tbuckley/cabot-search huggingface dataset:
A novel lean alloy of biodegradable Mg–2Zn with nanograins
Authors: Wenhui Wang, Carsten Blawert, Rui Zan, Yu Sun, Hongzhou Peng, Jiahua Ni, Pei Han, Tao Suo, Yang Song, Shaoxiang Zhang, Mikhail L. Zheludkevich, Xiaonong Zhang
Journal: Bioactive Materials (2021)

Lean alloy (low alloyed) is beneficial for long-term sustainable development of metal materials. Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of lean biomedical Mg alloy, but it is nearly impossible to realize. In the present study, the bulk nanocrystalline Mg alloy (average grain size: ~70 nm) was successfully obtained by hot rolling process of a lean Mg-2wt.%Zn (Z2) alloy and both high strength ((223 MPa (YS) and 260 MPa (UTS)) and good corrosion resistance (corrosion rate in vivo: 0.2 mm/year) could be achieved. The microstructure evolution during the rolling process was analyzed and discussed. Several factors including large strain, fine grains, strong basal texture, high temperature and Zn segregation conjointly provided the possibility for the activation of pyramidal <c+a> slip to produce nanocrystals. This finding could provide a new development direction and field of application for lean biomedical Mg alloys.
120P Prognostic significance of SAMHD1 expression in breast cancer
Authors: M. Margeli Vila, E. Felip, L. Gutierrez, E. Riveira, V. Quiroga, M. Romeo, B. Cirauqui, I. Teruel, A. Pous, A. Ferrando, A. Martinez-Cardús, E. Ballana
Journal: Annals of Oncology (2021)
Abstract 15776: Outcomes of Atrioventricular Septal Defects in Patients With and Without Trisomy 21: Analysis of the Inpatient Sample Database
Authors: Safwat A Aly, Ibrahim Qattea, Hany Z Aly
Journal: Circulation (2020)

Introduction: Atrioventricular septal defect (AVSD) is among the most common congenital heart diseases especially in infants with trisomy 21 (T21). However, the clinical outcomes of AVSD are largely limited to institutional reports. Aim: Using U.S.A. national database, the purpose of this study was to a) to assess the prevalence, mortality and outcomes of AVSD, and b) to determine the impact of T21 on its outcomes. Methods: We queried The US National Inpatient Sample from the Healthcare Cost and Utilization Project for patients with AVSD with and without T21 in the period 2002-2017. Patient characteristics, comorbidities, mortality, and healthcare utilization were evaluated for AVSD comparing those with and without T21. Results: During the study period, a total of 20,628,538 infants were born in the in the US, of them 67,020 (0.3%) had AVSD. T21 was diagnosed in 34,825 (52%). The incidence of AVSD ranged from 4.5-7.4/year. Common associated CHD were transposition of great arteries, tetralogy of Fallot, and truncus arteriosus at 10.9%, 4%, 0.4% respectively. The association with CHD was not different between AVSD with and without T21. During study period, 92% of patients underwent surgical repair. AVSD patients with T21 had greater mortality (4.4% vs 1.1%, p&lt;0.001) more frequent pulmonary hypertension (4.8% vs 2.7%, p&lt;0.001), longer median length of hospital stay (7 vs 3 days), and less incidence of arrhythmia (2.8% vs 6%, p&lt;0.001). Comparisons between AVSD with and without T21 are outlined in table 1. Conclusion: Almost half of infants with AVSD had T21. T21 is associated with greater mortality and pulmonary hypertension, longer hospitalization and less arrhythmia.
Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction
Authors: Etienne Puymirat, Guillaume Cayla, Tabassome Simon, Philippe G. Steg, Gilles Montalescot, Isabelle Durand-Zaleski, Alicia le Bras, Romain Gallet, Khalife Khalife, Jean-François Morelle, Pascal Motreff, Gilles Lemesle, Jean-Guillaume Dillinger, Thibault Lhermusier, Johanne Silvain, Vincent Roule, Jean-Noel Labèque, Grégoire Rangé, Grégory Ducrocq, Yves Cottin, Didier Blanchard, Anaïs Charles Nelson, Bernard De Bruyne, Gilles Chatellier, Nicolas Danchin
Journal: New England Journal of Medicine (2021)

