tbuckley/cabot-search huggingface dataset:
Delta variant (B.1.617.2) sublineages do not show increased neutralization resistance
Authors: Prerna Arora, Amy Kempf, Inga Nehlmeier, Luise Graichen, Anzhalika Sidarovich, Martin S. Winkler, Sebastian Schulz, Hans-Martin Jäck, Metodi V. Stankov, Georg M. N. Behrens, Stefan Pöhlmann, Markus Hoffmann
Journal: Cellular and Molecular Immunology (2021)
Nanostructured gold electrodes promote neural maturation and network connectivity
Authors: Ana Domínguez-Bajo, Juliana M. Rosa, Ankor González-Mayorga, Beatriz L. Rodilla, Ana Arché-Núñez, Esther Benayas, Pilar Ocón, Lucas Pérez, Julio Camarero, Rodolfo Miranda, M. Teresa González, Juan Aguilar, Elisa López-Dolado, María C. Serrano
Journal: Biomaterials (2021)

Progress in the clinical application of recording and stimulation devices for neural diseases is still limited, mainly because of suboptimal material engineering and unfavorable interactions with biological entities. Nanotechnology is providing upgraded designs of materials to better mimic the native extracellular environment and attain more intimate contacts with individual neurons, besides allowing for the miniaturization of the electrodes. However, little progress has been done to date on the understanding of the biological impact that such neural interfaces have on neural network maturation and functionality. In this work, we elucidate the effect of a gold (Au) highly ordered nanostructure on the morphological and functional interactions with neural cells and tissues. Alumina-templated Au nanostructured electrodes composed of parallel nanowires of 160 nm in diameter and 1.2 μm in length (Au-NWs), with 320 nm of pitch, are designed and characterized. Equivalent non-structured Au electrodes (Au-Flat) are used for comparison. By using diverse techniques in in vitro cell cultures including live calcium imaging, we found that Au-NWs interfaced with primary neural cortical cells for up to 14 days allow neural networks growth and increase spontaneous activity and ability of neuronal synchronization, thus indicating that nanostructured features favor neuronal network. The enhancement in the number of glial cells found is hypothesized to be behind these beneficial functional effects. The in vivo effect of the implantation of these nanostructured electrodes and its potential relevance for future clinical applicability has been explored in an experimental model of rat spinal cord injury. Subacute responses to implanted Au-NWs show no overt reactive or toxic biological reactions besides those triggered by the injury itself. These results highlight the translational potential of Au-NWs electrodes for in vivo applications as neural interfaces in contact with central nervous tissues including the injured spinal cord.
Association Between Hereditary Lobular Breast Cancer Due to <i>CDH1</i> Variants and Gastric Cancer Risk
Authors: Lauren A. Gamble, Alexander Rossi, Grace-Ann Fasaye, Chimene Kesserwan, Jonathan M. Hernandez, Andrew M. Blakely, Jeremy L. Davis
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer. <h3>Objective</h3> To assess gastric cancer risk among patients who received a diagnosis of hereditary lobular breast cancer (HLBC) owing to a germline loss-of-function variant in<i>CDH1</i>by establishing prevalence of signet ring cell carcinomas among asymptomatic patients. <h3>Design, Setting, and Participants</h3> A prospective cohort study of patients with germline<i>CDH1</i>pathogenic or likely pathogenic (P/LP) variants at a quaternary medical center were enrolled between October 2017 and January 2021. Data analysis was performed in May 2021. Analyses for associations were performed for these 3 patient groups: (1) family history of breast cancer and no gastric cancer in the HLBC group; (2) family history of gastric cancer and no breast cancer in the hereditary diffuse gastric cancer (HDGC) group; and (3) family history of both breast and gastric cancers in the mixed group. Categorical variables were compared using the Pearson χ<sup>2</sup>test. <h3>Main Outcomes and Measures</h3> The primary end point of this study was the prevalence of occult signet ring cell carcinoma of the stomach in patients with HLBC. Personal and family medical history, genotype, and pathologic data from risk-reducing total gastrectomy and surveillance endoscopy were examined. <h3>Results</h3> A total of 283 patients with<i>CDH1</i>P/LP variants (199 [70.3%] were female, and 259 [91.5%] were White; median age, 48 years [range, 18-81 years]) were enrolled in a prospective study of HDGC. The cohort consisted of 151 families. Patients were categorized according to family history of breast and/or gastric cancer: HLBC 15.5% [44 of 283 patients]), HDGC (16.2% [46 of 283 patients]), and mixed (68.2% [193 of 283 patients]). The HLBC group included 31 distinct families with 19<i>CDH1</i>variants; 10 of those variants were also present in the HDGC and mixed groups (52.6% [10 of 19 variants]). Nearly all of the patients with HLBC (93.8% [15 of 16 variants]) who elected for risk-reducing total gastrectomy owing to their underlying<i>CDH1</i>P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology (median age, 50 years [range, 21-67 years]). The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similar (94.7% [18 of 19 of variants];<i>P</i> = .98). <h3>Conclusions and Relevance</h3> Carriers of<i>CDH1</i>P/LP variants with no family history of gastric cancer exhibited high rates of occult signet ring cell gastric cancer. Germline<i>CDH1</i>P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history. These data may prove useful for counseling families with<i>CDH1</i>variants presumed to have HLBC.
Microfluidics-assisted optimization of highly adhesive haemostatic hydrogel coating for arterial puncture
Authors: Xingjie Yin, Jingli Ren, Wei Lan, Yu Chen, Mengping Ouyang, Hua Su, Lianbin Zhang, Jintao Zhu, Chun Zhang
Journal: Bioactive Materials (2021)

