tbuckley/cabot-search huggingface dataset:
“You gotta lift to get ripped”: injection lift myotomy
Authors: Bianca L. Di Cocco, Donevan R. Westerveld, David Carr-Locke, Kartik Sampath, Reem Z. Sharaiha, SriHari Mahadev
Journal: Endoscopy (2024)

Over the past several years, peroral endoscopic myotomy (POEM) has emerged as a first-line, minimally invasive therapy for achalasia [1]. In a traditional POEM procedure, injection is used to facilitate entry and dissection of a tunnel in the submucosal space [2]. Subsequently, a selective myotomy of the circular and variably longitudinal muscle fibers is performed with limited visualization of structures deep into the muscularis layer. Risks of the myotomy portion of POEM include injury to extraluminal structures and blood vessels, which can lead to pneumothorax, capnoperitoneum, and hemorrhage [3]. In this video, we present a novel technique that employs injection through the muscularis propria layer during the myotomy phase to facilitate a safer and more controlled myotomy ([Video 1]).
Genome Sequencing for Diagnosing Rare Diseases
Authors: Monica H. Wojcik, Gabrielle Lemire, Eva Berger, Maha S. Zaki, Mariel Wissmann, Wathone Win, Susan M. White, Ben Weisburd, Dagmar Wieczorek, Leigh B. Waddell, Jeffrey M. Verboon, Grace E. VanNoy, Ana Töpf, Tiong Yang Tan, Steffen Syrbe, Vincent Strehlow, Volker Straub, Sarah L. Stenton, Hana Snow, Moriel Singer-Berk, Josh Silver, Shirlee Shril, Eleanor G. Seaby, Ronen Schneider, Vijay G. Sankaran, Alba Sanchis-Juan, Kathryn A. Russell, Karit Reinson, Gianina Ravenscroft, Maximilian Radtke, Denny Popp, Tilman Polster, Konrad Platzer, Eric A. Pierce, Emily M. Place, Sander Pajusalu, Lynn Pais, Katrin Õunap, Ikeoluwa Osei-Owusu, Henry Opperman, Volkan Okur, Kaisa Teele Oja, Melanie O’Leary, Emily O’Heir, Chantal F. Morel, Andreas Merkenschlager, Rhett G. Marchant, Brian E. Mangilog, Jill A. Madden, Daniel MacArthur, Alysia Lovgren, Jordan P. Lerner-Ellis, Jasmine Lin, Nigel Laing, Friedhelm Hildebrandt, Julia Hentschel, Emily Groopman, Julia Goodrich, Joseph G. Gleeson, Roula Ghaoui, Casie A. Genetti, Janina Gburek-Augustat, Hanna T. Gazda, Vijay S. Ganesh, Mythily Ganapathi, Lyndon Gallacher, Jack M. Fu, Emily Evangelista, Eleina England, Sandra Donkervoort, Stephanie DiTroia, Sandra T. Cooper, Wendy K. Chung, John Christodoulou, Katherine R. Chao, Liam D. Cato, Kinga M. Bujakowska, Samantha J. Bryen, Harrison Brand, Carsten G. Bönnemann, Alan H. Beggs, Samantha M. Baxter, Tobias Bartolomaeus, Pankaj B. Agrawal, Michael Talkowski, Christina Austin-Tse, Rami Abou Jamra, Heidi L. Rehm, Anne O’Donnell-Luria
Journal: New England Journal of Medicine (2024)

Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly after a negative evaluation, remains poorly defined.
Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09)
Authors: Nizar M. Tannir, Maria Nirvana Formiga, Konstantin Penkov, Nikolay Kislov, Aleksandr Vasiliev, Nils Gunnar Skare, Walter Hong, Stanley Dai, Lily Tang, Anila Qureshi, Jonathan Zalevsky, Mary A. Tagliaferri, Daniel George, Neeraj Agarwal, Sumanta Pal, Omkar Marathe, Brendan Curti, Arif Hussain, Mehmet Asim Bilen, Sumanta Kumar Pal, Nizar M. Tannir, Edward Uchio, Seresh Nair, Richard Zuniga, William Clark, Neeraj Agarwal, William Tester, Emily Franks, Kamal Patel, Pedro C. Barata, Janaki Neela Sharma, Saba Radhi, Monika Joshi, Francis Parnis, Howard Gurney, Robert Zielinski, Alexander Guminski, David Campbell, Simon Fu, Alexandr Vasiliev, Evgeniy Kopyltsov, Konstantin Penkov, Oleg Gladkov, Dmitry Perlin, Dmitry Nosov, Vladimir Kheifets, Igor Lifirenko, Sergey Varlamov, Nikolay Kislov, Oleg Karyakin, Elena Zhiltsova, Natalia Fadeeva, Susana Kahl, Rubén Kowalyszyn, Norma Pilnik, Valeria Agostinetti Amuchastegui, Andrea Pastor, Rocío Vázquez, Diego Lucas Kaen, Mario Alfredo Brown Arnold, Felipe Salvador Palazzo, Gustavo Jarchum, Yanina Pfluger, Jorge Salinas, Juan Pablo Re, Sergio Jobim de Azevedo, Andre Poisi Fay, Celio Kussumoto, Roberto Odebrecht Rocha, Ubirajara Ferreira, Jeferson Jose da Fonseca Vinholes, Gustavo Colagiovanni Girotto, Victor Marcondes Lopes dos Santos, Maria Nirvana da Cruz Formiga, Manuela Zereu, Rita de Cassia Costamilan, Daniel D'Almeida Preto, Joao Paulo Holanda Soares, Nils Gunnar Skare, Ariel Galapo Kann, Rodrigo Cunha Guimaraes, Suelen Patricia dos Santos Martins, Alan Arrieira Azambuja, Jose Alberto Lopes Nogueira, Leandro Brust, Jose Getulio Martins Segalla, Maite de Liz Vassen Schurmann, Fabio Andre Franke, Silvio Correia Sales, Daniel de Castro Monteiro, Gisele Marinho dos Santos, Augusto Cesar de Andrade Mota, Jose Luis Martinez Lira, Eduardo Tellez Bernal, Denisse Anorve Bailon, Ivan Martinez Alvarez, Francisco Medina Soto, Carmen Laura Acevedo Zanabria, Alejandro Figueroa Torrejon, Jose David Zorrilla Silvera, Renzo Mauricio Salas Rojas, Sergio Panay, Alejandro Andres Acevedo Gaete, Mario Alberto Gorena Palominos, Pamela Victoria Salman Boghikian, Eugenia de las Nieves Loredo Fort, Eric Armando Orellana Ulunque, Valentina Isabel Hornig Epple, Sergio Fabian Elqueta Pinochet, Thomas Soh I. Peng, Ng Quan Sing, Pamela Crilley, Muhammad Ghani
Journal: Journal of Clinical Oncology (2024)

Bempegaldesleukin (BEMPEG) is a pegylated interleukin (IL)-2 cytokine prodrug engineered to provide controlled and sustained activation of the clinically validated IL-2 pathway, with the goal of preferentially activating and expanding effector CD8
DNA demethylating agents for chemoprevention of oncovirus-associated leukemogenesis
Authors: Yuta Yamamoto, Tatsuro Watanabe, Hiroshi Ureshino, Yuki Kurahashi, Yuki Fukuda-Kurahashi, Kazuharu Kamachi, Kazunori Kawasoe, Keisuke Kidoguchi, Satoshi Yamashita, Naoko Hattori, Toshikazu Ushijima, Shinya Kimura
Journal: Leukemia (2024)
Impact of epicardial adipose tissue on diastolic dysfunction in patients with chronic coronary syndrome and preserved left ventricular ejection fraction
Authors: Hirotoshi Ishikawa, Takatoshi Sugiyama, Kenichiro Otsuka, Hiroki Yamaura, Kana Hojo, Yasushi Kono, Asahiro Ito, Takanori Yamazaki, Kenei Shimada, Noriaki Kasayuki, Daiju Fukuda
Journal:  (2024)

This study aims to investigate the association between left ventricular diastolic dysfunction (LVDD) and epicardial adipose tissue (EAT) accumulation in patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF).
Protective function of sclerosing cholangitis on IBD
Authors: Tanja Bedke, Friederike Stumme, Miriam Tomczak, Babett Steglich, Rongrong Jia, Simon Bohmann, Agnes Wittek, Jan Kempski, Emilia G�ke, Marius B�ttcher, Dominik Reher, Anissa Franke, Maximilian Lennartz, Till Clauditz, Guido Sauter, Thorben Fr�ndt, S�ren Weidemann, Gisa Tiegs, Christoph Schramm, Nicola Gagliani, Penelope Pelczar, Samuel Huber
Journal: Gut (2024)

