tbuckley/cabot-search huggingface dataset:
NORMAL VALUES OF LEFT VENTRICULAR LONGITUDINAL AND CIRCUMFERENTIAL LAYER SPECIFIC STRAIN A META-ANALYSIS
Authors: Yann Ancedy, Abdelhah Moussaoui, Nathanaël Lapidus, Stephane Ederhy, Saroumadi Adavane-Scheuble, Laurie Soulat-Dufour, Pascal Nhan, Franck Boccara, Ariel Cohen
Journal: Journal of the American College of Cardiology (2020)
CLINICAL USE, INSURANCE APPROVAL, AND LIPID LOWERING OF PCSK9 INHIBITORS IN A LARGE HEALTH SYSTEM
Authors: Samip Sheth, Niccole Cuccolo, Regina Vassalo, Natalie Blaine, Donald Wharton, Joseph Favatella, Erik Hossain, Jihane Hajj, Gayley Webb, Archna Bajaj, Daniel Soffer, Daniel Rader, Douglas Jacoby
Journal: Journal of the American College of Cardiology (2020)
Drug interactions in ambulatory cancer patients receiving cancer-directed therapy
Authors: R. P. Riechelmann, L. Wang, I. F. Tannock, M. K. Krzyzanowska
Journal: Journal of Clinical Oncology (2006)

6129 Background: Cancer patients (pts) are susceptible to drug interactions (DI) because they receive multiple medications. Here we evaluate the epidemiology of potential DI in cancer patients. Methods: Ambulatory, adult pts with solid malignancies who were receiving antineoplastic treatment completed a questionnaire about drugs taken in the previous month. Drug Interactions Facts software was used to screen for potential DI and to classify them in terms of severity (major, moderate and minor, where major is a life-threatening interaction) and level of scientific evidence (1 to 5, with 1 being the highest level). Summary statistics and logistic regression were used to describe the results. Results: Between Sept -Dec 2005, 183 pts completed the questionnaire: median age was 61 (range 26–88), and 114 (62%) were women. Cancer sites included breast 63 (35%), gastrointestinal 45 (25%), and genitourinary 36 (20%). Treatment intent was palliative in 139 (60%). Most pts (76%) were receiving chemotherapy; 111 (66%) had at least one co-morbid condition, and 72 (47%) had abnormal liver and/or renal function. The median number of drugs per pt was 5 (range 0–16). Among the 183 pts, 131 potential DI were identified of which 65 (50%) were due to pharmacokinetic interactions. Sixteen (12%) of all potential DI were major, 94 (72%) were moderate, and 21 (16%) were minor. Fourteen (11%), 54 (41%), 5 (4%), 42 (32%), and 16 (12%) were supported by levels 1,2,3,4,5 of evidence respectively. Most potential DI involved non-chemotherapy agents such as warfarin, antihypertensives, and anti-inflammatory drugs. In multivariate analyses, number of comorbidities (p= .0001), number of drugs (p= .005), and cancer type (p= .03) were significant risk factors for DI. Conclusion: PotentialDI are common in oncology, and usually involve non-chemotherapeutic drugs. Risk factors for potential DI include comorbid illness, number of medications and type of cancer. Oncologists should be aware of such an important issue. No significant financial relationships to disclose.
Abstract 13111: A Deadly Sting: Recognizing Kounis Syndrome, a Rare Cause of Myocardial Infarction
Authors: Jugeet Kanwal, Janet Fontanella, Jonathan Finkel
Journal: Circulation (2019)

Background: Hymenoptera stings as allergic triggers have been recognized in medical literature as a potential cause of myocardial infarction. In the presence of such triggers, it has been termed Ko...
Demystifying morphomolecular alterations of vasculature in interstitial lung diseases
Authors: Toyoshi Yanagihara, Kirk D. Jones
Journal: European Respiratory Journal (2020)

