tbuckley/cabot-search huggingface dataset:
Time trends of drug specific adverse events among patients on androgen receptor antagonists: Implications for remote monitoring.
Authors: Lauren Fleshner, Sophie O'Halloran, Katherine Lajkosz, Jacob Wise, Miran Kenk, Susan Nguyen, Neil Eric Fleshner
Journal: Journal of Clinical Oncology (2021)

40 Background: In light of the global pandemic, reducing patient exposure via remote monitoring is desirable. Currently, advanced prostate cancer patients prescribed Abiraterone or Enzalutamide are scheduled for an in-person appointment monthly, to screen for adverse events (AEs). We set out to determine time trends of drug specific AEs in order to determine whether reducing in-person visits for patients taking either Abiraterone or Enzalutamide is feasible. Methods: This chart review was conducted on 667 unique advanced prostate cancer patients, being either metastatic hormone sensitive or castration resistant and utilizing Abiraterone or Enzalutamide. Patients who switched courses of treatment and received both drugs were included twice in the data, resulting in 828 “subjects” overall. Data were collected via accessing electronic patient records, to determine the first sign of an AE related to either Abiraterone or Enzalutamide. These AEs include; hypertension, elevated liver enzymes (bilirubin, AST, ALT) or hypokalemia. Survival analysis was used to determine the time to adverse event. All grade AEs are included in this analysis. Results: In this study, 425 and 403 patients received Enzalutamide and Abiraterone, respectively. In total, 36.3% of those who took Enzalutamide experienced an AE, compared to 43.4% of patients on Abiraterone. For patients utilizing Abiraterone, cumulative incidence of AEs at 3,6,9 and 12 months were: 65.0%, 81.2%, 90.9% and 93.9%, respectively. Among Enzalutamide users, cumulative incidence of AEs at 3,6,9 and 12 months were: 46.8%, 67.5%, 81.2% and 88.3%, respectively. The primary first AEs associated with Enzalutamide consumption were hypertension and liver dysfunction (77.48% and 22.52%). In the Abiraterone group, the first associated AEs were liver dysfunction (48.78%), hypertension (46.34%), and hypokalemia (4.88%). Conclusions: These data suggest that the likelihood of attaining AEs associated with Abiraterone or Enzalutamide utilization decreases over time and tend to occur within the first 6 months of therapy. Furthermore, the vast majority of these AEs can be remotely monitored via outside laboratories and remote blood pressure monitoring. In light of the COVID-19 crisis, remote monitoring after 6 months of taking Abiraterone or Enzalutamide would appear appropriate. Efforts to further safely reduce in person visits should be explored.
Racial/Ethnic Disparities in the Prevalence and Trends of Autism Spectrum Disorder in US Children and Adolescents
Authors: Jing Yuan, Minghui Li, Z. Kevin Lu
Journal: JAMA Network Open (2021)

This cross-sectional study uses data from the National Health Interview Survey to assess racial/ethnic disparities in the prevalence and trends of autism spectrum disorder among US children and adolescents.
Implementation of a Recuperation Unit and Hospitalization Rates Among People Experiencing Homelessness With COVID-19
Authors: Joshua A. Barocas, Mam Jarra Gai, Laura F. White, Deanna Faretra, Kerry Sachs, Miriam Komaromy
Journal: JAMA Network Open (2021)

This cohort study examines the association of the opening of a COVID-19 recuperation unit adjacent to a large safety-net hospital with COVID-19 hospitalization rates among people experiencing homelessness.
Association of cabozantinib residual concentration (Ctrough) and blood clearance (Cl/F) with toxicity (tox) and progressive disease (PD) in metastatic renal cell carcinoma (mRCC) patients (pts): Results from a monocentric pharmacokinetics (PK) study.
Authors: Luigi Cerbone, David Combarel, Stéphanie Foulon, Arthur Geraud, Carolina Alves, Emeline Colomba, Lucia Carril, Lisa Derosa, Ronan Flippot, Olivier Mir, Bernard Escudier, Angelo Paci, Laurence Albiges
Journal: Journal of Clinical Oncology (2021)

