tbuckley/cabot-search huggingface dataset:
Treatment of an impacted pancreatic duct stone by snare-assisted stone extraction and pancreatoscopy-guided lithotripsy
Authors: Michiel Bronswijk, Diederik Persyn, Philip Caenepeel, Schalk Willem Van der Merwe
Journal: Endoscopy (2021)

Ductal hypertension is regarded as one of the drivers of chronic pancreatitis-related pain and has therefore been the main target of therapy. Although previous randomized controlled trials have supported surgical decompression, endoscopic therapy of symptomatic chronic pancreatitis has undergone a true revolution over the past decade [1]. The advent of digital single-operator pancreatoscopy (DSOP) and endoscopic ultrasound-guided pancreatic drainage have radically changed our endoscopic approach, which is now aimed at complete ductal clearance [2] [3] [4].
Certainty and integration of options in animal movement
Authors: Hannah J. Williams, Kamran Safi
Journal: Trends in Ecology & Evolution (2021)

Physical energy defines the energy landscape and determines the species-specific cost of movement, thus influencing movement decisions. In unpredictable and dynamic environments, observing the locomotion of others increases individual certainty in the distribution of physical energy to increase movement efficiency. Beyond the physical energy landscape, social sampling increases certainty in all ecological landscapes that influence animal movement (including fear and resource landscapes), and individuals use energy to express each of these. We call for the development of an 'optimal movement theory' (OMT) that integrates the multidimensional reality of movement decisions by combining ecological landscapes according to a single expectation of energy cost-benefit, where social sampling provides up-to-date information under uncertain conditions. This mechanistic framework has implications for predicting individual movement patterns and for investigating the emergence of aggregations.
Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice
Authors: Xue-Song Zhang, Yue Sandra Yin, Jincheng Wang, Thomas Battaglia, Kimberly Krautkramer, Wei Vivian Li, Jackie Li, Mark Brown, Meifan Zhang, Michelle H. Badri, Abigail J.S. Armstrong, Christopher M. Strauch, Zeneng Wang, Ina Nemet, Nicole Altomare, Joseph C. Devlin, Linchen He, Jamie T. Morton, John Alex Chalk, Kelly Needles, Viviane Liao, Julia Mount, Huilin Li, Kelly V. Ruggles, Richard A. Bonneau, Maria Gloria Dominguez-Bello, Fredrik Bäckhed, Stanley L. Hazen, Martin J. Blaser
Journal: Cell Host & Microbe (2021)
Annals Graphic Medicine - COVID-19 and My Self-made Electronic Stethoscope
Authors: Hongguang Ding, Mengting Liu, Yin Wen, Shiying Zhang, Hongke Zeng
Journal: Annals of Internal Medicine (2021)

Web Exclusives27 July 2021Annals Graphic Medicine - COVID-19 and My Self-made Electronic StethoscopeFREEHongguang Ding, MD, Mengting Liu, MB, Yin Wen, MB, Shiying Zhang, MB, and Hongke ZengHongguang Ding, MDGuangdong Provincial People's Hospital, Guangzhou, China (H.D., M.L., Y.W., S.Z., H.Z.)Search for more papers by this author, Mengting Liu, MBGuangdong Provincial People's Hospital, Guangzhou, China (H.D., M.L., Y.W., S.Z., H.Z.)Search for more papers by this author, Yin Wen, MBGuangdong Provincial People's Hospital, Guangzhou, China (H.D., M.L., Y.W., S.Z., H.Z.)Search for more papers by this author, Shiying Zhang, MBGuangdong Provincial People's Hospital, Guangzhou, China (H.D., M.L., Y.W., S.Z., H.Z.)Search for more papers by this author, and Hongke ZengGuangdong Provincial People's Hospital, Guangzhou, China (H.D., M.L., Y.W., S.Z., H.Z.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G21-0027 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Hongguang Ding, MD; Mengting Liu, MB; Yin Wen, MB; Shiying Zhang, MB; Hongke ZengAffiliations: Guangdong Provincial People's Hospital, Guangzhou, China (H.D., M.L., Y.W., S.Z., H.Z.)Disclosures: The authors have reported no disclosures of interest. The forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G21-0027.Corresponding Author: Hongke Zeng, Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China; e-mail, zenghongke@gdph.org.cn.Author/Illustrator Information: Hongguang Ding, Mengting Liu, Yin Wen, and Shiying Zhang are all physicians in the Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences.This article was published at Annals.org on 27 July 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics August 2021Volume 174, Issue 8 Page: W91-W93 ePublished: 27 July 2021 Issue Published: August 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Thymosin β4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction
Authors: Shi Hua Tan, Sze Jie Loo, Yu Gao, Zhong Hao Tao, Li Ping Su, Chen Xu Wang, Sophia L. Zhang, Yong Hui Mu, Ying Hua Cui, Desiree Abdurrachim, Wei Hsin Wang, Janise Lalic, Kheng Choon Lim, Jun Bu, Ru San Tan, Teck Hock Lee, Jianyi Zhang, Lei Ye
Journal: Theranostics (2021)

