tbuckley/cabot-search huggingface dataset:
PTHrP Drives Pancreatic Cancer Growth and Metastasis and Reveals a New Therapeutic Vulnerability
Authors: Jason R. Pitarresi, Robert J. Norgard, Anna M. Chiarella, Kensuke Suzuki, Basil Bakir, Varun Sahu, Jinyang Li, Jun Zhao, Benoît Marchand, Maximilian D. Wengyn, Antony Hsieh, Il-Kyu Kim, Amy Zhang, Karine Sellin, Vivian Lee, Shigetsugu Takano, Yoji Miyahara, Masayuki Ohtsuka, Anirban Maitra, Faiyaz Notta, Richard Kremer, Ben Z. Stanger, Anil K. Rustgi
Journal: Cancer Discovery (2021)

Abstract Pancreatic cancer metastasis is a leading cause of cancer-related deaths, yet very little is understood regarding the underlying biology. As a result, targeted therapies to inhibit metastasis are lacking. Here, we report that the parathyroid hormone–related protein (PTHrP encoded by PTHLH) is frequently amplified as part of the KRAS amplicon in patients with pancreatic cancer. PTHrP upregulation drives the growth of both primary and metastatic tumors in mice and is highly enriched in pancreatic ductal adenocarcinoma metastases. Loss of PTHrP—either genetically or pharmacologically—dramatically reduces tumor burden, eliminates metastasis, and enhances overall survival. These effects are mediated in part through a reduction in epithelial-to-mesenchymal transition, which reduces the ability of tumor cells to initiate metastatic cascade. Spp1, which encodes osteopontin, is revealed to be a downstream effector of PTHrP. Our results establish a new paradigm in pancreatic cancer whereby PTHrP is a driver of disease progression and emerges as a novel therapeutic vulnerability. Significance: Pancreatic cancer often presents with metastases, yet no strategies exist to pharmacologically inhibit this process. Herein, we establish the oncogenic and prometastatic roles of PTHLH, a novel amplified gene in pancreatic ductal adenocarcinoma. We demonstrate that blocking PTHrP activity reduces primary tumor growth, prevents metastasis, and prolongs survival in mice. This article is highlighted in the In This Issue feature, p. 1601
Consequences of the COVID-19 pandemic for patients with metabolic diseases
Authors: Stefan R. Bornstein, Francesco Rubino, Barbara Ludwig, Hannes Rietzsch, Peter E. H. Schwarz, Roman N. Rodionov, Kamlesh Khunti, David Hopkins, Andreas L. Birkenfeld, Bernhard Boehm, Stephanie Amiel, Richard I. G. Holt, Jay S. Skyler, J. Hans DeVries, Eric Renard, Robert H. Eckel, Paul Zimmet, K. G. Alberti, Bruno Geloneze, Juliana C. Chan, Jean Claude Mbanya, Henry C. Onyegbutulem, Ambady Ramachandran, Abdul Basit, Mohamed Hassanein, Giatgen A. Spinas, Felix Beuschlein, Geltrude Mingrone
Journal: Nature Metabolism (2021)
Abstract 10322: Molecular Magnetic Resonance Imaging Allows in Vivo Evaluation of Ischemia-reperfusion Injury by Simultaneous Targeting of Activated Platelets and Myocardial Necrosis in Mice
Authors: Alexander Maier, Daniel Dürschmied, Dominik von Elverfedlt, Moritz Braig, Timo Heidt, Irene Neudorfer, Karlheinz Peter, Christoph Bode, Constantin von zur Muhlen
Journal: Circulation (2013)

Introduction: Inflammation and myocardial necrosis play important pathophysiological roles in ischemia-reperfusion injury after coronary artery occlusion. Detection of inflammatory activity by acti...
The lack of robust evidence for cleansing effects
Authors: Ivan Ropovik, Alessandro Sparacio, Hans IJzerman
Journal: Behavioral and Brain Sciences (2021)

Abstract The pattern of data underlying the successful replications of cleansing effects is improbable and most consistent with selective reporting. Moreover, the meta-analytic approach presented by Lee and Schwarz is likely to find an effect even if none existed. Absent more robust evidence, there is no need to develop a theoretical account of grounded procedures.
Applications of digital health for public health responses to COVID-19: a systematic scoping review of artificial intelligence, telehealth and related technologies
Authors: Dinesh Visva Gunasekeran, Rachel Marjorie Wei Wen Tseng, Yih-Chung Tham, Tien Yin Wong
Journal: npj Digital Medicine (2021)