292 Background: Cabozantinib is a TKI with a substantial efficacy in mRCC. It is associated with a relevant tox leading frequent dose modifications (DM) or drug discontinuations (DD). While an exposure/safety relation has been demonstrated for this drug, an exposure/efficacy relation is still unknown. Cl/F is a measure of elimination of a drug from blood or plasma and lower Cl/F of cabozantinib has been previously associated with increased DM rate in mRCC. Methods: We performed a monocentric PK (INDS MR 5612140520) study in patients with mRCC. Blood draw for assessment of cabozantinib PK was performed at least 8 hours from the last drug dose. Ctrough was estimated with the following equation: Ctrough=Cmeas*0,5DI-24/t1/2. Ctrough and Cl/F were compared in patients with or without a relevant tox and in PD pts vs SD/PR pts. Relevant tox was defined either as G3-4 tox or G2 tox leading to DM or DD. Differences in Ctrough and CL were assessed between the groups with Mann Withney U test. Results: From 01.10.19 to 31.08.20 66 pts were included in this analysis. Twenty one relevant tox and 29 PD were observed. Ctrough was higher in pts experiencing relevant tox than in those who did not: 624,6 ng/ml (IQR 494-1030,2 ng/ml) vs 505,2 ng/ml (IQR 329,2-910,2), p0.012. Conversely Cl/F was lower in relevant tox vs not tox1,85 l/h (IQR 1,4-2,2 l/h) vs 2.27 l/h (IQR 1,7-3,2), p 0.024. In PD pts, Ctrough was lower than in SD/PR pts: 419ng/ml (IQR 317,2 -549,1 ng/ml) vs 554 ng/ml (IQR 416,9-795,6), p 0.0105, while Cl/F was higher in PD patients: 2,6 l/h (IQR 2,14-3,44 l/h) vs SD/PR patients 1.9 l/h (1,930 l/h;IQR 1,35-2,53 l/h); p= 0.011. Time from day cycle 1 to PK blood draw was significatively longer in non-tox pts and numerically longer in PD pts, which have the lowest Ctrough and the highest Cl/F. Conclusions: Cabozantinib toxicity is associated to a higher Ctrough and a lower Cl/F. Cabozantinib PD is associated to a lower Ctrough and a higher Cl/F. Cl/F should be assessed alongside with Ctrough in Cabozantinib PK blood test; Ctrough may decrease and conversely Cl/F may increase with time on treatment. [Table: see text]
5Fr診断カテーテルは抵抗なく通過したが,radial ulner loopにて6FrGCが通過不能であった一例
Authors: 中岡幹彦, 岡田隆, 木戸淳道, 中川裕介, 中山雅由花, 内藤大督, 浦壁洋太
Journal: Circulation (2007)
Abstract PO-090: Application of deep learning methods in predicting survival and identifying high-risk populations from large optum real world breast cancer data
Authors: Han Wang, Xiaodong Luo, Meiqi Wu, LiMing Shen
Journal: Clinical Cancer Research (2021)

