tbuckley/cabot-search huggingface dataset:
The Albert Lasker Medical Awards. RU-486 as an antiprogesterone steroid. From receptor to contragestion and beyond
Authors: E E Baulieu
Journal: JAMA (1989)

The steroid RU-486 (mifepristone) is an antiprogesterone that works at the receptor level. It can interrupt pregnancy very early on (contragestion), mostly by interfering with the process of implantation and decidua function. It also may facilitate surgical evacuation of the uterus and certain difficult deliveries. It impedes ovulation when taken during the follicular phase. Also, RU-486 is the first antiglucocorticosteroid available for clinical use. It deserves further studies to assess its wide range of therapeutic potential. (<i>JAMA</i>. 1989;262:1808-1814)
117P Pregnancy-associated breast cancer (PABC): Demographics and outcome analysis from a lower and middle income country (LMIC)
Authors: J. Bajpai, S. Dandekar, V. Simha, T. Shylasree, R. Sarin, V. Bansal, J. Ghosh, S. Rath, N. Nair, S. Gulia, A. Patil, S. Gupta
Journal: Annals of Oncology (2020)
The role of gastric microbiota in gastric cancer
Authors: Oliver A. Stewart, Fen Wu, Yu Chen
Journal: Gut Microbes (2020)

Gastric cancer represents one of the leading causes of cancer deaths worldwide. Helicobacter pylori (H. pylori) infection is the strongest risk factor associated with gastric cancer. Due to new molecular techniques allowing greater identification of stomach microbes, investigators are beginning to examine the role that bacteria other than H. pylori play in gastric cancer development. Recently, researchers have investigated how the composition of the gastric microbiota varies among individuals with various stages of gastric disease. Specific microbes residing in the stomach have been preferentially associated with gastric cancer patients compared to individuals with a healthy gastric mucosa. Studies conducted on the insulin-gastrin (INS-GAS) transgenic mouse model have provided additional insight into the association between the gastric microbiota and gastric cancer. The purpose of this article is to review the current state of literature on the relationship between the gastric microbiota and gastric cancer based on clinical studies performed to date.
7P Prognostic value of the immune infiltration score in early breast cancer patients receiving dual HER2 blockade with trastuzumab and pertuzumab: An exploratory analysis of a randomized clinical trial
Authors: G. Wan, F. Cao, X. Cai, X. Yu, Z. Zuo, Y. Song, T. Xu, Y. Li, Y. Yu, X. Wang, X. Wang
Journal: Annals of Oncology (2020)
Reconstructing the Evolutionary History of Chromosomal Races on Islands: A Genome-Wide Analysis of Natural House Mouse Populations
Authors: Paolo Franchini, Andreas F Kautt, Alexander Nater, Gloria Antonini, Riccardo Castiglia, Axel Meyer, Emanuela Solano
Journal: Molecular Biology and Evolution (2020)

Chromosomal evolution is widely considered to be an important driver of speciation, as karyotypic reorganization can bring about the establishment of reproductive barriers between incipient species. One textbook example for genetic mechanisms of speciation are large-scale chromosomal rearrangements such as Robertsonian (Rb) fusions, a common class of structural variants that can drastically change the recombination landscape by suppressing crossing-over and influence gene expression by altering regulatory networks. Here, we explore the population structure and demographic patterns of a well-known house mouse Rb system in the Aeolian archipelago in Southern Italy using genome-wide data. By analyzing chromosomal regions characterized by different levels of recombination, we trace the evolutionary history of a set of Rb chromosomes occurring in different geographical locations and test whether chromosomal fusions have a single shared origin or occurred multiple times. Using a combination of phylogenetic and population genetic approaches, we find support for multiple, independent origins of three focal Rb chromosomes. The elucidation of the demographic patterns of the mouse populations within the Aeolian archipelago shows that an interplay between fixation of newly formed Rb chromosomes and hybridization events has contributed to shaping their current karyotypic distribution. Overall, our results illustrate that chromosome structure is much more dynamic than anticipated and emphasize the importance of large-scale chromosomal translocations in speciation.
Spinal astrogliosis in an animal model of cancer-induced bone pain
Authors: Eric Seidlitz, Marion Kalina, Gurmit Singh
Journal: Cancer Research (2006)

