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Background: In the United States (US), transgender women of color experience cyclical, interlocking systems of structural and institutional oppression rooted in racism and transphobia, which fuel economic vulnerability. Together, cycles of intersecting racism, transphobia, and economic vulnerability create conditions that give rise to extreme HIV inequities among transgender women of color. Microeconomic interventions - designed to improve financial standing by increasing income generation and access to financial resources through entrepreneurship, cash transfers, and training - have the potential to address structural factors underlying HIV inequities. Over the past few years, several trans-led organizations, including the Trans Sistas of Color Project, have integrated microeconomic strategies, specifically emergency assistance, into their programming. The aim of the current study is to conduct a pilot randomized controlled trial (RCT) to evaluate the feasibility and acceptability of a definitive subsequent RCT and explore initial evidence of an enhanced microeconomic intervention to increase income generation and improve HIV prevention and care continua outcomes., Methods: This is a two-arm waitlist randomized controlled trial in which transgender women of color will be randomly allocated to either usual care that includes the Trans Sistas of Color Project's existing microeconomic interventions, which includes the following: (1) US $250 in emergency assistance and (2) peer support to obtain legal gender affirmation (i.e., legal name and gender markers on identification documents) or the enhanced microeconomic intervention that includes usual care and will be enhanced to include the following: (1) 12 weekly educational group sessions on economic empowerment (i.e., job acquisition, income generation through micro-business, and financial literacy) and HIV prevention and care, (2) employment-focused mentoring, and (3) an unconditional grant (US $1200) for use towards acquiring self-led or formal employment. Participants in each condition will complete a baseline survey prior to randomization, a follow-up survey immediately following intervention completion, and 3-month survey after intervention completion. Participants will also complete qualitative exit interviews within 1 month of intervention completion for both conditions., Discussion: This study will be one of the first US-based pilot randomized clinical trials that builds upon existing community-led solutions to economic vulnerability to address HIV inequities. Findings will provide the necessary groundwork to examine intervention effectiveness in a future large-scale trial., Trials Registration: NCT06212544., Protocol Version: September 25, 2024, version 2., (© 2024. The Author(s).)

Objective: The primary objective was to determine the prognostic significance of circulating tumor DNA (ctDNA) in patients receiving neoadjuvant chemotherapy (NAC) for localized pancreatic ductal adenocarcinoma (PDAC) using digital droplet polymerase chain reaction (ddPCR)., Summary and Background Data: Increasingly, ctDNA is being used for clinical decision-making in a variety of solid malignancies. However, the detection and prognostic value of KRAS ctDNA as assessed by ddPCR during NAC has yet to be characterized., Methods: Patients with localized PDAC eligible to receive NAC were prospectively enrolled. Peripheral blood samples were obtained at diagnosis, after NAC, and after resection and analyzed for ctDNA using ddPCR. Log-rank tests and Cox proportional hazards model were used to assess for association with OS., Results: 84 patients were included in the analysis. Mutant KRAS ctDNA was detected in 49.3% of patients at diagnosis, 69.6% of patients after NAC, and 69.7% of patients after resection, respectively. There were 15 (17.9%) patients that cleared mutational ctDNA over the course of treatment. Clearance of ctDNA during NAC was associated with improved overall survival (OS) (18.4 mo. vs NR, P<0.05). Detection of mutant KRAS G12V after NAC and resection was associated with shorter OS (18.0 versus NR months, P<0.031). Detection of the KRAS G12V mutation after resection was associated with reduced OS (aHR 36.75, 95% CI 2.93-461.38)., Conclusions: Throughout treatment, KRAS ctDNA is detectable by ddPCR in patients with localized PDAC treated with NAC. Detection of mutant KRAS G12V after resection was associated with reduced OS., Competing Interests: Conflicts of interest: The authors have no pertinent conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance (CCUS) are recently recognized diagnostic entities that serve as an independent risk factors for cardiovascular disease and myeloid malignancy. CH is an incidental finding, and evaluation of the incidence of CH/CCUS-associated mutations in solid tumor next-generation sequencing samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed between February 2022 and April 2023 on next-generation sequencing data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. A total of 2479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS-associated mutations, with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified, and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommendations for these criteria as future guidelines for reporting are described. These variants are incidental findings that require more extensive follow-up or change in therapy management using a single institutional cohort., Competing Interests: Disclosure Statement None declared., (Copyright © 2024. Published by Elsevier Inc.)

Context.—: The distinction between well-differentiated epithelial favorable-histology Wilms tumor (EFHWT) and metanephric adenoma (MA) in children has historically been determined by the required absence of both a fibrous pseudocapsule and mitotic activity in MA. More recently these features have been allowed in adult MA. Mutations in exon 15 of the BRAF gene are reported in up to 88% of MAs but have not been reported in EFHWTs in children lacking MA features., Objective.—: To clarify the pathologic and molecular features used to distinguish between pediatric MA and EFHWT., Design.—: Stage I epithelial tumors classified as EFHWT on central review (36 patients) were identified from the Children's Oncology Group AREN03B2 study. Thirteen tumors had morphologic features overlapping those of MA and 23 lacked such features; 35 of 36 had tissue available for sequencing of BRAF., Results.—: Patients with EFHWTs with MA features (13) were older (mean, 8.4 versus 1.9 years; P < .001), had smaller tumor diameters (mean, 6.0 versus 9.7 cm; P < .001), and had fewer mitoses (mean, 1 versus 48 mitoses per 10 high-power fields; P < .001) than patients with EFHWT lacking MA features (23). All EFHWTs with MA features contained at least a partial fibrous pseudocapsule; 7 of 12 (58%) had a BRAF exon 15 mutation. No BRAF exon 15 mutations were identified in 23 EFHWTs lacking MA features. None of the 13 EFHWT patients with MA features have experienced relapse (median follow-up 5.9 years)., Conclusions.—: Pediatric epithelial neoplasms with features of MA that show partial encapsulation and/or modest mitotic activity may be classified as MAs. Although BRAF mutation supports the diagnosis of MA, it is not required for the diagnosis., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Introduction: There is an increasing demand to optimize the workflow and maximize tissue available for next-generation sequencing (NGS) for non-small cell carcinoma. We looked at transbronchial needle endobronchial ultrasound-guided bronchoscopy with transbronchial needle aspiration samples and evaluated the performance of supernatant (SN) fluid processed from a dedicated aspirate collected for NGS testing., Materials and Methods: Nineteen samples were collected and processed using a new workflow. Five aspirates were collected in formalin. One additional dedicated pass was collected fresh and centrifuged. The resulting cell pellet was added to formalin for cell block (CB) processing. DNA and RNA were extracted from concentrated SN for targeted testing using the Oncomine Precision Assay (Thermo Scientific, Waltham, MA). NGS results from the corresponding CB samples were used as "controls" for comparison., Results: Thirty-one mutations were detected in SN (Table 1). The most frequently mutated genes were TP53 (35%), EGFR (23%), KRAS (13%), CTNNB1 (6%), and ERBB2 (6%). There was 100% concordance between the mutations detected in SN and corresponding CBs with comparable variant allele frequencies. Turnaround time of NGS results was 1 day for SN compared to 4-10 days for CB., Conclusions: We were able to demonstrate the usefulness of SN for reliable rapid molecular results. We successfully incorporated the workflow for tissue handling and processing among our clinical, cytopathology, and molecular teams. Molecular results were available at the same time as the cytologic diagnosis, allowing for timely reporting of a comprehensive diagnosis. This approach is particularly useful in patients with advanced disease requiring urgent management., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Transgender and nonbinary (TNB) people experience economic and psychosocial inequities that make them more likely to be subject to financial and mental health harms exacerbated by the COVID-19 pandemic. Sustainable, multilevel interventions are needed to address these harms. The onset of the COVID-19 pandemic galvanized many TNB-led organizations to provide emergency financial and peer support for TNB people negatively impacted by the pandemic. However, the efficacy of these interventions has not been evaluated. The Creating Access to Resources and Economic Support (CARES) study seeks to assess the efficacy of feasible, acceptable, and community-derived interventions to reduce economic and psychological harms experienced by transgender people in the wake of the COVID-19 pandemic., Objective: The study aims to (1) compare the efficacy of microgrants with peer mentoring with that of microgrants without peer mentoring in reducing psychological distress, (2) examine mechanisms by which microgrants with or without peer mentoring may impact psychological distress, and (3) explore participants' intervention experiences and perceived efficacy., Methods: We will enroll 360 TNB adults into an embedded, mixed methods, 3-arm, and 12-month randomized controlled trial. Participants will be randomized 1:1:1 to arm A (enhanced usual care), which will receive a single microgrant plus monthly financial literacy education, arm B (extended microgrants), which will receive enhanced usual care plus monthly microgrants, or arm C (peer mentoring), which will receive extended microgrants combined with peer mentoring. All intervention arms last for 6 months, and participants complete semiannual, web-based surveys at 0, 6, and 12 months as well as brief process measures at 3 and 6 months. A subset of 36 participants, 12 (33%) per arm, will complete longitudinal in-depth interviews at 3 and 9 months., Results: Full recruitment began on January 8, 2024, and, as of July 26, 2024, a total of 138 participants have enrolled. Recruitment is expected to be completed no later than March 31, 2025, and the final study visit will take place in March 2026., Conclusions: This national, web-based study will demonstrate whether an intervention tailored to reduce material hardship and improve peer support among TNB adults will reduce psychological distress. Its equitable, community-academic partnership will ensure the rapid dissemination of study findings., Trial Registration: ClinicalTrials.gov NCT05971160; https://clinicaltrials.gov/study/NCT05971160., International Registered Report Identifier (irrid): DERR1-10.2196/63656., (©Tonia C Poteat, Sari L Reisner, Andrea L Wirtz, Larissa Jennings Mayo-Wilson, Carter Brown, Wiley Kornbluh, Ash Humphrey, Nancy Perrin. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.08.2024.)

