tbuckley/cabot-search huggingface dataset:
Identification of α‐fetoprotein‐specific T‐cell receptors for hepatocellular carcinoma immunotherapy
Authors: Wei Zhu, Yibing Peng, Lan Wang, Yuan Hong, Xiaotao Jiang, Qi Li, Heping Liu, Lei Huang, Juan Wu, Esteban Celis, Todd Merchen, Edward Kruse, Yukai He
Journal: Hepatology (2018)

Hepatocellular carcinoma (HCC) is the major form of liver cancer for which there is no effective therapy. Genetic modification with T‐cell receptors (TCRs) specific for HCC‐associated antigens, such as α‐fetoprotein (AFP), can potentially redirect human T cells to specifically recognize and kill HCC tumor cells to achieve antitumor effects. In this study, using lentivector and peptide immunization, we identified a population of cluster of differentiation 8 (CD8) T cells in human leukocyte antigen (HLA)‐A2 transgenic AAD mice that recognized AFP 158 epitope on human HCC cells. Adoptive transfer of the AFP 158 ‐specific mouse CD8 T cells eradicated HepG2 tumor xenografts as large as 2 cm in diameter in immunocompromised nonobese diabetic severe combined immunodeficient gamma knockout (NSG) mice. We then established T‐cell hybridoma clones from the AFP 158 ‐specific mouse CD8 T cells and identified three sets of paired TCR genes out of five hybridomas. Expression of the murine TCR genes redirected primary human T cells to bind HLA‐A2/AFP 158 tetramer. TCR gene‐engineered human T (TCR‐T) cells also specifically recognized HLA‐A2 + AFP + HepG2 HCC tumor cells and produced effector cytokines. Importantly, the TCR‐T cells could specifically kill HLA‐A2 + AFP + HepG2 tumor cells without significant toxicity to normal primary hepatocytes in vitro . Adoptive transfer of the AFP‐specific TCR‐T cells could eradicate HepG2 tumors in NSG mice. Conclusion: We have identified AFP‐specific murine TCR genes that can redirect human T cells to specifically recognize and kill HCC tumor cells, and those AFP 158 ‐specific TCRs have a great potential to engineer a patient's autologous T cells to treat HCC tumors. (H epatology 2018).
C-reactive protein as a prognostic factor in advanced urothelial carcinoma receiving chemotherapy or immunotherapy.
Authors: Yan Zhao, Gregory Russell Pond, Gurudatta Naik, Xiao X. Wei, Bradley Alexander McGregor, Guru Sonpavde
Journal: Journal of Clinical Oncology (2018)

