tbuckley/cabot-search huggingface dataset:
Deep learning for detection and segmentation of artefact and disease instances in gastrointestinal endoscopy
Authors: Sharib Ali, Mariia Dmitrieva, Noha Ghatwary, Sophia Bano, Gorkem Polat, Alptekin Temizel, Adrian Krenzer, Amar Hekalo, Yun Bo Guo, Bogdan Matuszewski, Mourad Gridach, Irina Voiculescu, Vishnusai Yoganand, Arnav Chavan, Aryan Raj, Nhan T. Nguyen, Dat Q. Tran, Le Duy Huynh, Nicolas Boutry, Shahadate Rezvy, Haijian Chen, Yoon Ho Choi, Anand Subramanian, Velmurugan Balasubramanian, Xiaohong W. Gao, Hongyu Hu, Yusheng Liao, Danail Stoyanov, Christian Daul, Stefano Realdon, Renato Cannizzaro, Dominique Lamarque, Terry Tran-Nguyen, Adam Bailey, Barbara Braden, James E. East, Jens Rittscher
Journal: Medical Image Analysis (2021)

The Endoscopy Computer Vision Challenge (EndoCV) is a crowd-sourcing initiative to address eminent problems in developing reliable computer aided detection and diagnosis endoscopy systems and suggest a pathway for clinical translation of technologies. Whilst endoscopy is a widely used diagnostic and treatment tool for hollow-organs, there are several core challenges often faced by endoscopists, mainly: 1) presence of multi-class artefacts that hinder their visual interpretation, and 2) difficulty in identifying subtle precancerous precursors and cancer abnormalities. Artefacts often affect the robustness of deep learning methods applied to the gastrointestinal tract organs as they can be confused with tissue of interest. EndoCV2020 challenges are designed to address research questions in these remits. In this paper, we present a summary of methods developed by the top 17 teams and provide an objective comparison of state-of-the-art methods and methods designed by the participants for two sub-challenges: i) artefact detection and segmentation (EAD2020), and ii) disease detection and segmentation (EDD2020). Multi-center, multi-organ, multi-class, and multi-modal clinical endoscopy datasets were compiled for both EAD2020 and EDD2020 sub-challenges. The out-of-sample generalization ability of detection algorithms was also evaluated. Whilst most teams focused on accuracy improvements, only a few methods hold credibility for clinical usability. The best performing teams provided solutions to tackle class imbalance, and variabilities in size, origin, modality and occurrences by exploring data augmentation, data fusion, and optimal class thresholding techniques.
Endoplasmic reticulum–associated degradation is required for nephrin maturation and kidney glomerular filtration function
Authors: Sei Yoshida, Xiaoqiong Wei, Gensheng Zhang, Christopher L. O’Connor, Mauricio Torres, Zhangsen Zhou, Liangguang Lin, Rajasree Menon, Xiaoxi Xu, Wenyue Zheng, Yi Xiong, Edgar Otto, Chih-Hang Anthony Tang, Rui Hua, Rakesh Verma, Hiroyuki Mori, Yang Zhang, Chih-Chi Andrew Hu, Ming Liu, Puneet Garg, Jeffrey B. Hodgin, Shengyi Sun, Markus Bitzer, Ling Qi
Journal: Journal of Clinical Investigation (2021)

