tbuckley/cabot-search huggingface dataset:
Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction
Authors: Maja Cikes, Ivo Planinc, Brian Claggett, Jonathan Cunningham, Davor Milicic, Nancy Sweitzer, Michele Senni, Mauro Gori, Gerard Linssen, Sanjiv J. Shah, Milton Packer, Marc Pfeffer, Michael R. Zile, Inder Anand, Lu-May Chiang, Carolyn S.P. Lam, Margaret Redfield, Akshay S. Desai, John J.V. McMurray, Scott D. Solomon
Journal: JACC Heart Failure (2022)

In this study, the authors sought to assess the relationship between AFF and outcomes, the treatment response to sacubitril/valsartan and first-detected AFF in patients with HFpEF enrolled in the PARAGON-HF trial.Atrial fibrillation and flutter (AFF) are common in heart failure with preserved ejection fraction (HFpEF) and increase the risk of adverse outcomes.A total of 4,776 patients formed 3 groups: those with AFF according to electrocardiography (ECG) at enrollment (n = 1,552; 33%), those with history of AFF but without AFF on ECG at enrollment (n = 1,005; 21%), and those without history of AFF or AFF on ECG at enrollment (n = 2,219, 46%). We assessed outcomes, treatment response to sacubitril/valsartan in each group, and the risk associated with first-detected AFF in patients without any known AFF. The primary outcome was a composite of total heart failure hospitalizations and cardiovascular death.History of AFF and AFF at enrollment were associated with higher risk of the primary outcome (risk ratio [RR]: 1.36 [95% CI: 1.12-1.65] and RR: 1.31 [1.11-1.54], respectively), than no AFF. Neither history of AFF nor AFF at enrollment modified the treatment effect of sacubitril/valsartan. Post randomization AFF occurred in 12% of patients without previous AFF and was associated with 2.8-fold higher risk of the primary outcome, but it was not influenced by sacubitril/valsartan.History of AFF and AFF on ECG at enrollment were associated with a higher risk of the primary outcome. First-detected AFF was not influenced by sacubitril/valsartan, yet it was associated with increased risk of all subsequent outcomes and may represent a potential target for future HFpEF trials. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
Gp350-anchored extracellular vesicles: promising vehicles for delivering therapeutic drugs of B cell malignancies
Authors: Huiqing Xiu, Xi Nan, Danfeng Guo, Jiaoli Wang, Jiahui Li, Yanmei Peng, Guirun Xiong, Shibo Wang, Changjun Wang, Gensheng Zhang, Yunshan Yang, Zhijian Cai
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Although chimeric antigen receptor-modified (CAR) T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia, its effect on Burkitt lymphoma (BL) and chronic B lymphocytic leukemia (B-CLL) is unsatisfactory. Moreover, fatal side effects greatly impede CAR T cell application. Extracellular vesicles (EVs) are excellent carriers of therapeutic agents. Nevertheless, EVs mainly accumulate in the liver when administered without modification. As an envelope glycoprotein of Epstein–Barr viruses, gp350 can efficiently bind CD21 on B cells. Here, gp350 was directly anchored onto red blood cell EVs (RBC-EVs) via its transmembrane region combined with low-voltage electroporation. The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs (RBC-EVs/gp350Etp) exhibited increased targeting to CD21+ BL and B-CLL relative to RBC-EVs. After the loading of doxorubicin or fludarabine, RBC-EVs/gp350Etp had powerful cytotoxicity and therapeutic efficacy on CD21+ BL or B-CLL, respectively. Moreover, RBC-EVs/gp350Etp loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal B cells. Therefore, our findings indicate that drug-loaded RBC-EVs/gp350Etp may be adopted in the treatment of CD21+ B cell malignancies.
Urgent versus elective laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage for high-risk grade II acute cholecystitis
Authors: Shiori Yamazaki, Akira Shimizu, Koji Kubota, Tsuyoshi Notake, Kiyotaka Hosoda, Kentaro Umemura, Atsushi Kamachi, Takamune Goto, Hidenori Tomida, Yuji Soejima
Journal: International Journal of Surgery (2022)
Two‐Photon Small‐Molecule Fluorogenic Probes for Visualizing Endogenous Nitroreductase Activities from Tumor Tissues of a Cancer Patient
Authors: Changmin Yu, Shuangxi Wang, Chenchen Xu, Yang Ding, Gaobin Zhang, Naidi Yang, Qiong Wu, Qicai Xiao, Limin Wang, Bin Fang, Chibin Pu, Jingyan Ge, Liqian Gao, Lin Li, Shao Q. Yao
Journal: Advanced Healthcare Materials (2022)

