tbuckley/cabot-search huggingface dataset:
Letter to the editor: Etiology and coagulation should be considered more
Authors: Guofeng Liu, Xiaoli Fan, Li Yang, Xuefeng Luo
Journal: Hepatology (2021)

Funding informationSupported by the National Natural Science Foundation of China (81770568) and 1·3·5 project for disciplines of excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University (2019HXFH025). To the editor, It was with great interest that we read the article by von Meijenfeldt et al.[1] In this study, the results showed MPO‐DNA complexes, as a special marker for neutrophil extracellular traps (NETs), were independent predictors of transplant‐free survival in patients with severe acute liver injury (ALI) or acute liver failure (ALF). This is an intriguing study; however, several points need a deep discussion. First, the authors showed that patients with acetaminophen (APAP) etiology had significantly lower plasma levels of MPO‐DNA complexes than patients with other etiologies. The timing of blood sampling due to rapid admission may be one of the reasons, as previous studies have revealed that neutrophil activation has been rarely observed at or before the peak of APAP‐induced ALI.[2] Moreover, a growing number of evidence have showed that neutrophils activation can also coordinate the resolution of inflammation, implying that there were two faces of neutrophil activation.[2] Hence, the role of neutrophil activation and NETs in APAP‐induced ALI and ALF remains unclear, even though innate immunity including neutrophils and macrophage activation has been found to be involved in this setting.[3,4] Second, it is not clear whether NETs can activate coagulation in liver diseases.[5] Hence, more in‐depth analysis about NETs and coagulation in this research may provide a more comprehensive understanding and is encouraged. First, plasma markers of thrombosis (e.g., plasma thrombin‐antithrombin complexes, D‐dimer levels), which were usually available in most clinical practice, could be recorded and analyzed. More importantly, as the interaction of NETs with platelets and coagulation factors may contribute to the formation of thrombi, colocalization of H3citB and platelets in the liver tissues by immunofluorescence could help determine whether there was an interaction between NETs with platelets in severe ALI and ALF. In conclusion, these data emphasize the need to classify the role of etiology and coagulation in NETs formation in severe ALI or ALF. CONFLICT OF INTEREST Nothing to report.
Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy
Authors: Oliver Van Oekelen, Adolfo Aleman, Bhaskar Upadhyaya, Sandra Schnakenberg, Deepu Madduri, Somali Gavane, Julie Teruya-Feldstein, John F. Crary, Mary E. Fowkes, Charles B. Stacy, Seunghee Kim-Schulze, Adeeb Rahman, Alessandro Laganà, Joshua D. Brody, Miriam Merad, Sundar Jagannath, Samir Parekh
Journal: Nature Medicine (2021)
76P Need for awareness about immune-related adverse events (iRAEs) among community physicians in India
Authors: V.P.B. Koyyala, S. Chandra, V. Goel, S. Pasricha, M. Gupta, B.S. Muppalla, K. Vanapala, S.K. Gupta, D. Gupta, S. Sen, V.K. Srinivasulu, P. Medisetty, R.S. Patnaik
Journal: Annals of Oncology (2021)
Corrigendum: Usefulness of a papilla fixation method with an innovative clipping system for bile duct cannulation
Authors: Ikuhiro Kobori, Yasumi Katayama, Masaru Kuwada, Kei Funada, Yoshinori Gyotoku, Akihiro Kitahama, Masaya Tamano
Journal: Endoscopy (2021)

Correction to: Usefulness of a papilla fixation method with an innovative clipping system for bile duct cannulationEndoscopy 2022; 54(04): E133-E134DOI: 10.1055/a-1353-4601
Error in Figure 2
Journal: JAMA Network Open (2021)