Podocytes are key to the glomerular filtration barrier by forming a slit diaphragm between interdigitating foot processes; however, the molecular details and functional importance of protein folding and degradation in the ER remain unknown. Here, we show that the SEL1L-HRD1 protein complex of ER-associated degradation (ERAD) is required for slit diaphragm formation and glomerular filtration function. SEL1L-HRD1 ERAD is highly expressed in podocytes of both mouse and human kidneys. Mice with podocyte-specific Sel1L deficiency develop podocytopathy and severe congenital nephrotic syndrome with an impaired slit diaphragm shortly after weaning and die prematurely, with a median lifespan of approximately 3 months. We show mechanistically that nephrin, a type 1 membrane protein causally linked to congenital nephrotic syndrome, is an endogenous ERAD substrate. ERAD deficiency attenuated the maturation of nascent nephrin, leading to its retention in the ER. We also show that various autosomal-recessive nephrin disease mutants were highly unstable and broken down by SEL1L-HRD1 ERAD, which attenuated the pathogenicity of the mutants toward the WT allele. This study uncovers a critical role of SEL1L-HRD1 ERAD in glomerular filtration barrier function and provides insights into the pathogenesis associated with autosomal-recessive disease mutants.
HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women
Authors: Selena Alonso, Marta Vidal, Gemma Ruiz-Olalla, Raquel González, Chenjerai Jairoce, M. Nelia Manaca, Miquel Vázquez-Santiago, Reyes Balcells, Anifa Vala, María Rupérez, Pau Cisteró, Laura Fuente-Soro, Evelina Angov, Ross L. Coppel, Benoit Gamain, David Cavanagh, James G. Beeson, Arsenio Nhacolo, Esperança Sevene, John J. Aponte, Eusébio Macete, Ruth Aguilar, Alfredo Mayor, Clara Menéndez, Carlota Dobaño, Gemma Moncunill
Journal: Journal of Infection (2021)
Interventions to Address the Opioid Crisis—Modeling Predictions and Consequences of Inaction
Authors: Nora D. Volkow, Carlos Blanco
Journal: JAMA Network Open (2021)

Benjamin P. Linas, MD, MPH; Alexandra Savinkina, MSPH; R. W. M. A. Madushani, PhD; Jianing Wang, MSc; Golnaz Eftekhari Yazdi, MSc; Avik Chatterjee, MD, MPH; Alexander Y. Walley, MD, MSc; Jake R. Morgan, PhD; Rachel L. Epstein, MD, MSc; Sabrina A. Assoumou, MD, MPH; Sean M. Murphy, PhD; Bruce R. Schackman, PhD; Stavroula A. Chrysanthopoulou, PhD; Laura F. White, PhD; Joshua A. Barocas, MD
Response to: ‘Correspondence on ‘Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician reported registry’ by Arnaud and Devilliers
Authors: Pedro M Machado, Martin Schäfer, Anja Strangfeld, Laure Gossec, Milena Gianfrancesco, Saskia Lawson-Tovey, Elsa F Mateus, Loreto Carmona, Kimme L Hyrich, Philip C Robinson, Jinoos Yazdany
Journal: Annals of the Rheumatic Diseases (2021)

We thank Arnaud and Devilliers1 for their correspondence on our article.2 They raise the important topic of risk prediction models for estimating the risk of COVID-19-related death, and the potential development of a risk prediction tool using data from our article.

We agree with the authors that patients using immunosuppressive/immunomodulatory agents have different risks, depending on factors such as their age, chronic conditions and specific drug therapies. However, we also recognise that there are significant limitations in using the estimates published in our manuscript to develop a COVID-19-related death risk prediction model to guide vaccination strategies. These limitations include:

1.  While robust models that predict the prognosis of COVID-19 are desirable to support decisions about shielding, hospital admission, treatment and population level interventions such as COVID-19 vaccination, this was not the primary aim of the published study. Importantly, it should be noted that owing to the voluntary nature of the registry there is an inherent selection bias, with an over-representation of severe cases, as discussed in our manuscript. Any model developed in a specific dataset will only reflect the risk for a particular patient under similar circumstances and receiving similar care. Therefore, in the same way that the hospitalisation and death rates reported in our article cannot be extrapolated to the entire population of patients with rheumatic diseases, a risk model developed using the …
Pulmonary Hemosiderosis with Calcification Associated with IgA Nephropathy
Authors: Jonah Rubin, Alyssa Sclafani, Timothy L. Helland, Amita Sharma, Jason H. Maley, Tyler J. Peck, Rachel S. Wallwork, Marcy B. Bolster, Sarita Berigei, Yolonda L. Colson, Martin K. Selig, Mari Mino-Kenudson, Lida P. Hariri
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Pulmonary Hemosiderosis with Calcification Associated with IgA Nephropathy." American Journal of Respiratory and Critical Care Medicine, 204(2), pp. e24–e25
DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features
Authors: Maritza S Mosella, Thais S Sabedot, Tiago C Silva, Tathiane M Malta, Felipe Segato Dezem, Karam P Asmaro, Michael Wells, Abir Mukherjee, Laila M Poisson, James Snyder, Ana C deCarvalho, Tobias Walbert, Todd Aho, Steven Kalkanis, Paula C Elias, Sonir R Antonini, Jack Rock, Houtan Noushmehr, Margaret Castro, Ana Valeria Castro
Journal: Neuro-Oncology (2021)

