tbuckley/cabot-search huggingface dataset:
Abstract P4-10-11: Eyebrow/eyelash loss among survivors
Authors: Elizabeth Cathcart-Rake, Charles L Loprinzi, Fergus Couch, Janet Olson, Brittany Dulmage, Maryam Lustberg, Nicole Larson, Kathryn J Ruddy
Journal: Cancer Research (2022)

Abstract Background: Eyebrow and eyelash loss are widely recognized as consequences of some chemotherapies, but prevalence and predictors are understudied. The purpose of this study was to evaluate real world experiences of eyebrow and eyelash loss during treatment for breast cancer. Methods: Breast cancer survivors participating in the ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR) were mailed a survey one year after diagnosis. Respondents were asked to recall their severity of eyebrow and eyelash loss since diagnosis, measured from “no loss” to “a little loss” to “a lot of loss” to “complete loss”. Results: 524 participants were mailed a survey including these questions between May 2020 and November 2020; the median time from diagnosis to survey completion was 12 months (range 6 months). Of the 265 participants whose responses were available for analysis (median age 60.8 years), 88 (33%) had received chemotherapy, including 39 (44%) who received doxorubicin and cyclophosphamide, 16 (18%) who received docetaxel and cyclophosphamide, 56 (64%) who received paclitaxel, and 11 (13%) who received carboplatin. 173 (65%) had received endocrine therapy: 56 (32%) of patients who received endocrine therapy received tamoxifen, and 115 (66%) received aromatase inhibitors. 124 (47%) reported at least a little eyebrow loss, and 22 (8%) reported complete loss. Forty-seven percent reported at least a little eyelash loss, and 27 (10%) reported complete loss (Table 1). In the subgroup of 88 patients who received chemotherapy, the rates of at least a little eyebrow and eyelash loss were 50% and 55%, respectively, and rates of complete loss were 8% and 9%. Rates of eyebrow and eyelash loss did not appear to differ significantly by age. Conclusion: Eyebrow and eyelash loss are frequently reported during breast cancer-directed therapy. Future investigations into the incidence and treatment of this side effect are needed. Table 1.&amp;lt;55 years old55+ years oldEyebrow Loss (N)%Eyelash Loss (N)%Eyebrow Loss (N)%Eyelash Loss (N)%No Loss4551%4753%9655%9353%A Little Loss2629%2225%3922%3922%A lot of loss1011%1112%2715%2514%Complete Loss89%910%148%1810%Funding Source: Breast Cancer Research Foundation (CLL) Clinic Citation Format: Elizabeth Cathcart-Rake, Charles L Loprinzi, Fergus Couch, Janet Olson, Brittany Dulmage, Maryam Lustberg, Nicole Larson, Kathryn J Ruddy. Eyebrow/eyelash loss among survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-11.
MULTI-MODALITY IDENTIFICATION OF APICAL POUCH/ANEURYSM IN APICAL HYPERTROPHIC CARDIOMYOPATHY
Authors: Ushasi Saraswati, Vidhu Anand, Megan K. Covington, Nandan Sadanand Anavekar, Jeffrey Benjamin Geske, Adelaide Maria Arruda-Olson, Kyle W. Klarich
Journal: Journal of the American College of Cardiology (2022)
When I use a word . . . . Memory, semantic and episodic
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

Although the Oslerian aphorism “Listen to the patient; he is telling you the diagnosis” is widely quoted as a truism, it is not the whole story. The patient’s tale is almost inevitably incomplete and needs to be augmented by skilful questioning. The complete diagnosis, which should be a thorough account of the condition, its causes and contributory factors, often comes only after the further additions of observation, examination, and investigations. In some cases the patient is unable to tell the tale properly or even at all. While in most cases the patient’s autobiographical search to remember the past relies primarily on voluntary episodic memory, in others, such as neurodegenerative disorders and cases of toxicological neural damage, episodic memory, voluntary or involuntary, may be impaired.
Abstract P5-12-13: Exploring the impact of the tumor microenvironment on nuclear morphometry: Lessons learned for sensitivity to cytotoxic treatment
Authors: Apekshya Chhetri
Journal: Cancer Research (2022)

