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Background: Use of heart failure-exacerbating medications (HFEMs) may lead to preventable episodes of acute decompensated heart failure (HF). HFEMs use is common in patients with HF, and there may be opportunities to reduce their use from the emergency department (ED)., Methods: We performed an observational study on patients with HF presenting to EDs within a healthcare system between 1 January 2016 and 31 December 2020. Patients with chronic HF were identified using diagnostic codes within the electronic health record. The cohort was restricted to ambulatory (i.e., discharged to home) ED encounters. Medications, either ordered in the ED or prescribed at ED discharge, were extracted from the medication administration record and identified as potential HFEMs based on the 2016 American Heart Association Scientific Statement. Descriptive statistics were used to summarize the prevalence of HFEM use during ambulatory ED encounters. Exploratory analyses to identify correlates of HFEM use were performed., Results: The study cohort included 23,907 ED encounters. ED administration or prescription of HFEMs occurred during 20% of ambulatory ED encounters. HFEM administration in the ED (17%) was more common than HFEM prescription at ED discharge (6%). The most common HFEMs administered in the ED included nonsteroidal anti-inflammatory drugs (11%) and albuterol (7%)., Conclusion: HFEM use is common in patients with HF seeking ED care, occurring in roughly one-fifth of ambulatory ED encounters. There may be opportunities to optimize medication use among patients with HF in the ED., Competing Interests: Declarations Funding Dr. Casey received support for the conception and conduct of this work from the Society of Academic Emergency Medicine Foundation (#A23-0022). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. Conflicts of Interest I/we have read and understood the Springer statement on Competing Interests. M.F.C. and P.G. disclose their roles in the Junior Investigator Intensive Program of the US Deprescribing Research Network (USDeN) funded by the National Institute on Aging (R24AG064025). P.G. is supported by a USDeN Pilot Grant. M.F.C. is supported by a Collaborative Award from the USDeN. There are no other conflicts of interests reported by any other authors. Ethics Approval The study was reviewed and approved with a waiver of consent by the University of North Carolina at Chapel Hill Institutional Review Board (IRB # 21-2888). Consent to Participate Not applicable (IRB granted waiver of exemption). Consent to Publish Not applicable. Data Availability The data and code that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are in controlled access data storage at University of North Carolina at Chapel Hill. Code Availability All statistical analyses were performed in Stata MP/16.1 and SAS 9.4. Code is available from the corresponding author upon reasonable request. Author Contributions Conceived the study: M.F.C., P.P.C., J.E.R., M.L.M. Study design: M.F.C., P.P.C., P.S., J.E.R., M.L.M. Obtained data: M.F.C., J.E.R., T.B. Managed and analyzed the data : M.F.C., S.V.C., T.B. Drafted the manuscript: M.F.C., A.M., J.H., M.L.M. Revision of manuscript: All. Final approval of manuscript: All authors read and approved the final version., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Outcomes from pancreatic ductal adenocarcinoma (PDAC) remain poor and better methods of prognostication and therapeutic approaches are needed. Recent advances in cancer genomics have led to the development of molecular subtypes of PDAC associated with clinical outcomes. Current evidence also suggests that the subtypes have differential response to first-line chemotherapy regimens. PDAC is also characterized by different stroma and immune environments. Further work is needed to confirm the utility of these subtypes to predicting response to different systemic therapies., Competing Interests: Disclosure PurIST was licensed to GeneCentric Therapeutics Inc (JJY). Funding JJY is supported by R01 CA199064, U01 CA274298, U24 CA211000, and P50 CA257911., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Indeterminate renal masses are increasingly incidentally found on cross-sectional imaging. 99m Tc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) scans can be used to identify oncocytomas and oncocytic renal neoplasms, including a subset of chromophobe renal cell carcinomas (chRCCs), which are viewed as false-positive., Procedure: Patients imaged with renal sestamibi scans between 2014 and 2023 were reviewed. Those patients with solitary tumors that were originally classified as chRCC were included in the analysis. Imaging with SPECT/CT from the liver dome down had been carried out 75 min after the administration of 925 MBq of 99m Tc-sestamibi. All available H&E and immunostained slides were re-reviewed and classified according to WHO 2022 criteria. Confirmatory immunohistochemical stains were performed in tumors considered morphologically suspicious for non-chRCC entities., Result: A total of 18 patients with solitary tumors were included in the final analysis. 13/18 (72.2%) tumors in this cohort remained classified as chRCC, with 4/18 (22.2%) being eosinophilic-variant chRCC. The reclassified tumors (5/18 [27.8%]) included 2/18 (11.1%) low-grade oncocytic tumor (LOT), 1/18 (5.5%) eosinophilic vacuolated tumor (EVT), and 2/18 (11.1%) unclassified low-grade oncocytic neoplasms. As such, only 2/9 (22.2%) qualitatively "hot" tumors were chRCC other than eosinophilic-variant and only 1/9 (11.1%) "cold" tumors was a histology other than chRCC., Conclusion: Based on current histopathologic classification methods, it is likely that the "false-positive" rate of uptake on renal sestamibi scans with chRCC has been over-stated. Further study is warranted to better refine the optimal utility of renal sestamibi scans for non-invasive risk stratification of indeterminate renal masses., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Objective: Meningiomas are the most common primary central nervous tumor and are often treated with radiation therapy. This study examines the long-term volumetric changes of intracranial meningiomas in response to radiation therapy. The objective is to analyze and model the volumetric changes following treatment., Methods: Data from a retrospective single-institution database (2005-2015) were used, with inclusion criteria being patients with a diagnosis of meningiomas, along with additional inclusion criteria consisting of treatment with radiation, having at least three magnetic resonance imaging (MRI) scans with one or more before and after radiation treatment, and the patients following up for at least eighteen months. Exclusion criteria consisted of patients less than 18 years old, patients receiving surgery and/or adjuvant chemotherapy following radiation, and patients without any available details regarding radiation treatment parameters. Tumor volumes were measured via T1-weighted post-contrast MRI and calculated using the ABC/2 ellipsoidal approximation, a method allowing for the measurement of non-linear growth volume reduction., Results: Of 48 meningioma patients considered, 10 % experienced post-radiation growth, while 75 % witnessed a ≥50 % decrease in volume over a follow-up period of 0.3-14.9 years. Median decay rate was 0.81, and within 1.17 years, 90 % achieved the predicted volume reduction. Predicted vs. actual volumes showed a mean difference of 0.009 ± 0.347 cc. Initial tumor volumes strongly correlated (Pearson's R=0.98, R-squared=0.96) with final asymptotic volumes, which had a median of 1.50 cc, with interquartile range (IQR) = [0.39, 3.67]., Conclusion: 90 % of patients achieved tumor-volume reduction at 1.17 years post-treatment, reaching a non-zero asymptote strongly correlated with initial tumor volume, and 75 % experienced at least a 50 % volume decrease. Individual volume changes for responsive meningiomas can be modeled and predicted using exponential decay curves., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: To assess the characteristics of patients enrolled in the ILD-PRO Registry., Methods: The ILD-PRO Registry is a multicentre US registry of patients with progressive pulmonary fibrosis. This registry is enrolling patients with an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis who have reticular abnormality and traction bronchiectasis on HRCT, and who meet criteria for ILD progression within the prior 24 months. Patient characteristics were analysed based on the number of patients with available data., Results: Of the first 491 patients enrolled, the majority were white (75.4%) and female (60.6%); 47.4% had a history of smoking. Reported ILDs were autoimmune disease-associated ILDs (47.2%), hypersensitivity pneumonitis (17.5%), idiopathic non-specific interstitial pneumonia (9.1%), interstitial pneumonia with autoimmune features (8.9%), unclassifiable ILD (7.6%), other ILDs (9.7%). At enrolment, median (Q1, Q3) FVC % predicted was 62.2 (49.4, 72.4) and DLco % predicted was 39.2 (30.2, 49.2). Median (Q1, Q3) total score on the St. George's Respiratory Questionnaire was 50.8 (35.9, 64.7). The most common comorbidities were gastroesophageal reflux disease (61.1%) and sleep apnoea (29.6%). Overall, 64.5% of patients were receiving immunosuppressive or cytotoxic therapy, 61.1% proton-pump inhibitors, 53.2% oral steroids, 19.8% nintedanib and 3.6% pirfenidone., Conclusions: Patients enrolled into the ILD-PRO Registry have a variety of ILD diagnoses, marked impairment in lung function and health-related quality of life, and high medication use. Longitudinal data from this registry will further our knowledge of the course of progressive pulmonary fibrosis., Trial Registration: ClinicalTrials.gov, NCT01915511; registered August 5, 2013., (© 2024. The Author(s).)