Chronic myeloid leukemia (CML) is associated with several breakpoint regions that result in different BCR::ABL1 fusion transcripts. These include the major breakpoint region (M-BCR), minor breakpoint region (m-BCR), and mu breakpoint region (u-BCR) corresponding to p210, p190, and p230 fusion transcripts, respectively. This patient is a 38-year-old female with a new diagnosis of CML in chronic phase. A novel p210 fusion transcript splice variant was detected with qualitative reverse transcription PCR and capillary electrophoresis. Subsequent FISH study was performed, which revealed 86.5% positive for the BCR::ABL1 fusion. Quantitative real-time polymerase chain reaction (PCR) showed a negative result for the p210 fusion transcript. The variant was further characterized by Sanger sequencing. This variant is in-frame and predicted to be functional. This case illustrates the need for a combination of different testing techniques to fully characterize the rare BCR::ABL1 fusion transcripts., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 J. Jean et al.)

Women employed by sex work (WESW) experience significant gaps in accessing necessary healthcare services, leading to unmet health needs. Yet, there is a dearth of literature on the barriers to medical care access among WESW in Uganda. We used data from the Kyaterekera baseline to examine the correlates of access to medical care among WESW, defined as the ability of individuals to obtain the necessary healthcare services they require in a timely, affordable, and equitable manner. The Kyaterekera study recruited 542 WESW aged 18-58 years from Southern Uganda. We conducted a multilevel linear regression model to determine the intrapersonal (age, education level, marital status, HIV knowledge, and asset ownership), interpersonal (family cohesion and domestic violence attitudes), and community (community satisfaction, sex work stigma and distance to health facility) level correlates of access to medical care among WESW. Intrapersonal and interpersonal factors were associated with access to medical care among WESW. There was no significant association between community level factors and access to medical care. WESW with secondary education (β = 0.928, 95% CI = 0.007, 1.849) were associated with increased access to medical care. WESW with high asset ownership (β = -1.154, 95% CI= -1.903, -0.405), high family cohesion (β = -0.069, 95% CI= -0.106, -0.031), and high domestic violence attitudes (β = -0.253, 95% CI= -0.438, -0.068) were associated with decreased access to medical care. The findings emphasize the critical need for targeted family strengthening interventions to enhance family support for WESW and address domestic violence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Thyroid carcinomas are the most common endocrine malignancy and commonly have alterations in the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/AKT signaling pathways in well-differentiated tumors. Alternative molecular alterations driving thyroid carcinomas have been identified rarely in the literature and are more likely to occur in poorly differentiated or anaplastic cases. In this study, uncommon genetic alterations such as MLH1, MSH2, NSD3::NUTM1, RET::SPECC1L, and G3BP2::FGFR2 were identified in patients with papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and differentiated high-grade thyroid carcinoma. Most of these tumors demonstrated an aggressive biological behavior. Atypical driver mutations in thyroid carcinomas can occur in patients with cancer predisposition syndromes as demonstrated by an NTRK1::TPM3 fusion in a patient with Li Fraumeni syndrome. In these settings of more aggressive disease, molecular testing targeting actionable fusions and mutations is important. As demonstrated in our case cohort, 100% of cases diagnosed as high-grade follicular-derived thyroid carcinoma had a mutation or fusion that is associated with worse prognosis, has a germline syndrome association requiring further work up, or an actionable mutation. This high yield seen in this cohort for molecular testing in patients with high-grade follicular-derived thyroid carcinoma suggests more routine molecular testing in this population would be a beneficial clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