Abstract Background Distinct genome-wide methylation patterns cluster pituitary neuroendocrine tumors (PitNETs) into molecular groups associated with specific clinicopathological features. Here we aim to identify, characterize, and validate methylation signatures that objectively classify PitNET into clinicopathological groups. Methods Combining in-house and publicly available data, we conducted an analysis of the methylome profile of a comprehensive cohort of 177 tumors (Panpit cohort) and 20 nontumor specimens from the pituitary gland. We also retrieved methylome data from an independent PitNET cohort (N = 86) to validate our findings. Results We identified three methylation clusters associated with adenohypophyseal cell lineages and functional status using an unsupervised approach. Differentially methylated probes (DMP) significantly distinguished the Panpit clusters and accurately assigned the samples of the validation cohort to their corresponding lineage and functional subtypes memberships. The DMPs were annotated in regulatory regions enriched with enhancer elements, associated with pathways and genes involved in pituitary cell identity, function, tumorigenesis, and invasiveness. Some DMPs correlated with genes with prognostic and therapeutic values in other intra- or extracranial tumors. Conclusions We identified and validated methylation signatures, mainly annotated in enhancer regions that distinguished PitNETs by distinct adenohypophyseal cell lineages and functional status. These signatures provide the groundwork to develop an unbiased approach to classifying PitNETs according to the most recent classification recommended by the 2017 WHO and to explore their biological and clinical relevance in these tumors.
Autophagic activation of IRF‐1 aggravates hepatic ischemia–reperfusion injury via JNK signaling
Authors: Shipeng Li, Jindan He, Hongwei Xu, Jiaxing Yang, Yutian Luo, Wenyue Song, Bingbing Qiao, Haiming Zhang
Journal: MedComm (2021)

Abstract Increasing evidence has accrued indicating that autophagy is associated with hepatic ischemia–reperfusion injury (IRI). This report demonstrates that interferon regulatory factor‐1 (IRF‐1) was upregulated in response to hepatic IRI and was associated with autophagic activation. As a result of these processes, there is an aggravation of liver damage, effects that can be offset by IRF‐1 depletion. In addition, these effects of IRF‐1 are associated with JNK pathway activation followed by increases in Beclin1 protein levels. This JNK‐induced autophagic cell death then leads to cell failure, and plays an important role in liver function damage. We conclude that IRF‐1 activates autophagy through JNK‐mediated autophagy. Accordingly, these findings indicating that the IRF‐1/JNK pathway activates autophagy to exacerbate liver IRI in this mouse model may provide new insights into novel protective therapies for hepatic IRI.
Epidemiology of HIV in the USA: epidemic burden, inequities, contexts, and responses
Authors: Patrick S Sullivan, Anna Satcher Johnson, Elizabeth S Pembleton, Rob Stephenson, Amy C Justice, Keri N Althoff, Heather Bradley, Amanda D Castel, Alexandra M Oster, Eli S Rosenberg, Kenneth H Mayer, Chris Beyrer
Journal: The Lancet (2021)
Renal, immunosupressive and pharmacokinetic effects of the substitution of intralipid (lip) for cremophor (cre) as vehicle for parenteral cyclosporine (csa) administration
Authors: E A Burdmann, T F Andoh, E B A Prado, N Franceschini, C K Fujihara, Roberto Zatz, W M Bennett
Journal: Journal of the American Society of Nephrology (1995)
m6A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma
Authors: Fanglin He, Jie Yu, Jie Yang, Shaoyun Wang, Ai Zhuang, Hanhan Shi, Xiang Gu, Xiaofang Xu, Peiwei Chai, Renbing Jia
Journal: Molecular Therapy (2021)