Abstract Globally, breast cancer remains the leading cause of death in females. While systemic therapy for breast cancer may work effectively in the early phases, for more than 10% of primary and 50% of metastatic cases, the disease eventually progresses, resisting treatments. To overcome this issue, recognizing markers of resistance as early as possible is critical. Microenvironmental factors influence tumors, and increased stiffness of the extracellular matrix (ECM) is associated with cancer progression. Additionally, neighboring cells such as non-neoplastic epithelial cells(that may constitute an important portion of the tumor microenvironment -TME) are suspected to affect tumors, but details on their impact are lacking. Here, we asked whether the response to increased ECM stiffness differed depending on the degree of aggressiveness of triple negative breast cancers (TNBC) and the presence of the non-neoplastic epithelium. We investigated two morphometric parameters, nuclear circularity and area (used in cancer pathology), and tumors’ sensitivity to cisplatin to assess tumor aggressiveness- with TNBC cultured at normal (770 Pa) and increased (2000 and 3300 Pa) collagen I stiffness. Reduced nuclear circularity and increased heterogeneity for this parameter in the cancer cell population resulted from higher matrix stiffness and were associated with decreased sensitivity to the cytotoxic drug, cisplatin, notably in the more invasive cancer type. Interestingly, the impact of stiffness increase was reduced by the conditioned medium from the non-neoplastic cells. These findings warrant further investigations to identify whether changes in nuclear circularity that illustrate a global nuclear reorganization affect gene expression profiles linked to cell survival. Citation Format: Apekshya Chhetri. Exploring the impact of the tumor microenvironment on nuclear morphometry: Lessons learned for sensitivity to cytotoxic treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-12-13.
TRENDS IN TESTING AND PREVALENCE OF ELEVATED LIPOPROTEIN(A) AMONG PATIENTS WITH AORTIC VALVE STENOSIS
Authors: Harpreet Bhatia, Gary Ma, Adam Taleb, Michael Wilkinson, Andrew Kahn, Bruno R. Cotter, Calvin Yeang, Anthony N. DeMaria, Mitul P. Patel, Ehtisham Mahmud, Ryan Robert Reeves, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2022)
Tim-3 mediates T cell trogocytosis to limit antitumor immunity
Authors: Ornella Pagliano, Robert M. Morrison, Joe-Marc Chauvin, Hridesh Banerjee, Diwakar Davar, Quanquan Ding, Tokiyoshi Tanegashima, Wentao Gao, Saranya R. Chakka, Richelle DeBlasio, Ava Lowin, Kevin Kara, Mignane Ka, Bochra Zidi, Rada Amin, Itay Raphael, Shuowen Zhang, Simon C. Watkins, Cindy Sander, John M. Kirkwood, Marcus Bosenberg, Ana C. Anderson, Vijay K. Kuchroo, Lawrence P. Kane, Alan J. Korman, Arvind Rajpal, Sean M. West, Minhua Han, Christine Bee, Xiaodi Deng, Xiao Min Schebye, Pavel Strop, Hassane M. Zarour
Journal: Journal of Clinical Investigation (2022)

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1–positive (PD-1+) Tim-3+CD8+ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on Tim-3+ APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen–specific CD8+ T cells and PD-1+Tim-3+ CD8+ TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of CD8+ TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in CD8+ T cells impeded the trogocytosis of CD8+ TILs in vivo. Trogocytosed CD8+ T cells presented tumor peptide–major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity.
OUTCOMES OF PERCUTANEOUS LEFT ATRIAL APPENDAGE OCCLUSION (LAAO) ON LEFT ATRIAL FUNCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Rosa N. Cruz Torres, Raahat Bansal, Abhishek Thandra, Shiva Ponamgi, Venkata Mahesh Alla, Ahmed Salah Ahmed Aboeata
Journal: Journal of the American College of Cardiology (2022)
RISK OF NEW-ONSET ATRIAL FIBRILLATION IN NEWLY DIAGNOSED CANCER PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Janeth Gomez-Perez, Veena Gujju, Christian Fleming, Muhammad Faraz Anwaar, Siddharth Agarwal, Shari Clifton, Jessica Reese, Abhishek Deshmukh, Zain Ul Abideen Asad
Journal: Journal of the American College of Cardiology (2022)
Implementation of patient-reported outcome measures into health care for men with localized prostate cancer
Authors: Udit Singhal, Ted A. Skolarus, John L. Gore, Matthew G. Parry, Ronald C. Chen, Julie Nossiter, Alan Paniagua-Cruz, Arvin K. George, Paul Cathcart, Jan van der Meulen, Daniela A. Wittmann
Journal: Nature Reviews Urology (2022)
LOWER THAN EXPECTED RATES OF MORTALITY AND BRONCHOPULMONARY DYSPLASIA AMONG A HIGH RISK GROUP OF EXTREMELY PREMATURE INFANTS FOLLOWING TRANSCATHETER CLOSURE OF PATENT DUCTUS ARTERIOSUS
Authors: Ranjit Philip, Michelle Santoso, Leah Apalodimas, Mimily Harsono, Sandeep Chilakala, Benjamin Rush Waller, Jason N. Johnson, Shyam Sathanandam
Journal: Journal of the American College of Cardiology (2022)
Immunocompromised rabbit model of chronic HEV reveals liver fibrosis and distinct efficacy of different vaccination strategies
Authors: Qiyu He, Fan Zhang, Jingyi Shu, Shuangshuang Li, Zhaochao Liang, Minghao Du, Xing Liu, Tianxu Liu, Manyu Li, Xin Yin, Qiuwei Pan, Fengmin Lu, Ling Wang, Lin Wang
Journal: Hepatology (2022)