In Uganda, women engaged in sex work (WESW) are a marginalized population at the intersection of multiple vulnerabilities. The Kyaterekera intervention is targeted at WESW in Rakai and the greater Masaka regions in Uganda and combines a traditional HIV risk-reduction approach with a savings-led economic empowerment intervention and financial literacy training. We estimated the economic costs of the Kyaterekera intervention from a program provider perspective using a prospective activity-based micro-costing method. All program activities and resource uses were measured and valued across the control arm receiving a traditional HIV risk-reduction intervention and the treatment arm receiving a matched individual development savings account and financial literacy training on top of HIV risk reduction. The total per-participant cost by arm was adjusted for inflation and discounted at an annual rate of 3% and presented in 2019 US dollars. The total per-participant costs of the control and intervention arms were estimated at $323 and $1,435, respectively, using the per-protocol sample. When calculated based on the intent-to-treat sample, the per-participant costs were reduced to $183 and $588, respectively. The key cost drivers were the capital invested in individual development accounts and personnel and transportation costs for program operations, linked to WESW's higher mobility and the dispersed pattern of hot spot locations. The findings provide evidence of the economic costs of implementing a targeted intervention for this marginalized population in resource-constrained settings and shed light on the scale of potential investment needed to better achieve the health equity goal of HIV prevention strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with enhanced transmissibility and immune escape have emerged periodically throughout the coronavirus disease 2019 (COVID-19) pandemic, but the impact of these variants on disease severity has remained unclear. In this single-center, retrospective cohort study, we examined the association between SARS-CoV-2 clade and patient outcome over a two-year period in Chicago, Illinois. Between March 2020 and March 2022, 14,252 residual diagnostic specimens were collected from SARS-CoV-2-positive inpatients and outpatients alongside linked clinical and demographic metadata, of which 2,114 were processed for viral whole-genome sequencing. When controlling for patient demographics and vaccination status, several viral clades were associated with risk for hospitalization, but this association was negated by the inclusion of population-level confounders, including case count, sampling bias, and shifting standards of care. These data highlight the importance of integrating non-virological factors into disease severity and outcome models for the accurate assessment of patient risk., Competing Interests: Declaration of interests M.G.I. has received research support, paid to Northwestern University, from AiCuris, GlaxoSmithKline Janssen, and Shire. M.G.I. is a paid consultant for Adagio, AlloVir, Celltrion, Cidara, Genentech, Roche, Janssen, Shionogi, Takeda, and Viracor Eurofins. M.G.I. is a paid member of the data and safety monitoring boards (DSMBs) of CSL Berhring, Janssen, Merck, SAB Biotherapeutics, Sequiris, and Takeda. J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences and is a paid consultant for Merck., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: With substance use rates increasing in Sub-Saharan Africa (SSA), an understanding of the accessibility and effectiveness of rehabilitative services for people who use alcohol and other drugs (AOD) is critical in the global efforts to diagnose and treat substance use disorders (SUD). This scoping review seeks to address the gaps in knowledge related to the types of research that have been conducted regarding inpatient or residential SUD treatment in SSA, the settings in which the research was conducted, and the study countries., Methods: A search of three databases, PubMED, Scopus, and African Index Medicus, was conducted for publications related to the treatment of SUD in inpatient or residential settings in SSA. Articles were screened at the title/abstract level and at full text by two reviewers. Articles eligible for inclusion were original research, conducted in SSA, published in English, included populations who received or were currently receiving treatment for SUD in inpatient or residential settings, or documented demand for SUD services., Results: This scoping review included 82 studies originating from 6 countries in SSA. Three themes emerged within the literature: access and demand for inpatient and residential SUD treatment, quality and outcomes of SUD treatment, and descriptions of the services offered and staffing of these facilities. Barriers to access include financial barriers, limited availability of services, and geographic concentration in cities. Women were shown to access residential and inpatient SUD treatment at lower rates than men, and certain racial groups face unique language and financial barriers in accessing services. Studies indicate mixed success of inpatient and residential SUD treatment in sustained SUD remission for patients., Conclusion: There are significant gaps in the literature, driven by a lack of longitudinal studies focused on patient outcomes following treatment and the use of a narrow definition of treatment success. Both structural and non-structural barriers, such as stigma and discrimination, are barriers to access. Further research is needed to evaluate approaches to mitigate these barriers and expand access to residential and inpatient SUD treatment., (© 2024. The Author(s).)

Gliomas harboring oncogenic ROS1 alterations are uncommon and primarily described in infants. Our goal was to characterize the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion-positive gliomas across all age groups. Through a retrospective multi-institutional collaboration, we report a collection of unpublished ROS1 fusion gliomas along with the characterization and meta-analysis of new and published cases. A cohort of 32 new and 58 published cases was divided into the following 3 age groups: 19 infants, 40 pediatric patients, and 31 adults with gliomas. Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups, and 10 other partner genes were identified. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/-10/CDKN2A deletion; amplification of CDK4, MDM2, and PDGFRA genes; and mutations involving TERTp, TP53, PIK3R1, PIK3CA, PTEN, and NF1 genes. Infant tumors showed few genomic alterations, whereas pediatric tumors showed moderate genomic complexity. The outcomes were significantly poorer in adult patients. Although not statistically significant, tumors in infant and pediatric patients with high-grade histology and in hemispheric locations appeared more aggressive than tumors with lower grade histology or those in nonhemispheric locations. In conclusion, this study is the largest to date to characterize the clinicopathological and molecular signatures of ROS1 fusion-positive gliomas from infant, pediatric, and adult patients. We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy., (Copyright © 2023. Published by Elsevier Inc.)

Background: The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms., Methods: We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed., Results: Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis., Conclusions: We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Background: Women engaged in commercial sex work (WESW) are at a higher risk of acquiring and transmitting HIV. WESW are highly mobile, and their mobility may increase their economic status, and increased access to healthcare and other social services. However, it may also facilitate the spread of HIV infection from higher to lower prevalence regions. This study examined the predictors of mobility among WESW in Uganda using a generalized estimating equations model., Methods: We defined and measured mobility as the change in residence by WESW between baseline, 6 months, and 12 months follow-up. Participants who changed places were considered mobile, and those who never changed were non-mobile. We used data from a longitudinal study, which recruited 542 WESW from Southern Uganda aged 18-55 years and constructed a Generalized Estimating Equations Model., Results: Findings show that 19.6% of WESW changed residence between baseline and 6 months of follow-up and 26.2% (cumulative) between baseline and 12 months of follow-up. Older women (OR = 0.966, 95% CI = 0.935, 0.997) were associated with decreased odds of mobility, whereas WESW who were HIV positive (OR = 1.475, 95% CI = 1.078, 2.018) and those from large households (OR = 1.066, 95% CI = 1.001, 1.134) were associated with increased odds of mobility. WESW residing in rural areas (OR = 0.535, 95% CI = 0.351, 0.817) were associated with decreased odds of mobility compared to those from fishing sites., Conclusion: The results indicate risk factors for mobility, further research is needed to determine the directionality of these factors in order to design interventions addressing mobility among WESW.

