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Bertha Alejandra Martinez-Cannon,1,2,* Regina Barragan-Carrillo,1,2,* Cynthia Villarreal-Garza2,3 1Hematology-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; 2Joven & Fuerte: Programa para la Atencion e Investigacion de Mujeres Jovenes con Cancer de Mama en Mexico, Mexico City, Mexico; 3Breast Cancer Center, Hospital Zambrano Hellion TecSalud, Tecnologico de Monterrey, San Pedro Garza Garcia, Nuevo Leon, Mexico*These authors contributed equally to this workCorrespondence: Bertha Alejandra Martinez-CannonHematology-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15, Belisario Dominguez Secc 16, Tlalpan, Mexico City, 14080, MexicoTel +52 55 5487 0900Email amtzcannon@gmail.comAbstract: Young women with breast cancer (YWBC) account for a variable proportion of patients diagnosed with breast cancer around the globe, with a higher prevalence in resource-limited settings than in high-income countries. This group represents a unique population that warrants special attention due to specific biological considerations and age-specific supportive care issues. This review aims to explore existing knowledge regarding YWBC’s needs, particularly in resource-restricted settings. To date, scarce information regarding the care of YWBC in resource-constrained countries is available, with most reports describing suboptimal care in terms of survivorship needs. Health care providers should implement actions to improve endocrine treatment adherence, referrals for fertility counseling and preservation, contraceptive use compliance, timely body image and sexual function interventions, comprehensive genetic risk assessments, and early quality of life and psychosocial health interventions. While high costs act as a barrier for optimal care in resource-limited settings, improving patient education represents a promising and cost-effective solution to improve patient care. Future research on developing tailored educational resources for YWBC in resource-limited settings should be considered a priority.Keywords: breast cancer, young women, unmet needs, disparities, resource-limited settings, low- and middle-income countries

Purpose: Research on disparities in prognosis and clinical characteristics between public and private healthcare sectors in developing countries remains limited. The study aimed to determine whether patients with public health coverage (1) have a greater mean tumor size at diagnosis compared to those with private health coverage; (2) exhibit differences in clinical staging and TNM classification between groups; and (3) show variations in demographic, clinical characteristics, histopathological findings, and surgical approaches among cohorts., Methods: A cross-sectional, multicenter study was conducted on 629 patients from both private and public healthcare sectors, all histologically confirmed and surgically treated for Renal Cell Carcinoma (RCC), between 2011 and 2021 in high-volume hospitals in Monterrey, Mexico. To compare variables between groups, we employed independent samples t-tests, Mann Whitney U nonparametric test, along with Pearson's chi-square test complemented by post hoc analyses., Results: Mean tumor size in the public group was 1.9 cm greater than in the private group (7.39 vs. 5.51 cm, p < 0.001). Patients in the public sector more frequently presented with larger tumors, a higher prevalence of risk factors (excluding BMI and hypertension), advanced disease (OR 2.12, 95% CI 1.43-3.16, p < 0.001), presence of symptoms, elevated TNM, lymphovascular invasion and a lower prevalence of minimally invasive surgery. A male-to-female ratio of 2.6:1 was noted in the private coverage group., Conclusions: This study highlights a notable association between public health coverage and a higher prevalence of advanced RCC, with tumors in private coverage patients being smaller yet larger than commonly reported. There is a crucial need to develop new health policies for early detection of renal cancer in developing countries., (© 2024. The Author(s).)

Background: Young women with breast cancer (YWBC) face unique challenges that can impact their sexual health. This study aimed to identify factors associated with sexual activity, function, and satisfaction in YWBC up to five years post-diagnosis., Methods: We conducted a prospective cohort study of 474 women aged ≤40 years diagnosed with non-metastatic breast cancer in Mexico. Sexual function and satisfaction were assessed using the Female Sexual Function Index and the Sexual Satisfaction Inventory, respectively. Factors associated with sexual health outcomes were examined using mixed-effects models., Results: The prevalence of sexual dysfunction increased from 33.6% at baseline to 52.9% at 4-5 years post-diagnosis. Factors associated with worse sexual function included older age (mean predicted FSFI score -1.35, p = .037), treatment-induced amenorrhea (-2.86, p < .001), depression (-4.11, p < .001), and anxiety (-2.13, p < .001). Lower sexual satisfaction was associated with lower educational attainment (mean predicted SSI score -5.61, p = .002), being single (-6.41, p < .001), treatment induced amenorrhea (-3.76, p = .004), bilateral oophorectomy (-8.21, p = .017), depression (-11.29, p < .001), and anxiety (-7.50, p < .001). Quality of life, body image, and systemic therapy side effects significantly impacted both outcomes. Three distinct trajectories of sexual function were identified: high (62.2%), intermediate (24.3%), and markedly declining (13.5%). Four trajectories of sexual satisfaction were found, ranging from intermediate-to-high (57.3%) to progressively worsening (27.5%)., Conclusion: Sexual dysfunction is prevalent and persistent among YWBC. Multiple biological, psychological, and social factors influence sexual health outcomes in this population. These findings highlight the importance of routine screening and tailored interventions to address the sexual health of YWBC throughout survivorship., (© The Author(s) 2024. Published by Oxford University Press.)

The distinction between noncancerous and cancerous breast tissues is challenging in clinical settings, and discovering new proteomics-based biomarkers remains underexplored. Through a pilot proteomic study (discovery cohort), we aimed to identify a protein signature indicative of breast cancer for subsequent validation using six published proteomics/transcriptomics data sets (validation cohorts). Sequential window acquisition of all theoretical (SWATH)-based mass spectrometry revealed 370 differentially abundant proteins between noncancerous tissue and breast cancer. Protein-protein interaction-based networks and enrichment analyses revealed dysregulation in pathways associated with extracellular matrix organization, platelet degranulation, the innate immune system, and RNA metabolism in breast cancer. Through multivariate unsupervised analysis, we identified a four-protein signature (OGN, LUM, DCN, and COL14A1) capable of distinguishing breast cancer. This dysregulation pattern was consistently verified across diverse proteomics and transcriptomics data sets. Dysregulation magnitude was notably higher in poor-prognosis breast cancer subtypes like Basal-Like and HER2 compared to Luminal A. Diagnostic evaluation (receiver operating characteristic (ROC) curves) of the signature in distinguishing breast cancer from noncancerous tissue revealed area under the curve (AUC) ranging from 0.87 to 0.9 with predictive accuracy of 80% to 82%. Upon stratifying, to solely include the Basal-Like/Triple-Negative subtype, the ROC AUC increased to 0.922-0.959 with predictive accuracy of 84.2%-89%. These findings suggest a potential role for the identified signature in distinguishing cancerous from noncancerous breast tissue, offering insights into enhancing diagnostic accuracy.