Objective There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%�80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism. Design Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3 + Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction. Results We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3 + Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3 + Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3 + expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis. Conclusion This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect.
The STOIC2021 COVID-19 AI challenge: Applying reusable training methodologies to private data
Authors: Luuk H. Boulogne, Julian Lorenz, Daniel Kienzle, Robin Schön, Katja Ludwig, Rainer Lienhart, Simon Jégou, Guang Li, Cong Chen, Qi Wang, Derik Shi, Mayug Maniparambil, Dominik Müller, Silvan Mertes, Niklas Schröter, Fabio Hellmann, Miriam Elia, Ine Dirks, Matías Nicolás Bossa, Abel Díaz Berenguer, Tanmoy Mukherjee, Jef Vandemeulebroucke, Hichem Sahli, Nikos Deligiannis, Panagiotis Gonidakis, Ngoc Dung Huynh, Imran Razzak, Reda Bouadjenek, Mario Verdicchio, Pasquale Borrelli, Marco Aiello, James A. Meakin, Alexander Lemm, Christoph Russ, Razvan Ionasec, Nikos Paragios, Bram van Ginneken, Marie-Pierre Revel
Journal: Medical Image Analysis (2024)

Challenges drive the state-of-the-art of automated medical image analysis. The quantity of public training data that they provide can limit the performance of their solutions. Public access to the training methodology for these solutions remains absent. This study implements the Type Three (T3) challenge format, which allows for training solutions on private data and guarantees reusable training methodologies. With T3, challenge organizers train a codebase provided by the participants on sequestered training data. T3 was implemented in the STOIC2021 challenge, with the goal of predicting from a computed tomography (CT) scan whether subjects had a severe COVID-19 infection, defined as intubation or death within one month. STOIC2021 consisted of a Qualification phase, where participants developed challenge solutions using 2000 publicly available CT scans, and a Final phase, where participants submitted their training methodologies with which solutions were trained on CT scans of 9724 subjects. The organizers successfully trained six of the eight Final phase submissions. The submitted codebases for training and running inference were released publicly. The winning solution obtained an area under the receiver operating characteristic curve for discerning between severe and non-severe COVID-19 of 0.815. The Final phase solutions of all finalists improved upon their Qualification phase solutions.
Retraction Note: Asiaticoside, a trisaccaride triterpene induces biochemical and molecular variations in brain of mice with parkinsonism
Authors: Uvarajan Sampath, Vanisree Arambakkam Janardhanam
Journal: Translational Neurodegeneration (2024)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/2047-9158-2-23.
Epithelial hypoxia maintains colonization resistance against Candida albicans
Authors: Hannah P. Savage, Derek J. Bays, Connor R. Tiffany, Mariela A.F. Gonzalez, Eli J. Bejarano, Thaynara P. Carvalho, Zheng Luo, Hugo L.P. Masson, Henry Nguyen, Renato L. Santos, Krystle L. Reagan, George R. Thompson, Andreas J. Bäumler
Journal: Cell Host & Microbe (2024)

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.
Longitudinal evolution of the HIV effective reproduction number following sequential expansion of treatment as prevention and pre-exposure prophylaxis in British Columbia, Canada: a population-level programme evaluation
Authors: Viviane D Lima, Jielin Zhu, Rolando Barrios, Junine Toy, Jeffrey B Joy, Brian G Williams, Reuben Granich, Zunyou Wu, Jason Wong, Julio S G Montaner
Journal: The Lancet HIV (2024)
Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine
Authors: Hulya Bayraktutan, Peter Symonds, Victoria A. Brentville, Cara Moloney, Charlotte Galley, Clare L. Bennett, Alvaro Mata, Lindy Durrant, Cameron Alexander, Pratik Gurnani
Journal: Biomaterials (2024)

DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection. In this study, we have engineered a range of polymer-based nanocarriers based on the poly(beta-amino ester) (PBAE) polycation platform to investigate the role that surface poly(ethylene glycol) (PEG) density has on pDNA encapsulation, formulation properties and gene transfectability both in vitro and in vivo. We achieved this by synthesising a non-PEGylated and PEGylated PBAE and produced formulations containing these PBAEs, and mixed polyplexes to tune surface PEG density. All polymers and co-formulations produced small polyplex nanoparticles with almost complete encapsulation of the cargo in all cases. Despite high gene transfection in HEK293T cells, only the fully PEGylated and mixed formulations displayed significantly higher expression of the reporter gene than the negative control in dendritic cells. Further in vivo studies with a bivalent SARS-CoV-2 pDNA vaccine revealed that only the mixed formulation led to strong antigen specific T-cell responses, however this did not translate into the presence of serum antibodies indicating the need for further studies into improving immunisation with polymer delivery systems.
Beyond success: unveiling the hidden potential of radiotherapy and immunotherapy in solid tumors
Authors: Yuze Wu, Ming Yi, Mengke Niu, Binghan Zhou, Qi Mei, Kongming Wu
Journal: Cancer Communications (2024)

Abstract Immunotherapy, particularly with immune checkpoint inhibitors, has significantly transformed cancer treatment. Despite its success, many patients struggle to respond adequately or sustain long‐lasting clinical improvement. A growing consensus has emerged that radiotherapy (RT) enhances the response rate and overall efficacy of immunotherapy. Although combining RT and immunotherapy has been extensively investigated in preclinical models and has shown promising results, establishing itself as a dynamic and thriving area of research, clinical evidence for this combination strategy over the past five years has shown both positive and disappointing results, suggesting the need for a more nuanced understanding. This review provides a balanced and updated analysis of the combination of immunotherapy and RT. We summarized the preclinical mechanisms through which RT boosts antitumor immune responses and mainly focused on the outcomes of recently updated clinical trials, including those that may not have met expectations. We investigated the optimization of the therapeutic potential of this combined strategy, including key challenges, such as fractionation and scheduling, lymph node irradiation, and toxicity. Finally, we offered insights into the prospects and challenges associated with the clinical translation of this combination therapy, providing a realistic perspective on the current state of research and potential future directions.
AVM: A Manually Curated Database of Aerosol-transmitted Virus Mutations, Human Diseases, and Drugs
Authors: Lan Mei, Yaopan Hou, Jiajun Zhou, Yetong Chang, Yuwei Liu, Di Wang, Yunpeng Zhang, Shangwei Ning, Xia Li
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Aerosol-transmitted viruses possess strong infectivity and can spread over long distances, earning the difficult-to-control title. They cause various human diseases and pose serious threats to human health. Mutations can increase the transmissibility and virulence of the strains, reducing the protection provided by vaccines and weakening the efficacy of antiviral drugs. In this study, we established a manually curated database (termed AVM) to store information on aerosol-transmitted viral mutations (VMs). The current version of the AVM contains 42,041 VMs (including 2613 immune escape mutations), 45 clinical information datasets, and 407 drugs/antibodies/vaccines. Additionally, we recorded 88 human diseases associated with viruses and found that the same virus can target multiple organs in the body, leading to diverse diseases. Furthermore, the AVM database offers a straightforward user interface for browsing, retrieving, and downloading information. This database is a comprehensive resource that can provide timely and valuable information on the transmission, treatment, and diseases caused by aerosol-transmitted viruses (http://www.bio-bigdata.center/AVM).
Deployment and validation of the CLL treatment infection model adjoined to an EHR system
Authors: Rudi Agius, Anders C. Riis-Jensen, Bettina Wimmer, Caspar da Cunha-Bang, Daniel Dawson Murray, Christian Bjorn Poulsen, Marianne B. Bertelsen, Berit Schwartz, Jens Dilling Lundgren, Henning Langberg, Carsten Utoft Niemann
Journal: npj Digital Medicine (2024)