Abstract Background and Aims HEV infection can lead to chronicity and rapid progression to liver fibrosis and cirrhosis in immunocompromised organ transplant recipients. Robust animal models are urgently needed to study the pathogenesis and test the efficacy of vaccines and antiviral drugs in immunosuppressed settings. Approach and Results Cyclosporin A was used to induce immunosuppression. Rabbits were challenged with genotype 3 or 4 HEV (i.e., the rabbit‐derived HEV3 and human‐derived HEV3 or HEV4). We assessed HEV markers within 13 weeks post inoculation (wpi) and pathological changes by hematoxylin and eosin and Masson staining at 4, 8, or 13 wpi. Chronic HEV infection was successfully established in immunocompromised rabbits. HEV RNA and/or antigens were detected in the liver, kidney, intestine, urine, and cerebrospinal fluid samples. Chronically infected animals exhibited typical characteristics of liver fibrosis development. Intrahepatic transcriptomic analysis indicated activation of both innate and adaptive immunity. Establishment of HEV chronicity likely contributed to the inhibited T‐cell immune response. Ribavirin is effective in clearing HEV infection in immunocompromised rabbits. Most interestingly, vaccination completed before immunosuppression conferred full protection against both HEV3 and HEV4 infections, but vaccination during immunosuppression was only partially protective, and the efficacy did not improve with increased or additional vaccine doses. Conclusions The immunocompromised rabbit model of both chronic HEV3 and HEV4 infection that was established captured the key features of chronic HEV infection in transplant patients, including liver fibrogenesis, and revealed the distinct effectiveness of vaccination administered before or under immunosuppression. This rabbit model is valuable for understanding the pathogenesis of chronic hepatitis E, as well as for evaluating antiviral agents and vaccines.
Normalization to Predicted Body Weight May Underestimate Mechanical Energy in Pediatric Acute Respiratory Distress Syndrome
Authors: Yukie Ito, Muneyuki Takeuchi, Yu Inata, Miyako Kyogoku, Justin C. Hotz, Anoopindar K. Bhalla, Christopher J. L. Newth, Robinder G. Khemani
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Normalization to Predicted Body Weight May Underestimate Mechanical Energy in Pediatric Acute Respiratory Distress Syndrome." American Journal of Respiratory and Critical Care Medicine, 205(11), pp. 1360–1363
Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness — United States and Puerto Rico, April 2020–March 2021
Authors: Jorge Munoz-Jordan, Jaime Cardona, Manuela Beltrán, Candimar Colón, Jarad Schiffer, Evelene Stewart-Clark, Briana Zellner, Vera Semenova, Yikun Li, Lily Tao Jia, Panagiotis Maniatis, Lucia Pawloski, Laura Adams, Gabriela Paz-Bailey, Vanessa Rivera-Amill, Freddy Medina
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The diagnosis of dengue disease, caused by the dengue virus (DENV) (a flavivirus), often requires serologic testing during acute and early convalescent phases of the disease. Some symptoms of DENV infection, such as nonspecific fever, are similar to those caused by infection with SARS-CoV-2, the virus that causes COVID-19. In studies with few COVID-19 cases, positive DENV immunoglobulin M (IgM) results were reported with various serologic tests, indicating possible cross-reactivity in these tests for DENV and SARS-CoV-2 infections (1,2). DENV antibodies can cross-react with other flaviviruses, including Zika virus. To assess the potential cross-reactivity of SARS-CoV-2, DENV, and Zika virus IgM antibodies, serum specimens from 97 patients from Puerto Rico and 12 U.S.-based patients with confirmed COVID-19 were tested using the DENV Detect IgM Capture enzyme-linked immunosorbent assay (ELISA) (InBios International).* In addition, 122 serum specimens from patients with confirmed dengue and 121 from patients with confirmed Zika virus disease (all from Puerto Rico) were tested using the SARS-CoV-2 pan-Ig Spike Protein ELISA (CDC).† Results obtained for DENV, Zika virus IgM, and SARS-CoV-2 antibodies indicated 98% test specificity and minimal levels of cross-reactivity between the two flaviviruses and SARS-CoV-2. These findings indicate that diagnoses of dengue or Zika virus diseases with the serological assays described in this report are not affected by COVID-19, nor do dengue or Zika virus diseases interfere with the diagnosis of COVID-19.
Detection of Azoxystrobin Fungicide and Metabolite Azoxystrobin-Acid in Pregnant Women and Children, Estimation of Daily Intake, and Evaluation of Placental and Lactational Transfer in Mice
Authors: Wenxin Hu, Chih-Wei Liu, Jessica A. Jiménez, Eric S. McCoy, Yun-Chung Hsiao, Weili Lin, Stephanie M. Engel, Kun Lu, Mark J. Zylka
Journal: Environmental Health Perspectives (2022)