Eli Ipp, MB; David Liljenquist, MD; Bruce Bode, MD; Viral N. Shah, MD; Steven Silverstein, MD; Carl D. Regillo, MD; Jennifer I. Lim, MD; SriniVas Sadda, MD; Amitha Domalpally, MD, PhD; Gerry Gray, PhD; Malavika Bhaskaranand, PhD; Chaithanya Ramachandra, PhD; Kaushal Solanki, PhD; EyeArt Study Group; Harvey B. DuBiner; Pauline Genter; Joyce Graham; Alan Johnson; Grace Levy-Clarke; Richard D. Pesavento; Mark D. Sherman; Brian T. Kim; Gerald B. Walman; Halis K. Akturk; Hal Joseph; Prakriti Joshee; Bruce Trippe; John M. Gilbert; Barbara A. Blodi; Susan Reed; James Reimers; Kris Lang; Holly Cohn; Ruth Shaw; Sheila Watson; Andrew Ewen; Nancy Barrett; Maria Swift; Jeffrey Gornbein
JHEP at a glance (December 2021)
Authors: Han Wang, Hongji Zhang, Yu Wang, Hai Huang, Dean Tian, Allan Tsung, Donghee Kim, Peter Konyn, Keeryth Sandhu, Brittany Dennis, Amanda Cheung, Aijaz Ahmed, Juul Mette, Diana Nielsen, Zachary Leeming, Eric Goodman, Arun Lefebvre, Vlad Sanyal, Ichiro Misumi, Joseph Mitchell, Makayla Lund, John Cullen, Stanley Lemon, Jason Whitmire, Cornelius Engelmann, Adam Herber, Annegret Franke, Peter Galle, Anett Schmiedeknecht, Thomas Berg, Jens Ricke, Regina Schinner, Max Seidensticker, Peter Malfertheiner, Maciej Pech, Bruno Sangro
Journal: Journal of Hepatology (2021)
Microbial co-occurrence complicates associations of gut microbiome with US immigration, dietary intake and obesity
Authors: Zheng Wang, Mykhaylo Usyk, Yoshiki Vázquez-Baeza, Guo-Chong Chen, Carmen R. Isasi, Jessica S. Williams-Nguyen, Simin Hua, Daniel McDonald, Bharat Thyagarajan, Martha L. Daviglus, Jianwen Cai, Kari E. North, Tao Wang, Rob Knight, Robert D. Burk, Robert C. Kaplan, Qibin Qi
Journal: Genome biology (2021)

Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos.The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus.Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.
Maintenance of response to oral octreotide compared with injectable somatostatin receptor ligands in patients with acromegaly: a phase 3, multicentre, randomised controlled trial
Authors: Maria Fleseriu, Alexander Dreval, Irina Bondar, Gulnar Vagapova, Djuro Macut, Yulia G Pokramovich, Mark E Molitch, Nina Leonova, Gerald Raverot, Elena Grineva, Yury E Poteshkin, Yossi Gilgun-Sherki, William H Ludlam, Gary Patou, Asi Haviv, Murray B Gordon, Nienke R Biermasz, Shlomo Melmed, Christian J Strasburger
Journal: The Lancet Diabetes & Endocrinology (2021)
Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis
Authors: Ajay K. Singh, Kevin Carroll, Vlado Perkovic, Scott Solomon, Vivekanand Jha, Kirsten L. Johansen, Renato D. Lopes, Iain C. Macdougall, Gregorio T. Obrador, Sushrut S. Waikar, Christoph Wanner, David C. Wheeler, Andrzej Więcek, Allison Blackorby, Borut Cizman, Alexander R. Cobitz, Rich Davies, Jo Dole, Lata Kler, Amy M. Meadowcroft, Xinyi Zhu, John J.V. McMurray
Journal: New England Journal of Medicine (2021)

Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels.In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25.A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups.Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).
Association of Gestational Age at Birth With Subsequent Suspected Developmental Coordination Disorder in Early Childhood in China
Authors: Jing Hua, Anna L. Barnett, Gareth J. Williams, Xiaotian Dai, Yuanjie Sun, Haifeng Li, Guixia Chen, Lei Wang, Junyan Feng, Yingchun Liu, Lan Zhang, Ling Zhu, Tingting Weng, Hongyan Guan, Yue Gu, Yingchun Zhou, Andrew Butcher, Wenchong Du
Journal: JAMA Network Open (2021)