Nitroreductase (NTR), a common enzymatic biomarker of hypoxia, is widely used to evaluate tumor microenvironments. To date, numerous optical probes have been reported for NTRs detection. Approaches capable of concisely guiding the probe design of NTRs suitable for deep-tissue imaging, however, are still lacking. As such, direct optical imaging of endogenous NTR activities from tumors derived from cancer patients is thus far not possible. Herein, aided by computational calculations, the authors have successfully developed a series of two-photon (TP) small-molecule fluorogenic probes capable of sensitively detecting general NTR activities from various biological samples; by optimizing the distance between the recognition moiety and the reactive site of NTRs from different sources, the authors have discovered and experimentally proven that X4 displays the best performance in both sensitivity and selectivity. Furthermore, X4 shows excellent TP excited fluorescence properties capable of directly monitoring/imaging endogenous NTR activities from live mammalian cells, growing zebrafish, and tumor-bearing mice. Finally, with an outstanding TP tissue-penetrating imaging property, X4 is used, for the first time, to successfully detect endogenous NTR activities from the liver lysates and cardia tissues of a cancer patient. The work may provide a universal strategy to design novel TP small-molecule enzymatic probes in future clinical applications.
Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant
Authors: Aurélien Sokal, Matteo Broketa, Giovanna Barba-Spaeth, Annalisa Meola, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, Matthieu Mahévas
Journal: Immunity (2022)
Increased expression of RUNX3 inhibits normal human myeloid development
Authors: Ana Catarina Menezes, Rachel Jones, Alina Shrestha, Rachael Nicholson, Adam Leckenby, Aleksandra Azevedo, Sara Davies, Sarah Baker, Amanda F. Gilkes, Richard L. Darley, Alex Tonks
Journal: Leukemia (2022)

RUNX3 is a transcription factor dysregulated in acute myeloid leukemia (AML). However, its role in normal myeloid development and leukemia is poorly understood. Here we investigate RUNX3 expression in both settings and the impact of its dysregulation on myelopoiesis. We found that RUNX3 mRNA expression was stable during hematopoiesis but decreased with granulocytic differentiation. In AML, RUNX3 mRNA was overexpressed in many disease subtypes, but downregulated in AML with core binding factor abnormalities, such as RUNX1::ETO. Overexpression of RUNX3 in human hematopoietic stem and progenitor cells (HSPC) inhibited myeloid differentiation, particularly of the granulocytic lineage. Proliferation and myeloid colony formation were also inhibited. Conversely, RUNX3 knockdown did not impact the myeloid growth and development of human HSPC. Overexpression of RUNX3 in the context of RUNX1::ETO did not rescue the RUNX1::ETO-mediated block in differentiation. RNA-sequencing showed that RUNX3 overexpression downregulates key developmental genes, such as KIT and RUNX1, while upregulating lymphoid genes, such as KLRB1 and TBX21. Overall, these data show that increased RUNX3 expression observed in AML could contribute to the developmental arrest characteristic of this disease, possibly by driving a competing transcriptional program favoring a lymphoid fate.
Reply: Identification of coronavirus particles by electron microscopy: a complementary tool for deciphering COVID-19
Authors: Sophia Havaki, Konstantinos Evangelou, Koralia Paschalaki, Russell Petty, Peter J. Barnes, Vassilis G. Gorgoulis
Journal: European Respiratory Journal (2022)

Having a significant experience in EM for more than 20 years, we are well aware of the ultrastructural features of all cellular organelles and their potential distortion by artifacts and also of the ultrastructural characteristics of viruses, including those of coronaviruses in infected cells and tissues as they have been extensively described [2–5].
Minimally invasive vs. open pancreatoduodenectomy in selected patients with peri-ampullary, non-pancreatic cancer: A systematic review and individual patient data meta-analysis
Authors: Bas A. Uijterwijk, Meidai Kasai, Daniël Lemmers, Benedetto Ielpo, Jony Van Hilst, Ki Byong Song, Palanivelu Chinnusamy, Jin-Young Jang, Marc Besselink, Mohammed Abu Hilal
Journal: International Journal of Surgery (2022)
Application of the SOFT, BAR and DRI scales in liver transplant patients in a third-level Mexican center
Authors: Alejandra Nunez-Venzor, Josue Israel Olivares-del-Moral, Lorena Lina-Lopez, Noel Marquez-Jurado, Pablo Magaña-Mainero, Carlos W. Florez-Zorrilla, Miguel Charco-Cruz, Aczel I. Sánchez-Cedillo, Elizabeth Buganza-Torio
Journal: International Journal of Surgery (2022)
Annals Story Slam - Early 2020
Authors: Riddhi S. Shah
Journal: Annals of Internal Medicine (2022)