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common and deadly eye cancer in adults. Both UM and CM originate from melanocytes and exhibit an aggressive growth pattern with high rates of metastasis and mortality. The integral membrane glycoprotein beta-secretase 2 (BACE2), an enzyme that cleaves amyloid precursor protein into amyloid beta peptide, has been reported to play a vital role in vertebrate pigmentation and metastatic melanoma. However, the role of BACE2 in ocular melanoma remains unclear. In this study, we showed that BACE2 was significantly upregulated in ocular melanoma, and inhibition of BACE2 significantly impaired tumor progression both in vitro and in vivo. Notably, we identified that transmembrane protein 38B (TMEM38B), whose expression was highly dependent on BACE2, modulated calcium release from endoplasmic reticulum (ER). Inhibition of the BACE2/TMEM38B axis could trigger exhaustion of intracellular calcium release and inhibit tumor progression. We further demonstrated that BACE2 presented an increased level of N6-methyladenosine (m6A) RNA methylation, which led to the upregulation of BACE2 mRNA. To our knowledge, this study provides a novel pattern of BACE2-mediated intracellular calcium release in ocular melanoma progression, and our findings suggest that m6A/BACE2/TMEM38b could be a potential therapeutic axis for ocular melanoma. Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common and deadly eye cancer in adults. Both UM and CM originate from melanocytes and exhibit an aggressive growth pattern with high rates of metastasis and mortality. The integral membrane glycoprotein beta-secretase 2 (BACE2), an enzyme that cleaves amyloid precursor protein into amyloid beta peptide, has been reported to play a vital role in vertebrate pigmentation and metastatic melanoma. However, the role of BACE2 in ocular melanoma remains unclear. In this study, we showed that BACE2 was significantly upregulated in ocular melanoma, and inhibition of BACE2 significantly impaired tumor progression both in vitro and in vivo. Notably, we identified that transmembrane protein 38B (TMEM38B), whose expression was highly dependent on BACE2, modulated calcium release from endoplasmic reticulum (ER). Inhibition of the BACE2/TMEM38B axis could trigger exhaustion of intracellular calcium release and inhibit tumor progression. We further demonstrated that BACE2 presented an increased level of N6-methyladenosine (m6A) RNA methylation, which led to the upregulation of BACE2 mRNA. To our knowledge, this study provides a novel pattern of BACE2-mediated intracellular calcium release in ocular melanoma progression, and our findings suggest that m6A/BACE2/TMEM38b could be a potential therapeutic axis for ocular melanoma.
Cardiac resynchronization therapy with versus without a defibrillator: insights from device interrogation and mode of death analysis.
Authors: P. Pieter Martens, F. H. Verbrugge, P. Nijst, M. Dupont, D. Nuyens, H. Van Herendael, M. Rivero-Ayerza, W. H. Tang, W. Mullens
Journal: European Journal of Heart Failure (2017)
Abstract 12253: Elevated Serum Immunoglobulin G4 Level Predicts Long-Term Cardiovascular Events Independent of Established Inflammatory Markers
Authors: Aiko Sakamoto, Nobukazu Ishizaka, Masae Uehara, Jiro Ando, Ryozo Nagai, Issei Komuro
Journal: Circulation (2018)

