tbuckley/cabot-search huggingface dataset:
Colonization by <i>Enterobacteriaceae</i> is crucial for acute inflammatory responses in murine small intestine via regulation of corticosterone production
Authors: Zélia Menezes-Garcia, Raquel Duque Do Nascimento Arifa, Leonardo Acúrcio, Camila Bernardo Brito, Júlia Oliveira Gouvea, Renata Lacerda Lima, Rafael Wesley Bastos, Ana Carolina Fialho Dias, Luana Pereira Antunes Dourado, Leandro F. S. Bastos, Celso Martins Queiroz-Júnior, Carlos Eduardo Dias Igídio, Rafael De Oliviera Bezerra, Leda Q. Vieira, Jacques R. Nicoli, Mauro Martins Teixeira, Caio T. Fagundes, Daniele G. Souza
Journal: Gut Microbes (2020)

Although dysbiosis in the gut microbiota is known to be involved in several inflammatory diseases, whether any specific bacterial taxa control host response to inflammatory stimuli is still elusive. Here, we hypothesized that dysbiotic indigenous taxa could be involved in modulating host response to inflammatory triggers. To test this hypothesis, we conducted experiments in germ-free (GF) mice and in mice colonized with dysbiotic taxa identified in conventional (CV) mice subjected to chemotherapy-induced mucositis. First, we report that the absence of microbiota decreased inflammation and damage in the small intestine after administration of the chemotherapeutic agent 5-fluorouracil (5-FU). Also, 5-FU induced a shift in CV microbiota resulting in higher amounts of Enterobacteriaceae, including E. coli, in feces and small intestine and tissue damage. Prevention of Enterobacteriaceae outgrowth by treating mice with ciprofloxacin resulted in diminished 5-FU-induced tissue damage, indicating that this bacterial group is necessary for 5-FU-induced inflammatory response. In addition, monocolonization of germ-free (GF) mice with E. coli led to reversal of the protective phenotype during 5-FU chemotherapy. E. coli monocolonization decreased the basal plasma corticosterone levels and blockade of glucocorticoid receptor in GF mice restored inflammation upon 5-FU treatment. In contrast, treatment of CV mice with ciprofloxacin, that presented reduction of Enterobacteriaceae and E. coli content, induced an increase in corticosterone levels. Altogether, these findings demonstrate that Enterobacteriaceae outgrowth during dysbiosis impacts inflammation and tissue injury in the small intestine. Importantly, indigenous Enterobacteriaceae modulates host production of the anti-inflammatory steroid corticosterone and, consequently, controls inflammatory responsiveness in mice.
Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial
Authors: Vincenzo Mazzaferro, Davide Citterio, Sherrie Bhoori, Marco Bongini, Rosalba Miceli, Luciano De Carlis, Michele Colledan, Mauro Salizzoni, Renato Romagnoli, Barbara Antonelli, Marco Vivarelli, Giuseppe Tisone, Massimo Rossi, Salvatore Gruttadauria, Stefano Di Sandro, Riccardo De Carlis, Maria Grazia Lucà, Massimo De Giorgio, Stefano Mirabella, Luca Belli, Stefano Fagiuoli, Silvia Martini, Massimo Iavarone, Gianluca Svegliati Baroni, Mario Angelico, Stefano Ginanni Corradini, Riccardo Volpes, Luigi Mariani, Enrico Regalia, Maria Flores, Michele Droz dit Busset, Carlo Sposito
Journal: The Lancet Oncology (2020)
Association of Early-Life Cognitive Enrichment With Alzheimer Disease Pathological Changes and Cognitive Decline
Authors: Shahram Oveisgharan, Robert S. Wilson, Lei Yu, Julie A. Schneider, David A. Bennett
Journal: JAMA Neurology (2020)