Although common in clinical practice, bleeding after tissue puncture may cause serious outcomes, especially in arterial puncture. Herein, gelatin-tannic acid composite hydrogels with varying compositions are prepared, and their adhesive properties are further optimized in microfluidic channel-based simulated vessels for haemostasis in arterial puncture. It is revealed that the composite hydrogels on the syringe needles used for arterial puncture should possess underwater adhesion higher than 4.9 kPa and mechanical strength higher than 86.0 kPa. The needles coated with the gelatin-tannic acid composite hydrogel completely prevent blood loss after both vein and arterial puncture in different animal models. This study holds great significance for the preparation of haemostatic needles for vessel puncture, and gelatin-tannic acid hydrogel coated needles may help to prevent complications associated with arterial puncture.
JAK Inhibitor Effectiveness in Giant-Cell Arteritis With Large-Vessel Involvement Assessed by 18F-FDG PET-CT
Authors: Kevin Prigent, Achille Aouba, Nicolas Aide, Hubert de Boysson
Journal: Clinical Nuclear Medicine (2021)

We report the case of a 76-year-old woman with relapsing giant-cell arteritis and large-vessel vasculitis demonstrated on 18F-FDG-PET/CT. Methotrexate and tocilizumab failed to achieve remission, and the patient ultimately exhibited a favorable clinical and radiological response to baricitinib, a JAK inhibitor. This case suggests that baricitinib may be a promising treatment for giant-cell arteritis-related large-vessel vasculitis and that 18F-FDG-PET/CT may be used to monitor therapeutic response.
Dead-End Hybridization in Walnut Trees Revealed by Large-Scale Genomic Sequence Data
Authors: Wei-Ping Zhang, Lei Cao, Xin-Rui Lin, Ya-Mei Ding, Yu Liang, Da-Yong Zhang, Er-Li Pang, Susanne S Renner, Wei-Ning Bai
Journal: Molecular Biology and Evolution (2021)

