tbuckley/cabot-search huggingface dataset:
Abstract 16693: PPP1R3A Regulates Cardiomyocyte Metabolism to Control Heart Failure: Investigation of Network-based Predictions
Authors: Victoria N Parikh, Pablo Cordero, Ayca Erbilgin, Kevin S Smith, Ray Hu, Stephen Montgomery, Kenneth B Margulies, Thomas P Cappola, Anna dePaoli-Roach, Euan A Ashley
Journal: Circulation (2017)

Heart failure is a deadly disease, and existing therapies are targeted at neurohormonal compensation rather than underlying mechanisms. Our prior network analysis of gene expression and genetic var...
Jane Hyslop Short
Authors: Helen Nelson
Journal: BMJ (2021)

Jane Merry was born in the manse in Shotts, Lanarkshire, where her father was a minister. She moved to Paisley aged 10 and attended Paisley Grammar School, where she excelled and won many prizes including the dux medal. During the war years she worked as a medical registrar in the department of Noah Morris at Stobhill Hospital. She became a member of the Royal Faculty of Physicians and Surgeons of Glasgow and completed her MD thesis on “Aspects of heart disease in old age with special reference …
Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits
Authors: Diego O. Borges, Rita S. Patarrão, Rogério T. Ribeiro, Rita Machado de Oliveira, Nádia Duarte, Getachew Debas Belew, Madalena Martins, Rita Andrade, João Costa, Isabel Correia, José Manuel Boavida, Rui Duarte, Luís Gardete-Correia, José Luís Medina, João F. Raposo, John G. Jones, Carlos Penha-Gonçalves, M. Paula Macedo
Journal: Metabolism (2021)
US abortions: Nine in 10 laws on access since 2017 increased restrictions, study finds
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

Most of the 227 laws passed by some 35 US states regarding access to abortion since 2017 restricted access to the procedure, and only 29 aimed to protect it, a study has found.

The study authors, from the University of Utah, said, “Access to abortion services is largely dependent on location. The numerous state restrictions on access to abortion services pose risks to women who are younger, of lower economic status, and racial minorities.” Their findings are published in JAMA Internal Medicine .1

Elisabeth Smith, a lawyer with the Center for Reproductive Rights, told The BMJ , “Over the past decade, more unconstitutional bans have been passed,” but these have been suspended …
Abstract PS7-67: Breast cancer subtype differences according to race/ethnicity
Authors: Jami Fukui, Surbhi Bansil, Anthony Silva, Jeffrey Killeen, Ian Pagano
Journal: Cancer Research (2021)

Abstract Background:Breast cancer incidence and mortality rate differ across racial/ethnic population in the US, little is known about Asian and Pacific Island subpopulations. For the Asian subgroups (Japanese, Chinese, Korean, Filipino, Vietnamese, etc.) in the U.S., overall incidence has increased over recent decades. From 2012-2016 Hawai’i incidence rates were significantly higher than the US overall for breast cancer, although cancer mortality rates in Hawai’i were significantly lower than the US overall for breast cancer. Significant disparities in breast cancer incidence and mortality exist, with Native Hawaiian and Filipino women particularly affected. Native Hawaiian women have the highest incidence and also have a 50% higher risk of breast cancer mortality compared to White women. In addition, there are dramatic racial/ethnic differences in mortality rates in the state, with Native Hawaiians having the highest mortality rates compared to all other major racial/ethnic groups. Methods:We examined unique breast cancer cases in a major health system in Hawai’i from 2013-2019 according to race/ethnicity. We found statically significant differences in breast cancer subtype according to race/ethnicity and menopausal status. Results:In 561 premenopausal breast cancer cases, we found that Native Hawaiians were less likely to have triple negative breast cancer (OR 0.2, p=0.02) and Japanese were less likely to have triple positive breast cancer (OR 0.17, p=0.002) compared to other race/ethnicities. In 1,954 postmenopausal breast cancer cases, we found that Filipino women were more likely to have hormone negative/HER2 positive breast cancer (OR 2.38, p=0.006) compared to other race/ethnicities. Table 1-Breast cancer subtype according to race/ethnicity in premenopausal women Table 2-Breast cancer subtype according to race/ethnicity in postmenopausal women Summary:Although behavioral, environmental, social, economic, and biological factors have been shown to influence risk and survival for breast cancer, they do not entirely explain the differences observed across populations. These findings show the need to characterize the underlying differences in breast tumor biology of breast cancer patients from different racial/ethnic groups to better understand known health disparities. Our hypothesis is that molecular characteristics are key contributors to the disparities in disease outcome across the different racial/ethnic groups. We have previously shown the importance of the tumor microenvironment differences in racial/ethnic groups in our population. Citation Format: Jami Fukui, Surbhi Bansil, Anthony Silva, Jeffrey Killeen, Ian Pagano. Breast cancer subtype differences according to race/ethnicity [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-67.
Modified endoscopic ultrasound-guided double-balloon-occluded gastroenterostomy bypass (M-EPASS): a pilot study
Authors: Amanda Marino, Ali Bessissow, Corey Miller, David Valenti, Louis Boucher, Prosanto Chaudhury, Jeffrey Barkun, Nauzer Forbes, Mouen A. Khashab, Myriam Martel, Yen-I Chen
Journal: Endoscopy (2021)

