tbuckley/cabot-search huggingface dataset:
S100A9 Links Inflammation and Repair in Myocardial Infarction
Authors: Goran Marinković, Duco Steven Koenis, Lisa de Camp, Robert Jablonowski, Naomi Graber, Vivian de Waard, Carlie Jacoba de Vries, Isabel Goncalves, Jan Nilsson, Stefan Jovinge, Alexandru Schiopu
Journal: Circulation Research (2020)

The alarmin S100A9 has been identified as a potential therapeutic target in myocardial infarction. Short-term S100A9 blockade during the inflammatory phase post-myocardial infarction inhibits systemic and cardiac inflammation and improves cardiac function long term.To evaluate the impact of S100A9 blockade on postischemic cardiac repair.We assessed cardiac function, hematopoietic response, and myeloid phagocyte dynamics in WT (wild type) C57BL/6 mice with permanent coronary artery ligation, treated with the specific S100A9 blocker ABR-238901 for 7 or 21 days. In contrast to the beneficial effects of short-term therapy, extended S100A9 blockade led to progressive deterioration of cardiac function and left ventricle dilation. The treatment reduced the proliferation of Lin-Sca-1+c-Kit+ hematopoietic stem and progenitor cells in the bone marrow and the production of proreparatory CD150+CD48-CCR2+ hematopoietic stem cells. Monocyte trafficking from the spleen to the myocardium and subsequent phenotype switching to reparatory Ly6CloMerTKhi macrophages was also impaired, leading to inefficient efferocytosis, accumulation of apoptotic cardiomyocytes, and a larger myocardial scar. The transcription factor Nur77 (Nr4a1 [nuclear receptor subfamily 4 group A member 1]) mediates the transition from inflammatory Ly6Chi monocytes to reparatory Ly6Clo macrophages. S100A9 upregulated the levels and activity of Nur77 in monocytes and macrophages in vitro and in Ly6Chi/int monocytes in vivo, and S100A9 blockade antagonized these effects. Finally, the presence of reparatory macrophages in the myocardium was also impaired in S100A9-/- mice with permanent myocardial ischemia, leading to depressed cardiac function long term.We show that S100A9 plays an important role in both the inflammatory and the reparatory immune responses to myocardial infarction. Long-term S100A9 blockade negatively impacts cardiac recovery and counterbalances the beneficial effects of short-term therapy. These results define a therapeutic window targeting the inflammatory phase for optimal effects of S100A9 blockade as potential immunomodulatory treatment in acute myocardial infarction.
Helena Legido-Quigley: proponent of health systems strengthening
Authors: Richard Lane
Journal: The Lancet (2020)

As Associate Professor in Health Systems at Saw Swee Hock School of Public Health at the National University of Singapore, Helena Legido-Quigley was able to observe at first-hand how the country responded to its first COVID-19 outbreak earlier this year. "It was striking how well Singapore was prepared, a legacy from the SARS era, with a dedicated infectious diseases hospital and 6 months of supplies of personal protective equipment and ventilators. The public health response was fast and efficient with good governance and effective health-risk communication", she says.
A Single Dose of NILV-Based Vaccine Provides Rapid and Durable Protection against Zika Virus
Authors: Min Wen Ku, François Anna, Philippe Souque, Stéphane Petres, Matthieu Prot, Etienne Simon-Loriere, Pierre Charneau, Maryline Bourgine
Journal: Molecular Therapy (2020)

Zika virus, a member of the Flaviviridae family, is primarily transmitted by infected Aedes species mosquitoes. In 2016, Zika infection emerged as a global health emergency for its explosive spread and the remarkable neurological defects in the developing fetus. Development of a safe and effective Zika vaccine remains a high priority owing to the risk of re-emergence and limited understanding of Zika virus epidemiology. We engineered a non-integrating lentiviralvector(NILV)-based Zika vaccine encoding the consensus pre-membrane and envelope glycoprotein of circulating Zika virus strains. We further evaluated the immunogenicity and protective efficacy of this vaccine in both immunocompromised and immunocompetent mouse models. A single immunization in both mouse models elicited a robust neutralizing antibody titer and afforded full protection against Zika challenge as early as 7 days post-immunization. This NILV-based vaccine also induced a long-lasting immunity when immunized mice were challenged 6 months after immunization. Altogether, our NILV Zika vaccine provides a rapid yet durable protection through a single dose of immunization without extra adjuvant formulation. Our data suggest a promising Zika vaccine candidate for an emergency situation, and demonstrate the capacity of lentiviral vector as an efficient vaccine delivery platform.
Response to: ‘Hydroxychloroquine is neutral in risk of chronic kidney disease in patients with systemic lupus erythematosus’ by Wuet al
Authors: Antonis Fanouriakis, George Bertsias, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2020)