Abstract Although hybridization plays a large role in speciation, some unknown fraction of hybrid individuals never reproduces, instead remaining as genetic dead-ends. We investigated a morphologically distinct and culturally important Chinese walnut, Juglans hopeiensis, suspected to have arisen from hybridization of Persian walnut (J. regia) with Asian butternuts (J. cathayensis, J. mandshurica, and hybrids between J. cathayensis and J. mandshurica). Based on 151 whole-genome sequences of the relevant taxa, we discovered that all J. hopeiensis individuals are first-generation hybrids, with the time for the onset of gene flow estimated as 370,000 years, implying both strong postzygotic barriers and the presence of J. regia in China by that time. Six inversion regions enriched for genes associated with pollen germination and pollen tube growth may be involved in the postzygotic barriers that prevent sexual reproduction in the hybrids. Despite its long-recurrent origination and distinct traits, J. hopeiensis does not appear on the way to speciation.
Paul Zimmet: A Voice for Diabetes
Authors: Jonathan E. Shaw
Journal: Diabetes Care (2021)

Paul Zimmet has been one of the leading figures, globally, in transforming the understanding and threat of diabetes from a Cinderella disease to a major plank of most governments’ health policies. His science, particularly a series of epidemiological studies, has been at the forefront of the campaign, but it is fueled by his genuine passion to improve the life of people with diabetes. After more than 50 years of working in the diabetes field, he continues to actively push the boundaries of our understanding of the condition.



Paul Zimmet



The Zimmet family has medicine running through its veins, but it was not always the somewhat privileged life of the professional classes. Paul Zimmet’s father, Jacob, was born in Tarnopol, Poland, and graduated in medicine from the University of Vienna in 1935. However, with rising anti-Semitism, the only position available to him was an unpaid one at the Tarnopol Hospital. Jacob realized there was no future in Poland, and in 1938, he, along with his wife and first child, Rena, fled Poland and fortunately was able to obtain passage to Australia. Of all the family that remained behind, only one survived the Nazi concentration camps. Australia was far from the horrors of the Holocaust, but life was still not easy, as Jacob had to requalify in medicine, which he achieved at the University of Adelaide in 1942.

Paul was born in 1941 and grew up in his father’s country medical practice in Whyalla, a small town nearly 400 km from the city of Adelaide. From such small beginnings, a dynasty of medicine began, as Paul, two of his siblings Rena and Leon, Paul’s two sons Hendrik and Marcel, and Paul’s nephew Adam entered the profession, and between them have specialized in diabetes, cardiology, pediatrics, and cardiac surgery.

Paul graduated from the …
Experimental and computational modeling for signature and biomarker discovery of renal cell carcinoma progression
Authors: Lindsay S. Cooley, Justine Rudewicz, Wilfried Souleyreau, Andrea Emanuelli, Arturo Alvarez-Arenas, Kim Clarke, Francesco Falciani, Maeva Dufies, Diether Lambrechts, Elodie Modave, Domitille Chalopin-Fillot, Raphael Pineau, Damien Ambrosetti, Jean-Christophe Bernhard, Alain Ravaud, Sylvie Négrier, Jean-Marc Ferrero, Gilles Pagès, Sebastien Benzekry, Macha Nikolski, Andreas Bikfalvi
Journal: Molecular Cancer (2021)

