also helps prevent politicization of wildlife populations. In Uganda, robust estimates of carnivore population size are rare in the literature. To overcome a near two-decade long data gap we initiated a survey of African lions, leopards, and spotted hyenas with the Uganda Wildlife Authority across six important protected areas. Surveys were conducted within a spatial capture-recapture framework, the industry gold-standard for monitoring carnivore populations. For lions, we used unstructured spatial sampling protocols (in the form of vehicle-based searches), while for leopards, and spotted hyenas we deployed camera traps. Our protocols were designed to obtain unambiguous individual identification photographs. This large-scale effort involved data collection by >100 local conservation stakeholders (including lodge guides, trophy hunters, university students, and government rangers). Locally extinct in three areas, we show lion numbers are precariously low in two of three sites where they still occur (Queen Elizabeth abundance=39.72, Posterior standard deviation (PSD)=7.96; Kidepo Valley abundance=22.23, PSD=11.67). Murchison Falls was identified as Uganda’s lion stronghold with an estimate of ∼240 individuals (PSD=34) and average park-wide densities of 7.43 individuals/100 km2 (PSD=1.05). Leopard densities were highest in Lake Mburo and Murchison Falls. In Murchison they reach some of the highest densities in Africa (14.06 individuals/100 km2, PSD=2.65). Spotted hyena densities were high compared to lions (range=6.15–45.31 individuals/100 km2), except in Lake Mburo where densities were markedly lower (park abundance=23 individuals in 370 km2, PSD=5.26). Our work has critical policy implications, and forms the foundation of the new Strategic Action Plan for Large Carnivore Conservation in Uganda (2023–2033). It also illustrates how cutting-edge, transparent and collaborative science, implemented by multiple wildlife conservation stakeholders can help gauge the conservation status of their wildlife resources.

Objectives: Lack of awareness of Alzheimer's disease (AD) among Black Americans may undermine their ability to identify potential AD risk. We examined Black Americans' perceptions and knowledge of AD, and views of a healthy brain, which may contribute to the development of effective and culturally sensitive strategies to address racial disparities in AD. Methods: We conducted a mixed-methods study, integrating a cross-sectional survey of 258 older (>55 years) Black participants and qualitative interviews with a sub-sample of N = 29. Both data sets were integrated to inform the results. Results: Participants endorsed having little knowledge of AD. While most participants reported practicing a healthy lifestyle to promote a healthy brain, the range of activities listed were limited. Participants made several suggestions to increase AD awareness, which includes using AD educational materials containing information that would benefit the whole family, not only older adults. Outreach approaches that address both individual behaviors and structural factors were also encouraged. Conclusion: Our findings identify ongoing needs to improve AD awareness among traditionally under-represented groups. Innovation: The study utilized novel approaches to examine participants' perspectives of AD that included a diverse sample of research naïve participants, and integrated exploration of participants' views of AD and brain health.

A vast multitude of tasks in histopathology could potentially benefit from the support of artificial intelligence (AI). Many examples have been shown in the literature and first commercial products with FDA or CE-IVDR clearance are available. However, two key challenges remain: (1) a scarcity of thoroughly annotated images, respectively the laboriousness of this task, and (2) the creation of robust models that can cope with the data heterogeneity in the field (domain generalization). In this work, we investigate how the combination of prototypical few-shot classification models and data augmentation can address both of these challenges. Based on annotated data sets that include multiple centers, multiple scanners, and two tumor entities, we examine the robustness and the adaptability of few-shot classifiers in multiple scenarios. We demonstrate that data from one scanner and one site are sufficient to train robust few-shot classification models by applying domain-specific data augmentation. The models achieved classification performance of around 90% on a multiscanner and multicenter database, which is on par with the accuracy achieved on the primary single-center single-scanner data. Various convolutional neural network (CNN) architectures can be used for feature extraction in the few-shot model. A comparison of nine state-of-the-art architectures yielded that EfficientNet B0 provides the best trade-off between accuracy and inference time. The classification of prototypical few-shot models directly relies on class prototypes derived from example images of each class. Therefore, we investigated the influence of prototypes originating from images from different scanners and evaluated their performance also on the multiscanner database. Again, our few-shot model showed a stable performance with an average absolute deviation in accuracy compared to the primary prototypes of 1.8% points. Finally, we examined the adaptability to a new tumor entity: classification of tissue sections containing urothelial carcinoma into normal, tumor, and necrotic regions. Only three annotations per subclass (e.g., muscle and adipose tissue are subclasses of normal tissue) were provided to adapt the few-shot model, which obtained an overall accuracy of 93.6%. These results demonstrate that prototypical few-shot classification is an ideal technology for realizing an interactive AI authoring system as it only requires few annotations and can be adapted to new tasks without involving retraining of the underlying feature extraction CNN, which would in turn require a selection of hyper-parameters based on data science expert knowledge. Similarly, it can be regarded as a guided annotation system. To this end, we realized a workflow and user interface that targets non-technical users.

