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Purpose of Review: This review examines contemporary strategies for managing brain metastases (BM) from common cancers such as lung, breast, and melanoma. We evaluate the efficacy and applicability of targeted therapies and immunotherapies, exploring their potential to cross the blood–brain barrier and improve patient outcomes. Recent Findings: Recent studies have shown that tyrosine kinase inhibitors, immune checkpoint inhibitors, and ADCs effectively treat BM. These treatments can overcome the challenges posed by the blood–brain barrier and improve therapeutic outcomes. ADCs are promising because they can deliver cytotoxic agents directly to tumor cells, which reduces systemic toxicity and increases drug delivery efficiency to the brain. Personalized medicine is becoming increasingly significant in treatment decisions, with biomarkers playing an essential role. Advances in molecular genetics and drug development have led to more refined treatments, emphasizing the precision medicine framework. Summary: The management of BM is evolving, driven by drug efficacy, resistance mechanisms, and the need for personalized medicine. Integrating ADCs into treatment regimens represents a significant advancement in targeting metastatic brain tumors. Despite these advances, BM management still presents considerable challenges, requiring ongoing research and multi-institutional trials to optimize therapeutic strategies. This review outlines the current state and future directions in treating BM, highlighting the critical need for continued innovation and comprehensive clinical evaluations to improve survival rates and quality of life for affected patients. [ABSTRACT FROM AUTHOR]

Data regarding racial disparities in the incidence, treatment, and outcomes of diffuse large B-cell lymphoma (DLBCL) is limited in the adolescent and young adult (AYA) population. We utilized the surveillance, epidemiology, and end-result (SEER) registry research plus database to evaluate racial/ethnic disparities in 8605 AYA patients with DLBCL. Race/ethnicity was categorized into three main subsets: non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and 'other races' that included Hispanics (H), American Indian/Alaskan Native (AI/AN), Asian or Pacific Islander (A/PI). NHB were more likely to present with advanced stage disease (p < 0.001) and B symptoms (p < 0.001) and were less likely to receive chemotherapy (p < 0.001) compared to non-Hispanic white (NHW) patients and other races respectively. NHB patients had inferior 5-year disease specific survival (DSS) (70% vs 85% vs 80%, p < 0.001) and 5-year overall survival (OS) (66% vs 82% vs 77%, p < 0.001) compared to NHW and other races respectively. Black race was independently associated with both inferior DSS (HR 1.55, 95% CI 1.17–2.05, p = 0.002) and OS (HR 1.41, 95% CI 1.10–1.83, p = 0.007) after adjusting for age, gender, stage, presence of B symptoms, receipt of chemotherapy and radiation. NHB-DLBCL patients also had a lower 1-year relative survival rate (RSR) compared to NHW and other races. The low RSR in NHB patients persisted up to 5 years from diagnosis unlike NHW and other races. Our study shows that despite significant therapeutic advances in DLBCL over the last two decades, NHB AYA patients with DLBCL continue to have inferior survival outcomes compared to other ethnic and racial groups with disparities arising as early as the first year of diagnosis. [ABSTRACT FROM AUTHOR]

A substantial amount of research, resources, and effort has been invested in the search for a 'holy grail' of twenty-first century leadership competencies. Ironically, despite the increasing significance of leadership and the substantial investments in uncovering the attributes of successful leaders, concerns persist regarding the quality of leadership worldwide. While the literature extensively outlines 'what' twenty-first century-ready leaders should embody, there remains a gap in outlining 'how' to nurture such leaders. We contrast existing practices that have focused on teaching functional content and relying on retrospective and deficit-based competency models by advocating for a strengths-based perspective. While there has been an increasing interest in positive psychology, which promotes a shift away from prevalent deficit correction approaches towards a framework that emphasises social-emotional and meta-cognitive strengths, character strengths have received little attention in corporate leader development programmes. We argue that nurturing character strengths offers a more sustainable, self-reinforcing process for twenty-first century leader development to overcome the limitations of short-lived leadership training results that fade over time. The Values in Action Classification of Character Strengths and Virtues provides a robust framework for identifying and nurturing these strengths. However, character strengths have traditionally been viewed as personal attributes, rather than leadership competencies. We challenge traditional views on leader development by arguing that character strengths reflect the competencies required of twenty-first century-ready leaders, as these more 'humane' characteristics remain relevant over time and valued across cultures because they represent qualities that are universally appreciated in defining 'what makes a good person'. [ABSTRACT FROM AUTHOR]

The cell cycle is the sequence of events orchestrated by a complex network of cell cycle proteins. Unlike normal cells, mature neurons subsist in a quiescent state of the cell cycle, and aberrant cell cycle activation triggers neuronal death accompanied by neurodegeneration. The periodicity of cell cycle events is choreographed by various mechanisms, including DNA damage repair, oxidative stress, neurotrophin activity, and ubiquitin-mediated degradation. Given the relevance of cell cycle processes in cancer and neurodegeneration, this review delineates the overlapping cell cycle events, signaling pathways, and mechanisms associated with cell cycle aberrations in cancer and the major neurodegenerative disorders. We suggest that dysregulation of some common fundamental signaling processes triggers anomalous cell cycle activation in cancer cells and neurons. We discussed the possible use of cell cycle inhibitors for neurodegenerative disorders and described the associated challenges. We propose that a greater understanding of the common mechanisms driving cell cycle aberrations in cancer and neurodegenerative disorders will open a new avenue for the development of repurposed drugs. Cell cycle activation and cell cycle re-entry are the two critical cellular phenomena associated with cancer and neurodegeneration, respectively. Various regulatory proteins, such as cyclin-dependent kinases (CDKs), cyclins, and checkpoint kinases, control the cell cycle dynamics at different phases. Further, the integrity of cell cycle is controlled by different mechanisms like DNA damage response, oxidative stress, neurotrophin activity, and the ubiquitin–proteasome system (UPS), the alterations which play an essential role in the pathogenesis of both cancer and neurodegenerative disorders. Pharmacological targeting of important cell cycle regulatory molecules like the application of CDK inhibitors, PARP inhibitors, checkpoint kinase inhibitors, and microtubule inhibitors holds great promise for treating various human cancers and can be repurposed for different neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

GI fellowships do not mandate curricula in career development. Often, fellows resort to peer mentorship for guidance. Fellows should recognize that the path to a successful career varies greatly based on how one defines and measures success. Keywords are preferr Through introspection, fellows will be able to craft their ideal post-fellowship position that balances wants versus needs. In this article, we cover four practical tips for trainees entering the job negotiation process. [ABSTRACT FROM AUTHOR]

GI fellowships do not mandate curricula in career development. Often, fellows resort to peer mentorship for guidance. Fellows should recognize that the path to a successful career varies greatly based on how one defines and measures success. Through introspection, fellows will be able to craft their ideal post-fellowship position that balances wants versus needs. In this article, we cover the breadth of post-fellowship opportunities available with a focus on unique considerations for LGBTQ+ and IMG trainees. [ABSTRACT FROM AUTHOR]