Normal hepatic arterial anatomy consists of the right hepatic artery and left hepatic artery branching from the common hepatic artery. Despite this being the most common configuration, many variations have been described. Here, we present a rare variant of hepatic arterial anatomy- a replaced right hepatic artery with direct aortic origin. Additionally, the patient was found to have a dorsal pancreatic artery originating from the replaced right hepatic artery This was angiographically identified during mapping for transarterial radioembolization for hepatocellular carcinoma. The unique anatomy in this case and the effect it had on transarterial radioembolization planning described herein demonstrates the necessity of understanding variant hepatic arterial anatomy in endovascular hepatic interventions., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

An ongoing challenge in academic radiology is balancing the need to read the scans and generate relative value units (RVUs) with the need to ensure academic leadership and the consistent production of impactful publications. Indeed, the tripartite mission of academic radiology (i.e. clinical care, research, and teaching) does not lend itself to obvious answers in an era when institutions and departments are increasingly focused on RVU generation. Even the minority of radiologists who are interested in pursuing the academic mission and accept academic jobs are likely to find their time increasingly squeezed by massive volumes of scans to read and the priority placed on RVU generation. There are often no incentives for impactful academic work, leading to a decreasing relative number of manuscript submissions from U.S.-based researchers. With the lack of external incentivization for publication, writing and publishing papers must instead be driven by intrinsic enjoyment and a sense of accomplishment. The ability to think of an idea, to get a group of co-authors together, to acquire the data and/or put together the idea into a form that is ready for final publication, and to see that process through to the end is rewarded only by personal satisfaction. Perhaps, in the era of RVU generation, publishing papers in a form of defiance of a system that is hampering the academic mission., Competing Interests: Declaration of competing interest The authors declare they have no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Structural modification based on existing drugs, which ensures the safety of marketed drugs, is an essential approach in developing new drugs. In this study, we modified the structure of cabotegravir by introducing the front alkyne on the core structure through chemical reaction, resulting in the synthesis of 9 compounds resembling 1,2,3-triazoles. The potential of these new cabotegravir derivatives as tumor suppressors in gastrointestinal tumors was investigated. Based on the MTT experiment, most compounds showed a reduction in the viability of KYSE30 and HCT116 cells. Notably, derivatives 5b and 5h exhibited the most significant inhibitory effects. To further explore the effects of derivatives 5b and 5h on gastrointestinal tumors, KYSE30 cells were chosen as a representative cell line. Both derivatives can effectively curtail the migration and invasion capabilities of KYSE30 cells and induce apoptosis in a dose-dependent manner. We further demonstrated these derivatives induce cell apoptosis in KYSE30 cells by inhibiting the expression of Stat3 protein and Smad2/3 protein. Based on the above results, we suggest they show promise in developing drugs for esophageal squamous cell carcinoma., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Introduction: The formative period of the specialty of gynecologic oncology was from 1968 to 1972 and became a board-certified specialty in 1973. During this formation there were no Black physicians participating in this process. We chronicle and document the incorporation of the first three board-certified Black physicians in the specialty of gynecologic oncology here for historical purposes., Methods: We highlight the hostile climate experienced by Black physicians before and during the formation of gynecologic oncology, review the acceptance and training of the first three Black physicians in the specialty and recognize their significant contributions to the field., Results: The biographies and the narrative of these men describe their impact and contribution to medicine. We chronicle the historic presence of the first board-certified Black gynecologic oncologists and pelvic surgeons in the United States., Conclusion: These three men represent the Black Founding Fathers of gynecologic oncology. Their perseverance in the face of adversity and commitment to excellence have left an indelible impact on the institutions that they developed, the individuals that they trained, and the patients that they served., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC 50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization., (© 2024. The Author(s).)

Introduction: Endometrial cancer is the most commonly diagnosed female genital tract malignancy in the United States of America. Racial disparities surrounding this particular disease have been extensively investigated for over 26-years. We sought to determine if research in this area has led to any significant improvements in this disparity., Methods: We performed a rapid systematic review of English language publications on racial disparities in endometrial cancer among African American (AAW) and white American women (WAW), from 1997 to 2023. We looked at trends in incidence and survival; impact of known poor prognostic factors (stage at diagnosis, histological subtypes, grade); co-morbidities; differences in treatment (surgery, radiation and chemotherapy); socioeconomic factors; differences in biological and genetic markers; and policies/declarations., Results: During the period under review (1997-2023), there was a notable increase in both disease incidence (39%) and mortality (26%) rates for AAW, in comparison to WAW among whom the incidence rates increased by 2% and mortality rates rose, but 9% less than for AAW. It should be noted that the current incidence rate of 29.4% in AAW represent a reversal of what is was 26-years ago, when the incidence rate was 17.8%. In comparison to WAW, AAW had a higher prevalence of poor prognostic variables, more co-morbidities, lower income levels, less insurance coverage, and were more frequently under treated with surgery, chemotherapy and radiation. To date no actionable molecular/genetic markers have been identified. We were unable to locate any published recommendations or active programs of implementation strategies/policies designed to effectively mitigate the documented racial disparity., Conclusion: Racial disparities in disease incidence and mortality in endometrial cancer rates between WAW and AAW have widened during a 26-year period of robust research, suggesting that current research alone is not enough to eliminate this disparity. Based on this rapid systematic review we have identified and analyzed the impact of causation variables on this disparity. Additionally, we have made strong and pertinent recommendations for the benefit of mitigating this escalating racial disparity., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Inc. All rights reserved.)