The widespread adoption of electric vehicles (EVs) underscores the urgent need for innovative approaches to estimate their lithium-ion batteries’ state of health (SOH), which is crucial for ensuring safety and efficiency. This study introduces SOH-TEC, a transformer encoder-based model that processes raw time-series battery and vehicle-related data from a single EV trip to estimate the SOH. Unlike conventional methods that rely on lab-experimented battery cycle data, SOH-TEC utilizes real-world EV operation data, enhancing practical application. The model is trained and evaluated on a real-world dataset collected over nearly three years from three EVs. This dataset includes reliable SOH labels obtained through periodic constant-current full-discharge tests using a chassis dynamometer. Despite the challenges posed by noisy EV real-world data, the model shows high accuracy, with a mean absolute error of 0.72% and a root mean square error of 1.17%. Moreover, our proposed pre-training strategies with unlabeled data, particularly SOH ordinal comparison, significantly enhance the model’s performance; using only 50% of the labeled data achieves results nearly identical to those obtained with the full dataset. Self-attention map analysis reveals that the model primarily focuses on stationary or consistent driving periods to estimate SOH. While the study is constrained by a dataset featuring repetitive driving patterns, it highlights the significant potential of transformer for SOH estimation in EVs and offers valuable insights for future data collection and model development.

Introduction: To minimize the risk of developing foot-ulcers, persons with diabetes are given the advice to daily inspect their feet and to apply skincare formulations. However, commercially available skincare products have rarely been developed and evaluated for diabetes foot care specifically. The primary aim of this randomized controlled trial (RCT) is to evaluate the effects in reducing foot xerosis in persons with diabetes without foot-ulcers using two skincare creams containing different humectants (interventions) against a cream base non-humectant (comparator). Secondary outcomes are to evaluate differences on skin barrier integrity, low-molecular weight biomarkers and skin microbiota, microcirculation including transcutaneous oxygen pressure, degree of neuropathy, and HbA1c between intervention-comparator creams. Methods: Two-armed double-blind RCT, registered in ClinicalTrials.gov Identifier: NCT06427889. With 80 % power, two-tailed significance of 2.5 % in each arm, 39 study persons is needed in each arm, total 78 persons, 98 including dropouts, to be able to prove a reduction of at least one category in the Xerosis Severity Scale with the intervention creams compared to the comparator. In one arm, each participant will treat one foot with one of the intervention creams (Oviderm® or Canoderm®), while the opposite foot will be treated with the comparator cream (Decubal®lipid cream), twice a day. If needed, participants are enrolled after a wash-out period of two weeks. The participants will undergo examinations at baseline, day 14 and day 28. Discussion: This RCT evaluate the potential effects of humectants in skin creams against foot xerosis in persons with diabetes.

The present study investigates the use of SO42-/TiO2Nb2O5 (STNO) catalyst prepared through the modified sol-gel method in the process of xylose dehydration to furfural. The reaction was carried out in a biphasic solvent consisting of toluene and water. The catalyst used in this study was subjected to several characterization methods, including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The textural properties of the catalyst were evaluated by conducting N2 adsorption and desorption measurements using the Brunauer-Emmett-Teller (BET) method. The impact of catalyst dosage, resident time, xylose concentration, and reaction temperature in the dehydration of xylose to produce furfural was explored. The study employed response surface methodology to identify the optimal operational parameters that would result in the highest furfural selectivity. At a reaction temperature of 150 °C and a reaction time of 180 min, a maximum conversion of xylose of 98 mol%, furfural selectivity of 74 mol%, and a furfural yield of 63 mol% was obtained. The activation energy for the synthesized catalyst was determined to be 26.7 KJ/mol. The results of this investigation show the great potential that sulfated titanium-niobium mixed oxides have in transforming biomass resources into value-added compounds.