<b>Focusing on remodelling-associated angiogenesis, both sprouting and intussusceptive, Ackermann and co-workers present histopathology, microvascular anatomy and gene expression in three main subtypes of interstitial lung disease: UIP, NSIP and AFE</b>http://bit.ly/2NtmV6D
IMPACT OF PREDIABETES ON LONG-TERM OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 23,019 PROCEDURES
Authors: Rupak Desai, Rushikkumar Bhuva, Sonali Sachdeva, Ankit Vyas, Ahmed Mahmood, Muhammad Uzair Lodhi, Hee Kong Fong, Nanush Damarlapally, Kishorbhai Gangani, Rajesh Sachdeva, Gautam Kumar
Journal: Journal of the American College of Cardiology (2020)
Validation of tumor bearing Nude rats as a model to study anticancer drug pharmacokinetic/pharmacodynamic (PK/PD) relationships
Authors: Francis Bichat, Olivier Duchamp, Nicolas Hoffmann, Amandine Bataille, Julien Eon, Virginie Bari, Nadine Narboux, Nicolas Guilbaud, Philippe Genne
Journal: Cancer Research (2004)

5411  A key issue in the clinical development of anticancer drugs is to have as much reliable information as possible from relevant preclinical in vivo models. The Nude rat was selected as an appropriate model for human tumor grafting, assessment to surgery, repeated sampling strategy and since this animal specie has a metabolism closer to human than mouse. In this work, we demonstrated that the activity of cytochrome P450 (CYP)1A, 2B and 2E related detoxifying enzymes was higher in liver and kidneys of Nude mice than in Nude rat and human. In contrast, the activity of CYP1A, 2E, 3A related detoxifying enzymes was higher in intestine of Nude rats than in Nude mice. The aim of this study was to validate the Nude rat model to establish PK/PD relationships for chemotherapeutic agents defining a rationale of treatment schedule for clinical development. Studies were performed with paclitaxel (PXL), a clinically active anticancer agent for which metabolism has been described in rodents and human. Catheter was implanted into the left femoral vein of Nude rats. Human Calu-6 lung tumor cells were inoculated in the flank of catheterised rats. The Calu-6 tumor bearing Nude rats received IV bolus injections of PXL at 5 mg/kg once a day for 4 consecutive days (Q1DX4, D0-D3) or a continuous IV infusion of PXL at 20, 80 and 200 mg/kg in a 4-day period. The PK of PXL was studied at D0 and D3 for the IV bolus route and every day for the continuous IV infusion route. PXL concentrations in plasma were measured by validated HPLC/MS-MS method using docetaxel as internal standard. At the end of treatment, a biliary drain was implanted in rats to access the PXL metabolism. The PXL metabolites were identified by HPLC/MS-MS method. Tumors were excised to assess molecular markers of PXL antitumor efficacy. A lethality of Nude rats was observed 3 and 4 days after the start of PXL infusion at 80 and 200 mg/kg, respectively. Between D0-D4, the increase in tumor volume was 90% for control; 1% for IV bolus and 10% for IV infusion at 20 mg/kg. Despite toxicity of PXL, tumor volume decreased of 25% for rats treated by continuous infusion of PXL at 80 mg/kg. The PXL plasma exposure increased with a dose-dependent relationship after continuous IV infusion of PXL. Five major metabolites of PXL such as 3’p-OH-PXL, 2m-OH-PXL, 8-OH-PXL, 10-deacetyl-PXL and Baccatin III were identified in bile of treated-rats. Additional tumor markers such as apoptosis and tubulin polymers were measured. All final results were plotted together to correlate PK and PD of PXL. The Nude rat xenograft model appears to be appropriate for providing useful data for the determination of the optimal schedule of administration, both therapeutic and toxic effects, pharmacokinetics and metabolism, and to contribute to the clinical development approach of chemotherapeutic agents.
Coding and noncoding drivers of mantle cell lymphoma identified through exome and genome sequencing
Authors: Prasath Pararajalingam, Krysta M. Coyle, Sarah E. Arthur, Nicole Thomas, Miguel Alcaide, Barbara Meissner, Merrill Boyle, Quratulain Qureshi, Bruno M. Grande, Christopher Rushton, Graham W. Slack, Andrew J. Mungall, Constantine S. Tam, Rishu Agarwal, Sarah-Jane Dawson, Georg Lenz, Sriram Balasubramanian, Randy D. Gascoyne, Christian Steidl, Joseph Connors, Diego Villa, Timothy E. Audas, Marco A. Marra, Nathalie A. Johnson, David W. Scott, Ryan D. Morin
Journal: Blood (2020)
ALL-CAUSE MORTALITY OF PATIENTS WITH CHRONIC LUNG DISEASE AND SEVERE AORTIC STENOSIS TREATED WITH TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Garrett A. Welle, Madeline Mahowald, Fahad Alqahtani, Kaniz Fatema, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2020)
Electro-acupuncture for joint pain related to aromatase inhibitors among breast cancer survivors: A randomized placebo-controlled trial.
Authors: Jun J Mao, Sharon Xie, John T Farrar, Carrie Tompkins Stricker, Marjorie Bowman, Deborah Bruner, Angela DeMichele
Journal: Journal of Clinical Oncology (2013)