Abstract Introduction We recently developed a double-balloon device, using widely available existing technology, to facilitate endoscopic ultrasound-guided gastroenterostomy (EUS-GE). Our aim is to assess the feasibility of this modified approach to EUS-guided double-balloon-occluded gastroenterostomy bypass (M-EPASS). Methods This was a single-center retrospective study of consecutive patients undergoing M-EPASS from January 2019 to August 2020. The double-balloon device consists of two vascular balloons that optimize the distension of a targeted small-bowel segment for EUS-guided stent insertion. The primary end point was the rate of technical success. Results 11 patients (45 % women; mean [standard deviation (SD)] age 64.9 [8.6]) with malignant gastric outlet obstruction were included. Technical and clinical success (ability to tolerate an oral diet) were achieved in 91 % (10/11) and 80 % (8/10) of patients, respectively. There was one adverse event (9 %) due to stent migration. Two patients (18 %) required re-intervention for stent obstruction secondary to food impaction. The mean (SD) time to a low residue diet was 3.5 (2.4) days. Conclusion M-EPASS appears to facilitate the technique of EUS-GE, potentially enhancing its safety and clinical adoption. Larger studies are needed to validate this innovative approach to gastric outlet obstruction.
EZH2 inactivation in RAS-driven myeloid neoplasms hyperactivates RAS-signaling and increases MEK inhibitor sensitivity
Authors: Johannes Lorenz Berg, Bianca Perfler, Stefan Hatzl, Barbara Uhl, Andreas Reinisch, Gudrun Pregartner, Andrea Berghold, Thomas Penz, Michael Schuster, Klaus Geissler, Andreas Prokesch, Carsten Müller-Tidow, Gerald Hoefler, Karl Kashofer, Albert Wölfler, Heinz Sill, Veronica Caraffini, Armin Zebisch
Journal: Leukemia (2021)
クローン病患者における2002年後に有意に減少した再手術の速度【JST・京大機械翻訳】
Authors: Shinagawa Takahide, Hata Keisuke, Ikeuchi Hiroki, Fukushima Kouhei, Futami Kitaro, Sugita Akira, Uchino Motoi, Watanabe Kazuhiro, Higashi Daijiro, Kimura Hideaki, Araki Toshimitsu, Mizushima Tsunekazu, Itabashi Michio, Ueda Takeshi, Koganei Kazutaka, Oba Koji, Ishihara Soichiro, Suzuki Yasuo
Journal: Clinical Gastroenterology and Hepatology (2020)
Haemodynamic effects of the nitroxyl donor cimlanod (<scp>BMS</scp>‐986231) in chronic heart failure: a randomized trial
Authors: Ninian N. Lang, Faheem A. Ahmad, John G. Cleland, Christopher M. O'Connor, John R. Teerlink, Adriaan A. Voors, Jorg Taubel, Anke R. Hodes, Mohamed Anwar, Ravi Karra, Yasushi Sakata, Shiro Ishihara, Roxy Senior, Abhishek Khemka, Narayana G. Prasad, Mary M. DeSouza, Dietmar Seiffert, June Y. Ye, Paul D. Kessler, Maria Borentain, Scott D. Solomon, G. Michael Felker, John J.V. McMurray
Journal: European Journal of Heart Failure (2021)

Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF).In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with cimlanod (29 ± 9 mL/m2 ; P = 0.03) and NTG (28 ± 8 mL/m2 ; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo.In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure.
Thromboprophylaxis with Fixed Dose, 1mg/Kg/Day, Low Molecular Weight Heparin in Adults Undergoing Induction with Asparaginase for Acute Lymphoblastic Leukemia. Results of a Single Institution Cohort Study
Authors: Luai S Al Rabadi, Sven Reid Olson, Joseph J. Shatzel, Thomas G. Deloughery, Brandon Hayes-Lattin
Journal: Blood (2017)
Microbiota‐Driven Activation of Intrahepatic B Cells Aggravates NASH Through Innate and Adaptive Signaling
Authors: Fanta Barrow, Saad Khan, Gavin Fredrickson, Haiguang Wang, Katrina Dietsche, Preethy Parthiban, Sacha Robert, Thomas Kaiser, Shawn Winer, Adam Herman, Oyedele Adeyi, Marialena Mouzaki, Alexander Khoruts, Kristin A. Hogquist, Christopher Staley, Daniel A. Winer, Xavier S. Revelo
Journal: Hepatology (2021)

