tbuckley/cabot-search huggingface dataset:
Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome– a pilot study
Authors: Van T. Pham, Sophie Fehlbaum, Nicole Seifert, Nathalie Richard, Maaike J. Bruins, Wilbert Sybesma, Ateequr Rehman, Robert E. Steinert
Journal: Gut Microbes (2021)

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.
Neutrophils in asthma: the good, the bad and the bacteria
Authors: Helena Crisford, Elizabeth Sapey, Geraint B Rogers, Steven Taylor, Prasad Nagakumar, Ravi Lokwani, Jodie L Simpson
Journal: Thorax (2021)

Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics. Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients. The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic. In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.
Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors
Authors: Jian-Guo Zhou, Anna-Jasmina Donaubauer, Benjamin Frey, Ina Becker, Sandra Rutzner, Markus Eckstein, Roger Sun, Hu Ma, Philipp Schubert, Claudia Schweizer, Rainer Fietkau, Eric Deutsch, Udo Gaipl, Markus Hecht
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The predictive power of novel biological markers for treatment response to immune checkpoint inhibitors (ICI) is still not satisfactory for the majority of patients with cancer. One should identify valid predictive markers in the peripheral blood, as this is easily available before and during treatment. The current interim analysis of patients of the ST-ICI cohort therefore focuses on the development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with metastatic cancer to ICI targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. Methods A total of 104 patients were prospectively enrolled. 54 immune cell subsets were prospectively analyzed in patients’ peripheral blood by multicolor flow cytometry before treatment with ICI (pre-ICI; n=89), and after the first application of ICI (n=65). Pre-ICI, patients were randomly allocated to a training (n=56) and a validation cohort (n=33). Univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator Cox model were used to create a predictive immune signature, which was also checked after the first ICI, to consider the dynamics of changes in the immune status. Results Whole blood samples were provided by 89 patients pre-ICI and by 65 patients after the first ICI. We identified a LIPS which is based on five immune cell subtypes: CD14 high monocytes, CD8+/PD-1 + T cells, plasmacytoid dendritic cells, neutrophils, and CD3 + /CD56 + /CD16 + natural killer (NK)T cells. The signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting overall survival (OS) benefit in both the training and the validation cohort. In both cohorts, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI 0.12 to 0.56, p=0.00025; HR 0.30, 95% CI 0.10 to 0.91, p=0.024, respectively). Regarding the whole cohort, LIPS also predicted progression-free survival (PFS). The identified LIPS was not affected by clinicopathological features with the exception of brain metastases. NKT cells and neutrophils of the LIPS can be used as dynamic predictive biomarkers for OS and PFS after first administration of the ICI. Conclusion Our study identified a predictive LIPS for survival of patients with cancer treated with PD-1/PD-L1 ICI, which is based on immune cell subsets in the peripheral whole blood. Trial registration number NCT03453892 .
Innovating and invigorating the clinical trial infrastructure for glomerular diseases
Authors: Laura Barisoni, Jonathan Barratt, Kirk Campbell, Lauren Eva, Barbara S. Gillespie, Debbie Gipson, Tobias Huber, Meg Jardine, Elaine Kamil, Matthias Kretzler, Lauren Lee, Elena Levtchenk, Ali Poyan Mehr, Patrick H. Nachman, Jun Oh, Moin Saleem, Stuart J. Shankland, Kimberly Smith, Irv Smokler, William Smoyer, Josh Tarnoff, Aliza Thompson, Howard Trachtman, Suneel Udani, Marina Vivarelli, Patrick Walker, Melissa West, Brad H. Rovin
Journal: Kidney International (2021)
Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy
Authors: Benedikt Strunz, Jonna Bister, Hanna Jönsson, Iva Filipovic, Ylva Crona-Guterstam, Egle Kvedaraite, Natalie Sleiers, Bogdan Dumitrescu, Mats Brännström, Antonio Lentini, Björn Reinius, Martin Cornillet, Tim Willinger, Sebastian Gidlöf, Russell S. Hamilton, Martin A. Ivarsson, Niklas K. Björkström
Journal: Science Immunology (2021)

Human uterine NK cells continuously differentiate in response to the monthly regeneration of the endometrium and during pregnancy.
Semaphorins: From Angiogenesis to Inflammation in Rheumatoid Arthritis
Authors: Jérôme Avouac, Sonia Pezet, Eloïse Vandebeuque, Cindy Orvain, Virginie Gonzalez, Grégory Marin, Gaël Mouterde, Claire Daïen, Yannick Allanore
Journal: Arthritis & Rheumatology (2021)