1000  Pain associated with malignancy in bone is a significant source of morbidity in breast and prostate cancer metastases. Understanding the unique pathophysiological mechanisms leading to bone pain is essential to the development of effective therapies. It is accepted that astroglial activation plays a role in the development of chronic bone pain, although it is unclear whether this is causative to the structural encoding of nociceptive signals and whether opiate analgesics influence the process. We examined spinal astrogliosis in a mouse model of cancer-induced bone pain with opiate analgesia and monitored disease progression with non-invasive optical imaging techniques. This was confirmed by histology. Rat prostate cancer cells (MATLyLu) expressing a green fluorescent protein (GFP) tag were injected into the right femur of 11 Balb/c nude mice (plus 5 mice as non-injected controls). Three injected and one control animal received twice daily doses of an opiate analgesic (buprenorphine, 0.05 mg/kg s.c.) throughout the experiment. Behavioral evidence for bone pain was referenced by measurement of mechanical allodynia with a Touch Test Sensory Evaluator (Stoelting, Wood Dale, IL). Tumor growth was assessed non-invasively with in vivo fluorescence imaging using a thermoelectrically cooled camera (Andor Ikon; excitation = 440-495 nm, emission = 505-580 nm). Skin temperatures were measured using an infrared camera (FLIR ThermaCam SC2000) to assess localized or systemic inflammatory responses. At the end of the experiment, x-rays (Faxitron Model MX-20) were used to determine the extent of osteolysis, then the spinal cord, kidneys, and both femurs were harvested for processing. The femurs were decalcified, paraffin embedded, and analyzed by both fluorescence microscopy and hematoxylin & eosin. Immunohistochemistry on the spinal cords employed a polyclonal rabbit anti-bovine antibody to Glial Fibrillary Acidic Protein (GFAP; Dako N1506) with kidney as a negative control. Results show little evidence to support an interaction of opiate analgesia with astroglial activation. However, the imaging data suggest a possible impact on tumor growth, although this may be model-specific. Interestingly, astrocyte activation occurred without x-ray or histological evidence for significant osteolysis, but this may also be unique to the cells used. Temperature and GFAP data corroborate that the induced pain is bone tumour specific and not likely due to a significant inflammatory component. Astrocyte activation without osteolysis suggests that tumor-specific factors may be involved in the process. (Supported by: Canadian Institutes of Health Research)
52P Characterising clinicopathological and biological parameters predictive of outcome for patients diagnosed with invasive lobular carcinoma
Authors: P. Simpson, A. McCart Reed, J. Kutasovic, C. Coorey, L. Kuo, H. Nguyen, W. Pei, J. Ong, A. Sokolova, E. Evans, A. Porter, S. Lakhani
Journal: Annals of Oncology (2020)
Association of clinical and radiographic findings with the outcomes of 93 patients with COVID-19 in Wuhan, China
Authors: Lingli Li, Lian Yang, Shan Gui, Feng Pan, Tianhe Ye, Bo Liang, Yu Hu, Chuansheng Zheng
Journal: Theranostics (2020)

Rationale: To retrospectively analyze serial chest CT and clinical features in patients with coronavirus disease 2019 (COVID-19) for the assessment of temporal changes and to investigate how the changes differ in survivors and nonsurvivors. Methods: The consecutive records of 93 patients with confirmed COVID-19 who were admitted to Wuhan Union Hospital from January 10, 2020, to February 22, 2020, were retrospectively reviewed. A series of chest CT findings and clinical data were collected and analyzed. The serial chest CT scans were scored on a semiquantitative basis according to the extent of pulmonary abnormalities. Chest CT scores in different periods (0 - 5 days, 6 - 10 days, 11 - 15 days, 16 - 20 days, and > 20 days) since symptom onset were compared between survivors and nonsurvivors, and the temporal trend of the radiographic-clinical features was analyzed. Results: The final cohort consisted of 93 patients: 68 survivors and 25 nonsurvivors. Nonsurvivors were significantly older than survivors. For both survivors and nonsurvivors, the chest CT scores were not different in the first period (0 - 5 days) but diverged afterwards. The mortality rate of COVID-19 monotonously increased with chest CT scores, which positively correlated with the neutrophil-to-lymphocyte ratio, neutrophil percentage, D-dimer level, lactate dehydrogenase level and erythrocyte sedimentation rate, while negatively correlated with the lymphocyte percentage and lymphocyte count. Conclusions: Chest CT scores correlate well with risk factors for mortality over periods, thus they may be used as a prognostic indicator in COVID-19. While higher chest CT scores are associated with a higher mortality rate, CT images taken at least 6 days since symptom onset may contain more prognostic information than images taken at an earlier period.
Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial
Authors: A. Demols, I. Borbath, M. Van den Eynde, G. Houbiers, M. Peeters, R. Marechal, T. Delaunoit, J.-C. Goemine, S. Laurent, S. Holbrechts, M. Paesmans, J.-L. Van Laethem
Journal: Annals of Oncology (2020)
Comparison of 2 Interventions for Liquid Aspiration on Pneumonia Incidence
Authors: JoAnne Robbins, Gary Gensler, Jacqueline Hind, Jeri A. Logemann, Anne S. Lindblad, Diane Brandt, Herbert Baum, David Lilienfeld, Steven Kosek, Donna Lundy, Karen Dikeman, Marta Kazandjian, Gary D. Gramigna, Susan McGarvey-Toler, Patricia J. Miller Gardner
Journal: Annals of Internal Medicine (2008)