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype–environment interaction in retina. Here, the authors perform genome-wide mapping of DNA methylation and expression quantitative trait loci, revealing associations among genotype, epigenome and transcriptome, uncovering genes and gene-environment interactions contributing to age-related macular degeneration (AMD). [ABSTRACT FROM AUTHOR]

Using Social Media The use of social media (SoMe) has become more widespread at medical conferences, whereby attendees report events and talks throughout the day. Dr. Daniela Guerrero Vinsard, a third-year GI fellow at Mayo Clinic, shares that her work was declined for presentation when submitted for the first time to a GI conference. Declarations Conflict of interest Joseph Sleiman, Nikki Duong, Elizabeth S. Aby, Daniela Guerrero Vinsard, Rashmi Advani and Mohammad Bilal have no conflict of interest related to this manuscript. As social organisms, humans value personal and collegial interactions above almost every other form of communication. [Extracted from the article]

Wastewater surveillance of coronavirus disease 2019 (COVID-19) commonly applies reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentrations in wastewater over time. In most applications worldwide, maximal sensitivity and specificity of RT-qPCR has been achieved, in part, by monitoring two or more genomic loci of SARS-CoV-2. In Ontario, Canada, the provincial Wastewater Surveillance Initiative reports the average copies of the CDC N1 and N2 loci normalized to the fecal biomarker pepper mild mottle virus. In November 2021, the emergence of the Omicron variant of concern, harboring a C28311T mutation within the CDC N1 probe region, challenged the accuracy of the consensus between the RT-qPCR measurements of the N1 and N2 loci of SARS-CoV-2. In this study, we developed and applied a novel real-time dual loci quality assurance and control framework based on the relative difference between the loci measurements to the City of Ottawa dataset to identify a loss of sensitivity of the N1 assay in the period from July 10, 2022 to January 31, 2023. Further analysis via sequencing and allele-specific RT-qPCR revealed a high proportion of mutations C28312T and A28330G during the study period, both in the City of Ottawa and across the province. It is hypothesized that nucleotide mutations in the probe region, especially A28330G, led to inefficient annealing, resulting in reduction in sensitivity and accuracy of the N1 assay. This study highlights the importance of implementing quality assurance and control criteria to continually evaluate, in near real-time, the accuracy of the signal produced in wastewater surveillance applications that rely on detection of pathogens whose genomes undergo high rates of mutation. [ABSTRACT FROM AUTHOR]

Background: Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class is efficacious in the treatment and prevention of right heart failure has not been explored. Hypothesis: We hypothesized that SGLT2 inhibition would reduce the structural, functional, and molecular responses to pressure overload of the right ventricle. Methods: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (0.5 mg/kg/day) or vehicle by oral gavage. After 6 weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses. Results: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content, and alteration in calcium handling protein expression (all p < 0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, phospho-AMPK and LC3I/II ratio expression (all p < 0.05). Significance: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined. [ABSTRACT FROM AUTHOR]

Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis. The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Neutrophil dysfunction has a role in the pathogenesis of complications in Type II (non-insulin-dependent) diabetes mellitus. Neutrophils adhere through expression of the β2integrin CD11b/CD18 which closely associates with the actin cytoskeleton. The aim of this study was to investigate the effect of actin polymerisation on CD11b expression and exocytosis of the primary granule marker CD69 in neutrophils from patients with Type II diabetes. Methods. Neutrophils were activated with fMLP or PMA, actin polymerisation was inhibited with cytochalasin D. Cells were stained for CD11b and CD69 expression and intracellular F-actin was measured with phalloidin-FITC. Cellular fluorescence was measured by flow cytometry. Actin content of Triton X-100 fractions of cells was measured by SDS-PAGE and Coomassie blue staining. Results. PMA caused an increase in neutrophil F-actin that was greater in control subjects than in patients with Type II diabetes (50.8% vs 33.4%, p<0.001) and correlated with actin integrated optical density (IOD) by SDS-PAGE (r=0.74, p=0.01). Loss of CD11b from cell surfaces only occurred in neutrophils with high F-actin. The proportion of cells losing CD11b was lower in patients than in control subjects (23.1% vs 37.5%, p<0.001) and lowest in patients with additional cardiovascular risk markers (20.1% vs 27.7%; p<0.05). Cytochalasin D prevented loss of CD11b (p<0.001). CD69 expression was reduced in patients with Type II diabetes (22.6% vs 36.4%, p<0.001) and correlated with F-actin content (r=0.78, p<0.0001). Conclusion/interpretation. In Type II diabetes impaired neutrophil actin polymerisation leads to persistent expression of CD11b and reduced exocytosis of primary granules and could contribute to the pathogenesis of diabetic complications. [ABSTRACT FROM AUTHOR]

Autoclave consolidation is used to manufacture continuous fiber composites in applications that have strict part porosity requirements. The applied positive pressure in this process is attractive for reduction in part porosity. However, some part geometries can cause porosity issues even under positive pressure. One is the concave corner seen in an L-bracket geometry. Higher porosity is seen in areas of high curvature, hindering part quality. Since the autoclave process takes several hours and prepreg material is expensive, trial-and-error methods of resolving issues are not practical. In this work, a unique physics-based viscoelastic model is proposed to describe the mechanical behavior of uncured continuous fiber thermoset prepreg undergoing consolidation under hydrostatic pressure. This model considers stress due to compaction of the fiber network, compression of voids in the resin, and viscous stress from resin flow relative to fibers. The constitutive expressions for these are coupled to important mechanisms that occur during autoclave consolidation. The viscoelastic model is incorporated into the finite element analysis software ABAQUS/Standard using a UMAT subroutine. Numerical results are validated by analytic solutions and experimental comparison for flat and L-bracket geometries. A parametric study identifies important process and material parameters that influence the quality of the manufactured part. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota–gut–brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-to-nucleus signaling, and the microbiota–gut–brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs. Neurodegenerative diseases and neuropsychiatric diseases both share a common signaling molecule and molecular phenomenon, namely, pro-inflammatory cytokines, γCaMKII and MAPK/ERK, chemokine receptors, BBB permeability, and the gut–microbiota–brain axis. Studies have demonstrated that any alterations in the signaling mentioned above molecules and molecular phenomena lead to the pathophysiology of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and neuropsychiatric disorders, such as bipolar disorder, schizophrenia, depression, anxiety, autism spectrum disorder, and post-traumatic stress disorder. [ABSTRACT FROM AUTHOR]

