Patient Understanding and Perception of Urology Resident Training, Role, and Capabilities.

INTRODUCTION: We sought to identify patient understanding of urology residents and comfort with being cared for by residents. Through this pilot study, we aim to propose educational objectives to improve this knowledge gap and ultimately allow for an improved patient experience. METHODS: A prospective survey was distributed from September 2022 to October 2022. A patient knowledge about residents (KAR) score was calculated by combining correct responses to 5 questions (maximum = 5). Another score evaluating patient opinion of residents was calculated using Likert scale questions (range 3-19; higher scores correlate with positive opinion) denoting patient outlook on residents. RESULTS: A total of 88 surveys were completed. The average ± SD patient age was 62.7 ± 15.2 years. Patients previously seen by a resident had significantly higher KAR scores (3.591 ± 1.210) compared to patients never interacting with a resident or unsure (KAR = 2.381 ± 1.324; P < .0001). Additionally, those with higher levels of education had greater KAR scores (graduate-level KAR = 3.792 ± 1.179; P = .002). No variables were found to have a statistically significant impact on patients' average opinion of residents. CONCLUSIONS: Current patient understanding of the role of a urology resident is suboptimal. Given this knowledge gap, we hope to propose educational approaches to help aid in patient understanding of resident physicians, who play a critical role in their clinical care.

Top-cited articles in andrology journals from 2013-2022: a bibliometric analysis.

Bibliometric analyses serve to identify influential articles that have shaped medical practice and fostered new research ideas. Over the past decade, research in andrology has witnessed exponential growth, with an increasing number of academic publications, collaborations, and research innovations. However, there is a lack of literature that has identified the top-cited andrology articles. We conducted a bibliometric analysis to identify the top 1000 citations in andrology journals, with a focus on the top funding agencies, authors, institutions, countries/regions, and journals. To perform this analysis, we identified the top-cited articles in andrology journals as indexed in the Web of Science Core Collection. From 2013 through 2022, we found a total of 9827 articles published in andrology journals. The top publishers included "Andrology," the "Asian Journal of Andrology," and "Andrologia." The top affiliations contributing to research include the Cleveland Clinic Foundation (269 publications), Egyptian Knowledge Bank (EKB) (265), and Shanghai Jiao Tong University (202). Funding was primarily provided by notable agencies such as the National Natural Science Foundation of China (905 grants), United States Department of Health Human Services (321), and National Institutes of Health (NIH USA) (317). The present bibliometric analysis highlights andrology research from 2013 through 2022, offering key insights into leading contributors, influential authors, prominent funding sources, and major trends in the field.

Matriglycan maintains t-tubule structural integrity in cardiac muscle.

Maintaining the structure of cardiac membranes and membrane organelles is essential for heart function. A critical cardiac membrane organelle is the transverse tubule system (called the t-tubule system) which is an invagination of the surface membrane. A unique structural characteristic of the cardiac muscle t-tubule system is the extension of the extracellular matrix (ECM) from the surface membrane into the t-tubule lumen. However, the importance of the ECM extending into the cardiac t-tubule lumen is not well understood. Dystroglycan (DG) is an ECM receptor in the surface membrane of many cells, and it is also expressed in t-tubules in cardiac muscle. Extensive posttranslational processing and O-glycosylation are required for DG to bind ECM proteins and the binding is mediated by a glycan structure known as matriglycan. Genetic disruption resulting in defective O-glycosylation of DG results in muscular dystrophy with cardiorespiratory pathophysiology. Here, we show that DG is essential for maintaining cardiac t-tubule structural integrity. Mice with defects in O-glycosylation of DG developed normal t-tubules but were susceptible to stress-induced t-tubule loss or severing that contributed to cardiac dysfunction and disease progression. Finally, we observed similar stress-induced cardiac t-tubule disruption in a cohort of mice that solely lacked matriglycan. Collectively, our data indicate that DG in t-tubules anchors the luminal ECM to the t-tubule membrane via the polysaccharide matriglycan, which is critical to transmitting structural strength of the ECM to the t-tubules and provides resistance to mechanical stress, ultimately preventing disruptions in cardiac t-tubule integrity.