Rationale: Previous studies have shown that human embryonic stem cell-derived cardiomyocytes improved myocardial recovery when administered to infarcted pig and non-human primate hearts.However, the engraftment of intramyocardially delivered cells is poor and the effectiveness of clinically relevant doses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in large animal models of myocardial injury remains unknown.Here, we determined whether thymosin β4 (Tb4) could improve the engraftment and reparative potency of transplanted hiPSC-CMs in a porcine model of myocardial infarction (MI).Methods: Tb4 was delivered from injected gelatin microspheres, which extended the duration of Tb4 administration for up to two weeks in vitro.After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10 8 hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.Myocardial recovery was assessed by cardiac magnetic resonance imaging (MRI), arrhythmogenesis was monitored with implanted loop recorders, and tumorigenesis was evaluated via whole-body MRI.Results: In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation.In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function, and reduced infarct size.hiPSC-CM implantation did not increase incidence of ventricular arrhythmia and did not induce tumorigenesis in the immunosuppressed pigs.Conclusions: Co-treatment with Tb4-microspheres and hiPSC-CMs was safe and enhanced the reparative potency of hiPSC-CMs for myocardial repair in a large-animal model of MI.
Abstract 16525: A Genetic Link Between Thoracic and Abdominal Aortic Disease Revealed by Fibulin-4 Deficiency
Authors: Natasja Ramnath, Kim Van der Heiden, Lambert Speelman, Paula van Heijningen, Marcel Vermeij, Ellen Rouwet, Roland Kanaar, Jeroen Essers
Journal: Circulation (2011)

Deficiency of the FBLN4 gene, encoding the extracellular matrix protein Fibulin-4, induces thoracic aortic aneurysm formation. In Fibulin-4 knockdown mice, we have identified fibulin-4 dose depende...
MO33-7 Preparedness for COVID-19 pandemic and impact on medical oncology for breast cancer
Authors: Lina Inagaki, Takayo Fukuda, Natsue Uehiro, Akemi Kataoka, Hidetomo Morizono, Mami Kurata, Saori Kawai, Jun Masuda, Tomoko Shibayama, Yukinori Ozaki, Mari Hosonaga, Ippei Fukada, Kokoro Kobayashi, Fumikata Hara, Takayuki Kobayashi, Takayuki Ueno, Toshimi Takano, Yoshinori Ito, Shunji Takahashi, Shinji Ohno
Journal: Annals of Oncology (2021)
Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events
Authors: Bilal A Siddiqui, Jinesh S Gheeya, Rohit Goswamy, Tharakeswara K Bathala, Devaki Shilpa Surasi, Jianjun Gao, Amishi Shah, Matthew T Campbell, Pavlos Msaouel, Sangeeta Goswami, Jennifer Wang, Amado J Zurita, Eric Jonasch, Paul G Corn, Ana M Aparicio, Arlene O Siefker-Radtke, Padmanee Sharma, Sumit K Subudhi, Nizar Tannir
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallenge may be associated with improved antitumor responses. However, data are limited on response duration after ICT rechallenge, particularly after severe irAEs. Objective To evaluate safety and efficacy of ICT rechallenge after moderate-to-severe irAEs in patients with renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer. Methods In this retrospective cohort study, medical records from September 25, 2013, to June 1, 2020, for patients with genitourinary (GU) cancers at MD Anderson Cancer Center who were rechallenged with the same or different ICT following irAEs were reviewed. Demographics, ICT exposure, irAEs (grade and treatment), ICT discontinuation or rechallenge, rates of subsequent irAEs (new or recurrent) and antitumor activity (objective response rates and response duration) were reviewed. Results Sixty-one patients with RCC, UC, and prostate cancer were rechallenged with ICT after experiencing 105 total irAEs. Objective response rates after rechallenge, that is, upgrade in response, were 14% in RCC (4/28), 21% in UC (3/14), and 0% in prostate cancer. All seven patients who achieved upgrade in response had initial grade 2 or 3 irAEs. Responses were durable among these seven patients, with median radiographic progression-free survival not reached (range: 3.7–66.4 months) as of the March 8, 2021, data cut-off (median follow-up 40.9 months (95% CI 35.3 to 46.5)). All achieved complete response except one patient who was lost to follow-up. The rate of subsequent grade 3 or 4 irAEs after rechallenge was 30%, with no fatal irAEs. The rate of recrudescence of the same irAE was 26% (16/61). 54% of patients received corticosteroids (33/61), and 21% received targeted immunosuppression (13/61) for the initial irAEs. Conclusions and relevance ICT rechallenge after moderate-to-severe irAEs was associated with deep and durable responses in a subset of patients with RCC and UC, with acceptable safety and no fatal events. Strategies to enable ICT resumption after moderate-to-severe irAEs, such targeted immunosuppression, warrant further study.
MO30-2 Prognostic factors for non-small cell lung cancer patients with brain metastases (HOT 1701)
Authors: Yoshihito Ohhara, Tetsuya Kojima, Osamu Honjo, Noriyuki Yamada, Toshitaka Sato, Mamoru Kunisaki, Kei Takamura, Taichi Takashina, Noriaki Sukoh, Hisashi Tanaka, Yasutaka Kawai, Yuka Fujita, Fumiko Sugaya, Fumihiro Hommura, Toshiyuki Harada, Ryoichi Honda, Ichiro Kinoshita, Toraji Amano, Oizumi Satoshi, Hirotoshi Akita
Journal: Annals of Oncology (2021)
Association Between <i>NEDD4L</i> Variation and the Genetic Risk of Acute Appendicitis
Authors: Apostolos Gaitanidis, Haytham M. A. Kaafarani, Mathias A. Christensen, Kerry Breen, April Mendoza, Peter J. Fagenholz, George C. Velmahos, Maha R. Farhat
Journal: JAMA Surgery (2021)