Abstract Real-World Evidence (RWE) contains abundant observational data collected during routine clinical practice. With such large-scale and high-dimensional data, we can leverage the power of neural networks to increase the capacity of classical survival models in predicting the risk of breast cancer patients, and identifying potential prognosis-associated factors retrospectively. The target cohorts were extracted based on diagnosis code, biomarker, and mastectomy procedure code, we further identified metastatic breast cancer cases according to secondary diagnosis code and physician notes. Our features consist of demographic and vital data, cancer-related measurement, and medication history, which was divided into several lines of therapy. Considering the dynamic nature of cancer therapy, time-dependent survival models are more suitable to model the hazard given the current features. Therefore, we extended the proportional-hazard-based DeepSurv and logistic-hazard-based Nnet-survival to accommodate time-dependent features, and further incorporated recurrent neural networks to make better use of sequential medication information. We trained the model on the training set (70%), tuned the hyperparameters via Bayesian Optimization on the validation set (10%), and evaluated the model with c-index and integrated brier score on the test set (20%). Compared with the classical linear cox model and pooled logistic regression, the proposed model outperformed these baselines by a significant margin, indicating the promise of using deep learning and the time-dependent prognosis model for survival prediction and risk stratification in cancer patients. In addition, the output from the neural network was interpreted with SHAP values and Integrated Gradient (IG), which shed some light on the effect of adjuvant hormone therapy, especially AI and SERM, on recurrence and overall survival. Further, our model can be improved with more collected data and a better approach to handling error and missingness in the data. Citation Format: Han Wang, Xiaodong Luo, Meiqi Wu, LiMing Shen. Application of deep learning methods in predicting survival and identifying high-risk populations from large optum real world breast cancer data [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-090.
Pipeline of anti‐<i>Mycobacterium abscessus</i> small molecules: Repurposable drugs and promising novel chemical entities
Authors: Anna Egorova, Mary Jackson, Victor Gavrilyuk, Vadim Makarov
Journal: Medicinal Research Reviews (2021)

Abstract The Mycobacterium abscessus complex is a group of emerging pathogens that are difficult to treat. There are no effective drugs for successful M. abscessus pulmonary infection therapy, and existing drug regimens recommended by the British or the American Thoracic Societies are associated with poor clinical outcomes. Therefore, novel antibacterial drugs are urgently needed to contain this global threat. The current anti‐ M. abscessus small‐molecule drug development process can be enhanced by two parallel strategies—discovery of compounds from new chemical classes and commercial drug repurposing. This review focuses on recent advances in the finding of novel small‐molecule agents, and more particularly focuses on the activity, mode of action and structure–activity relationship of promising inhibitors from five different chemical classes—benzimidazoles, indole‐2‐carboxamides, benzothiazoles, 4‐piperidinoles, and oxazolidionones. We further discuss some other interesting small molecules, such as thiacetazone derivatives and benzoboroxoles, that are in the early stages of drug development, and summarize current knowledge about the efficacy of repurposable drugs, such as rifabutin, tedizolid, bedaquiline, and others. We finally review targets of therapeutic interest in M. abscessu s that may be worthy of future drug and adjunct therapeutic development.
Roxadustat for Renal Anemia in ESRD from PKD Patients: Is It Safe Enough?
Authors: Fei Liu, Jingjing Wang, Qing Ye, Haidong Fu, Jianhua Mao
Journal: Journal of the American Society of Nephrology (2021)

Akizawa et al. [1][1] report roxadustat's noninferiority to darbepoetin alfa in treating hemodialysis-dependent CKD anemia in their phase 3 study. However, in this trial, we could not find the exact data of the primary disease of CKD or the proportion that polycystic kidney disease (PKD)[1][1
神経幹細胞は放射状線維足場を介して軸索誘導を誘導する【JST・京大機械翻訳】
Authors: Kaur Navjot, Han Wenqi, Li Zhuo, Madrigal M. Pilar, Shim Sungbo, Pochareddy Sirisha, O Gulden Forrest, Li Mingfeng, Xu Xuming, Xing Xiaojun, Takeo Yutaka, Li Zhen, Lu Kangrong, Imamura Kawasawa Yuka, Ballester-Lurbe Begona, Moreno-Bravo Juan Antonio, Chedotal Alain, Terrado Jose, Perez-Roger Ignacio, J Koleske Anthony, Sestan Nenad
Journal: Neuron (2020)
Listening to Latinx Patient Perspectives on COVID-19 to Inform Future Prevention Efforts
Authors: India J. Ornelas, Gbenga Ogedegbe
Journal: JAMA Network Open (2021)

Lilia Cervantes, MD; Marlene Martin, MD; Maria G. Frank, MD; Julia F. Farfan, BS; Mark Kearns, MD; Luis A. Rubio, MD; Allison Tong, PhD; Andrea Matus Gonzalez, BNutrSc; Claudia Camacho, BS; Adriana Collings, MPH; William Mundo, MPH; Neil R. Powe, MD; Alicia Fernandez, MD
Benzamide derivative radiotracers targeting melanin for melanoma imaging and therapy: Preclinical/clinical development and combination with other treatments
Authors: Jacques Rouanet, Mercedes Quintana, Philippe Auzeloux, Florent Cachin, Françoise Degoul
Journal: Pharmacology & Therapeutics (2021)