Due to genetic, hormonal, and environmental factors, alongside increased life expectancy, breast cancer (BC) survivors have an increased risk of developing a second primary malignancy. Therefore, regular screening for other types of cancer is of utmost importance for their comprehensive care. This cross-sectional study evaluated BC survivors' compliance with cervical, lung, and colorectal cancer screening, and identified facilitators and barriers influencing adherence. Fifty-two BC survivors answered the study's survey. A total of three (6%) cases of second primary malignancies were self-reported. Cervical cancer screening was performed within the past 3 years among 37/50 (74%) eligible participants. Only 7/24 (29%) eligible participants underwent colorectal cancer screening within the last 10 years, including six colonoscopies and 1 occult blood test. No participant had an indication for lung cancer screening. The primary reason for noncompliance with both cervical and colorectal cancer screening was lack of physician's recommendation, accounting for 79% and 88% of cases, respectively. Nearly all participants (98%) affirmed that BC survivors should undergo screening for other types of cancer. Most (96%) stated that, if recommended by a physician, they would agree to undergo screening for other neoplasms. Even though most BC survivors acknowledged its importance, screening particularly for colorectal cancer exhibited suboptimal rates. Oncologists could play a crucial role in increasing cancer screening uptake by reminding patients of their corresponding recommendations to detect other types of cancer., Competing Interests: Declaration of competing interest The authors declare no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake., Methods: Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months., Results: Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO., Conclusion: The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset., Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05., Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS., Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Breast cancer is a leading cause of cancer-related deaths in females, and the hormone receptor-positive subtype is the most frequent. Breast cancer is a common source of brain metastases; therefore, we aimed to generate a brain metastases prediction model in females with hormone receptor-positive breast cancer., Methods: The primary cohort included 3,682 females with hormone receptor-positive breast cancer treated at a single center from May 2009 to May 2020. Patients were randomly divided into a training dataset (n = 2,455) and a validation dataset (n = 1,227). In the training dataset, simple logistic regression analyses were used to measure associations between variables and the diagnosis of brain metastases and to build multivariable models. The model with better calibration and discrimination capacity was tested in the validation dataset to measure its predictive performance., Results: The variables incorporated in the model included age, tumor size, axillary lymph node status, clinical stage at diagnosis, HER2 expression, Ki-67 proliferation index, and the modified Scarff-Bloom-Richardson grade. The area under the curve was 0.81 (95 % CI 0.75-0.86), p < 0.001 in the validation dataset. The study presents a guide for the clinical use of the model., Conclusion: A brain metastases prediction model in females with hormone receptor-positive breast cancer helps assess the individual risk of brain metastases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Young women with breast cancer (BC) may experience bone mineral density (BMD) loss secondary to cancer treatment effects on estrogen levels. Studies assessing BMD in BC patients have had a limited representation of young women. This multicenter retrospective study analyzed the frequency of low BMD and associated factors in this age group., Methods: Women diagnosed with stage 0-III BC at ≤40 years, treated with chemotherapy and/or endocrine therapy between 2010 and 2020 at 5 Mexican BC referral centers were eligible. Demographic, clinical and treatment data were collected, as well as bone dual-energy X-ray absorptiometry (DEXA) results. Low BMD was defined as lumbar or femoral neck T-score < -1.0 or Z-score ≤ -2.0., Results: A total of 1259 patients were included; median age at diagnosis was 36 years (21-40). Overall, 93% received chemotherapy and 65% endocrine therapy (tamoxifen was received at some point by 61%, aromatase inhibitors by 17%, and GnRH agonists/bilateral oophorectomy by 21%). DEXA scans were documented in 254 (20%), of which 163 (64%; 95% confidence interval [CI] 58%-70%) had a low BMD report. Low BMD was associated with receiving aromatase inhibitors (Odds ratio [OR] 1.92; 95% CI 1.13-3.24), and GnRH agonists/bilateral oophorectomy (OR 2.25; 95% CI 1.21-4.21)., Conclusion: The suboptimal frequency of BMD monitoring observed displays an alarming disregard for bone health in young patients. Thus, a high proportion of women with low BMD are potentially being missed and precluded from the opportunity to receive timely interventions. Particular focus should be put on BMD monitoring among patients treated with aromatase inhibitors, GnRH agonists or bilateral oophorectomy., Competing Interests: Disclosure The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Preterm birth is the leading cause of mortality in newborns, with very-low-birth-weight infants usually experiencing several complications. Breast milk is considered the gold standard of nutrition, especially for preterm infants with delayed gut colonization, because it contains beneficial microorganisms, such as Lactobacilli and Bifidobacteria ., Aim: To analyze the gut microbiota of breastfed preterm infants with a birth weight of 1500 g or less., Methods: An observational study was performed on preterm infants with up to 36.6 wk of gestation and a birth weight of 1500 g or less, born at the University Hospital Dr. José Eleuterio González at Monterrey, Mexico. A total of 40 preterm neonates were classified into breast milk feeding (BM) and mixed feeding (MF) groups (21 in the BM group and 19 in the MF group), from October 2017 to June 2019. Fecal samples were collected before they were introduced to any feeding type. After full enteral feeding was achieved, the composition of the gut microbiota was analyzed using 16S rRNA gene sequencing. Numerical variables were compared using Student's t -test or using the Mann-Whitney U test for nonparametric variables. Dominance, evenness, equitability, Margalef's index, Fisher's alpha, Chao-1 index, and Shannon's diversity index were also calculated., Results: No significant differences were observed at the genus level between the groups. Class comparison indicated higher counts of Alphaproteobacteria and Betaproteobacteria in the initial compared to the final sample of the BM group ( P < 0.011). In addition, higher counts of Gammaproteobacteria were detected in the final than in the initial sample ( P = 0.040). According to the Margalef index, Fisher's alpha, and Chao-1 index, a decrease in species richness from the initial to the final sample, regardless of the feeding type, was observed ( P < 0.050). The four predominant phyla were Bacteroidetes, Actinobacteria, Firmicutes , and Proteobacteria, with Proteobacteria being the most abundant. However, no significant differences were observed between the initial and final samples at the phylum level., Conclusion: Breastfeeding is associated with a decrease in Alphaproteobacteria and Betaproteobacteria and an increase of Gammaproteobacteria , contributing to the literature of the gut microbiota structure of very low-birth-weight, preterm., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs)., Methods: Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010-22 (development cohort) and 2018-22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls., Results: Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis β coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84-0.91) and 0.82 (0.73-0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI -0.5 to -0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity., Conclusion: The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data., Competing Interests: Competing interests: RGN: consultant for Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; stock options in Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze; principal investigator of the ENDOLOW trial and DUSK trial; stock options in Viz-AI, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Tulavi Therapeutics, Vastrax, Piraeus Medical, Brain4Care, Quantanosis AI, and Viseon. SAS: grant from National Institutes of Health (R01NS121154); consultant for Penumbra and Imperative Care; ownership of Motif Neurosciences. DCH: consultant for Stryker Neurovascular, Cerenovus, Chiesi USA, Brainomix, Poseydon Medical; consulting/DSMB for Jacobs Institute/Medtronic, Vesalio, Rapid Pulse; stock options in VizAI and Motif Neurotech., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Declaration of interests CEC reports grants from Breast Cancer Now, Cancer Research UK (CRUK), Addenbrooke's Charitable Trust, and the National Institute for Health and Care Research (NIHR); participation in the Independent Data Monitoring Committees for the UK PivotalBoost trial (chair), the PROTIS phase III sinonasal proton versus IMRT trial (member), the TORPEdO Proton Beam Therapy trial (member); and a leadership role for the Lancet Breast Cancer Commission (chair). CHB reports grants and research support from AbbVie, Nektar Therapeutics, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, Henlius, Shanghai Henlius Biotech, GSK, Janssen, OBI Pharma, Eli Lilly, Seagen, Checkpoint Therapeutics, Roche, Bristol Myers Squibb, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda Pharmaceuticals, TRIO Pharmaceuticals, PharmaMar, Celgene, Myovant, PPD, Syneos Health, DOCS, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, and Medpace; ownership or stocks in Tummi and MEDSir; and participation in advisory boards and consulting activities for Boehringer Ingelheim, GSK, Novartis, Pfizer, Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Eli Lilly, Sanofi, and Daiichi Sankyo. DAC reports research grants and support from Exact Sciences and Novartis; consulting fees from Eli Lilly, Novartis, Seagen, Daiichi Sankyo, Erytech Pharma, Carnall Farrar, Sapience, and Sanofi; payment or honoraria for lectures and presentations from Exact Sciences, Gilead, Eli Lilly, and Pfizer; participation on data safety monitoring or advisory boards for Novartis, AstraZeneca, and Grail; unremunerated leadership roles for Make Seconds Count (chair of charity trustees) and the Breast International Group (chair of board of not-for-profit research organisation); and receipt of funding for analysis and medical writing for Eli Lilly and Novartis. FC reports payment or honoraria for lectures and presentations and support for attending meetings and travel from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, Gilead, GSK, IQVIA, Macrogenics, Medscape, MSD, Merus, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva Pharmaceuticals, and Touch Independent Medical Education; institutional financial support for clinical trials from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Fresenius, Genentech, Gilead, GSK, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, MediGene, MedImmune, MSD, Millenium, Pfizer, Pierre Fabre, Roche, Sanofi, Sonus, Tesaro, Tigris, Wilex, and Wyeth; a leadership role for the ABC Global Alliance and ABC Consensus Conference and Guidelines (president); and membership of ESMO, ESO, EORTC-BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, and ASPIC. WC reports honoraria from AstraZeneca, Pfizer, MSD, and Eisai. PAF reports a former role in the scientific advisory committee of Breast Cancer Trials Australia and New Zealand cooperative group (chair). RJ reports support from the Susan G Komen Foundation; grants from the National Institutes of Health (NIH), the Doris Duke Charitable Foundation, the Greenwall Foundation, and the American Cancer Society; serving as an expert witness for Kleinbard and Hawks Quindel Law; roles in the Board of Directors of ASCO (former member), ASTRO's Ethics Committee (chair), and the Women in Radiation Oncology Affinity Group (chair); membership on the Medical Advisory Board for Blue Cross Blue Shield Association; stock options for their advisory board role in Equity Quotient; and personal fees from the NIH, Doris Duke Charitable Foundation, and the Greenwall Foundation. FMK reports research grants from the ABC Global Alliance, Breast Cancer Now, Merck Serono WHO, MSD, Avon Cosmetics, the US Cancer Pain Relief Committee, and the Medical Research Council; consulting fees from Merck Serono and Instituto Tecnológico y de Estudios Superiores de Monterrey Mexico; and leadership roles for the Board of Directors of Women in Global Health (unpaid member), Tómatelo a Pecho (unpaid president and founder), the Mexican Health Foundation (unpaid Senior Economist), and the Board of Directors of the International Association for Hospice and Palliative Care (unpaid member). SAMcI reports grant funding from the NIHR, CRUK, and Breast Cancer Now; honoraria from Roche, MSD, AstraZeneca, Becton, Dickinson and Company; travel and conference support from Roche, Eli Lilly, and MSD; membership of advisory boards for Eli Lilly, MSD, Roche, and Novartis; and roles for the UK National Cancer Research Institute Breast Research Group (unpaid chair) and the Royal College of Surgeons Breast Surgical Specialty Lead (unpaid). K-AP reports clinical trial funding from AstraZeneca (paid to institution) and unremunerated previous participation in AstraZeneca advisory boards. LR reports grants from the European Commission Horizon 2020 and the German Research Foundation and a role in the International Association for Hospice and Palliative Care (Chair of Board of Directors). MKT reports grants from Addenbrooke's Charitable Trust and CRUK. FA reports grants from Novartis, Pfizer, AstraZeneca, Eli Lilly, Daiichi Sankyo, and Roche and consulting fees from MedImmune, Gilead, Relay Therapeutics, and Guardant Health. JEA reports speaker honoraria from AstraZeneca, Pfizer, Novartis, and Eisai and conference travel support from AstraZeneca. ISB reports participation in the Roche advisory board for ESMO. JMB reports research grants from Breast Cancer Now, AstraZeneca, MSD, Puma Biotechnology, Clovis Oncology, Pfizer, Janssen-Cilag, Novartis, Eli Lilly, Roche, CRUK, and the NIHR. MAF is funded by a Conquer Cancer Breast Cancer Research Foundation Career Development Award for Diversity and Inclusion supported by the Breast Cancer Research Foundation and reports financial support from the WeShare project. AF reports consultancy work for Oxford Immune Algorithmics; grants from Addenbrooke's Charitable Trust and the Ann McLaren Building Preclinical Imaging Suite of the University of Cambridge; and travel support from the University of Cambridge. DIR reports support from the University of Chicago Center for Global Health. DN reports research support from Cepheid; a grant from the US National Cancer Institute; and an unpaid leadership role with the WHO Global Breast Cancer Initiative. WER reports grants from the Cambia Health Foundation, the Robert Wood Johnson Foundation, and the Rita and Alex Hillman Foundation; and book royalties from Springer Publishing and Jones & Bartlett Learning. JR reports funding from the NIHR and support from AstraZeneca for attendance at a teaching event. DS reports a leadership role at the Jamaica Cancer Care and Research Institute (co-director). HS reports membership of the Breast Cancer Now Tissue Bank Advisory Board and voluntary patient membership of the Independent Cancer Patients' Voice charity; an honorarium from the CRUK Precision Grand Challenge; and support for travel expenses from Breast Cancer Now, CRUK, the Association of Breast Surgeons UK, and Breast International Group. IV-L reports grants from Resilience; consulting fees from Novartis, AstraZeneca, and Amgen; payment or honoraria for lectures and presentations from Novartis, Sandoz, Amgen, AstraZeneca, and Pfizer; and support for travel and attending meetings from Novartis. CV-G reports grants from AstraZeneca and Roche; consulting fees from Roche, Novartis, Pfizer, and Eli Lilly; honoraria from Roche, Myriad Genetics, and Novartis; and support for attending meetings and travel from Roche, MSD Oncology, and Pfizer. All other authors declare no competing interests.

