tbuckley/cabot-search huggingface dataset:
Quality of Life and Patient Satisfaction After Antibiotic Therapy vs Appendectomy for Uncomplicated Appendicitis
Authors: Peter C. Minneci, Katherine J. Deans
Journal: JAMA Surgery (2020)

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Abstract P460: Genetic Risk for Obesity Across the Transition From Young to Older Adulthood: A Pathway Based Analysis
Authors: Ruixue Hou, Annie Green Howard, Hsiao-Chuan Tien, Mariaelisa Graff, Wei Huang, Jinxiu Shi, Haifeng Wang, Penny Gordon-larsen
Journal: Circulation (2020)

Background: Genetics and lifestyle behaviors are key contributors to obesity. However, few studies explicitly examine the differential genetic association with BMI across critical lifecycle periods between young adulthood and later adulthood. Hypothesis: We anticipate that genetic risk will be directly associated with BMI in young adulthood and there will be a strong indirect association with BMI later in life, as a result the increased risk of BMI associated with young adulthood. Methods: For 7,397 Chinese adult participants (age 18 to 65y) of the China Health and Nutrition Survey (CHNS; 1991-2015), we calculated an obesity polygenic risk score (PRS) based on BMI-related SNPs selected from the largest BMI GWAS in 700,000 individuals of European ancestry from UK biobank and GIANT consortium, weighted by effect size estimated from the GWAS study. We used linear mixed models to estimate BMI across all periods of adulthood, adjusting for calendar time and sex. In a subsample of participants with three measurements across 24 years (n=1220), we used pathway based analysis to estimate the direct effects of genetic risk in association with BMI during young (18-35y), middle (35-45y), and later (45-65y) adulthood as well as the indirect genetic effects of at later adulthood through BMI at each of these earlier periods in life. Results: In the full sample, the linear mixed model-adjusted mean BMI (Standard Error (SE)) was 22.4 (0.04) kg/m 2 at young adulthood, 23.1 (0.04) kg/m 2 at middle adulthood and 23.2 (0.04) kg/m 2 at later adulthood, adjusting for sex and calendar year. In the subsample, a one standard deviation higher obesity PRS was directly associated with a 0.38 (0.07 SE) and 0.21 (0.06 SE) kg/m 2 higher BMI in young and middle adulthood, respectively. We found no evidence of a direct estimated effect of PRS in later adulthood (age 45-64y), but evidence of an indirect association between obesity PRS and BMI in later adulthood (age 45-64y). For example, we found a one standard deviation higher PRS was indirectly associated with 0.31 (0.06 SE) kg/m 2 higher BMI at age 35-45y through BMI at age 18-35y, and a 0.25 (0.05 SE) kg/m 2 higher BMI at age 45-65y through BMI at age 18-35y and subsequently BMI at age 35-45y. Conclusion: We observed a strong direct association between polygenic risk for obesity in young adulthood (age 18-35y), with persistence through age 35-45y and into age 45-65y.
Communicating Science in the Time of a Pandemic
Authors: Richard Saitz, Gary Schwitzer
Journal: JAMA (2020)