To study the potential role of semaphorins in the pathogenesis of rheumatoid arthritis (RA).Microarray experiments were performed on Affymetrix GeneChip Human Exon 1.0 ST arrays in RA endothelial cells (ECs) and control ECs derived from circulating progenitors. Expression of class 3 and class 4 semaphorins and their receptors in the serum of RA patients and healthy controls was assessed by immunohistochemical analysis in synovial tissue and by enzyme-linked immunosorbent assay.Microarray analysis revealed differential expression of class 3 and class 4 semaphorins and their receptors in RA ECs. Semaphorin 4A (SEMA4A), plexin D1, and neuropilin 1 messenger RNA (mRNA) levels were markedly increased in RA ECs by 1.75-, 2.21-, and 1.68-fold, respectively. Stimulation with tumor necrosis factor (TNF) led to a 2-fold increase in SEMA4A mRNA levels in RA ECs, and deficient SEMA4A expression modified RA EC angiogenic properties. Class 3 and class 4 semaphorins as well as their receptors were overexpressed in RA synovial tissue. A respective 1.30-fold increase and 1.54-fold increase in SEMA4A and SEMA3E, as well as a 24% decrease in SEMA3A, was observed in the serum of RA patients. Serum levels of SEMA4A, SEMA4D, and SEMA3A correlated with levels of inflammation and proangiogenic markers. In 2 independent cohorts of patients with low disease activity or with RA in remission, the presence of SEMA4A identified patients with residual disease activity.Gene expression profiling of ECs identified class 3 and class 4 semaphorins as potential biomarkers and therapeutic candidates in RA, with confirmed overexpression in ECs, synovial vessels, and serum, and correlation with validated markers of inflammation and angiogenesis. Thus, semaphorins might be novel and appealing EC-derived inflammatory and proangiogenic targets in RA.
Abstract 16411: Intraoperative Nicardipine Use During Rewarming in Norwood Procedures
Authors: Nathaniel Parchment, Sari D Holmes, Stephanie Kahntroff, Teresa Niemiec, Anne Savarese, Brian Donahue, Alicia Chaves, Geoffrey L Rosenthal, Kristopher B Deatrick, Sunjay Kaushal
Journal: Circulation (2020)

Introduction: Postoperative tissue edema Norwood procedures contributes significantly to outcomes. As nicardipine preserves ventricular function after hypothermic ischemic arrest, nicardipine treatment could support post-Norwood ventricular function, and decrease edema to improve patient outcomes. Methods: All Norwood procedures completed at a single institute between 1/1/2012 - 12/31/2019 were retrospectively reviewed, and the use of nicardipine during rewarming was initiated midway through the study period. We investigated the effects of nicardipine during rewarming on 12-month postoperative mortality, postoperative intubation times, open chest duration, and disposition at discharge. Results: Thirty-six Norwood procedures were completed, of whom 14 received nicardipine intraoperatively during the rewarming period. The nicardipine group demonstrated significantly lower 12-month postoperative mortality (0% vs 32%, p-value: 0.028) and significantly greater discharges to home (64% vs 18%, p-value: 0.005). The nicardipine group had lower median length of postoperative intubation (123 vs 146 hrs, p-value: 0.311) and open sternum time (2 [1-3] vs 3 [2-5] days, p-value: 0.067), but these analyses did not reach statistical significance (Fig 1). Conclusion: This study demonstrates the safety of nicardipine treatment during Norwood and significant decrease 12-month mortality and increase in discharge to home, with potential for reduced post-Norwood intubation and open sternum times. This study provides the basis for a prospective randomized controlled trial to demonstrate survival benefit provided by intraoperative nicardipine usage during Norwoods.
Height in adolescence as a risk factor for glioma subtypes: a nationwide retrospective cohort study of 2.2 million subjects
Authors: Roi Tschernichovsky, Lior H Katz, Estela Derazne, Matan Ben-Zion Berliner, Maya Simchoni, Hagai Levine, Lital Keinan-Boker, Alexandra Benouaich-Amiel, Andrew A Kanner, Yosef Laviv, Asaf Honig, Elizabeth Dudnik, Tali Siegal, Jacob Mandel, Gilad Twig, Shlomit Yust-Katz
Journal: Neuro-Oncology (2021)