Opinion Statement: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life., (© 2024. The Author(s).)

Purpose: Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico., Methods: Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges., Results: Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1 / 2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership ( P = .04) and believing GCRA was useful ( P < .001)., Conclusion: Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

Introduction: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy., Methods: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data., Results: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%)., Conclusion: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite advances in breast cancer care, breast cancer in young women (BCYW) faces unique challenges, diagnostic delays, and limited awareness in many countries. Here, we discuss the challenges and consequences associated with the delayed diagnosis of BCYW. The consequences of delayed diagnosis in young women - which generally varies among developed, developing, or underdeveloped countries - are severe due to a faster breast tumor growth rate than tumors in older women, also contributing to advanced cancer stages and poorer outcomes. Though there are many underlying reasons for diagnostic delays due to age, the article delves explicitly deep into the diagnostic delay of BCYW, focusing on healthcare providers, potential contributing factors, its consequences, and the urgent need to start minimizing such incidences. The article suggests several strategies to address these issues, including increasing awareness, developing educational programs for healthcare providers to identify signs and symptoms in young women, developing clear diagnostic guidelines, and improving screening strategies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To prospectively chart pathways of risk and resiliency following childhood trauma studies need to address three limitations of prior work: 1) recruit beyond social service/ treatment settings; 2) include broad spectrum of trauma types and 3) cast a broad longitudinal measurement framework of both clinical diagnoses and traumatic exposures. The Texas-Childhood Trauma Research Network (TX-CTRN) is a multi-site collaboration that addresses these limitations. In this baseline-only report, we examined domains of trauma and evaluated the concurrent predictive validity of various traumatic event scoring schemas for clinical diagnoses., Methods: Broad-base recruitment of 8-20 year-olds (N = 1289) included trauma centers, emergency departments, pediatric and primary care clinics, and other community settings. Assessments were comprehensive and based on clinical interviews by trained research interviewers., Results: Factor analyses supported a five-factor solution of trauma domains including unintentional/acute, intentional/interpersonal, bullying, in-home versus community witnessed interpersonal harms. Trauma burden scoring schemas were examined for their predictive superiority. Domain-specific counts of traumas that met DSM-5 post-traumatic-stress disorder (PTSD) Criterion-A was the best overall schema in distinguishing among youth with no diagnosis, comorbidities, those with depression, suicidality, substance misuse, and PTSD., Limitations: There were no assessments of neglect., Conclusions: Findings largely aligned with earlier studies on the relative importance of intentional interpersonal traumas and showed bullying may be an important source of traumatic stress that independently adds to prediction of several diagnoses and should be considered in clinical practice., Competing Interests: Declaration of competing interest Drs. Aksan Clark, Dodd, Taylor, Shahidullah, Richmond, Wagner, Cisler, Cross, Garza, have reported no biomedical financial interests or potential conflicts of interest. PJR serves on a data safety monitoring board for Sunovion Pharmaceuticals. DJN has received research support from Eli Lilly, Glaxo SmithKline (GSK), Janssen, the National Alliance for Research on Schizophrenia and Depression (NARSAD), Navitor, Sage Therapeutics, Takeda Pharmaceuticals, the Texas Health & Human Services Commission, and Wyeth. He has served on speakers' bureaus and/or received honoraria from Astra-Zeneca, Eli Lilly, GSK, Pfizer and Wyeth. He has served on advisory boards for GSK, Janssen, Merck, and Sage Therapeutics. He has served as a consultant to Sage Therapeutics. Neither he nor family members have ever held equity positions in biomedical or pharmaceutical corporations. CBM, in the last three years, served as a consultant to AbbVie, ANeuroTech (division of Anima BV), Signant Health, Magstim, Inc., Intra-Cellular Therapies, Inc., EMA Wellness, Sage, Silo Pharma, Engrail Therapeutics, Pasithea Therapeutic Corp., EcoR1, GoodCap Pharmaceuticals, Inc., Senseye, Clexio, EmbarkBio, SynapseBio, BioXcel Therapeutics. He is a stockholder with Seattle Genetics, Antares, Inc., Corcept Therapeutics Pharmaceuticals Company, EMA Wellness, Precisement Health, Relmada Therapeutics. He has served on advisory boards for ANeuroTech (division of Anima BV), Brain and Behavior Research Foundation (BBRF), Anxiety and Depression Association of America (ADAA), Skyland Trail, Signant Health, Laureate Institute for Brain Research (LIBR), Inc., Heading Health, Pasithea Therapeutic Corp., Sage. He has served on the Board of Directors for Gratitude America, ADAA, Lucy Scientific Discovery, Inc. He holds the following patents: Method and devices for transdermal delivery of lithium (US 6375,990B1); Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7148,027B2)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Identification and management of major depressive disorder (MDD) in children and adolescents remains a significant area of public health need. The process for identifying depression (e.g. screening) and management (e.g. measurement based care [MBC]) is substantially enhanced by utilization of clinical measures and rating scales. Measures can be self- or caregiver reported or clinician rated. They can aid recognition of at-risk individuals for future assessment and assist in clinical diagnosis and management of depression. In addition to assessing symptoms of depression, rating scales can be used to assess important associated features (e.g. anxiety, trauma) and functional outcomes (e.g. quality of life, performance/productivity). In this manuscript, we discuss practical considerations for clinicians and researchers when selecting rating instruments for assessing depression, associated factors, functioning, and treatment outcomes (i.e. adherence and side effects) as part of MBC in youth and provide a summary of rating scales commonly used in research and clinical settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited., Methods: A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken., Results: A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia., Conclusions: Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety., (© 2023. The Author(s).)

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers., Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers., Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023., Exposure: Pregnancy after breast cancer., Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes., Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival., Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival., Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Objective: To evaluate psychometrically and provide crosswalks between 3 self-report measures of depressive symptomatology in youth in psychiatric care settings. Ratings included the Patient Health Questionnaire for Adolescents (PHQ-A), a widely used 9-item self-report; the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR 16 ); and the 5-item Very Quick Inventory of Depressive Symptomatology-Self-Report (VQIDS-SR 5 ), a recent effort to create a bridge from the QIDS-SR 16 to clinical practice., Methods: Data from the Texas Youth Depression and Suicide Research Network Registry (August 26, 2020-May 11, 2022) were included in this work. At first visit, 795 depressed or suicidal adolescent (12-20 years of age) psychiatric outpatients completed the PHQ-A, QIDS-SR 16 , and VQIDS-SR 5 . Classical test theory and item-response theory (IRT) analyses were conducted. Crosswalks among total scales were created. Sensitivity to change over 1-month follow-up was assessed for all 3 scales (n = 682)., Results: Cronbach alphas were 0.86 (PHQ-A), 0.80 (QIDS-SR 16 ), and 0.76 (VQIDS-SR 5 ). Item total correlations were 0.49-0.72, 0.29-0.64, and 0.43-0.61, respectively. All 3 scales were unidimensional and sensitive to change over a 1-month period. IRT analyses revealed satisfactory item performance. Modest but significant associations were found between baseline to 1-month changes in PHQ-A and VQIDS-SR 5 total scores ( r  = 0.50, P  < .0001) and between PHQ-A and QIDS-SR 16 total scores ( r  = 0.56; P  < .0001). Categorical thresholds of severity (ie, mild, moderate, severe, and very severe) were comparable between PHQ-A and QIDS-SR 16 ., Conclusions: The PHQ-A, QIDS-SR 16 , and VQIDS-SR 5 are unidimensional, psychometrically acceptable self-reports of depressive prevalence or severity in adolescents and young adults in this sample. Total scale scores on any measure can be converted reliably to those on any other., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Competing Interests: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, and the U.S. National Cancer Institute, the authors alone are responsible for the views expressed in this article; these views do not necessarily represent the decisions, policy, or views of these institutions. CF received support from the American Association for the Study of Liver Diseases for attending meetings and conferences.