<h3>Importance</h3> It remains unknown whether children born at different degrees of prematurity, early term, and post term might have a higher risk of developmental coordination disorder (DCD) compared with completely full-term children (39-40 gestational weeks). <h3>Objective</h3> To differentiate between suspected DCD in children with different gestational ages based on a national representative sample in China. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted in China from April 1, 2018, to December 31, 2019. A total of 152 433 children aged 3 to 5 years from 2403 public kindergartens in 551 cities of China were included in the final analysis. A multilevel regression model was developed to determine the strength of association for different gestational ages associated with suspected DCD when considering kindergartens as clusters. <h3>Main Outcomes and Measures</h3> Children's motor performance was assessed using the Little Developmental Coordination Disorder Questionnaire, completed by their parents. Gestational age was determined according to the mother's medical records and divided into 7 categories: completely full term (39 to 40 weeks' gestation), very preterm (&lt;32 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), late term (41 weeks), and post term (&gt;41 weeks). <h3>Results</h3> A total of 152 433 children aged 3 to 5 years (mean [SD] age, 4.5 [0.8] years), including 80 370 boys (52.7%) and 72 063 girls (47.3%), were included in the study. There were 45 052 children (29.6%) aged 3 years, 59 796 (39.2%) aged 4 years, and 47 585 (31.2%) aged 5 years. Children who were born very preterm (odds ratio [OR], 1.35; 95% CI, 1.23-1.48), moderately preterm (OR, 1.18; 95% CI, 1.02-1.36), late preterm (OR, 1.24; 95% CI, 1.16-1.32), early term (OR, 1.11; 95% CI, 1.06-1.16), and post term (OR, 1.17; 95% CI, 1.07-1.27) were more likely to be classified in the suspected DCD category on the Little Developmental Coordination Disorder Questionnaire than completely full-term children after adjusting for the same characteristics. Additionally, there was no association with suspected DCD in younger (aged 3 years) early-term and postterm children by stratified analyses. <h3>Conclusions and Relevance</h3> In this cohort study, every degree of prematurity at birth, early-term birth, and postterm birth were associated with suspected DCD when compared with full-term birth. These findings have important implications for understanding motor development in children born at different gestational ages. Long-term follow-up and rehabilitation interventions should be considered for children born early and post term.
Neutrophils and neutrophil extracellular trap components: Emerging biomarkers and therapeutic targets for age-related eye diseases
Authors: Irene Martínez-Alberquilla, Xavier Gasull, Patricia Pérez-Luna, Rubén Seco-Mera, Javier Ruiz-Alcocer, Almudena Crooke
Journal: Ageing Research Reviews (2021)

Age-related eye diseases, including dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy, represent a major global health issue based on their increasing prevalence and disabling action. Unraveling the molecular mechanisms underlying these diseases will provide novel opportunities to reduce the burden of age-related eye diseases and improve eye health, contributing to sustainable development goals achievement. The impairment of neutrophil extracellular traps formation/degradation processes seems to be one of these mechanisms. These traps formed by a meshwork of DNA and neutrophil cytosolic granule proteins may exacerbate the inflammatory response promoting chronic inflammation, a pivotal cause of age-related diseases. In this review, we describe current findings that suggest the role of neutrophils and their traps in the pathogenesis of the above-mentioned age-related eye diseases. Furthermore, we discuss why these cells and their constituents could be biomarkers and therapeutic targets for dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy. We also examine the therapeutic potential of some neutrophil function modulators and provide several recommendations for future research in age-related eye diseases.
121O RATIONALE 309: A randomized, global, double-blind, phase III trial of tislelizumab (TIS) vs placebo, plus gemcitabine + cisplatin (GP), as first-line treatment for recurrent/metastatic nasopharyngeal cancer (RM-NPC)
Authors: Y. Yang, J. Pan, H. Wang, S. Qu, N. Chen, X. Chen, Y. Sun, X. He, C. Hu, L. Lin, Q. Yu, S. Wang, G. Wang, F. Lei, J. Wen, K. Yang, Z. Lin, Y. Wu, W. Fang, L. Zhang
Journal: Annals of Oncology (2021)
A Novel Isoform of COL4A1 in the Regulation of Vascular Intercellular Communication
Authors: Lei Huang, Maryam Ajmal, Aisha Ajmal, Yue Zhao, Tong Li, Lingfang Zeng
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Vascular interventions have transformed the outlook towards improved patient-outcomes following atherosclerotic lesions
Geographical distribution of TTS cases following AZD1222 (ChAdOx1 nCoV-19) vaccination
Authors: Karina Soboleva, Nirmal Kumar Shankar, Madhavi Yadavalli, Cátia Ferreira, Nadia Foskett, Kert Putsepp, Lisa Beth Ferstenberg, Magnus Nord, Hugo Gomes da Silva, Prakash Bhuyan
Journal: The Lancet Global Health (2021)
Myelofibrosis: Genetic Characteristics and the Emerging Therapeutic Landscape
Authors: Ayalew Tefferi, Naseema Gangat, Animesh Pardanani, John D. Crispino
Journal: Cancer Research (2021)