Structural composites supercapacitors are manufactured by converting commercial carbon fabrics into electrodes by applying a surface treatment without changing their sizing chemistry, integrating electrolytes with single and hybrid material components in the forms of solution, gel, and film, with glass fabrics as a separator to prevent short-circuit in the system. Carbon fabrics are treated by applying stepwise dip-coating method including graphene oxide (GO) coating, Fe2O3 treatment and reduction steps in aqueous medium. Four configured supercapacitors are tested by changing electrodes and electrolytes. Supercapacitor with reduced GO (rGO) and rGO-Fe2O3 coated carbon fabric electrodes with mesoporous PVA-KOH film electrolyte in the laminated structure covered by insulator films demonstrates 46% charge retention at 1 V after 30 s, 21 Ω charge transfer resistance, 120 mWh/kg energy density, 3.12 W/kg power density, and 0.35 mF/g specific capacitance. Electrolytes in gel and solution forms do not display any capacitance behavior in cyclic voltammetry analysis and exhibit lower energy densities compared to the film electrolyte. PVA-KOH film electrolyte provides a synergistic effect with resized commercial grade carbon fabric electrodes through its homogenous impregnation on electrode surfaces which is responsible for the enhancement of charge-storage behavior of the fabricated structural supercapacitors. [ABSTRACT FROM AUTHOR]

Optimizing the pharmacokinetics (PK) of a drug candidate to support oral dosing is a key challenge in drug development. PK parameters are usually estimated from the concentration–time profile following intravenous administration; however, traditional methods are time-consuming and expensive. In recent years, quantitative structure–pharmacokinetic relationship (QSPKR), an in silico tool that aims to develop a mathematical relationship between the structure of a molecule and its PK properties, has emerged as a useful alternative to experimental testing. Due to the complex nature of the various processes involved in dictating the fate of a drug, the development of adequate QSPKR models that can be used in real-world pre-screening situations has proved challenging. Given the crucial role played by a molecule's ionization state in determining its PK properties, this work aims to build predictive QSPKR models for PK parameters in humans using an ionization state-based strategy. We divide a high-quality dataset into clusters based on ionization state at physiological pH and build global and ion subset-based 'local' models for three major PK parameters: plasma clearance (CL), steady-state volume of distribution (VDss), and half-life (t1/2). We use a robust methodology developed in our lab entitled 'EigenValue ANalySis' that accounts for the stereospecificity in drug disposition and use the support vector machine algorithm for model building. Our findings suggest that categorizing compounds in accordance with ionization state does not result in improved QSPKR models. The narrow ranges in the endpoints along with redundancies in the data adversely affect the ion subset-based QSPKR models. We suggest alternative approaches such as elimination route-based models that account for drug–transporter interactions for CL and chemotype-specific QSPKR for VDss. [ABSTRACT FROM AUTHOR]

Selecting regions of interest (ROI) is a common step in medical image analysis across all imaging modalities. An ROI is a subset of an image appropriate for the intended analysis and identified manually by experts. In modern pathology, the analysis involves processing multidimensional and high resolution whole slide image (WSI) tiles automatically with an overwhelming quantity of structural and functional information. Despite recent improvements in computing capacity, analyzing such a plethora of data is challenging but vital to accurate analysis. Automatic ROI detection can significantly reduce the number of pixels to be processed, speed the analysis, improve accuracy and reduce dependency on pathologists. In this paper, we present an ROI detection method for WSI and demonstrated it for human epidermal growth factor receptor 2 (HER2) grading for breast cancer patients. Existing HER2 grading relies on manual ROI selection, which is tedious, time-consuming and suffers from inter-observer and intra-observer variability. This study found that the HER2 grade changes with ROI selection. We proposed an ROI detection method using Vision Transformer and investigated the role of image magnification for ROI detection. This method yielded an accuracy of 99% using 20 × WSI and 97% using 10 × WSI for the ROI detection. In the demonstration, the proposed method increased the diagnostic agreement to 99.3% with the clinical scores and reduced the time to 15 seconds for automated HER2 grading. [ABSTRACT FROM AUTHOR]

Purpose: Although the cardioprotective benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors are now widely appreciated, the mechanisms underlying these benefits remain unresolved. Tumor necrosis factor receptor superfamily member 12a (Tnfrsf12a) is a receptor for tumor necrosis factor superfamily member 12 (Tnfsf12). Tnfrsf12a is highly inducible and plays a key role in the development of cardiac hypertrophy and heart failure. Here we set out to determine if SGLT2 inhibition affects the Tnfsf12/Tnfrsf12a system in the stressed myocardium. Methods: C57BL/6N mice that had undergone sham or transverse aortic constriction (TAC) surgery were treated with either the SGLT2 inhibitor empagliflozin (400 mg/kg diet; 60–65 mg/kg/day) or standard chow alone and were followed for 8 weeks. Tnfrsf12a expression in mouse hearts was assessed by in situ hybridization, qRT-PCR, and immunoblotting. Results: Left ventricular (LV) mass, end-systolic volume, and end-diastolic volume were all increased in TAC mice and were significantly lower with empagliflozin. Myocyte hypertrophy and interstitial fibrosis in TAC hearts were similarly attenuated with empagliflozin. Tnfrsf12a expression was upregulated in mouse hearts following TAC surgery but not in the hearts of empagliflozin-treated mice. In cultured cardiomyocytes, Tnfrsf12a antagonism attenuated the increase in cardiomyocyte size that was induced by phenylephrine. Conclusion: Empagliflozin attenuates LV enlargement in mice with hypertrophic heart failure. This effect may be mediated, at least in part, by a reduction in loading conditions which limits upregulation of the inducible, proinflammatory, and prohypertrophic TNF superfamily receptor, Tnfrsf12a. Disruption of the Tnfsf12/Tnfrsf12a feed forward system may contribute to the cardioprotective benefits of SGLT2 inhibition. [ABSTRACT FROM AUTHOR]