In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear.
Genomic and transcriptional alterations in first-line chemotherapy exert a potentially unfavorable influence on subsequent immunotherapy in NSCLC
Authors: Yayi He, Linsong Chen, Lishu Zhao, Shiying Dang, Guifeng Liu, Shinji Sasada, Patrick C. Ma, Nico van Zandwijk, Rafael Rosell, Helmut H. Popper, Hao Wang, Minlin Jiang, Haoyue Guo, Xinyi Liu, Shifu Chen, Xiaoni Zhang, Mingyan Xu, Bo Zhu, Ming Liu, Caicun Zhou
Journal: Theranostics (2021)

Background: Recent studies in non-small cell lung cancer (NSCLC) patients have demonstrated that first-line immunotherapy is associated with better therapeutic response than second-line treatment. So far, the mechanisms need to be explored. It prompted us to evaluate the association between first-line chemotherapy and subsequent immunotherapy in NSCLC as well as its underlying mechanisms at the genomic and transcriptomic level. Methods: We launched a prospective, observational clinical study, paired tumor biopsies before and after chemotherapy were collected from NSCLC patients without tyrosine kinase inhibitor (TKI)-related driver gene mutations. The analyses included genomic and transcriptional changes performed by next-generation sequencing (NGS)-based whole-exome sequencing (WES) and messager ribonucleic acid (mRNA) sequencing. Characteristic mutational alterations in 1574 genes were investigated based on mutational status, clinicopathological factors, and chemotherapy responses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, neoantigen prediction and intratumoral heterogeneity evaluation were also performed. Results: Samples and information from 32 NSCLC patients without TKI-related driver gene mutations were obtained. We found that the total number of single nucleotide variants (SNV)/insertion-deletion (INDEL) mutations did not change significantly after chemotherapy. The tumor mutation burden (TMB) decreased significantly after chemotherapy in smoking patients and the decreased TMB correlated with a better survival of smoking patients. The change in copy number variations (CNVs) exhibited a decreasing trend during chemotherapy. Subsequent analysis at mRNA level revealed a significant decrease in the expression levels of genes related to antigen processing and presentation as well as other factors relevant for response to immunotherapy. Pathway enrichment analysis confirmed that the immune-related signaling pathways or biological processes were decreased after first-line chemotherapy. Conclusions: Our study presents an explanation for the unsatisfactory results of immunotherapy when given after chemotherapy, and suggests that first-line chemotherapy is able to influence the tumor microenvironment and decrease the efficacy of subsequent immunotherapy. The study was registered at ClinicalTrials.gov, number NCT03764917, and has completed enrolment; patients are still in follow-up.
Achieving safe drinking water and clean cooking for all
Authors: Joshua Kearns, Riley E Mulhern
Journal: The Lancet Global Health (2021)

The Viewpoint by Isha Ray and Kirk Smith (March, 2021)1 makes a welcome critique of interventions to provide safe drinking water and clean cooking in poor communities, arguing that household-level interventions have been mostly unsuccessful because they do not appropriately account for the lived realities of people who are poor, and proposes utility-scale interventions as an alternative.
AMI後の乳頭筋断裂によるMR,急性心不全に対しPCI,MVRを行い救命し得た一例
Authors: Oda Takeshi, Sagara Shuichiro, Miyahara Daisuke, Shojima Masahiro, Sakashita Hideki, Yamawaki Tooru, Tashiro Hideki, Yasunaga Hiroshi, Todo Akishige
Journal: Circulation (2008)
Resolving inflammation by TAM receptor activation
Authors: Juliana P. Vago, Flávio A. Amaral, Fons A.J. van de Loo
Journal: Pharmacology & Therapeutics (2021)

The control of inflammation is strictly regulated to ensure the adequate intensity and duration of an inflammatory response, enabling the removal of the trigger factors and the restoration of the integrity of the tissues and their functions. This process is coordinated by anti-inflammatory and pro-resolving mediators that regulate the cellular and molecular events necessary to restore homeostasis, and defects in this control are associated with the development of chronic and autoimmune diseases. The TAM family of receptor tyrosine kinases—Tyro3, Axl, and MerTK—plays an essential role in efferocytosis, a key process for the resolution of inflammation. However, new studies have demonstrated that TAM receptor activation not only reduces the synthesis of pro-inflammatory mediators by different cell types in response to some stimuli but also stimulates the production of anti-inflammatory and pro-resolving molecules that control the inflammation. This review provides a comprehensive view of TAM receptor family members as important players in controlling inflammatory responses through anti-inflammatory and pro-resolving actions.
129TiP Metformin (MF) in the prevention of hyperglycemia (HG) in patients (pts) with PIK3CA-mutated, hormone receptor (HR)[+]/HER2[–] advanced breast cancer (ABC) treated with alpelisib (ALP) plus fulvestrant (F): METALLICA
Authors: A. Llombart Cussac, J.M. Pérez-Garcia, S. Blanch, P. Tolosa, M. Ruiz Borrego, M. Gion Cortes, A. Fernádez, A. Urruticoechea, E. Galve, J.F. Cueva Banuelos, J. Ponce, J.L. Alonso, M. Capelán, E. Martínez, B. Bermejo De Las Heras, B. Rojas, T. Martos, A. López, F. Gómez-Peralta, J. Cortés
Journal: Annals of Oncology (2021)
Abstract 17010: Predicting Risk of Sudden Death With QT Interval-Prolonging Medications
Authors: Nanki Chugh, Sol Bloomfield, Oliver Leitner, Audrey Uy-Evanado, Sumeet Chugh, Kyndaron Reinier
Journal: Circulation (2020)