Abstract Background Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. Methods The cohort included 2 223 168 adolescents between the ages of 16 and 19 years. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47 635 745 person-years. Cox proportional hazard models were used to estimate the hazard ratio (HR) for glioma and glioma subtypes according to height, body mass index (BMI), and sex. Results A total of 1195 patients were diagnosed with glioma during the study period. Mean (SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10-cm increase) was positively associated with the risk for glioma of any type (HR: 1.15; P = .002). The association was retained in subgroup analyses for low-grade glioma (HR: 1.17; P = .031), high-grade glioma (HR: 1.15; P = .025), oligodendroglioma (HR: 1.31; P = .015), astrocytoma (HR: 1.12; P = .049), and a category of presumed IDH-mutated glioma (HR: 1.17; P = .013). There was a trend toward a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; P = .07). After stratification of the cohort by sex, height remained a risk factor for men but not for women. Conclusions The previously established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.
Abstract PD15-02: Cx3cl1-cx3cr1 axis in liver metastasis of triple negative breast cancer
Authors: Woohang Heo, Hye-Youn Son, Ju hee Kim, Kyu Jin Lee, Myeonghee Jeon, Songbin Li, Jeehee Jang, Dong-Young Noh, Wonsik Han, Hyeong-Gon Moon
Journal: Cancer Research (2021)

Abstract Triple negative breast cancer (TNBC) is a breast cancer subtype with increased risk of distant metastasis, especially to visceral organs. However, the detailed molecular mechanism underlying the visceral metastasis of TNBC is unknown. We used three patient-derived xenograft models derived from TNBC tumors with different metastatic capacities. PDX1 and PDX2 model developed distant metastasis in only lung and liver, respectively. In contrast, PDX3 tumor metastasized to both lung and liver. RNA sequencing of the primary tumor and distant metastatic sites of these three PDX models was performed. The gene expression profiles of the primary tumors of the three models showed minimally overlapping genes. However, the microenvironment gene expression profiles, measured by using the sequencing reads aligned to mouse genome, showed distinct difference between the models. Among the differentially expressed genes, we identified Cx3cr1 as a significantly upregulated gene in the liver microenvironment of the PDX models that metastasized to liver. Next, we used 4T1 syngeneic mouse mammary carcinoma model to validate the Cx3cr1 in the mouse liver tissues. Interestingly, the Cx3cr1 up-regulation occurred during the pre-metastatic period, and Cx3cl1, the ligand of the Cx3cr1, was also up-regulated in the liver tissue prior to the development of metastasis suggesting the Cx3cr1 regulates the formation of pre-metastatic niche. Cx3cl1, the ligand of the Cx3cr1, was also up-regulated in the liver tissue prior to the development of metastasis. These data suggest that Cx3cl1 and Cx3cr1-mediated tumor-microenvironment interaction is critical in developing liver metastasis in TNBC. Cx3cl1 increased the invasion and migration of Raw264.7 monocyte/macrophage cells and this effect was abrogated by the Cx3cr1 silencing in Raw264.7 cells or treating Cx3cl1 neutralizing antibody. Pathway analysis of the RNA sequencing data showed that genes involved in extracellular matrix remodeling was significantly dysregulated in the liver tissues including Lysyl Oxidase (Lox). Cx3cl1 treatment in Raw264.7 cells resulted in increased expression of Lox and MMP9 mRNA in three-dimensional culture system. The Raw264.7 cells caused increased invasion of 4T1 cells in vitro. In conclusion, our data suggest that Cx3cl1-Cx3cr1 axis plays critical role during the liver metastasis of TNBC. Citation Format: Woohang Heo, Hye-Youn Son, Ju hee Kim, Kyu Jin Lee, Myeonghee Jeon, Songbin Li, Jeehee Jang, Dong-Young Noh, Wonsik Han, Hyeong-Gon Moon. Cx3cl1-cx3cr1 axis in liver metastasis of triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD15-02.
Abstract 12570: Fructolysis is Essential and Sufficient in Angiogenesis
Authors: Chang Chun, Heejae Chun, Chao Chen, Rajesh Mohandas, Mark Segal
Journal: Circulation (2018)

Newly sprouting angiogenic vessels metabolize a large amount of glucose inducing a low glucose micro-environment within tumors. In glucose insufficiency, fructose replaces glucose to support metabo...
The role of mortality concerns in separation and connection effects: comment on Lee and Schwarz
Authors: Dylan E. Horner, Jeff Greenberg
Journal: Behavioral and Brain Sciences (2021)