Abstract The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed healthcare services, faced with the twin challenges in acutely meeting the medical needs of patients with COVID-19 while continuing essential services for non-COVID-19 illnesses. The need to re-invent, re-organize and transform healthcare and co-ordinate clinical services at a population level is urgent as countries that controlled initial outbreaks start to experience resurgences. A wide range of digital health solutions have been proposed, although the extent of successful real-world applications of these technologies is unclear. This study aims to review applications of artificial intelligence (AI), telehealth, and other relevant digital health solutions for public health responses in the healthcare operating environment amidst the COVID-19 pandemic. A systematic scoping review was performed to identify potentially relevant reports. Key findings include a large body of evidence for various clinical and operational applications of telehealth (40.1%, n = 99/247). Although a large quantity of reports investigated applications of artificial intelligence (AI) (44.9%, n = 111/247) and big data analytics (36.0%, n = 89/247), weaknesses in study design limit generalizability and translation, highlighting the need for more pragmatic real-world investigations. There were also few descriptions of applications for the internet of things (IoT) (2.0%, n = 5/247), digital platforms for communication (DC) (10.9%, 27/247), digital solutions for data management (DM) (1.6%, n = 4/247), and digital structural screening (DS) (8.9%, n = 22/247); representing gaps and opportunities for digital public health. Finally, the performance of digital health technology for operational applications related to population surveillance and points of entry have not been adequately evaluated.
Abstract 14996: Effectiveness of Cardiac Resynchronization Therapy in Patients with End-Stage Phase of Hypertrophic Cardiomyopathy: Comparison with Idiopathic Dilated Cardiomyopathy
Authors: Ikutaro Nakajima, Takashi Noda, Koji Miyamoto, Yuko Yamada, Hideo Okamura, Kazuhiro Satomi, Takeshi Aiba, Wataru Shimizu, Naohiko Aihara, Shiro Kamakura
Journal: Circulation (2011)

Background: Evolution into dilated-hypokinetic phase of hypertrophic cardiomyopathy (D-HCM) represents an ominous change. Generally, patients with D-HCM were thought to be refractory to intensive m...
Individual Differences in Response to Antidepressants
Authors: Marta M. Maslej, Toshiaki A. Furukawa, Andrea Cipriani, Paul W. Andrews, Marcos Sanches, Anneka Tomlinson, Constantin Volkmann, Robert A. McCutcheon, Oliver Howes, Xin Guo, Benoit H. Mulsant
Journal: JAMA Psychiatry (2021)

Antidepressants are commonly used to treat major depressive disorder (MDD). Antidepressant outcomes can vary based on individual differences; however, it is unclear whether specific factors determine this variability or whether it is at random.To investigate the assumption of systematic variability in symptomatic response to antidepressants and to assess whether variability is associated with MDD severity, antidepressant class, or study publication year.Data used were updated from a network meta-analysis of treatment with licensed antidepressants in adults with MDD. The Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, and PsycInfo were searched from inception to March 21, 2019. Additional sources were international trial registries and sponsors, drug companies and regulatory agencies' websites, and reference lists of published articles. Data were analyzed between June 8, 2020, and June 13, 2020.Analysis was restricted to double-blind, randomized placebo-controlled trials with depression scores available at the study's end point.Baseline means, number of participants, end point means and SDs of total depression scores, antidepressant type, and publication year were extracted.Log SDs (bln σ̂) were derived for treatment groups (ie, antidepressant and placebo). A random-slope mixed-effects model was conducted to estimate the difference in bln σ̂ between treatment groups while controlling for end point mean. Secondary models determined whether differences in variability between groups were associated with baseline MDD severity; antidepressant class (selective serotonin reuptake inhibitors and other related drugs; serotonin and norepinephrine reuptake inhibitors; norepinephrine-dopamine reuptake inhibitors; noradrenergic agents; or other antidepressants); and publication year.In the 91 eligible trials (18 965 participants), variability in response did not differ significantly between antidepressants and placebo (bln σ̂, 1.02; 95% CI, 0.99-1.05; P = .19). This finding is consistent with a range of treatment effect SDs (up to 16.10), depending on the association between the antidepressant and placebo effects. Variability was not associated with baseline MDD severity or publication year. Responses to noradrenergic agents were 11% more variable than responses to selective serotonin reuptake inhibitors (bln σ̂, 1.11; 95% CI, 1.01-1.21; P = .02).Although this study cannot rule out the possibility of treatment effect heterogeneity, it does not provide empirical support for personalizing antidepressant treatment based solely on total depression scores. Future studies should explore whether individual symptom scores or biomarkers are associated with variability in response to antidepressants.
Abstract 14983: Impact of Hypertrophic Cardiomyopathy on Predicting Thromboembolism or Death in Non-valvular Atrial Fibrillation Under Anticoagulant Therapy
Authors: Toyonobu Tsuda, Kenshi Hayashi, Tetsuo Konno, Akihiro Nomura, Yoshihiro Tanaka, Yoji Nagata, Ryota Teramoto, Kenji Sakata, Noboru Fujino, Hiroshi Furusho, Masayuki Takamura, Masa-aki Kawashiri, Masakazu Yamagishi
Journal: Circulation (2017)