Background and Aims Nonalcoholic steatohepatitis is rapidly becoming the leading cause of liver failure and indication for liver transplantation. Hepatic inflammation is a key feature of NASH but the immune pathways involved in this process are poorly understood. B lymphocytes are cells of the adaptive immune system that are critical regulators of immune responses. However, the role of B cells in the pathogenesis of NASH and the potential mechanisms leading to their activation in the liver are unclear. Approach and Results In this study, we report that NASH livers accumulate B cells with elevated pro‐inflammatory cytokine secretion and antigen‐presentation ability. Single‐cell and bulk RNA sequencing of intrahepatic B cells from mice with NASH unveiled a transcriptional landscape that reflects their pro‐inflammatory function. Accordingly, B‐cell deficiency ameliorated NASH progression, and adoptively transferring B cells from NASH livers recapitulates the disease. Mechanistically, B‐cell activation during NASH involves signaling through the innate adaptor myeloid differentiation primary response protein 88 (MyD88) as B cell–specific deletion of MyD88 reduced hepatic T cell–mediated inflammation and fibrosis, but not steatosis. In addition, activation of intrahepatic B cells implicates B cell–receptor signaling, delineating a synergy between innate and adaptive mechanisms of antigen recognition. Furthermore, fecal microbiota transplantation of human NAFLD gut microbiotas into recipient mice promoted the progression of NASH by increasing the accumulation and activation of intrahepatic B cells, suggesting that gut microbial factors drive the pathogenic function of B cells during NASH. Conclusion Our findings reveal that a gut microbiota–driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH through innate and adaptive immune mechanisms.
Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis
Authors: Charles E. Gaber, Alan C. Kinlaw, Jessie K. Edwards, Jennifer L. Lund, Til Stürmer, Sharon Peacock Hinton, Virginia Pate, Luther A. Bartelt, Robert S. Sandler, Anne F. Peery
Journal: Annals of Internal Medicine (2021)

Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain.To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis.Active-comparator, new-user, retrospective cohort studies.Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015).Immunocompetent adults with diverticulitis in the outpatient setting.Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate.1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery.In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]).Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed.Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes.National Institutes of Health.
Exosomal miR-500a-5p derived from cancer-associated fibroblasts promotes breast cancer cell proliferation and metastasis through targeting USP28
Authors: Bing Chen, Yuting Sang, Xiaojin Song, Dong Zhang, Lijuan Wang, Wenjing Zhao, Yiran Liang, Ning Zhang, Qifeng Yang
Journal: Theranostics (2021)

The tumor microenvironment contributes to tumor progression and metastasis. Cancer-associated fibroblasts (CAFs) form a major cellular component of the tumor microenvironment. In this study, we further explored the mechanisms underlying the tumor-promoting roles of CAFs. Methods: Patient-derived CAFs and normal fibroblasts (NFs) were isolated from breast carcinomas and adjacent normal breast tissue. Exosomes were isolated by ultracentrifugation and CAF-derived exosomal microRNAs were screened using next-generation sequencing technology. MiR-500a-5p expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization; Tumor cell proliferation was determined by MTT assays and three-dimensioned (3D) cultures, and tumor metastasis was determined by Transwell assays in vitro. In vivo assays were performed in a nude mouse subcutaneous xenograft model. Results: We confirmed that CAF-derived exosomes significantly promoted the proliferation and metastasis of breast cancer cells. MiR-500a-5p was highly expressed in MDA-MB-231 and MCF7 cells treated with CAF-derived exosomes. The upregulation of miR-500a-5p was also confirmed in CAFs and CAF-derived exosomes. MiR-500a-5p was transferred from CAFs to the cancer cells, and subsequently promoted proliferation and metastasis by binding to ubiquitin-specific peptidase 28 (USP28). Conclusions: The present study demonstrates that CAFs promote breast cancer progression and metastasis via exosomal miR-500a-5p and indicate that inhibiting CAF-derived miR-500a-5p is an alternative modality for the treatment of breast cancer.
Abstract PS19-13: Palmitate exacerbates breast tumorigenesis in vitro via induction of a senescent-like phenotype in fibroblasts
Authors: Brittany Susanne Harlow, Albert Davalos, Andrew Brenner, Christopher Jolly, Stefano Tiziani, Steve Hursting, Linda deGraffenried
Journal: Cancer Research (2021)