Primary myelofibrosis (PMF) is one of three myeloproliferative neoplasms (MPN) that are morphologically and molecularly inter-related, the other two being polycythemia vera (PV) and essential thrombocythemia (ET). MPNs are characterized by JAK-STAT-activating JAK2, CALR, or MPL mutations that give rise to stem cell-derived clonal myeloproliferation, which is prone to leukemic and, in case of PV and ET, fibrotic transformation. Abnormal megakaryocyte proliferation is accompanied by bone marrow fibrosis and characterizes PMF, while the clinical phenotype is pathogenetically linked to ineffective hematopoiesis and aberrant cytokine expression. Among MPN-associated driver mutations, type 1-like CALR mutation has been associated with favorable prognosis in PMF, while ASXL1, SRSF2, U2AF1-Q157, EZH2, CBL, and K/NRAS mutations have been shown to be prognostically detrimental. Such information has enabled development of exclusively genetic (GIPSS) and clinically integrated (MIPSSv2) prognostic models that facilitate individualized treatment decisions. Allogeneic stem cell transplantation remains the only treatment modality in MF with the potential to prolong survival, whereas drug therapy, including JAK2 inhibitors, is directed mostly at the inflammatory component of the disease and is therefore palliative in nature. Similarly, disease-modifying activity remains elusive for currently available investigational drugs, while their additional value in symptom management awaits controlled confirmation. There is a need for genetic characterization of clinical observations followed by in vitro and in vivo preclinical studies that will hopefully identify therapies that target the malignant clone in MF to improve patient outcomes.
148P A phase II study of tislelizumab plus chemotherapy in EGFR mutated advanced non-squamous NSCLC patients failed to EGFR TKI therapies: First analysis
Authors: B. Han, P. Tian, Y. Zhao, X. Yu, Q. Guo, Z. Yu, X. Zhang, Y. Li, L. Chen, X. Shi, Y. Zhang, J. Wang
Journal: Annals of Oncology (2021)
Can Improved Use of Biomarkers Alter the Fate of PI3K Pathway Inhibitors in the Clinic?
Authors: Emily C. Erickson, Alex Toker
Journal: Cancer Research (2021)

Abstract The high frequency of PI3K pathway alterations in cancer has motivated numerous efforts to develop drugs targeting this network. Although many potent and selective inhibitors have been developed and evaluated in preclinical models, their progress to clinical approval has been limited. Here we discuss the pressing need to develop improved biomarker strategies to guide patient selection and improve assessment of patient responses to PI3K pathway inhibitors to address unresolved issues surrounding the efficacy and tolerability of these compounds in patients with cancer.
Complete resection of an esophageal tubular duplication with high grade squamous intraepithelial neoplasia by endoscopic submucosal dissection
Authors: Li Ma, Kun Zhao, Yuejuan Zhang, Keyu Ren, Lipeng Jin, Hao Yuan, Baoguo He
Journal: Endoscopy (2021)