Opioid use disorder (OUD) is associated with a history of early-life adversity (ELA), an association that is particularly strong in women. In a rodent model, we previously found that ELA enhances risk for opioid addiction selectively in females, but the mechanisms for this effect are unclear. Here, we show that ELA robustly alters cFos responses to opioid drugs in females’ nucleus accumbens (NAc) and basolateral amygdala (BLA), but not elsewhere. We further identify delta opioid receptors (DOR), which mature in the first week of life and thus later than kappa or mu opioid receptors, as a potential mediator of ELA's impacts on reward circuit functions. Accordingly, DOR mRNA in NAc was persistently reduced in adult females with ELA history. Moreover, pharmacological stimulation of NAc DORs increased opioid demand in control females (recapitulating the ELA phenotype), while blocking DORs in ELA females conversely reduced high-effort drug consumption, simulating the control rearing phenotype. These findings support a role for NAc DORs in mediating ELA-induced opioid vulnerability. In contrast, BLA neurons expressing DOR protein do not overlap heroin- responsive cells in ELA rats, arguing against a direct relationship of BLA DORs to heroin's addiction-relevant actions in the brain. Together, these results suggest a novel and selective role for NAc DORs in contributing to enduring, ELA-provoked vulnerability to OUD.

Summary: A wide selection of behavioral assays in systems neuroscience relies on head-fixation protocols to integrate in vivo multi-photon imaging approaches. For this, simultaneous pupillometry and locomotion tracking in head-fixed mice are used to measure behavioral responses and identify neural correlates. Here, we present an open-source protocol for assembling a complete head-fixation system that integrates pupillometry and locomotion-estimated tracking with multi-photon calcium imaging. We include detailed procedures for head-fixation and for data collection. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Persistence of HIV-1 in cellular reservoirs results in lifelong infection, with cure achieved only in rare cases through ablation of marrow-derived cells. We report on optimization of an approach that could potentially be aimed at eliminating these reservoirs, hijacking the HIV-1 alternative splicing process to functionalize the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) cell suicide system through targeted RNA trans-splicing at the HIV-1 D4 donor site. AUG1-deficient HSVtk therapeutic pre-mRNA was designed to gain an in-frame start codon from HIV-1 tat1. D4-targeting lentiviral vectors were produced and used to transduce HIV-1-expressing cells, where trans-spliced HIV-1 tat/HSVtk mRNA was successfully detected. However, translation of catalytically active HSVtk polypeptides from internal AUGs in HSVtkΔAUG1 caused GCV-mediated cytotoxicity in uninfected cells. Modifying these sites in the D4 opt 2 lentiviral vector effectively mitigated this major off-target effect. Promoter choice was optimized for increased transgene expression. Affinity for HIV-1 RNA predicted in silico correlated with the propensity of opt 2 payloads to induce HIV-1 RNA trans-splicing and killing of HIV-1-expressing cells with no significant effect on uninfected cells. Following latency reversing agent (LRA) optimization and treatment, 45% of lymphocytes in an HIV-1-infected latency model could be eliminated with D4 opt 2/GCV. Further development would be warranted to exploit this approach.

Purpose: Randomized studies demonstrated the oncological equivalence of (ultra-)hypofractionation compared to a 5-week schedule in postoperative radiotherapy of breast cancer. Due to the low incidence and long latency of secondary malignancies, there are currently no reliable clinical data regarding the influence of fractionation regimens on the development of secondary malignancies. Material and methods: For 20 patients with right or left-sided breast cancer, postoperative treatment plans were created using 3D-CRT (n = 10) or VMAT (n = 10) for three different fractionation schedules: 5-week schedule with 50.4Gy in 1.8Gy (28fx), hypofractionation with 40.05Gy in 2.67Gy (15fx) and ultra-hypofractionation with 26Gy in 5.2Gy (5fx). The EARs (absolute additional cases of disease per 10,000 patient-years) for secondary malignancies in the lung, contralateral breast, esophagus, liver, thyroid, spinal cord, bones and soft tissue were calculated using a fraction-dependent dose-response model. Results: Based on risk modulation, (ultra-)hypofractionation resulted in significantly lower EARs for lung cancer (LC), contralateral breast cancer (CBC) and soft tissue sarcoma (STS) (p