Background: Increasing number of breast cancer survivors in the USA have led to greater focus on the long-term health outcomes and surveillance care among these women. However limited evidence exists of use of surveillance mammography among breast cancer survivors and how it varies across racial/ethnic groups. Methods: We conducted a systematic review of the literature to explore disparities in use of surveillance mammogram among women breast cancer survivors by searching for relevant studies published between 2000 and 2020 from Medline (Ovid), PubMed (National Library of Medicine), and PsycINFO (Ovid) bibliographic databases. Two authors independently screened titles, abstracts, and full texts of all articles that reported surveillance mammography use across racial/ethnic groups. Data on study design, screening eligibility, sample size, operational definition, and/or measure of the use of a surveillance mammogram among breast cancer survivors and the association between race/ethnicity and use of a surveillance mammogram were summarized in the evidence tables. Results: We identified 1544 records from the three databases, and 30 studies examined the use of surveillance mammograms among breast cancer survivors across race/ethnic groups. Of these, 21 provided adjusted estimates of racial/ethnic disparities in use of surveillance mammograms, and 15 of these reported statistically significant disparities. In summary, most studies reported that non-white women (mainly Blacks and Hispanics) were less likely to receive a timely surveillance mammogram compared to White. Conclusion: This study extends the evidence of racial/ethnic disparities beyond completion of initial treatment by finding similar disparities in receipt of surveillance mammograms among breast cancer survivors. Implication for Cancer Survivors: Our findings identify a need to improve efforts to increase post-treatment use of surveillance mammography among racial/ethnic minority women to reduce these gaps and improve overall clinical and quality of life outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Although there were initial concerns that the public health response to the COVID-19 pandemic would adversely affect glycemic control in people with type 1 diabetes, several early continuous glucose monitor (CGM) studies reported an unexpected slight improvement in glucose metrics. Early emerging adulthood (roughly spanning the ages of 18–24 years) is often a vulnerable time in the life of a person with type 1 diabetes. Here, we set out to determine how the care and glucose management of emerging adults with type 1 diabetes changed over a period of approximately 2 years from the start of the COVID-19 pandemic. Methods: This was a retrospective study of a tertiary referral, multidisciplinary young adult diabetes clinic, spanning before and after the 777-day state of emergency in the City of Toronto. Results: Of 130 emerging adults with type 1 diabetes (80 male, 50 female; mean age 21.0 ± 2.1 years), baseline pre-pandemic HbA1c values were available for 120 individuals. During 24.9 ± 5.4 months of follow-up before and after the start of the COVID-19 pandemic, HbA1c fell from 8.5 ± 1.7% (69.3 ± 18.8 mmol/mol) to 8.1 ± 1.9% (65.2 ± 20.5 mmol/mol) (P < 0.05), with change in HbA1c from pre-lockdown levels being sustained throughout the second year of the pandemic. Over the same period, CGM use rose from 43% to 83%, primarily through increased uptake of intermittently scanned CGM, which is covered through the Ontario Drug Benefit program. Change in HbA1c was most evident in Dexcom G6 real-time CGM users − 0.7 ± 1.2% (− 9.8 ± 17.1 mmol/mol) (P < 0.01 vs. self-monitoring of blood glucose). Conclusion: Among emerging adults with type 1 diabetes attending a multidisciplinary clinic in a high-income country, glycated hemoglobin levels are on average 0.4% (4.1 mmol/mol) lower than they were before the pandemic. This reduction in HbA1c is unlikely to be a consequence of early strict lockdowns given the length of time of follow-up. Rather, improved glycemic control coincided with increased utilization of wearable diabetes devices. [ABSTRACT FROM AUTHOR]

CD30 is overexpressed in several lymphoma types, including classic Hodgkin lymphoma (cHL), some peripheral T-cell lymphomas (PTCL), and some cutaneous T-cell lymphomas. The antibody–drug conjugate brentuximab vedotin targets CD30-positive cells and has been evaluated for the treatment of various lymphoma entities. This narrative review summarizes 10 years of experience with brentuximab vedotin for the treatment of CD30-positive lymphomas, discusses novel therapies targeting CD30 in development, and highlights remaining controversies relating to CD30-targeted therapy across lymphoma types. The collective body of evidence for brentuximab vedotin demonstrates that exploitation of CD30 can provide sustained benefits across a range of different CD30-positive lymphomas, in both clinical trials and real-world settings. Preliminary experience with brentuximab vedotin in combination with immune checkpoint inhibitors for relapsed/refractory cHL is encouraging, but further exploration is required. The optimal use of brentuximab vedotin for first-line therapy of PTCL remains to be determined. Further research is required on brentuximab vedotin treatment in high-risk patient populations, and in rare lymphoma subtypes, for which no standard of care exists. Novel therapies targeting CD30 include chimeric antigen receptor therapies and bispecific antibody T-cell engagers, which may be expected to further improve outcomes for patients with CD30-positive lymphomas in the coming years. [ABSTRACT FROM AUTHOR]

The microstructural evolution of a T800 2 × 2 twill weave carbon fiber/benzoxazine resin composite was quantified through the pyrolytic decomposition region of 250–800°C. In performing kinetic analysis, three stages of mass loss were identified and quantified through a non-isothermal kinetics model. The kinetics model parameters were determined at each state of the reaction, and the corresponding decomposition gases were analyzed to gain insight into pyrolytic reactions. The kinetics model was then used to design a heat treatment cycle that isolated each stage of the reaction so that the effects on the progression of the porous microstructure could be characterized. In the first stage of the reaction, the nucleation and growth of voids were dominant. In the second stage, the initiation of microcracks within the matrix was observed. The third stage saw the formation of an interconnected porous network in which cracks propagated throughout the composite and formed a continuous pathway from the surface to the centermost voids. To evaluate these microstructural features, X-ray computed tomography was utilized. In doing so, the various damage phenomena including void size, the degree of open and closed porosity, and the crack density were quantified. [ABSTRACT FROM AUTHOR]

Background and Aims: Female representation among gastroenterology (GI) fellows has remained around 30%, yet women comprise over 50% of internal medicine (IM) residents. We aim to identify the gender-specific barriers of IM residents toward pursuing GI. Methods: We surveyed IM residents in the Northeast by emailing 168 IM programs a survey link to be distributed to their residents. A 4-point Likert barrier scale and bivariate analysis were performed with "yes" and "no," where "yes" was analyzed as "somewhat of a barrier" and above. Females received a third table assessing female-specific barriers. Significance was set at < 0.05. Results: Of 215 survey responses, 56.3% (n = 121) were female. Response rate could not be determined due to resident identity protection and inconsistent responses of survey dissemination from programs. Females had significantly greater concerns about fertility, maternity leave, radiation exposure, work-life balance, stress, and burnout compared to males (p < 0.05). For females, 48.7% felt a lack of gender diversity in GI, 54.6% felt a lack of female GI mentors, and 43.7% felt there is a lack of respect as a female in GI. No gender differences existed in motivation to pursue GI, exposure to GI, and access to GI mentors, or GI-related research. Conclusions: Our study reveals that female IM trainees had greater concerns surrounding fertility, radiation exposure, and maternity leave compared to male IM trainees. Lack of gender diversity and lack of female GI mentors were noted barriers for female IM trainees. Addressing these barriers may help increase female representation in GI. [ABSTRACT FROM AUTHOR]

Chromatin organization and enhancer-promoter contacts establish unique spatiotemporal gene expression patterns in distinct cell types. Non-coding genetic variants can influence cellular phenotypes by modifying higher-order transcriptional hubs and consequently gene expression. To elucidate genomic regulation in human retina, we mapped chromatin contacts at high resolution and integrated with super-enhancers (SEs), histone marks, binding of CTCF and select transcription factors. We show that topologically associated domains (TADs) with central SEs exhibit stronger insulation and augmented contact with retinal genes relative to TADs with edge SEs. Merging genome-wide expression quantitative trait loci (eQTLs) with topology map reveals physical links between 100 eQTLs and corresponding eGenes associated with retinal neurodegeneration. Additionally, we uncover candidate genes for susceptibility variants linked to age-related macular degeneration and glaucoma. Our study of high-resolution genomic architecture of human retina provides insights into genetic control of tissue-specific functions, suggests paradigms for missing heritability, and enables the dissection of common blinding disease phenotypes. The genome-wide high-resolution chromatin contact of the human retina identifies genetic control of cell-type specific gene expression pattern, missing heritability in retinopathies, and candidate genes/variants for diseases including AMD and glaucoma. [ABSTRACT FROM AUTHOR]

