tbuckley/cabot-search huggingface dataset:
Development of <scp><i>TP53</i></scp> mutations over the course of therapy for acute myeloid leukemia
Authors: Yasmin Alwash, Joseph D. Khoury, Mehrnoosh Tashakori, Rashmi Kanagal‐Shamanna, Naval Daver, Farhad Ravandi, Tapan M. Kadia, Marina Konopleva, Courtney D. Dinardo, Ghayas C. Issa, Sanam Loghavi, Koichi Takahashi, Elias Jabbour, Veronica Guerra, Steven Kornblau, Hagop Kantarjian, Nicholas J. Short
Journal: American Journal of Hematology (2021)

TP53 mutations in acute myeloid leukemia (AML) are associated with resistance to standard treatments and dismal outcomes. The incidence and prognostic impact of the emergence of newly detectable TP53 mutations over the course of AML therapy has not been well described. We retrospectively analyzed 200 patients with newly diagnosed TP53 wild type AML who relapsed after or were refractory to frontline therapy. Twenty-nine patients (15%) developed a newly detectable TP53 mutation in the context of relapsed/refractory disease. The median variant allelic frequency (VAF) was 15% (range, 1.1%-95.6%). TP53 mutations were more common after intensive therapy versus lower-intensity therapy (23% vs. 10%, respectively; p = 0.02) and in patients who had undergone hematopoietic stem cell transplant versus those who had not (36% vs. 12%, respectively; p = 0.005). Lower TP53 VAF was associated with an increased likelihood of complete remission (CR) or CR with incomplete hematologic recovery (CRi) compared to higher TP53 VAF (CR/CRi rate of 41% for VAF < 20% vs. 13% for VAF ≥ 20%, respectively). The median overall survival (OS) after acquisition of TP53 mutation was 4.6 months, with a 1-year OS rate of 19%. TP53 VAF at relapse was significantly associated with OS; the median OS of patients with TP53 VAF ≥ 20% was 3.5 months versus 6.1 months for those with TP53 VAF < 20% (p < 0.05). In summary, new TP53 mutations may be acquired throughout the course of AML therapy. Sequential monitoring for TP53 mutations is likely to be increasingly relevant in the era of emerging TP53-targeting therapies for AML.
Recombinant<i>Mycobacterium smegmatis</i>delivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model
Authors: Hyein Jeong, So-Young Lee, Hyejun Seo, Bum-Joon Kim
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Macrophage migration inhibitory factor (MIF) is a pleotropic inflammatory cytokine that is overexpressed in a number of cancer types including most types of human cancer. Inhibition of MIF signaling can restore anticancer immune responses in tumor microenvironments. In this study, we aimed to develop a therapeutic vaccine capable of inhibiting tumor development by inducing anti-MIF immune responses. Methods We introduced a recombinant Mycobacterium smegmatis (rSmeg-hMIF-hIL-7) vaccine that could deliver a fusion protein of human macrophage migration inhibitory factor (MIF) and interleukin 7, which could act as a target antigen and as an adjuvant of cancer vaccine, respectively. We checked the anticancer potential of the vaccine in a tumor-bearing mouse model. Results We found that rSmeg-hMIF-hIL-7 showed enhanced oncolytic activity compared with PBS, BCG or Smeg in MC38-bearing mice, and there was an increase in the humoral and cell-mediated immune responses against MIF. rSmeg-hMIF-hIL-7 can also induce a neutralizing effect regarding MIF tautomerase activity in the serum of vaccinated mice. We also found downregulation of MIF, CD74, and CD44, which are related to the MIF signaling pathway and PI3K/Akt and MMP2/9 signaling, which are regulated by MIF in the tumor tissue of rSmeg-hMIF-hIL-7-vaccinated mice, suggesting a significant role of the anti-MIF immune response to rSmeg-hMIF-hIL-7 in its anticancer effect. In addition, rSmeg-hMIF-hIL-7 treatment led to enhanced activation of CD4 + and CD8 + T cells in the tumor regions of vaccinated mice, also contributing to the anticancer effect. This trend was also found in LLC-bearing and PanO2-bearing mouse models. In addition, rSmeg-hMIF-hIL-7 treatment exerted an enhanced anticancer effect with one of the immune checkpoint inhibitors, the anti-PD-L1 antibody, in a tumor-bearing mouse model. Conclusions In conclusion, our data showed that rSmeg-hMIF-hIL-7 exerts a strong antitumor immune response in mice, possibly by inhibiting the MIF-dependent promotion of tumorigenesis by the anti-MIF immune response and via enhanced cytotoxic T cell recruitment into tumor microenvironments. We also found that it also exerted an enhanced anticancer effect with immune checkpoint inhibitors. These results suggest that rSmeg-hMIF-hIL-7 is a potential adjuvant for cancer immunotherapy. This is the first report to prove anticancer potential of immunotherapeutic vaccine targeting immune response against MIF.
Patch testing with ammonium persulfate: The North American Contact Dermatitis Group Experience, 2015-2018
Authors: Erin M. Warshaw, Jenna L. Ruggiero, Joel G. DeKoven, Melanie D. Pratt, Jonathan I. Silverberg, Howard I. Maibach, Kathryn A. Zug, Amber R. Atwater, James S. Taylor, Margo J. Reeder, Denis Sasseville, Joseph F. Fowler, Anthony F. Fransway, Donald V. Belsito, Vincent A. DeLeo, Marie-Claude Houle, Cory A. Dunnick
Journal: Journal of the American Academy of Dermatology (2021)
The role of cigarette smoking-derived pollutants in the risk of mortality in idiopathic pulmonary fibrosis
Authors: Hee-Young Yoon, Sun-Young Kim, Ok-Jin Kim, Jin Woo Song
Journal: European Respiratory Journal (2021)