We examined the factors associated with consistent condom use among women engaged in sex work in the Southern parts of Uganda. We used baseline data from a longitudinal study involving WESW from 19 hotspots in Southern Uganda. We conducted hierarchical models to determine the individual, economic, behavioral, and health-related factors associated with consistent condom use. We found that, alcohol use (b=-0.48, 95% CI=-0.77, -0.19), accepting money for condomless sex (b=-0.33, 95% CI=-0.38, -0.28), multiple customers (b=-0.01, 95% CI=-0.01, -0.005), being married (b = 0.50, 95% CI = 0.01, 0.99), owning more assets (b = 0.08, 95% CI = 0.05, 0.13), having another income earner in the household (b = 0.55, 95% CI = 0.27, 0.83), condom use self-efficacy (b = 0.11, 95% CI = 0.03, 0.19), condom use communication (b = 0.06, 95% CI = 0.001, 0.12), and being knowledgeable about HIV/STIs transmission (b = 0.08, 95% CI = 0.01, 0.15) were associated with consistent condom use. Additionally, 29% of the women were consistent condom users. Hence, there is need to implement interventions that promote consistent condom use among WESW., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The HIV burden remains a critical public health concern and women engaged in sex work [WESW] are at significantly higher risk compared to the general adult population. Similar to other sub-Saharan African countries, Uganda reports high rates of HIV prevalence among WESW. Yet, they have not been targeted by theory-informed HIV prevention intervention approaches., Methods: We conducted semi-structured in-depth interviews with 20 WESW upon intervention completion to explore their experiences with an evidence-based HIV risk reduction intervention that was implemented as part of a combination intervention tested in a clinical trial in Uganda (2018-2023. Specifically, we explored their initial motivations and concerns for participating in the intervention, barriers and facilitators to attendance, and their feedback on specific intervention characteristics., Results: The main expectations revolved around access to health-related information, including information on STIs, HIV, and PrEP as well as on how one can protect themselves while engaging in sex work. Initial concerns were around potential breach of confidentiality and fear of arrest. The main facilitators for session attendance were the motivation to learn health-related information, the attitude of facilitators, and the incentives received for participation, whereas main challenges were related to family commitments and work schedules. WESW appreciated the group format of the intervention and found the location and times of the intervention delivery acceptable., Discussion and Conclusions: Overall, our findings suggest that the HIV risk reduction intervention was appropriate and acceptable to WESW. Yet, WESW experience unique concerns and barriers that need to be accounted for when designing interventions targeting this population, especially in resource-limited settings where sex work is illegal and highly stigmatized., Clinical Trial Registration: NCT03583541., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sensoy Bahar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the advent of next-generation sequencing (NGS), identifying and better understanding genetic mutations in cancer pathways has become more feasible. A mutation now commonly reported in NGS panels is the SETD2 gene (H3K36 trimethyltransferase). However, its contributions to colorectal cancer (CRC) are not well described. In this study, we describe the clinicopathologic characteristics of SETD2-mutated CRC, determine common mutation sites on the SETD2 gene, and correlate these mutations with the loss of H3K36 trimethylation and the aberrant expression of beta-catenin. By searching pathology reports at our institution which included the 161-gene NGS panel from 2019 to 2021, we identify 24 individuals with SETD2-mutated CRC. All samples were evaluated for microsatellite status, H3K36 trimethylation, and beta-catenin via immunohistochemistry. In this cohort of 24 SETD2-mutated CRC individuals (a median age of 62.4 years [interquartile range: 49.1-73.6]), 10 (41.7%) patients presented at American Joint Committee on Cancer (AJCC) tumor stage II, seven (29.2%) at stage III, six (25%) at stage IV, and one (4.2%) at stage I. Most tumors studied were adenocarcinomas with no further specification (22, 92%), and most tumors were microsatellite stable (18, 82.5%). Thirty-three mutation locations were represented by 24 patients, with one patient having six mutations in the SETD2 gene and two patients having three mutations. The dominant mutation type is missense mutations (N = 29, 87.9%), and no mutation hotspots were found. Only two samples lost trimethylation of histone H3K36, both from individuals with multiple SETD2 mutations and aberrant nuclear beta-catenin expression. SETD2-mutated CRC is similar in clinical and histologic presentation to other commonly reported CRC. SETD2 mutations were missense dominantand showed no hotspots, and multiple mutations are likely necessary for loss of H3K36 trimethylation. These results warrant further study on determining a role of SETD2-histone H3K36 pathway in CRC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Monkeypox has recently been described as a public health emergency of international concern by the World Health Organization and a public health emergency by the United States. If the outbreak continues to grow, rapid scalability of laboratory testing will be imperative. During the early days of the coronavirus disease 2019 (COVID-19) pandemic, laboratories improved the scalability of testing by using a direct-to-PCR approach. To improve the scalability of monkeypox testing, a direct real-time PCR protocol for the detection of monkeypox virus was validated. The assay retains the sensitivity and accuracy of the indirect assay while eliminating the need for nucleic acid extraction kits, reducing laboratory technologist time per sample and decreasing exposure to an infectious agent. The direct method will make it easier for laboratories across the world to rapidly develop, validate, and scale testing for monkeypox virus., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Anal squamous cell carcinoma (SCC) is a human papillomavirus (HPV)-mediated malignancy with increasing incidence. Human immunodeficiency virus (HIV) infection is a significant risk factor for anal SCC; however, it is unknown if HIV infection alters anal lesion progression and HPV strain profile. This study aims to determine whether HIV coinfection is associated with progression of HPV-mediated anal lesions and on their HPV strain diversity. This is a retrospective cohort study of adults with anal squamous intraepithelial lesion (SIL) who presented for anorectal sampling between 2010 and 2019. Using the full cohort, we performed clinicopathologic epidemiologic analysis of HIV coinfection on lesion progression. Using a subset of patients, we conducted molecular analysis of HPV strain diversity as related to HIV status and progression. Our cohort included 2203 individuals, of which 940 (43%) were HIV+. HIV+ status was associated with faster progression at all levels of dysplasia. Our molecular cohort included 329 adults, of which 190 (57.8%) were HIV+. HIV+ status was associated with higher HPV strain diversity (median: 7 [5-9] versus median: 4 [4-6], P < .001). Latent class analysis identified specific HPV strain signatures associated with progression. We demonstrate that HIV+ individuals had faster rates of anal SIL progression and that almost all HPV strains were more prevalent in anal samples from HIV+ adults. Our results imply that HIV + adults with anal SIL should undergo more frequent screening and obtain HPV genotyping at initial presentation, as it shows value as a biomarker of lesion progression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Women engaged in sex work (WESW) have an elevated risk of the human immunodeficiency virus (HIV) and sexually transmitted infections (STI). Estimates are three times higher than the general population. Understanding the predictors of HIV and STI among WESW is crucial in developing more focused HIV and STI prevention interventions among this population. The study examined the prevalence and predictors of HIV and STI among WESW in the Southern part of Uganda., Methodology: Baseline data from the Kyaterekera study involving 542 WESW (ages 18-55) recruited from 19 HIV hotspots in the greater Masaka region in Uganda was utilized. HIV and STI prevalence was estimated using blood and vaginal fluid samples bioassay. Hierarchical regression models were used to determine the predictors of HIV and STI among WESW., Results: Of the total sample, 41% (n = 220) were found to be HIV positive; and 10.5% (n = 57) tested positive for at least one of the three STI (Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis) regardless of their HIV status. Older age (b = 0.09, 95%CI = 0.06, 0.13, p≤0.001), lower levels of education (b = -0.79, 95%CI = -1.46, -0.11, p≤0.05), fewer numbers of children in the household (b = -0.18, 95%CI = -0.36, -0.01), p≤0.05), location (i.e., fishing village (b = 0.51, 95%CI = 0.16, 0.85, p≤0.01) or small town (b = -0.60, 95%CI = -0.92, -0.28, p≤0.001)), drug use (b = 0.58, 95%CI = 0.076, 1.08, p≤0.05) and financial self-efficacy (b = 0.05, 95%CI = -0.10, 0.00, p≤0.05), were associated with the risk of HIV infections among WESW. Domestic violence attitudes (b = -0.24, 95%CI = -0.42, -0.07, p≤0.01) and financial distress (b = -0.07, 95%CI = -0.14, -0.004, p≤0.05) were associated with the risk of STI infection among WESW., Conclusion: Study findings show a high prevalence of HIV among WESW compared to the general women population. Individual and family level, behavioural and economic factors were associated with increased HIV and STI infection among WESW. Therefore, there is a need for WESW focused HIV and STI risk reduction and economic empowerment interventions to reduce these burdens., Competing Interests: The authors have declared that no competing interests exist.