Background/significance: Over 168,000 women are living with metastatic breast cancer (MBC) in the USA. More efficacious treatments have lengthened overall survival, but these treatments often result in a myriad of symptoms and financial burden that may negatively impact perceptions of cancer treatment and medication-taking behavior. Purpose: To explore cancer treatment–specific medication beliefs among women undergoing cancer treatment for MBC. Methods: A qualitative study was conducted using semi-structured interviews that were audio recorded and transcribed verbatim. A thematic analysis was conducted using ATLAS.ti 8.0 software. Inter-rater reliability was set at a threshold of 0.80. Participants were recruited from a National Cancer Institute–designated comprehensive care center. Eligibility included ≥18 years old, English speaking, confirmed MBC diagnosis, and able/willing to complete interviews via telephone or Zoom. Results: Participants (n = 16) were largely Caucasian (86.7%) and non-Hispanic (93.3%). Mean age was 55.62 years. Three major themes were revealed, with corresponding subthemes: (1) positive cancer treatment–specific medication beliefs highlighting the benefit of treatment (relief of cancer-related symptoms and medication efficacy: delayed disease progression/extended survival); (2) negative cancer treatment–specific medication beliefs that caused concern for cancer treatment (medication symptoms, side effects and drug-drug interactions, financial toxicity, lack of guarantee medication would work); and (3) dialectical cancer treatment–specific medication beliefs indicating the benefits of cancer treatment outweigh the risks. Conclusion: Overall, participants noted that the benefits of cancer treatment outweighed the risks in the context of metastatic disease. Participants understood their prognosis and that they depended on their cancer treatment for survival. Oncology providers should continue to assess and address medication beliefs over the treatment trajectory and assist MBC patients with the decisional balance between the risk and benefit of continued cancer treatment. [ABSTRACT FROM AUTHOR]

Locally advanced cancers remain therapeutically challenging to eradicate. The most successful treatments continue to combine decades old non-targeted chemotherapies with radiotherapy that unfortunately increase normal tissue damage in the irradiated field and have systemic toxicities precluding further treatment intensification. Therefore, alternative molecularly guided systemic therapies are needed to improve patient outcomes when applied with radiotherapy. In this work, we report a trimodal precision cytotoxic chemo-radio-immunotherapy paradigm using spatially targeted auristatin warheads. Tumor-directed antibodies and peptides conjugated to radiosensitizing monomethyl auristatin E (MMAE) specifically produce CD8 T cell dependent durable tumor control of irradiated tumors and immunologic memory. In combination with ionizing radiation, MMAE sculpts the tumor immune infiltrate to potentiate immune checkpoint inhibition. Here, we report therapeutic synergies of targeted cytotoxic auristatin radiosensitization to stimulate anti-tumor immune responses providing a rationale for clinical translational of auristatin antibody drug conjugates with radio-immunotherapy combinations to improve tumor control. Monomethyl auristatin (MMAE), also known for its radiosensitizer properties, is a common antibody drug conjugate used for cancer therapy. Here the authors show that, in combination with radiotherapy, tumor-directed antibodies or peptides conjugated to MMAE promote anti-tumor immune responses, improving response to checkpoint inhibitors in preclinical cancer models. [ABSTRACT FROM AUTHOR]

Objective: To synthesize the evidence for incidence, pathophysiology, etiology, and protocol-based management of hyperammonemia in lung transplant patients. Background: Elevated ammonia levels are toxic to the brain, and hyperammonemia results in a potentially fatal complication for lung transplant recipients. The hallmark of this condition is ammonia production being way out of proportion to the degree of liver derangement. While there are many hypotheses, the cause remains obscure. Methods: A retrospective review of patients with hyperammonemia following lung transplantation was done to understand the pathophysiology, various treatment modalities, and its impact on patient mortality and morbidity. Studies in the English literature were identified through an electronic database search from PubMed/MEDLINE, Ovid Embase, Google Scholar, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, and ClinicalTrials.gov until June 2020. No restriction of dates were used, and the search was up until June 2020. Discussion: Mortality among patients with hyperammonemia following lung transplantation is high. Multi-modal treatment approaches include avoiding nephrotoxic drugs, use of bowel decontamination, nitrogen scavengers, branched-chain amino acids, adjustment of immunosuppression, antibiotics like fluoroquinolones or azithromycin, and renal replacement therapy. However, there remains a scarcity of preoperative screening protocol for patients at risk of hyperammonemia as well evidence-based post-operative management guidelines. Intermittent hemodialysis, compared to continuous venovenous hemodialysis, provides better patient outcomes. Conclusion: Early detection of patients at risk by appropriate screening, along with maintaining a high degree of suspicion for hyperammonemia and multi-modal treatment approach, is the key to successful patient outcomes. Further prospective observational studies would facilitate development of protocol-based treatment of this potentially fatal condition. [ABSTRACT FROM AUTHOR]

To investigate aldo–keto reductase 1C3 (AKR1C3) expression in T and B acute lymphoblastic leukemia/lymphoma (ALL) patients. Three commercial antibodies were evaluated for AKR1C3 immunohistochemistry (IHC) staining performance: Polyclonal Thermofisher scientific (Clone#PA523667), rabbit monoclonal Abcam [EPR16726] (ab209899) and Sigma/Millipore anti-AKR1C3 antibody, mouse monoclonal, clone NP6.G6.A6, purified from hybridoma cell culture. Initial optimization was performed on cell line controls: HCT116 (negative control); genetically modified cell line HCT116 with AKR1C3 overexpression; Nalm and TF1 cell lines. Twenty normal bone marrows from archival B and T-ALL patient samples were subsequently examined. AKR1C3 expression levels in these samples were evaluated by immunohistochemistry, Protein Wes and quantitative RT-PCR. Sigma/Millipore Anti-AKR1C3 antibody (mouse monoclonal, clone NP6.G6.A6) showed higher specificity compared to rabbit polyclonal antibody by immunohistochemistry. H-score was used to quantify percent of nuclear immunoreactivity for AKR1C3 with varying disease involvement. T-ALL samples had a higher H-score (172–190) compared to B-ALL cases (H-score, 30–160). The AKR1C3 expression in peripheral blood by Protein Wes and RT-qPCR showed concordance in relapsed/refractory and/or minimal residual T-ALL cases. Sigma/Millipore Anti-AKR1C3 antibody and mouse monoclonal, clone NP6.G6.A6 can be used to aid in AKR1C expression of T-ALL and in cases of relapsed/refractory and/or minimal residual disease. [ABSTRACT FROM AUTHOR]

