tbuckley/cabot-search huggingface dataset:
Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers
Authors: Jinzhu Mao, Dongxu Wang, Junyu Long, Xu Yang, Jianzhen Lin, Yiwei Song, Fucun Xie, Ziyu Xun, Yanyu Wang, Yunchao Wang, Yiran Li, Huishan Sun, Jingnan Xue, Yang Song, Bangyou Zuo, Junwei Zhang, Jin Bian, Ting Zhang, Xiaobo Yang, Lei Zhang, Xinting Sang, Haitao Zhao
Journal: Journal for ImmunoTherapy of Cancer (2021)

The gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.Patients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.In total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.We demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.
Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021
Authors: Gabriela Paz-Bailey, Laura Adams, Joshua M. Wong, Katherine A. Poehling, Wilbur H. Chen, Veronica McNally, Robert L. Atmar, Stephen H. Waterman
Journal: MMWR Recommendations and Reports (2021)

Dengue is a vectorborne infectious disease caused by dengue viruses (DENVs), which are predominantly transmitted by Aedes aegypti and Aedes albopictus mosquitos. Dengue is caused by four closely related viruses (DENV-1-4), and a person can be infected with each serotype for a total of four infections during their lifetime. Areas where dengue is endemic in the United States and its territories and freely associated states include Puerto Rico, American Samoa, the U.S. Virgin Islands, the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the Dengvaxia vaccine in the United States. The vaccine is a live-attenuated, chimeric tetravalent dengue vaccine built on a yellow fever 17D backbone. Dengvaxia is safe and effective in reducing dengue-related hospitalizations and severe dengue among persons who have had dengue infection in the past. Previous natural infection is important because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination. Dengvaxia was licensed by the Food and Drug Administration for use among children and adolescents aged 9-16 years (referred to in this report as children). ACIP recommends vaccination with Dengvaxia for children aged 9-16 having evidence of a previous dengue infection and living in areas where dengue is endemic. Evidence of previous dengue infection, such as detection of anti-DENV immunoglobulin G with a highly specific serodiagnostic test, will be required for eligible children before vaccination.
Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-centre, randomised controlled trial
Authors: Julien D Schulberg, Emily K Wright, Bronte A Holt, Amy L Hamilton, Tom R Sutherland, Alyson L Ross, Sara Vogrin, Ashley M Miller, William C Connell, Mark Lust, Nik S Ding, Gregory T Moore, Sally J Bell, Edward Shelton, Britt Christensen, Peter De Cruz, Yuwei J Rong, Michael A Kamm
Journal: The Lancet. Gastroenterology & hepatology (2021)
Misconduct in public office?
Authors: Martin McKee
Journal: BMJ (2021)

Civil society organisations have a critical role in a democracy, holding governments to account for their actions.This is especially important in the United Kingdom, where the prime minister wields a level of power that is, in comparison with other western parliamentary democracies, quite exceptional, especially when they have a large parliamentary majority.Many of the checks and balances that a US president or German chancellor faces are absent in the UK.
Hitting the Right Spot: Advances in the Treatment of NSCLC With Uncommon EGFR Mutations
Authors: Joshua K. Sabari, John V. Heymach, Beth Sandy
Journal: Journal of the National Comprehensive Cancer Network (2021)

An understanding of the biology of uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is evolving. These mutations are important for the selection of targeted therapy and the development of resistance. The advent of genomic profiling has led to guideline-recommended molecular testing to identify patients with NSCLC who carry uncommon EGFR mutations to aid in the selection of appropriate targeted therapy. This article discusses the efficacy and safety of current and emerging targeted therapies for the treatment of uncommon EGFR mutations in NSCLC to aid in developing patient-specific treatment plans.
Effect of increased alcohol consumption during COVID‐19 pandemic on alcohol‐associated liver disease: A modeling study
Authors: Jovan Julien, Turgay Ayer, Elliot B. Tapper, Carolina Barbosa, William N. Dowd, Jagpreet Chhatwal
Journal: Hepatology (2021)