Background: Poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) improve progression free survival among patients with HER2 negative (HER2-ve) advanced breast cancer (ABC) and a BRCA1 or BRCA2 mutation compared to chemotherapy (CT). The objective of this prospective study was to evaluate the clinical benefit of PARPi treatment in terms of response, outcomes and survival by breast cancer type and treatment in a Latin-American population., Methods: From September 2019 to April 2023, we analyzed the data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA1 or BRCA2, or in the homologous recombination repair genes, treated with olaparib or talazoparib in daily clinical practice by oncologist from Argentina and México. real-world objective response rate (rwORR), best response rate, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were analysed with R software and RStudio version 14.0., Results: After a median follow-up of 18.07 months (95% CI 10.53-30.07), 51 patients were treated with PARPi. Mean age at starting treatment was 47.08 years. 62.7% had ER + ve/HER2-ve and 35.3% had triple negative breast cancer (TNBC). 62.7% and 37.3% of patients received talazoparib and olaparib, respectively. BRCA 1 and 2 germline mutations were the most common alterations found in 96% of patients. 37.5% of patients received platinum-based CT in the (neo)adjuvant/metastatic setting. At the time to starting PARPi treatment, 57.5% had visceral metastasis, the median number of metastatic sites was 2 (range 1-4), the median number of lines was 2 (range 0-8), and 23.5% and 31.4% received PARPi in the 1st line and 2nd line, respectively.The rwORR was 47.0%, and the median real-world progression-free survival-1 (rwPFS 1 ) was 7.77 months (95% CI 5.67-14.7). There was a tendency of better rwPFS 1 in patients with versus without previous CT in the advance setting, 6.37 months (95% CI 5.03-8.73) and 14.30 months (95% CI 6.47-NR), respectively ( p 0.084). The median rwOS was 26.97 months (95% CI 13.50-NR) and higher in the subgroup of patients naïve for CT versus previous exposure to CT in the advance setting, the median rwOS was 32.1 months (95% CI 27.0-NR) versus 13.0 (95% CI10.1-NR), respectively ( p 0.022). The medium real-world progression-free survival-2 (next treatment after PARPi failure) was 4.00 months (95% CI 3.43-7.13). Treatment was discontinued due to adverse events in 4.0% of patients., Conclusion: This is the first evidence in a Latin-American population that replicates the data already published in randomised clinical trials and other scanty real-world evidence studies in this field, showing positive results in rwORR and rwPFS, and encouraging data in rwOS. Notably, there was a high proportion of patients with visceral progression even with visceral crisis and need for CT. Interestingly, there were similar rwOS results among subgroups (TNBC versus ER + ve/HER2-ve, talazoparib versus olaparib, etc)., Competing Interests: The authors declare that they have no conflict of interest., (© the authors; licensee ecancermedicalscience.)

Background: American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was initiated in 2020 to develop predictive models for treatment outcomes in youth with depression and/or suicidality. This report presents the study rationale, design and baseline characteristics of the first 1000 participants., Methods: TX-YDSRN consists of the Network Hub (coordinating center), 12 medical school "Nodes" (manage/implement study), each with 1-5 primary care, inpatient, and/or outpatient Sub-Sites (recruitment, data collection). Participants are 8-20-year-olds who receive treatment or screen positive for depression and/or suicidality. Baseline data include mood and suicidality symptoms, associated comorbidities, treatment history, services used, and social determinants of health. Subsequent assessments occur every two months for 24 months., Results: Among 1000 participants, 68.7 % were 12-17 years, 24.6 % were ≥ 18 years, and 6.7 % were < 12. Overall, 36.8 % were non-Hispanic Caucasian, 73.4 % were female, and 79.9 % had a primary depressive disorder. Nearly half of the sample reported ≥1 suicide attempt, with rates similar in youth 12-17 years old (49.9 %) and those 18 years and older (45.5 %); 29.9 % of children <12 reported at least one suicide attempt. Depression and anxiety scores were in the moderate-severe range for all age groups (Patient Health Questionnaire for Adolescents [PHQ-A]: 12.9 ± 6.4; Generalized Anxiety Disorder [GAD-7]: 11.3 ± 5.9)., Limitations: The sample includes youth who are receiving depression care at enrollment and may not be representative of non-diagnosed, non-treatment seeking youth., Conclusions: The TX-YDSRN is one of the largest prospective longitudinal cohort registries designed to develop predictive models for outcome trajectories based on disorder heterogeneity, social determinants of health, and treatment availability., Competing Interests: Declaration of competing interest Dr. Trivedi has provided consulting services to Alkermes Inc., Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc., Compass Pathfinder Limited, GH Research Limited, Heading Health Inc., Janssen, Legion Health Inc., Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc., Merck Sharp & Dhome LLC, Naki Health, Ltd., Neurocrine Biosciences Inc., Noema Pharma AG, Orexo US Inc., Otsuka American Pharmaceutical Inc., Otsuka Canada Pharmaceutical Inc., Otsuka Pharmaceutical Development & Commercialization Inc., Praxis Precision Medicines Inc., SAGE Therapeutics, Sparian Biosciences Inc., Takeda Pharmaceutical Company Ltd., WebMD. He sits on the Scientific Advisory Board of Alto Neuroscience Inc., Cerebral Inc., Compass Pathfinder Limited, Heading Health, GreenLight VitalSign6 Inc., Legion Health Inc., Merck Sharp & Dohme Corp, Orexo US Inc., Signant Health. He holds stock in Alto Neuroscience Inc., Cerebral Inc., Circular Genomics Inc., GreenLight VitalSign6 Inc., Legion Health Inc. Additionally, he has received editorial compensation from American Psychiatric Association, and Oxford University Press. Dr. Blader reports having received consultant and speakers' honoraria from Supernus Pharmaceuticals. Dr. Brown has received consulting fees from Sage and Biogen Pharmaceuticals. Dr. Hughes reports receiving research funding to her institution from NIH and the American Foundation for Suicide Prevention (AFSP). She reports receiving support from the Society of Clinical Child and Adolescent Psychology, the Jed Foundation, and Mental Health in Mind, International AB, and consulting on quality improvement interventions for depression and suicidal/self-harm behavior. She receives book royalties from Guilford Press. Dr. Kennard receives royalties from Guilford, Press, Inc.; and serves on the board of trustees for the Jerry M. Lewis, III, MD Research Foundation. Dr. Soares has served as an advisor or consultant for Asofarma, Boehringer Ingelheim, Johnson & Johnson, Livanova, Pfizer, Pulvinar Neuro LLC, Relmada, Sanofi, and Sunovian. He has received research grants from Alkermes, Allergan, and Compass and holds less than U.S. $5000 in Atai Life Sciences stock. Dr. Soutullo reports for the period 2018–2022 non-personal research funds from Lundbeck and Janssen; is a consultant/advisory board member of Editorial Médica Panamericana, EUNETHYDIS (European Network on Hyperkinetic Disorder), NeuroTech Solutions Ltd. (Israel), Limbix Health DSMB (United States), MEDEA (Spain), Tech Innosphere Engineering LTD (Germany), and Shire/now part of Takeda (Spain); received speaker's bureau fees from Bial (Portugal), Cuquerella Medical Consulting (Spain), Medice (Germany), Rubio (Spain), Tecnofarma (Peru), and Shire/now part of Takeda (Spain), and royalties from Editorial Médica Panamericana (Spain). Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, and Jessica Kingsley. Dr. Wakefield serves as an Executive Committee Member of the Texas Child Mental Health Care Consortium. Drs. Minhajuddin, Slater, Baronia, DeFelippis, Farmer, Garza, Liberzon, Martin, and Mrs. Mayes have no declarations to report., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Wieacker-Wolff syndrome is an ultra-rare disease with X-linked inheritance characterized by arthrogryposis, intellectual disability, microcephaly, and distal limb muscle atrophy. Ophthalmic abnormalities such as ptosis, strabismus, and oculomotor apraxia have been reported in half of the patients. Wieacker-Wolff syndrome female-restricted (WRWFFR) is an even rarer disease recently used for females with a more severe phenotype., Materials and Methods: Clinical geneticist and ophthalmic examination, neuroimaging, and exome sequencing., Results: A 4 years-old girl with developmental and language delay, microcephaly, camptodactyly, digital pads, and arthrogryposis was identified by the clinical geneticist. Ophthalmic examination revealed deep-set eyes, high hyperopic astigmatism in both eyes, and reduced retinal nerve fiber layer thickness measured by optical coherence tomography. Exome sequencing identified a novel, probably pathogenic variant in the ZC4H2 gene NM&#95;018684.3:c.145A>T p. (Lys49*) in heterozygosis., Discussion: WRWFFR is an ultra-rare disease with X-linked inheritance by variants in the ZC4H2 gene. This case reports a girl with a novel nonsense variant in the ZC4H2 gene and a severe phenotype; previous reports have identified WRWFFR in females with large deletions and nonsense mutations which could explain the manifestations in the current case report. A complete ophthalmic examination should be considered in patients with WRWFFR to detect the possibly associated optic nerve involvement and other previously described manifestations such as ptosis and strabismus.