Communicating Science in the Time of a PandemicDuring the global SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, disseminating study findings (such as by preprints, news releases, news stories, or social media) and publishing the results of studies of testing and treatment in scientific journals increased quickly.As of July 6, a PubMed search for COVID-19 yielded almost 30 000 reports.In the context of a rapid increase in cases, hospitalizations, and deaths from COVID-19 (coronavirus disease 2019), clinicians, patients, policy makers, and the public at large are understandably eager for results of studies of prognosis, diagnosis, and treatment.Because of the urgency to implement the findings of research to stem the pandemic and its effects, clear and complete communication of study results is even more important than usual. Communication Flaws and FailuresGovernmentreports,journalism,talkshows,andpublicrelations news releases from industry and academic institutions have often failed to communicate the results of studies well, and these failures have important consequences.Failures of communication include (1) a focus on single study results without the context of other studies or acknowledgment that single studies are rarely definitive; (2) overemphasis on results, particularly relative effects, without recognition of important limitations; and (3) communications based on incomplete reports of studies and reports of studies that have not been adequately reviewed.Communications regarding studies involving remdesivir, dexamethasone, and hydroxychloroquine illustrate some of these issues.
Epicardial Adipose Tissue and Invasive Hemodynamics in Heart Failure With Preserved Ejection Fraction
Authors: Thomas M. Gorter, Gijs van Woerden, Michiel Rienstra, Michael G. Dickinson, Yoran M. Hummel, Adriaan A. Voors, Elke S. Hoendermis, Dirk J. van Veldhuisen
Journal: JACC Heart Failure (2020)
O-9 Discordant prognostic significance of negative lymph node size in patients with oesophageal cancer treated with either surgery or neoadjuvant chemotherapy and surgery: Results from the MRC OE02 trial
Authors: M. Kloft, J. Ruisch, M. Nankivell, W. Allum, D. Cunningham, R. Langley, H. Grabsch
Journal: Annals of Oncology (2020)
Exploiting the Microhomology-Mediated End-Joining Pathway in Cancer Therapy
Authors: Jeffrey Patterson-Fortin, Alan D. D'Andrea
Journal: Cancer Research (2020)

Repair of DNA double-strand breaks (DSB) is performed by two major pathways, homology-dependent repair and classical nonhomologous end-joining. Recent studies have identified a third pathway, microhomology-mediated end-joining (MMEJ). MMEJ has similarities to homology-dependent repair, in that repair is initiated with end resection, leading to single-stranded 3' ends, which require microhomology upstream and downstream of the DSB. Importantly, the MMEJ pathway is commonly upregulated in cancers, especially in homologous recombination-deficient cancers, which display a distinctive mutational signature. Here, we review the molecular process of MMEJ as well as new targets and approaches exploiting the MMEJ pathway in cancer therapy.
Clinical Characteristics of Patients With Coronavirus Disease 2019 (COVID-19) Receiving Emergency Medical Services in King County, Washington
Authors: Betty Y. Yang, Leslie M. Barnard, Jamie M. Emert, Christopher Drucker, Leilani Schwarcz, Catherine R. Counts, David L. Murphy, Sally Guan, Kosuke Kume, Karen Rodriquez, Tracie Jacinto, Susanne May, Michael R. Sayre, Thomas Rea
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The ability to identify patients with coronavirus disease 2019 (COVID-19) in the prehospital emergency setting could inform strategies for infection control and use of personal protective equipment. However, little is known about the presentation of patients with COVID-19 requiring emergency care, particularly those who used 911 emergency medical services (EMS). <h3>Objective</h3> To describe patient characteristics and prehospital presentation of patients with COVID-19 cared for by EMS. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included 124 patients who required 911 EMS care for COVID-19 in King County, Washington, a large metropolitan region covering 2300 square miles with 2.2 million residents in urban, suburban, and rural areas, between February 1, 2020, and March 18, 2020. <h3>Exposures</h3> COVID-19 was diagnosed by reverse transcription–polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swabs. Test results were available a median (interquartile range) of 5 (3-9) days after the EMS encounter. <h3>Main Outcomes and Measures</h3> Prevalence of clinical characteristics, symptoms, examination signs, and EMS impression and care. <h3>Results</h3> Of the 775 confirmed COVID-19 cases in King County, EMS responded to 124 (16.0%), with a total of 147 unique 911 encounters. The mean (SD) age was 75.7 (13.2) years, 66 patients (53.2%) were women, 47 patients (37.9%) had 3 or more chronic health conditions, and 57 patients (46.0%) resided in a long-term care facility. Based on EMS evaluation, 43 of 147 encounters (29.3%) had no symptoms of fever, cough, or shortness of breath. Based on individual examination findings, fever, tachypnea, or hypoxia were only present in a limited portion of cases, as follows: 43 of 84 encounters (51.2%), 42 of 131 (32.1%), and 60 of 112 (53.6%), respectively. Advanced care was typically not required, although in 24 encounters (16.3%), patients received care associated with aerosol-generating procedures. As of June 1, 2020, mortality among the study cohort was 52.4% (65 patients). <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that screening based on conventional COVID-19 symptoms or corresponding examination findings of febrile respiratory illness may not possess the necessary sensitivity for early diagnostic suspicion, at least in the prehospital emergency setting. The findings have potential implications for early identification of COVID-19 and effective strategies to mitigate infectious risk during emergency care.
P-158 Clinical impact of oral intake in third-line treatment for advanced gastric cancer
Authors: T. Ogata, Y. Narita, R. Kumanishi, T. Nakazawa, Y. Matsubara, K. Kato, K. Nozawa, K. Honda, T. Masuishi, H. Bando, S. Kadowaki, M. Ando, M. Tajika, K. Muro
Journal: Annals of Oncology (2020)
Cellular Senescence Promotes Skin Carcinogenesis through p38MAPK and p44/42MAPK Signaling
Authors: Fatouma Alimirah, Tanya Pulido, Alexis Valdovinos, Sena Alptekin, Emily Chang, Elijah Jones, Diego A. Diaz, Jose Flores, Michael C. Velarde, Marco Demaria, Albert R. Davalos, Christopher D. Wiley, Chandani Limbad, Pierre-Yves Desprez, Judith Campisi
Journal: Cancer Research (2020)