Background: The ongoing pandemic has re-emphasized how QT-prolonging drugs can increase risk of sudden cardiac death (SCD), but azithromycin and hydroxychloroquine are only 2 of many such medications. There remains a critical need to identify individuals who are at high risk of SCD based on their demographic and clinical profile. Hypothesis: A modified Tisdale Score (TS), originally designed to assess risk of QTc (corrected QT interval) prolongation with QT-prolonging drugs, could also predict risk of SCD. Methods: From the ongoing Oregon Sudden Unexpected Death Study (ORESUDS), we identified a subgroup of SCD patients with coronary artery disease (CAD) and controls (individuals with and without CAD but no history of SCD) on at least one QT-prolonging medication enrolled between 2002 and 2020. Analysis was restricted to subjects with available pre-arrest medical history, including ECGs with QT interval available and details of prescribed medications. We identified QT prolonging drugs from the comprehensive list at crediblemeds.com. Our TS included age, sex, use of loop diuretics, serum potassium levels, history of acute myocardial infarction, history of heart failure, and number of QT prolonging drugs. We used a univariate logistic regression to determine the predictive power of the modified TS for SCD. We performed a backwards stepwise logistic regression considering race/ethnicity, diabetes, and hypertension in addition to TS to improve SCD prediction. Results: A total of 964 cases (60% male, mean age 68 years) and 668 controls (62% male, mean age 67 years) met inclusion criteria. TS ranged from 0 to 12 and mean TS was 5.86 ± 2.93 in cases and 4.29 ± 2.74 in controls (p &lt; 0.001). A 1-unit increase in the modified TS was a significant predictor of SCD (odds ratio (OR) 1.21, 95% confidence interval, 1.17 to 1.26). In the multivariable model predicting SCD, both the modified TS (OR 1.20, 95% CI, 1.15 to 1.25) and diabetes (OR 1.42, 95% CI, 1.14 to 1.78) were significant independent predictors of SCD. Conclusion: A modified Tisdale Score predicts SCD, and history of diabetes could potentially enhance the utility of this user-friendly clinical tool. These findings have implications for prescription of QT-prolonging drugs, especially during the ongoing pandemic.
Abstract 16592: Excessive MCU-Mediated Mitochondrial Calcium Uptake During Chronic Stress Impairs Cardiac Contractility
Authors: Joanne F Garbincius, Timothy S Luongo, Jonathan P Lambert, Adam S Mangold, Emma K Murray, Alycia N Hildebrand, Pooja Jadiya, John W Elrod
Journal: Circulation (2020)