436 Background: Clinical prognostic factors have been reported for patients receiving systemic chemotherapy. We hypothesized that markers of tissue damage and inflammation may be prognostic. We conducted a retrospective study to evaluate the prognostic impact of serum lactate dehydrogenase (LDH) and C-reactive protein (CRP) in patients with metastatic UC. Methods: We collected data for patients with metastatic UC receiving systemic therapy and measured serum LDH and CRP at baseline before initiating therapy. The variables collected were recognized clinical prognostic factors (performance status [PS], visceral metastasis, hemoglobin, albumin) and outcomes (time to failure [TTF], overall survival [OS]). TTF was defined as time from initiation of therapy to discontinuation of agent for any reason. LDH and CRP were evaluated on a log-continuous scale. The Kaplan-Meier method was used to estimate times to events. Cox proportional hazards regression and logistic regression were used to study the association of factors with TTF and OS. All tests were 2-sided and significance was defined as p≤0.05. Results: A total of 36 patients were available with a median age of 74 years. The systemic therapy was platinum-based chemotherapy in 18 patients (50%), PD1/PD-L1 inhibitor in 8 patients (22.2%) and the remaining received other agents (taxane or investigational). Twenty-nine (80.5%) had PS 0-1, 13 (36.1%) had visceral metastasis and 16 (44.4%) had received prior platinum-based chemotherapy. A total of 31 patients were evaluable for this analysis with 5 inevaluable due to missing data or inadequate follow-up. On multivariable analyses, only CRP was associated with TTF (HR 1.55 [95% CI: 1.10, 2.20], p = 0.013) and OS (HR 1.77 [95% CI1.10, 2.85], p = 0.018). The limitations of a small dataset and retrospective analysis apply. Conclusions: In patient with advanced UC receiving systemic chemotherapy or PD1/PD-L1 inhibitors as first-line or salvage therapy, CRP was significantly prognostic for both TTF and OS, while other factors were not. Given the potentially powerful prognostic impact of CRP, investigation in larger datasets is warranted to enable better prognostic stratification.
Rabies Vaccine Hesitancy and Deaths Among Pregnant and Breastfeeding Women — Vietnam, 2015–2016
Authors: Huong T.T. Nguyen, Cuc H. Tran, Anh D. Dang, Huong G.T. Tran, Thiem D. Vu, Thach N. Pham, Hoang V. Nguyen, Anh N.K. Nguyen, Emily G. Pieracci, Duong N. Tran
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Human rabies deaths are preventable through prompt administration of postexposure prophylaxis (PEP) with rabies immune globulin and rabies vaccine after exposure to a rabid animal (1); there are no known contraindications to receiving PEP (1,2). Despite widespread availability of PEP in Vietnam, in 2015 the Ministry of Health (MoH) received reports of pregnant and breastfeeding women with clinically diagnosed rabies. MoH investigated factors associated with these rabies cases. MoH found that, during 2015-2016, among 169 cases reported in Vietnam, two probable cases of rabies were reported in breastfeeding mothers and four in pregnant women, all of whom had been bitten by dogs. All six patients died. Three of the four pregnant women had cesarean deliveries. One of the three newborns died from complications believed to be unrelated to rabies; the fourth pregnant woman contracted rabies too early in pregnancy for the fetus to be viable. Two of the patients sought care from a medical provider or traditional healer; however, none sought PEP after being bitten. In each case, families reported the patient's fear of risk to the fetus or breastfed child as the primary barrier to receiving PEP. These findings highlight the need for public health messaging about the safety and effectiveness of PEP in preventing rabies among all persons with exposures, including pregnant and breastfeeding women.
COMPARISON OF CORONARY FLOW RESERVE IN NORMAL PERFUSION PATIENTS WITH AND WITHOUT CORONARY RISK FACTORS USING CADMIUM ZINC TELLURIDE BASED GAMMA CAMERA
Authors: Gustavo Daquarti, Alejandro Meretta, Daniel Rosa, Mariana Corneli, Eugenia Aguirre, Magali Gobbo, Carlos Rapallo, Osvaldo Masoli
Journal: Journal of the American College of Cardiology (2018)
The Second Amendment and a Well-Regulated Firearms Environment
Authors: Lawrence O. Gostin, Sarah Duranske
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
JAVELIN Gastric 100: Phase 3 trial of avelumab (anti-PD-L1) maintenance therapy versus continuation of first-line chemotherapy in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC).
Authors: Markus H. Moehler, Min-Hee Ryu, Keun-Wook Lee, Hasan Senol Coskun, Rachel Wong, Mustafa Ozguroglu, Hyun-Choel Chung, Artem Poltoratsky, Akihito Tsuji, Chia-Jui Yen, Alina Muntean, Samuel le Sourd, Gina M. Vaccaro, Julien Taieb, Narikazu Boku, Maitreyi Sharma, Huiling Xiong, Ilaria Conti, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2018)

TPS195 Background: Outcomes with first-line (1L) chemotherapy for GC/GEJC are limited and new strategies to increase efficacy without added toxicity are needed. Avelumab, a human anti-PD-L1 IgG1 monoclonal antibody, is approved for metastatic Merkel cell carcinoma (US and EU) and advanced urothelial carcinoma after progression on platinum therapy (US). In phase 1 studies in advanced GC/GEJC, avelumab showed antitumor activity and a manageable safety profile, including in a subgroup of patients (pts) without progression on 1L chemotherapy who received avelumab as maintenance therapy. JAVELIN Gastric 100 (NCT02625610) is a global, randomized, open-label, phase 3 trial comparing maintenance therapy with avelumab vs continuation of 1L chemotherapy in pts with advanced GC/GEJC who have not progressed after 12 weeks of 1L oxaliplatin/fluoropyrimidine chemotherapy. Methods: Eligible pts have histologically confirmed, unresectable, measurable, locally advanced or metastatic GC/GEJC adenocarcinoma, no prior chemotherapy for advanced disease, no prior therapy targeting T-cell coregulatory proteins, and ECOG PS of 0–1. Pts are not preselected based on PD-L1 expression and pts with HER2+ tumors are excluded. Approximately 466 pts who achieve at least stable disease following 12 weeks of 1L oxaliplatin/fluoropyrimidine chemotherapy will be randomized 1:1 to receive maintenance therapy with either avelumab 10 mg/kg by IV infusion Q2W or continuation of 1L chemotherapy. Maintenance therapy is given until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are overall survival and progression-free survival. Secondary endpoints include best overall response, quality of life measures, safety (NCI-CTCAE v4.03), and tumor biomarkers. Responses are evaluated per RECIST 1.1 and adjudicated by independent review committee. Enrollment is ongoing at sites in North/South America, Asia-Pacific, and Europe. Clinical trial information: NCT02625610.
FDG PET/CT of Chromophobe Renal Cell Carcinoma With Sarcomatoid Differentiation
Authors: Chee H. Lee, Vivek Kesari, Teklu Legesse, Wengen Chen
Journal: Clinical Nuclear Medicine (2018)