9639 Background: Arthralgia is a common and debilitating symptom in a significant proportion of breast cancer patients receiving aromatase inhibitors (AIs). Methods: We conducted a randomized, placebo-controlled trial of electro-acupuncture compared to waitlist control (WLC) and sham acupuncture in postmenopausal women with breast cancer who self-attributed their arthralgia to taking AIs. Acupuncturists delivered ten treatments of tailored acupuncture with 2 Hz electro-stimulation via a TENS unit. Sham acupuncture used non-penetrating Streitberger needles at non-traditional acupuncture points and lacked electro-stimulation. The primary endpoint was pain severity measured by the Brief Pain Inventory (BPI) between electro-acupuncture and WLC at Week 8; durability of response at Week 12 and comparison of electro to sham acupuncture were secondary aims. Results: Sixty-seven patients were randomized to the three arms. The mean reduction in BPI pain severity was significantly greater in the electro-acupuncture group than WLC group at both Week 8 (-2.2 vs. -0.2 p=0.0004) and Week 12 (-2.4 vs. -0.2, p&lt;0.0001). The BPI pain-related interference also improved significantly in the electro-acupuncture group compared to WLC group at Weeks 8 (-2.0 vs. +0.2, p=0.0006) and 12 (-2.1 vs. -0.1, p=0.0034). Sham acupuncture reduced pain severity (-2.3) and pain-related interference (-1.5) at Week 8 similar to electro-acupuncture (p= non-significant); however, the effect of sham acupuncture appeared to decrease at Week 12 for pain severity (-1.7) and pain-related inference (-1.3). Conclusions: Electro-acupuncture significantly improved AI-related arthralgia over “usual care” with clinically important and durable changes in symptoms. Treatment effects were similar between the electro and sham groups at Week 8, suggesting that a large component of acupuncture effect is mediated through the process of acupuncture delivery rather than the specificity of needle placement or needle penetration of skin. Research is needed to evaluate the long term effects of electro-acupuncture to improve AI-related arthralgia. Clinical trial information: NCT01013337.
CLINICAL OUTCOMES FOLLOWING TRANSCATHETER MITRAL VALVE REPAIR VERSUS MEDICAL THERAPY FOR SECONDARY MITRAL REGURGITATION IN PATIENTS WITH PREVIOUSLY IMPLANTED CARDIAC RESYNCHRONIZATION THERAPY: THE COAPT TRIAL
Authors: Ioanna Kosmidou, JoAnn Lindenfeld, William Abraham, Saibal Kar, None Kar, Scott Lim, Jacob M. Mishell, Brian Whisenant, Robert M. Kipperman, Konstantinos Boudoulas, Yiran Zhang, Zixuan Zhang, Michael Mack, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)
A Uniquely Complex Mitochondrial Proteome from Euglena gracilis
Authors: Michael J Hammond, Anna Nenarokova, Anzhelika Butenko, Martin Zoltner, Eva Lacová Dobáková, Mark C Field, Julius Lukeš
Journal: Molecular Biology and Evolution (2020)