We introduced a terminal alkyne into the core structure of dolutegravir, resulting in the synthesis of 34 novel dolutegravir-1,2,3-triazole compounds through click chemistry. These compounds exhibited remarkable inhibitory activities against two hepatocellular carcinoma cell lines, Huh7 and HepG2. Notably, compounds 5e and 5p demonstrated exceptional efficacy, particularly against Huh7 cells, with IC 50 values of 2.64 and 5.42 μM. Additionally, both compounds induced apoptosis in Huh7 cells, suppressed tumor cell clone formation, and elevated reactive oxygen species (ROS) levels, further promoting tumor cell apoptosis. Furthermore, compounds 5e and 5p activated the LC3 signaling pathway, inducing autophagy, and triggered the γ-H2AX signaling pathway, resulting in DNA damage in tumor cells. Compound 5e exhibited low toxicity, highlighting its potential as a promising anti-tumor drug.

Background: Black Americans have the highest prevalence of hypertension in the USA. Black immigrants, who, by definition, have time-limited exposure to the USA, may provide insight into the relationship between exposure to the US environment, Black race, and hypertension., Methods: This is a cross-sectional analysis of pooled National Health Interview Survey (2004-2017) data of foreign-born White European and Black adults (N = 11,516). Multivariable robust Poisson regressions assessed the relationship between self-reported hypertension and duration of the residency (< 5, 5-9, 10-14, ≥ 15 years) among Black, Black African, Black Caribbean, and White European foreign-born residents., Results: In multivariable analyses-controlling for age, sex, education, poverty-to-income ratio, insurance status, recent encounter with a clinician, and BMI-Black foreign-born residents (PR = 1.40, 95% CI = 1.03, 1.90) and Black Africans (10-14 years.: PR = 1.70, 95% CI = 1.13, 2.56; ≥ 15 years.: PR = 1.56, 95% CI = 1.04, 2.34) with a duration of residency of at least 15 and 10 years, respectively, had a greater prevalence of hypertension than those with duration less than 5 years. A nonsignificant positive association between a duration of residency of at least 15 years (compared to less than 5 years) and self-reported hypertension was observed for White Europeans (PR 1.49, 95% CI = 0.88, 2.51) and Black Caribbeans (PR = 1.09, 95% CI = 0.69, 1.72)., Conclusion: Duration of residency is particularly associated with hypertension among Black Africans after migration to the USA. This discrepancy may be explained by differences in primary care utilization and awareness of hypertension diagnoses among recent African immigrants, along with greater stress associated with living in the USA., (© 2023. W. Montague Cobb-NMA Health Institute.)

Alzheimer's disease (AD) involves a complex pathological process that evolves over years, and its etiology is understood as a classic example of gene-environment interaction. The notion that exposure to microbial organisms may play some role in AD pathology has been proposed and debated for decades. New evidence from model organisms and -omic studies, as well as epidemiological data from the recent COVID-19 pandemic and widespread use of vaccines, offers new insights into the "germ hypothesis" of AD. To review new evidence and identify key research questions, the Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium and workshop: "New Approaches for Understanding the Potential Role of Microbes in Alzheimer's disease." Discussion centered around the antimicrobial protection hypothesis of amyloid accumulation, and other mechanisms by which microbes could influence AD pathology including immune cell activation, changes in blood-brain barrier, or direct neurotoxicity. This summary of proceedings reviews the content presented in the symposium and provides a summary of major topics and key questions discussed in the workshop., Competing Interests: This symposium was supported by funding from Dr. Leslie Norins and Mrs. Rainey Norins and the Benter Foundation and further supported by the NIH (P30AG072958; R38AG065762 to HEW). The work presented by symposium speakers receives grant funding. Monica M. Diaz is supported by the NIH (K23MH131466), the Alzheimer's Association (AARGD-22-924896) and the American Academy of Neurology. Kenneth E. Schmader received support from the Duke Pepper Older Americans Independence Center (NIA P30AG028716). Manolis Kellis has received NIH support from the following grants: AG054012|AD-complexity, AG058002|AD-dissection, AG062377|AD-endosomes, AG081017|ADpathogens, NS129032|VCID, NS110453|ADRD, NS115064|Vascular, AG062335|AD-Psychosis, AG074003|SexAD., (Published by Elsevier Inc.)