Background: Inflammation is a principal contributor to the progression of atherosclerosis. However, it remains unclear whether immunoglobulin G4 (IgG4)-related immuno-inflammation may directly prom...
Patient Perceptions of Cardiac Electrophysiology Procedural Postponement at an Urban Center During the SARS-CoV-2 Pandemic
Authors: A. S. L. Roberge, A. Haddad, B. Khazan, J. Noto, L. Tragesser, R. Garber, C. Gangireddy, E. Cronin, A. Basil, G. Yesenosky, R. Greenberg, A. Vaidya, M. Brisco-Bacik, J. M. Cooper, I. Whitman
Journal: Circulation (2020)
Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial
Authors: Günter U Höglinger, Irene Litvan, Nuno Mendonca, Deli Wang, Hui Zheng, Beatrice Rendenbach-Mueller, Hoi-Kei Lon, Ziyi Jin, Nahome Fisseha, Kumar Budur, Michael Gold, Davis Ryman, Hana Florian, Anwar Ahmed, Ikuko Aiba, Alberto Albanese, Kelly Bertram, Yvette Bordelon, James Bower, Jared Brosch, Daniel Claassen, Carlo Colosimo, Jean-Christophe Corvol, Paola Cudia, Antonio Daniele, Luc Defebvre, Erika Driver-Dunckley, Antoine Duquette, Roberto Eleopra, Alexandre Eusebio, Victor Fung, David Geldmacher, Lawrence Golbe, Francisco Grandas, Deborah Hall, Taku Hatano, Günter U Höglinger, Lawrence Honig, Jennifer Hui, Diana Kerwin, Akio Kikuchi, Thomas Kimber, Takashi Kimura, Rajeev Kumar, Irene Litvan, Peter Ljubenkov, Stefan Lorenzl, Albert Ludolph, Zoltan Mari, Nikolaus McFarland, Wassilios Meissner, Pablo Mir Rivera, Hidek Mochizuki, John Morgan, Renato Munhoz, Noriko Nishikawa, John O`Sullivan, Tomoko Oeda, Hideki Oizumi, Osamu Onodera, Fabienne Ory-Magne, Elizabeth Peckham, Ronald Postuma, Aldo Quattrone, Joseph Quinn, Stefano Ruggieri, Justyna Sarna, Paul E Schulz, John Slevin, Michele Tagliati, Daryl Wile, Zbigniew Wszolek, Tao Xie, Theresa Zesiewicz
Journal: The Lancet Neurology (2021)
Different disease, same challenges: Social determinants of tuberculosis and COVID-19
Authors: R. Duarte, A. Aguiar, M. Pinto, I. Furtado, S. Tiberi, K. Lönnroth, G.B. Migliori
Journal: Pulmonology (2021)

Infectious diseases, such as tuberculosis (TB) and the novel coronavirus (COVID-19) relate to environmental factors, understanding of which is essential to inform policy and practice and tackle them effectively. The review follows the conceptual framework offered by the World Health Organization Commission on Social Determinants of Health (defined as "all those material, psychological and behavioural circumstances linked to health and generically indicated as risk factors' in the conventional epidemiological language"). It describes the social factors behind TB and COVID-19, the commonalities between the two diseases, and what can be learned so far from the published best practices. The social determinants sustaining TB and COVID-19 underline the importance of prioritising health and allocating adequate financial and human resources to achieve universal health coverage and health-related social protection while addressing the needs of vulnerable populations. Rapid and effective measures against poverty and other major social determinants and sources of inequality are urgently needed to develop better health in the post-COVID-19 world.
Distinguishing bacterial versus non-bacterial causes of febrile illness – A systematic review of host biomarkers
Authors: B. Leticia Fernandez-Carballo, Camille Escadafal, Emily MacLean, Anokhi J. Kapasi, Sabine Dittrich
Journal: Journal of Infection (2021)