We performed a gastroscopy in a 46-year-old man with upper abdominal pain, which revealed an esophageal tubular duplication (27 cm from the incisors) ([Fig. 1 a]) and red thickened mucosa (approximately 6 mm in diameter) at its distal opening ([Fig. 1 b]). Magnifying gastroscopy detected clear boundaries of this mucosal patch, which contained type B1 blood vessels and was diagnosed as being squamous high grade neoplasia. Histopathological examination of the biopsy subsequently confirmed this diagnosis. Neither an enhanced computed tomography (CT) scan of the chest or an upper gastrointestinal angiography showed any abnormalities.
Association Between Antiseizure Drug Monotherapy and Mortality for Patients With Poststroke Epilepsy
Authors: David Larsson, Arton Baftiu, Cecilie Johannessen Landmark, Mia von Euler, Eva Kumlien, Signild Åsberg, Johan Zelano
Journal: JAMA Neurology (2021)

There is little evidence to guide the choice of antiseizure medication (ASM) for patients with poststroke epilepsy. Theoretical concerns about detrimental effects of ASMs on survival exist. Enzyme-inducing drugs could interfere with secondary stroke prevention. The US Food and Drug Administration recently issued a safety announcement about the potential proarrhythmic properties of lamotrigine.To investigate whether mortality varies with specific ASMs among patients with poststroke epilepsy.A cohort study was conducted using individual-level data from linked registers on all adults in Sweden with acute stroke from July 1, 2005, to December 31, 2010, and subsequent onset of epilepsy before December 31, 2014. A total of 2577 patients receiving continuous ASM monotherapy were eligible for the study. Data were analyzed between May 27, 2019, and April 8, 2021.The dispensed ASM (Anatomical Therapeutic Chemical code N03A) determined exposure status, and the first dispensation date marked the start of treatment.The primary outcome, all-cause death, was analyzed using Cox proportional hazards regression with carbamazepine as the reference. Cardiovascular death (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I0-I99 as the underlying cause) was assessed using Fine-Gray competing risk regression models.A total of 2577 patients (1400 men [54%]; median age, 78 years [IQR, 69-85 years]) were included. The adjusted hazard ratio of all-cause death compared with carbamazepine was 0.72 (95% CI, 0.60-0.86) for lamotrigine, 0.96 (95% CI, 0.80-1.15) for levetiracetam, 1.40 (95% CI, 1.23-1.59) for valproic acid, 1.16 (95% CI, 0.88-1.51) for phenytoin, and 1.16 (95% CI, 0.81-1.66) for oxcarbazepine. The adjusted hazard ratio of cardiovascular death compared with carbamazepine was 0.76 (95% CI, 0.61-0.95) for lamotrigine, 0.77 (95% CI, 0.60-0.99) for levetiracetam, 1.40 (95% CI, 1.19-1.64) for valproic acid, 1.02 (95% CI, 0.71-1.47) for phenytoin, and 0.71 (95% CI, 0.42-1.18) for oxcarbazepine.This cohort study's findings suggest differences in survival between patients treated with different ASMs for poststroke epilepsy. Patients receiving lamotrigine monotherapy had significantly lower mortality compared with those receiving carbamazepine. The opposite applied to patients prescribed valproic acid, who had a higher risk of cardiovascular and all-cause death. Levetiracetam was associated with a reduced risk of cardiovascular death compared with carbamazepine, but there was no significant difference in overall mortality.
Neutrophil DREAM come true: The not-so-impossible quest for mechanisms of neutrophil function and heterogeneity
Authors: John C. Gomez, Claire M. Doerschuk
Journal: The Journal of Experimental Medicine (2021)

Neutrophil functions and responses are heterogeneous, and the nature and categorization of this heterogeneity is achieving considerable interest. Work by Li et al. in this issue of JEM (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211083) identifies how a transcriptional repressor, DREAM, regulates adhesion of neutrophils to endothelial cells and their transmigration into tissue. This study offers a mechanism for heterogeneity in this critical response of neutrophils to inflammatory stimuli.