tbuckley/cabot-search huggingface dataset:
Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States
Authors: Susan M. Domchek, Song Yao, Fei Chen, Chunling Hu, Steven N. Hart, David E. Goldgar, Katherine L. Nathanson, Christine B. Ambrosone, Christopher A. Haiman, Fergus J. Couch, Eric C. Polley, Julie R. Palmer
Journal: JAMA Oncology (2021)

The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes in US Black women compared with non-Hispanic White women with breast cancer is poorly described.To determine whether US Black and non-Hispanic White women with breast cancer have a different prevalence of PVs in 12 cancer susceptibility genes.Multicenter, population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Participants were Black and non-Hispanic White women diagnosed with breast cancer, unselected for family history or age at diagnosis. Data were collected from June 1993 to June 2020; data analysis was performed between September 2020 and February 2021.Prevalence of germline PVs in 12 established breast cancer susceptibility genes.Among 3946 Black women (mean [SD] age at diagnosis, 56.5 [12.02] y) and 25 287 non-Hispanic White women (mean [SD] age at diagnosis, 62.7 [11.14] y) with breast cancer, there was no statistically significant difference by race in the combined prevalence of PVs in the 12 breast cancer susceptibility genes evaluated (5.65% in Black vs 5.06% in non-Hispanic White women; P = .12). The prevalence of PVs in CHEK2 was higher in non-Hispanic White than Black patients (1.29% vs 0.38%; P < .001), whereas Black patients had a higher prevalence of PVs in BRCA2 (1.80% vs 1.24%; P = .005) and PALB2 (1.01% vs 0.40%; P < .001). For estrogen receptor-negative breast cancer, the prevalence of PVs was not different except for PALB2, which was higher in Black women. In women diagnosed before age 50 years, there was no difference in overall prevalence of PVs in Black vs non-Hispanic White women (8.83% vs 10.04%; P = .25), and among individual genes, only CHEK2 PV prevalence differed by race. After adjustment for age at diagnosis, the standardized prevalence ratio of PVs in non-Hispanic White relative to Black women was 1.08 (95% CI, 1.02-1.14), and there was no longer a statistically significant difference in BRCA2 PV prevalence.This large population-based case-control study revealed no clinically meaningful differences in the prevalence of PVs in 12 breast cancer susceptibility genes between Black and non-Hispanic White women with breast cancer. The findings suggest that there is not sufficient evidence to make policy changes related to genetic testing based on race alone. Instead, all efforts should be made to ensure equal access to and uptake of genetic testing to minimize disparities in care and outcomes.
AB0807 TOAST-STUDY: TREATMENT AND OSTEOARTHRITIS, WHAT ARE PEOPLE SAYING ON TWITTER?
Authors: A. Mouamnia, A. Desvages
Journal: Annals of the Rheumatic Diseases (2021)