Alcohol consumption increased during the COVID-19 pandemic in 2020 in the United States. We projected the effect of increased alcohol consumption on alcohol-associated liver disease (ALD) and mortality.
Abstract 13678: Validation of the Termination of Resuscitation Rules in Detroit
Authors: Adam D Chalek, Arqam Husain, Robert B Dunne
Journal: Circulation (2021)

Introduction: 326,000 patients suffer from an out of hospital cardiac arrest (OHCA) each year. The Termination of Resuscitation (TOR) criteria, which recommends termination when the arrest is unwitnessed by EMS, no shocks are administered, and no ROSC occurs, guides physicians in determining the futility of continuing CPR and transporting patients to the hospital. We examined compliance with current BLS TOR rules as well as assessed an alternate set of rules, with the goal of retrospectively deriving improved TOR guidelines for OHCAs in Detroit. Methods: This is a retrospective study utilizing non-traumatic OHCA cases in Detroit from January 1, 2017 to December 31, 2019, which includes time before and after BLS TOR guidelines were officially implemented (June 1, 2018). Data is extracted from the Detroit Cardiac Arrest Registry (DCAR). Patients younger than 18 years of age and arrests of traumatic origin or those with no resuscitation attempted were excluded. Results: BLS TOR criteria was applied to the pre-TOR implementation data with resulting specificity of 79% (95% CI: 50.7-80.8) and PPV of 97.3% (95% CI: 95.5-98.6). Survival to hospital discharge when termination was recommended was projected at 2.9% (13/444). Overall transportation rate was 85% (559/656). Post-TOR implementation, specificity was 88.9% (95% CI: 78.6-99.1) and PPV was 99.1% (95% CI: 98.3-99.9). Survival to hospital discharge was 0.88% (4/453) with a 69% (451/650) overall transportation rate. Post-hoc addition of age or EMS time to patient side increased transportation rates to 81% (529/650) and 88% (571/650), respectively, and decreased false positive terminations to 0.84% (2/237) and 0% (0/148), respectively. Conclusion: Overall survival when TOR was recommended as well as futile transportation rates decreased since the implementation of the BLS TOR guidelines in Detroit. Addition of EMS time to patient side or patient age to the current TOR guidelines suggested improved performance. Although the additional criteria resulted in higher transportation rates, these factors may be useful for physicians to consider when deciding to transport patients who meet the current TOR criteria. However, further derivation and validation are needed to create optimal TOR guidelines.
The utilization of HCWs surveillance as an early warning of COVID-19 epidemic activity in the community
Authors: Amal Al Maani, Adil Al Wahaibi, Weam Nazer, Najla Al-Zadjali, Jokha Al Rawahi, Iman Al-Beloushi, Jabir Al-Sooti, Abdullah Alqayoudhi, Seif Al-Abri
Journal: Journal of Infection (2021)
Rituximab Impairs B Cell Response But Not T Cell Response to <scp>COVID</scp>‐19 Vaccine in Autoimmune Diseases
Authors: Samuel Bitoun, Julien Henry, Delphine Desjardins, Christelle Vauloup‐Fellous, Nicolas Dib, Rakiba Belkhir, Lina Mouna, Candie Joly, Marie Bitu, Bineta Ly, Juliette Pascaud, Raphaèle Seror, Anne‐Marie Roque Afonso, Roger Le Grand, Xavier Mariette
Journal: Arthritis & Rheumatology (2021)

Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine.We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools.A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response.RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response.
Long covid: research must guide future management
Authors: Anthony S David
Journal: BMJ (2021)