Euglena gracilis is a metabolically flexible, photosynthetic, and adaptable free-living protist of considerable environmental importance and biotechnological value. By label-free liquid chromatography tandem mass spectrometry, a total of 1,786 proteins were identified from the E. gracilis purified mitochondria, representing one of the largest mitochondrial proteomes so far described. Despite this apparent complexity, protein machinery responsible for the extensive RNA editing, splicing, and processing in the sister clades diplonemids and kinetoplastids is absent. This strongly suggests that the complex mechanisms of mitochondrial gene expression in diplonemids and kinetoplastids occurred late in euglenozoan evolution, arising independently. By contrast, the alternative oxidase pathway and numerous ribosomal subunits presumed to be specific for parasitic trypanosomes are present in E. gracilis. We investigated the evolution of unexplored protein families, including import complexes, cristae formation proteins, and translation termination factors, as well as canonical and unique metabolic pathways. We additionally compare this mitoproteome with the transcriptome of Eutreptiella gymnastica, illuminating conserved features of Euglenida mitochondria as well as those exclusive to E. gracilis. This is the first mitochondrial proteome of a free-living protist from the Excavata and one of few available for protists as a whole. This study alters our views of the evolution of the mitochondrion and indicates early emergence of complexity within euglenozoan mitochondria, independent of parasitism.
Glycine Enhances Satellite Cell Proliferation, Cell Transplantation, and Oligonucleotide Efficacy in Dystrophic Muscle
Authors: Caorui Lin, Gang Han, Hanhan Ning, Jun Song, Ning Ran, Xianfu Yi, Yiqi Seow, HaiFang Yin
Journal: Molecular Therapy (2020)

The need to distribute therapy evenly systemically throughout the large muscle volume within the body makes Duchenne muscular dystrophy (DMD) therapy a challenge. Cell and exon-skipping therapies are promising but have limited effects, and thus enhancing their therapeutic potency is of paramount importance to increase the accessibility of these therapies to DMD patients. In this study, we demonstrate that co-administered glycine improves phosphorodiamidate morpholino oligomer (PMO) potency in mdx mice with marked functional improvement and an up to 50-fold increase of dystrophin in abdominal muscles compared to PMO in saline. Glycine boosts satellite cell proliferation and muscle regeneration by increasing activation of mammalian target of rapamycin complex 1 (mTORC1) and replenishing the one-carbon unit pool. The expanded regenerating myofiber population then results in increased PMO uptake. Glycine also augments the transplantation efficiency of exogenous satellite cells and primary myoblasts in mdx mice. Our data provide evidence that glycine enhances satellite cell proliferation, cell transplantation, and oligonucleotide efficacy in mdx mice, and thus it has therapeutic utility for cell therapy and drug delivery in muscle-wasting diseases. The need to distribute therapy evenly systemically throughout the large muscle volume within the body makes Duchenne muscular dystrophy (DMD) therapy a challenge. Cell and exon-skipping therapies are promising but have limited effects, and thus enhancing their therapeutic potency is of paramount importance to increase the accessibility of these therapies to DMD patients. In this study, we demonstrate that co-administered glycine improves phosphorodiamidate morpholino oligomer (PMO) potency in mdx mice with marked functional improvement and an up to 50-fold increase of dystrophin in abdominal muscles compared to PMO in saline. Glycine boosts satellite cell proliferation and muscle regeneration by increasing activation of mammalian target of rapamycin complex 1 (mTORC1) and replenishing the one-carbon unit pool. The expanded regenerating myofiber population then results in increased PMO uptake. Glycine also augments the transplantation efficiency of exogenous satellite cells and primary myoblasts in mdx mice. Our data provide evidence that glycine enhances satellite cell proliferation, cell transplantation, and oligonucleotide efficacy in mdx mice, and thus it has therapeutic utility for cell therapy and drug delivery in muscle-wasting diseases.
Abstract 15796: Downregulation of the Macrophage Migration Inhibitory Factor Pathway in Advanced Heart Failure
Authors: Yina Ma, Kenneth Bedi, Lin Leng, Richard Bucala, Kenneth B Margulies, Lawrence Young
Journal: Circulation (2018)

Background: Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (DDT) are cytokines highly expressed in cardiomyocytes and have autocrine-paracrine effects, signal...
Natural history of malignant bone disease in gastric cancer: Final results of a multicenter bone metastasis survey.
Authors: Nicola Silvestris, Francesco Pantano, Toni Ibrahim, Teresa Gamucci, Fernando De Vita, Paolo Pedrazzoli, Sandro Barni, Evaristo Maiello, Gianmauro Numico, Vincenzo Catalano, Rossana Berardi, Francesco Di Costanzo, Saverio Cinieri, Antonio Russo, Anna Elisabetta Brunetti, Daniele Santini
Journal: Journal of Clinical Oncology (2013)