Web Exclusives29 April 2022Annals Story Slam - Early 2020FREERiddhi S. Shah, MDRiddhi S. Shah, MDGreater Danbury Community Health Center/Connecticut Institute for Communities, Danbury, Connecticut (R.S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W22-0012 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Early 2020 "Early 2020," by Dr. Riddhi S. Shah (Duration 5:19)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Author, Article, and Disclosure InformationAuthors: Riddhi S. Shah, MDAffiliations: Greater Danbury Community Health Center/Connecticut Institute for Communities, Danbury, Connecticut (R.S.S.)Corresponding Author: Riddhi S. Shah, MD; e-mail, riddhishahmd@gmail.com.This article was published at Annals.org on 29 April 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6 Page: SS1 ePublished: 29 April 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...
A fluorinated peptide with high serum- and lipid-tolerence for the delivery of siRNA drugs to treat obesity and metabolic dysfunction
Authors: Jin Qiu, Qianqian Fan, Sainan Xu, Dongmei Wang, Juntong Chen, Sainan Wang, Tianhui Hu, Xinran Ma, Yiyun Cheng, Lingyan Xu
Journal: Biomaterials (2022)
Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial
Authors: Jagdeep Nanchahal, Catherine Ball, Ines Rombach, Lynn Williams, Nicola Kenealy, Helen Dakin, Heather O'Connor, Dominique Davidson, Paul Werker, Susan J Dutton, Marc Feldmann, Sarah E Lamb
Journal: The Lancet Rheumatology (2022)

Dupuytren's disease is a common fibrotic condition that causes the fingers to flex irreversibly into the palm. Treatments for late-stage disease all have limitations, and there is no approved treatment for early-stage disease. We identified tumour necrosis factor as a therapeutic target in Dupuytren's disease, and in a dose ranging trial found 40 mg adalimumab in 0·4 mL to be most efficacious. Here we aimed to assess the effects of intranodular injection of adalimumab in early-stage disease.
Role of Diet Quality in the Association Between Excess Weight and Psychosocial Problems in a Large Sample of Children in Spain
Authors: José Francisco López-Gil, Iván Cavero-Redondo, Estela Jiménez-López, Bruno Bizzozero-Peroni, Alicia Saz-Lara, Arthur Eumann Mesas
Journal: JAMA Network Open (2022)

The role of healthy eating in the association between excess weight and psychosocial health among children is unknown.
Impact of total mesopancreas excision on postoperative tumor recurrence
Authors: Alejandro Serrablo-Requejo, Sandra Paterna-López, Marta Gutiérrez-Díez, María Teresa Abadía-Forcén, Mario Serradilla-Martín, Pablo Sancho-Pardo, Consuelo Artigas-Marco
Journal: International Journal of Surgery (2022)
Risk factors for portal vein thrombosis after adult-to-adult living donor liver transplantation
Authors: Amr Badawy, Toshimi Kaido, Takayuki Anazawa, Takashi Ito, Shintaro Yagi, Naoko Kamo, Koichiro Hata, Kojiro Taura, Shinji Uemoto
Journal: International Journal of Surgery (2022)
Safety and efficacy of major hepatopancreatoduodenectomy for perihilar cholangiocarcinoma
Authors: Akira Shimizu, Koji Kubota, Tsuyoshi Notake, Kiyotaka Hosoda, Kentaro Umemura, Atsushi Kamachi, Takamune Goto, Hidenori Tomida, Shiori Yamazaki, Yuji Soejima
Journal: International Journal of Surgery (2022)
ILC1s control leukemia stem cell fate and limit development of AML
Authors: Zhenlong Li, Rui Ma, Shoubao Ma, Lei Tian, Ting Lu, Jianying Zhang, Bethany L. Mundy-Bosse, Bin Zhang, Guido Marcucci, Michael A. Caligiuri, Jianhua Yu
Journal: Nature Immunology (2022)
Liver transplantation in a patient with persistently positive nasopharyngeal swab for SARS-CoV-2 virus after a recent infection
Authors: Tamer Shaker, Jessica Fisher, Anant Dinesh, Roy Kiberange, Varvara Kirchner, Sarwat Khalil, Karam Obeid, Nicholas Lim, Srinath Chinnakotla
Journal: International Journal of Surgery (2022)
Response to letter
Authors: Colin Crooks, Joe West, Tim Card, Dominick Shaw, Mark Simmonds, Andrew Fogarty
Journal: European Respiratory Journal (2022)