Federally qualified health centers (FQHCs) that provide comprehensive health services, including integrated behavioral health (IBH), transitioned to deliver care via telehealth during the COVID-19 pandemic. This study explored how FQHCs adapted IBH services using telehealth. A mixed-method design was used, pairing a survey disseminated to FQHC administrators with a structured interview. Of the 46 administrators who participated in the survey, 14 (30.4%) reported delivering IBH using telecommunication prior to the pandemic. Since COVID-19, almost all of the FQHCs surveyed used telecommunication to deliver IBH (n = 44, 95.7%). Nine interviews with FQHC administrators resulted in the four themes: telehealth was essential; core components of IBH were impacted; payment parity and reimbursement were a concern; and telehealth addressed workforce issues. Findings confirm the necessity of telehealth for FQHCs during COVID-19. However due to the lack of co-location, warm-handoffs and other core components of IBH were limited., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mounting evidence suggests considerable diversity in brain aging trajectories, primarily arising from the complex interplay between age, genetic, and environmental risk factors, leading to distinct patterns of micro- and macro-cerebral aging. The underlying mechanisms of such effects still remain unclear. We conducted a comprehensive association analysis between cerebral structural measures and prevalent risk factors, using data from 36,969 UK Biobank subjects aged 44-81. Participants were assessed for brain volume, white matter diffusivity, Apolipoprotein E (APOE) genotypes, polygenic risk scores, lifestyles, and socioeconomic status. We examined genetic and environmental effects and their interactions with age and sex, and identified 726 signals, with education, alcohol, and smoking affecting most brain regions. Our analysis revealed negative age-APOE-ε4 and positive age-APOE-ε2 interaction effects, respectively, especially in females on the volume of amygdala, positive age-sex-APOE-ε4 interaction on the cerebellar volume, positive age-excessive-alcohol interaction effect on the mean diffusivity of the splenium of the corpus callosum, positive age-healthy-diet interaction effect on the paracentral volume, and negative APOE-ε4-moderate-alcohol interaction effects on the axial diffusivity of the superior fronto-occipital fasciculus. These findings highlight the need of considering age, sex, genetic, and environmental joint effects in elucidating normal or abnormal brain aging., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction: At UNC, venous thromboembolism (VTE) patients are treated with a heparin nomogram including fixed-dose titration boluses to correct subtherapeutic heparin correlation values (HCVs). The bolus dose often exceeds the recommended loading dose in underweight patients, therefore raising concern for an increased bleeding risk. This evaluation aims to assess the safety of these titration boluses for underweight patients., Materials and Methods: Adult patients receiving intravenous heparin for VTE treatment and requiring at least one titration bolus were included. The underweight patients had a body mass index (BMI) <18.5 kg/m 2 while the patients in the control group had a BMI of 18.5-29.9 kg/m 2 . The primary outcome was the percentage of patients with a supratherapeutic HCV after the first titration bolus. Secondary outcomes included the percentage of patients with a supratherapeutic HCV requiring holding of the infusion, time to stable HCV, and clinically significant bleeding., Results: One hundred fifty-eight patients met inclusion criteria, with similar baseline characteristics between groups. There were 13.9 % of patients in both groups who had a supratherapeutic HCV after the first titration bolus. More underweight patients required holding of heparin. All patients took over 48 h to reach a stable HCV. There was no difference in clinically significant bleeding., Conclusions: Despite finding no significant difference, there remains clinical concern for increased bleeding risk in underweight patients as this population required heparin to be held due to supratherapeutic HCVs more often. More evidence is needed to evaluate the safety of fixed-dose heparin titration boluses in underweight patients due to the limited scope of this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Low- and middle-income countries often lack access to mental health services, leading to calls for integration within other primary care systems. In sub-Saharan Africa, integration of depression treatment in non-communicable disease (NCD) settings is feasible, acceptable, and effective. However, leadership and implementation climate challenges often hinder effective integration and quality of services. The aim of this study was to identify discrete leadership strategies that facilitate overcoming barriers to the integration of depression care in NCD clinics in Malawi and to understand how clinic leadership shapes the implementation climate., Methods: We conducted 39 in-depth interviews with the District Medical Officer, the NCD coordinator, one NCD provider, and the research assistant from each of the ten Malawian NCD clinics (note one District Medical Officer served two clinics). Based on semi-structured interview guides, participants were asked their perspectives on the impact of leadership and implementation climate on overcoming barriers to integrating depression care into existing NCD services. Thematic analysis used both inductive and deductive approaches to identify emerging themes and compare among participant type., Results: The results revealed how engaged leadership can fuel a positive implementation climate where clinics had heightened capacity to overcome implementation barriers. Effective leaders were approachable and engaged in daily operations of the clinic and problem-solving. They held direct involvement with and mentorship during the intervention, providing assistance in patient screening and consultation with treatment plans. Different levels of leadership utilized their respective standings and power dynamics to influence provider attitudes and perceptions surrounding the intervention. Leaders acted by informing providers about the intervention source and educating them on the importance of mental healthcare, as it was often undervalued. Lastly, they prioritized teamwork and collective ownership for the intervention, increasing provider responsibility., Conclusion: Training that prioritizes leadership visibility and open communication will facilitate ongoing Malawi Ministry of Health efforts to scale up evidence-based depression treatment within NCD clinics. This proves useful where extensive and external monitoring may be limited. Ultimately, these results can inform successful strategies to close implementation gaps to achieve integration of mental health services in low-resource settings through improved leadership and implementation climate., Trial Registration: These findings are reported from ClinicalTrials.gov, NCT03711786. Registered on 18/10/2018. https://clinicaltrials.gov/ct2/show/NCT03711786 ., (© 2023. The Author(s).)

Background: Globally, mental health disorders rank as the greatest cause of disability. Low and middle-income countries (LMICs) hold a disproportionate share of the mental health burden, especially as it pertains to depression. Depression is highly prevalent among those with non-communicable diseases (NCDs), creating a barrier to successful treatment. While some treatments have proven efficacy in LMIC settings, wide dissemination is challenged by multiple factors, leading researchers to call for implementation strategies to overcome barriers to care provision. However, implementation strategies are often not well defined or documented, challenging the interpretation of study results and the uptake and replication of strategies in practice settings. Assessing implementation strategy fidelity (ISF), or the extent to which a strategy was implemented as designed, overcomes these challenges. This study assessed fidelity of two implementation strategies (a 'basic' champion strategy and an 'enhanced' champion + audit and feedback strategy) to improve the integration of a depression intervention, measurement based care (MBC), at 10 NCD clinics in Malawi. The primary goal of this study was to assess the relationship between the implementation strategies and MBC fidelity using a mixed methods approach., Methods: We developed a theory-informed mixed methods fidelity assessment that first combined an implementation strategy specification technique with a fidelity framework. We then created corresponding fidelity indicators to strategy components. Clinical process data and one-on-one in-depth interviews with 45 staff members at 6 clinics were utilized as data sources. Our final analysis used descriptive statistics, reflexive-thematic analysis (RTA), data merging, and triangulation to examine the relationship between ISF and