Abstract Cellular senescence entails an irreversible growth arrest that evolved in part to prevent cancer. Paradoxically, senescent cells secrete proinflammatory and growth-stimulatory molecules, termed the senescence-associated secretory phenotype (SASP), which is correlated with cancer cell proliferation in culture and xenograft models. However, at what tumor stage and how senescence and the SASP act on endogenous tumor growth in vivo is unknown. To understand the role of senescence in cancer etiology, we subjected p16-3MR transgenic mice, which permit the identification and selective elimination of senescent cells in vivo, to the well-established two-step protocol of squamous cell skin carcinoma, in which tumorigenesis is initiated by a carcinogen 7,12-dimethylbenz[α]anthracene, and then promoted by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We show that TPA promotes skin carcinogenesis by inducing senescence and a SASP. Systemic induction of senescence in nontumor-bearing p16-3MR mice using a chemotherapy followed by the two-step carcinogenesis protocol potentiated the conversion of benign papillomas to carcinomas by elevating p38MAPK and MAPK/ERK signaling. Ablation of senescent cells reduced p38MAPK and MAPK/ERK signaling, thereby preventing the progression of benign papillomas to carcinomas. Thus, we show for the first time that senescent cells are tumor promoters, not tumor initiators, and that they stimulate skin carcinogenesis by elevating p38MAPK and MAPK/ERK signaling. These findings pave the way for developing novel therapeutics against senescence-fueled cancers. Significance: These findings identify chemotherapy-induced senescence as a culprit behind tumor promotion, suggesting that elimination of senescent cells after chemotherapy may reduce occurrence of second cancers decades later.
Physician mothers of children with complex needs: untapped wisdom, resilience, and a hidden workforce
Authors: Raka Maitra
Journal: BMJ (2020)

In 2018 a research paper and linked editorial discussed the challenges and discrimination faced by physician mothers.12 Physician mothers who have children with complex needs do not find their voices in the literature, hear their stories of resilience, or know of avenues where their insights could enrich healthcare delivery and leadership. In the NHS workforce, clinicians with children with complex needs …
Abstract 15005: Efficacy and Safety of Percutaneous Coronary Interventions Using Titanium-Nitride-Oxide Coated Bioactive Stents versus Drug-Eluting Stents in Coronary Artery Disease. A Systematic Literature Review and Meta-Analysis
Authors: Frederic Daoud, Louis Letinier, Nicholas Moore, Pierre Coste, Pasi karjalainen
Journal: Circulation (2018)

Introduction: Drug-eluting stents (DES) have mostly replaced bare-metal stents in percutaneous coronary interventions (PCI). Platforms and Eluted drugs have evolved to improve efficacy and reduce a...
Phospho BAD decreases breast cancer cell proliferation by inhibiting c-jun activation of the CRE in cyclin D1
Authors: Romaine I. Fernando, Jay Wimalasena
Journal: Cancer Research (2005)