Cutaneous melanoma arises from proliferating melanocytes, cells specialized in the production of melanin. This property means melanin can be considered as a target for monitoring melanoma patients using nuclear imaging or targeted radionuclide therapy (TRT). Since the 1970s, many researchers have shown that specific molecules can interfere with melanin. This paper reviews some such molecules: benzamide structures improved to increase their pharmacokinetics for imaging or TRT. We first describe the characteristics and biosynthesis of melanin, and the main features of melanin tracers. The second part summarizes the preclinical and corresponding clinical studies on imaging. The last section presents TRT results from ongoing protocols and discusses combinations with other therapies as an opportunity for melanoma non-responders or patients resistant to treatments.
Fast track research approval “here to stay,” says regulator
Authors: Rebecca Coombes
Journal: BMJ (2021)

The regulator of UK research says it wants to sustain “in peacetime” the fast track methods it developed for reviewing research during the covid-19 pandemic.

At the height of the pandemic, the Health Research Authority (HRA) cut around 90% off its research approval timeline. Speaking this week, Juliet Tizzard, director of policy and partnership at the regulator, told how around 700 covid-19 studies were reviewed in total over the past year, half of these within 36 hours and some within 24 hours.

“We had to prioritise the urgent stuff. We provided a fast track review service, prioritising the urgent public health studies identified by the chief medical officer and delivered by the National Institute for Health Research …
Holding Out Hope After Traumatic Brain Injury
Authors: Jennifer A. Kim, Kevin N. Sheth
Journal: JAMA Neurology (2021)

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Carbohydrate epitopes currently recognized as targets for IgE antibodies
Authors: Thomas A. Platts‐Mills, Christiane Hilger, Uta Jappe, Marianne van Hage, Gabriele Gadermaier, Edzard Spillner, Jonas Lidholm, Behnam Keshavarz, Rob C. Aalberse, Ronald van Ree, Richard E. Goodman, Anna Pomés
Journal: Allergy (2021)

Abstract Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub‐Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE‐binding glycans recognized up to 2008 were considered to be “classical” cross‐reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE‐binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose‐alpha‐1,3‐galactose (alpha‐gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha‐gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross‐reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub‐Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website ( www.allergen.org ). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.
Treatment of aggressive prostate cancers in real life: Initiation, schedule, and management of triptorelin treatment (TALISMAN)—Design of the study.
Authors: Thierry Lebret, Jerome Rigaud, Gilles Crehange, Nathalie Pello Leprince Ringuet, Anne-Sophie Grandoulier, Antoine Thiery-Vuillemin
Journal: Journal of Clinical Oncology (2021)