The familial aspect of acute appendicitis (AA) has been proposed, but its hereditary basis remains undetermined.To identify genomic variants associated with AA.This genome-wide association study, conducted from June 21, 2019, to February 4, 2020, used a multi-institutional biobank to retrospectively identify patients with AA across 8 single-nucleotide variation (SNV) genotyping batches. The study also examined differential gene expression in appendiceal tissue samples between patients with AA and controls using the GSE9579 data set in the National Institutes of Health's Gene Expression Omnibus repository. Statistical analysis was conducted from October 1, 2019, to February 4, 2020.Single-nucleotide variations with a minor allele frequency of 5% or higher were tested for association with AA using a linear mixed model. The significance threshold was set at P = 5 × 10-8.A total of 29 706 patients (15 088 women [50.8%]; mean [SD] age at enrollment, 60.1 [17.0] years) were included, 1743 of whom had a history of AA. The genomic inflation factor for the cohort was 1.003. A previously unknown SNV at chromosome 18q was found to be associated with AA (rs9953918: odds ratio, 0.99; 95% CI, 0.98-1.00; P = 4.48 × 10-8). This SNV is located in an intron of the NEDD4L gene. The heritability of appendicitis was estimated at 30.1%. Gene expression data from appendiceal tissue donors identified NEDD4L to be among the most differentially expressed genes (14 of 22 216 genes; β [SE] = -2.71 [0.44]; log fold change = -1.69; adjusted P = .04).This study identified SNVs within the NEDD4L gene as being associated with AA. Nedd4l is involved in the ubiquitination of intestinal ion channels and decreased Nedd4l activity may be implicated in the pathogenesis of AA. These findings can improve the understanding of the genetic predisposition to and pathogenesis of AA.
P58-7 Aortitis after the use of granulocyte colony stimulating factors: A case of right lower gingival carcinoma
Authors: Masaya Watanabe, Yusuke Kanemasa, Yuka Morita, An Ohigashi, Taichi Tamura, Shohei Nakamura, Yu Yagi, Akihiko Kageyama, Tatsu Shimoyama, Yasushi Omuro
Journal: Annals of Oncology (2021)
Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder
Authors: Yating Wan, Tao Zuo, Zhilu Xu, Fen Zhang, Hui Zhan, Dorothy CHAN, Ting-Fan Leung, Yun Kit Yeoh, Francis K L Chan, Ruth Chan, Siew C Ng
Journal: Gut (2021)

Objective The gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD. Design We performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model. Results ASD and chronological age had the most significant and largest impacts on children’s faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p&lt;0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p&lt;0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum. Conclusions Gut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.
O9-1 Updated results of a phase 2 study of niraparib in heavily pretreated high-grade serous ovarian cancer patients in Japan
Authors: Kazuhiro Takehara, Eiji Kondo, Satoshi Yanagida, Toshiaki Nakamura, Junzou Hamanishi, Kenichi Harano, Kosei Hasegawa, Takeshi Hirasawa, Kensuke Hori, Shinichi Komiyama, Motoki Matsuura, Hidekatsu Nakai, Hiroko Nakamura, Jun Sakata, Tsutomu Tabata, Munetaka Takekuma, Yoshihito Yokoyama, Yoichi Kase, Toru Sugiyama, Daisuke Aoki
Journal: Annals of Oncology (2021)
Evidence of gene–gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins
Authors: R. Kjærsgaard Andersen, S.B. Clemmensen, L.A. Larsen, J.v.B. Hjelmborg, N. Ødum, G.B.E. Jemec, K. Christensen
Journal: British Journal of Dermatology (2021)