Calcium (Ca 2+ ) uptake into the mitochondrial matrix occurs via the mitochondrial Ca 2+ uniporter channel (mtCU) and tunes mitochondrial metabolism to meet acute changes in cellular ATP demand. However, the role of mtCU-dependent mitochondrial Ca 2+ ( m Ca 2+ ) uptake in regulating homeostatic heart function and adaptation to chronic increases in workload remain controversial. We subjected mice with tamoxifen-inducible, cardiomyocyte-specific gain (flox-stop-MCU x αMHC-MCM, MCU-Tg) or loss ( Mcu fl/fl x αMHC-MCM , Mcu- cKO) of MCU function to 2wk isoproterenol (iso) infusion to test the hypothesis that m Ca 2+ uptake through MCU contributes to functional adaptation to sustained catecholamine signaling. Neither gain nor loss of MCU function altered baseline cardiac structure or function. Fractional shortening was increased after 2d of iso infusion in MCM control mice, but loss of MCU blocked this effect. In contrast, fractional shortening declined significantly after 7-14d of iso in MCU-Tg mice. MCU-Tg mice also exhibited increased LV dilation, heart mass, and lung edema compared to controls after 14d of iso. Acute treatment of MCU-Tg cardiomyocytes in vitro with the Ca 2+ ionophore ionomycin revealed increased ROS production and a trend towards increased sensitivity to Ca 2+ -induced cell death. In agreement, Evans blue dye exclusion assays revealed increased cardiomyocyte necrosis in MCU-Tg hearts following iso. Therefore, we deleted the mPTP regulator cyclophilin D (CypD) in MCU-Tg mice to test whether cardiomyocyte dropout due to m Ca 2+ overload-induced mPTP contributed to iso-induced contractile dysfunction. Unexpectedly, CypD deletion failed to attenuate contractile dysfunction and hypertrophic remodeling, and increased rather than attenuated iso-induced cardiomyocyte death in MCU-Tg mice. We conclude that while MCU-dependent m Ca 2+ uptake is required for the heart’s initial contractile response to catecholaminergic stress, under prolonged stimulation augmented m Ca 2+ uptake becomes deleterious and predisposes to cardiomyocyte death and heart failure. Our findings support the notion that the detrimental effects of sustained MCU-dependent m Ca 2+ uptake are mediated by mechanisms distinct from mitochondrial permeability transition.
Abstract 16995: Anti-Inflammatory and Immuno-Modulatory Properties of Neonatal MSC
Authors: Sudhish Sharma, Rachana Mishra, Progyaparamita Saha, Muthukumar Gunasekaran, Aakash Shah, Mohamed Abdullah, Sunjay Kaushal
Journal: Circulation (2020)

Background: Anti-inflammatory and immunomodulatory properties are prerequisites for the success of cell therapy as shown by adult Mesenchymal Stem cells (MSC) by reducing both B- and T-lymphocyte proliferation, in a paracrine dependent manner. Proteomics of neonatal MSCs (nMSCs) has identified the superior quality of secretome containing a significantly higher number of anti-inflammatory (68 vs 21 in aMSCs) molecules. Hypothesis: nMSCs have potent anti-inflammatory and immunomodulatory characteristics as compared to other cell types currently being used as cell therapy. Methods: nMSC were tested and compared to other cell types for: a) Hypo-immunogenicity (expression of MHCII in the presence of IFN-gamma), b) immunogenicity (reduce proliferation of human CD4+ T-cells in a co-culture mixed lymphocyte reaction (MLR), c) anti-inflammatory properties (reduce IL-8 secretion of macrophages in the presence of Nigericin, d) systematic immune response (using rat myocardial infarction (MI) model (IL10, TNF-a and IL12)) and e) Immunomodulation (CD4+ cells to T reg CD4 + /CD25 + /FoxP3 + ). Results: Expression of MHCII on nMSCs, after 72 hours of exposure to IFN-gamma and proliferation of CD4 + cells in MLR was significantly (40±3.8% and 55±4.3%, n=5) reduced as compared to aMSC or CDC. IL8 was measured in the supernatants of nMSC derived secretome reduced the secretion of IL8 from activated macrophages in a dose dependent manner (150 ug protein/ml). Intravenous injection of nMSCs in a rat MI model significantly reduced serum levels of of TNF-α and IL-12 while upregulated IL-10 and improving myocardial function. While BM-MSCs and aMSCs failed to significantly modulate immune system, nMSC significantly increased the number of Treg cells as compared to CDC. Similar results were observed with Pig IRI model. Conclusions: Together, in a head-to-head comparison, nMSCs outperformed all other competitive cell types currently under investigation for their tissue repairing role, including CDCs and BM-MSCs to achieve the highest clinical efficacy.
Use patient reported outcome measures (PROMs) in treatment of long covid
Authors: Philip Berry
Journal: BMJ (2021)

The challenges outlined in Sivan and colleagues’ commentary on Ayoubkhani and colleagues’ evidence of the scope and scale of long covid may be even greater than described.1