5417  Previously we had shown that BAD plays a critical role in apoptosis of MCF-7 breast CA cells (MBC, 15:3266,2004). Recently we have observed that BAD is a regulator of cell proliferation in the MCF-7 cell line (AACR 2004 Abs# 4824). App 20% of endogenous BAD is localized in the nucleus. Phosphorylated (p) BAD (S136) can also be observed in the nucleus where as both S136 and S112 pBAD is localized in the nuclear fraction upon over expression of wild type (wt) BAD. Over expressed wtBAD inhibited E2 induced proliferation fraction (PF) but dual phosphorylation site mutant (S136A/S112A (dmBAD)) did not. Removal of endogenous BAD by specific siRNA appeared to increase PF following E2 treatment. Endogenous cyclin D1 (CD1) was also increased by siRNA for BAD. WtBAD but not dmBAD inhibited serum or E2 stimulated CD1 synthesis. Using CRE and AP-1 mutants of the CD1 reporter we found that BAD inhibits expression of CD1 mainly through the CRE element, whereas dmBAD was ineffective. This inhibition appears to be mediated by the ability of wtBAD but not dmBAD to interact with c-jun. BAD appears to inhibit phospho c-jun formation by inhibiting Erk as well as JNK. Thus we demonstrate a novel role for BAD in cell cycle regulation which is dependent on phosphorylation of S112/136 residues but not on BAD/BCL2 interaction. (supported by NIH)
Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines
Authors: Manuel Valiente, Amanda E.D. Van Swearingen, Carey K. Anders, Amos Bairoch, Adrienne Boire, Paula D. Bos, Diana M. Cittelly, Neta Erez, Gino B. Ferraro, Dai Fukumura, Brunilde Gril, Meenhard Herlyn, Sheri L. Holmen, Rakesh K. Jain, Johanna A. Joyce, Mihaela Lorger, Joan Massague, Josh Neman, Nicola R. Sibson, Patricia S. Steeg, Frits Thorsen, Leonie S. Young, Damir Varešlija, Adina Vultur, Frances Weis-Garcia, Frank Winkler
Journal: Cancer Research (2020)

Abstract Spread of cancer to the brain remains an unmet clinical need in spite of the increasing number of cases among patients with lung, breast cancer, and melanoma most notably. Although research on brain metastasis was considered a minor aspect in the past due to its untreatable nature and invariable lethality, nowadays, limited but encouraging examples have questioned this statement, making it more attractive for basic and clinical researchers. Evidences of its own biological identity (i.e., specific microenvironment) and particular therapeutic requirements (i.e., presence of blood–brain barrier, blood–tumor barrier, molecular differences with the primary tumor) are thought to be critical aspects that must be functionally exploited using preclinical models. We present the coordinated effort of 19 laboratories to compile comprehensive information related to brain metastasis experimental models. Each laboratory has provided details on the cancer cell lines they have generated or characterized as being capable of forming metastatic colonies in the brain, as well as principle methodologies of brain metastasis research. The Brain Metastasis Cell Lines Panel (BrMPanel) represents the first of its class and includes information about the cell line, how tropism to the brain was established, and the behavior of each model in vivo. These and other aspects described are intended to assist investigators in choosing the most suitable cell line for research on brain metastasis. The main goal of this effort is to facilitate research on this unmet clinical need, to improve models through a collaborative environment, and to promote the exchange of information on these valuable resources.
Abstract 12523: Color M-Mode Echocardiography Derived Left Ventricular Diastolic Indices in Infants Strongly Correlate With Left Ventricular Linear Dimensions
Authors: Collin T Erickson, Brett Meyers, Ling Li, Mary Craft, Pavlos Vlachos, David A Danford, Shelby Kutty
Journal: Circulation (2018)