MBC intervention fidelity., Results: Our mixed methods analysis revealed how ISF may moderate the relationship between the strategies and MBC fidelity. Leadership engagement and implementation climate were critical for clinics to overcome implementation barriers and preserve implementation strategy and MBC fidelity. Descriptive statistics determined champion strategy fidelity to range from 61 to 93% across the 10 clinics. Fidelity to the audit and feedback strategy ranged from 82 to 91% across the 5 clinics assigned to that condition. MBC fidelity ranged from 54 to 95% across all clinics. Although correlations between ISF and MBC fidelity were not statistically significant due to the sample of 10 clinics, associations were in the expected direction and of moderate effect size. A coefficient for shared depression screening among clinicians had greater face validity compared to depression screening coverage and functioned as a proximal indicator of implementation strategy success., Conclusion: Fidelity to the basic and enhanced strategies varied by site and were influenced by leadership engagement and implementation climate. Champion strategies may benefit from the addition of leadership strategies to help address implementation barriers outside the purview of champions. ISF may moderate the relationship between strategies and implementation outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: As demonstrated by a plethora of studies, compromised executive functions (EF) and language are implicated in mechanisms of auditory verbal hallucinations (AVH), but the contribution of their interaction to AVH remains unclear. We hypothesized that schizophrenia patients with history of AVH (AVHh+) vs. without history of AVH (AVHh-) have a specific deficit of executive control of language and alterations in functional connectivity (FC) between the brain regions involved in EF and language, and these neuropsychological and neurophysiological traits are associated with each other., Methods: To explore the executive control of language and its contribution to AVH, we used an integrative approach involving analysis of neuropsychological and resting-state fMRI data of 34 AVHh+, 16 AVHh-, and 40 healthy controls. We identified the neuropsychological and FC measures that differentiated between AVHh+, AVHh-, and HC, and tested the associations between them., Results: AVHh+ were characterized by decreased category and phonological verbal fluency, utterance length, productivity in the planning tasks, and poorer retelling. AVHh+ had decreased FC between the left inferior frontal gyrus and the anterior cingulate cortex. Productivity in category verbal fluency was associated with the FC between these regions., Conclusions: Poor executive control of word retrieval and deficient programming of sentence and narrative related to more general deficits of planning may be the neuropsychological traits specific for AVHh+. A neurophysiological trait specific for AVHh+ may be a decreased FC between regions involved in language production and differentiation between alien- vs. self-generated speech and between language production vs. comprehension., Competing Interests: Declaration of competing interest This study was supported by the Russian Foundation for Basic Research, Grant No. 18-013-01214., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men, causing a huge number of deaths each year. Traditional chemotherapy for PCa mostly focused on targeting androgen receptors. However, some of the patients would develop resistance to hormonal therapy. In these cases, it is suggested for these patients to administer treatments in combination with other chemotherapeutics. Current chemotherapeutics for metastatic castration-resistant PCa could hardly reach satisfying effects, therefore it is crucial to explore novel agents with low cytotoxicity. Herein, a common drug against the human immunodeficiency virus (HIV), the dolutegravir (DTG) was modified to become a series of dolutegravir-1,2,3-triazole derivatives. Among these compounds, the 4d and 4q derivatives were verified with high anti-tumor efficiency, suppressing the proliferation of the prostate cancer cells PC3 and DU145. These compounds function by binding to the poly (adenosine diphosphate-ribose) polymerase (PARP), inactivating the PARP and inducing DNA damage in cancer cells. It is noteworthy that the 4d and 4q derivatives showed almost no impact on normal cells and mice. Thereby, the results reveal that these dolutegravir-1,2,3-triazole compounds are potential chemotherapeutics for PCa treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lower extremity trauma is one of the most common injury patterns seen in emergency medical and surgical practice. Vascular injuries occur in less than one percent of all civilian fractures. However, if not treated promptly, such injuries can lead to ischemia and death. Computed tomography angiography (CTA) is the non-invasive imaging gold standard and plays a crucial part in the decision-making process for treating lower extremity trauma. A novel, FDA-approved 3D reconstruction technique known as cinematic rendering (CR) yields photorealistic reconstructions of lower extremity vascular injuries depicting clinically important aspects of those injuries, aiding in patient workup and surgical planning, and thus improving patient outcomes. In this article, we provide clinical examples of the use of CR in evaluating lower extremity vascular injuries, including the relationship of these injuries to adjacent osseous structures and overlying soft tissues, and its role in management of lower extremity trauma., (© 2023. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Objectives: Urolithiasis represents a leading cause of emergency department (ED) presentation nationally, affecting approximately 10% of Americans. However, most patients require neither hospital admission nor surgical intervention. This study investigates patient and facility factors associated with potentially avoidable ED visits and their economic consequences., Study Design: Retrospective analysis., Methods: Patients presenting to the ED for index urolithiasis events were selected using Florida and New York all-payer data from the 2016 Healthcare Cost and Utilization Project state databases. Avoidable visits were defined as subsequent ED encounters following initial ED presentation that did not result in intervention, admission, or referral to an acute care facility. Utilizing multivariable logistic and linear regression, researchers discerned patient and facility factors predictive of avoidable ED presentations and associated costs., Results: Of the 167,102 ED encounters for urolithiasis, 7.9% were potentially avoidable, totaling $94,702,972 in potential yearly cost savings. Mean encounter-level costs were higher for unavoidable vs avoidable visits ($5885 vs $2098). In contrast, mean episode-based costs were similar for avoidable and unavoidable episodes ($7200 vs $7284). Receiving care in small metropolitan (vs large metropolitan) communities was associated with potentially avoidable visits, whereas increased comorbidities and Hispanic ethnicity were protective against avoidable visits., Conclusions: The incidence of ED use for subsequent urolithiasis care reveals opportunity for enhanced outpatient availability to reduce hospital-based costs. Several nonclinical factors are associated with potentially avoidable ED visits for urolithiasis, which, if appropriately targeted, may represent an opportunity to reduce health care spending without compromising the quality of care delivery.

Background: In ovulating psychiatric patients experiencing suicidality, suicidal ideation (SI) often peaks perimenstrually. Our recent double-blind, placebo-controlled, crossover randomized clinical trial (RCT; NCT03720847) showed that perimenstrual administration of estradiol and progesterone (EP) can prevent this peak in SI and depressed mood. In this pre-registered follow-up analysis, we studied how the menstrual cycle and experimental manipulation affected two neurobiological systems associated with the menstrual cycle and suicide risk: GABAergic neuroactive steroids (NAS) and peripheral cytokines., Methods: In 26 psychiatric outpatients with natural menstrual cycles and past-month SI, we analyzed serum samples from three blood draws (midluteal, perimenstrual, midfollicular) per experimental condition (EP vs placebo) timed to a luteinizing hormone-surge ovulation test. Using gas chromatography/mass spectrometry (GC/MS), we measured the progesterone (P4)-derived pregnane NAS (3α,5α)- 3-hydroxypregnan20-one (3α,5α-THP), (3α,5β)- 3-hydroxypregnan-20-one (3α,5β-THP), (3α,5α)- 3,21-dihydroxypregnan-20-one (3α,5α-THDOC), (3α,5α)- 3-hydroxyandrostan-17-one (3α,5α-A), the androstane NAS (3α,5β)- 3-hydroxyandrostan-17-one (3α,5β-A), (3α,5α,17β)-androstane-3,17-diol (3α,5α-A-diol), (3α,5β,17β)-androstane-3,17-diol (3α,5β-A-diol), and their precursor pregnenolone. High sensitivity multiplex assay kits quantified peripheral cytokines