We thank Drs Wu et al for their interest in our manuscript1 and the stimulating data they provide regarding the value of hydroxychloroquine (HCQ) in the prevention of chronic kidney disease (CKD) in patients with systemic lupus erythematosus (SLE).2 We agree with the authors that the evidence behind the recommendation for a 50% reduction in HCQ dose in patients with lupus nephritis (LN) and a glomerular filtration rate (GFR) less than 30% is not supported by high-level evidence (although it is known that excretion of the drug is carried out principally by direct renal clearance).3 4 Nevertheless, CKD is considered a risk factor for the most important side effect of HCQ, retinal toxicity ; …
Phase I/IIa Study of Genetically Engineered NY-ESO-1 SPEAR T-Cells Administered Following Autologous Stem Cell Transplant in HLA-a*02+ Patients with Advanced Multiple Myeloma: Long Term Follow-up (NCT01352286)
Authors: Aaron P. Rapoport, Edward A Stadtmauer, Karen Chagin, Thomas Faitg, Malini Iyengar, Trupti Trivedi, Elliot Norry, Tom Holdich, Gwendolyn Binder-Scholl, Rafael Amado, Frank Fang
Journal: Blood (2017)
59P Primary tumour and circulating tumour cell (CTC) copy number alterations (CNAs) in triple negative breast cancer (TNBC) patients (pts) treated with neoadjuvant chemotherapy (NAC)
Authors: S. Di Cosimo, M. Silvestri, M. Dugo, M. Vismara, C. Reduzzi, G. Pruneri, S. Folli, V. Cappelletti, M.G. Daidone
Journal: Annals of Oncology (2020)
A fully automatic deep learning system for COVID-19 diagnostic and prognostic analysis
Authors: Shuo Wang, Yunfei Zha, Weimin Li, Qingxia Wu, Xiaohu Li, Meng Niu, Meiyun Wang, Xiaoming Qiu, Hongjun Li, He Yu, Wei Gong, Yan Bai, Li Li, Yongbei Zhu, Liusu Wang, Jie Tian
Journal: European Respiratory Journal (2020)

Coronavirus disease 2019 (COVID-19) has spread globally, and medical resources become insufficient in many regions. Fast diagnosis of COVID-19 and finding high-risk patients with worse prognosis for early prevention and medical resource optimisation is important. Here, we proposed a fully automatic deep learning system for COVID-19 diagnostic and prognostic analysis by routinely used computed tomography. We retrospectively collected 5372 patients with computed tomography images from seven cities or provinces. Firstly, 4106 patients with computed tomography images were used to pre-train the deep learning system, making it learn lung features. Following this, 1266 patients (924 with COVID-19 (471 had follow-up for &gt;5 days) and 342 with other pneumonia) from six cities or provinces were enrolled to train and externally validate the performance of the deep learning system. In the four external validation sets, the deep learning system achieved good performance in identifying COVID-19 from other pneumonia (AUC 0.87 and 0.88, respectively) and viral pneumonia (AUC 0.86). Moreover, the deep learning system succeeded to stratify patients into high- and low-risk groups whose hospital-stay time had significant difference (p=0.013 and p=0.014, respectively). Without human assistance, the deep learning system automatically focused on abnormal areas that showed consistent characteristics with reported radiological findings. Deep learning provides a convenient tool for fast screening of COVID-19 and identifying potential high-risk patients, which may be helpful for medical resource optimisation and early prevention before patients show severe symptoms.
Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study
Authors: Joseph A Lewnard, Vincent X Liu, Michael L Jackson, Mark A Schmidt, Britta L Jewell, Jean P Flores, Chris Jentz, Graham R Northrup, Ayesha Mahmud, Arthur L Reingold, Maya Petersen, Nicholas P Jewell, Scott Young, Jim Bellows
Journal: BMJ (2020)