Introduction: Color M-mode (CMM) has been shown to be a reliable method to assess ventricular diastolic function in adults. We analyzed left ventricular (LV) diastology in children from birth to tw...
P-153 Novel ultrasonographic scoring system of sinusoidal obstruction syndrome associated with oxaliplatin-based chemotherapy in patients with gastrointestinal cancer
Authors: R. Saito, M. Nishida, T. Iwai, Y. Kikuchi, Y. Yoshino, I. Yokota, R. Takagi, Y. Kawamoto, K. Ito, S. Nakano, H. Nakatsumi, S. Yuki, Y. Komatsu, N. Sakamoto
Journal: Annals of Oncology (2020)
Perturbation of Specific Signaling Pathways Is Involved in Initiation of Mouse Liver Fibrosis
Authors: Liping Chen, Ping Guo, Wenxue Li, Fei Fang, Wei Zhu, Junling Fan, Fangping Wang, Yuanyuan Gao, Qun Zhao, Qing Wang, Yongmei Xiao, Xiumei Xing, Daochuan Li, Tieliu Shi, Dianke Yu, Michael Aschner, Lihua Zhang, Wen Chen
Journal: Hepatology (2020)

Background and Aims To identify the regulatory role of protein phosphatase 2A (PP2A) in the development of liver disease, we generated a mouse model with hepatocyte‐specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit). Approach and Results Homozygote (HO) mice and matched wild‐type littermates were investigated at 3, 6, 9, 12, 15, and 18 months of age. Pathological examination showed that PP2A Aα deficiency in hepatocytes resulted in progressive liver fibrosis phenotype from 9 months of age. No hepatocyte death was observed in HO mice. However, perturbation of pathways including epidermal growth factor receptor 1 (EGFR1), amino acid metabolism, and translation factors as well as leptin and adiponectin led to pronounced hepatic fibrosis. In vitro studies demonstrated the involvement of specific B subunit complexes in the regulation of EGFR1 signaling pathway and cross talk between defected hepatocytes and stimulation of interstitial hyperplasia. It is noteworthy that HO mice failed to develop hepatocellular carcinoma for as long as 22 months of age. We further demonstrate that PP2A Aβ–containing holoenzymes played a critical role in preventing hepatocyte apoptosis and antagonizing tumorigenesis through specific pathways on Aα loss. Furthermore, PP2A Aα and Aβ were functionally distinct, and the Aβ isoform failed to substitute for Aα in the development of inflammation and liver fibrosis. Conclusions These observations identify pathways that contribute to the pathogenesis of liver fibrosis and provide putative therapeutic targets for its treatment.
Human inborn errors of immunity: An expanding universe
Authors: Luigi D. Notarangelo, Rosa Bacchetta, Jean-Laurent Casanova, Helen C. Su
Journal: Science Immunology (2020)

Molecular, cellular, and clinical studies of human inborn errors of immunity have revolutionized our understanding of their pathogenesis, considerably broadened their spectrum of immunological and clinical phenotypes, and enabled successful targeted therapeutic interventions. These studies have also been of great scientific merit, challenging a number of immunological notions initially established in inbred mice while revealing previously unrecognized mechanisms of host defense by leukocytes and other cells and of both innate and adaptive tolerance to self.
Towards precision dosing of vancomycin in critically ill patients: an evaluation of the predictive performance of pharmacometric models in ICU patients
Authors: C.B. Cunio, D.W. Uster, J.E. Carland, H. Buscher, Z. Liu, J. Brett, M. Stefani, G.R.D. Jones, R.O. Day, S.G. Wicha, S.L. Stocker
Journal: Clinical Microbiology and Infection (2020)
P-332 Real-world data study of BRAF mutant metastatic colorectal cancer patients across the Greater Manchester region prior to BEACON trial results
Authors: R. Cairns, M. Brown, M. Al-Ani, G. Burghel, S. Mullamitha, F. Marti Marti, J. Hasan, K. Kamposioras, A. Alchawaf, V. Lavin, N. Alam, C. Arthur, V. Misra, M. Nasralla, M. Saunders, A. Wallace, M. Braun, J. Barriuso
Journal: Annals of Oncology (2020)
P-341 Capecitabine/mitomycin versus 5-fluorouracil/mitomycin in combination with simultaneous integrated boost-intensity modulated radiation therapy for anal cancer
Authors: L. Mineur, B. Calderon, L. Cartier, F. Plat, C. Toullec, M. Belkacemi, L. Vazquez, R. Boustany
Journal: Annals of Oncology (2020)