Abstract Using terror management theory and research findings, we expand the framework provided by Lee and Schwarz to highlight the potential link between separation and connection effects to existential, death-related concerns. Specifically, we address how death awareness may motivate separation and connection behaviors and how engaging in these behaviors may serve a protective terror management function.
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma
Authors: Nikhil C. Munshi, Larry D. Anderson, Nina Shah, Deepu Madduri, Jesús Berdeja, Sagar Lonial, Noopur Raje, Yi Lin, David Siegel, Albert Oriol, Philippe Moreau, Ibrahim Yakoub-Agha, Michel Delforge, Michele Cavo, Hermann Einsele, Hartmut Goldschmidt, Katja Weisel, Alessandro Rambaldi, Donna Reece, Fabio Petrocca, Monica Massaro, Jamie N. Connarn, Shari Kaiser, Payal Patel, Liping Huang, Timothy B. Campbell, Kristen Hege, Jesús San-Miguel
Journal: New England Journal of Medicine (2021)

Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma.
Endoscopic closure of a large gastric mucosal defect after endoscopic submucosal dissection using a novel endoscopic string-with-knotter suture device
Authors: Wei-hui Liu, Zhao-shen Li, Dong Wang
Journal: Endoscopy (2021)

Complete defect closure after endoscopic submucosal dissection (ESD) could decrease delayed adverse events [1]. Although various endoscopic instruments are used to suture post-ESD defects, such as the Overstitch device [2] and loop string-assisted clip device [3], these devices either cost a lot or require complicated manipulation. Therefore, we developed a string-with-knotter device (VDK-FH-A-11-180; Jiangsu Vedkang Medical Science and Technology Co., Changzhou, Jiangsu, China) [4] to easily and reliably close a gastric post-ESD defect ([Video 1]).
Effect of Collaborative Care on Persistent Postconcussive Symptoms in Adolescents
Authors: Carolyn A. McCarty, Douglas F. Zatzick, Lyscha A. Marcynyszyn, Jin Wang, Robert Hilt, Thomas Jinguji, Celeste Quitiquit, Sara P. D. Chrisman, Frederick P. Rivara
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Despite the high level of impairment for adolescents with persistent postconcussive symptoms, few studies have tested whether such problems can be remediated. <h3>Objective</h3> To examine whether collaborative care treatment is associated with improvements in postconcussive, quality of life, anxiety, and depressive symptoms over 1 year, compared with usual care. <h3>Design, Setting, and Participants</h3> The Collaborative Care Model for Treatment of Persistent Symptoms After Concussion Among Youth II Trial was a randomized clinical trial conducted from March 2017 to May 2020 with follow-up assessments at 3, 6, and 12 months. Participants were recruited from pediatric primary care, sports medicine, neurology, and rehabilitation clinics in western Washington. Adolescents aged 11 to 18 years with a diagnosed sports-related or recreational-related concussion within the past 9 months and with at least 3 symptoms persisting at least 1 month after injury were eligible. Data analysis was performed from June to September 2020. <h3>Interventions</h3> The collaborative care intervention included cognitive behavioral therapy and care management, delivered mostly through telehealth, throughout the 6-month treatment period, with enhanced medication consultation when warranted. The comparator group was usual care provided in specialty clinics. <h3>Main Outcomes and Measures</h3> Primary outcomes were adolescents’ reports of postconcussive, quality of life, anxiety, and depressive symptoms. Secondary outcomes were parent-reported symptoms. <h3>Results</h3> Of the 390 eligible adolescents, 201 (51.5%) agreed to participate, and 200 were enrolled (mean [SD] age, 14.7 [1.7] years; 124 girls [62.0%]), with 96% to 98% 3- to 12-month retention. Ninety-nine participants were randomized to usual care, and 101 were randomized to collaborative care. Adolescents who received collaborative care reported significant improvements in Health Behavior Inventory scores compared with usual care at 3 months (3.4 point decrease; 95% CI, −6.6 to −0.1 point decrease) and 12 months (4.1 point decrease; 95% CI, −7.7 to −0.4 point decrease). In addition, youth-reported Pediatric Quality of Life Inventory scores at 12 months improved by a mean of 4.7 points (95% CI, 0.05 to 9.3 points) in the intervention group compared with the control group. No differences emerged by group over time for adolescent depressive or anxiety symptoms or for parent-reported outcomes. <h3>Conclusions and Relevance</h3> Although both groups improved over time, youth receiving the collaborative care intervention had fewer symptoms and better quality of life over 1 year. Intervention delivery through telehealth broadens the reach of this treatment. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03034720