Acute febrile illnesses (AFIs) represent a major disease burden globally; however, the paucity of reliable, rapid point-of-care testing makes their diagnosis difficult. A simple tool for distinguishing bacterial versus non-bacterial infections would radically improve patient management and reduce indiscriminate antibiotic use. Diagnostic tests based on host biomarkers can play an important role here, and a target product profile (TPP) was developed to guide development.To qualitatively evaluate host biomarkers that can distinguish bacterial from non-bacterial causes of AFI.The PubMed database was systematically searched for relevant studies published between 2015 and 2019.Studies comparing diagnostic performances of host biomarkers in patients with bacterial versus non-bacterial infections were included.Studies involving human participants and/or human samples were included.We collected information following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A risk of bias assessment was performed, based on a modified QUADAS-2 (Quality Assessment of Diagnostic Accuracy Score 2).We identified 1107 publications. Following screening, 55 publications were included, with 265 biomarker entries. Entries mostly comprised protein biomarkers (58.9%), followed by haematological, RNA, and metabolite biomarkers (15.5%, 8.7%, 12.5%). Sensitivity/specificity was reported for 45.7% of biomarker entries. We assessed a high overall risk of bias for most entries (75.8%). In studies with low/medium risk of bias, four biomarker entries tested in blood samples had sensitivity/specificity of more than 0.90/0.80. Only 12 additional biomarker entries were identified with sensitivity/specificity of more than 0.65/0.65.Most recently assessed biomarkers represent well-known biomarkers, e.g. C-reactive protein and procalcitonin. Some protein biomarkers with the highest reported performances include a combined biomarker signature (CRP, IP-10, and TRAIL) and human neutrophil lipocalin (HNL). Few new biomarkers are in the pipeline; however, some RNA signatures show promise. Further high-quality studies are needed to confirm these findings.
Centyrin ligands for extrahepatic delivery of siRNA
Authors: Donna Klein, Shalom Goldberg, Christopher S. Theile, Richard Dambra, Kathleen Haskell, Elise Kuhar, Tricia Lin, Rubina Parmar, Muthiah Manoharan, Mark Richter, Meizhen Wu, Jeannine Mendrola Zarazowski, Vasant Jadhav, Martin A. Maier, Laura Sepp-Lorenzino, Karyn O’Neil, Vadim Dudkin
Journal: Molecular Therapy (2021)

RNA interference (RNAi) offers the potential to treat disease at the earliest onset by selectively turning off the expression of target genes, such as intracellular oncogenes that drive cancer growth. However, the development of RNAi therapeutics as anti-cancer drugs has been limited by both a lack of efficient and target cell-specific delivery systems and the necessity to overcome numerous intracellular barriers, including serum/lysosomal instability, cell membrane impermeability, and limited endosomal escape. Here, we combine two technologies to achieve posttranscriptional gene silencing in tumor cells: Centyrins, alternative scaffold proteins binding plasma membrane receptors for targeted delivery, and small interfering RNAs (siRNAs), chemically modified for high metabolic stability and potency. An EGFR Centyrin known to internalize in EGFR-positive tumor cells was site-specifically conjugated to a beta-catenin (CTNNb1) siRNA and found to drive potent and specific target knockdown by free uptake in cell culture and in mice inoculated with A431 tumor xenografts (EGFR amplified). The generalizability of this approach was further demonstrated with Centyrins targeting multiple receptors (e.g., BCMA, PSMA, and EpCAM) and siRNAs targeting multiple genes (e.g., CD68, KLKb1, and SSB1). Moreover, by installing multiple conjugation handles, two different siRNAs were fused to a single Centyrin, and the conjugate was shown to simultaneously silence two different targets. Finally, by specifically pairing EpCAM-binding Centyrins that exhibited optimized internalization profiles, we present data showing that an EpCAM Centyrin CTNNb1 siRNA conjugate suppressed tumor cell growth of a colorectal cancer cell line containing an APC mutation but not cells with normal CTNNb1 signaling. Overall, these data demonstrate the potential of Centyrin-siRNA conjugates to target cancer cells and silence oncogenes, paving the way to a new class of anticancer drugs.