Back in February 2021, the UK government announced that £18.5m is being invested into clinical research into long covid by UK Research and Innovation (UKRI). 1 In light of public and medical concern about the long term effects of covid-19 infection, this is welcome.In 1988, colleagues and I published an article in The BMJ called "Post viral fatigue: time for a new approach." 2This was an attempt by young researchers to make the case that viewing the syndrome through a more unified mental-physical health lens and epidemiological orientation might counteract the increasingly polarised debate between patients with post-viral fatigue or myalgic encephalomyelitis (ME) and their doctors.We called for a clearer operational case definition, a biopsychosocial approach, and an end to emotive language all round.A generation later and our calls remain current.
Corrigendum to ‘Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers’
Authors: G. Fossard, F. Broussais, I. Coelho, S. Bailly, E. Nicolas-Virelizier, E. Toussaint, C. Lancesseur, F. Le Bras, E. Willems, E. Tchernonog, T. Chalopin, R. Delarue, R. Gressin, A. Chauchet, E. Gyan, G. Cartron, C. Bonnet, C. Haioun, G. Damaj, P. Gaulard, L. Fornecker, H. Ghesquières, O. Tournilhac, M. Gomesda Silva, R. Bouabdallah, G. Salles, E. Bachy
Journal: Annals of Oncology (2021)
Dissecting the Oncogenic Roles of Keratin 17 in the Hallmarks of Cancer
Authors: Gabriella Baraks, Robert Tseng, Chun-Hao Pan, Saumya Kasliwal, Cindy V. Leiton, Kenneth R. Shroyer, Luisa F. Escobar-Hoyos
Journal: Cancer Research (2021)

There is an unmet need to identify and validate tumor-specific therapeutic targets to enable more effective treatments for cancer. Heterogeneity in patient clinical characteristics as well as biological and genetic features of tumors present major challenges for the optimization of therapeutic interventions, including the development of novel and more effective precision medicine. The expression of keratin 17 (K17) is a hallmark of the most aggressive forms of cancer across a wide range of anatomical sites and histological types. K17 correlates with shorter patient survival, predicts resistance to specific chemotherapeutic agents, and harbors functional domains that suggest it could be therapeutically targeted. Here, we explore the role of K17 in the hallmarks of cancer and summarize evidence to date for K17-mediated mechanisms involved in each hallmark, elucidating functional roles that warrant further investigation to guide the development of novel therapeutic strategies.
Extensive bone marrow capillary network masquerading as fungal hyphae in a patient with systemic lupus erythematosus
Authors: Dominic Seet, Shir Ying Lee, Melissa Ooi, Ju Ee Seet, Jiacai Cho, Anselm Mak
Journal: Arthritis & Rheumatology (2021)

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Outcomes of intracranial germinoma—A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies
Authors: Kyung-Nam Koh, Ru Xin Wong, Dong-Eun Lee, Jung Woo Han, Hwa Kyung Byun, Hong In Yoon, Dong-Seok Kim, Chuhl Joo Lyu, Hyoung Jin Kang, Kyung Taek Hong, Joo Ho Lee, Il Han Kim, Ji Hoon Phi, Seung-Ki Kim, Tai-Tong Wong, Hsin-Lun Lee, I-Chun Lai, Yu-Mei Kang, Young-Shin Ra, Seung Do Ahn, Ho Joon Im, Wen Shen Looi, Sharon Yin Yee Low, Enrica Ee Kar Tan, Hyun Jin Park, Sang Hoon Shin, Hiroshi Fuji, Chang-Ok Suh, Yi-Wei Chen, Joo-Young Kim
Journal: Neuro-Oncology (2021)

Abstract Background This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes. Methods A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken. Results From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had β-human chorionic gonadotropin values &amp;lt;50 mIU/mL. The 5/10-year overall survival (OS) and recurrence-free survival (RFS) rates were 97.2%/96.2% and 89.9%/86.9%, respectively. RFS was predicted by the radiotherapy (RT) field, with focal RT having the worst outcome, whereas chemotherapy usage had no impact on survival. Among patients who received chemotherapy, response to chemotherapy did not predict survival outcomes. In M0 patients, primary basal ganglia tumors predicted a worse RFS. In patients with bifocal tumors, an extended field RT was associated with better outcomes. In multivariable analysis, only RT fields were associated with RFS. In relapsed patients, salvage rates were high at 85.7%. Additionally, patients who received salvage RT had a better outcome (91.6% vs. 66.7%). Conclusions Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease.
Epithelial colonization by gut dendritic cells promotes their functional diversification
Authors: Claudia A. Rivera, Violaine Randrian, Wilfrid Richer, Yohan Gerber-Ferder, Maria-Graciela Delgado, Aleksandra S. Chikina, Annika Frede, Chiara Sorini, Mathieu Maurin, Hana Kammoun-Chaari, Sara M. Parigi, Christel Goudot, Mar Cabeza-Cabrerizo, Sylvain Baulande, Sonia Lameiras, Pierre Guermonprez, Caetano Reis e Sousa, Marc Lecuit, Hélène D. Moreau, Julie Helft, Danijela Matic Vignjevic, Eduardo J. Villablanca, Ana-Maria Lennon-Duménil
Journal: Immunity (2021)