Introduction: Previous reports showed that dilated or hypertrophic cardiomyopathy can be a risk of thromboembolism. However, it has been still uncertain if the presence of HCM itself can be a risk ...
Abstract P156: Effect of Socioeconomic and Demographic Factors on Control of Cardiovascular Risk in Elderly Hispanics
Authors: Adriana J Higuera, David E Timaran, Eric B Rosero, Carlos H Timaran
Journal: Circulation (2012)

Introduction: In elderly Hispanics, the causes contributing to poor control of cardiovascular risk factors (CRF) are not well understood. The purpose of this study was to assess the effect of demographic and socioeconomic factors on CRF control among non-institutionalized elderly Hispanics. Methods: A prospective cohort of 350 elderly Hispanics was studied. A face-to-face interview was conducted to obtain data on comorbidities and demographic and socioeconomic characteristics. Anthropometric and blood pressure measurements were obtained for all participants. Fasting blood samples were collected to assess levels of blood glucose, LDL, HDL and total cholesterol. Univariate and logistic regression analyses were performed to test whether socioeconomic and demographic characteristics were independently associated with adequate control of hypertension, dyslipidemia, and diabetes. Results: Most subjects (72.5%) were women. Median age was 71 (interquartile range, 64-79) years. The prevalence of hypertension, diabetes, and dyslipidemia was 68%, 65%, and 64%, respectively. Of these, 93% of hypertensive, 87% of diabetics, and 78% of dyslipidemic subjects were on pharmacologic treatment. Adequate control of the CRF was achieved in 33%, 70%, and 68% of hypertensive, diabetic, and dyslipidemic subjects, respectively. In general, 63.5% of the subjects had at least one risk factor not controlled. Univariate analyses revealed that only the level of trust in the health care system was significantly associated with adequate control of dyslipidemia ( P =0.03) but not with control of the other risk factors. Multivariate analyses revealed that level of education (odds ratio [OR], 0.92; 95% confidence interval [95%CI], 0.86-0.99; P =0.03) and understanding of information obtained from health care provider (OR, 1.48; 95% CI, 1.01-2.1; P =0.04) were independently associated with adequate control of blood pressure. No other significant associations were found. Conclusions: Despite high rates of treatment, elderly Hispanics in our cohort exhibit poor control of cardiovascular risk factors. Demographic and socioeconomic characteristics do not seem to have a strong effect on CRF control among elderly Hispanics.
Severe clinical relapse in an immunocompromised host with persistent SARS-CoV-2 infection
Authors: Philipp A. Reuken, Andreas Stallmach, Mathias W. Pletz, Christian Brandt, Nico Andreas, Sabine Hahnfeld, Bettina Löffler, Sabine Baumgart, Thomas Kamradt, Michael Bauer
Journal: Leukemia (2021)
Maternal Stroke: A Call for Action.
Authors: Islam Y Elgendy, Syed Bukhari, Amr F Barakat, Carl J Pepine, Kathryn J Lindley, Eliza C Miller
Journal: Circulation (2021)