Background: Osteoarthritis is a very common chronic disease. The information needs of patients vary depending on the health issue. Social media sites represent a novel source of health information and advice for patients with chronic diseases, such as osteoarthritis. Almost half of them use the internet to look for health related information [1] . No study has assessed the impact of social media on osteoarthritis and its treatment. Objectives: The purpose of this study was to evaluate frequently discussed osteoarthritis treatments on the social media Twitter. Methods: We retrospectively analyzed tweets, published between 1 st and 31 st January 2020, containing the keywords “osteoarthritis”. Only English language tweets were included. Tweets referred to veterinary medicine were excluded. Results: 3587 tweets were analyzed. We identified 1737 tweets related to osteoarthritis treatment between 1 st and 31 st January 2020 (49.8%) (Figure 1). Dietary interventions were the most discussed treatment (18.3%, n=318/1737), including fruits, vegetables and plants (n=101), dietary supplements and vitamins (n=80), and spices (n=19). Physical medicine and rehabilitation (17.6%, n=305/1737) including sport (n=151), physiotherapy (n=70) and rehabilitation (n=57), were commonly discussed. Local therapies for osteoarthritis were also discussed by Twitter users (15.8%, n=274/1737). These included topical treatments such as anti-inflammatory gels and creams (n=23), and more invasive local treatments including intra-articular joint injections with corticosteroid (n=56), hyaluronans (n=29), stem cells (n=97), and Platelet-Rich Plasma (n=52). The frequently used systemic drugs were analgesia and non-steroidal anti-inflammatory drugs (n=113). Surgery and interventional radiology (genicular artery embolization) were also discussed (11.5%, n=199/1737). 5.6% tweets (n=97/1737) were related to alternative therapies. Predominant themes were related to marijuana (n=23), acupuncture treatment (n=17), homeopathy (n=10). Last but not least, 356 tweets (20.5%) referred to other websites including health programs. Conclusion: Our results demonstrate that osteoarthritis treatment is frequently discussed in published tweets. Thereby, social media could have an impact on behaviors and adherence on medication, and it seems interesting that learned societies, involved in osteoarthritis treatment, communicate more using social media. Figure 1. Osteoarthritis treatment discussed in published tweets References: [1]Wagner TH, Baker LC, Bundorf MK, Singer S. Use of the Internet for health information by the chronically ill. Prev Chronic Dis 2004;1(4):A13. Disclosure of Interests: None declared
Loss of a 7q gene,<i>CUX1</i>, disrupts epigenetically driven DNA repair and drives therapy-related myeloid neoplasms
Authors: Molly K. Imgruet, Julian Lutze, Ningfei An, Bonnie Hu, Saira Khan, Jeffrey Kurkewich, Tanner C. Martinez, Donald Wolfgeher, Sandeep K. Gurbuxani, Stephen J. Kron, Megan E. McNerney
Journal: Blood (2021)
POS0382 EXPANSION OF CD4+/CD8+ DOUBLE-POSITIVE T CELLS IS ASSOCIATED WITH A SEVERE DISEASE COURSE IN RHEUMATOID ARTHRITIS
Authors: P. Nguyen, K. Rothe, M. Melzer, M. Krasselt, M. Pierer, U. Wagner
Journal: Annals of the Rheumatic Diseases (2021)

Background: CD4 + /CD8 + double-positive T (dpT) cells are a set of pathologic T cells, representing about 1% of peripheral blood T cells and increasing with age in healthy individuals. Patients with rheumatoid arthritis (RA) more frequently have expanded dpT cells compared to age-matched controls, up to a frequency of 8% [1]. However, whether dpT cell expansion harbors clinical significance in RA is not known. Objectives: The goal of the study was to assess possible associations of DPT expansion with clinical features of patients with RA. Methods: In this cross-sectional study, dpT cells were measured in RA patients (n=70) via fluorescence-activated flow cytometry. Clinical data including age, sex, disease duration, treatment history, disease activity parameters, and radiographic structural damage was collected. Radiographs of hands and feet were used to determine the modified Sharp/van der Heijde (SvdH) score. Expansion of dpT cells was defined as a frequency of &gt;2% of the total T cell pool, based on reference ranges determined in a large cohort of healthy individuals [2]. Mann-Whitney-U test was used to compare groups and X 2 test was used for contingency tables. Statistical analyses were conducted using GraphPad Prism v8 (GraphPad Software, San Diego, USA). Results: DpT cells were expanded in more than a quarter of our cohort (n=19, 27.1%). Patients with expanded dpT cells more often used biologics or targeted synthetic DMARDs than patients with low dpT cells (68.4% vs. 38%, p=0.02). Radiographic damage was also significantly worse in patients with DPT expansion, as shown in their higher SvdH score (median 24.5 vs. 6, p=0.008) and its component scores for erosion (median 19 vs. 0, p=0.004) and joint space narrowing (median 8 vs. 2, p=0.017) (figure 1A). There was no difference regarding sex, age, disease duration, seropositivity and disease activity between the groups (figure 1B). Conclusion: DpT cell expansion is associated with higher scores of radiographic structural damage despite more frequent use of highly effective therapeutics. An expansion of dpT cells is not uncommon in RA, and affected patients represent a subset at high risk for a more severe disease course. References: [1]Quandt D, Rothe K, Scholz R, et al. Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis. PLoS ONE 2014; 9 :e93293. doi:10.1371/journal.pone.0093293 [2]Apoil PA, Puissant-Lubrano B, Congy-Jolivet N, et al. Reference values for T, B and NK human lymphocyte subpopulations in adults. Data Brief 2017; 12 :400–4. doi:10.1016/j.dib.2017.04.019 Figure 1. DpT cell expansion is associated with radiographic progression. SvdH, modified Sharp/van der Heijde Score; DpT, CD4 + /CD8 + double-positive T cells. Disclosure of Interests: None declared
Adverse events reported to the U.S. Food and Drug Administration Adverse Event Reporting System for tisagenlecleucel
Authors: Graça M. Dores, Christopher Jason, Manette T. Niu, Silvia Perez‐Vilar
Journal: American Journal of Hematology (2021)