IL-1β, IL-6, and TNF-α., Results: P4-derived NAS fluctuated in parallel with P4 and increased with exogenous perimenstrual administration of EP. Conversely, androstane NAS either did not fluctuate or fluctuated inversely from P4, and these NAS decreased with exogenous EP. Peripheral cytokines did not show cyclical patterns, but each significantly predicted SI, depressed mood, or anxiousness. Concomitant SSRI medication use predicted lower androstane NAS., Conclusions: While preliminary and exploratory, our findings provide critical descriptive context for future studies. Further, our work presents menstrual cycle-related patterns for ten frequently-studied biomarkers, allowing for improved quality of comparisons involving naturally-cycling populations in research., Competing Interests: Declaration of Competing Interest Dr. Pinna is a paid consultant to PureTech Health (Boston, MA, USA), GABA Therapeutics, and NeuroTrauma Sciences (Alpharetta, GA, USA). He has two patent applications, one on N-palmitoylethanolamine (PEA) and peroxisome proliferator-activated receptor alpha (PPAR-α) agonists US20180369171A1 allowed in May 16, 2023, and one on allopregnanolone analogs US11266663B2 allowed in March 8, 2022, in the treatment of neuropsychiatric disorders., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and treatment strategies, median survival remains disappointingly low. Inflammatory processes involving nitric oxide (NO), critically contribute to glioma formation. The inducible isoform of NO synthase (iNOS) is highly overexpressed in gliomas and has been linked to resistance against temozolomide (TMZ) treatment, neoplastic transformation, and modulation of immune response. While both in vitro and in vivo studies showed the potential of iNOS inhibitors as effective treatments for gliomas, no clinical trials on gliomas have been published. This review aims to summarize the available evidence regarding iNOS as a target for glioma treatment, focusing on clinically relevant data., Methods: Following PRISMA guidelines, we conducted a systematic review by searching PubMed/Medline, and Embase databases in May 2023. We included studies that investigated the impact of NOS inhibitors on glioma cells using L-NMMA, CM544, PBN, 1400W or l-NAME either alone or combined with TMZ. We extracted data on the NOS inhibitor used, subtype, study setting, animal model or cell lines employed, obtained results, and safety profile. Our inclusion criteria encompassed original articles in English or Spanish, studies with an untreated control group, and a primary outcome focused on the biological effects on glioma cells., Results: Out of 871 articles screened from the aforementioned databases, 37 reports were assessed for eligibility. After excluding studies that did not utilize glioma cells or address the designated outcome, 11 original articles satisfied the inclusion and exclusion criteria. Although no NOS inhibitor has been tested in a published clinical trial, three inhibitors have been evaluated using in vivo models of intracranial gliomas. l-NAME, 1400W, and CM544 were tested in vitro. Co-administration of l-NAME, or CM544 with TMZ showed superior results in vitro compared to individual agent testing., Conclusion: Glioblastomas remain a challenging therapeutic target. iNOS inhibitors exhibit substantial potential as treatment options for oncologic lesions, and they have demonstrated a safe toxicity profile in humans for other pathological conditions. Research endeavors should be focused on investigating their potential effects on brain tumors., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants., Methods: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine., Results: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) and approximately 20% (in each Asian site). Of the five models tested, the logistic regression model performed best with an area under the curve of 0.72, an accuracy of 61% and a recall of 72%. All of the top performing models identified clinical site, maternal weight, hypertensive disorders, severe antepartum hemorrhage and antenatal care as key variables in predicting LBW., Conclusions: Predictive modeling can identify women at high risk for delivering a LBW infant with good sensitivity using clinical variables available prior to delivery in LMICs. Such modeling is the first step in the development of a clinical decision support tool to assist providers in decision-making regarding referral of these women prior to delivery. Consistent referral of women at high-risk for delivering a LBW infant could have extensive public health consequences in LMICs by directing limited resources for advanced neonatal care to the infants at highest risk., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The USA is experiencing a reckoning with racial injustice and graduate medical education programs are seeking ways to address this important topic in training. Fellows in hematology/oncology at the University of North Carolina recognized this important gap and adapted a curriculum for medical residents on racial equity to a subspecialty audience. Aims were (1) to improve knowledge and awareness about implicit bias and systemic racism and (2) introduce methods to address racial inequities. We used lived experiences and collated materials from scientific literature and lay media to illustrate key points. The course explored the effects of implicit bias on individual, clinical, and health system levels, anchored in Kahneman's two-system theory. Videos, journal articles, and group discussion were employed to appeal to many learning styles. A post-curriculum survey assessed perceptions of racial inequality in medicine and the series' effects using a Likert scale. Twenty-nine participants completed the survey (12 fellows), 71% reported improved awareness of racial inequities, and 61% reported improved comfort level in addressing racial inequities. All participants recognized at least "some" racial inequity in medicine, and over 75% of participants indicated interest in further sessions. Formulation of an educational curriculum by fellows and delivered in a division-wide setting was feasible and well received by participants, filling a key educational gap. We encourage other institutions to take similar steps to highlight issues of systemic racism and move our field in the right direction., (© 2023. The Author(s) under exclusive licence to American Association for Cancer Education.)

Purpose of Review: Many factors have been reported to contribute to the development of food allergy. Here, we summarize the role of environmental exposure to foods as a major risk factor for developing food allergy., Recent Findings: Peanut proteins are detectable and biologically active in household environments, where infants spend a majority of their time, providing an environmental source of allergen exposure. Recent evidence from clinical studies and mouse models suggests both the airway and skin are routes of exposure that lead to peanut sensitization. Environmental exposure to peanut has been clearly associated with the development of peanut allergy, although other factors such as genetic predisposition, microbial exposures, and timing of oral feeding of allergens also likely contribute. Future studies should more comprehensively assess the contributions of each of these factors for a variety of food allergens to provide more clear targets for prevention of food allergy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Although paclitaxel is a promising first-line chemotherapeutic drug for ovarian cancer, acquired resistance to paclitaxel is one of the leading causes of treatment failure, limiting its clinical application. Asparagus officinalis has been shown to have anti-tumorigenic effects on cell growth, apoptosis, cellular stress and invasion of various types of cancer cells and has also been shown to synergize with paclitaxel to inhibit cell proliferation in ovarian cancer., Methods: Human ovarian cancer cell lines MES and its PTX-resistant counterpart MES-TP cell lines were used and were treated with Asparagus officinalis and paclitaxel alone as well as in combination. Cell proliferation, cellular stress, invasion and DMA damage were investigated and the synergistic effect of a combined therapy analyzed., Results: In this study, we found that Asparagus officinalis combined with low-dose paclitaxel synergistically inhibited cell proliferation, induced cellular stress and apoptosis and reduced cell invasion in paclitaxel-sensitive and -resistant ovarian cancer cell lines. The combined treatment effects were dependent on DNA damage pathways and suppressing microtubule dynamics, and the AKT/mTOR pathway and microtubule-associated proteins regulated the inhibitory effect through different mechanisms in paclitaxel-sensitive and -resistant cells., Conclusion: These findings suggest that the combination of Asparagus officinalis and paclitaxel have potential clinical implications for development as a novel ovarian cancer treatment strategy., (© 2022. The Author(s).)

Brain tumor incidence is on the rise, and glioblastoma comprises the majority of primary tumors. Despite maximal safe resection and adjuvant chemoradiation, median survival for high-grade glioma remains poor. For this reason, it is important to develop and incorporate new treatment strategies. Oncolytic virotherapy has emerged as a viable new therapeutic entity to fill this gap. Preclinical research has shown oncolytic virotherapy to be a robust and effective treatment option for brain tumors, and clinical trials for both adult and pediatric high-grade glioma are underway. The unique and protected environment of the nervous system, in part due to the blood-brain barrier, prevents traditional systemic therapies from achieving adequate penetration. Brain tumors are also heterogenous in nature due to their diverse molecular profiles, further complicating systemic treatment efforts. Oncolytic viruses may serve to fill this gap in brain tumor treatment given their amenability to genetic modification and ability to target unique tumor epitopes. In addition, direct inoculation of the oncolytic virus agent to the tumor bed following surgical resection absolves risk of systemic side effects and ensures adequate delivery. As virotherapy transitions from bench to bedside, it is important to discuss factors to make this transition more seamless. In this article, we describe the current clinical evidence as it pertains to oncolytic virotherapy and the treatment of brain tumors as well as factors to consider for its incorporation into neurosurgical workflow.

Background: Impoverished African Americans (AA) with hypertension face poor health outcomes., Purpose: To conduct a cluster-randomized trial testing two interventions, alone and in combination, to improve blood pressure (BP) control in AA with persistently uncontrolled hypertension., Methods: We engaged primary care practices serving rural Alabama and North Carolina residents, and in each practice we recruited approximately 25 AA adults with persistently uncontrolled hypertension (mean systolic BP >140 mmHg over the year prior to enrollment plus enrollment day BP assessed by research assistants ≥140/90 mmHg). Practices were randomized to peer coaching (PC), practice facilitation (PF), both PC and PF (PC + PF), or enhanced usual care (EUC). Coaches met with participants from PC and PC + PF practices weekly for 8 weeks then monthly over one year, discussing lifestyle changes, medication adherence, home monitoring, and communication with the healthcare team. Facilitators met with PF and PC + PF practices monthly to implement ≥1 quality improvement intervention in each of four domains. Data were collected at 0, 6, and 12 months., Results: We recruited 69 practices and 1596 participants; 18 practices (408 participants) were randomized to EUC, 16 (384 participants) to PF, 19 (424 participants) to PC, and 16 (380 participants) to PC + PF. Participants had mean age 57 years, 61% were women, and 56% reported annual income <$20,000., Limitations: The PF intervention acts at the practice level, possibly missing intervention effects in trial participants. Neither PC nor PF currently has established clinical reimbursement mechanisms., Conclusions: This trial will fill evidence gaps regarding practice-level vs. patient-level interventions for rural impoverished AA with uncontrolled hypertension., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alyssa Adams - None. Muna Anabtawi, DDS – None. Lynn Andreae, PhD – None. Elizabeth Baquero, EDD – chair of education advisory board of MedExplain, Inc., a company commercializing a patient education platform based on the Patient Activated Learning System (palsforhealth.com). Joanna Bryan, MS – None. Andrea Cherrington, MD, MPH – None. Debra Clark, MPH – None. Doyle Cummings, PharmD – None. Jacqueline Halladay, MD, MPH - None. James Hollenberg, MD – None. Ethel Johnson – None. Suzanne Oparil – research funding from CinCor Pharma Inc. (site PI for a primary aldosterone study), George Clinical Pty (site PI for GMRx2 treatment of hypertension), and Higi (site PI for a blood pressure validation study); advisory roles for CinCor Pharma Inc. (Scientific Advisory Board for primary aldosteronism and hypertension) and Preventric Diagnostics, LLC (Chair of the Medical and Technology Committee, 2019–2022); and Editor-in-Chief of Current Hypertension Reports (Springer Science Business Media LLC) until 12/2023. Erica Richman, PhD - None. Joshua Richman, PhD, MD – None. Monika Safford, MD – owner of MedExplain, Inc., a company commercializing a patient education platform based on the Patient Activated Learning System (palsforhealth.com). James Shikany, Dr.P·H - None. Orysya Soroka, PhD – None. James Tillman – None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

End-stage renal disease (ESRD) continues to be a disease process with a high rate of hospitalization and mortality. There has been little innovation in nephrology over the last few decades compared to revolutionary high-tech advancements in other areas like oncology and cardiovascular medicine. Kidney transplantation, the only available alternative to renal replacement therapy, is limited in its availability. It is essential to have advances in this field to improve the efficiency of currently available treatments and devise new therapies. The current description of renal replacement therapy is inappropriate as it only replaces the filtration function of the failed kidney without addressing its other vital metabolic, endocrinologic, and immunologic roles and portability. Hence, it is critical to have newer therapies focusing on total replacement and portability, not just clearance. This review will address the developments in hemodialysis therapy. Advances in hemodialysis therapy include hemodiafiltration, portable machines, wearable artificial kidneys, and bioartificial kidneys. Although promising, newer technologies in this direction are still far from clinical application. Several organizations and enterprises including the Kidney Health Initiative and Kidney X: The Kidney Innovation Accelerator, as well as The Advancing American Kidney Health Initiative, are working in tandem to develop new therapies that could customize the treatment of ESRD., Competing Interests: The authors declare that they have no competing interests.Peter Kotanko is an employee of the Renal Research Institute, a wholly owned subsidiary of Fresenius Medical Care (FMC) and holds stock in FMC.No competing interests were disclosed., (Copyright: © 2023 Roy-Chaudhury P et al.)

Food allergy impacts up to 10 % of the population and can result in life-threatening anaphylactic reactions. The pathogenesis of food allergy is not entirely understood but the disruption in naturally occurring oral tolerance is presumed to be involved. Research has been directed not only toward prevention of food allergy but on the restoration of oral tolerance by various means including immunotherapy (oral, sublingual, and epicutaneous), as well as adjunctive therapies including biologicals and probiotics. This review paper briefly discusses the involvement of oral tolerance in the pathogenesis of food allergy and how food allergy might be prevented; however, the main focus is on the potential for restoration of oral tolerance with various treatment modalities (oral immunotherapy with and without adjunctive therapies)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This proceedings article presents the scope of pediatric coma and disorders of consciousness based on presentations and discussions at the First Pediatric Disorders of Consciousness Care and Research symposium held on September 14th, 2021. Herein we review the current state of pediatric coma care and research opportunities as well as shared experiences from seasoned researchers and clinicians. Salient current challenges and opportunities in pediatric and neonatal coma care and research were identified through the contributions of the presenters, who were Jose I. Suarez, MD, Nina F. Schor, MD, PhD, Beth S. Slomine, PhD Erika Molteni, PhD, and Jan-Marino Ramirez, PhD, and moderated by Varina L. Boerwinkle, MD, with overview by Mark Wainwright, MD, and subsequent audience discussion. The program, executively planned by Varina L. Boerwinkle, MD, Mark Wainwright, MD, and Michelle Elena Schober, MD, drove the identification and development of priorities for the pediatric neurocritical care community., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Interventional radiology has had an expanding role in women's health over the past few decades, with recent accelerated growth and development. Interventional radiology is fundamental in the treatment of multiple conditions that affect women, including pelvic venous disease, uterine fibroids, and adenomyosis, and in postpartum management. Patient workup, classification, and treatment techniques have continued to evolve as interventional radiology has become more prevalent in the treatment of patients affected by these conditions. The authors provide a review of the pathophysiology of, patient workup for, and treatment of pelvic venous disease and uterine artery embolization for various disease processes. The authors also highlight updates from the past 5-10 years in diagnosis, classification, and treatment strategies. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Objective: The Lifestyle Intervention for oVarian cancer Enhanced Survival (LIVES) is a national study of a combined diet and physical activity intervention for stage II-IV ovarian cancer survival, an under-represented cancer in lifestyle behavioral intervention research. Here, we present the data on recruitment, retention, and baseline demographic, clinical and lifestyle behavior characteristics of the LIVES study participants., Methods: The LIVES study (NRG Oncology/GOG 0225) is a Phase III diet plus physical activity intervention trial testing the hypothesis that ovarian cancer survivors in the lifestyle intervention will demonstrate better progression-free survival than those in the control condition. Study interventions were delivered via centralized telephone-based health coaching. Baseline descriptive statistics were computed for demographic, clinical, and lifestyle behavior characteristics., Results: The LIVES study exceeded its recruitment goals, enrolling 1205 ovarian cancer survivors from 195 NRG/NCORP-affiliated oncology practices across 49 states from 2012 to 2018. The mean age of enrollees was 59.6 years; the majority (69.4%) with stage III disease; 89% White, 5.5% Hispanic; 64% overweight/obese. Baseline self-reported diet showed a mean daily intake of 6.6 servings of fruit and vegetables, 62.7 fat grams, and 21.7 g of fiber. Physical activity averaged 13.0 MET-hours/week of moderate to vigorous physical activity; 50.9 h/week of sedentary time. Retention rates exceeded 88%., Conclusion: The LIVES study demonstrates efficiency in recruiting and retaining ovarian cancer survivors in a 24-month study of diet and physical activity intervention with a primary endpoint of progression free survival that will be reported., Trial Registration: ClinicalTrials.govNCT00719303., Competing Interests: Declaration of Competing Interest Dr. Austin Miller reports that his institution received grants from the following: Vascular Biogenics LTD, Advaxis, Abbvie. Dr. Miller also reports participating on the Steering Committee for AstraZeneca as well as receiving institutional support from both Regeneron and GSK. Dr. Michael Gold received honoraria from ASCCP as an Educational Course Speaker. Dr. Matthew Powell received support from the NIH/NIH to NCTN NRG Oncology Network. Dr. Powell also reports participating on Advisory Boards for the following entities: GSK/Tesaro, Clovis Oncology, Merck, AstraZeneca, Eisai and SeaGen. Dr. Kristin Bixel reports receiving intuitive unrestricted research grant to the GOG for funding of randomized controlled trial (ROCC). Additionally, Dr. Bixel reports serving on Advisory Boards for Intuitive and Merck and receiving honoraria from both of these entities. Dr. Ratner reports receiving consulting fees from Aspire and has stock in same. Dr. Warner Huh reports receiving consulting fees from AstraZeneca and receiving payment for expert testimony from Shook, Hardy & Bacon LLP. Dr. Basen-Engquist reports MPI, R01CA186700, Study of biomarkers in ovarian cancer: Modulation by activity & diet intervention, MD Anderson subcontract from University of Arizona. She also receives grant from NCI, R21CA239079, Reducing breast cancer risk through modifying boy composition and decreasing inflammation in normal weight women. Dr. Basen-Engquist also reports pilot study grant from NCI, R21 CA215410 as well as receiving funding from Cancer Prevention & Research Institute of Texas: PP170023 &PP200028, Active Living After Cancer: Combining a physical activity program with survivor navigation and she received honoraria for Speaking from the both NCI as well as the University of New Mexico Cancer Center, Gynecologic Oncology Group and Yale University for Faculty TREC training program. Dr. Basen-Engquist also reports receiving support for travel from the National Cancer Policy Forum, National Academies of Science, Engineering, and Medicine and Yale University. She also participated as an Independent Safety Monitor for Boston University, digital health supported weight management intervention delivered by community health workers among public housing residents (R01CA238335). Dr. Basen-Engquist reports serving as President of the American Society of Preventive Oncology. Dr. Walker reports serving in a leadership role for NCORP. Dr. Lisa Kachnic reports NCI NCORP Funding and serving as Associate NCORP PI Support and Chair of Cancer Control Support. All other authors have no conflict of interest related to this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: In this article, we discuss recent advances in germline genetic testing for patients with breast cancer and highlight current limitations and impacts on clinical care. We also provide an update on the therapeutic implications of having a germline mutation, including targeted systemic therapy options for treating early and metastatic breast cancer., Recent Findings: Approximately 5 to 10% of women diagnosed with breast cancer have a pathogenic variant in a hereditary cancer susceptibility gene, which has significant implications for managing these patients. Previously, testing was done mainly to inform screening and risk-reduction treatment; however, more recently, germline genetic results have significant systemic therapy implications that can meaningfully improve outcomes in breast cancer patients, especially with oral poly-ADP-ribose polymerase (PARP) inhibitors. These systemic therapy advances implore a shift in paradigm for whom to test moving forward and how to modify the existing testing models to meet the increasing demand for germline testing, which is expected to grow exponentially., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Adeno-associated virus (AAV) vectors are stored and shipped frozen which poses logistic and economic barriers for global access to these therapeutics. To address this issue, we developed a method to stabilize AAV serotype 9 (AAV9) in a film matrix that can be stored at ambient temperature and administered by systemic injection., Methods: AAV9 expressing the luciferase transgene was mixed with formulations, poured into molds and films dried under aseptic conditions. Films were packaged in individual particle-free bags with foil overlays and stored at various temperatures under controlled humidity. Recovery of AAV9 from films was determined by serial dilution of rehydrated film in media and infection of HeLa RC32 cells. Luciferase expression was compared to that of films rehydrated immediately after drying. Biodistribution of vector was determined by in vivo imaging and quantitative real-time PCR. Residual moisture in films was determined by Karl Fischer titration., Results: AAV9 embedded within a film matrix and stored at 4 °C for 5 months retained 100% of initial titer. High and low viscosity formulations maintained 90 and 85% of initial titer after 6 months at 25 °C respectively. AAV was not detected after 4 months in a Standard Control Formulation under the same conditions. Biodistribution and transgene expression of AAV stored in film at 25 or 4 °C were as robust as vector stored at -80 °C in a Standard Control Formulation., Conclusions: These results suggest that storage of AAV in a film matrix facilitates easy transport of vector to remote sites without compromising in vivo performance., (© 2022. The Author(s).)