Indicators of early-life cognitive enrichment (ELCE) have been associated with slower cognitive decline and decreased dementia in late life. However, the mechanisms underlying this association have not been elucidated.To examine the association of ELCE with late-life Alzheimer disease (AD) and other common dementia-related pathological changes.This clinical-pathological community-based cohort study, the Rush Memory and Aging Project, followed up participants before death for a mean (SD) of 7.0 (3.8) years with annual cognitive and clinical assessments. From January 1, 1997, through June 30, 2019, 2044 participants enrolled, of whom 1018 died. Postmortem data were leveraged from 813 participants. Data were analyzed from April 12, 2019, to February 20, 2020.Four indicators of ELCE (early-life socioeconomic status, availability of cognitive resources at 12 years of age, frequency of participation in cognitively stimulating activities, and early-life foreign language instruction) were obtained by self-report at the study baseline, from which a composite measure of ELCE was derived.A continuous global AD pathology score derived from counts of diffuse plaques, neuritic plaques, and neurofibrillary tangles.The 813 participants included in the analysis had a mean (SD) age of 90.1 (6.3) years at the time of death, and 562 (69%) were women. In a linear regression model controlled for age at death, sex, and educational level, a higher level of ELCE was associated with a lower global AD pathology score (estimate, -0.057; standard error, 0.022; P = .01). However, ELCE was not associated with any other dementia-related pathological changes. In addition, a higher level of ELCE was associated with less cognitive decline (mean [SD], -0.13 [0.19] units per year; range, -1.74 to 0.85). An indirect effect through AD pathological changes constituted 20% of the association between ELCE and the rate of late-life cognitive decline, and 80% was a direct association.These findings suggest that ELCE was associated with better late-life cognitive health, in part through an association with fewer AD pathological changes.
A 10‐year review of surgical management of dermatofibrosarcoma protuberans*
Authors: A. Durack, S. Gran, M.D. Gardiner, A. Jain, E. Craythorne, C.M. Proby, J. Marsden, C.A. Harwood, R.N. Matin, A Affleck, A Ahmed, A Akhtar, R Atkar, K Bisarya, S Chinthapalli, M Chowdry, R Coelho, M Fawzy, L Hanna‐Bashara, L. Hughes, S Jing, R Jones, C Kokkinos, S Manam, A Matthews, C McGrath, C Mitchell, A Murphy, R Pinder, C Scarsbrook, K Tang, Z.C. Venables, J Warbrick‐Smith, B.L.M. Way, B.E. Wright
Journal: British Journal of Dermatology (2020)

Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer. Standard treatment in the UK is either wide local excision (WLE) or Mohs micrographic surgery (MMS). It is unclear which approach has the lower recurrence rate.We undertook a retrospective comparative review of surgical management of DFSP in the UK National Health Service in order to define (i) current surgical practice for primary and recurrent DFSP, (ii) local recurrence rates for primary DFSP and (iii) survival outcomes for DFSP.A retrospective clinical case-note review of patients with histologically confirmed DFSP (January 2004 to December 2013) who have undergone surgical treatment.The surgical management of 483 primary and 64 recurrent DFSP in 11 plastic surgery and 15 dermatology departments was analysed. Almost 75% of primary DFSP (n = 362) were treated with WLE and 20% (n = 97) with MMS. For recurrent DFSP, 69% (n = 44) and 23% (n = 15) of patients underwent WLE and MMS, respectively. Recurrent primary DFSP occurred in six patients after WLE and none after MMS. The median follow-up time was 25·5 months (interquartile range 6·8-45·1) for new and 19·8 (IQR 4·5-44·5) for recurrent DFSP [Correction added on 1 Feb 2021, after first online publication: 4.8 years (interquartile range 3.5-5.8) was incorrect], with eight reported deaths during the follow-up analysis period (one confirmed to be DFSP related).WLE was the most common surgical modality used to treat DFSP across the UK. The local recurrence rate was very low, occurring only after WLE. Although a prospective randomized controlled trial may provide more definitive outcomes, in the absence of a clearly superior surgical modality, treatment decisions should be based on patient preference, clinical expertise and cost.