Abstract The U.S. Food and Drug Administration (FDA) approved the first chimeric antigen receptor T‐cell therapy, tisagenlecleucel, in August 2017. We sought to describe adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS) for tisagenlecleucel in the post‐marketing period. We searched FAERS reports to identify U.S. patients treated with tisagenlecleucel between August 30, 2017‐August 31, 2019. We reviewed individual reports, calculated AE frequencies and reporting rates (RRs), and used Empirical Bayesian Geometric Mean methods to identify disproportionate reporting. We identified 646 de‐duplicated reports with a median age at AE of 18 (interquartile range: 11–56) years. The overall RR was 81.0%, and more than 95% of reports described a serious outcome. Cytokine release syndrome (CRS) was the most frequently reported AE (51.1%) with a RR of 41.4%; neurotoxicity was reported less frequently (21.2%), with a RR of 17.2%. Most disproportionately reported AEs were listed on the package insert or confounded by indication. We identified 13 subsequent neoplasms (SPN), the majority occurring within 6 months of tisagenlecleucel administration, and none reporting evidence of insertional mutagenesis. A total of 165 reports (26%) described a death outcome; most deaths occurred &gt;30 days after treatment. The majority of deaths (64%) were due to progression of the underlying lymphoid neoplasm, and few (&lt;5%) were attributed to CRS or neurotoxicity. We did not identify new safety concerns reported for tisagenlecleucel in the post‐marketing period. Reporting rates for CRS and neurotoxicity were lower than identified in the prelicensure clinical trials.
RNA-Sequencing of Isolated Cell Populations Expressing Human APOL1 Risk Variants Reveals Molecular Correlates of Sickle Cell Nephropathy in Zebrafish Podocytes
Authors: Joseph L Bundy, Blair R Anderson, Ludmila Francescatto, Melanie E Garrett, Karen L Soldano, Marilyn J. Telen, Erica E Davis, Allison E Ashley-Koch
Journal: Blood (2017)
A new therapeutic approach against metastatic renal cell carcinoma: The combination of connexin gene function and Src inhibitor.
Authors: Tomohiro Yano, Eriko Fujimoto, Koichi Ueno, Haruna Satoh, Yoko Yonezawa, Kiyokazu Hagiwara, Hiroshi Yamasaki
Journal: Cancer Research (2004)

2206  We have reported that connexin (Cx)32 gene, a member of gap junction, acts as tumor suppressor with certain cell specificity. That is, Cx preferentially exerts tumor-suppressive effect on the tumor from normal progenitor cell in which the particular Cx is naturally expressed. We have also determined that Cx32 was specifically down-regulated in human primary and metastatic renal cell carcinoma (RCC) and that the Cx gene acts as a tumor suppressor gene against the RCC. Since the management of the metatstatic RCC remains a therapeutic challenge, we tried to investigate a possibility on the establishment of a new cancer therapy based on the tumor-suppressive effects of Cx32 gene against the RCC. In this study, we established Cx32-expressed clones in a metastatic RCC cell line in order to estimate the above possibility. In the RCC cell line, Cx32 had negative growth control in vivo as well as in vitro. Flow cytometric analysis showed that the negative growth control was dependent on G1 arrest in cell cycle, and the G1 arrest was mainly caused by Cx32-depenent inactivation of some growth signal transductions. Furthermore, a Src inhibitor not only reinforced the in vitro Cx32-dependent negative growth control but also induced apoptosis, leading to the effectively cytotoxic effects against the RCC cell. As well with the in vitro data, the Src inhibitor reinforced Cx32-dependent negative growth control of the RCC cell in xenograft model. Also, this effect was partly dependent on Cx32-mediated bystander killer effect through gap junctional intercellular communication. By this killer effect, it is expected that the efficiency dose of Src inhibitor against the metastatic RCC is significantly reduced. These data suggest that the combination therapy of Cx32 and Src inhibitor is a promising new cancer therapy against the metastatic RCC.
MYD88 Mutation Status Impacts Overall Survival and Risk of Histological Transformation in Waldenstrom's Macroglobulinemia
Authors: Steven P Treon, Zachary Hunter, Joshua Gustine, Kirsten Meid, Lian Xu, Xia Liu, Guang Yang, Manit Munshi, Robert Manning, Nickolas Tsakmaklis, Maria Demos, Amanda Kofides, Maria Luisa Guerrera, Jiaji Chen, Gloria Chan, Christopher Patterson, Toni Dubeau, Patricia Severns, Jorge J. Castillo
Journal: Blood (2017)
AB0621 THE MAIN CAUSES OF MORTALITY IN PATIENTS WITH OSTEOPOROTIC HIP FRACTURES
Authors: J. Averkieva, M. Letaeva, O. Malyshenko, M. Koroleva, T. Raskina
Journal: Annals of the Rheumatic Diseases (2021)