We report the case of a 49-year-old white man with a chromophobe renal cell carcinoma associated with sarcomatoid differentiation, an uncommon yet an aggressive form of dedifferentiated renal cell carcinoma. In opposite to the conventional renal cell carcinoma, which may not always demonstrate avid FDG activity, the sarcomatoid differentiated chromophobe renal cell carcinoma shows intense FDG uptake on PET. This case highlights the role of FDG PET/CT in staging and restaging this type of rare renal cell carcinoma.
MSc in functional and clinical anatomy
Authors: Rhys Morris, Priam Heire
Journal: BMJ (2012)

The MSc in functional and clinical anatomy at the University of Birmingham is a part time taught course designed to help participants develop a better understanding of anatomy, particularly its clinical applications.

This course is suitable for clinicians at all levels who are keen to develop their knowledge of anatomy and research skills while working full time. It is applicable to trainees in a variety of specialties, such as radiology and gynaecology, as well as to surgical trainees, and it will be useful for general practitioners wanting to develop special interests. 

The degree also provides a useful grounding for anyone considering an academic training job; and the opportunity to do original research for the dissertation provides a superb foundation for further postgraduate courses such as an MD or PhD. As it is part time, the course is suitable for people training or working outside the West Midlands.

The programme runs for two academic years, …
Live attenuated oral <i>Salmonella</i> platform for effective T- and B-cell targeting of PD-L1.
Authors: Sébastien Wieckowski, Heiko Smetak, Iris Kobl, Lilli Podola, Anne-Lucie Nugues, Philippe Slos, Amine Adda Berkane, Ming Wei, Klaus M. Breiner, Albrecht Meichle, Marc Mansour, Matthias Schroff, Philipp Beckhove, Heinz Lubenau
Journal: Journal of Clinical Oncology (2018)

74 Background: Significant progresses have been recently achieved in cancer vaccines, yet novel immunization solutions to deliver efficiently tumor-associated antigens to professional antigen-presenting cells, and to overcome the peripheral tolerance and the immunosuppressive tumor microenvironment that prevent the eradication of cancer in most of patients, are urgently needed. VAXIMM is developing a unique and versatile oral T-cell vaccination platform based on the FDA-approved live-attenuated Salmonella Typhi strain Ty21a vaccine Vivotif, capable of delivering tumor-associated antigens encoded in DNA expression construct to the gut-associated lymphoid tissue, breaking immune tolerance and inducing effective anti-tumor immunity. Methods: This study summarizes the immunogenicity and antileukemia efficacy of VXM10 vaccines based on the live-attenuated Salmonella Typhimurium strain SL7207, transformed with a eukaryotic expression plasmid encoding different variants of the murine PD-L1 protein. Results: The antileukemia activity of VXM10 was evaluated in the FBL-3 disseminated model of leukemia, in which the tumor cells strongly express PD-L1. Multiple oral administrations of VXM10 vaccines produced a strong anti-tumor effect, with 100% of surviving animals 80 days after challenge with FBL3 leukemia in the highest dose groups. Moreover, 100% of long-term surviving mice resisted re-challenge with FBL-3 cells, demonstrating that vaccination with VXM10 generated a potent memory T cell response against the leukemia. Importantly, full leukemia control was achieved in both prophylactic and therapeutic settings. Upon immunization with VXM10 vaccines, T cell response was raised against PD-L1 epitopes after in vitro restimulation of the splenocytes, and anti-PD-L1 antibodies were detected in the serum. The precise mechanism of action of VXM10 vaccines is currently being investigated. Conclusions: This study provides further evidence that VAXIMM’s oral T-cell vaccination platform can be employed to stimulate anti-tumor immunity against antigens of the immune checkpoint regulatory protein PD-L1. These data paved the way for advancing the development of VXM10 into clinical development.
Publisher Correction: BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome
Authors: Gabrielle Olley, Morad Ansari, Hemant Bengani, Graeme R. Grimes, James Rhodes, Alex von Kriegsheim, Ana Blatnik, Fiona J. Stewart, Emma Wakeling, Nicola Carroll, Alison Ross, Soo-Mi Park, Wendy A. Bickmore, Madapura M. Pradeepa, David R. FitzPatrick
Journal: Nature Genetics (2019)
Tumor Progression Locus 2 in Hepatocytes Potentiates Both Liver and Systemic Metabolic Disorders in Mice
Authors: Jun Gong, Chun Fang, Peng Zhang, Pi‐Xiao Wang, Yixing Qiu, Li‐Jun Shen, Li Zhang, Xue‐Yong Zhu, Song Tian, Feng Li, Zhihua Wang, Zan Huang, Aibing Wang, Xiao‐Dong Zhang, Zhi‐Gang She
Journal: Hepatology (2018)