We thank M.J. Tobin and A. Jubran for their interest in our data [1]. As they state, it is an extension of a body of work that they helped establish over 30 years ago. Inaccuracy of pulse oximetry measurements of oxygen saturation in darker-skinned individuals <https://bit.ly/3rVzRpN>
Impact of tumor size on outcome of hepatectomy for hepatocellular carcinoma: A nationwide propensity score adjusted analysis
Authors: Suk Kyun Hong, Kwang-Woong Lee, Sola Lee, Su young Hong, Sanggyun Suh, Eui Soo Han, YoungRok Choi, Nam-Joon Yi, Kyung-Suk Suh
Journal: International Journal of Surgery (2022)
Part I: Cutaneous manifestations of cardiovascular disease
Authors: Jamie Karch, Aishwarya Raja, Henriette De La Garza, Antonio De Jesus Diaz Zepeda, Allen Shih, Mayra B.C. Maymone, Tania J. Phillips, Eric Secemsky, Neelam Vashi
Journal: Journal of the American Academy of Dermatology (2022)
Endothelial BACE1 Impairs Cerebral Small Vessels via Tight Junctions and eNOS
Authors: Haoyue Zhou, Feng Gao, Xiaoli Yang, Tingting Lin, Zhenxing Li, Qiong Wang, Yang Yao, Lei Li, Xinxin Ding, Kaibin Shi, Qiang Liu, Hong Bao, Zhenyu Long, Zujun Wu, Robert Vassar, Xin Cheng, Rena Li, Yong Shen
Journal: Circulation Research (2022)

Background: Cerebral small vessel injury, including loss of endothelial tight junctions, endothelial dysfunction, and blood-brain barrier breakdown, is an early and typical pathology for Alzheimer's disease, cerebral amyloid angiopathy, and hypertension-related cerebral small vessel disease. Whether there is a common mechanism contributing to these cerebrovascular alterations remains unclear. Studies have shown an elevation of BACE1 (β-site amyloid precursor protein cleaving enzyme 1) in cerebral vessels from cerebral amyloid angiopathy or Alzheimer's disease patients, suggesting that vascular BACE1 may involve in cerebral small vessel injury. Methods: To understand the contribution of vascular BACE1 to cerebrovascular impairments, we combined cellular and molecular techniques, mass spectrometry, immunostaining approaches, and functional testing to elucidate the potential pathological mechanisms. Results: We observe a 3.71-fold increase in BACE1 expression in the cerebral microvessels from patients with hypertension. Importantly, we discover that an endothelial tight junction protein, occludin, is a completely new substrate for endothelial BACE1. BACE1 cleaves occludin with full-length occludin reductions and occludin fragment productions. An excessive cleavage by elevated BACE1 induces membranal accumulation of caveolin-1 and subsequent caveolin-1-mediated endocytosis, resulting in lysosomal degradation of other tight junction proteins. Meanwhile, membranal caveolin-1 increases the binding to eNOS (endothelial nitric oxide synthase), together with raised circulating Aβ (β-amyloid peptides) produced by elevated BACE1, leading to an attenuation of eNOS activity and resultant endothelial dysfunction. Furthermore, the initial endothelial damage provokes chronic reduction of cerebral blood flow, blood-brain barrier leakage, microbleeds, tau hyperphosphorylation, synaptic loss, and cognitive impairment in endothelial-specific BACE1 transgenic mice. Conversely, inhibition of aberrant BACE1 activity ameliorates tight junction loss, endothelial dysfunction, and memory deficits. Conclusions: Our findings establish a novel and direct relationship between endothelial BACE1 and cerebral small vessel damage, indicating that abnormal elevation of endothelial BACE1 is a new mechanism for cerebral small vessel disease pathogenesis.
Operating room time savings in Germany- and UK-based hospitals with 3D- VS. 2D-imaging technology in laparoscopic surgery: Meta analysis and budget impact model – Health economic evaluation
Authors: R. Wahba, A. Urbanski, R.R. Datta, R. Kleinert, L. Bruno, A. Zervakis, M.N. Thomas
Journal: International Journal of Surgery (2022)