To test strategies for avoiding aspiration pneumonia in cognitively impaired elderly patients, Robbins and colleagues randomly assigned 515 patients age 50 years or older with dementia or Parkinson...
EVOLVE: A Multicenter Open-Label Single-Arm Clinical and Translational Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer after PARP Inhibition Progression
Authors: Stephanie Lheureux, Ana Oaknin, Swati Garg, Jeffrey P. Bruce, Ainhoa Madariaga, Neesha C. Dhani, Valerie Bowering, Justin White, Sarah Accardi, Qian Tan, Marsela Braunstein, Katherine Karakasis, Iulia Cirlan, Stephanie Pedersen, Tiantiam Li, Lorena Fariñas-Madrid, Yeh Chen Lee, Zhihui (Amy) Liu, Trevor J. Pugh, Amit M. Oza
Journal: Clinical Cancer Research (2020)

Abstract Purpose: PARP inhibitors (PARPi) are standard-of-care therapy for high-grade serous ovarian cancer (HGSOC). We investigated combining cediranib (antiangiogenic) with olaparib (PARPi) at emergence of PARPi resistance. Patients and Methods: The proof-of-concept EVOLVE study (NCT02681237) assessed cediranib–olaparib combination therapy after progression on a PARPi. Women with HGSOC and radiographic evidence of disease progression were enrolled into one of three cohorts: platinum sensitive after PARPi; platinum resistant after PARPi; or progression on standard chemotherapy after progression on PARPi (exploratory cohort). Patients received olaparib tablets 300 mg twice daily with cediranib 20 mg once daily until progression or unacceptable toxicity. The coprimary endpoints were objective response rate (RECIST v1.1) and progression-free survival (PFS) at 16 weeks. Archival tissue (PARPi-naïve) and baseline biopsy (post-PARPi) samples were mandatory. Genomic mechanisms of resistance were assessed by whole-exome and RNA sequencing. Results: Among 34 heavily pretreated patients, objective responses were observed in 0 of 11 (0%) platinum-sensitive patients, 2 of 10 (20%) platinum-resistant patients, and 1 of 13 (8%) in the exploratory cohort. Sixteen-week PFS rates were 55%, 50%, and 39%, respectively. The most common grade 3 toxicities were diarrhea (12%) and anemia (9%). Acquired genomic alterations at PARPi progression were reversion mutations in BRCA1, BRCA2, or RAD51B (19%); CCNE1 amplification (16%); ABCB1 upregulation (15%); and SLFN11 downregulation (7%). Patients with reversion mutations in homologous recombination genes and/or ABCB1 upregulation had poor outcomes. Conclusions: This is currently the largest post-PARPi study identifying genomic mechanisms of resistance to PARPis. In this setting, the activity of cediranib–olaparib varied according to the PARPi resistance mechanism.
Temporal trends in socioeconomic inequalities in HIV testing: an analysis of cross-sectional surveys from 16 sub-Saharan African countries
Authors: Pearl Anne Ante-Testard, Tarik Benmarhnia, Anne Bekelynck, Rachel Baggaley, Eric Ouattara, Laura Temime, Kévin Jean
Journal: The Lancet Global Health (2020)