Abstract Background: Obesity is associated with a worse breast cancer prognosis, conferring an increased risk of recurrence and mortality. At the same time, recent evidence suggests that obesity is also correlated with development of cellular senescence, an inflammatory state associated with exacerbation of breast tumorigenesis in preclinical models. As obese individuals present greater levels of inflammation at baseline, research efforts are warranted to examine the means by which obesity promotes the development of a senescent phenotype, which may further exacerbate inflammation. Additionally, studies have yet to determine whether obesity-induced senescence modulates the tumorigenic process in the context of breast cancer specifically. Methods: To this end, we exposed fibroblasts to the obesity-associated circulating factor palmitate and used qPCR and western immunoblotting to assess the expression of genes and proteins involved in the senescent state, including interleukin (IL)-1a, IL-6, IL-8, senescence-associated beta-galactosidase (SA-beta-gal), and matrixmetalloproteinase (MMP)-9. As a mechanistic investigation, we next assessed the impact of palmitate on activation of NF-kB signaling using western immunoblotting, immunofluorescence, and NF-kB luciferase reporter assays. Finally, we utilized cell counting, MTT, wound healing, and colony formation assays to examine the impact of these palmitate-exposed fibroblasts on breast cancer cell proliferation, viability, motility, and survival, respectively. Results: We found that palmitate induced fibroblast gene expression of IL-1a, IL-6, and IL-8, major components of the senescent secretome, as well as expression of the senescent markers SA-beta-gal and MMP-9. The mechanism at least partially involved activation of NF-kB, responsible for production of about 75% of senescent secretome components. More importantly, these palmitate-exposed fibroblasts were of pathological impact, exacerbating in vitro measures of breast cancer cell aggressiveness. Conclusions: These findings contribute to our understanding of the impact of obesity-associated factors on breast tumorigenesis, demonstrating a mechanistic link between palmitate and the pro-tumorigenic effects of senescent cells. Our studies will ultimately aid in the identification of a therapeutic target that can be used to improve the comparably worse outcomes of the obese breast cancer patient. Citation Format: Brittany Susanne Harlow, Albert Davalos, Andrew Brenner, Christopher Jolly, Stefano Tiziani, Steve Hursting, Linda deGraffenried. Palmitate exacerbates breast tumorigenesis in vitro via induction of a senescent-like phenotype in fibroblasts [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-13.
Abstract PS2-22: The sensitivity and specificity of routine breast cancer pathology based on breast core biopsies compared with pathology based on surgical resections
Authors: Claudia Lundgren, Fanny Sjöberg, Helena Olofsson, Henrik Lindman
Journal: Cancer Research (2021)

Abstract Background: Several studies have reported good or reasonable concordance of biomarker panel based on core needle biopsies (CNB) and the pathology based on the surgical specimen (SS). However, as neoadjuvant therapy (NAC) is becoming more common, the result from the preoperative CNB is crucial as it is the only source for the subtyping of the breast tumor. Incorrect results of subtype could result in suboptimal choice of NAC. The aim of this study was to estimate the sensitivity and specificity of biomarkers and surrogate subtypes based on CNB compared with the surgical specimen (SS) in a three-year cohort of primary breast cancer patients diagnosed at Uppsala University Hospital. Patients and Methods: We collected data from all patients diagnosed with breast cancer at the University Hospital Uppsala, between 1st of September 2015 and 31st of August 2018 (n=837). Of these, 319 primary operated tumors were available with full biomarker information on CNB and SS. An additional 71 tumors from patients treated with NAC could be identified (not reported). Histopathological results from CNB and SS (n= 319) were used to divide the tumors in five subtypes; luminal A, luminal B, triple negative (TNBC), HER2-luminal and HER2 non-luminal. Results: The sensitivity/specificity of CNB for the expression of estrogen receptor was 100%/100%, progesterone receptor 96%/77%, HER2 by IHC3+ 77%/99%, Grade 3 49%/89% and high Ki67 72%/78%. The sensitivity and specificity of CNB and SS in subtype TNBC and HER2 non-luminal subtypes was 100%. Out of 37 cases with HER2-luminal subtype, 27 were correctly diagnosed by CNB (sensitivity 73%, specificity 100%). The sensitivity for correct diagnosis of luminal A was 76% with a specificity of 83% and luminal B subtype had a sensitivity of 74% and 99% specificity. Conclusions CNB was very reliable in defining TNBC and HER2 non-luminal subtypes, but less accurate in diagnosing luminal subtypes. There is a clear risk for underdiagnosis of HER2-luminal tumors. These patients might therefore receive suboptimal treatment when treated with NAC. Citation Format: Claudia Lundgren, Fanny Sjöberg, Helena Olofsson, Henrik Lindman. The sensitivity and specificity of routine breast cancer pathology based on breast core biopsies compared with pathology based on surgical resections [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-22.