4091 Background: Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature few data on the natural history of bone disease in this malignancy are available. Methods: A retrospective, observational multicenter study aimed to define the natural history of GC patients with bone metastasis was conducted in 22 Italian hospital centres in which these patients received diagnosis and treatment of disease from 1998 to 2011. Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. Results: Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one; less than half of the patients (31%) experienced at least one event and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid (ZOL) before the first SRE, median time to its appearance was significantly prolonged compared to control (7 months vs 4 months for control; P:0.0005). Conclusions: To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Furthermore, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis.
CARDIAC CATHETERIZATION FOR OUT OF HOSPITAL VENTRICULAR FIBRILLATION ARREST LEADS TO HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY DIAGNOSIS INFLUENCING OPTIMAL VASOPRESSOR CHOICE
Authors: Ramon Lee, Jena Pizula, Jeffrey Tran, Haroon Yousaf, Anilkumar Mehra
Journal: Journal of the American College of Cardiology (2020)
MULTIPLE OPEN-HEART SURGERIES, A DEBILITATING STROKE AND RESTING HYPOXEMIA IN AN ADULT WITH BUBBLES IN THE LEFT ATRIUM ON ECHOCARDIOGRAPHY
Authors: Hisham Hakeem, Omar Kakish, Muhammad Khakwani, Swaiman Singh, Aeliya Kazmi, Sergio Waxman, Rajiv Verma, Marc Cohen, Gautam Karteek Visveswaran
Journal: Journal of the American College of Cardiology (2020)
The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord
Authors: Xiaowei Li, Chi Zhang, Agnes E. Haggerty, Jerry Yan, Michael Lan, Michelle Seu, Mingyu Yang, Megan M. Marlow, Inés Maldonado-Lasunción, Brian Cho, Zhengbing Zhou, Long Chen, Russell Martin, Yohshiro Nitobe, Kentaro Yamane, Hua You, Sashank Reddy, Da-Ping Quan, Martin Oudega, Hai-Quan Mao
Journal: Biomaterials (2020)
IL33 Is a Key Driver of Treatment Resistance of Cancer
Authors: Chie Kudo-Saito, Takahiro Miyamoto, Hiroshi Imazeki, Hirokazu Shoji, Kazunori Aoki, Narikazu Boku
Journal: Cancer Research (2020)

Abstract Recurrence and treatment resistance are major causes of cancer-associated death. There has been a growing interest in better understanding epithelial–mesenchymal transition, stemness of cancer cells, and exhaustion and dysfunction of the immune system for which numerous genomic, proteomic, microenvironmental, and immunologic mechanisms have been demonstrated. However, practical treatments for such patients have not yet been established. Here we identified IL33 as a key driver of polyploidy, followed by rapid proliferation after treatment. IL33 induction transformed tumor cells into polyploid giant cells, showing abnormal cell cycle without cell division accompanied by Snail deregulation and p53 inactivation; small progeny cells were generated in response to treatment stress. Simultaneously, soluble IL33 was released from tumor cells, leading to expansion of receptor ST2-expressing cells including IL17RB+GATA3+ cells, which promoted tumor progression and metastasis directly and indirectly via induction of immune exhaustion and dysfunction. Blocking IL33 with a specific mAb in murine IL33+ metastatic tumor models abrogated negative consequences and successfully elicited antitumor efficacy induced by other combined treatments. Ex vivo assays using tumor tissues and peripheral blood mononuclear cells of patients with cancer validated the clinical relevancy of these findings. Together, these data suggest that targeting the IL33-ST2 axis is a promising strategy for diagnosis and treatment of patients likely to be resistant to treatments in the clinical settings. Significance: These findings indicate that the functional role of IL33 in cancer polyploidy contributes to intrinsic and extrinsic mechanisms underlying treatment failure.
Opportunities and challenges integrating resource-rational analysis with developmental perspectives
Authors: Kimele Persaud, Ilona Bass, Joseph Colantonio, Carla Macias, Elizabeth Bonawitz
Journal: Behavioral and Brain Sciences (2020)

Abstract Lieder and Griffiths present the computational framework “resource-rational analysis” to address the reverse-engineering problem in cognition. Here we discuss how developmental psychology affords a unique and critical opportunity to employ this framework, but which is overlooked in this piece. We describe how developmental change provides an avenue for ongoing work as well as inspiration for expansion of the resource-rational approach.