Current guidelines recommend that Acute Myeloid Leukemia (AML) patients with NPM1 mutations should be monitored for measurable residual disease by quantifying the transcripts and normalizing them to ABL1 transcripts. In this short report, a simple and highly accurate method to quantify the NPM1 mutant transcript normalized to the wild-type NPM1 transcript is presented. The percent mutant transcript correlates very well to the corresponding mutant allele frequency as determined by DNA-based methods allowing direct comparison of investigational studies that use RNA-based or DNA-based methods for monitoring NPM1 mutations., Competing Interests: The author declares no conflict of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

The 2021 WHO Classification of Tumors of the Central Nervous System includes several tumor types and subtypes for which the diagnosis is at least partially reliant on utilization of whole genome methylation profiling. The current approach to array DNA methylation profiling utilizes a reference library of tumor DNA methylation data, and a machine learning-based tumor classifier. This approach was pioneered and popularized by the German Cancer Research Network (DKFZ) and University Hospital Heidelberg. This research group has kindly made their classifier for central nervous system tumors freely available as a research tool via a web-based portal. However, their classifier is not maintained in a clinical testing environment. Therefore, the Northwestern Medicine (NM) classifier was developed and validated. The NM classifier was validated using the same training and validation data sets as the DKFZ group. Using the DKFZ validation data set, the NM classifier's performance showed high concordance (92%) and comparable accuracy (specificity 94.0% versus 84.9% for DKFZ, sensitivity 88.6% versus 94.7% for DKFZ). Receiver-operator characteristic curves showed areas under the curve of 0.964 versus 0.966 for NM and DKFZ classifiers, respectively. In addition, in-house validation was performed and performance was compared using both classifiers. The NM classifier performed comparably well and is currently offered for clinical testing., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: The global HIV burden remains a public health concern. Women engaged in sex work (WESW) are at higher risk of acquiring HIV compared to the general adult population. Uganda reports high rates of HIV prevalence among WESW. While WESW in Uganda have long been the subject of surveillance studies, they have not been targeted by theory-informed HIV prevention intervention approaches. In this study, we explored the perceived benefits of an evidence-based HIV risk reduction intervention that was implemented as part of a combination intervention tested in a clinical trial in Uganda., Methods: As part of a larger randomized clinical trial, we conducted semi-structured in-depth interviews with 20 WESW selected using a stratified purposive sampling. All interviews were conducted in Luganda, language spoken in the study area, and audio-recorded. They were transcribed verbatim and translated to English. Thematic analysis was used to analyze the data., Results: WESW's narratives focused on: (1) condom use; (2) alcohol/drug consumption; (3) PrEP use; (4) "handling" customers; and (5) "massaging" customers. WESW agreed that male condom was one of the important learning points for them and planned to continue using them while female condoms were received with mixed reactions. Many women appreciated receiving information about the risks of consuming alcohol and drugs, and discussed how they reduced/ eliminated their consumption. PrEP information was appreciated though identified by fewer WESW. Handling a client was discussed as a helpful strategy for safer sex through improved ability to convince customers to use condoms or avoiding sex. Massaging was also beneficial to avoid penetrative sex, but similar to female condom, massaging also yielded mixed perceptions., Conclusion: WESW found the intervention beneficial and described ways in which it improved their ability to engage in safer sex and stay healthy. The fact that WESW identified other strategies beyond condom use as helpful underlines the importance of adopting a comprehensive approach to behavioral interventions targeting HIV prevention even when combined with other interventions. Additionally, WESW's narratives suggest that incorporating the tenets of social cognitive theory and harm reduction approaches in HIV prevention among this population can result in risk behavior change., (© 2022. The Author(s).)

Objectives: To determine maternal vs fetal origin for blood in placental intervillous thrombi (IVTs)., Methods: We used comparative analysis of microsatellites (short tandem repeats [STRs]), sex chromosome fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) for fetal (ɑ-fetoprotein [AFP]) and maternal (immunoglobulin M [IgM]) serum proteins to distinguish the origin of IVTs. Using an informatics approach, we tested the association between IVTs and fetomaternal hemorrhage (FMH)., Results: In 9 of 10 cases, the preponderance of evidence showed that the thrombus was mostly or entirely maternal in origin. In 1 case, the thrombus was of mixed origins. STR testing was prone to contamination by entrapped fetal villi. FISH was useful but limited only to cases with male fetuses. IgM showed stronger staining than AFP in 9 cases, supporting maternal origin. By informatics, we found no association between IVTs and FMH., Conclusions: Evidence supports a maternal origin for blood in IVTs. IHC for IgM and AFP may be clinically useful in determining maternal vs fetal contribution to IVTs., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Women engaged in sex work (WESW) are disproportionately affected by HIV. In Uganda, HIV prevalence among WESW is estimated at 37%, accounting for 18% of all new infections in the country. WESW experience poverty, gender-based violence, and other issues that reduce their power and limit their ability to negotiate condom use. Female-controlled strategies, including pre-exposure prophylaxis (PrEP), may afford women more transmission protection, but barriers to access and use persist. This cross-sectional study examined baseline PrEP acceptability and initiation among WESW recently enrolled in a randomized clinical trial in Uganda to test the impact of a combination HIV risk reduction and economic empowerment intervention on sexual risk outcomes (clinicaltrials.gov, NCT03583541)., Methods: A total of 542 WESW from 19 high HIV-prevalent geographical areas were enrolled in the Kyaterekera study between June 2019 and March 2020. Women were eligible for the study if they: (1) were age 18 or over; (2) reported engagement in transactional sex (a sex act in exchange for pay) in the past 30 days; and (3) reported engagement in one or more episodes of unprotected sex in the past 30 days. Women completed a baseline assessment, were tested for HIV and other sexually transmitted infections (STIs) at enrollment, and were connected with antiretroviral therapy (ART), STI treatment, or PrEP, based on need and interest. Descriptive statistics examined baseline data on PrEP acceptability and initiation. Independent variables (i.e. years in sex work, recent sexual coercion, perceived HIV and sex work stigmas, harmful alcohol use, barriers to medical care, and social support) were derived from the empirical literature and women's self-report. Bivariate analysis was performed to test associations between main effects of these variables. Using binomial logistic regression, predictive models were evaluated for two distinct outcomes-PrEP acceptability and PrEP initiation/uptake., Findings: At baseline, 59% of women ( n  = 322) tested HIV negative. Among WESW testing negative, 11% ( n  = 36) were already PrEP enrolled. Most women reported willingness to use PrEP ( n  = 317; 91%). Slightly over half of WESW not already on PrEP agreed to initiate PrEP ( n  = 158; 55%). Logistic regression models demonstrate that acceptability of or willingness to use PrEP was significantly associated with fewer years engaged in sex work (AOR= ·18, 95% CI 0·05-·66, p <·01) and greater perceived social support from family (AOR= 1·39, 95% CI 1·03 -1.88, p <·05). PrEP initiation was negatively associated with greater perceived social support from friends (AOR=·81, 95% CI ·68-0·97, p <·05) and positively associated with higher perceived stigma due to sex work among family members (AOR=2·20, 95% CI 1·15-4·22, p <·05)., Interpretation: Despite endorsing PrEP use, many WESW remain reluctant to use it. This gap in prevention practice highlights the heart of a failing PrEP prevention cascade. Findings point to the important role family and friend support may play in destigmatizing sex work and PrEP use for women. Social and structural-level efforts are needed to improve educational messaging and to integrate positive messaging into health promotion campaigns for women and their families, while also working toward decriminalizing sex work., Funding: This paper was made possible with funding from United States National Institute of Mental Health (Grant number: R01MH116768)., Competing Interests: We declare no competing interests., (© 2022 The Author(s).)