Maternal mortality rates have been steadily increasing in the United States, and cardiovascular mortality is the leading cause of death among pregnant and postpartum women. Maternal stroke accounts for a significant burden of cardiovascular mortality. Data suggest that rates of maternal stroke have been increasing in recent years. Advancing maternal age at the time of birth and the increasing prevalence of traditional cardiovascular risk factors, and other risk factors, as well, such as hypertensive disorders of pregnancy, migraine, and infections, may contribute to increased rates of maternal stroke. In this article, we provide an overview of the epidemiology of maternal stroke, explore mechanisms that may explain increasing rates of stroke among pregnant women, and identify key knowledge gaps for future investigation in this area.
Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment
Authors: Hilma J. van der Horst, A. Vera de Jonge, Ida H. Hiemstra, Anne T. Gelderloos, Daniella R. A. I. Berry, Nathalie J. Hijmering, Hendrik F. van Essen, Daphne de Jong, Martine E. D. Chamuleau, Sonja Zweegman, Esther C. W. Breij, Margaretha G. M. Roemer, Tuna Mutis
Journal: Blood Cancer Journal (2021)

Abstract Epcoritamab (DuoBody-CD3xCD20, GEN3013) is a novel bispecific IgG1 antibody redirecting T-cells toward CD20 + tumor cells. Here, we assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed (ND) and relapsed/refractory (RR) B-NHL patients. In the presence of T-cells from a healthy donor, epcoritamab demonstrated potent activity against primary tumor cells, irrespective of prior treatments, including CD20 mAbs. Median lysis of 65, 74, and 84% were achieved in diffuse large B-cell lymphoma ( n = 16), follicular lymphoma ( n = 15), and mantle cell lymphoma ( n = 8), respectively. Furthermore, in this allogeneic setting, we discovered that the capacity of B-cell tumors to activate T-cells was heterogeneous and showed an inverse association with their surface expression levels of the immune checkpoint molecule Herpesvirus Entry Mediator (HVEM). In the autologous setting, when lymph node (LN)-residing T-cells were the only source of effector cells, the epcoritamab-dependent cytotoxicity strongly correlated with local effector cell-to-target cell ratios. Further analyses revealed that LN-residing-derived or peripheral blood-derived T-cells of B-NHL patients, as well as heathy donor T-cells equally mediated epcoritamab-dependent cytotoxicity. These results show the promise of epcoritamab for treatment of newly-diagnosed or relapsed/refractory B-NHL patients, including those who became refractory to previous CD20-directed therapies.
Precisely Tuned Inhibition of HIF Prolyl Hydroxylases Is Key for Cardioprotection After Ischemia
Authors: Aline Jatho, Anke Zieseniss, Katja Brechtel-Curth, Atsushi Yamamoto, Mathew L. Coleman, Ana M. Vergel Leon, Daniel Biggs, Ben Davies, Chris W. Pugh, Peter J. Ratcliffe, Dörthe M. Katschinski
Journal: Circulation Research (2021)
Covid-19: Recognise long covid as occupational disease and compensate frontline workers, say MPs
Authors: Matthew Limb
Journal: BMJ (2021)

Recognise long covid as occupational disease and compensate frontline workers, say MPs Matthew LimbMPs have stepped up pressure on ministers to recognise "long covid" as an occupational disease and to compensate frontline health and other key workers living with its "debilitating" effects.
A Validation Study of the Recommended Change in Residual Tumor Descriptors Proposed by the International Association for the Study of Lung Cancer for Patients With pN2 NSCLC
Authors: Jae Kwang Yun, Geun Dong Lee, Sehoon Choi, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park, Hyeong Ryul Kim
Journal: Journal of Thoracic Oncology (2021)
Abstract 16460: Differential Effect of the Emory Risk Score on Early versus Late Pacemaker Implantation in TAVR Patients
Authors: NACHIKET MADHAV APTE, Farhad Sami, AMIT SHRESHTA, Tarun Dalia, Sagar Ranka, ALEX COURTNEY, Eric S Hockstad, MUELHEBACH GREGORY, George Zorn, Mark A Wiley, Martin Emert, Rigoberto Ramirez, Raghuveer Dendi, Seth Sheldon, Madhu Reddy, PETER TADROS, Rhea C Pimentel
Journal: Circulation (2020)