Automated vs. manual coding of neuroimaging reports via natural language processing, using the international classification of diseases, tenth revision.

Objective: Natural language processing (NLP) can generate diagnoses codes from imaging reports. Meanwhile, the International Classification of Diseases (ICD-10) codes are the United States' standard for billing/coding, which enable tracking disease burden and outcomes. This cross-sectional study aimed to test feasibility of an NLP algorithm's performance and comparison to radiologists' and physicians' manual coding. Methods: Three neuroradiologists and one non-radiologist physician reviewers manually coded a randomly-selected pool of 200 craniospinal CT and MRI reports from a pool of >10,000. The NLP algorithm (Radnosis, VEEV, Inc., Minneapolis, MN) subdivided each report's Impression into "phrases", with multiple ICD-10 matches for each phrase. Only viewing the Impression, the physician reviewers selected the single best ICD-10 code for each phrase. Codes selected by the physicians and algorithm were compared for agreement. Results: The algorithm extracted the reports' Impressions into 645 phrases, each having ranked ICD-10 matches. Regarding the reviewers' selected codes, pairwise agreement was unreliable (Krippendorff α = 0.39-0.63). Using unanimous reviewer agreement as "ground truth", the algorithm's sensitivity/specificity/F2 for top 5 codes was 0.88/0.80/0.83, and for the single best code was 0.67/0.82/0.67. The engine tabulated "pertinent negatives" as negative codes for stated findings (e.g. "no intracranial hemorrhage"). The engine's matching was more specific for shorter than full-length ICD-10 codes (p = 0.00582x10-3). Conclusions: Manual coding by physician reviewers has significant variability and is time-consuming, while the NLP algorithm's top 5 diagnosis codes are relatively accurate. This preliminary work demonstrates the feasibility and potential for generating codes with reliability and consistency. Future works may include correlating diagnosis codes with clinical encounter codes to evaluate imaging's impact on, and relevance to care.

Evidence to support health system prioritization of health behaviors in the COVID-19 era.

BACKGROUND: Since the COVID-19 pandemic health systems have shifted necessarily from chronic to infectious disease treatment, but chronic disease remains critical. One large health system uniquely tracks member health behaviors. This analysis compares data from select months of an ongoing monthly cross-sectional survey before and during the pandemic. METHODS: Responses in April 2019 (pre-pandemic), April 2020 (early pandemic) or April 2021 (later pandemic) were included in the primary analysis (N = 252). Differences in meeting health behavior guidelines were analyzed via logistic regression. RESULTS: A significant decline was seen for physical activity (19% not meeting guidelines pre-pandemic vs. 41% later pandemic) but not fruit/vegetable, alcohol, or sleep from early to later pandemic. Prevalence of women not meeting tobacco guidelines increased from early (5%) to later pandemic (10%) while prevalence in men decreased (10% vs 4% respectively). The percent of people not thinking about the good things that happen to them fluctuated closely with reports of new COVID-19 cases. CONCLUSIONS: Findings show the nuance of changing health behaviors throughout the pandemic. Results should be used by health systems to tailor support based on insights from the pandemic experience.

A pilot trial of a brief intervention for cannabis use supplemented with a substance-free activity session or relaxation training.

OBJECTIVE: Cannabis use is increasing among college students and commonly co-occurs with anxiety symptoms in this age group. Interventions that reduce anxiety may also reduce cannabis use. Behavioral economic theory suggests that substance use reductions are most likely when there is an increase in substance-free reinforcement. This randomized pilot trial evaluated the efficacy of a brief motivational intervention (BMI) for cannabis supplemented by either a substance-free activity session (SFAS) or a relaxation training (RT) session for reducing cannabis use, problems, craving, and anxiety symptoms. METHOD: One hundred thirty-two college students (Mage = 19.9; 54% female; 67% White, 31% Black) who reported five or more past-month cannabis use days were randomized to: (a) assessment-only (AO); (b) BMI plus SFAS; or (c) BMI plus RT. Participants in the BMI conditions received two individual counselor-administered sessions plus a brief phone booster session. Outcomes were evaluated 1- and 6-months postintervention. RESULTS: Relative to assessment, both BMI + SFAS and BMI + RT were associated with significant reductions in cannabis problems and craving at 1-month follow-up, and significant reductions in anxiety at 6-month follow-up. Relative to AO, BMI + RT was associated with significant reductions in cannabis use at 1-month follow-up. There were no differences between BMI conditions. CONCLUSIONS: This pilot trial was not adequately powered to conclusively evaluate relative efficacy but provides preliminary support for the short-term efficacy of both two-session interventions for reducing anxiety and cannabis-related risk among nontreatment seeking emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Penile Strangulation: Analysis of Postextrication Follow-Up, Sequelae, and a Review of Literature.

Numerous case reports exist on penile strangulation injuries and extrication methods; however, the care and long-term consequences of penile strangulation injuries have been under-reported. Our aim is to investigate the long-term outcomes and sequalae following penile strangulation injuries. The PubMed Medline database was searched using the keyword string "penile strangulation," "penis strangulation," and "constriction" for all studies reporting outcomes of published penile strangulation injuries. Articles were evaluated for follow-up after strangulation injury, strangulating agent, extricating agent, and sequelae of injury. Fifty-six studies resulted with reports of 100 cases of penile strangulation and extrication from January 2000 to December 2019. The mean patient age was 41 (range: 3-86) years. Twenty-four (24/100) cases reported sequalae following extrication. Follow-up ranged from 2 weeks to 7 years with median follow-up time in the 7- to 12-month grouping. Metal rings comprised 36% (36/100) of strangulation agents and 50% of reported incidents were attributed to sexual activity. To our knowledge, this is the only study focusing on long-term outcomes after penile strangulation. This review provides a summary of 56 studies that document penile strangulation injuries over the last 20 years. Although a wide array of penile strangulation injuries have been documented in the literature, reports lack secondary management and long-term outcomes after removal of the strangulation device. We recommend that providers report long-term penile strangulation outcomes for future urologic evaluations after extrication.

Reporting and impact of subsequent cycle toxicities in oncology phase I clinical trials.

BACKGROUND/AIMS: As oncology treatments evolve, classic assumptions of toxicity associated with cytotoxic agents may be less relevant, requiring new design strategies for trials intended to inform dosing strategies for agents that may be administered beyond a set number of defined cycles. We describe the overall incidence of dose-limiting toxicities during and after cycle 1, frequency of reporting subsequent cycle toxicities, and the impact of post-cycle 1 dose-limiting toxicities on conclusions drawn from oncology phase 1 clinical trials. METHODS: We conducted a systematic review of subsequent cycle toxicities in oncology phase I clinical trials published in the Journal of Clinical Oncology from 2000 to 2020. We used chi-square tests and multivariate logistic regression to describe predictors of reporting subsequent cycle toxicity data. RESULTS: From 2000 to 2020, we identified 489 articles reporting on therapeutic phase 1 clinical trials. Of these, 421 (86%) reported data regarding cycle 1 dose-limiting toxicities and 170 (35%) reported data on cycle 1 dose modifications. Of the trials that reported cycle 1 dose-limiting toxicities, the median percentage of patients that experienced cycle 1 dose-limiting toxicities was 8.89%. Only 47 (9.6%) publications reported on post-cycle 1 dose-limiting toxicities and only 92 (19%) reported on dose modifications beyond cycle 1. Of the trials that reported post-cycle 1 dose-limiting toxicities, the median percentage of patients that experienced post-cycle 1 dose-limiting toxicities was 14.8%. Among the 371 studies with a recommended phase 2 dose, 89% did not report whether post-cycle 1 toxicities impacted the recommended phase 2 dose. More recent year of publication was independently associated with reduced odds of reporting subsequent cycle toxicity. CONCLUSION: Reporting of subsequent cycle toxicity is uncommon in oncology phase I clinical trial publications and becoming less common over time. Guidelines for reporting of phase I oncology clinical trials should expand to include toxicity data beyond the first cycle.

A comprehensive analysis of neuroblastoma incidence, survival, and racial and ethnic disparities from 2001 to 2019.

BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR). METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI). RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per million persons [95% CI: 8.2, 8.5], with an AAPC of 0.4% [95% CI: -0.1, 0.9]. Five-year relative survival from the NPCR dataset (n = 10,676) was 79.7% [95% CI: 78.9, 80.5]. Patients aged less than 1 year had the highest 5-year relative survival (92.5%). Five-year relative survival was higher for non-Hispanic White patients (80.7%) or Hispanic patients (80.8%) compared to non-Hispanic Black patients (72.6%). CONCLUSION: Neuroblastoma incidence was stable during 2003-2019. Differences in relative survival exist by sex, age, race/ethnicity, and stage; patients who were male, older, non-Hispanic Black, or with distant disease had worse survival. Future studies could seek to assess the upstream factors driving disparities in survival, and evaluate interventions to address inequities and improve survival across all groups.

Deep Mutational Scanning in Disease-related Genes with Saturation Mutagenesis-Reinforced Functional Assays (SMuRF).

Interpretation of disease-causing genetic variants remains a challenge in human genetics. Current costs and complexity of deep mutational scanning methods hamper crowd-sourcing approaches toward genome-wide resolution of variants in disease-related genes. Our framework, Saturation Mutagenesis-Reinforced Functional assays (SMuRF), addresses these issues by offering simple and cost-effective saturation mutagenesis, as well as streamlining functional assays to enhance the interpretation of unresolved variants. Applying SMuRF to neuromuscular disease genes FKRP and LARGE1, we generated functional scores for over 99.8% of all possible coding single nucleotide variants and resolved 310 clinically reported variants of uncertain significance with high confidence, enhancing clinical variant interpretation in dystroglycanopathies. SMuRF also demonstrates utility in predicting disease severity, resolving critical structural regions, and providing training datasets for the development of computational predictors. Our approach opens new directions for enabling variant-to-function insights for disease genes in a manner that is broadly useful for crowd-sourcing implementation across standard research laboratories.

Deafening Silence of Male Infertility.

Think about 6 loved ones of reproductive age in your life. Now imagine that 1 of these 6 individuals is suffering from infertility. Perhaps they feel alone and isolated, unable to discuss their heartbreak with their closest friends, family, and support network. Suffering in silence. In this editorial, we discuss the infertility journey through the lens of the patients, the providers, and the scientists who struggle with infertility each and every day. Our goal is to open a dialogue surrounding infertility, with an emphasis on dismantling the longstanding societal barriers to acknowledging male infertility as a disease. Through education, communication, compassion, and advocacy, together we can all begin to break the deafening silence of male infertility.

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma.

PURPOSE: Phase 1 study assessing the safety and toxicity of cabozantinib in combination with topotecan and cyclophosphamide for relapsed osteosarcoma and Ewing sarcoma. METHODS: Oral cabozantinib (25 mg/m2 ) was administered daily for 21 (dose level 1) or 14 (dose level -1B) days. Topotecan (0.75 mg/m2 ) and cyclophosphamide (250 mg/m2 ) were administered intravenously (IV) on days 1-5. A modified 3+3 design based upon first cycle dose-limiting toxicities (DLT) was used for dose escalation. RESULTS: Twelve patients with a median age of 15 (12.9-33.2) years were enrolled (seven with Ewing sarcoma; five with osteosarcoma); all were evaluable for toxicity. At dose level 1, three of six patients developed first cycle DLT: grade 3 epistaxis, grade 3 transaminitis, and prolonged grade 2 thrombocytopenia. Six patients were enrolled on dose level -1B (interrupted cabozantinib, given days 8-21), with one first cycle DLT (grade 3 pneumothorax) observed. Of the 10 response evaluable patients, one had partial response (Ewing sarcoma), seven had stable disease, and two had progressive disease. CONCLUSIONS: The recommended phase 2 doses and schedules for this combination are topotecan 0.75 mg/m2 IV days 1-5, cyclophosphamide 250 mg/m2 IV days 1-5, and cabozantinib 25 mg/m2 days 8-21. Non-concomitant administration of cabozantinib with cytotoxic therapy in this population has acceptable toxicity, while allowing for potential disease control.

Identification of Matriglycan by Dual Exoglycosidase Digestion of α-Dystroglycan.

Matriglycan is a linear polysaccharide of alternating xylose and glucuronic acid units [-Xyl-α1,3-GlcA-ß1,3]n that is uniquely synthesized on α-dystroglycan (α-DG) and is essential for neuromuscular function and brain development. It binds several extracellular matrix proteins that contain laminin-globular domains and is a receptor for Old World arenaviruses such as Lassa Fever virus. Monoclonal antibodies such as IIH6 are commonly used to detect matriglycan on α-DG. However, endogenous expression levels are not sufficient to detect and analyze matriglycan by mass spectrometry approaches. Thus, there is a growing need to independently confirm the presence of matriglycan on α-DG and possibly other proteins. We used an enzymatic approach to detect matriglycan, which involved digesting it with two thermophilic exoglycosidases: ß-Glucuronidase from Thermotoga maritima and α-xylosidase from Sulfolobus solfataricus. This allowed us to identify and categorize matriglycan on α-DG by studying post-digestion changes in the molecular weight of α-DG using SDS-PAGE followed by western blotting with anti-matriglycan antibodies, anti-core α-DG antibodies, and/or laminin binding assay. In some tissues, matriglycan is capped by a sulfate group, which renders it resistant to digestion by these dual exoglycosidases. Thus, this method can be used to determine the capping status of matriglycan. To date, matriglycan has only been identified on vertebrate α-DG. We anticipate that this method will facilitate the discovery of matriglycan on α-DG in other species and possibly on other proteins. Key features • Analysis of endogenous matriglycan on dystroglycan from any animal tissue. • Matriglycan is digested using thermophilic enzymes, which require optimum thermophilic conditions. • Western blotting is used to assay the success and extent of digestion. • Freshly purified enzymes work best to digest matriglycan.

Predictors of Stigma, Guilt, and Shame among Adults Bereaved by Fatal Overdose.

With the spectacular rise of US overdose deaths, bereavement for these affected families has become a matter of increasing concern. Qualitative research has highlighted the role of stigmatization as well as guilt and shame among this population. However, the magnitude and pre-death predictors of stigmatization, guilt, and shame have yet to be assessed quantitatively. In the current study, we assess the magnitude of stigmatization, guilt, and shame among 115 adults bereaved by overdose by drawing comparisons with 185 adults bereaved by suicide. Results revealed no significant differences regarding overall levels of stigmatization, guilt, and shame between the overdose and suicide bereaved. Among the overdose bereaved, regression models indicated a number of pre-death factors associated with stigmatization, guilt, and shame, such as the frequency of the decedent's drug use, family drug use severity, and interpersonal conflict between the bereaved and the decedent. Implications and future directions for research are discussed.

Evolution of an extreme hemoglobin phenotype contributed to the sub-Arctic specialization of extinct Steller's sea cows.

The extinct Steller's sea cow (Hydrodamalis gigas; †1768) was a whale-sized marine mammal that manifested profound morphological specializations to exploit the harsh coastal climate of the North Pacific. Yet despite first-hand accounts of their biology, little is known regarding the physiological adjustments underlying their evolution to this environment. Here, the adult-expressed hemoglobin (Hb; α2ß/δ2) of this sirenian is shown to harbor a fixed amino acid replacement at an otherwise invariant position (ß/δ82Lys→Asn) that alters multiple aspects of Hb function. First, our functional characterization of recombinant sirenian Hb proteins demonstrates that the Hb-O2 affinity of this sub-Arctic species was less affected by temperature than those of living (sub)tropical sea cows. This phenotype presumably safeguarded O2 delivery to cool peripheral tissues and largely arises from a reduced intrinsic temperature sensitivity of the H. gigas protein. Additional experiments on H. gigas ß/δ82Asn→Lys mutant Hb further reveal this exchange renders Steller's sea cow Hb unresponsive to the potent intraerythrocytic allosteric effector 2,3-diphosphoglycerate, a radical modification that is the first documented example of this phenotype among mammals. Notably, ß/δ82Lys→Asn moreover underlies the secondary evolution of a reduced blood-O2 affinity phenotype that would have promoted heightened tissue and maternal/fetal O2 delivery. This conclusion is bolstered by analyses of two Steller's sea cow prenatal Hb proteins (Hb Gower I; ζ2ε2 and HbF; α2γ2) that suggest an exclusive embryonic stage expression pattern, and reveal uncommon replacements in H. gigas HbF (γ38Thr→Ile and γ101Glu→Asp) that increased Hb-O2 affinity relative to dugong HbF. Finally, the ß/δ82Lys→Asn replacement of the adult/fetal protein is shown to increase protein solubility, which may have elevated red blood cell Hb content within both the adult and fetal circulations and contributed to meeting the elevated metabolic (thermoregulatory) requirements and fetal growth rates associated with this species cold adaptation.

In 1741, shipwrecked naturalist Georg Wilhelm Steller made detailed observations of large marine mammals grazing on seaweed in the shallow waters surrounding a remote island in the North Pacific Ocean. Within thirty years, these 'Steller's sea cows' had been hunted to extinction. Unlike their remaining tropical relatives ­ dugongs and manatees ­ Steller's sea cows were specialized to cold, sub-Arctic environments. Measuring up to 10 meters long, they were much larger than other sea cow species. This, along with having very thick skin, helped them to reduce heat loss. Previous work showed that the hemoglobin protein ­ which binds to and carries oxygen around mammalian bodies ­ of Steller's sea cows had a decreased affinity for oxygen, resulting in greater delivery of oxygen to organs and tissues. It was thought that this could be an adaptation to fuel heightened metabolic heat production in cold conditions. Studies of ancient DNA also identified the substitution of a single building block in the Steller's sea cow hemoglobin protein that is not present in other mammals and was suspected to underlie this modification. To determine how this unique substitution affects Steller's sea cow hemoglobin function ­ and whether it contributed to their ability to live in cold environments ­ Signore et al. generated hemoglobin proteins of Steller's sea cows, dugongs and Florida manatees. Testing their biochemical properties showed that this single exchange profoundly alters multiple aspects of how the Steller's sea cow hemoglobin works. Alongside reducing hemoglobin's oxygen affinity, the Steller's sea cow substitution also makes the protein more soluble, potentially increasing the level of hemoglobin within red blood cells. Additionally, it eliminates hemoglobin sensitivity to a molecule involved in oxygen binding ­ known as DPG ­ saving energy by no longer requiring production of this molecule. Furthermore, the same substitution makes hemoglobin less sensitive to changes in temperature, which would have helped to safeguard the delivery of oxygen to cool limbs and other extremities, reducing costly heat loss. Together, these changes in hemoglobin would have helped the Steller's sea cow to more efficiently transport oxygen around the body. Importantly, generating and testing Steller's sea cow pre-natal hemoglobins suggested this substitution may have also helped to enhance the fetal growth rate of these immense marine mammals by improving gas exchange between the mother and fetus. Signore et al. have revealed how a mutated form of hemoglobin allowed an extinct mammal to adapt to an extreme environment. Similar methods could be used to understand the physiological attributes of other extinct animals. In the future, this increased understanding of hemoglobin mutations could aid the development of human hemoglobin substitutes for therapeutic uses.