The introduction of fluorine in compounds plays a crucial role in drug development as it greatly influences their final pharmacokinetic and dynamic properties. Due to the prevalence of fluorine in FDA-approved drugs in recent years, identifying the mechanisms driving their chemical transformations has become crucial in the drug discovery landscape. 19F NMR spectroscopy is a powerful analytical technique that allows for the examination of fluorine-containing compounds, offering valuable information about their structure, dynamics, and reactivity. NMR spectra can be interpreted through the leveraging of Density Functional Theory (DFT). However, the screening of compounds and discovery of feasible drug candidates is limited due to its computational cost. Here, we present a machine learning approach to accelerate the prediction of DFT-calculated 19F NMR chemical shifts. The fluorine atoms’ features in the models were derived from their local three-dimensional environments, representing their neighboring atoms within a radius of n Å away from the given fluorine atom in the compound. A comparative analysis of thirteen regression models was conducted using features extracted from 501 fluorinated compounds in our laboratory’s chemical inventory. Among the models, Gradient Boosting Regression (GBR) exhibited the highest performance, achieving a mean absolute error of 3.31 ppm with a local environment radius of 3 Å. This demonstrates a comparable accuracy to DFT calculations while reducing computational time from several hundred seconds to milliseconds. 3 Å was also found to be the most optimal radius across all models when encoding features for local atomic environments.

Current downstream processing of monoclonal antibodies (mAbs) is limited in throughput and requires harsh pH conditions for mAb elution from Protein A affinity ligands. The use of an engineered calcium-dependent ligand (ZCa) in magnetic separation applications promises improvements due to mild elution conditions, fast processability, and process integration prospects. In this work, we synthesized and evaluated three magnetic nanoparticle types immobilized with the cysteine-tagged ligand ZCa-cys. Ligand homodimers were physically immobilized onto bare iron oxide nanoparticles (MNP) and MNP coated with tetraethyl orthosilicate (MNP@TEOS). In contrast, ZCa-cys was covalently and more site-directedly immobilized onto MNP coated with (3-glycidyloxypropyl)trimethoxysilane (MNP@GPTMS) via a preferential cysteine-mediated epoxy ring opening reaction. Both coated MNP showed suitable characteristics, with MNP@TEOS@ZCa-cys demonstrating larger immunoglobulin G (IgG) capacity (196 mg g−1) and the GPTMS-coated particles showing faster magnetic attraction and higher IgG recovery (88 %). The particles pave the way for the development of calcium-dependent magnetic separation processes.

A 76-year-old man with a history of malignant pleural mesothelioma treated with pembrolizumab underwent FDG-PET/CT for restaging. The images demonstrated FDG uptake overlying the right hepatic and splenic artery, which were new from the previous FDG-PET/CT 2.5 years prior before the patient started pembrolizumab, suspicious for vasculitis. A follow-up MRI supported the diagnosis with evidence of celiac, splenic, common hepatic, and right hepatic artery involvement. Pembrolizumab was discontinued and the patient received a short course of oral glucocorticoids. Subsequent FDG-PET/CT performed 14 months after initiation of treatment for vasculitis demonstrated resolution of vasculitis. Immune checkpoint inhibitors can cause vasculitis, which can be recognized on FDG-PET/CT and lead to appropriate treatment.

Robot-assisted imaging-guided sentinel lymph node biopsy is a novel technique that has not been widely investigated in testicular germ cell tumor (GCT). Current staging strategies have poor accuracy for prediction of occult metastatic disease in clinical stage I GCT. Feasibility studies have used 99mTc-nanocolloid staining during laparoscopic procedures. The RAISN trial is investigating robot-assisted lymph node resection guided by indocyanine green fluorescence imaging. This new diagnostic approach is potentially more precise and easier to apply, and is widely available. Confirmation of its utility could change the management of newly diagnosed GCT by reducing overtreatment and treatment-related toxicity.

ABSTRACT: Although dietary phosphorus (P) deprivation extending from the dry period into early lactation impairs health and productivity of cows, restricting dietary P supply during the dry period not only appears to be innocuous but rather effectively mitigates hypocalcemia during the first wk of lactation. To investigate possible negative metabolic effects of P deprivation during the dry period, the present study tested the hypothesis that restricted dietary P supply during the dry period alters the liver transcriptome of dairy cows during the periparturient period. Thirty late-pregnant multiparous Holstein-Friesian dairy cows entering their second, third, or fourth lactation were assigned to either a dry cow ration with low (LP, 0.16% P in DM) or adequate P content (AP, 0.35% in DM) during the last 4 wk of the dry period (n = 15/group). Liver transcriptomics, which was carried out in a subset of 5 second-parity cows of each group (n = 5), and determination of selected hormones and metabolites in blood of all cows, was performed ∼1 wk before calving and on d 3 postpartum. Liver tissue specimens and blood samples were obtained by a micro-invasive biopsy technique from the right tenth intercostal space and puncture of a jugular vein, respectively. One hundred seventy-five hepatic transcripts were expressed differentially between LP versus AP cows in late pregnancy, and 165 transcripts differed between LP versus AP cows in early lactation (fold change >1.3 and