Introduction: The Emory risk score has been developed to predict new pacemaker implantation in patients undergoing TAVR procedures. There is limited data on assessing risk of early versus late pacemaker implantation in these patients. Hypothesis: The Emory risk score is similar for patients with both early and late pacemaker implantation in TAVR patients. Methods: A single center observational study was performed at our tertiary care center. All patients who underwent pacemaker implantation after TAVR procedures were included. Patients were categorized as early or late if they had pacemaker implantation within the same admission versus implantation post discharge. Standard statistical tests were used for analysis with two-sided p value &lt;0.05 considered significant. IRB approval was obtained for the study Results: A total of 97 patients were studied between January 2017 to April 2020. The mean age was 77.5 ± 7 years and females were 41.2%. At baseline patients with early implantation of pacemakers (n=66) had a higher proportion of underlying RBBB (45.2% vs 23.3%, p=0.43), higher valve size as well as a higher incidence of valve oversizing &gt; 146% (43.9 % vs 19.4 %, p =0.23)when compared to patients with late pacemakers(n=31). There was no difference between patient characteristics, baseline comorbidities, pre procedural ECG parameters as well as use of beta blocking agents. Late pacemaker implantations were associated with a overall lower Emory Risk score (1.06±1.41 vs 1.70±1.35, p =0.037). Conclusions: The Emory Risk score is significantly different for early and late pacemaker implantation. Further studies are needed evaluate risk of late pacemaker implantation.
In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy
Authors: Linda Petrone, Elisa Petruccioli, Tonino Alonzi, Valentina Vanini, Gilda Cuzzi, Saeid Najafi Fard, Concetta Castilletti, Fabrizio Palmieri, Gina Gualano, Pietro Vittozzi, Emanuele Nicastri, Luciana Lepore, Alba Grifoni, Andrea Antinori, Alessandra Vergori, Giuseppe Ippolito, Fabrizio Cantini, Delia Goletti
Journal: Journal of Infection (2021)

Baricitinib seems a promising therapy for COVID-19. To fully-investigate its effects, we in-vitro evaluated the impact of baricitinib on the SARS-CoV-2-specific-response using the whole-blood platform.
Abstract PS17-29: Surgically induced weight loss corrects obesity associated tumor progression and improves responsiveness to immunotherapy
Authors: Laura Sipe, Mehdi Chaib, Emily B Korba, Mary C Lovely, Jared C Clements, Neena A John, Ajeeth K Pingili, Joseph F Pierre, Liza Makowski
Journal: Cancer Research (2021)

Abstract Background: Obesity leads to a higher risk of cancer invasion, metastases, recurrence, mortality, and impaired therapeutic response through various mechanisms. One of these mechanisms is microenvironment dysfunction, where changes in immune cells, microbes, metabolites, and growth factors contribute to tumor aggressiveness. We study obesity-induced changes to the tumor microenvironment in Triple Negative Breast Cancer (TNBC), an aggressive subtype associated with obesity. The goal to compare tumor progression in lean vs. obese vs. weight loss manipulations to identify causal and targetable pathways associated with reprogramming the tumor microenvironment. Clinically, bariatric surgery induced weight loss reduced the risk of BC, with the greatest benefit detected in pre-menopausal patients with ER- tumors, like TNBC. We hypothesize surgically-induced weight loss will diminish obesity-associated tumor progression. Methods: To study weight gain and loss that best mimics human adiposity, we utilized obesogenic C57BL/6 females with a syngeneic orthotopic transplant of TNBC cells. Female mice placed on a high fat diet (HFD) at weaning became obese compared to mice on a low fat diet (LFD). After 16 weeks on an HFD diet, mice underwent the bariatric surgery Vertical Sleeve Gastrectomy (VSG). The VSG resulted in reduced body weight, adiposity, and correction of metabolic profiles compared to obese mice. Two weeks post-surgery, TNBC cells were OT into the mammary fat. Results: As expected, tumor growth was increased in obese mice compared to lean. Importantly, surgical weight loss rescued obese tumor progression. We identified key changes in tumor infiltrating of immune cells that could be responsible for the beneficial effects of bariatric surgery on tumor progression. We then exploited these changes with immunotherapy, which was uniquely effective in mice that underwent bariatric surgery. Conclusions: In conclusion obesity promotes a pro-tumor microenvironment, that can be corrected through surgically induced weight loss. Citation Format: Laura Sipe, Mehdi Chaib, Emily B Korba, Mary C Lovely, Jared C Clements, Neena A John, Ajeeth K Pingili, Joseph F Pierre, Liza Makowski. Surgically induced weight loss corrects obesity associated tumor progression and improves responsiveness to immunotherapy [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 PS17-29.