Overall increases in the uptake of HIV testing in the past two decades might hide discrepancies across socioeconomic groups. We used data from population-based surveys done in sub-Saharan Africa to quantify socioeconomic inequalities in uptake of HIV testing, and to establish trends in testing uptake in the past two decades.We analysed data from 16 countries in sub-Saharan Africa where at least one Demographic and Health Survey was done before and after 2008. We assessed the country-specific and sex-specific proportions of participants who had undergone HIV testing in the previous 12 months across wealth and education groups, and quantified socioeconomic inequalities with both the relative and slope indices of inequalities. We assessed time trends in inequalities, and calculated mean results across countries with random-effects meta-analyses.We analysed data for 537 784 participants aged 15-59 years (most aged 15-49 years) from 32 surveys done between 2003 and 2016 (16 before 2008, and 16 after 2008) in Cameroon, Côte d'Ivoire, DR Congo, Ethiopia, Guinea, Kenya, Lesotho, Liberia, Malawi, Mali, Niger, Rwanda, Sierra Leone, Tanzania, Zambia, and Zimbabwe. A higher proportion of female participants than male participants reported uptake of HIV testing in the previous 12 months in five of 16 countries in the pre-2008 surveys, and in 14 of 16 countries in the post-2008 surveys. After 2008, in the overall sample, the wealthiest female participants were 2·77 (95% CI 1·42-5·40) times more likely to report HIV testing in the previous 12 months than were the poorest female participants, whereas the richest male participants were 3·55 (1·85-6·81) times more likely to report HIV testing than in the poorest male participants. The mean absolute difference in uptake of HIV testing between the richest and poorest participants was 11·1 (95% CI 4·6-17·5) percentage points in female participants and 15·1 (9·6-20·6) in male participants. Over time (ie, when pre-2008 and post-2008 data were compared), socioeconomic inequalities in the uptake of HIV testing in the previous 12 months decreased in male and female participants, whereas absolute inequalities remained similar in female participants and increased in male participants.Although relative socioeconomic inequalities in uptake of HIV testing in sub-Saharan Africa has decreased, absolute inequalities have persisted or increased. Greater priority should be given to socioeconomic equity in assessments of HIV-testing programmes.INSERM-ANRS (France Recherche Nord and Sud Sida-HIV Hépatites).
Abstract 15419: Automated Assessment of High-Risk Coronary Plaques Using Fully Integrated Catheter-Based Label-Free Fluorescence Lifetime Imaging (FLIm)-Optical Coherence Tomography (OCT)
Authors: Sun Won Kim, Hyeong Soo Nam, Woo Jae Kang, Joon Woo Song, Min Woo Lee, Young Dae Joo, Wang-Yuhl Oh, Hongki Yoo, Jin Won Kim
Journal: Circulation (2018)

Introduction: Machine learning (ML) can be applied to enhance biomedical imaging diagnostics, however, its feasibility in intracoronary multi-modal imaging has not been evaluated. This study aimed ...
Update on Extensively Drug-Resistant <i>Salmonella</i> Serotype Typhi Infections Among Travelers to or from Pakistan and Report of Ceftriaxone-Resistant <i>Salmonella</i> Serotype Typhi Infections Among Travelers to Iraq — United States, 2018–2019
Authors: Louise K. François Watkins, Alison Winstead, Grace D. Appiah, Cindy R. Friedman, Felicita Medalla, Michael J. Hughes, Meseret G. Birhane, Zachary D. Schneider, Perrine Marcenac, Samir S. Hanna, Gauri Godbole, Kelly A . Walblay, Ashley E. Wiggington, Molly Leeper, Elizabeth H. Meservey, Kaitlin A. Tagg, Jessica C. Chen, Abdinasir Abubakar, Faris Lami, Asaad M. Asaad, Vickneswaran Sabaratnam, Aamer Ikram, Kristina M. Angelo, Allison Walker, Eric Mintz
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Ceftriaxone-resistant Salmonella enterica serotype Typhi (Typhi), the bacterium that causes typhoid fever, is a growing public health threat. Extensively drug-resistant (XDR) Typhi is resistant to ceftriaxone and other antibiotics used for treatment, including ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole (1). In March 2018, CDC began enhanced surveillance for ceftriaxone-resistant Typhi in response to an ongoing outbreak of XDR typhoid fever in Pakistan. CDC had previously reported the first five cases of XDR Typhi in the United States among patients who had spent time in Pakistan (2). These illnesses represented the first cases of ceftriaxone-resistant Typhi documented in the United States (3). This report provides an update on U.S. cases of XDR typhoid fever linked to Pakistan and describes a new, unrelated cluster of ceftriaxone-resistant Typhi infections linked to Iraq. Travelers to areas with endemic Typhi should receive typhoid vaccination before traveling and adhere to safe food and water precautions (4). Treatment of patients with typhoid fever should be guided by antimicrobial susceptibility testing whenever possible (5), and clinicians should consider travel history when selecting empiric therapy.
Endocrine Autoimmune Disease as a Fragility of Immune Surveillance against Hypersecreting Mutants
Authors: Yael Korem Kohanim, Avichai Tendler, Avi Mayo, Nir Friedman, Uri Alon
Journal: Immunity (2020)