Opportunity cost (OC) analysis is key when evaluating surgical techniques. Operating room (OR) time is one potential source of OC in laparoscopic surgery. This study quantifies differences in OR time between 3D- and 2D-imaging technology in laparoscopic surgery, translates these into OC and models the economic impact in real-world hospitals.First a systematically performed literature review and meta-analysis were conducted. Then, methods to translate OR time savings into OC were theorised and a budget impact model was created. After that, the potential time savings of real-world hospital case mixes were extrapolated. Finally, the opportunity costs of not using 3D-imaging in laparoscopic surgery were evaluated.Average OR time saving per laparoscopic procedure was -19.4 min (-24.3; -14.5) (-14%) in favour of 3D. The Budget Impact Model demonstrated an economic impact of using 3D-laparoscopy instead of 2D laparoscopy, ranging from £183,045-£866,316 in the British and 73,049€-437,829€ in German hospitals, modelling a mixture of cost savings and performing additional procedures (earning additional revenue).The OC analysis revealed significant economic benefits of introducing 3D-imaging technology in laparoscopic surgery, on the basis that average procedure time is reduced. Utilising the saved OR time to perform additional procedures was the biggest driver of OC. Hospital case mix and procedure volume indicated the magnitude of the OC.
Long-term mortality following SARS-CoV-2 infection: A national cohort study from Estonia
Authors: Anneli Uusküla, Tuuli Jürgenson, Heti Pisarev, Raivo Kolde, Tatjana Meister, Anna Tisler, Kadri Suija, Ruth Kalda, Marko Piirsoo, Krista Fischer
Journal: The Lancet Regional Health - Europe (2022)

The objective of this study was to describe 12-month mortality following SARS-CoV-2 infection compared with a reference population with no history of SARS-CoV-2.Nationwide cohort study using electronic health care data on SARS-CoV-2 RNA positive cases (n= 66,287) and reference group subjects (n=254,969) with linkage to SARS-CoV-2 testing and death records.People infected with SARS-COV-2 had more than three times the risk of dying over the following year compared with those who remained uninfected (aHR 3·1, 95%CI 2·9-3·3). Short-term mortality (up to 5 weeks post-infection) was significantly higher among COVID-19 group (1623·0/10 000) than in the reference group (118/10 000). For COVID-19 cases aged 60 years or older, increased mortality persisted until the end of the first year after infection, and was related to increased risk for cardiovascular (aHR 2·1, 95%CI 1·8-2·3), cancer (aHR 1·5, 95%CI 1·2-1·9), respiratory system diseases (aHR 1·9, 95%CI 1·2-3·0), and other causes of death (aHR 1·8, 95%CI 1·4-2·2).Increased risk of death from SARS-CoV-2 is not limited to the acute illness: SARS-CoV-2 infection carries a substantially increased mortality in the following 12 months. This excess death mainly occurs in older people and is driven by broad array of causes of death.Research was carried out with the support of Estonian Research Council (grants PRG1197, PRG198), European Regional Development Fund (RITA 1/02-120) and European Social Fund via IT Academy program.
Endoscopic excision as a viable alternative to major resection for early duodenal cancers: A population-based cohort study
Authors: Yongqiang Zheng, Pengcheng Yang, Jiayuan Chen, Kai Yu, Yuzhong Ye, Lei Zhang, Xiaohua Hou, Deshen Wang
Journal: International Journal of Surgery (2022)

Duodenal cancer presents an elusive therapeutic challenge for clinicians to treat because of its highly malignant behavior and anatomical complexity. Endoscopic excision has been administered to treat early-stage cancers of upper gastrointestinal tract, especially esophagus and stomach cancer. There is currently a scarcity of data regarding the application and efficacy of endoscopic resection for early duodenal cancer due to its rarity. This study aimed at exploring the prevalence and efficacy of endoscopic excision in treatment for early duodenal cancer in comparison with major surgery.This cohort study retrospectively collected patients with primary Tis/T1-N0-M0 duodenal cancer in the Surveillance, Epidemiology, and End Results database from 2004 to 2017. Prevalence of endoscopic excision in duodenal cancer treatment, overall survival (OS) and disease-specific survival (DSS) of patients who received different tumor-resection procedures were estimated.A total of 1354 patients with Tis/T1-stage duodenal cancer were identified. Most patients (69.4%) underwent tumor resection as initial treatments. Among them, 65.7% underwent endoscopic excision, while 34.3% underwent major surgery. The multivariable Cox analyses revealed that endoscopic excision was associated with a significantly favorable OS (HR: 0.70; 95% CI: 0.52-0.95, p = 0.02) and DSS (HR: 0.32; 95% CI: 0.17-0.60, p < 0.001), compared to major surgery, for Tis/T1-stage cancer patients. In addition to cancer-related deaths (p < 0.001), endoscopic resection manifested significantly lower cumulative mortality rate of post-operative infectious diseases (p = 0.03).Endoscopic resection currently accounted for approximately two-thirds of all procedures to resect Tis/T1-stage duodenal tumor. Endoscopic resection represents a viable therapeutic option in the management of Tis/T1-stage duodenal cancer for its oncological superiorities to major surgery and its capacity to reduce operative traumas and morbidities.