Renal Cell Carcinoma (RCC) is difficult to treat with 5-year survival rate of 10% in metastatic patients. Main reasons of therapy failure are lack of validated biomarkers and scarce knowledge of the biological processes occurring during RCC progression. Thus, the investigation of mechanisms regulating RCC progression is fundamental to improve RCC therapy.In order to identify molecular markers and gene processes involved in the steps of RCC progression, we generated several cell lines of higher aggressiveness by serially passaging mouse renal cancer RENCA cells in mice and, concomitantly, performed functional genomics analysis of the cells. Multiple cell lines depicting the major steps of tumor progression (including primary tumor growth, survival in the blood circulation and metastatic spread) were generated and analyzed by large-scale transcriptome, genome and methylome analyses. Furthermore, we performed clinical correlations of our datasets. Finally we conducted a computational analysis for predicting the time to relapse based on our molecular data.Through in vivo passaging, RENCA cells showed increased aggressiveness by reducing mice survival, enhancing primary tumor growth and lung metastases formation. In addition, transcriptome and methylome analyses showed distinct clustering of the cell lines without genomic variation. Distinct signatures of tumor aggressiveness were revealed and validated in different patient cohorts. In particular, we identified SAA2 and CFB as soluble prognostic and predictive biomarkers of the therapeutic response. Machine learning and mathematical modeling confirmed the importance of CFB and SAA2 together, which had the highest impact on distant metastasis-free survival. From these data sets, a computational model predicting tumor progression and relapse was developed and validated. These results are of great translational significance.A combination of experimental and mathematical modeling was able to generate meaningful data for the prediction of the clinical evolution of RCC.
Inhibition of gasdermin D-dependent pyroptosis attenuates the progression of silica-induced pulmonary inflammation and fibrosis
Authors: Meiyue Song, Jiaxin Wang, Youliang Sun, Junling Pang, Xiaona Li, Yuan Liu, Yitian Zhou, Peiran Yang, Tianhui Fan, Ying Liu, Zhaoguo Li, Xianmei Qi, Baicun Li, Xinri Zhang, Jing Wang, Chen Wang
Journal: Acta Pharmaceutica Sinica B (2021)

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.
Abstract 16820: Albuminuria and Outcomes in Patients With Non-ST-segment Elevation Acute Coronary Syndromes: Results From the TRACER Trial
Authors: Axel Akerblom, Robert Clare, Yuliya Lokhnygina, Lars Wallentin, Claes Held, Frans Van de Werf, David Moliterno, Uptal Patel, Sergio Leonardi, Paul Armstrong, Robert Harrington, Harvey White, Philip Aylward, Kenneth Mahaffey, Pierluigi Tricoci
Journal: Circulation (2015)