Background: Azoxystrobin (AZ) is a broad-spectrum strobilurin fungicide that is used in agriculture and was recently added to mold- and mildew-resistant wallboards. AZ was found to have toxic effects in animals at embryonic stages and was listed as a frontline target for biomonitoring in children. Objectives: This study investigated exposure to AZ in pregnant women and young children, whether AZ could be transferred from an exposed mother to offspring, and whether AZ or one of its primary metabolites, AZ-acid, was neurotoxic in vitro. Methods: We quantified AZ-acid, a sensitive indicator of AZ exposure, in urine samples collected from 8 pregnant women (12 urine samples) and 67 children (40–84 months old; 96 urine samples) with high-resolution mass spectrometry. Gestational and lactational transfer was assessed in C57Bl/6 mice. Neurotoxicity of AZ and AZ-acid was investigated in vitro with mouse cortical neuron cultures. Results: AZ-acid was present above the limit of quantification (0.01 ng/mL) in 100% of the urine samples from pregnant women and in 70% of the urine samples from children, with median concentration of 0.10 and 0.07 ng/mL, and maximal concentration of 2.70 and 6.32 ng/mL, respectively. Studies in mice revealed that AZ transferred from the mother to offspring during gestation by crossing the placenta and entered the developing brain. AZ was also transferred to offspring via lactation. High levels of cytotoxicity were observed in embryonic mouse cortical neurons at concentrations that modeled environmentally relevant exposures. Discussion: Our study suggested that pregnant women and children were exposed to AZ, and at least 10% of the children (2 out of 20 that were evaluated at two ages) showed evidence of chronic exposure. Future studies are warranted to evaluate whether chronic AZ exposure affects human health and development. https://doi.org/10.1289/EHP9808
It Is Time to Change the Standard of Medication Abortion
Authors: Jennifer Karlin, Jamila Perritt
Journal: JAMA Internal Medicine (2022)

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Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis
Authors: Laura Fabbri, Samuel Moss, Fasihul A Khan, Wenjie Chi, Jun Xia, Karen Robinson, Alan Robert Smyth, Gisli Jenkins, Iain Stewart
Journal: Thorax (2022)