Tumor progression locus 2 (TPL2), a serine/threonine kinase, has been regarded as a potentially interesting target for the treatment of various diseases with an inflammatory component. However, the function of TPL2 in regulating hepatocyte metabolism and liver inflammation during the progression of nonalcoholic fatty liver disease (NAFLD) is poorly understood. Here, we report that TPL2 protein expression was significantly increased in fatty liver from diverse species, including humans, monkeys, and mice. Further investigations revealed that compared to wild‐type (WT) littermates, hepatocyte‐specific TPL2 knockout (HKO) mice exhibited improved lipid and glucose imbalance, reserved insulin sensitivity, and alleviated inflammation in response to high‐fat diet (HFD) feeding. Overexpression of TPL2 in hepatocytes led to the opposite phenotype. Regarding the mechanism, we found that mitogen‐activated protein kinase kinase 7 (MKK7) was the specific substrate of TPL2 for c‐Jun N‐terminal kinase (JNK) activation. TPL2‐MKK7‐JNK signaling in hepatocytes represents a promising drugable target for treating NAFLD and associated metabolic disorders. Conclusion: In hepatocytes, TPL2 acts as a key mediator that promotes both liver and systemic metabolic disturbances by specifically increasing MKK7‐JNK activation.
Working as a locum senior house officer
Authors: Anju Soni
Journal: BMJ (2006)

A locum job gives you the chance to work with a range of consultants in different subspecialties and to hone your clinical skills. But to start with you may feel completely lost and disoriented: you don't know the staff or the patients and you won't know your way around. Here are some tips on making the most of a locum senior house …
THE USE OF CARDIAC MRI TO DETECT MYOCARDIAL FIBROSIS AND DEVELOPMENT OF RESTRICTIVE CARDIAC PHYSIOLOGY AFTER HTX
Authors: Derek Leong, Jignesh Patel, Daniel Berman, Sadia Dimbil, Ryan Levine, Louise Thomson, Balaji Tamarappoo, Michelle Kittleson, Fardad Esmailian, Lawrence Czer, Jon Kobashigawa
Journal: Journal of the American College of Cardiology (2018)
Fine Particulate Air Pollution and the Expression of microRNAs and Circulating Cytokines Relevant to Inflammation, Coagulation, and Vasoconstriction
Authors: Renjie Chen, Huichu Li, Jing Cai, Cuicui Wang, Zhijing Lin, Cong Liu, Yue Niu, Zhuohui Zhao, Weihua Li, Haidong Kan
Journal: Environmental Health Perspectives (2018)