Some endocrine organs are frequent targets of autoimmune attack. Here, we addressed the origin of autoimmune disease from the viewpoint of feedback control. Endocrine tissues maintain mass through feedback loops that balance cell proliferation and removal according to hormone-driven regulatory signals. We hypothesized the existence of a dedicated mechanism that detects and removes mutant cells that missense the signal and therefore hyperproliferate and hypersecrete with potential to disrupt organismal homeostasis. In this mechanism, hypersecreting cells are preferentially eliminated by autoreactive T cells at the cost of a fragility to autoimmune disease. The "autoimmune surveillance of hypersecreting mutants" (ASHM) hypothesis predicts the presence of autoreactive T cells in healthy individuals and the nature of self-antigens as peptides from hormone secretion pathway. It explains why some tissues get prevalent autoimmune disease, whereas others do not and instead show prevalent mutant-expansion disease (e.g., hyperparathyroidism). The ASHM hypothesis is testable, and we discuss experimental follow-up.
The COVID-19 Pandemic
Authors: Thomas C. Erren, Philip Lewis, David M. Shaw
Journal: Circulation (2020)

oronavirus disease 2019 (COVID-19) has the world in a firm grip.Individuals everywhere face challenges among novel conditions.As a result, countless unplanned or natural experiments (NEs) with health and disease, where conditions are altered in a way that is not within researchers' control, are underway. 1Such experiments can be tantalizing, with possibly immense statistical power and causal insights that would otherwise not be achievable in controlled experimental studies or nonexperimental observational studies.According to the New York Times, a 40% to 60% reduction in myocardial infarctions (MIs) during the pandemic has been observed anecdotally.Related NEs abound with questions: "Are MI rates really down?" "How many MIs may be missed or misdiagnosed?""Do people with mild MI no longer visit hospitals because they fear contracting COVID-19?"NEs are unique means to understand how policies and large-scale interventions may impact health. 2 However, although the impact of COVID-19 gives great statistical power, this comes with great responsibility.This article outlines 4 ethical and scientific imperatives for the study of NEs arising from the COVID-19 pandemic.It focuses on physical distancing (PD) as a key intervention that triggers NEs.
Basic Mechanisms of Diabetic Heart Disease
Authors: Rebecca H. Ritchie, E. Dale Abel
Journal: Circulation Research (2020)

Diabetes mellitus predisposes affected individuals to a significant spectrum of cardiovascular complications, one of the most debilitating in terms of prognosis is heart failure. Indeed, the increasing global prevalence of diabetes mellitus and an aging population has given rise to an epidemic of diabetes mellitus-induced heart failure. Despite the significant research attention this phenomenon, termed diabetic cardiomyopathy, has received over several decades, understanding of the full spectrum of potential contributing mechanisms, and their relative contribution to this heart failure phenotype in the specific context of diabetes mellitus, has not yet been fully resolved. Key recent preclinical discoveries that comprise the current state-of-the-art understanding of the basic mechanisms of the complex phenotype, that is, the diabetic heart, form the basis of this review. Abnormalities in each of cardiac metabolism, physiological and pathophysiological signaling, and the mitochondrial compartment, in addition to oxidative stress, inflammation, myocardial cell death pathways, and neurohumoral mechanisms, are addressed. Further, the interactions between each of these contributing mechanisms and how they align to the functional, morphological, and structural impairments that characterize the diabetic heart are considered in light of the clinical context: from the disease burden, its current management in the clinic, and where the knowledge gaps remain. The need for continued interrogation of these mechanisms (both known and those yet to be identified) is essential to not only decipher the how and why of diabetes mellitus-induced heart failure but also to facilitate improved inroads into the clinical management of this pervasive clinical challenge.
86P Patients (pts) preference for different administration methods of trastuzumab (T) in pts with HER2+ early breast cancer (BC) treated within the GAIN-2 trial
Authors: M. Reinisch, M. Untch, T. Reimer, R.J.C. Mahlberg, M. Aydogdu, T. Hitschold, C. Jackisch, F. Marmé, H-J. Lück, E. Ladda, S. Schmatloch, M. Schmidt, P. Klare, B.V. Sinn, E. Stickeler, S. Seiler, J. Rey, N. Klutinus, V. Möbus, S. Loibl
Journal: Annals of Oncology (2020)
Efficacy and Toxicity Profile of Carfilzomib Based Regimens for Treatment of Multiple Myeloma, a Systematic Review
Authors: Adeela Mushtaq, Azka Latif, Vikas Kapoor, Faiza Hassan Warraich, Sami Ullah Warraich, Ahmad Iftikhar, Pavan Tenneti, Raahem Nayab Zafar, Atlantis Dawn Russ, Ivo Abraham, Ali McBride, Faiz Anwer
Journal: Blood (2017)