Dendritic cells (DCs) patrol tissues and transport antigens to lymph nodes to initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population composed of distinct subsets that can exhibit different activation states and functions. How tissue-specific cues orchestrate DC diversification remains elusive. Here, we show that the small intestine included two pools of cDC2s originating from common pre-DC precursors: (1) lamina propria (LP) CD103
Case 37-2021: A 60-Year-Old Man with Fevers, Fatigue, Arthralgias, a Mouth Ulcer, and a Rash
Authors: Zachary S. Wallace, Karen Rodriguez, Jonathan Dau, Donald B. Bloch, Samantha N. Champion
Journal: New England Journal of Medicine (2021)

A 60-year-old man presented with ongoing fevers and fatigue, a tongue ulcer, dry scaly nodules on the face and hands, and migratory arthralgias in the wrists, fingers, elbows, and shoulders. CT revealed dependent reticular opacities throughout the lower lobes of the lungs. Hypoxemia developed. A diagnostic test was performed.
Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight
Authors: Carolyn D. Hurst, Guo Cheng, Fiona M. Platt, Mauro A.A. Castro, Nour-al-dain S. Marzouka, Pontus Eriksson, Emma V.I. Black, Olivia Alder, Andrew R.J. Lawson, Sia V. Lindskrog, Julie E. Burns, Sunjay Jain, Jo-An Roulson, Joanne C. Brown, Jan Koster, A. Gordon Robertson, Inigo Martincorena, Lars Dyrskjøt, Mattias Höglund, Margaret A. Knowles
Journal: Cell Reports Medicine (2021)

Understanding the molecular determinants that underpin the clinical heterogeneity of non-muscle-invasive bladder cancer (NMIBC) is essential for prognostication and therapy development. Stage T1 disease in particular presents a high risk of progression and requires improved understanding. We present a detailed multi-omics study containing gene expression, copy number, and mutational profiles that show relationships to immune infiltration, disease recurrence, and progression to muscle invasion. We compare expression and genomic subtypes derived from all NMIBCs with those derived from the individual disease stages Ta and T1. We show that sufficient molecular heterogeneity exists within the separate stages to allow subclassification and that this is more clinically meaningful for stage T1 disease than that derived from all NMIBCs. This provides improved biological understanding and identifies subtypes of T1 tumors that may benefit from chemo- or immunotherapy.
2021 Updated European Association of Urology Guidelines on the Use of Adjuvant Pembrolizumab for Renal Cell Carcinoma
Authors: Jens Bedke, Laurence Albiges, Umberto Capitanio, Rachel H. Giles, Milan Hora, Thomas B. Lam, Börje Ljungberg, Lorenzo Marconi, Tobias Klatte, Alessandro Volpe, Yasmin Abu-Ghanem, Saeed Dabestani, Sergio Fernández-Pello, Fabian Hofmann, Teele Kuusk, Rana Tahbaz, Thomas Powles, Axel Bex
Journal: European Urology (2021)
Statin Use Is Associated With Diabetes Progression
Authors: Anita Slomski
Journal: JAMA (2021)

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NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming
Authors: Yanxia Rao, Siling Du, Baozhi Yang, Yuqing Wang, Yuxin Li, Ruofan Li, Tian Zhou, Xiangjuan Du, Yang He, Yafei Wang, Xin Zhou, Ti-Fei Yuan, Ying Mao, Bo Peng
Journal: Neuron (2021)