Screening endoscopy in patients with cirrhosis: screening of varices and gastrointestinal neoplasia
Authors: Rodrigo Liberal, Rui Morais, Margarida Marques, Joao Santos Antunes, Guilherme Macedo
Journal: Endoscopy (2020)

See also:Safe and effective digestive endoscopic resection in patients with cirrhosis: a single-center experienceEndoscopy 2020; 52(04): 276-284DOI: 10.1055/a-1089-9459See also:Reply to Liberal et al.Endoscopy 2020; 52(07): 624-624DOI: 10.1055/a-1175-6844
Facts and Hopes in Immunotherapy of Soft-Tissue Sarcomas
Authors: Javier Martín-Broto, David S. Moura, Brian A. Van Tine
Journal: Clinical Cancer Research (2020)

Abstract Sarcomas are mesenchymal tumors, encompassing more than 175 subtypes, each one with their own genetic complexities. As a result, immunotherapy approaches have not been universally successful across the wide range of diverse subtypes. The actual state of science and the current clinical data utilizing immunotherapy within the soft-tissue sarcomas (STS) will be detailed in this review. More precisely, the review will focus on: (i) the role of the immune microenvironment in the development and activity of new therapeutic approaches; (ii) the recent identification of the sarcoma immune class (SIC) groups, especially group SIC E with its B-cell signature that predicts immunotherapy response; (iii) the clinical trials using PD-1 and/or CTLA-4 inhibitors, which serves as reference for response data, (iv) the promising clinical activity from the combination of anti-angiogenics agents with PD-1 inhibitors, (v) the adapted T-cell therapies for synovial sarcoma that target either NY-ESO or MAGEA4; and (vi) the role for localized therapy using the virotherapy T-VEC with PD-1 inhibitors. Herein, we present the facts and the hopes for the patients with sarcoma, as the field is rapidly advancing its understanding of what and where to use the various types of immunotherapies.
Everolimus (EVE) exposure as a predictor of toxicity (Tox) in renal cell cancer (RCC) patients (Pts) in the adjuvant setting: Results of a pharmacokinetic analysis for SWOG S0931 (EVEREST), a phase III study (NCT01120249).
Authors: Timothy W. Synold, Melissa Plets, Catherine M. Tangen, Elisabeth I. Heath, Ganesh S. Palapattu, Philip C. Mack, Mark N. Stein, Maxwell V. Meng, Primo Lara, Nicholas J. Vogelzang, Ian Murchie Thompson, Christopher W. Ryan
Journal: Journal of Clinical Oncology (2017)

4566 Background: S0931 is assessing recurrence-free survival in RCC pts randomized to receive EVE versus placebo for one year following nephrectomy. To date, there has been a higher than expected dropout rate due to bothersome tox. Previous reports have shown an association between EVE trough levels and both tox and disease response in RCC pts. Therefore, we have assessed EVE trough levels to evaluate the relationship between measured exposure and probability of tox. This analysis has been approved by the DSMC. Methods: Patients received 10 mg daily EVE or placebo for nine 6-week cycles. Pre-dose whole blood samples collected pre-cycle 2 and pre-cycle 3 were analyzed for EVE. Pts with pre-cycle 2 and/or pre-cycle 3 EVE results were used in the analysis. When both trough levels were available, results were averaged. Pts were segregated into quartiles (Q) based on EVE levels and logistic regression was used to model the following adverse event outcomes using EVE trough as a predictor; any grade 3+ tox, grade 2+ triglycerides, grade 2+ hyperglycemia, grade 2+ oral mucositis, grade 2+ rash, and premature stopping of EVE. Hazard and odds ratios were adjusted for age, BMI and performance status. Results: This study reached its accrual goal and closed on 9/15/2016 with 1545 (775 EVE) randomized patients. A total of 386 pts are included in this preliminary analysis. Median EVE trough was 12.8 ng/mL (range 3.1, 75.6) per 10 mg dose. Event rates for tox were: any grade 3+ tox = 46%, grade 2+ triglycerides = 33%, grade 2+ hyperglycemia = 15%, grade 2+ oral mucositis = 34%, grade 2+ rash = 15%, and premature stopping of EVE = 40%. The risk of grade 2+ triglycerides was increased in Q2 and Q3 vs Q1 (OR = 2.95; p = 0.001 and OR = 3.48; p &lt; 0.001). The risk of grade 2+ rash was increased in Q2 and Q4 vs Q1 (OR = 2.95; p = 0.02 and OR = 3.20; p = 0.01). There was also a trend towards an increased risk of any grade 3+ tox in Q3 vs Q1 (OR = 1.72; p = 0.07). Conclusions: This analysis has identified significant associations between EVE exposure and the probability of tox. EVE analysis is ongoing and the final results will be presented. Clinical trial information: NCT01120249.