Introduction: Patients with acute coronary syndromes (ACS) and kidney dysfunction are at increased risk of recurrent cardiovascular (CV) adverse events. Urinary albumin excretion (albuminuria) has been independently associated with CV outcomes. However, in a high-risk population of patients with ACS, the additional prognostic information of albuminuria to estimated glomerular filtration rate (eGFR) is less clear. Hypothesis: We studied the relationship between albuminuria and CV death and myocardial infarction (MI) in 12,944 patients with non-ST-segment elevation (NSTE)-ACS. Methods: Albuminuria was collected routinely at baseline by dipsticks and stratified into no/trace albuminuria, microalbuminuria (≥30mg/dL), and macroalbuminuria (≥300mg/dL). Baseline serum creatinine was obtained. Kaplan-Meier event rates for CV death, and the combination of CV death or MI were calculated. Multivariable adjusted Cox regression models, with baseline characteristics and biomarkers, and the addition of eGFR (Chronic Kidney Disease - Epidemiology (CKD-EPI) equation), were assessed. Results: Levels of albuminuria were available in 9736 patients (75.2%), and both serum creatinine and albuminuria measurements in 9473 (73.2%) patients. More patients with macroalbuminuria, compared with patients with no albuminuria, had diabetes (66% vs. 27%) or hypertension (86% vs. 68%) There was a significant increased risk in CV events with macroalbuminuria, which was significant in the adjusted model but did not remain significant when eGFR was added to the model (Table). Conclusions: High-risk patients with NSTE-ACS and albuminuria at presentation have an increased risk of adverse CV outcomes. However, in the present cohort, albuminuria did not provide additional independent prognostic value to eGFR.
OA06.01 Validation of the 8th Ed TNM: Invasive Size for Pathologic T Descriptor in Stage I-IIA Resected Nonmucinous Adenocarcinomas
Authors: Y. Li, J. Choe, K.S. Tan, W. Cheema, N. Rekhtman, P. Adusumilli, W. Travis
Journal: Journal of Thoracic Oncology (2021)
P16-3 Maintenance therapy in HER2 and hormone receptor-positive breast cancer
Authors: Shengnan Bao, Fan Yang, Chunxiao Sun, Yijia Hua, Mengzhu Yang, Yiqi Yang, Yinghong Xie, Xueqi Yan, Yuchen Zhang, Tianyu Zeng, Ziyi Fu, Hao Wu, Xiang Huang, Jun Li, Wei Li, Yongmei Yin
Journal: Annals of Oncology (2021)
Clinical and molecular correlates from a predominantly adult cohort of patients with short telomere lengths
Authors: Abhishek A. Mangaonkar, Alejandro Ferrer, Filippo Pinto E. Vairo, Caleb W. Hammel, Carri Prochnow, Naseema Gangat, William J. Hogan, Mark R. Litzow, Steve G. Peters, J. P. Scott, James P. Utz, Misbah Baqir, Eva M. Carmona-Porquera, Sanjay Kalra, Hiroshi Sekiguchi, Shakila P. Khan, Douglas A. Simonetto, Eric W. Klee, Patrick S. Kamath, Anja C. Roden, Avni Y. Joshi, Cassie C. Kennedy, Mark E. Wylam, Mrinal M. Patnaik
Journal: Blood Cancer Journal (2021)
Primary Sjögren’s Syndrome – a randomised, controlled, blinded dose-ranging trial with ianalumab (VAY736), offering two ways to suppress B Cells
Authors: Simon Bowman, Robert Fox, Thomas Dörner, Xavier Mariette, Athena Papas, Thomas Grader-Beck, Benjamin Fisher, Filipe Barcelos, Salvatore De Vita, Hendrik Schulze-Koops, Robert Moots, Guido Junge, Janice Woznicki, Monika Sopala, Wen-Lin Luo, Wolfgang Hueber
Journal: The Lancet (2021)
Abstract 18272: Impact of Body Mass Index and Gender on Left Atrial Size and the Presence of Atrial Fibrillation
Authors: Luis Gruberg, Puja B Parikh, Aditi Malhotra, Smadar Kort
Journal: Circulation (2011)