Introduction: Female gastroenterologists comprise 19% of the gastroenterology (GI) workforce, despite females making up 30% of GI fellows and over 50% of medical students in the USA. Barriers to pursuing GI fellowship have not been studied at the resident level. We aimed to determine multiple barriers that may prevent internal medicine (IM) residents from pursuing GI fellowship.Our multi-center team distributed an IRB-approved electronic survey to residents in IM residency programs nationwide. Multiple rounds of emails with survey description and link were sent to program directors and coordinators to forward to their residents. Four-point Likert barrier scales were used where “not a barrier” was analyzed as “no” and “somewhat a barrier” to “extreme barrier” was analyzed as “yes.” Frequencies and Chi-square tests (p < 0.05) were used to compare barriers by gender.The mean age was 29.9 years. 287 (52.9%) were female. Compared to males, female residents were more likely to report concerns regarding maternity/paternity leave, child care during or after training, fertility, and delaying pregnancy as significant barriers to applying for GI fellowship (Fig. 1). Lack of mentorship, lack of same-sex mentorship, lack of gender diversity, and compensation inequality were greater concerns compared to males (Fig. 1). Financial obligations, job availability, debt burden, family obligations, and paternity/maternity leave were significant barriers for trainees with 1 or more children compared to trainees with no children (p < 0.05) (Fig. 2). In a gender-based sub-analysis, female married trainees perceived paternity/maternity leave, childcare, delayed pregnancy, and lack of same-sex mentors to be greater barriers compared to male married trainees (p < 0.05).Our study revealed several gender-specific, parental, and marital-based barriers that may prevent IM residents from pursuing fellowship training in GI. Potential interventions for female trainees include structured mentorship pathways, better resources for parental leave, and interventions to reduce stress/burnout and improve work–life balance.Methods: Female gastroenterologists comprise 19% of the gastroenterology (GI) workforce, despite females making up 30% of GI fellows and over 50% of medical students in the USA. Barriers to pursuing GI fellowship have not been studied at the resident level. We aimed to determine multiple barriers that may prevent internal medicine (IM) residents from pursuing GI fellowship.Our multi-center team distributed an IRB-approved electronic survey to residents in IM residency programs nationwide. Multiple rounds of emails with survey description and link were sent to program directors and coordinators to forward to their residents. Four-point Likert barrier scales were used where “not a barrier” was analyzed as “no” and “somewhat a barrier” to “extreme barrier” was analyzed as “yes.” Frequencies and Chi-square tests (p < 0.05) were used to compare barriers by gender.The mean age was 29.9 years. 287 (52.9%) were female. Compared to males, female residents were more likely to report concerns regarding maternity/paternity leave, child care during or after training, fertility, and delaying pregnancy as significant barriers to applying for GI fellowship (Fig. 1). Lack of mentorship, lack of same-sex mentorship, lack of gender diversity, and compensation inequality were greater concerns compared to males (Fig. 1). Financial obligations, job availability, debt burden, family obligations, and paternity/maternity leave were significant barriers for trainees with 1 or more children compared to trainees with no children (p < 0.05) (Fig. 2). In a gender-based sub-analysis, female married trainees perceived paternity/maternity leave, childcare, delayed pregnancy, and lack of same-sex mentors to be greater barriers compared to male married trainees (p < 0.05).Our study revealed several gender-specific, parental, and marital-based barriers that may prevent IM residents from pursuing fellowship training in GI. Potential interventions for female trainees include structured mentorship pathways, better resources for parental leave, and interventions to reduce stress/burnout and improve work–life balance.Results: Female gastroenterologists comprise 19% of the gastroenterology (GI) workforce, despite females making up 30% of GI fellows and over 50% of medical students in the USA. Barriers to pursuing GI fellowship have not been studied at the resident level. We aimed to determine multiple barriers that may prevent internal medicine (IM) residents from pursuing GI fellowship.Our multi-center team distributed an IRB-approved electronic survey to residents in IM residency programs nationwide. Multiple rounds of emails with survey description and link were sent to program directors and coordinators to forward to their residents. Four-point Likert barrier scales were used where “not a barrier” was analyzed as “no” and “somewhat a barrier” to “extreme barrier” was analyzed as “yes.” Frequencies and Chi-square tests (p < 0.05) were used to compare barriers by gender.The mean age was 29.9 years. 287 (52.9%) were female. Compared to males, female residents were more likely to report concerns regarding maternity/paternity leave, child care during or after training, fertility, and delaying pregnancy as significant barriers to applying for GI fellowship (Fig. 1). Lack of mentorship, lack of same-sex mentorship, lack of gender diversity, and compensation inequality were greater concerns compared to males (Fig. 1). Financial obligations, job availability, debt burden, family obligations, and paternity/maternity leave were significant barriers for trainees with 1 or more children compared to trainees with no children (p < 0.05) (Fig. 2). In a gender-based sub-analysis, female married trainees perceived paternity/maternity leave, childcare, delayed pregnancy, and lack of same-sex mentors to be greater barriers compared to male married trainees (p < 0.05).Our study revealed several gender-specific, parental, and marital-based barriers that may prevent IM residents from pursuing fellowship training in GI. Potential interventions for female trainees include structured mentorship pathways, better resources for parental leave, and interventions to reduce stress/burnout and improve work–life balance.Conclusion: Female gastroenterologists comprise 19% of the gastroenterology (GI) workforce, despite females making up 30% of GI fellows and over 50% of medical students in the USA. Barriers to pursuing GI fellowship have not been studied at the resident level. We aimed to determine multiple barriers that may prevent internal medicine (IM) residents from pursuing GI fellowship.Our multi-center team distributed an IRB-approved electronic survey to residents in IM residency programs nationwide. Multiple rounds of emails with survey description and link were sent to program directors and coordinators to forward to their residents. Four-point Likert barrier scales were used where “not a barrier” was analyzed as “no” and “somewhat a barrier” to “extreme barrier” was analyzed as “yes.” Frequencies and Chi-square tests (p < 0.05) were used to compare barriers by gender.The mean age was 29.9 years. 287 (52.9%) were female. Compared to males, female residents were more likely to report concerns regarding maternity/paternity leave, child care during or after training, fertility, and delaying pregnancy as significant barriers to applying for GI fellowship (Fig. 1). Lack of mentorship, lack of same-sex mentorship, lack of gender diversity, and compensation inequality were greater concerns compared to males (Fig. 1). Financial obligations, job availability, debt burden, family obligations, and paternity/maternity leave were significant barriers for trainees with 1 or more children compared to trainees with no children (p < 0.05) (Fig. 2). In a gender-based sub-analysis, female married trainees perceived paternity/maternity leave, childcare, delayed pregnancy, and lack of same-sex mentors to be greater barriers compared to male married trainees (p < 0.05).Our study revealed several gender-specific, parental, and marital-based barriers that may prevent IM residents from pursuing fellowship training in GI. Potential interventions for female trainees include structured mentorship pathways, better resources for parental leave, and interventions to reduce stress/burnout and improve work–life balance. [ABSTRACT FROM AUTHOR]