Hyperprogression to camrelizumab in a patient with esophageal squamous cell carcinoma harboring EGFR kinase domain duplication
Authors: Wei Wang, Meihong Wu, Minglu Liu, Zhengqing Yan, Guoqiang Wang, Dongliang Mao, Mei Wang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Previous studies have reported that the amplification of some genes, such as Murine Double Minute 2 or 4 and Epidermal Growth Factor Receptor ( EGFR ), may be related to hyperprogressive disease (HPD). Exploring somatic gene alterations might be an effective method to predict HPD. Herein we characterize the somatic alterations in a patient with esophageal squamous cell carcinoma (ESCC) who developed HPD to investigate the potential origins of HPD. Case presentation A man in his mid-40s was diagnosed with ESCC. After the failure of first-line treatment with cisplatin and docetaxel, the patient participated in a phase III randomized, open, multicenter clinical trial (CTR20170307) and subsequently received camrelizumab. After 4 weeks of immunotherapy, the tumor size increased by 79% compared with baseline imaging; the progressive pace was 2.5-fold higher than preimmunotherapy, and a new liver metastasis appeared. A rare EGFR exon 2–28 duplication was discovered in both preimmunotherapy and postimmunotherapy tumor tissues. Conclusion This is the first report on a patient with ESCC harboring rare EGFR kinase domain duplication in exons 2–28 and developing HPD in the process of camrelizumab treatment. This case suggested that EGFR kinase domain duplication might be associated with HPD. Administration of immune checkpoint inhibitor monotherapy in this subgroup of patients harboring EGFR kinase domain duplication should be performed with caution. These results need to be further confirmed in a larger cohort of patients.
A case series: 3-dimensional computed tomographic study of the superior orbital vessels: Superior orbital arcades and their relationships with the supratrochlear artery and supraorbital artery
Authors: Zhi-Feng Liao, Wei-Jin Hong, Li-Yao Cong, Cheng-En Luo, Wen-Feng Zhan, Jia-Qia Ke, Sheng-Kang Luo
Journal: Journal of the American Academy of Dermatology (2020)
Risk-Benefit Comparisons Between Shorter and Longer Durations of Adjuvant Chemotherapy in High-Risk Stage II Colorectal Cancer—Reply
Authors: Alberto Zaniboni, Fausto Petrelli, Roberto Labianca
Journal: JAMA Oncology (2020)

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A Woman in Her 90s With Dyspnea on Exertion and a Systolic and Diastolic Murmur
Authors: Orly Leiva, Leonard Stuart Lilly, Thomas A. Gaziano
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Localized mandibular infection affects remote in vivo bioreactor bone generation
Authors: Emma Watson, Brandon T. Smith, Mollie M. Smoak, Alexander M. Tatara, Sarita R. Shah, Hannah A. Pearce, Katie J. Hogan, Jonathan Shum, James C. Melville, Issa A. Hanna, Nagi Demian, Joseph C. Wenke, George N. Bennett, Jeroen J.J.P. van den Beucken, John A. Jansen, Mark E. Wong, Antonios G. Mikos
Journal: Biomaterials (2020)
The Way Forward in Congenital Heart Disease Research
Authors: Ari M. Cedars, Shelby Kutty
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
The MD Anderson Prostate Cancer Patient-derived Xenograft Series (MDA PCa PDX) Captures the Molecular Landscape of Prostate Cancer and Facilitates Marker-driven Therapy Development
Authors: Nallasivam Palanisamy, Jun Yang, Peter D.A. Shepherd, Elsa M. Li-Ning-Tapia, Estefania Labanca, Ganiraju C. Manyam, Murali K. Ravoori, Vikas Kundra, John C. Araujo, Eleni Efstathiou, Louis L. Pisters, Xinhai Wan, Xuemei Wang, Elba S. Vazquez, Ana M. Aparicio, Shannon L. Carskadon, Scott A. Tomlins, Lakshmi P. Kunju, Arul M. Chinnaiyan, Bradley M. Broom, Christopher J. Logothetis, Patricia Troncoso, Nora M. Navone