Purpose: CCHS is an extremely rare congenital disorder requiring artificial ventilation as life support. Typically caused by heterozygous polyalanine repeat expansion mutations (PARMs) in the PHOX2B gene, identification of a relationship between PARM length and phenotype severity has enabled anticipatory management. However, for patients with non-PARMs in PHOX2B (NPARMs, ~10% of CCHS patients), a genotype-phenotype correlation has not been established. This comprehensive report of PHOX2B NPARMs and associated phenotypes, aims at elucidating potential genotype-phenotype correlations that will guide anticipatory management., Methods: An international collaboration (clinical, commercial, and research laboratories) was established to collect/share information on novel and previously published PHOX2B NPARM cases. Variants were categorized by type and gene location. Categorical data were analyzed with chi-square and Fisher's exact test; further pairwise comparisons were made on significant results., Results: Three hundred two individuals with PHOX2B NPARMs were identified, including 139 previously unreported cases. Findings demonstrate significant associations between key phenotypic manifestations of CCHS and variant type, location, and predicted effect on protein function., Conclusion: This study presents the largest cohort of PHOX2B NPARMs and associated phenotype data to date, enabling genotype-phenotype studies that will advance personalized, anticipatory management and help elucidate pathological mechanisms. Further characterization of PHOX2B NPARMs demands longitudinal clinical follow-up through international registries., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Background: We present a yet to be described association of SARS-CoV-2 infection with Kikuchi-Fujimoto disease., Case Presentation: A 32-year-old physician with history of SARS-CoV-2 infection presented to the emergency department with 2 weeks of fever, chills, and right sided cervical lymphadenopathy. He was treated empirically for presumed folliculitis with worsening of symptoms leading to repeat presentation to the emergency department. Extensive workup was unrevealing of an infectious cause and needle biopsy of the lesion was unrevealing. An excisional lymph node biopsy revealed follicular hyperplasia with necrotic foci showing abundance of histiocytes at the edge of necrosis with CD8 predominance of T-cells. Final diagnosis was deemed to be Kikuchi-Fujimoto disease. Antibiotic therapy was discontinued, and the patient's symptoms resolved with steroid therapy and expectant management., Conclusions: This is the first report of a patient developing Kikuchi-Fujimoto disease following SARS-CoV-2 infection. Clinicians should be aware of Kikuchi-Fujimoto disease as a possibility when approaching patients with hyper-inflammatory states who present with cervical lymphadenopathy., (© 2021. The Author(s).)

Published risk stratification models of solitary fibrous tumor (SFT) have been associated with distant metastases outside the central nervous system (CNS), but have not been studied for tumors occurring in the CNS. In a retrospective review, we identified 72 cases of solitary fibrous tumor or hemangiopericytoma (HPC) diagnosed between January 2011 and December 2020 at our institution. The tumors involved the central nervous system (N = 17), thoracic cavity (N = 28), and extrathoracic sites (N = 27). The risk of local recurrence, distant metastasis, or death at 5 years was 57% (95% CI 23%, 76%) in the CNS, 24% (95% CI 2%, 41%) in the thoracic cavity, and 13% (95% CI 0%, 25%) in extrathoracic sites. By contrast, the risk of distant metastasis or death at 5 years was 13% (95% CI 0%, 29%) in CNS primaries, 5% (95% CI 0%, 14%) in thoracic primaries, and 14% (95% CI 0%, 27%) in extrathoracic primaries. Using the published 3- and 4-variable risk stratification models by Demicco et al., we retrospectively assessed our cases for risk of local recurrence, distant metastasis, and death. For tumors outside the CNS, we show that three- and four-variable risk stratification models were associated with recurrence-free survival in addition to the previously known association with distant metastasis (all P < 0.05). In contrast, inside the CNS, we show that neither risk model is a significantly associated with clinical behavior, and that WHO grade is likely the best available prognostic tool, though none of the differences were significant. The lack of significant differences can be likely explained by the younger median age (47 years vs 61 years) and smaller median tumor size (3.5 cm vs 5.6 cm), downgrading the risk stratification scores in CNS compared to non-CNS primaries. In conclusion, existing risk stratification models of SFT are not associated with clinical behavior for tumors arising inside the CNS, but are associated with local recurrence in addition to distant metastasis outside the CNS., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background: Transgender women in the United States (U.S.) experience a disproportionate burden of HIV infection and challenges to engagement in HIV prevention and care. This excess burden is driven by structural and economic inequities. Microeconomic interventions may be effective strategies for reducing HIV inequities for this population. However, few studies have explored transgender women's preferences for microeconomic interventions to address structural determinants of HIV vulnerability., Methods: We conducted individual interviews with 19 adult transgender women in 2 U.S. cities (Richmond, VA and St. Louis, MO) who reported one or more sexual risk behaviors and recent economic hardship related to employment/income, housing, or food security. Interviews were recorded, transcribed, and analyzed using thematic content analysis., Results: The majority (74%) of transgender women were racial/ethnic minorities with mean age of 26.3 years. 89% were currently economically vulnerable; and 23% were employed full-time. 37% reported living with HIV. Participants expressed strong support for unrestricted vouchers, with many expressing the need for funds to support gender-affirming interventions. Assistance with how to budget and save and support for job acquisition, career planning, and employment sustainment were also preferred, including access to non-stigmatizing employment. Visible transgender leadership, group empowerment, and small (rather than large) numbers of participants were considered important aspects of intervention design for transgender women, including outreach through existing transgender networks to facilitate inclusion. Incorporating HIV counseling and testing to reduce vulnerability to HIV was acceptable. However, transgender women enrolled in the study preferred that HIV not be the focus of an intervention., Conclusions: Flexible microeconomic interventions that support gender affirming interventions, improve financial literacy, and provide living-wage non-stigmatizing employment are desired by economically vulnerable transgender women. While not focused on HIV, such interventions have the potential to reduce the structural drivers of HIV vulnerability among transgender women., (© 2021. The Author(s).)