Prostate, breast, colorectal, cervical, and lung cancers are the leading cause of cancer in Latin America and the Caribbean (LAC) accounting for nearly 50% of cancer cases and cancer deaths in the region. Following the IARC Code Against Cancer methodology, a group of Latin American experts evaluated the evidence on several medical interventions to reduce cancer incidence and mortality considering the cancer burden in the region. A recommendation to limit the use of HRT was issued based on the risk associated to develop breast, endometrial, and ovarian cancer and on growing concerns related to the over-the-counter and without prescription sales, which in turn bias estimations on current use in LAC. In alignment with WHO breast and cervical cancer initiatives, biennial screening by clinical breast examination (performed by trained health professionals) from the age of 40 years and biennial screening by mammography from the age of 50 years to 74, as well as cervical screening by HPV testing (either self-sampling or provider-sampling) every 5-10 years for women aged 30-64 years, were recommended. The steadily increasing rates of colorectal cancer in LAC also led to recommend colorectal screening by occult blood testing every two years or by endoscopic examination of the colorectum every 10 years for both men and women aged 50-74 years. After evaluating the evidence, the experts decided not to issue recommendations for prostate and lung cancer screening; while there was insufficient evidence on prostate cancer mortality reduction by prostate-specific antigen (PSA) testing, there was evidence of mortality reduction by low-dose computed tomography (LDCT) targeting high-risk individuals (mainly heavy and/or long-term smokers) but not individuals with average risk to whom recommendations of this Code are directed. Finally, the group of experts adapted the gathered evidence to develop a competency-based online microlearning program for building cancer prevention capacity of primary care health professionals., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Trauma patients are susceptible to coagulopathy and dysfunctional immune responses. Mesenchymal stromal cells (MSCs) are at the forefront of the cellular therapy revolution with profound immunomodulatory, regenerative, and therapeutic potential. Routine assays to assess immunomodulation activity examine MSC effects on proliferation of peripheral blood mononuclear cells (PBMCs) and take 3-7 days. Assays that could be done in a shorter period of time would be beneficial to allow more rapid comparison of different MSC donors. The studies presented here focused on assays for MSC suppression of mitogen-stimulated PBMC activation in time frames of 24 h or less., Methods: Three potential assays were examined-assays of apoptosis focusing on caspase activation, assays of phosphatidyl serine externalization (PS+) on PBMCs, and measurement of tumor necrosis factor alpha (TNFα) levels using rapid ELISA methods. All assays used the same initial experimental conditions: cryopreserved PBMCs from 8 to 10 pooled donors, co-culture with and without MSCs in 96-well plates, and PBMC stimulation with mitogen for 2-72 h., Results: Suppression of caspase activity in activated PBMCs by incubation with MSCs was not robust and was only significant at times after 24 h. Monitoring PS+ of live CD3+ or live CD4+/CD3+ mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, 2 h, although no increase in the percentage of PS+ cells was seen with time. The ability of MSC in co-culture to suppress PBMC PS+ externalization compared favorably to two concomitant assays for MSC co-culture suppression of PBMC proliferation, at 72 h by ATP assay, or at 96 h by fluorescently labeled protein signal dilution. TNFα release by mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, with accumulating signal over time. However, suppression levels with MSC co-culture was reliably seen only after 24 h., Discussion: Takeaways from these studies are as follows: (1) while early measures of PBMC activation is evident at 2-6 h, immunosuppression was only reliably detected at 24 h; (2) PS externalization at 24 h is a surrogate assay for MSC immunomodulation; and (3) rapid ELISA assay detection of TNFα release by PBMCs is a robust and sensitive assay for MSC immunomodulation at 24 h., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Herzig, Christy, Montgomery, Cantu-Garza, Barrera, Lee, Mucha, Talackine, Abaasah, Bynum and Cap.)

Beginning in 2022, Nuevo Leon, Mexico, experienced an outbreak of rickettsioses that is still ongoing despite multidisciplinary control efforts. A total of 57 cases have been confirmed, particularly affecting children. We report a high mortality rate among hospitalized persons in Nuevo Leon. Continuing efforts are required to control the outbreak.

Background: Patients' lack of knowledge about their own disease may function as a barrier to shared decision-making and well-being. This study aimed to evaluate the impact of written educational materials on breast cancer patients., Methods: This multicenter, parallel, unblinded, randomized trial included Latin American women aged ≥18 years with a recent breast cancer diagnosis yet to start systemic therapy. Participants underwent randomization in a 1:1 ratio to receive a customizable or standard educational brochure. The primary objective was accurate identification of molecular subtype. Secondary objectives included identification of clinical stage, treatment options, participation in decision-making, perceived quality of information received, and illness uncertainty. Follow-up occurred at 7-21 and 30-51 days post-randomization., Clinicaltrials: gov identifier: NCT05798312., Results: One hundred sixty-five breast cancer patients with a median age of 53 years and 61 days from diagnosis were included (customizable: 82; standard: 83). At first available assessment, 52%, 48%, and 30% identified their molecular subtype, disease stage, and guideline-endorsed systemic treatment strategy, respectively. Accurate molecular subtype and stage identification were similar between groups. Per multivariate analysis, customizable brochure recipients were more likely to identify their guideline-recommended treatment modalities (OR: 4.20,p = 0.001). There were no differences between groups in the perceived quality of information received or illness uncertainty. Customizable brochure recipients reported increased participation in decision-making (p = 0.042)., Conclusions: Over one third of recently diagnosed breast cancer patients are incognizant of their disease characteristics and treatment options. This study demonstrates a need to improve patient education and shows that customizable educational materials increase patients' understanding of recommended systemic therapies according to individual breast cancer characteristics., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide. Neoadjuvant therapy (NAT) is increasingly being used to reduce tumor burden prior to surgical resection. However, current techniques for assessing tumor response have significant limitations. Additionally, drug resistance is commonly observed, raising a need to identify biomarkers that can predict treatment sensitivity and survival outcomes. Circulating microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been shown to play a significant role in cancer progression as tumor inducers or suppressors. The expression of circulating miRNAs has been found to be significantly altered in breast cancer patients. Moreover, recent studies have suggested that circulating miRNAs can serve as non-invasive biomarkers for predicting response to NAT. Therefore, this review provides a brief overview of recent studies that have demonstrated the potential of circulating miRNAs as biomarkers for predicting the clinical response to NAT in BC patients. The findings of this review will strengthen future research on developing miRNA-based biomarkers and their translation into medical practice, which could significantly improve the clinical management of BC patients undergoing NAT.