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Advances in prostate cancer lag behind other tumor types partly due to the paucity of models reflecting key milestones in prostate cancer progression. Therefore, we develop clinically relevant prostate cancer models. Experimental Design: Since 1996, we have generated clinically annotated patient-derived xenografts (PDXs; the MDA PCa PDX series) linked to specific phenotypes reflecting all aspects of clinical prostate cancer. Results: We studied two cell line–derived xenografts and the first 80 PDXs derived from 47 human prostate cancer donors. Of these, 47 PDXs derived from 22 donors are working models and can be expanded either as cell lines (MDA PCa 2a and 2b) or PDXs. The histopathologic, genomic, and molecular characteristics (androgen receptor, ERG, and PTEN loss) maintain fidelity with the human tumor and correlate with published findings. PDX growth response to mouse castration and targeted therapy illustrate their clinical utility. Comparative genomic hybridization and sequencing show significant differences in oncogenic pathways in pairs of PDXs derived from different areas of the same tumor. We also identified a recurrent focal deletion in an area that includes the speckle-type POZ protein-like (SPOPL) gene in PDXs derived from seven human donors of 28 studied (25%). SPOPL is a SPOP paralog, and SPOP mutations define a molecular subclass of prostate cancer. SPOPLdeletions are found in 7% of The Cancer Genome Atlas prostate cancers, which suggests that our cohort is a reliable platform for targeted drug development. Conclusions: The MDA PCa PDX series is a dynamic resource that captures the molecular landscape of prostate cancers progressing under novel treatments and enables optimization of prostate cancer–specific, marker-driven therapy.
Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Dmitriy Zamarin, Omid Hamid, Asha Nayak-Kapoor, Solmaz Sahebjam, Mario Sznol, Agron Collaku, Floyd E. Fox, Margaret A. Marshall, David S. Hong
Journal: Clinical Cancer Research (2020)

The study goal was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-C-C chemokine receptor 4 (anti-CCR4) mAb targeting effector regulatory T cells (eTreg), in combination with mAb checkpoint inhibitors durvalumab or tremelimumab.This was a multicenter, phase I, dose escalation study, followed by disease-specific cohort expansion (NCT02301130). Mogamulizumab dose escalation proceeded with concurrent dose escalation of durvalumab or tremelimumab in patients with advanced solid tumors. Cohort expansion occurred with mogamulizumab 1 mg/kg plus durvalumab 10 mg/kg or tremelimumab 10 mg/kg in patients with advanced pancreatic cancer.Forty patients were enrolled during dose escalation, followed by 24 patients during dose expansion. No dose-limiting toxicities occurred during dose escalation. No new or unexpected toxicities were seen. Tolerability, the primary endpoint, was acceptable utilizing mogamulizumab 1 mg/kg plus durvalumab or tremelimumab 10 mg/kg in the combined dose escalation and dose expansion cohorts (each n = 19). At these doses, the objective response rate was 5.3% (95% confidence interval, 0.1%-26.0%; one partial response) with each combination treatment. At all doses, mogamulizumab treatment led to almost complete depletion of peripheral eTregs, as well as reduction of intratumoral Tregs in the majority of patients. There was no clear correlation of clinical response with peripheral or intratumoral reduction in CCR4+ eTregs or with baseline degree of CCR4+ expression.Mogamulizumab in combination with durvalumab or tremelimumab did not result in potent antitumor efficacy in patients with advanced solid tumors. Tolerability of mogamulizumab 1 mg/kg combined with durvalumab or tremelimumab 10 mg/kg was acceptable.
Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease
Authors: Christoph Schultheiß, Lisa Paschold, Donjete Simnica, Malte Mohme, Edith Willscher, Lisa von Wenserski, Rebekka Scholz, Imke Wieters, Christine Dahlke, Eva Tolosa, Daniel G. Sedding, Sandra Ciesek, Marylyn Addo, Mascha Binder
Journal: Immunity (2020)