Abstract Objective To understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States. Design Prospective cohort study. Setting Kaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state. Participants 1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington). Main outcome measures Cumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number ( R E ) describing transmission dynamics was estimated for each region. Results As of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in R E were identified over the study period within each region. Conclusions Among residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.
A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial
Authors: Assiamira Ferrara, Monique M Hedderson, Susan D Brown, Samantha F Ehrlich, Ai-Lin Tsai, Juanran Feng, Maren Galarce, Santica Marcovina, Patrick Catalano, Charles P Quesenberry
Journal: The Lancet Diabetes & Endocrinology (2020)
Use of High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia
Authors: Muhammad Hammadah, Jeong Hwan Kim, Ayman Samman Tahhan, Bryan Kindya, Chang Liu, Yi-An Ko, Ibhar Al Mheid, Kobina Wilmot, Ronnie Ramadan, Ayman Alkhoder, Fahad Choudhary, Mohamad Mazen Gafeer, Naser Abdelhadi, Pratik Pimple, Pratik Sandesara, Bruno B. Lima, Amit J. Shah, Laura Ward, Michael Kutner, J. Douglas Bremner, David S. Sheps, Paolo Raggi, Laurence S. Sperling, Viola Vaccarino, Arshed A. Quyyumi
Journal: Annals of Internal Medicine (2018)

Although guidelines recommend against routine surveillance cardiac stress testing for patients with known, stable ischemic heart disease, such testing is frequently performed. This study evaluated ...
The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD
Authors: Kate A. Markey, Jonas Schluter, Antonio L. C. Gomes, Eric R. Littmann, Amanda J. Pickard, Bradford P. Taylor, Paul A. Giardina, Daniela Weber, Anqi Dai, Melissa D. Docampo, Gabriel K. Armijo, Ann E. Slingerland, John B. Slingerland, Katherine B. Nichols, Daniel G. Brereton, Annelie G. Clurman, Ruben J. Ramos, Arka Rao, Amy Bush, Lauren Bohannon, Megan Covington, Meagan V. Lew, David A. Rizzieri, Nelson Chao, Molly Maloy, Christina Cho, Ioannis Politikos, Sergio Giralt, Ying Taur, Eric G. Pamer, Ernst Holler, Miguel-Angel Perales, Doris M. Ponce, Sean M. Devlin, Joao Xavier, Anthony D. Sung, Jonathan U. Peled, Justin R. Cross, Marcel R. M. van den Brink
Journal: Blood (2020)
Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer
Authors: Hae-Ock Lee, Yourae Hong, Hakki Emre Etlioglu, Yong Beom Cho, Valentina Pomella, Ben Van den Bosch, Jasper Vanhecke, Sara Verbandt, Hyekyung Hong, Jae-Woong Min, Nayoung Kim, Hye Hyeon Eum, Junbin Qian, Bram Boeckx, Diether Lambrechts, Petros Tsantoulis, Gert De Hertogh, Woosung Chung, Taeseob Lee, Minae An, Hyun-Tae Shin, Je-Gun Joung, Min-Hyeok Jung, Gunhwan Ko, Pratyaksha Wirapati, Seok Hyung Kim, Hee Cheol Kim, Seong Hyeon Yun, Iain Bee Huat Tan, Bobby Ranjan, Woo Yong Lee, Tae-You Kim, Jung Kyoon Choi, Young-Joon Kim, Shyam Prabhakar, Sabine Tejpar, Woong-Yang Park
Journal: Nature Genetics (2020)
Reply
Authors: Christophe Bureau, Jean-Pierre Vinel
Journal: Hepatology (2013)