Introduction Persisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up of people hospitalised with COVID-19 and viral pneumonitis. Methods Systematic review and random effects meta-analysis of proportions using studies of adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV or influenza pneumonia and followed up within 12 months. Searches performed in MEDLINE and Embase. Primary outcomes were proportion of radiological sequelae on CT scans; restrictive impairment; impaired gas transfer. Heterogeneity was explored in meta-regression. Results Ninety-five studies (98.9% observational) were included in qualitative synthesis, 70 were suitable for meta-analysis including 60 SARS-CoV-2 studies with a median follow-up of 3 months. In SARS-CoV-2, the overall estimated proportion of inflammatory sequelae was 50% during follow-up (0.50; 95% CI 0.41 to 0.58; I 2 =95%), fibrotic sequelae were estimated in 29% (0.29; 95% CI 0.22 to 0.37; I 2 =94.1%). Follow-up time was significantly associated with estimates of inflammatory sequelae (−0.036; 95% CI −0.068 to –0.004; p=0.029), associations with fibrotic sequelae did not reach significance (−0.021; 95% CI −0.051 to 0.009; p=0.176). Impaired gas transfer was estimated at 38% of lung function tests (0.38 95% CI 0.32 to 0.44; I 2 =92.1%), which was greater than restrictive impairment (0.17; 95% CI 0.13 to 0.23; I 2 =92.5%), neither were associated with follow-up time (p=0.207; p=0.864). Discussion Sequelae consistent with parenchymal lung disease were observed following COVID-19 and other viral pneumonitis. Estimates should be interpreted with caution due to high heterogeneity, differences in study casemix and initial severity. PROSPERO registration number CRD42020183139.
A Phase I Study Investigating AZD8186, a Potent and Selective Inhibitor of PI3Kβ/δ, in Patients with Advanced Solid Tumors
Authors: Atish D. Choudhury, Celestia S. Higano, Johann S. de Bono, Natalie Cook, Dana E. Rathkopf, Kari B. Wisinski, Juan Martin-Liberal, Mark Linch, Elisabeth I. Heath, Richard D. Baird, Javier García-Carbacho, Miguel Quintela-Fandino, Simon T. Barry, Elza C. de Bruin, Steve Colebrook, George Hawkins, Teresa Klinowska, Brijesh Maroj, Ganesh Moorthy, Peter G. Mortimer, Michele Moschetta, Myria Nikolaou, Liz Sainsbury, Geoffrey I. Shapiro, Lillian L. Siu, Aaron R. Hansen
Journal: Clinical Cancer Research (2022)

Abstract Purpose: To characterize safety and tolerability of the selective PI3Kβ inhibitor AZD8186, identify a recommended phase II dose (RP2D), and assess preliminary efficacy in combination with abiraterone acetate or vistusertib. Patients and Methods: This phase I open-label study included patients with advanced solid tumors, particularly prostate cancer, triple-negative breast cancer, and squamous non–small cell lung cancer. The study comprised four arms: (i) AZD8186 monotherapy dose finding; (ii) monotherapy dose expansion; (iii) AZD8186/abiraterone acetate (with prednisone); and (iv) AZD8186/vistusertib. The primary endpoints were safety, tolerability, and identification of the RP2D of AZD8186 monotherapy and in combination. Secondary endpoints included pharmacokinetics (PK), pharmacodynamics, and tumor and prostate-specific antigen (PSA) responses. Results: In total, 161 patients were enrolled. AZD8186 was well tolerated across all study arms, the most common adverse events being gastrointestinal symptoms. In the monotherapy dose-finding arm, four patients experienced dose-limiting toxicities (mainly rash). AZD8186 doses of 60-mg twice daily [BID; 5 days on, 2 days off (5:2)] and 120-mg BID (continuous and 5:2 dosing) were taken into subsequent arms. The PKs of AZD8186 were dose proportional, without interactions with abiraterone acetate or vistusertib, and target inhibition was observed in plasma and tumor tissue. Monotherapy and combination therapy showed preliminary evidence of limited antitumor activity by imaging and, in prostate cancer, PSA reduction. Conclusions: AZD8186 monotherapy had an acceptable safety and tolerability profile, and combination with abiraterone acetate/prednisone or vistusertib was also tolerated. There was preliminary evidence of antitumor activity, meriting further exploration of AZD8186 in subsequent studies in PI3Kβ pathway–dependent cancers.
NETWORK META-ANALYSIS OF THE COMPARATIVE EFFICACY OF PULMONARY VASODILATORS IN PATIENTS WITH CONGENITAL HEART DISEASE-ASSOCIATED PULMONARY HYPERTENSION
Authors: Jun Yasuhara, Kae Watanabe, Takuro Shirasu, Yuichi Matsuzaki, Hisato Takagi, Naokata Sumitomo, Toshiki Kuno
Journal: Journal of the American College of Cardiology (2022)