Background: Increasing life expectancy is one of the main achievements of modern medicine. However, longevity is inevitably associated with the growth of so-called “age-associated diseases,” among which osteoporosis occupies an important place. Objectives: To study the causes of mortality in patients with hip osteoporotic fractures during 12 months after injury. Methods: Traced the causes of mortality 432 patients with osteoporotic hip fractures were under observation: 328 women and 104 men. The mean age of women was 75.4 ± 9.27 years, the mean age of men was 71.5 ± 10.39 years. Results: This study traced the causes of deaths by the main classes of ICD-10. It was found that 6 months after a hip fracture in 63 (66.3%) patients, death occurred from diseases of the circulatory system: in men - 13 (59.0%) cases and in women - 50 (68.4%) (p = 0.9). Respiratory diseases, as a cause of death, were identified in 18 (18.9%) patients (in men - 5 (22.9%) cases and in women - 13 (17.8%) (p = 0.1)), neoplasms - in 10 (10.5%) men and women: 2 (9.1%) and 8 (10.9%) cases, respectively (p = 0.5). Diseases of the digestive system accounted for a small percentage of the total number of deaths (3.2%), without statistically significant differences by gender (in men - 1 (4.5%) case and in women - 2 (2.9%) cases (p = 0.75)). Among the dead men, 1 (1.1%) death from an infectious disease was registered. 12 months after the fracture, most of the deaths in both men and women were due to diseases of the circulatory system. The total number of deaths was 93 (67.8%): in men - 22 (66.0%) cases, in women - 71 (68.3%) (p = 0.65). Respiratory diseases caused death in 23 (16.8%) patients: in men - 5 (15.1%) cases and in women - 18 (17.3%) (p = 0.31). There is an increase in the number of deaths from neoplasms to 15 (10.9%) cases without statistically significant differences by gender: in men - 3 (9.09%) cases and in women - 12 (11.5%) (p = 0, 45). Diseases of the digestive system, as a cause of death, were identified in 5 (3.6%) men and women (2 (6.06%) and 3 (2.9%) cases, respectively (p = 0.1)). No new cases of deaths from infectious diseases were registered. Conclusion: Most of the deceased men and women had cardiovascular and respiratory diseases. There were no statistically significant differences registered in the structure of mortality by gender for all classes of diseases. Disclosure of Interests: None declared.
Hyperthyroidism Incidentally Noted on Lymphoscintigraphy
Authors: Yong Liu, Guansheng Tong, Zhe Wen, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2021)

A 43-year-old woman with edema in both left upper limb and lower limb underwent lymphoscintigraphy to evaluate possible lymphedema. Two separate lymphoscintigraphies, one for the lower and the other for the upper limbs, were performed with interval of 3 days. Incidentally, an activity in the region of the thyroid glands was noted in the delayed images of both studies. Subsequently, Graves disease was diagnosed based on the patient's symptoms and the results of laboratory examinations.
Advanced Human BBB‐on‐a‐Chip: A New Platform for Alzheimer's Disease Studies
Authors: Jeong‐Kee Yoon, Jaehoon Kim, Zachary Shah, Ashi Awasthi, Advay Mahajan, YongTae Kim
Journal: Advanced Healthcare Materials (2021)