We thank T. Yasuma and co-workers for their valuable comments on our paper describing the association between individual-level long-term concentrations of air pollutants at the residential addresses of patients with idiopathic pulmonary fibrosis (IPF) and mortality among them [1]. We agree that the release of nitrogen dioxide (NO2) or particulate matter in cigarette smoke is one of the considerations in interpreting our results. Thus, we stratified all patients into ever- and non-smokers according to their smoking status and analysed the effect of air pollutants on mortality risk in these patients using our health analysis models that included different sets of confounders (figure 1). The effect of air pollutants on mortality risk in patients with IPF is independent of their smoking status <https://bit.ly/3rLUAva>
Clare Gerada: Happy birthday, NHS
Authors: Clare Gerada
Journal: BMJ (2021)

On 5 July 2021 the NHS had its 73rd birthday. To mark this occasion, I—along with others drawn from the health, social care, and voluntary sectors, as well as patients, carers, and scientists—attended a service of commemoration and thanksgiving at St Paul’s Cathedral. On the day, the NHS was also honoured with a George Cross from the Queen in recognition of how the organisation, and of course all of those who have worked in it, have served this country since 1948.

The NHS is a remarkable achievement, which despite its problems continues to do (almost) what it set out to do …
Low Expression of GFI-1 Gene Is Associated with Chemotherapy-Resistant in Acute Myeloid Leukemia through Influencing the Level of HO-1
Authors: Bingqing Cheng, Jishi Wang, Sishi Tang, Kunling Yu, Xinyao Li, Danna Wei, Yongling Guo, Qin Fang
Journal: Blood (2017)
Abstract PO-070: Bimodality of gene expression in cancer patient tumors as interpretable biomarkers for drug sensitivity
Authors: Wail Ba-alawi, Sisira Kadambat Nair, Bo Li, Anthony Mammoliti, Petr Smirnov, Arvind Singh Mer, Linda Penn, Benjamin Haibe-Kains
Journal: Clinical Cancer Research (2021)

Abstract Identifying biomarkers predictive of cancer cells’ response to drug treatment constitutes one of the main challenges in precision oncology. Recent large-scale cancer pharmacogenomic studies have boosted the research for finding predictive biomarkers by profiling thousands of human cancer cell lines at the molecular level and screening them with hundreds of approved drugs and experimental chemical compounds. Many studies have leveraged these data to build predictive models of response using various statistical and machine learning methods. However, a common challenge in these methods is the lack of interpretability as to how they make the predictions and which features were the most associated with response, hindering the clinical translation of these models. To alleviate this issue, we develop a new machine learning pipeline based on the recent LOBICO approach that explores the space of bimodally expressed genes in multiple large in vitro pharmacogenomic studies and builds multivariate, nonlinear, yet interpretable logic-based models predictive of drug response. Using our method, we used a compendium of three of the largest pharmacogenomic data sets to build robust and interpretable models for 101 drugs that span 17 drug classes with high validation rate in independent datasets. Citation Format: Wail Ba-alawi, Sisira Kadambat Nair, Bo Li, Anthony Mammoliti, Petr Smirnov, Arvind Singh Mer, Linda Penn, Benjamin Haibe-Kains. Bimodality of gene expression in cancer patient tumors as interpretable biomarkers for drug sensitivity [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-070.
P-273 Mucinous colorectal cancer in Tunisian patients: A controversial clinicopathological type
Authors: H. Guettiti Tounsi, D. Wider, S. Ben Nasr, F. Letaief-ksontini, A. Jaballah, I. Ben Ayed, A. Mezlini, A. Haddauoi, S. Boubaker
Journal: Annals of Oncology (2021)
A Prospective Cohort Study of Stability in Preferred Place of Death Among Patients With Stage IV Cancer in Singapore
Authors: Chetna Malhotra, Ling En Koh, Irene Teo, Semra Ozdemir, Isha Chaudhry, Eric Finkelstein
Journal: Journal of the National Comprehensive Cancer Network (2021)