Background/Objective: Severe hypocalcemia is common in critically ill patients. There are different mechanisms. To our knowledge, there are no data about the acute presentation of hypocalcemia at the time of diagnosis of aplastic anemia (AA). The objective of this case report was to describe the case of hypoparathyroidism with severe hypocalcemia in a critically ill patient with AA. Case Report: A 60-year-old man presented with severe hypocalcemia with a calcium level of 6.1 mg/dL (reference range, 8.6-10.3 mg/dL) and hypoparathyroidism with a parathyroid hormone level of 11 pg/mL (reference range, 12-88 pg/mL). He developed a critical state caused by newly diagnosed AA and its complications, such as an acute decrease in the platelet value to a critically low level of 2 × 103/cmm, complicated by neutropenic fever and lower gastrointestinal bleeding. After the initiation of immunosuppressive therapy for AA, his parathyroid hormone-calcium metabolism improved and remained stable but did not normalize completely. Discussion: In our patient, hypoparathyroidism with hypocalcemia may have been caused by cytokine-related upregulation of the calcium-sensing receptor in the setting of AA. On the other hand, given the severity of the initial hypocalcemia and only partial improvement in calcium homeostasis with residual mild hypocalcemia after treatment initiation for AA, autoimmune causes cannot be entirely ruled out, nor could a combination of cytokine-mediated and autoimmune causes. Conclusion: It is essential to treat the underlying causes of hypocalcemia, which, in this case, were AA and hypoparathyroidism.

Balo's concentric sclerosis (BCS) is a rare subtype of multiple sclerosis. Advanced MRI metrics, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), mean diffusivity (MD), and the ratio of total N-acetylaspartate concentration/total creatine concentration (tNAA/tCr) using proton magnetic resonance spectroscopy (1H-MRS), are commonly used in research studies to investigate the effect of a disease modifying therapy (DMT). We report a patient diagnosed with BCS, receiving ocrelizumab, and provide a comparison of the lesion volume, T1-gadolinium lesion volume, MTR, FA, MD, and MRS metrics at baseline, 6- and 12-month follow-up. There was a reduction in Balo's lesion volume on fluid-attenuated inversion recovery (FLAIR) imaging observed in our patient from baseline (23.925 mL) to 12-month follow-up (2.391 mL), with the largest decrease from baseline to 6-month follow-up (3.650 mL). There was no T1-gadolinium enhancement seen at month 6 and 12. The MTR of the lesion did not change significantly (baseline = 50.9%, 6-month = 49.9%, 12-month =50.1%) but the FA increased from 0.188 (at baseline) to 0.304 (at 6 months), while the 12-month follow-up FA was 0.297. We also noted a reduction in MD from baseline (1.333 × 10−3 mm2/s) to 6-month follow-up (1.037 × 10−3 mm2/s), while the 12-month follow-up MD was 1.086 × 10−3 mm2/s. There was a 10.3% increase in tNAA/tCr from 1.583 (at month 0) to 1.747 (at month 12). Our results demonstrate for the first time a direct effect of ocrelizumab on BCS lesions. To validate our findings, more observations are needed in a larger group of BCS patients.

The conventional metered dose inhaler (MDI) has long served as a cornerstone in the management of asthma and chronic obstructive pulmonary disease (COPD), affecting millions annually. Despite its advantages, a persistent challenge is seen in the form of patient education and the unchanged design of these inhalers since their inception in 1956. This lack of progress in MDI design has inadvertently contributed to incidences of foreign body inhalation. In this case presentation we report a 50-year-old male with a past medical history of asthma, who faced an incident of foreign body inhalation with use of his inhaler. The patient aspirated a dime when he administered his inhaler, as it had become lodged in the device's mouthpiece, which was uncapped. This case, like many others, demonstrates the need for innovative changes in MDI inhaler design. While numerous articles or cases concentrate on foreign body removal, the primary objective of this case report is to investigate preventative measures and solutions aimed at averting incidents of inhalation.