Introduction: The primary objective of this study was to determine whether Altmetric score, number of reads, and citations for paediatric cardiology manuscripts correlate with one another. A secondary objective was to determine the extent to which factors mediated citation number for paediatric cardiology manuscripts., Methods: Data for this study came from manuscripts published in Cardiology in the Young (2010-2021). Data were extracted by using data shared on the journal website. Spearman's correlation analyses were conducted between manuscript reads, citations, and Altmetric score. Regression analyses were conducted with number of citations as the dependent variable and year of publication, publication type, number of reads, and Altmetric score as independent variables., Results: A total of 2642 manuscripts were included in the final analyses. Reads and citations had poor correlation (r-value 0.32); reads and Altmetric score had negligible correlation (r-value 0.26); and Altmetric score and citations had negligible correlation (r-value 0.07). Year of publication was independently associated with number of citations (β -0.95, p-value <0.01). Manuscript type was independently associated with number of citations (β 1.04, p-value <0.01). Number of reads was independently associated with citations (β 0.01, p-value <0.01). Altmetric score was independently associated with number of citations (β 0.05, p-value <0.01)., Conclusion: This study describes the correlation of reads, citations, and Altmetric score in manuscripts published in Cardiology in the Young , demonstrating poor correlation, at best, between these metrics. Each bibliometric index seems to represent a different phenomenon of manuscript consumption. No single bibliometric index in isolation offers ample representation of manuscript consumption.

Here, we report the draft genome sequences of 4 Bordetella pertussis isolates which correspond to major clones isolated between 2008 and 2014 from two outbreaks in northeastern Mexico. The B. pertussis clinical isolates belong to the ptxP3 lineage, and they are grouped into two major clusters, defined by the fimH allele., Competing Interests: The authors declare no conflict of interest.

Background: This study evaluated the psychometric properties of the 9-item Concise Health Risk Tracking Self-Report (CHRT-SR 9 ), a measure of suicidality, in adolescent psychiatric outpatients., Methods: Altogether, 933 depressed or suicidal adolescents (12-20 years of age), receiving treatment at psychiatric outpatient clinics in Texas, completed the 16-item CHRT-SR at baseline and one month later. CHRT-SR 9 was extracted from CHRT-SR 16 using multigroup confirmatory factor analysis. Sex and age measurement invariance, classical test theory, item response theory (IRT), and concurrent validity analyses (against the suicidal ideation Item 9 of Patient Health Questionnaire-Adolescent (PHQ-A)) were conducted., Results: The CHRT-SR 9 demonstrated excellent model fit with four factors (pessimism, helplessness, despair, and suicidal thoughts). Measurement invariance was upheld. Acceptable item-total correlations (0.56-0.80) and internal consistency (Spearman-Brown 0.78-0.89) were revealed. IRT analyses showed a unidimensional instrument with excellent item performance. Using the CHRT-SR 9 total score as a measure of overall suicidality and comparing it against levels of PHQ-A Item 9, the mean (standard deviation) of CHRT-SR 9 total score was 8.64 (SD = 5.97) for no-risk (0 on Item 9), 17.05 (SD = 5.00) for mild, 23.16 (SD = 5.05) for moderate, and 26.96 (SD = 5.24) for severe-risk (3 on Item 9). Significant differences (p-value<0.0001) indicated that CHRT-SR 9 total score distinguished between levels of suicidal risk. Furthermore, CHRT-SR 9 was sensitive to change over a one-month period., Limitations: Whether CHRT-SR 9 predicts actual suicidal attempts in adolescents is not well defined., Conclusion: The CHRT-SR 9 is an easy-to-administer, user-friendly self-report with good psychometric qualities which makes it an excellent screening measure of suicidal risk in adolescent psychiatric outpatients., Competing Interests: Conflict of interest Dr. Trivedi has provided consulting services to Alkermes Inc, Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc, Compass Pathfinder Limited, GH Research Limited, Heading Health Inc, Janssen, Legion Health Inc, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc, Merck Sharp & Dhome LLC, Naki Health, Ltd., Neurocrine Biosciences Inc, Noema Pharma AG, Orexo US Inc, Otsuka American Pharmaceutical Inc, Otsuka Canada Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Praxis Precision Medicines Inc, SAGE Therapeutics, Sparian Biosciences Inc, Takeda Pharmaceutical Company Ltd, WebMD. He sits on the Scientific Advisory Board of Alto Neuroscience Inc, Cerebral Inc., Compass Pathfinder Limited, Heading Health, GreenLight VitalSign6 Inc, Legion Health Inc, Merck Sharp & Dohme Corp, Orexo US Inc, Signant Health. He holds stock in Alto Neuroscience Inc, Cerebral Inc, Circular Genomics Inc, GreenLight VitalSign6 Inc, Legion Health Inc. Additionally, he has received editorial compensation from American Psychiatric Association, and Oxford University Press. Dr. A. John Rush has received consulting fees from Compass Inc., Curbstone Consultant LLC, Emmes Corp., Evecxia Therapeutics, Inc., Holmusk Technologies, Inc., ICON, PLC, Johnson and Johnson (Janssen), Liva-Nova, MindStreet, Inc., Neurocrine Biosciences Inc., Otsuka-US; speaking fees from Liva-Nova, Johnson and Johnson (Janssen); and royalties from Wolters Kluwer Health, Guilford Press and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named co-inventor on two patents: U.S. Patent No. 7,795,033: Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS; and U.S. Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S. Dr. Emslie is a consultant for Lundbeck, Neuronetics and Otsuka. He receives research support from the American Foundation for Suicide Prevention, Janssen Research & Development and Pharmaceuticals, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the State of Texas. Dr. Jha has received contract research grants from Acadia Pharmaceuticals, Neurocrine Bioscience, Navitor/Supernus and Janssen Research & Development, educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network, consultant fees from Eleusis Therapeutics US, Inc., Janssen Global Services, Janssen Scientific Affairs, Worldwide Clinical Trials/Eliem, and Guidepoint Global, and honoraria from North American Center for Continuing Medical Education, Medscape/WebMD, Clinical Care Options, and Global Medical Education. Dr. Brown has received consulting fees from Sage and Biogen Pharmaceuticals. Dr. Kennard receives royalties from Guilford, Press, Inc.; and serves on the board of trustees for the Jerry M. Lewis, III, MD Research Foundation. Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, and Jessica Kingsley. Dr. Blader reports having received consultant and speaker's honoraria from Supernus Pharmaceuticals. Ms. Fuselier and Drs. Nandy, Garza, Gushanas, Minhajuddin, Wakefield and Slater do not have any conflicts to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: High flow oxygen therapy (HFO) is a widely used intervention for pulmonary complications. Amid the coronavirus infectious disease 2019 (COVID-19) pandemic, HFO became a popular alternative to conventional oxygen supplementation therapies. Risk stratification tools have been repurposed -and new ones developed- to estimate outcome risks among COVID-19 patients. This study aims to provide a simple risk stratification system to predict invasive mechanical ventilation (IMV) or death among COVID-19 inpatients on HFO., Methods: Among 529 adult inpatients with COVID-19 pneumonia, we selected unadjusted clinical risk factors for developing the composite endpoint of IMV or death. The risk for the primary outcome by each category was estimated using a Cox proportional hazards model. Bootstrapping was used to validate the results., Results: Age above 62, eGFR under 60 ml/min, room air SpO2 ≤89 % upon admission, history of hypertension, history of diabetes, and any comorbidity (cancer, cardiovascular disease, COPD/ asthma, hypothyroidism, or autoimmune disease) were considered for the score. Each of the six criteria scored 1 point. The score was further simplified into 4 categories: 1) 0 criteria, 2) 1 criterion, 3) 2-3 criteria, and 4) ≥4 criteria. Taking the first category as the reference, risk estimates for the primary endpoint were HR; 2.94 [1.67 - 5.26], 4.08 [2.63 - 7.05], and 6.63 [3.74 - 11.77], respectively. In ROC analysis, the AUC for the model was 0.72., Conclusions: Our score uses simple criteria to estimate the risk for IMV or death among COVID-19 inpatients with HFO. Higher category reflects consistent increases in risk for the endpoint., Competing Interests: Conflicts of interest None., (Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Symptoms of irritability, anxiety, panic, and insomnia are common in patients with depression, and their worsening after antidepressant treatment initiation is associated with poorer long-term outcomes. The Concise Associated Symptom Tracking (CAST) scale was developed to measure these symptoms in adults with major depressive disorder (MDD). Here, we evaluate the psychometric properties of CAST in an ongoing community-based observational study involving children, adolescents, and young adults. Individuals from the ongoing Texas Youth Depression and Suicide Research Network (TX-YDSRN; N = 952) with CAST data available were included. Fit statistics [Goodness of Fit Index (GFI), Comparative Fit Index (CFI), and Root Mean Square Error of Approximation (RMSEA)] from confirmatory factor analyses were used to evaluate the five- and four-domain structure of CAST. Item response theory (IRT) analyses were also used. Individuals were grouped based on age (in years) as youths (8-17) and young adults (18-20). Correlations with other clinical measures were used to inform construct validity. Four-domain (irritability, anxiety, panic, and insomnia) 12-item structure of CAST (CAST-12) was optimal for youths (N = 709, GFI = 0.906, CFI = 0.919, RMSEA = 0.095) and young adults (N = 243, GFI = 0.921, CFI = 0.938, RMSEA = 0.0797) with Cronbach's alpha of 0.87 and 0.88, respectively. Slope of each item exceeded 1.0 on IRT analyses suggesting adequate discrimination for each item. Scores on irritability, anxiety, panic, and insomnia were significantly correlated with similar items on other scales. Together these findings suggest that CAST-12 is a valid self-report measure of irritability, anxiety, insomnia, and panic in youths and young adults., Competing Interests: Declaration of competing interest Dr. Jha has received contract research grants from Acadia Pharmaceuticals, Neurocrine Bioscience, Navitor/Supernus and Janssen Research & Development, educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network, consultant fees from Eleusis Therapeutics US, Inc, Janssen Global Services, Janssen Scientific Affairs, Worldwide Clinical Trials/Eliem and Inversargo, and Guidepoint Global, and honoraria from North American Center for Continuing Medical Education, Medscape/WebMD, Clinical Care Options, and Global Medical Education. Dr. Blader reports having received consultant and speakers' honoraria from Supernus Pharmaceuticals. Dr. Brown has received consulting fees from Sage and Biogen Pharmaceuticals. Dr. Kennard receives royalties from Guilford, Press, Inc; and serves on the board of trustees for the Jerry M. Lewis, III, MD Research Foundation. Dr. Soutullo reports for the period 2018–2022 non-personal research funds from Lundbeck and Janssen; is a consultant/advisory board member of Editorial Médica Panamericana, EUNETHYDIS (European Network on Hyperkinetic Disorder), NeuroTech Solutions Ltd (Israel), Limbix Health DSMB (United States), MEDEA (Spain), Tech Innosphere Engineering LTD (Germany), and Shire/now part of Takeda (Spain); received speaker's bureau fees from Bial (Portugal), Cuquerella Medical Consulting (Spain), Medice (Germany), Rubio (Spain), Tecnofarma (Peru), and Shire/now part of Takeda (Spain), and royalties from Editorial Médica Panamericana (Spain). Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, and Jessica Kingsley. Dr. Trivedi has provided consulting services to Alkermes Inc, Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc, Compass Pathfinder Limited, GH Research Limited, Heading Health Inc, Janssen, Legion Health Inc, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc, Merck Sharp & Dhome LLC, Naki Health, Ltd., Neurocrine Biosciences Inc, Noema Pharma AG, Orexo US Inc, Otsuka American Pharmaceutical Inc, Otsuka Canada Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Praxis Precision Medicines Inc, SAGE Therapeutics, Sparian Biosciences Inc, Takeda Pharmaceutical Company Ltd, WebMD. He sits on the Scientific Advisory Board of Alto Neuroscience Inc, Cerebral Inc., Compass Pathfinder Limited, Heading Health, GreenLight VitalSign6 Inc, Legion Health Inc, Merck Sharp & Dohme Corp, Orexo US Inc, Signant Health. He holds stock in Alto Neuroscience Inc, Cerebral Inc, Circular Genomics Inc, GreenLight VitalSign6 Inc, Legion Health Inc. Additionally, he has received editorial compensation from American Psychiatric Association, and Oxford University Press. Drs. Minhajuddin, Slater, Garza, Shotwell, Wakefield, and Mrs. Mayes have no declarations to report., (Copyright © 2023. Published by Elsevier Ltd.)