Advance care planning (ACP) involves documentation of patients' preferred place of death (PoD). This assumes that patients' preferred PoD will not change over time; yet, evidence for this is inconclusive. We aimed to assess the extent and correlates of change in patients' preferred PoD over time.Using data from a cohort study of patients with advanced cancer in Singapore, we analyzed preferred PoD (home vs institution including hospital, hospice, and nursing home vs unclear) among 466 patients every 6 months for a period of 2 years. At each time point, we assessed the proportion of patients who changed their preferred PoD from the previous time point. Using a multinomial logistic regression model, we assessed patient factors (demographics, understanding of disease stage, ACP, recent hospitalization, quality of life, symptom burden, psychologic distress, financial difficulty, prognosis) associated with change in their preferred PoD.More than 25% of patients changed their preferred PoD every 6 months, with no clear trend in change toward home or institution. Patients psychologically distressed at the time of the survey had increased likelihood of changing their preferred PoD to home (relative risk ratio [RRR], 1.02; 95% CI, 1.00-1.05) and to an institution (RRR, 1.06; 95% CI, 1.02-1.10) relative to no change in preference. Patients hospitalized in the past 6 months were more likely to change their preferred PoD to home (RRR, 1.56; 95% CI, 1.07-2.29) and less likely to change to an institution (RRR, 0.50; 95% CI, 0.28-0.88) relative to no change in preference.The present study provides evidence of instability in the preferred PoD of patients with advanced cancer. ACP documents need to be updated regularly to ensure they accurately reflect patients' current preference.
Air pollution and poverty: a deadly combination in idiopathic pulmonary fibrosis?
Authors: Lucile Sesé, Isabella Annesi-Maesano, Catherine Cavalin, Hilario Nunes
Journal: European Respiratory Journal (2021)

<b>Socioeconomic level influences co-exposure throughout life, and by the time IPF appears, social conditions and environmental exposures have already been at work for many years</b>https://bit.ly/3iAmS8R
E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group
Authors: Roisin M. Connolly, Fengmin Zhao, Kathy D. Miller, Min-Jung Lee, Richard L. Piekarz, Karen L. Smith, Ursa A. Brown-Glaberman, Jennifer S. Winn, Bryan A. Faller, Adedayo A. Onitilo, Mark E. Burkard, George T. Budd, Ellis G. Levine, Melanie E. Royce, Peter A. Kaufman, Alexandra Thomas, Jane B. Trepel, Antonio C. Wolff, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2021)

Endocrine therapy resistance in advanced breast cancer remains a significant clinical problem that may be overcome with the use of histone deacetylase inhibitors such as entinostat. The ENCORE301 phase II study reported improvement in progression-free survival (PFS) and overall survival (OS) with the addition of entinostat to the steroidal aromatase inhibitor (AI) exemestane in advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial
Authors: Firdausi Qadri, Farhana Khanam, Xinxue Liu, Katherine Theiss-Nyland, Prasanta Kumar Biswas, Amirul Islam Bhuiyan, Faisal Ahmmed, Rachel Colin-Jones, Nicola Smith, Susan Tonks, Merryn Voysey, Yama F Mujadidi, Olga Mazur, Nazmul Hasan Rajib, Md Ismail Hossen, Shams Uddin Ahmed, Arifuzzaman Khan, Nazia Rahman, Golap Babu, Melanie Greenland, Sarah Kelly, Mahzabeen Ireen, Kamrul Islam, Peter O'Reilly, Karin Sofia Scherrer, Virginia E Pitzer, Kathleen M Neuzil, K Zaman, Andrew J Pollard, John D Clemens
Journal: The Lancet (2021)

BackgroundTyphoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings.MethodsWe did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110.Findings41 344 children were vaccinated in April–May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI −12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed.InterpretationVi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses.FundingThe study was funded by the Bill & Melinda Gates Foundation.
Hip Osteonecrosis in Pediatric Leukemia/Lymphoma Patients Treated with Glucocorticoids: Retrospective Analysis in a Single Institute
Authors: Yuki Arakawa, Makiko Mori, Masahiro Sugawa, Jun Noguchi, Ryota Kawakami, Toshikazu Itabashi, Masato Yanagi, Kiyotaka Isobe, Motohiro Kato, Eiji Oguma, Katsuaki Taira, Katsuyoshi Koh
Journal: Blood (2017)
P-155 A phase I study of FLOT as first-line therapy for Japanese patients with advanced gastric cancer including patients with or without severe peritoneal metastasis
Authors: K. Shiraishi, T. Masuishi, T. Ogata, K. Sugiyama, N. Nishikawa, K. Shibata, C. Kudo, N. Takayanagi, Y. Narita, H. Uda, S. Kadowaki, M. Ando, C. Kitagawa, M. Kataoka, K. Muro
Journal: Annals of Oncology (2021)
Upper respiratory tract SARS-CoV-2 RNA loads in symptomatic and asymptomatic children and adults
Authors: Rosa Costa, Felipe Bueno, Eliseo Albert, Ignacio Torres, Silvia Carbonell-Sahuquillo, Ana Barrés-Fernández, David Sánchez, Carmelo Padrón, Javier Colomina, María Isabel Lázaro Carreño, José Rafael Bretón-Martínez, Cecilia Martínez-Costa, David Navarro
Journal: Clinical Microbiology and Infection (2021)
Toripalimab with chemotherapy as first-line treatment for advanced biliary tract tumors: Update analytic results of an open-label phase II clinical study (JS001-ZS-BC001).
Authors: Wei Li, Yiyi Yu, Xiaojing Xu, Xi Guo, Yueqi Wang, Qian Li, Yan Wang, Yuehong Cui, Houbao Liu, Qing Hao, Yueting Qu, Lujia Huang, Tianshu Liu
Journal: Journal of Clinical Oncology (2021)

e16170 Background: A phase II clinical study was conducted to evaluate the safety and efficacy of toripalimab, a novel PD-1 inhibitor, combined with chemotherapy in patients with advanced biliary tract cancers (aBTCs) (NCT03796429). The preliminary results indicated the combination treatment is well tolerable and effective. Methods: Treatment naive patients with aBTCs received toripalimab (240mg intravenously every three weeks) combined with chemotherapy (gemcitabine 1000 mg/m2 d1, d8 + S-1 40-60mg bid D1-14, Q21d). The treatment continued until the disease progress or having intolerable effects. The primary endpoints of the study were progression free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), safety and treatment biomarkers. Results: At data cutoff (January 24, 2021), fifty aBTC patients were enrolled at Shanghai Zhongshan Hospital. Among these patients, 56% are males. The median age of the study participants was 62 years of age. The median follow-up time was 10 months (ranged from 4 to 19 months). The primary tumor type was intrahepatic cholangiocarcinoma (ICC) accounting for 48% of total cases, followed by gallbladder cancer (GBC) (40.0%), and extrahepatic cholangiocarcinoma (ECC) (12.0%). At the time of data collection, 48 eligible patients were included for data analysis. The median PFS was 7.0 months（95%CI, 5.5-9.1 months）and median OS was 16.0 months (95%CI, 12.1 to unreachable). The ORR was 27.1 % and disease control rate was 87.5% including 13 partial response (PR) and 29 stable disease (SD) cases. The most treatment related AEs (TRAE) were leukopenia (92.0%), anemia (86.0%) and rash (52.0%). Grade III/IV non-hematological TRAEs were seen in 12 patients (24.0%), including rash (n = 3), infection (n = 6), immune-related colitis (n = 1), immune-related pneumonitis (n = 1) and mucositis (n = 1). Grade III/IV hematological TRAEs were seen in 62% patients. 6 patients discontinued the study drug due to TRAE. Serious adverse events (SAE) were seen in 8 patients and 2 patients died of biliary obstruction complicated with infection. Forty-nine patients were included in biomarker analysis. The most mutated genes were TP53 (51%), KRAS (20%), CDKN2A (18%) and SMAD4 (16%). Patients with activated PI3K signaling pathway had significantly shorter PFS (P = 0.026). Tumor mutational burden (TMB) could not serve as a predictor for the efficacy of immunotherapy combined with chemotherapy. Conclusions: The clinical study of toripalimab combined with chemotherapy continued to show tolerance and efficacy in patients with aBTCs. Gene mutation profiling by NGS suggested mutated PI3K pathway might assocate with shorter PFS. Clinical trial information: NCT03796429.
Textbook of Abnormal Psychology
Journal: JAMA (1934)

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サイクリン依存性キナーゼ-9は心筋細胞における増生反応に必要とされるp300/GATA-4複合体の新規構成物質である
Authors: Sunagawa Yoichi, Morimoto Tatsuya, Kawamura Teruhisa, Takaya Tomohide, Wada Hiromichi, Shimatsu Akira, Fujita Masatoshi, Kita Toru, Hasegawa Kouji
Journal: Circulation (2007)