Information on bronchoalveolar lavage (BAL) in patients with COVID-19 is limited, and clinical correlation has not been reported. This study investigated the key features of BAL fluids from COVID-19 patients and assessed their clinical significance. A total of 320 BAL samples from 83 COVID-19 patients and 70 non-COVID-19 patients (27 patients with other respiratory viral infections) were evaluated, including cell count/differential, morphology, flow cytometric immunophenotyping, and immunohistochemistry. The findings were correlated with clinical outcomes. Compared to non-COVID-19 patients, BAL from COVID-19 patients was characterized by significant lymphocytosis (p < 0.001), in contrast to peripheral blood lymphopenia commonly observed in COVID-19 patients and the presence of atypical lymphocytes with plasmacytoid/plasmablastic features (p < 0.001). Flow cytometry and immunohistochemistry demonstrated that BAL lymphocytes, including plasmacytoid and plasmablastic cells, were composed predominantly of T cells with a mixture of CD4+ and CD8+ cells. Both populations had increased expression of T-cell activation markers, suggesting important roles of helper and cytotoxic T-cells in the immune response to SARS-CoV-2 infection in the lung. More importantly, BAL lymphocytosis was significantly associated with longer hospital stay (p < 0.05) and longer requirement for mechanical ventilation (p < 0.05), whereas the median atypical (activated) lymphocyte count was associated with shorter hospital stay (p < 0.05), shorter time on mechanical ventilation (p < 0.05) and improved survival. Our results indicate that BAL cellular analysis and morphologic findings provide additional important information for diagnostic and prognostic work-up, and potential new therapeutic strategies for patients with severe COVID-19., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The novel coronavirus, severe acute respiratory syndrome coronavirus 2, causing coronavirus disease 2019 (COVID-19) remains a global health threat and a significant source of human morbidity and mortality. While the virus primarily induces lung injury, it also has been reported to cause hepatic sequelae., Methods: We aimed to detect the virus in formalin-fixed tissue blocks and document the liver injury patterns in patients with COVID-19 compared with a control group., Results: We were able to detect viral RNA in the bronchioalveolar cell blocks (12/12, 100%) and formalin-fixed, paraffin-embedded tissue of the lung (8/8, 100%) and liver (4/9, 44%) of patients with COVID-19. Although the peak values of the main liver enzymes and bilirubin were higher in the patients with COVID-19 compared with the control group, the differences were not significant. The main histologic findings were minimal to focal mild portal tract chronic inflammation (7/8, 88%, P < .05) and mild focal lobular activity (6/8, 75%, P = .06)., Conclusions: We found that most patients who died of COVID-19 had evidence of mild focal hepatitis clinically and histologically; however, the virus was detected in less than half of the cases., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives. To investigate the long-term impacts of a family economic intervention on physical, mental, and sexual health of adolescents orphaned by AIDS in Uganda. Methods. Students in grades 5 and 6 from 48 primary schools in Uganda were randomly assigned at the school level (cluster randomization) to 1 of 3 conditions: (1) control (n = 487; 16 schools), (2) Bridges (1:1 savings match rate; n = 396; 16 schools), or (3) Bridges PLUS (2:1 savings match rate; n = 500; 16 schools). Results. At 24 months, compared with participants in the control condition, Bridges and Bridges PLUS participants reported higher physical health scores, lower depressive symptoms, and higher self-concept and self-efficacy. During the same period, Bridges participants reported lower sexual risk-taking intentions compared with the other 2 study conditions. At 48 months, Bridges and Bridges PLUS participants reported better self-rated health, higher savings, and lower food insecurity. During the same period, Bridges PLUS participants reported reduced hopelessness, and greater self-concept and self-efficacy. At 24 and 48 months, Bridges PLUS participants reported higher savings than Bridges participants. Conclusions. Economic interventions targeting families raising adolescents orphaned by AIDS can contribute to long-term positive health and overall well-being of these families. Trial Registration. ClinicalTrials.gov registration no. NCT01447615.

Background: The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we aimed to investigate the phylogenetic characteristics of SARS-CoV-2 infections in Chicago, Illinois, and assess their relationship to clinical parameters., Methods: We performed whole-genome sequencing of SARS-CoV-2 isolates collected from COVID-19 patients in Chicago in mid-March, 2020. Using these and other publicly available sequences, we performed phylogenetic, phylogeographic, and phylodynamic analyses. Patient data was assessed for correlations between demographic or clinical characteristics and virologic features., Findings: The 88 SARS-CoV-2 genome sequences in our study separated into three distinct phylogenetic clades. Clades 1 and 3 were most closely related to viral sequences from New York and Washington state, respectively, with relatively broad distributions across the US. Clade 2 was primarily found in the Chicago area with limited distribution elsewhere. At the time of diagnosis, patients infected with Clade 1 viruses had significantly higher average viral loads in their upper airways relative to patients infected with Clade 2 viruses, independent of disease severity., Interpretation: These results show that multiple variants of SARS-CoV-2 were circulating in the Chicago area in mid-March 2020 that differed in their relative viral loads in patient upper airways. These data suggest that differences in virus genotype can impact viral load and may influence viral spread., Funding: Dixon Family Translational Research Award, Northwestern University Clinical and Translational Sciences Institute (NUCATS), National Institute of Allergy and Infectious Diseases (NIAID), Lurie Comprehensive Cancer Center, Northwestern University Emerging and Re-emerging Pathogens Program., Competing Interests: Declaration of Competing Interests The authors declare no competing financial interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: Molecular testing has become essential for the optimal workup of central nervous system (CNS) tumors. There is a vast array of testing from which to choose, and it can sometimes be challenging to appropriately incorporate findings into an integrated report. This article reviews various molecular tests and provides a concise overview of the most important molecular findings in the most commonly encountered CNS tumors., Recent Findings: Many molecular alterations in CNS tumors have been identified over recent years, some of which are incorporated into the 2016 World Health Organization (WHO) classification and the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) updates. Array-based methylation profiling has emerged over the past couple of years and will likely replace much of currently used ancillary testing for diagnostic purposes. A combination of next-generation sequencing (NGS) panel and copy number array is ideal for diffuse gliomas and embryonal tumors, with a low threshold to employ in other tumor types. With the recent advances in molecular diagnostics, it will be ever more important for the pathologist to recognize the molecular testing available, which tests to perform, and to appropriately integrate results in light of clinical, radiologic, and histologic findings.

T-cell therapy-related acute lymphoblastic leukemia (T-t-ALL) is a rare condition associated with previous cytotoxic therapy for another disease. Here we report T-t-ALL with inv(11)(q21q23), which involves KMT2A and MAML2, a transcriptional coactivator of NOTCH proteins, that occurred after chemotherapy for Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. This case describes the youngest patient with T-t-ALL harboring inv(11)(q21q23) and is the first independent report following an initial series also occurring in children. Our results lend further support to the observation that the KMT2A-MAML2 fusion gene resulting from inv(11)(q21q23) is likely a recurrent cytogenetic abnormality in T-t-ALL and appears to be associated with pediatric cases.

Background: Entrepreneurship education has demonstrated positive impacts in low-resource contexts. However, there is limited evidence of such programs evaluated among Native American (NA) youth in a rural reservation. Methods: A 2:1 randomized controlled trial evaluated the impact of the Arrowhead Business Group (ABG) entrepreneurship education program on entrepreneurship knowledge, economic empowerment, and social well-being among 394 NA youth. An intent to treat analysis using mixed effects regression models examined within and between study group differences from baseline to 24 months. An interaction term measured change in the intervention relative to change in the control. ABG participants were purposively sampled to conduct focus groups and in-depth interviews. Results: Significant intervention vs. control group improvements were sustained at 12 months for entrepreneurship knowledge and economic confidence/security. Significant within-group improvements were sustained for ABG participants at 24 months for connectedness to parents, school, and awareness of connectedness. Qualitative data endorses positive impacts on social well-being among ABG participants. Conclusion: Observed effects on entrepreneurship knowledge, economic empowerment, and connectedness, supplemented by the experiences and changes as described by the youth themselves, demonstrates how a strength-based youth entrepreneurship intervention focused on developing assets and resources may be an innovative approach to dually address health and economic disparities endured in Native American communities., Competing Interests: The authors declare no conflict of interest.

Background: Adolescence is a critical period of human development, however, limited research on programs to improve health and well-being among younger adolescents living in conflict-affected and humanitarian settings exists. The purpose of this study was to assess the comparative effectiveness of an economic empowerment program on young adolescent outcomes in a complex humanitarian setting., Methods: This longitudinal, mixed methods study examined the relative effectiveness of an integrated parent (Pigs for Peace, PFP) and young adolescent (Rabbits for Resilience, RFR) animal microfinance/asset transfer program (RFR + PFP) on adolescent outcomes of asset building, school attendance, mental health, experienced stigma, and food security compared to RFR only and PFP only over 24 months. A sub-sample of young adolescents completed in-depth qualitative interviews on the benefits and challenges of participating in RFR., Results: Five hundred forty-two young adolescents (10-15 years) participated in three groups: RFR + PFP (N = 178), RFR only (N = 187), PFP only (N = 177). 501 (92.4%) completed baseline surveys, with 81.7% (n = 442) retention at endline. The group by time interaction (24 months) was significant for adolescent asset building (X 2  = 16.54, p = .002), school attendance (X 2  = 12.33, p = .015), and prosocial behavior (X 2  = 10.56, p = .032). RFR + PFP (ES = 0.31, ES = 0.38) and RFR only (ES-0.39, ES = 0.14) adolescents had greater improvement in asset building and prosocial behavior compared to PFP only, respectively. The odds of missing two or more days of school in the past month were 78.4% lower in RFR only and 45.1% lower in RFR + PFP compared to PFP only. No differences between groups in change over time were found for internalizing behaviors, experienced stigma, or food security. Differences by age and gender were observed in asset building, prosocial behavior, school attendance, experienced stigma, and food security. The voices of young adolescents identified the benefits of the RFR program through their ability to pay for school fees, help their families meet basic needs, and the respect they gained from family and community. Challenges included death of rabbits and potential conflict within the household on how to use the rabbit asset., Conclusion: These findings underscore the potential for integrating economic empowerment programs with both parents and young adolescents to improve economic, educational, and health outcomes for young adolescents growing up in rural and complex humanitarian settings., Trial Registration: NCT02008695. Retrospectively registered 11 December 2013.

Background: Sub-Saharan Africa (SSA) has the highest number of people living with HIV/AIDS, with Nigeria, South Africa, and Uganda accounting for 48% of new infections. A systematic review of the HIV burden among women engaged in sex work (WESW) in 50 low- and middle-income countries found that they had increased odds of HIV infection relative to the general female population. Social structural factors, such as the sex work environment, violence, stigma, cultural issues, and criminalization of sex work are critical in shaping sexually transmitted infection (STI)/HIV risks among WESW and their clients in Uganda. Poverty is the most commonly cited reason for involvement in sex work in SSA. Against this backdrop, this study protocol describes a randomized controlled trial (RCT) that tests the impact of adding economic empowerment to traditional HIV risk reduction (HIVRR) to reduce new incidence of STIs and HIV among WESW in Rakai and the greater Masaka regions in Uganda., Methods: This three-arm RCT will evaluate the efficacy of adding savings, financial literacy and vocational training/mentorship to traditional HIVRR on reducing new incidence of STI infections among 990 WESW across 33 hotspots. The three arms (n = 330 each) are: 1) Control group: only HIVRR versus 2) Treatment group 1: HIVRR plus Savings plus Financial Literacy (HIVRR + S + FL); and 3) Treatment group 2: HIVRR plus S plus FL plus Vocational Skills Training and Mentorship (V) (HIVRR + S + FL + V). Data will be collected at baseline (pre-test), 6, 12, 18 and 24-months post-intervention initiation. This study will use an embedded experimental mixed methods design where qualitative data will be collected post-intervention across all conditions to explore participant experiences., Discussion: When WESW have access to more capital and/or alternative forms of employment and start earning formal income outside of sex work, they may be better able to improve their skills and employability for professional advancement, thereby reducing their STI/HIV risk. The study findings may advance our understanding of how best to implement gender-specific HIV prevention globally, engaging women across the HIV treatment cascade. Further, results will provide evidence for the intervention's efficacy to reduce STIs and inform implementation sustainability, including costs and cost-effectiveness., Trial Registration: ClinicalTrials.gov , ID: NCT03583541 .

Background: Economic vulnerability, such as homelessness and unemployment, contributes to the HIV risk among racial minorities in the U.S., who are disproportionately infected. Yet, few economic-strengthening interventions have been adapted for HIV prevention in economically-vulnerable African-American young adults. Engaging Microenterprise for Resource Generation and Health Empowerment (EMERGE) is a feasibility randomized clinical trial of an HIV prevention microenterprise intervention with integrated text messages ("nudges") that are informed by behavioral economic principles. The trial aims to reduce sexual risk behaviors and increase employment and uptake of HIV preventive behaviors., Methods/design: In total, 40 young adults who are African-American, aged 18-24, live in Baltimore City, have experienced at least one episode of homelessness in the last 12 months, are unemployed or underemployed (fewer than 10 h per week), are not enrolled in school, own a cell phone with text messaging, and report at least one episode of unprotected or unsafe sex in the prior 12 months will be recruited from two community-based organizations providing residential supportive services to urban youth. Participants will undergo a 3-week run-in period and thereafter be randomly assigned to one of two groups with active interventions for 20 weeks. The first group ("comparison") will receive text messages with information on job openings. The second group ("experimental") will receive text messages with information on job openings plus information on HIV prevention and business educational sessions, a mentored apprenticeship, and a start-up grant, and business and HIV prevention text messages based on principles from behavioral economics. The two primary outcomes relate to the feasibility of conducting a larger trial. Secondary outcomes relate to employment, sexual risk behaviors, and HIV preventive practices. All participants will be assessed using an in-person questionnaire at pre-intervention (prior to randomization) and at 3 weeks post-intervention. To obtain repeated, longitudinal measures, participants will be assessed weekly using text message surveys from pre-intervention up to 3 weeks post-intervention., Discussion: This study will be one of the first U.S.-based feasibility randomized clinical trials of an HIV prevention microenterprise intervention for economically-vulnerable African-American young adults. The findings will inform whether and how to conduct a larger efficacy trial for HIV risk reduction in this population., Trial Registration: ClinicalTrials.gov, NCT03766165 . Registered on 4 December 2018.

Sinonasal glomangiopericytoma (SNGP) is a neoplasm arising in the nasal cavity and paranasal sinuses that shows perivascular myoid differentiation. The diagnosis of SNGP may be diagnostically challenging due to a large number of potential mimics. In the present study, we sought to characterize the histological and molecular features of six cases of SNGP found in prior surgical pathology records over a 15-year period. The average age at diagnosis was 48.5 years (range: 31-78 years), and the male-to-female ratio was 1:1. Imaging studies in all six cases demonstrated avidly enhancing, lobulated soft tissue masses in the nasal cavity, extending into the sinuses and nasopharynx. Histologically, the tumors were unencapsulated and composed of a proliferation of closely packed, bland, and uniform spindle cells growing deep to an intact surface respiratory epithelium. The cells were separated by a distinctive vascular network ranging from capillaries to large vascular spaces. All cases demonstrated strong positivity for smooth muscle actin, cyclin D1, CD99, and β-catenin (100%). Targeted sequencing revealed recurrent CTNNB1 missense mutations in all cases tested. Additionally, TLE1 was positive in all cases which has not been previously reported. No tested cases harbored SS18 translocations. We found that while no single marker resolves immunohistochemical overlap between SNGP and its histologic mimics, an extended immunohistochemical panel that includes β-catenin, cyclin D1, STAT6, smooth muscle actin, pan-cytokeratin cocktails, S100, and SOX10 helps to support the diagnosis of SNGP in diagnostically challenging cases without the need for molecular studies., (Copyright © 2019 Elsevier GmbH. All rights reserved.)