Teams with staff able to tackle symptoms related to multiple systems will be essential. The “guiding hand” that is often absent when patients attend multiple parallel clinics will need to be visible and effective. An additional skillset will include a good understanding of medically unexplained …
Survival After Implantable Cardioverter-Defibrillator Shocks
Authors: Mehmet K. Aktaş, Arwa Younis, Wojciech Zareba, Valentina Kutyifa, Helmut Klein, James P. Daubert, Mark Estes, Scott McNitt, Bronislava Polonsky, Ilan Goldenberg
Journal: Journal of the American College of Cardiology (2021)
Abstract P123: Prospective Association Between Periodontal Disease And Brain Imaging Markers Of Cerebrovascular And Neurodegenerative Disease: The Atherosclerosis Risk In Communities Study
Authors: Hamdi S Adam, Kamakshi Lakshminarayan, Wendy Wang, Faye L Norby, Thomas Mosley, Keenan Walker, Rebecca F Gottesman, Katie Meyer, Timothy M Hughes, James S Pankow, Dean Wong, Clifford Jack, Souvik Sen, Pamela L Lutsey, James D Beck, Ryan Demmer
Journal: Circulation (2021)

Background: Periodontal disease (PD) is associated positively with neurocognitive outcomes. Few studies have investigated the relationship between PD and indicators of brain aging and vascular changes. Hypothesis: PD is associated with greater cerebral small vessel disease, lower total and regional brain volumes and elevated β-amyloid (Aβ) deposition. Methods: We included 6,793 participants who received full-mouth periodontal examinations and tooth counts at Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities Study. We used a modified 3-level version of the Periodontal Profile Class to categorize PD based on severity and extent of gingival inflammation and tissue loss. Among participants who attended Visit 5 (2011-2013), n=1,306 received a brain MRI and n=248 received a PET scan. Total brain volume, Alzheimer’s disease signature volume, and presence of microhemorrhages and cerebral infarctions were ascertained via 3T MRI; Aβ deposition was assessed from PET. We regressed brain volumes on baseline PD status using weighted multivariable linear regression. Presence of cerebrovascular microhemorrhages, infarctions, or elevated Aβ (standardized uptake value ratio&gt;1.2) were regressed on PD category using logistic models. We examined the interaction between Apolipoprotein E ε4 ( APOE ) allele possession and PD categories on the Aβ outcome. Results: Prevalence of baseline periodontal disease was 73% (959/1306) and 87% (206/248) among the MRI and PET subgroups, respectively. PD was not associated with volumetric brain measures nor microhemorrhages. PD was inversely associated with the odds of subcortical and lacunar infarctions. PD and Aβ were not associated in main effect or interaction analyses, although there was a notably stronger association among carriers of APOE . Conclusion: PD was not associated with altered brain structure, cerebral microhemorrhages or elevated Aβ deposition. Counter to the hypothesis, PD and complete tooth loss were inversely associated with cerebral infarctions.
Abstract 14742: Deep Learning of Intracardiac Electrograms in Atrial Arrhythmia
Authors: Miguel Rodrigo, Albert J Rogers, Prasanth Ganesan, Mahmood Alhusseini, Sanjiv M Narayan
Journal: Circulation (2020)

Introduction: Intracardiac devices detect atrial fibrillation (AF) by rate and regularity, but any inaccuracies may cause inappropriate use of anticoagulants or anti-arrhythmic medications. Hypothesis: Machine learning of raw intracardiac electrograms can identify AF from other atrial arrhythmias better than traditional measures of rate or regularity and without using specific electrophysiological analyses such as dominant frequency (DF). Methods: In 86 persistent AF patients (25 female, age 65±11) we recorded 64 unipolar intracardiac electrograms over 60 seconds prior to ablation (fig A). We trained deep learning models (comprising 2X1D-convolutional layers and 2 dense layers) on successive 4-sec segments labelled AF or Flutter/tachycardia (AFL), using 10-fold cross-validation with 80% of patients for training and an independent 20% for testing. We compared results to classical statistical and machine learning (ML) analyses of electrograms featurized by 30 metrics of cycle length (CL), DF and autocorrelation-based metrics (AC; fig B). Results: Identification of AF varied between methods, but was modest for features of CL (c-statistic 0.70), DF (0.67) and AC (0.75). ML that combined features improved results: linear combination (c-statistic 0.95 ± 0.04), Bagged trees (0.92 ± 0.06), k-nearest neighbors (0.92 ± 0.06) and support vector machines (0.95 ± 0.04). Deep learning using raw electrograms as input (no featurization) provided AUC of 0.95 ± 0.05 (fig C). Conclusions: Detailed machine learning of raw intracardiac electrograms identified AF more accurately than traditional indices of rate, regularity, and dominant frequency. This approach could reclassify AF detection from devices to improve management, and may reveal novel AF phenotypes with distinct clinical courses.