Background: Atrial fibrillation (AF) is frequently observed in overweight and obese adults. There is limited data on whether increased body mass index (BMI) is independently associated with left atrial (LA) enlargement or the presence of AF. We sought to evaluate the impact of BMI on LA size and presence of AF and to assess whether it is gender specific. Methods: We reviewed 1,200 consecutive transthoracic echocardiograms performed at a tertiary care medical center. A total of 701 tests were excluded due to significant mitral valve disease or incomplete LA assessment. LA measurements obtained included A-P diameter from parasternal long axis view, LA area (LAA) and volume (LAV) from apical 2- and 4-chamber views and indexed LA volume to body surface area (LAVI). Patients were divided into three groups according to BMI: normal BMI between 18.5 and 24.9, overweight with a BMI between 25 and 30 and obese with a BMI greater than 30. Results: Among 499 patients included in this analysis, 259 (51.9%) were female and 240 (48.1%) were male. Of these, 151 (30.1%) had normal BMI, 181 (36.3%) were overweight and 167 (33.5%) were obese. Obese patients were younger, hypertensive, diabetic, and had larger LA diameter, LAA, and LAV, but similar LAVI. Using multivariate analysis, BMI and gender were both found to be independently associated with LA diameter (p&lt;0.001 for both) and LAA (p&lt;0.001 for both) but not LAVI or the presence of AF. Predictors of LA diameter in men and women included age, BMI, and right ventricular systolic pressure (RVSP). Left ventricular ejection fraction (LVEF) was an independent predictor of LA diameter and LAA in women but not men. Predictors of AF included LAVI (OR 1.046, 95%CI 1.023-1.070) in men and LAA (OR 1.227, 95%CI 1.130-1.333) and age (per year) (OR 1.041, 95%CI 1.008-1.075) in women. Conclusions: BMI and gender are independent predictors of LA diameter and LAA but not of LAVI or AF. However, LAVI is an independent predictor of AF in men, whereas LAA and age are independent predictors of AF in women.
VP8-2021: Adjuvant abemaciclib combined with endocrine therapy (ET): Updated results from monarchE
Authors: J. O'Shaughnessy, P. Rastogi, N. Harbeck, M. Toi, R. Hegg, J. Sohn, V. Guarneri, J. Cortes, E. Hamilton, R. Wei, A. Shahir, B. San Antonio, S.C. Nabinger, S. Tolaney, M. Martin, S.R.D. Johnston
Journal: Annals of Oncology (2021)
FP08.04 Tumour Spread Through Air Space (STAS) In Lung Metastases
Authors: A. Sandri, L. Righi, E. Falco, F. Napoli, V. Zambelli, L. Errico, S. Novello, S. Sobrero, R. Rapanà, F. Vaisitti, F. Leo
Journal: Journal of Thoracic Oncology (2021)
OA01.02 Impact of COVID-19 Outbreak on Lung Cancer Diagnosis and Continuum of Care: Data From an Italian Multicenter Study
Authors: L. Cantini, G. Mentrasti, S. Siena, G. Pasello, A. Galetti, E. Caliman, D. Rocco, V. Adamo, C. Genova, A. Morabito, S. Gori, E. Rijavec, R. Chiari, S. Oldani, A. Caglio, M. De Tursi, A. Cortellini, F. Morgillo, C. Bennati, A. Guida, G.P. Spinelli, R. Emili, E. Roca, A. Indini, A. De Toma, I. Vallini, V. D'Emilio, V. Cognigni, F. Pecci, A. Migliore, L. Della Gravara, S. Frega, L. Zullo, E. Zattarin, F. Citarella, A. Russo, S. Fancelli, S. Oresti, R. Berardi
Journal: Journal of Thoracic Oncology (2021)
1MO Multi-omic characterization of lung tumors identify AKT and EZH2 as potential therapeutic targets in adenocarcinoma-to-squamous transdifferentiation
Authors: Á. Quintanal-Villalonga, H. Taniguchi, Y.A. Zhan, M.M. Hasan, S.S. Chavan, F. Uddin, V. Allaj, P. Manoj, N. Shah, M. Ciampricotti, U. Bhanot, J. Egger, J. Qiu, E. De Stanchina, N. Rekhtman, B. Houck-Loomis, R.P. Koche, H.A. Yu, T. Sen, C.M. Rudin
Journal: Annals of Oncology (2021)
Early and short‐term intensive management after discharge for patients hospitalized with acute heart failure: a randomized study (<scp>ECAD‐HF</scp>)
Authors: Damien Logeart, Emmannuelle Berthelot, Nicolas Bihry, Romain Eschalier, Muriel Salvat, Philippe Garcon, Jean‐Christophe Eicher, Ariel Cohen, Jean‐Michel Tartiere, Alireza Samadi, Erwan Donal, Pascal deGroote, Nathan Mewton, Nicolas Mansencal, Pierre Raphael, Nachwan Ghanem, Marie‐France Seronde, Christophe Chavelas, Yann Rosamel, Florence Beauvais, Jean‐Philippe Kevorkian, Abdourahmane Diallo, Eric Vicaut, Richard Isnard
Journal: European Journal of Heart Failure (2021)
P40.17 Palliative Radiotherapy Decreased K+ and Ca2+of the Blood in Patients With Stage IV Lung Cancer
Authors: W. Xu, L. Ma, Z. Liang, C. Zhao, F. Zhang, L. Xu, Y. Zhang, W. Chen, Z. Chen, J. Zha, Y. Han, Y. Qu, J. Zhang, L. Yang, F.M. Kong
Journal: Journal of Thoracic Oncology (2021)
A novel prodrug and its nanoformulation suppress cancer stem cells by inducing immunogenic cell death and inhibiting indoleamine 2, 3-dioxygenase
Authors: Jiankun Guan, Yuxin Wu, Xin Liu, Huimin Wang, Ningbing Ye, Zheng Li, Chen Xiao, Zhijie Zhang, Zifu Li, Xiangliang Yang
Journal: Biomaterials (2021)