We thank Dr. Thabut et al. for their interesting comments following the publication of our study that compares Psychometric Hepatic Encephalopathy Score (PHES) and Critical Flicker Frequency (CFF) to predict post-TIPS encephalopathy in patients with cirrhosis.1 Since specific normative data for PHES are not yet available in France, we used the Spanish algorithm because it was validated in Latin countries (such as France)2, 3 and also because Toulouse is only 150 km north of Spain. Using the same algorithm, Dr. Thabut et al. found that minimal hepatic encephalopathy (MHE) is underdiagnosed by PHES in cirrhosis patients in northern France. They also concluded that PHES should be validated in each country before its use for MHE diagnosis. However, the reliability of the test in a specific patient is not warranted by such validation. Actually, not all patients originate from their residing country. For example, should we use in France the Spanish algorithm for a patient born and raised in Spain? A Japanese algorithm for Japanese patients? Then how long after their settling in a country should we switch to the specific algorithm of that country? Actually, it will be much more difficult to have a set of different PHES specifically tailored for particular education and cultural backgrounds. On the contrary, CFF is readily available, fast to perform, and can be used for all patients independently of their education level, age, residing country, or training. Combined with our results, this confirms the advantages of CFF over PHES. Christophe Bureau, M.D., Ph.D. Jean-Pierre Vinel, M.D. Service d'hepato-gastro-enterologie CHU Toulouse Hopital Purpan et Universite Paul Sabatier Toulouse, France
Molecular analysis of inverted tumors of the urinary bladder
Authors: Arndt Hartmann, Matthias Eiber, Joke Van Oers, Ellen Zwarthoff, Peter Wild, Robert Stoehr, Theo Van der Kwast, Guido Sauter, John C. Cheville, Mahul Amin, Ferdinand Hofstaedter, Regine Schneider-Stock, Hagen J. Blaszyk
Journal: Cancer Research (2005)

3148  Aim: Inverted papilloma of the urinary tract (IP) is thought to be benign, but some urothelial carcinomas show a prominent inverted growth pattern (invUC) which may pose a diagnostic dilemma to the pathologist and clinician. Ancillary markers may help to resolve diagnostically challenging cases and may contribute to the ongoing discussion of a possible malignant potential of some IP. We previously detected a frequent inverted growth pattern in urothelial carcinomas of the ureter and renal pelvis with microsatellite instability and loss of mismatch repair protein expression, raising the possibility that inverted growth of urothelial tumors in general could be associated with a mutator phenotype. The aim of the present study was to characterize the most frequent molecular alterations detected in urothelial carcinomas in a well defined cohort of inverted tumors of the urinary bladder. Methods: Seventy-two cases diagnosed as IP were reviewed by 5 uropathologists. Final diagnosis was IP in 63 and invUC in 9 cases. Expression of CK20, p53, Mib-1, MSH2, MLH1 and MSH6 was studied by immunohistochemistry. Mutation in FGFR3 was analyzed by SNAPShot analysis. Promoter methylation of p16, DAPK, E-cadherin, RASSF1 and MLH1 was investigated by methylation-specific PCR. Microsatellite analysis to detect deletions of chromosome 9p/q and 17p (LOH) and microsatellite instability (MSI) using the Bethesda consensus marker panel for HNPCC diagnosis was performed. Tissue microarrays of the inverted tumors were constructed and investigated for aneuploidy and p16 homozygous deletions using FISH (Urovysion). Results: In contrast to inverted tumors of the upper urinary tract, microsatellite instability in IP or invUC of the bladder was not detected. Mismatch repair protein expression was retained in all tumors. IP had very infrequently deletions at chromosomes 9p/q or 17p and promoter methylation of the genes investigated (all  10% favour a diagnosis of invUC, which could help resolve histologically ambiguous cases. A mutator phenotype with microsatellite instability and loss of mismatch repair protein expression is infrequent in bladder tumors, even in a selected cohort with inverted growth pattern.
Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome
Authors: Anouchka P. Laurent, Rishi S. Kotecha, Sébastien Malinge
Journal: Leukemia (2020)