Abstract The blood−brain barrier (BBB) is a unique vascular structure that serves as a molecular transport gateway for the maintenance of brain homeostasis. Chronic disruption or breakdown of the BBB reportedly leads to neurodegenerative diseases. Nonetheless, research on human BBB pathophysiology and drug development remains highly dependent on studies using inherently different animals. Moreover, more studies have shown that animal models are not appropriate in modeling Alzheimer's disease (AD), underlining the importance of in vitro models of the human BBB with physiological relevance. In this review, recent advances in human BBB‐on‐a‐chip technologies are highlighted and their potential for pathogenesis studies and drug prescreening for AD treatment are discussed.
Risk factors for acquisition of colistin-resistant Klebsiella pneumoniae and expansion of a colistin-resistant ST307 epidemic clone in hospitals in Marseille, France, 2014 to 2017
Authors: Sophie Alexandra Baron, Nadim Cassir, Mouna Hamel, Linda Hadjadj, Nadia Saidani, Gregory Dubourg, Jean-Marc Rolain
Journal: Eurosurveillance (2021)

Background France is a low prevalence country for colistin resistance. Molecular and epidemiological events contributing to the emergence of resistance to colistin, one of the 'last-resort' antibiotics to treat multidrug-resistant Gram-negative infections, are important to investigate. Aim This retrospective (2014 to 2017) observational study aimed to identify risk factors associated with acquisition of colistin-resistant Klebsiella pneumoniae (CRKP) in hospitals in Marseille, France, and to molecularly characterise clinical isolates. Methods To identify risk factors for CRKP, a matched-case–control (1:2) study was performed in two groups of patients with CRKP or colistin-susceptible K. pneumoniae respectively. Whole-genome-sequences (WGS) of CRKP were compared with 6,412 K. pneumoniae genomes available at the National Center for Biotechnology Information (NCBI). Results Multivariate analysis identified male sex and contact with a patient carrying a CRKP as significant independent factors (p &lt; 0.05) for CRKP acquisition, but not colistin administration. WGS of nine of 14 CRKP clinical isolates belonged to the same sequence type (ST)307. These isolates were from patients who had been hospitalised in the same wards, suggesting an outbreak. Comparison of the corresponding strains’ WGS to K. pneumoniae genomes in NCBI revealed that in chromosomal genes likely playing a role in colistin resistance, a subset of five specific mutations were significantly associated with ST307 (p &lt; 0.001). Conclusion A ST307 CRKP clone was identified in this study, with specific chromosomal mutations in genes potentially implicated in colistin resistance. ST307 might have a propensity to be or become resistant to colistin, however confirming this requires further investigations.
Radiology-guided percutaneous approach is superior to EUS for performing liver biopsies
Authors: Kaveh Hajifathalian, Kenneth J Chang, Reem Z Sharaiha
Journal: Gut (2021)

We read with interest the study titled ‘Radiology-guided percutaneous approach is superior to EUS for performing liver biopsies’ by Bang et al .1 Authors conclude that radiology-guided percutaneous liver biopsy is superior based on comparing the proportion of optimal samples obtained, defined as a sample with length of ≥25 mm and complete portal tracts (CPTs) of ≥11. Further evaluation of the results in this study shows no significant difference between the two methods regarding the number of CPTs, but a significantly higher sample length in the percutaneous group.

We propose that the results and the conclusions of the study are misleading and not generalisable to clinical practice. The main flaw of this study is the use of a suboptimal technique for performing the endoscopic ultrasound …
Abstract 15079: Prevalence and Prognostic Implications of Depression in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Neela D Thangada, Vijay Agusala, Colby Ayers, Ambarish Pandey
Journal: Circulation (2019)

Introduction: One in four individuals with HFpEF are diagnosed with depression. The prognostic implications of prevalent and new onset depression in patients with HFpEF are unknown. Methods: Partic...
Patients Favor Surgical Repair of Ruptured ACL
Authors: Anita Slomski
Journal: JAMA (2021)

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