Abstract Research algorithms are seldom externally validated or integrated into clinical practice, leaving unknown challenges in deployment. In such efforts, one needs to address challenges related to data harmonization, the performance of an algorithm in unforeseen missingness, automation and monitoring of predictions, and legal frameworks. We here describe the deployment of a high-dimensional data-driven decision support model into an EHR and derive practical guidelines informed by this deployment that includes the necessary processes, stakeholders and design requirements for a successful deployment. For this, we describe our deployment of the chronic lymphocytic leukemia (CLL) treatment infection model (CLL-TIM) as a stand-alone platform adjoined to an EPIC-based Danish Electronic Health Record (EHR), with the presentation of personalized predictions in a clinical context. CLL-TIM is an 84-variable data-driven prognostic model utilizing 7-year medical patient records and predicts the 2-year risk composite outcome of infection and/or treatment post-CLL diagnosis. As an independent validation cohort for this deployment, we used a retrospective population-based cohort of patients diagnosed with CLL from 2018 onwards ( n = 1480). Unexpectedly high levels of missingness for key CLL-TIM variables were exhibited upon deployment. High dimensionality, with the handling of missingness, and predictive confidence were critical design elements that enabled trustworthy predictions and thus serves as a priority for prognostic models seeking deployment in new EHRs. Our setup for deployment, including automation and monitoring into EHR that meets Medical Device Regulations, may be used as step-by-step guidelines for others aiming at designing and deploying research algorithms into clinical practice.
A suite of genome-engineered hepatic cells provides novel insights into the spatiotemporal metabolism of apolipoprotein B and apolipoprotein B–containing lipoprotein secretion
Authors: Amber Meurs, Klevis Ndoj, Marlene van den Berg, Goran Marinković, Matteo Tantucci, Tineke Veenendaal, Jan Albert Kuivenhoven, Judith Klumperman, Noam Zelcer
Journal: Cardiovascular Research (2024)

Apolipoprotein B (APOB)-containing very LDL (VLDL) production, secretion, and clearance by hepatocytes is a central determinant of hepatic and circulating lipid levels. Impairment of any of the aforementioned processes is associated with the development of multiple diseases. Despite the discovery of genes and processes that govern hepatic VLDL metabolism, our understanding of the different mechanistic steps involved is far from complete. An impediment to these studies is the lack of tractable hepatocyte-based systems to interrogate and follow APOB in cells, which the current study addresses.
Batf-Dependent Th17 cells act through IL23R pathway to promote prostate adenocarcinoma initiation and progression
Authors: Sen Liu, Seleste L Rivero, Bing Zhang, Keyi Shen, Zixuan Li, Tianhua Niu, Brian G Rowan, S Michal Jazwinski, Asim B Abdel-Mageed, Chad Steele, Alun R Wang, Oliver Sartor, Qiuyang Zhang
Journal: JNCI Journal of the National Cancer Institute (2024)

The role of Th17 cells in prostate cancer (PCa) is not fully understood. The transcription factor BATF controls the differentiation of Th17 cells. Mice deficient in Batf do not produce Th17 cells.
Different dosage forms of GnRHa with endocrine therapy in premenopausal hormone Receptor-Positive breast cancer
Authors: Jinna Lin, Yiye Ouyang, Yudong Li, Liang Jin, Shunying Li, Yujie Liu, Yaping Yang, Qianfeng Shi, Mengdi Zhu, Zijie Cai, Jingru Wang, Nianqiu Liu, Yue Hu, Zongqi Wu, Mengzi Wu, Lok Lam Wong, Xiaoting Jiang, Qi Wang, Wang Yang, Qiang Liu
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Despite the wide use of a 3-month gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a 1-month GnRH agonist regimen when combined with selective estrogen receptor modulators or aromatase inhibitors, especially in younger patients. Methods This retrospective cohort study included 1109 premenopausal hormone receptor–positive breast cancer patients treated with GnRH agonist plus selective estrogen receptor modulator or aromatase inhibitor. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1-month or 3-month GnRH agonist in cohorts and different subgroups was analyzed. Results Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1-month and 3-month groups achieved more than 90% E2 inhibition within 24 months (94.53% vs 92.84%, with a 95% confidence interval for the difference ranging from −4.78% to 1.41%), confirming the noninferiority of 3-month GnRH agonist. Both 1-month and 3-month GnRH agonist rapidly and consistently reduced E2 levels. Of the patients, 60 (6.3%) experienced incomplete ovarian function suppression, with similar rates in the 1-month and 3-month groups (5.5% vs 7.2%). Incomplete ovarian function suppression mainly occurred within the first 12 months, with age younger than 40 years and no prior chemotherapy being the risk factors. Similar disease-free survival and overall survival were found in the 1-month and 3-month groups and in patients with complete and incomplete ovarian function suppression (P &amp;gt; .05). Conclusions The ovarian function suppression with 3-month GnRH agonist was not inferior to that with 1-month GnRH agonist, regardless of age or combination with a selective estrogen receptor modulator or an aromatase inhibitor.