Structural and numerical alterations of chromosome 21 are extremely common in hematological malignancies. While the functional impact of chimeric transcripts from fused chromosome 21 genes such as TEL-AML1, AML1-ETO, or FUS-ERG have been extensively studied, the role of gain of chromosome 21 remains largely unknown. Gain of chromosome 21 is a frequently occurring aberration in several types of acute leukemia and can be found in up to 35% of cases. Children with Down syndrome (DS), who harbor constitutive trisomy 21, highlight the link between gain of chromosome 21 and leukemogenesis, with an increased risk of developing acute leukemia compared with other children. Clinical outcomes for DS-associated leukemia have improved over the years through the development of uniform treatment protocols facilitated by international cooperative groups. The genetic landscape has also recently been characterized, providing an insight into the molecular pathogenesis underlying DS-associated leukemia. These studies emphasize the key role of trisomy 21 in priming a developmental stage and cellular context susceptible to transformation, and have unveiled its cooperative function with additional genetic events that occur during leukemia progression. Here, using DS-leukemia as a paradigm, we aim to integrate our current understanding of the role of trisomy 21, of critical dosage-sensitive chromosome 21 genes, and of associated mechanisms underlying the development of hematological malignancies. This review will pave the way for future investigations on the broad impact of gain of chromosome 21 in hematological cancer, with a view to discovering new vulnerabilities and develop novel targeted therapies to improve long term outcomes for DS and non-DS patients.
After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy
Authors: Thomas Rauen, Stephanie Wied, Christina Fitzner, Frank Eitner, Claudia Sommerer, Martin Zeier, Britta Otte, Ulf Panzer, Klemens Budde, Urs Benck, Peter R. Mertens, Uwe Kuhlmann, Oliver Witzke, Oliver Gross, Volker Vielhauer, Johannes F.E. Mann, Ralf-Dieter Hilgers, Jürgen Floege, Jürgen Floege, Frank Eitner, Thomas Rauen, Marcus J. Moeller, Horst Weihprecht, Klemens Budde, Harm Peters, Saban Elitok, Markus Bieringer, Ralf Schindler, Ulrich Frei, Sima Canaan–Kühl, Christiane Erley, Karsten Schlieps, Uwe Kuhlmann, Frans Zandvoort, Bernd Hohenstein, Christian Hugo, Catrin Palm, Karl Hilgers, Oliver Witzke, Oliver Gross, Ulf Panzer, Hermann Haller, Anna Bertram, Claudia Sommerer, Martin Zeier, Gunter Wolf, Martin Busch, Thomas Rath, Stephan Ziefle, Thomas Benzing, Franziska Grundmann, Peter R. Mertens, Stefan Westphalen, Urs Benck, Uwe Göttmann, Volker Vielhauer, Michael Fischereder, Oliver Sarkar, Marianna Stefanidou, Johannes F.E. Mann, Britta Otte, Hermann Pavenstädt, Bernhard Banas, Alexander Boeger, Nils Heyne, Ferruh Artunc, Helmut Reichel, Thomas Mettang, Christoph Wanner, Thomas Metzger, Stephanie Wied, Christina Fitzner, Ralf-Dieter Hilgers
Journal: Kidney International (2020)
Automated ultrasound assessment of amniotic fluid index using deep learning
Authors: Hyun Cheol Cho, Siyu Sun, Chang Min Hyun, Ja-Young Kwon, Bukweon Kim, Yejin Park, Jin Keun Seo
Journal: Medical Image Analysis (2021)

The estimation of antenatal amniotic fluid (AF) volume (AFV) is important as it offers crucial information about fetal development, fetal well-being, and perinatal prognosis. However, AFV measurement is cumbersome and patient specific. Moreover, it is heavily sonographer-dependent, with measurement accuracy varying greatly depending on the sonographer's experience. Therefore, the development of accurate, robust, and adoptable methods to evaluate AFV is highly desirable. In this regard, automation is expected to reduce user-based variability and workload of sonographers. However, automating AFV measurement is very challenging, because accurate detection of AF pockets is difficult owing to various confusing factors, such as reverberation artifact, AF mimicking region and floating matter. Furthermore, AF pocket exhibits an unspecified variety of shapes and sizes, and ultrasound images often show missing or incomplete structural boundaries. To overcome the abovementioned difficulties, we develop a hierarchical deep-learning-based method, which consider clinicians' anatomical-knowledge-based approaches. The key step is the segmentation of the AF pocket using our proposed deep learning network, AF-net. AF-net is a variation of U-net combined with three complementary concepts - atrous convolution, multi-scale side-input layer, and side-output layer. The experimental results demonstrate that the proposed method provides a measurement of the amniotic fluid index (AFI) that is as robust and precise as the results from clinicians. The proposed method achieved a Dice similarity of 0.877±0.086 for AF segmentation and achieved a mean absolute error of 2.666±2.986 and mean relative error of 0.018±0.023 for AFI value. To the best of our knowledge, our method, for the first time, provides an automated measurement of AFI.