The health effects of e-cigarettes remain relatively unknown, including their impact on sleep quality. We previously showed in a pilot study that females who smoke both conventional tobacco and vape e-cigarettes (dual users) had decreased sleep quality (measurement of how well an individual is sleeping) and increased sleep latency (amount of time to fall asleep), suggesting an influence by gender. Cough is also known to adversely impact sleep quality and may be caused by inhalant use. As a result, we undertook this study to assess the impact of e-cigarette, conventional tobacco, and dual use on sleep quality, sleep latency, cough, and drug use. Participants (n = 1198) were recruited through online surveys posted to social media sites with a monetary incentive. Participants were grouped by inhalant use, with 8% e-cigarette users, 12% conventional tobacco users, 30% dual users, and 51% non-smokers/non-vapers. Dual use of e-cigarettes and conventional tobacco was associated with increased sleep latency relative to non-smokers/non-vapers by multivariable linear regression (mean difference of 4.08; 95% CI: 1.12 to 7.05, raw p = 0.007, adjusted p = 0.042); however, dual usage was not significantly associated with sleep quality relative to non-smokers/non-vapers (mean difference 0.22, 95%CI: (−0.36, 0.80), raw p = 0.452, adjust p = 0.542). Dual use was also associated with a higher reporting of cough (p = 0.038), as well as increased marijuana (p < 0.001) and cocaine (p < 0.001) usage. This study demonstrates that dual use is associated with longer sleep latency, and suggests that the shared component of nicotine may be a driver. Because sleep broadly impacts multiple aspects of human health, defining the associations of e-cigarettes and vaping devices on sleep is critical to furthering our understanding of their influence on the body. [ABSTRACT FROM AUTHOR]

Carbon–carbon composites (CCCs) are a unique form of carbon fiber-reinforced materials that exhibit excellent thermomechanical properties under extreme environmental conditions. Due to the need for the retention of mechanical properties at temperatures exceeding 2000 °C, CCCs have been utilized in heat shields, rocket nozzles, aircraft brakes, and leading edge material in hypersonic vehicles. In order to expand the applicability of CCCs, the fabrication process must be modified such that there is a reduction in cost or processing time. It is hypothesized that maximizing the permeability of the composite, during processing, will grant the largest reduction in the fabrication time as it leads to a larger volume of pores filled during re-densification. This review attempts to capture the various parameters that have led to increased permeability, as well as outlining process modifications that have demonstrated influence over the carbonized microstructure. In addition, this review seeks to differentiate itself by systematically outlining research advances that have been made in each step of the fabrication process. In doing so, scientific gaps that exist can be expounded upon while simultaneously summarizing what is necessary to advance the field. [ABSTRACT FROM AUTHOR]

Background: mRNA COVID-19 vaccines are known to provide an immune response seen on FDG PET studies. However, the time course of this metabolic response is unknown. We here present a temporal metabolic response to mRNA COVID-19 vaccination in oncology patients undergoing standard of care FDG PET. Methods: 262 oncology patients undergoing standard of care FDG PET were included in the analysis. 231 patients had at least one dose of mRNA COVID-19 vaccine while 31 patients had not been vaccinated. The SUVmax of the lymph nodes ipsilateral to the vaccination was compared to the contralateral to obtain an absolute change in SUVmax (ΔSUVmax). Results: ΔSUVmax was more significant at shorter times between FDG PET imaging and COVID-19 mRNA vaccination, with a median ΔSUVmax of 2.6 (0–7 days), 0.8 (8–14 days), and 0.3 (> 14 days), respectively. Conclusion: Consideration should be given to performing FDG PET at least 2 weeks after the COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

During the coronavirus disease 2019 (COVID-19) pandemic, gun violence (GV) in the United States (U.S.) was postulated to increase strain on already taxed healthcare resources, such as blood products, intensive care beds, personal protective equipment, and even hospital staff. This report aims to estimate the relative risk of GV in the U.S. during the pandemic compared to before the pandemic. Daily police reports corresponding to gun-related injuries and deaths in the 50 states and the District of Columbia from February 1st, 2019, to March 31st, 2021 were obtained from the GV Archive. Generalized linear mixed-effects models in the form of Poisson regression analysis were utilized to estimate the state-specific rates of GV. Nationally, GV rates were 30% higher between March 01, 2020, and March 31, 2021 (during the pandemic), compared to the same period in 2019 (before the pandemic) [intensity ratio (IR) = 1.30; 95% CI 1.29, 1.32; p < 0.0001]. The risk of GV was significantly higher in 28 states and significantly lower in only one state. National and state-specific rates of GV were higher during the COVID-19 pandemic compared to the same timeframe 1 year prior. State-specific steps to mitigate violence, or at a minimum adequately prepare for its toll during the COVID-19 pandemic, should be taken. [ABSTRACT FROM AUTHOR]

Purpose of Review: The goal of this article is to highlight how and why urinalyses and urine cultures are misused, review quality improvement interventions to optimize urine culture utilization, and highlight how to implement successful, sustainable interventions to improve urine culture practices in the acute care setting. Recent Findings: Quality improvement initiatives aimed at reducing inappropriate treatment of asymptomatic bacteriuria often focus on optimizing urine test utilization (i.e., urine culture stewardship). Urine culture stewardship interventions in acute care hospitals span the spectrum of quality improvement initiatives, ranging from strong systems-based interventions like suppression of urine culture results to weaker interventions that focus on clinician education alone. While most urine culture stewardship interventions have met with some success, overall results are mixed, and implementation strategies to improve sustainability are not well understood. Summary: Successful diagnostic stewardship interventions are based on an assessment of underlying key drivers and focus on multifaceted and complementary approaches. Individual intervention components have varying impacts on effectiveness, provider autonomy, and sustainability. The best urine culture stewardship strategies ultimately include both technical and socio-adaptive components with long-term, iterative feedback required for sustainability. [ABSTRACT FROM AUTHOR]

A field study on the relationship between rodent fauna and crop ecosystem of the Indian Desert and its two main systems was undertaken in 5 villages and 7 dhanis near Jodhpur. Out of twelve rodent species, Meriones hurrianae had a highest relative abundance followed by Tatera indica indica, and Rattus meltada pallidior. Rodent fauna in the winter irrigated crops and fields was more diversified (11 species) than rainfed summer crops and fields (10 species). M. hurrianae was a predominant species in rainfed crop fields while, T. indica along with M. hurrianae was a codominant species in irrigated winter crops. Rattus gleadowi and Vandeleuria oleracea from summer crop fields and Mus cervicolor phillipsi in irrigated crop fields, were altogether absent. Relative abundance of Funambulus pennanti, R. meltada, Mus booduga, Golunda ellioti gujerati and T. indica increased from rainfed to irrigated crop systems, whereas, reverse trend was witnessed for Rattus rattus rufescens, M. hurrianae and two Gerbillus spp. ( nanus and gleadowi). Occurrence patterns of different rodent species in the crop ecosystem of Indian desert as a whole and in irrigated and rainfed crop systems in particular have been critically discussed keeping in view their ecological, physiological, behavioural and biological patterns. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses a study on optic nerve decompression for the treatment of severe traumatic optic neuropathy. While the authors agree with the study's conclusion, they raise concerns about its limitations. The study was conducted at a single institution, which may limit the generalizability of the findings. Additionally, the study had a single surgeon performing all the surgeries, which introduces potential bias. The authors suggest conducting the study in a multicenter setting with multiple surgeons and randomizing patients to different surgical techniques to enhance the quality and reliability of the outcomes. [Extracted from the article]