TPS173 Background: Prostate cancer (PCa) treatment management mostly depends on tumor aggressiveness and patient frailty. Guidelines recommend an intensification of treatment in high risk PCa, with a longer duration of androgen deprivation therapy (ADT), and, for more advanced cases, an administration for life, on top of which additional treatments may be proposed. This implies a holistic management of the patient, including management of comorbidities and ADT side effects. Triptorelin is a widely used gonadotropin-releasing hormone agonist (GnRHa). Generating data on the use of triptorelin in real life will help physicians to analyze the parameters influencing the choice of the planned duration of treatment. Methods: This prospective, multicenter, non-interventional study is conducted in France. Patients are recruited by urologists, radiation oncologists and medical oncologists. Main inclusion criteria are a histologically confirmed PCa, eligible for triptorelin therapy in its label, with a planned total duration of triptorelin treatment of at least 12 months. Decision of triptorelin treatment is made before the inclusion in the study, in the routine practice. 3 visits are planned: V1 (baseline), V2 (at 6 months), V3 (at 12 months). Primary objective of the study is to describe the proportion of patients treated continuously with triptorelin during 12 months following treatment initiation. 786 patients are planned to be enrolled, this will allow to estimate the proportion of patients treated continuously with triptorelin during 12 months following treatment initiation for an expected proportion of 80% with a precision of 3 % taking into account a drop out rate of 15%. Main secondary objectives are to describe the planned total duration of triptorelin treatment and main reason of choice, to identify parameters (tumor aggressiveness criteria, patient frailty...) associated with this planned duration, to describe the formulation and route of administration of triptorelin and reasons of choice, to identify parameters associated with this choice, to describe the change from baseline in quality of life evaluated through QLQ-PR25 questionnaire, and to describe the safety of triptorelin in the real world setting. An interim analysis on baseline data will be performed once 50% of patients are enrolled. It will focus on planned total duration of triptorelin at initiation, main reasons of choice according to circumstances of prescription, formulation and route of administration, and their reasons of choice. Clinical trial information: NCT04593420.
HIF1α epigenetically repressed macrophages via CRISPR/Cas9-EZH2 system for enhanced cancer immunotherapy
Authors: Yan Dong, Siyan Zhang, Xiaotong Gao, Dandan Yin, Tingting Wang, Zhelong Li, Zhuo Wan, Mengying Wei, Ying Luo, Guodong Yang, Li Liu
Journal: Bioactive Materials (2021)

Immune suppressive microenvironment in tumor emerges as the main obstacle for cancer immunotherapy. In this study, we identified that HIF1α was activated in the tumor associated macrophages and acted as an important factor for the immune suppressive microenvironment. Epigenetically silencing of Hif1α via histone H3 methylation in the promoter region was achieved by CRISPR/dCas9-EZH2 system, in which histone H3 methylase EZH2 was recruited to the promoter region specifically. The Hif1α silenced macrophage, namely HERM (Hif1α Epigenetically Repressed Macrophage) manifested as inheritable tumor suppressing phenotype. In the subcutaneous B16-F10 melanoma syngeneic model, intratumoral injection of HERMs reprogrammed the immune suppressive microenvironment to the active one, reducing tumor burden and prolonging overall survival. Additionally, HERMs therapy remarkably inhibited tumor angiogenesis. Together, our study has not only identified a promising cellular and molecular target for reverting immune suppressive microenvironment, but also provided a potent strategy for reprogramming tumor microenvironment via epigenetically reprogrammed macrophages.
Christine Beatrice Marenah
Authors: Kirsten Marenah, Dallas Swallow
Journal: BMJ (2021)

Christine Beatrice Marenah came from St Ives, Cornwall, where her father was a greengrocer. She attended Penzance Girls’ Grammar School before leaving Cornwall for London, where she studied at Bedford College, University of London. She graduated in 1970 with a BSc (Hons) First class in biochemistry. She then studied at the Galton Laboratory under Professor Harry Harris, achieving her PhD in human genetics in 1973, before going on to Clare College, Cambridge, and obtaining her BA (Cantab) medical sciences tripos in 1975.

Between 1980 and 1985 Christine was a lecturer in chemical pathology and metabolic disorders at St Thomas’ Hospital Medical School. In 1985, she moved to Nottingham, where she became consultant chemical pathologist …
Functionalizing DNA nanostructures with natural cationic amino acids
Authors: Dong Wang, Chunfa Chen, Qian Liu, Qianwen Zhao, Di Wu, Yue Yuan, Chaowang Huang, Xiaorong Sun, Chunji Huang, David Tai Leong, Guansong Wang, Hang Qian
Journal: Bioactive Materials (2021)

Complexing self-assembled DNA nanostructures with various functional guest species is the key to unlocking new and exciting biomedical applications. Cationic guest species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties. Herein, we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures. Natural l-arginine and l-lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner. The self-assembly processes are demonstrated to be pH- and concentration-dependent and are achieved at constant temperatures. Moreover, the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37 °C. Substituting l-arginine with its D form enhances its serum stability. Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts. The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane. Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized guest molecules for a designed application. The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures.