Search

Deepika Sirohi,1 Steven C Smith,2,3 Neeraj Agarwal,4 Benjamin L Maughan4 1Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT, USA; 2Department of Pathology, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA; 3Department of Urology, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA; 4Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA Abstract: Over the past few decades, the classification system of renal cell carcinoma (RCC) variants has witnessed tremendous and ongoing refinement driven by genomic profiling and morphological correlation that have provided valuable insights into tumor biology and characterization of this heterogeneous subset of tumors. The importance of accurate classification cannot be understated given the downstream impact on treatment decisions, risk stratification, and need for genetic testing. While the morphologic heterogeneity across these tumors is increasingly being recognized, all non-clear-cell RCCs are commonly categorized under one therapeutic category with management strategies that largely derive from clear-cell RCCs. As research in metastatic RCC progresses, there is a growing focus on rare subtypes and unclassified tumors, which is rapidly changing the treatment paradigm for non-clear-cell RCC. This review focuses on the histomorphologic diagnostic challenges of unclassified RCCs discussing the utility of contemporary diagnostic tools. It further discusses the current state of knowledge and guidelines for management of this class of tumors. Keywords: pathology, classification, morphology, management

Sarah C Smith, AA Jolijn Hendriks, Jemma Regan, Nick Black Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK Background: In research in residential care, health-related quality of life (HRQL) is usually measured using either observational methods or standardized questionnaires. DEMQOL-Proxy is a standardized questionnaire measuring HRQL of people with dementia and is usually reported by a family carer. However, not all residents have a family carer who visits often enough to act as a proxy. Objectives: We evaluated the psychometric performance of DEMQOL-Proxy when reported on behalf of people with dementia in residential care by a “trained proxy” (DEMQOL-Proxy-TP). Participants: We recruited a sample of 87 people with dementia living in care homes around the UK. Methods: We used modern psychometric methods (based on the Rasch model) to evaluate DEMQOL-Proxy-TP (on behalf of 85 residents) in a cross-sectional study. We evaluated scale-to-sample targeting, ordering of item thresholds, item fit to the model and differential item functioning (sex, age, type of dementia), local independence, unidimensionality and reliability on the full set of items (31 items) and also a smaller item set (26 items). Results: The smaller item set (DEMQOL-Proxy-TP-26) performed better than the original item set and was found to fit the model (p = 0.68). Nevertheless, 17 items were found to have disordered thresholds, and 24 pairs of items showed local dependency (residual correlations >0.3). There were also some areas where scale-to-sample targeting could be improved. Conclusion: After resolving the identified anomalies, DEMQOL-Proxy-TP can provide adequate measurement of HRQL of people with dementia living in residential care, particularly when no family carer is available. This can be interpreted at the group level but is not yet robust enough for use at the individual level. Future work will compare these results with the psychometric performance of DEMQOL-Proxy reported by family carers and DEMQOL self-reported by the residents. Keywords: dementia, DEMQOL-Proxy, health-related quality of life, Rasch Measurement Theory, trained proxy

Soot emission has been the focus of numerous studies due to the numerous applications in industry, as well as the harmful effects caused to the environment. Thus, the purpose of this work is to analyze the soot formation in a flat flame burner using premixed compressed natural gas and air, where these quasi-adiabatic flames have one-dimensional characteristics. The measurements were performed applying the light extinction technique. The air/fuel equivalence ratiowas varied to assess the soot volume fractions for different flame configurations. Soot production along the flamewas also analyzed by measurements at different heights in relation to the burner surface. Results indicate that soot volume fraction increases with the equivalence ratio. The higher regions of the flamewere analyzed in order to map the soot distribution on these flames. The results are incorporated into the experimental database for measurement techniques calibration and for computational models validation of soot formation in methane premixed laminar flames, where the equivalence ratio ranging from 1.5 up to 8.

Competing Interests: Conflicts of Interest and Source of Funding: S.C.S. discloses a consulting and authorship royalties relationship with Elsevier Publishing/Amirsys and a consulting relationship with Franklin.AI, both topically unrelated to the subject of this manuscript. For the remaining authors, none were declared.

Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

Aims: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe., Methods and Results: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy., Conclusion: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility., (© 2024 John Wiley & Sons Ltd.)

An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID 50 ] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%-60% (50% inhibitory concentration [IC 50 ] < 50 μg/mL) and total lineage-concentrations estimates of 50-200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: The Accreditation Council for Pharmacy Education (ACPE) 2025 Standards charge pharmacy programs to assess student readiness for Advanced Pharmacy Practice Experiences (APPEs), but the method of assessment is not defined. This report describes the process of developing, implementing, and refining an APPE readiness assessment (ARA) that can be adapted to individual institutional needs and learning outcomes., Educational Activity: The ARA at The University of Texas at El Paso School of Pharmacy, a Hispanic-serving institution, is comprised of two practice areas: drug information and the Pharmacist Patient Care Process, each with multiple objective structured clinical examinations (OSCEs) to mimic how students will apply these skills in required APPE rotations. The ARA has been adapted for administration both virtually and in-person. Students are required to attain a 70 % average across all five OSCEs, with an opportunity to retest on any failed areas prior to progression into the APPE year., Critical Analysis of the Educational Activity: Since initial implementation in 2021, faculty experience and student performance informed changes to the assessment, rubrics, and integration of skills throughout the curriculum. The average overall ARA score was an 89.13 % in 2021 and ranged from 79.74 to 82.3 % in 2022-2024. Typically, less than 10 % of the class required re-testing, however, in 2023 16 % of the class had an ARA average less than 70 % requiring re-testing. Written skills are consistently the lowest performing area for students, potentially due to language discordance between students' preferred language and the language of the assessment., Competing Interests: Declaration of competing interest The authors have no financial or personal conflicts of interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline-directed medical therapy for these patients., Methods and Results: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in-hospital all-cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF-less). SMuRF-less patients had higher in-hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19-1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in-hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07-1.70]). Guideline-directed optimal medical therapy (receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58-1.67]) in SMuRF-less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66-0.98]). Sensitivity analyses were consistent with these results., Conclusions: SMuRF-less patients were associated with an increased risk of in-hospital mortality. Guideline-directed medical therapy was less effective in SMuRF-less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF-less patients., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

The American Heart Association (AHA), founded in 1924, is anchored in the core belief that scientific research can lead the way to better prevention, treatment, recovery, and ultimately a cure for cardiovascular disease. Historically, the association's involvement in international efforts centered on scientific cooperation. Activities mostly involved AHA leadership presenting at international scientific meetings and leaders from other countries sharing scientific and medical information at AHA meetings. Although the AHA's and American Stroke Association's international efforts have expanded substantially since those early days, global knowledge exchange remains the bedrock of its international endeavors. As the AHA turns 100, we reflect on the successful global efforts in prevention, resuscitation, global advocacy, quality improvement, and health equity that have guided the organization to a place of readiness for "advancing health and hope, for everyone, everywhere." Motivated by the enormous potential for population health gains in an aging world, the AHA is entering its second century with redoubled commitment to improving global cardiovascular and cerebrovascular health for all.

Background: The PedsQL™ 4.0 Generic Core Scales (GSC) have been translated into over 60 languages, but use in the sub-Saharan African region is limited. This study aimed to cross-culturally adapt and validate the PedsQL™ 4.0 GCS child self-report and teen self-report versions into the Chichewa language for Malawi., Methods: The English (USA) versions were adapted (translation, back translation and cognitive interviews to evaluate conceptual equivalence) into Chichewa. We recruited 289 children (8-17 years) in Blantyre, Malawi. Classical psychometrics at the item level (missing data, endorsement frequencies, item redundancy) and scale level (internal consistency, convergent, discriminant and known groups validity) was used to evaluate the new Chichewa versions., Results: Six items were found to need cultural adaptation for Malawi. There were problems with missing data (< 5%) and adjacent endorsement frequency (< 10%) among younger children. Internal consistency reliability was acceptable (Cronbach α > 0.7). Convergent validity was generally strong (correlations > 0.4). Discriminant validity (p > 0.05) was evident with respect to gender and age, but not for school grade (p < 0.05). Effect sizes indicating known groups validity were in the expected direction but of variable magnitude., Conclusion: We have successfully adapted the PedsQL™ 4.0 GCS child self-report and teen self-report into Chichewa for use in Malawi. Many aspects of the psychometric evaluation were promising, though some elements were more mixed and we have not yet been able to evaluate test-retest reliability or responsiveness. We suggest that the PedsQL™4.0 GCS child and teen self-reports should be used with caution among children and adolescents in Malawi., (© 2024. The Author(s).)

The evolution of classification of renal tumors has been impacted since the turn of the millennium by rapid progress in histopathology, immunohistochemistry, and molecular genetics. Together, these features have enabled firm recognition of specific, classic types of renal cell carcinomas, such as clear cell renal cell carcinoma, that in current practice trigger histologic-type specific management and treatment protocols. Now, the fifth Edition World Health Classification's new category of "Molecularly defined renal carcinomas" changes the paradigm, defining a total of seven entities based specifically on their fundamental molecular underpinnings. These tumors, which include TFE3-rearranged, TFEB-altered, ELOC-mutated, fumarate hydratase-deficient, succinate dehydrogenase-deficient, ALK-rearranged, and SMARCB1-deficient renal medullary carcinoma, encompass a wide clinical and histopathologic phenotypic spectrum of tumors. Already, important management aspects are apparent for several of these entities, while emerging therapeutic angles are coming into view. A brief, clinically-oriented introduction of the entities in this new category, focusing on relevant diagnostic, molecular, and management aspects, is the subject of this review., Competing Interests: Declaration of competing interest No AI was employed in preparation of this manuscript. The authors declare that there are no conflicts of interest regarding this article. SCS discloses consulting/royalty income from Elsevier/Amirsys publishing that does not pose a conflict with this content., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Photoreduction of carbon dioxide (CO 2 ) on plasmonic structures is of great interest in photocatalysis to aid selectivity. While species commonly found in reaction environments and associated intermediates can steer the reaction down different pathways by altering the potential energy landscape of the system, they are often not addressed when designing efficient plasmonic catalysts. Here, we perform an atomistic study of the effect of the hydroxyl group (OH) on CO 2 activation and hot electron generation and transfer using first-principles calculations. We show that the presence of OH is essential in breaking the linear symmetry of CO 2 , which leads to a charge redistribution and a decrease in the OCO angle to 134°, thereby activating CO 2 . Analysis of the partial density of states (pDOS) demonstrates that the OH group mediates the orbital hybridization between Au and CO 2 resulting in more accessible states, thus facilitating charge transfer. By employing time-dependent density functional theory (TDDFT), we quantify the fraction of hot electrons directly generated into hybridized molecular states at resonance, demonstrating a broader energy distribution and an 11% increase in charge-transfer in the presence of OH groups. We further show that the spectral overlap between excitation energy and plasmon resonance plays a critical role in efficiently modulating electron transfer processes. These findings contribute to the mechanistic understanding of plasmon-mediated reactions and demonstrate the importance of co-adsorbed species in tailoring the electron transfer processes, opening new avenues for enhancing selectivity.

Background and Objective: Radical prostatectomy (RP) is an established treatment for localised prostate cancer that can have a significant impact on urinary and sexual function, with recovery over time. Our aim was to describe functional recovery in the first year after RP, reporting descriptive outcomes alongside validated patient-reported outcome measure scores (Expanded Prostate Cancer Index Composite, EPIC-26)., Methods: Men undergoing RP between September 2015 and November 2019 completed EPIC-26 at baseline and 1, 3, 6, and 12 mo., Key Findings and Limitations: Overall, 2030 men consented to participation, underwent RP, and completed EPIC-26. At baseline, 97% were pad-free (1928/1996; 95% confidence interval [CI] 96-97%) and 77% were leak-free and pad-free (1529/1996; 95% CI 75-78), with a median EPIC-26 incontinence domain score of 100 (interquartile range [IQR] 86-100). At 12 mo, 65% were pad-free (904/1388; 95% CI 63-68%) and 42% were leak-free and pad-free (583/1388; 95% CI 39-45%), with a median EPIC-26 score of 76 (IQR 61-100). While one in three men reported wearing a pad at 12 mo, fewer than one in ten men needed more than 1 pad/d. At baseline, 1.9% reported a "moderate or big problem" with urine leakage, which increased to 9.7% at 12 mo. At baseline, the median sexual domain score among 1880 men was 74 (IQR 43-92) and 52% had erections sufficient for intercourse without medication (975/1880; 95% CI 50-54%). Among these 975 men, 630 responded at 12 mo, of whom 17% reported sufficient erections for intercourse (105/630; 95% CI 14-20%), without medication in 6% (37/630; 95% CI 4-8%) and needing medication in 11% (68/630; 95% CI 9-13%); the median EPIC-26 domain score was 26 (IQR 13-57)., Conclusions and Clinical Implications: Reporting of functional outcomes after RP in terms of easily understood concepts such as pad-free and leak-free status, and erections with and with medication, alongside the classical report using EPIC-26 domain scores, increases the understanding of RP recovery patterns over the first year., Patient Summary: At 12 months after surgery for prostate cancer, one in ten men reported a moderate or big problem with urine leakage and one in five men reported sufficient erections., (© 2024 The Authors.)

Regional variations in acute coronary syndrome (ACS) management and outcomes have been an enormous public health issue. However, studies have yet to explore how to reduce the variations. The National Chest Pain Center Program (NCPCP) is the first nationwide, hospital-based, comprehensive, continuous quality improvement program for improving the quality of care in patients with ACS in China. We evaluated the association of NCPCP and regional variations in ACS healthcare using generalized linear mixed models and interaction analysis. Patients in the Western region had longer onset-to-first medical contact (FMC) time and time stay in non-percutaneous coronary intervention (PCI) hospitals, lower rates of PCI for ST-elevation myocardial infarction (STEMI) patients, and higher rates of medication usage. Patients in Central regions had relatively lower in-hospital mortality and in-hospital heart failure rates. Differences in the door-to-balloon time (DtoB) and in-hospital mortality between Western and Eastern regions were less after accreditation (β = -8.82, 95% confidence interval (CI) -14.61 to -3.03; OR = 0.79, 95%CI 0.70 to 0.91). Similar results were found in differences in DtoB time, primary PCI rate for STEMI between Central and Eastern regions. The differences in PCI for higher-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients among different regions had been smaller. Additionally, the differences in medication use between Eastern and Western regions were higher after accreditation. Regional variations remained high in this large cohort of patients with ACS from hospitals participating in the NCPCP in China. More comprehensive interventions and hospital internal system optimizations are needed to further reduce regional variations in the management and outcomes of patients with ACS., (Copyright © 2024. Published by Elsevier B.V.)

The diagnosis and reporting of prostatic adenocarcinoma have evolved from the classic framework promulgated by Dr Donald Gleason in the 1960s into a complex and nuanced system of grading and reporting that nonetheless retains the essence of his remarkable observations. The criteria for the "Gleason patterns" originally proposed have been continually refined by consensuses in the field, and Gleason scores have been stratified into a patient-friendly set of prognostically validated and widely adopted Grade Groups. One product of this successful grading approach has been the opportunity for pathologists to report diagnoses that signal carefully personalized management, placing the surgical pathologist's interpretation at the center of patient care. At one end of the continuum of disease aggressiveness, personalized diagnostic care means to sub-stratify patients with more indolent disease for active surveillance, while at the other end of the continuum, reporting histologic markers signaling aggression allows sub-stratification of clinically significant disease. Whether contemporary reporting parameters represent deeper nuances of more established ones (eg, new criteria and/or quantitation of Gleason patterns 4 and 5) or represent additional features reported alongside grade (intraductal carcinoma, cribriform patterns of carcinoma), assessment and grading have become more complex and demanding. Herein, we explore these newer reporting parameters, highlighting the state of knowledge regarding morphologic, molecular, and management aspects. Emphasis is made on the increasing value and stakes of histopathologists' interpretations and reporting into current clinical risk stratification and treatment guidelines., Competing Interests: S.C.S. reports financial relationships that do not represent a conflict regarding this manuscript, including royalties for consulting and authorship from Elsevier/Amirsys Publishing. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Recent years have seen the recognition and establishment of numerous subtypes of renal cell carcinoma (RCC), including adoption of an entire category of "molecularly defined renal carcinomas" in the fifth Edition of World Health Organization Classification. To add value, new diagnostic entities should be clinicopathologically distinct, or better, imply specific management and treatment angles, especially if adjunctive testing is needed for diagnosis. One such promising future treatment angle for a molecularly defined subtype, TFEB -amplified RCC, is immunotherapy, for which recent scholarship has demonstrated frequent expression of PD-L1. Herein, we report a case of metastatic TFEB -amplified RCC, where the patient experienced a long-term, complete response to PDL1-directed therapy, which had been serendipitously used years ago under a renal tumor subtype-agnostic indication. This promising experience suggests formal exploration of immunotherapy for these tumors., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.