Purpose: To determine whether interim 3′-deoxy-3′-[18F]fluorothymidine (iFLT) PET/CT is a superior predictor of progression-free survival (PFS) compared with interim 18F-fluorodeoxyglucose (iFDG) PET/CT in patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). Methods: Ninety-two prospectively enrolled patients with DLBCL underwent both FLT-PET/CT and FDG-PET/CT 18–24 days after two cycles of R-CHOP/R-EPOCH. Deauville-criteria, PERCIST1.0, standardized uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume were used to interpret iFDG-PET/CT while dichotomous visual interpretation was used to interpret iFLT-PET/CT and the results were compared with the 3- and 5-year PFS. Results: iFLT-PET/CT was negative in 67 (73%) and positive in 25 (27%) patients. iFDG-PET/CT by Deauville criteria was negative (Deauville scores [DS] of 1–3) in 53 (58%) and positive (DS = 4–5) in 39 (42%) patients. Of the 67 iFLT-PET/CT-negative patients, 7 (10.4%) progressed at a median of 14.1 months whereas 14/25 (56.0%) iFLT-PET/CT-positive patients progressed at a median of 7.8 months (P <.0001). Of the 53 Deauville-negative patients, 9 (17.0%) progressed at a median of 14.1 months whereas 12/39 (30.8%) Deauville-positive patients progressed at a median of 5.6 months (P =.11). In multivariate analysis, including iFLT-PET/CT, PERCIST, interim TLG, and interim SUVmax, only iFLT-PET/CT was an independent predictor for 3- and 5-year PFS (P <.0001 and P =.001, respectively). Conclusions: In patients with DLBCL given R-CHOP/R-EPOCH, iFLT-PET/CT is a superior independent predictor of outcome compared with iFDG-PET/CT. [ABSTRACT FROM AUTHOR]

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Purpose: The role of established breast cancer risk factors and clinical characteristics of the first breast cancer in the development of contralateral breast cancer (CBC) among postmenopausal women is unclear. Methods: We identified 10,934 postmenopausal women diagnosed with a first primary breast cancer between 1995 and 2011 in the NIH-AARP Diet and Health Study. CBC was defined as a second primary breast cancer diagnosed in the contralateral breast ≥ 3 months after the first breast cancer. Exposures included pre-diagnosis risk factors (lifestyle, reproductive, family history) and clinical characteristics of the first breast cancer. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Over a median follow-up of 6.8 years, 436 women developed CBC. We observed an increasing trend in CBC risk by age (p-trend = 0.002) and decreasing trend by year of diagnosis (p-trend = 0.001) of the first breast cancer. Additional risk factor associations were most pronounced for endocrine therapy (HR 0.68, 95% CI 0.53–0.87) and family history of breast cancer (HR 1.38, 95% CI 1.06–1.80, restricted to invasive first breast cancer). No associations were found for lifestyle (body mass index, physical activity, smoking, alcohol) or reproductive factors (age at menarche, parity, age at first birth, age at menopause). Conclusions: This study suggests that clinical characteristics of the first breast cancer and family history of breast cancer, but not pre-diagnosis lifestyle and reproductive factors, are strongly associated with CBC risk among postmenopausal women. Future studies are needed to understand how these factors contribute to CBC etiology and to identify further opportunities for prevention. [ABSTRACT FROM AUTHOR]

Background: Data suggest that there were disparities in H1N1 vaccine uptake, and these may inform COVID-19 vaccination efforts. We conducted a systematic review to evaluate disparities in H1N1 vaccine uptake, factors contributing to disparities, and interventions to reduce them.Methods: We searched English-language articles in MEDLINE ALL, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from database inception through May 8, 2020. Observational studies examining H1N1 vaccine uptake by race/ethnicity, socioeconomic status, rurality, and disability status in US settings were included. Two reviewers independently assessed study eligibility. Single-reviewer data abstraction was confirmed by a second reviewer. We conducted independent dual quality assessment, and collective strength of evidence assessment.Results: We included 21 studies. African American/Black, Latino, and low-socioeconomic status participants had disproportionately lower H1N1 vaccination rates (low- to moderate-strength evidence). However, Latinos were more likely than Whites to intend to be vaccinated, and African American/Blacks and participants with lower-socioeconomic status were just as likely to intend to be vaccinated as their White and higher-socioeconomic status counterparts (low-strength evidence). Vaccine uptake for other groups has been insufficiently studied. Factors potentially contributing to disparities in vaccine uptake included barriers to vaccine access, inadequate information, and concerns about vaccine safety and efficacy. Studies were largely cross-sectional. Many of the studies are a decade old and were conducted in the context of a different pandemic. The categorization of racial and ethnic groups was not consistent across studies and not all groups were well-studied.Discussion: Efforts to avoid disparities in COVID-19 vaccination uptake should prioritize vaccine accessibility and convenience in African American/Black, Latino, and low-SES communities; engage trusted stakeholders to share vaccine information; and address concerns about vaccine safety and efficacy.Primary Funding Source: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development.Protocol Registration: PROSPERO CRD42020187078. [ABSTRACT FROM AUTHOR]

The galanin receptor family of proteins is present throughout the central nervous system and endocrine system. It comprises of three subtypes—GalR1, GalR2, and GalR3; all of which are G-protein-coupled receptors. Galanin predominantly acts as an inhibitory, hyper-polarizing neuromodulator, which has several physiological as well as pathological functions. Galanin has a role in mediating food intake, memory, sexual behavior, nociception and is also associated with diseases such as Alzheimer's disease, epilepsy, diabetes mellitus, and chronic pain. However, the understanding of signaling mechanisms of the galanin family of neuropeptides is limited and an organized pathway map is not yet available. Therefore, a detailed literature mining of the publicly available articles pertaining to the galanin receptor was followed by manual curation of the reactions and their integration into a map. This resulted in the cataloging of molecular reactions involving 64 molecules into five categories such as molecular association, activation/inhibition, catalysis, transport, and gene regulation. For enabling easy access of biomedical researchers, the galanin–galanin receptor signaling pathway data was uploaded to WikiPathways (https://www.wikipathways.org/index.php/Pathway:WP4970), a freely available database of biological pathways. [ABSTRACT FROM AUTHOR]