Glycine is a major neurotransmitter involved in several fundamental neuronal processes. The identity of the metabotropic receptor mediating slow neuromodulatory effects of glycine is unknown. We identified an orphan G protein-coupled receptor, GPR158, as a metabotropic glycine receptor (mGlyR). Glycine and a related modulator, taurine, directly bind to a Cache domain of GPR158, and this event inhibits the activity of the intracellular signaling complex regulator of G protein signaling 7-G protein β5 (RGS7-Gβ5), which is associated with the receptor. Glycine signals through mGlyR to inhibit production of the second messenger adenosine 3',5'-monophosphate. We further show that glycine, but not taurine, acts through mGlyR to regulate neuronal excitability in cortical neurons. These results identify a major neuromodulatory system involved in mediating metabotropic effects of glycine, with implications for understanding cognition and affective states.

Introduction: A high prevalence of advanced breast cancer (BC) is a common scenario in Latin America. In Peru, the frequency of BC at Stages III/IV is ≈50% despite implementation of a programme for breast cancer screening (BCS) along the country. We carried out a study to assess the feasibility and develop an instrument to evaluate the knowledge, barriers and perception about BCS in a nationwide pilot study in Peru among candidates for BCS., Methods: We conducted a systematic review of 2,558 reports indexed in PubMed, Scopus, Web of Science, Medline-Ovid and EMBASE, regarding to our study theme. In total, 111 were selected and a 51-items survey was developed (eight items about sociodemographic characteristics). Patients were recruited in public hospitals or private clinics, in rural and urban areas of nine departments of Peru., Results: We surveyed 488 women from: Lima (150), Cajamarca (93), Ica (59), Arequipa (56), Loreto (48), Ancash (38), Junín (15), Puerto Maldonado (15) and Huancavelica (14); 27.9% of them were from rural areas. The mean of age was 53.3 years (standard deviation ± 9.1). Regarding education level, 29.8% had primary, 33.2% secondary and 37.0% higher education. In total, 28.7% of women did not know the term 'mammogram' and 47.1% reported never receiving a BCS (36.9% from urban and 73.5% from rural population). In women that underwent BCS, only 67% knew it is for healthy women. In total, 54.1% of patients had low levels of knowledge about risk factors for BC (i.e. 87.5% of women respond that injuries in the breast produce cancer). Cultural, economic and geographic barriers were significantly associated with having a mammogram where 56.9% of participants considered a cost ≤ 7 USD as appropriate. Mammogram was perceived as too painful for 54.9% of women. In addition, women with a self-perception of low-risk for BC and a fatalistic perception of cancer were less likely to have a BCS., Conclusion: We found that it is feasible to conduct a large-scale study in Peru. The results of this pilot study highlight an urgent need of extensive education and awareness about BCS in Peru., Competing Interests: The authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)