Summary Background Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss-of-function mutations, has a widely unknown genetic aetiology. Objectives To estimate the relative importance of genetic and environmental factors underlying susceptibility to HS. Methods Via the Danish Twin Registry and the Danish National Patient Registry we pulled together information on zygosity with that of HS status. Cases of HS were identified by the International Classification of Diseases (ICD)-8 (705·91) and ICD-10 (L73·2). Heritability was assessed by the classic biometric model and the possibility of gene–gene interaction via the multilocus modelling approach. Results Among 100 044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic. Monozygotic twins had a case-wise concordance rate of 28% [95% confidence interval (CI) 7–49], corresponding to a familial risk of 73 (95% CI 13–133) times that of the background population. The biometrical modelling suggested a heritability of 0·80 (95% CI 0·67–0·93), and the multilocus index estimate was 230 (95% CI 60–400). This is highly indicative of gene–gene interactions, with the possibility of up to six interacting loci. Conclusions This twin study was substantially larger and employed a more valid phenotype than previous studies. Genetics account for the majority of HS susceptibility, and HS is most likely caused by gene–gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a single-nucleotide polymorphism (SNP)–SNP level should be implemented in future HS genome-wide association studies.
Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression
Authors: Jingjing Qi, Adeline Crinier, Bertrand Escalière, Youqiong Ye, Zhengting Wang, Tianyu Zhang, Luciana Batista, Hongzhi Liu, Liwen Hong, Ningbo Wu, Mingnan Zhang, Lei Chen, Yingbin Liu, Lei Shen, Emilie Narni-Mancinelli, Eric Vivier, Bing Su
Journal: Cell Reports Medicine (2021)

Innate lymphoid cells (ILCs) are tissue-resident lymphocytes differing from conventional T lymphocytes in having no antigen-specific receptors. ILCs include natural killer (NK) cells, helper-like ILC1s, ILC2s, and ILC3s, and lymphoid tissue-inducer (LTi) cells. Tumor ILCs are frequently found in various cancers, but their roles in cancer immunity and immunotherapy remain largely unclear. We report here the single-cell characterization of blood and gut helper-like ILC subsets in healthy conditions and in colorectal cancer (CRC). The healthy gut contains ILC1s, ILC3s, and ILC3/NKs, but no ILC2s. Additional tumor-specific ILC1-like and ILC2 subsets were identified in CRC patients. Signaling lymphocytic activation molecule family member 1 (SLAMF1) was found to be selectively expressed on tumor-specific ILCs, and higher levels of SLAMF1+ ILCs were observed in the blood of CRC patients. The SLAMF1-high group of CRC patients had a significantly higher survival rate than the SLAMF1-low group, suggesting that SLAMF1 is an anti-tumor biomarker in CRC.
CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial
Authors: Jay Y. Spiegel, Shabnum Patel, Lori Muffly, Nasheed M. Hossain, Jean Oak, John H. Baird, Matthew J. Frank, Parveen Shiraz, Bita Sahaf, Juliana Craig, Maria Iglesias, Sheren Younes, Yasodha Natkunam, Michael G. Ozawa, Eric Yang, John Tamaresis, Harshini Chinnasamy, Zach Ehlinger, Warren Reynolds, Rachel Lynn, Maria Caterina Rotiroti, Nikolaos Gkitsas, Sally Arai, Laura Johnston, Robert Lowsky, Robbie G. Majzner, Everett Meyer, Robert S. Negrin, Andrew R. Rezvani, Surbhi Sidana, Judith Shizuru, Wen-Kai Weng, Chelsea Mullins, Allison Jacob, Ilan Kirsch, Magali Bazzano, Jing Zhou, Sean Mackay, Scott J. Bornheimer, Liora Schultz, Sneha Ramakrishna, Kara L. Davis, Katherine A. Kong, Nirali N. Shah, Haiying Qin, Terry Fry, Steven Feldman, Crystal L. Mackall, David B. Miklos
Journal: Nature Medicine (2021)

Abstract Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19 − or CD19 lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial ( NCT03233854 ) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL ( n = 17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL ( n = 21), 62% of patients responded with 29% CR. Relapses were CD19 −/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22 −/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.