MicroRNAs (miRNAs) are a key factor in epigenetic regulation of gene expression, but miRNA responses to fine particulate matter (PM2.5) air pollution and their potential contribution to cardiovascular effects of PM2.5 are unknown.We explored the potential influence of PM2.5 on the expression of selected cytokines relevant to systemic inflammation, coagulation, and vasoconstriction, and on miRNAs that may regulate their expression.We designed a double-blind, randomized crossover study in which true and sham air purifiers were used to expose 55 healthy young adult students in Shanghai, China, to reduced or ambient levels of indoor PM2.5 during two-week periods, and we measured the expression (mRNA and protein) of 10 serum cytokines, and miRNAs that target them, after each intervention period. We used linear mixed-effect models to estimate associations of the intervention, and time-weighted personal PM2.5 exposures, with the cytokines, mRNA, and miRNAs; we also explored potential mediation by miRNAs.The findings were generally consistent for associations with the intervention and for associations with an interquartile range increase in time-weighted PM2.5. Specifically, higher PM2.5 exposure was positively associated with the expression (mRNA, protein, or both) of interleukin-1 (encoded by IL1), IL6, tumor necrosis factor (encoded by TNF), toll-like receptor 2 (encoded by TLR2), coagulation factor 3 (encoded by F3), and endothelin 1 (encoded by EDN1), and was negatively associated with miRNAs (miR-21-5p, miR-187-3p, miR-146a-5p, miR-1-3p, and miR-199a-5p) predicted to target mRNAs of IL1, TNF, TLR2, and EDN1.Our findings require confirmation but suggest that effects of PM2.5 on cardiovascular diseases may be related to acute effects on cytokine expression, which may be partly mediated through effects of PM2.5 on miRNAs that regulate cytokine expression. https://doi.org/10.1289/EHP1447.
Induction of fetal hemoglobin synthesis by CRISPR/Cas9-mediated editing of the human β-globin locus
Authors: Chiara Antoniani, Vasco Meneghini, Annalisa Lattanzi, Tristan Felix, Oriana Romano, Elisa Magrin, Leslie Weber, Giulia Pavani, Sara El Hoss, Ryo Kurita, Yukio Nakamura, Thomas J. Cradick, Ante S. Lundberg, Matthew Porteus, Mario Amendola, Wassim El Nemer, Marina Cavazzana, Fulvio Mavilio, Annarita Miccio
Journal: Blood (2018)
Pegylated interferon Alfa-2a and hydroxyurea in polycythemia vera and essential thrombocythemia: differential cellular and molecular responses
Authors: Tsewang Tashi, Sabina Swierczek, Soo Jin Kim, Mohamed E. Salama, Jihyun Song, Nahla Heikal, Katherine Y. King, Kim Hickman, Scott Litton, Josef T. Prchal
Journal: Leukemia (2018)
TCEB1-mutated renal cell carcinoma in relation to renal cell carcinoma with smooth muscle stroma in tuberous sclerosis complex.
Authors: Megan Parilla, Mir Alikhan, Jeremy Segal, Sabah Kadri, Carrie M Fitzpatrick, Tatjana Antic
Journal: Journal of Clinical Oncology (2018)

699 Background: TCEB1-mutated renal cell carcinomas (RCC) are a subtype of RCC which are distinct from both clear cell and clear cell papillary RCCs. These tumors are well-circumscribed, have predominantly tubular and papillary architecture, and have thick intersecting fibromuscular bands imparting a renal angiomyoadenomatous tumor (RAT)-like morphology. Tuberous sclerosis (TSC) patients have an increased risk of developing a number of tumors, including RCC. The histomorphology of RCCs in TSC have been well documented with 30-52% demonstrating “RCC with smooth muscle stroma” morphology, referred to as “TSC-associated papillary RCC (PRCC).” Interestingly the histologic features of TSC-associated PRCC are identical to that of the RAT-like TCEB1-mutated tumors. Methods: A total of 5 patients were found in our archives with histology that matched TSC-associated PRCC /RAT-like morphology. All 5 cases were retrieved and the formalin-fixed, paraffin-embedded blocks were reviewed with a representative block sent for molecular analysis on the UCMC-OncoPlus panel, a 1,213 gene targeted hybrid capture NGS panel. Variant and copy number calling was performed using custom-designed computational pipelines. A subset of cases had additional immunohistochemical stains preformed. Results: These 5 cases all revealed mutations in either TSC1, TSC2 or TCEB1 genes. Conclusions: The TCEB1 gene encodes the protein elonginC, a protein which complexes with VHL. A loss of elonginC results in a VHL complex which is unable to ubiquitinate HIF1-alpha. Non-degraded HIF1-alpha ultimately activates the transcription of a number of genes which lead to tumorgenesis. Interestingly, TSC1 and TSC2 protein products are also responsible for inactivating HIF1-alpha through RHEB/mTORC1/4E-BP1. This intimate molecular relationship with linked pathways of tumorgenesis, coupled identical histomorphology, suggests that TSC-associated PRCC and RAT-like RCC with TCEB1 mutation are the same tumor type.
Stop bashing psychiatry, royal college urges medical students
Authors: Caroline White
Journal: BMJ (2016)

Badmouthing of psychiatry by doctors and medical students stigmatises mental ill health and has an impact on medical career choices, the Royal College of Psychiatrists has warned.

The college is launching a campaign to bolster initiatives to expose the negative effects of “bashing” and badmouthing of psychiatry. The BASH campaign will be led through “psych socs,” which make up the largest single group of student societies in medical schools, said Simon Wessely, president of the Royal College of Psychiatrists.

“The current generation of students don’t put up with the things we used to,” Wessely told BMJ Careers. “Derogatory comments about race, sexuality, and gender are not common now, and when they do occur students …