tbuckley/cabot-search huggingface dataset:
Point mutation in<i>CD19</i>facilitates immune escape of B cell lymphoma from CAR-T cell therapy
Authors: Zhen Zhang, Xinfeng Chen, Yonggui Tian, Feng Li, Xuan Zhao, Jinyan Liu, Chang Yao, Yi Zhang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Tumor relapse due to mutation in CD19 can hinder the efficacy of chimeric antigen receptor (CAR)-T cell therapy. Herein, we focused on lymphoma patients whose B cells exhibited a point mutation in CD19 of B cells after CAR-T cell infusion. Methods The CAR-T and CD19 + B cells from peripheral blood or bone marrow were assessed using flow cytometry. Genome sequencing was conducted to identify the molecular characteristics of CAR-T and CD19 + B cells from pre-relapse and postrelapse samples. CD19 in CARs comprising single chain fragments variable (scFV) antibody with FMC63 or 21D4 was constructed. The cytotoxic efficacy of CAR-T cells was also evaluated via in vitro and in vivo experiments. Results A patient with high-grade B cell lymphoma exhibited complete response, but the lymphoma relapsed in her left breast at 6 months after CD19 CAR (FMC63)-T cell infusion. A mutation was found in exon 3 of CD19 (p.163. R-L) in malignant B cells of the patient. In two lymphoma patients who exhibited resistance to CAR-T cell therapy, a mutation was detected in exon 3 of CD19 (p.174. L-V). Functional analysis revealed that FMC63 CAR-T cells exhibited antitumor ability against wild-type CD19 + cells but were unable to eradicate these two types of mutated CD19 + cells. Interestingly, 21D4 CAR-T cells were potentially capable of eradicating these mutated CD19 + cells and exhibiting high antitumor capacity against CD19 + cells with loss of exon 1, 2, or 3. Conclusions These findings suggest that point mutation can facilitate immune escape from CAR-T cell therapy and that alternative CAR-T cells can effectively eradicate the mutated B cells, providing an individualized therapeutic approach for lymphoma patients showing relapse.
Nano-needle strontium-substituted apatite coating enhances osteoporotic osseointegration through promoting osteogenesis and inhibiting osteoclastogenesis
Authors: Zhen Geng, Luli Ji, Zhaoyang Li, Jing Wang, Hongyan He, Zhenduo Cui, Xianjin Yang, Changsheng Liu
Journal: Bioactive Materials (2020)

Implant loosening remains a major clinical challenge for osteoporotic patients. This is because osteoclastic bone resorption rate is higher than osteoblastic bone formation rate in the case of osteoporosis, which results in poor bone repair. Strontium (Sr) has been widely accepted as an anti-osteoporosis element. In this study, we fabricated a series of apatite and Sr-substituted apatite coatings via electrochemical deposition under different acidic conditions. The results showed that Ca and Sr exhibited different mineralization behaviors. The main mineralization products for Ca were CaHPO4·2H2O and Ca3(PO4)2 with the structure changed from porous to spherical as the pH values increased. The main mineralization products for Sr were SrHPO4 and Sr5(PO4)3OH with the structure changed from flake to needle as the pH values increased. The in vitro experiment demonstrated that coatings fabricated at high pH condition with the presence of Sr were favorable to MSCs adhesion, spreading, proliferation, and osteogenic differentiation. In addition, Sr-substituted apatite coatings could evidently inhibit osteoclast differentiation and fusion. Moreover, the in vivo study indicated that nano-needle like Sr-substituted apatite coating could suppress osteoclastic activity, improve new bone formation, and enhance bone-implant integration. This study provided a new theoretical guidance for implant coating design and the fabricated Sr-substituted coating might have potential applications for osteoporotic patients.
Prevalence of financial and health insurance literacy and their association with financial hardship in cancer patients.
Authors: Nandita Khera, Nan Zhang, Rahma M. Warsame, Talal Hilal, Rema Padman, Nilay Shah, Joan M. Griffin
Journal: Journal of Clinical Oncology (2020)

70 Background: The prevalence of health insurance literacy (HIL) and financial literacy (FL) in cancer patients is not well described. Further, a better understanding of the association between these constructs and the domains of financial hardship (FH) can guide potential interventions. Methods: We examined the prevalence of HIL and FL and FH in cancer patients on active treatment at our institution. HIL and FL were assessed using Health Insurance Literacy Measure (HILM) and 5 questions from the National Financial Capability Study respectively. COST FACIT and National Health Interview Survey (NHIS) questions were used to examine overall FH and its 3 domains (material, behavioral and psychological hardship). Pearson correlation coefficient was used to describe the relation between the COST score and FH domains assessed by NHIS questions. Logistic regression analysis was performed to determine the associations of overall FH (measured by COST FACIT) with FL and HIL. Results: Among 256 patients approached, 202 completed questionnaires. Median age was 67 (range 22 to 91) years. 51% were male, 93% Whites and 5% were Hispanic. 69% had a solid tumor with 37% stage IV. Median number of lines of treatment was 4 (range 1 to 18). 21% were currently employed, 59% had ≥college degree, 41% had private insurance and 42% had monthly income≥$7000. 50% participants answered at least 4/5 FL questions correctly, indicating high FL. Being male, White, having insurance, higher education and income ≥$7000 were associated with higher FL. 72% of participants had high HIL, and they were more likely to be Non-Hispanic, married and have received more lines of treatment. FL significantly correlated with HIL (r = 0.29, p &lt; .001). 65% patients endorsed FH based on NHIS questions (10% behavioral, 20% material, and 62% psychological hardship). 48% patients had FH based on a COST score &lt; 28 (Median score), which correlated with material (r = -0.59, p &lt; .001), psychological (r = -0.55, p &lt; .001) and behavioral FH (r = -0.42, p &lt; .001). The association between FH and HIL was not significant (OR 0.78; p = 0.08), though higher FL was associated with lower FH (OR 0.69; p = 0.02). Conclusions: Despite high FL and HIL (as compared to national standards), the prevalence of FH in our relatively affluent patient cohort was high, driven mainly by psychological hardship. We did not find strong association between the HIL and FH unlike in the reported literature. Our findings behoove us to develop tailored interventions to address unique domains of the FH in a diverse population.
Trends in prevalence of acute stroke impairments: A population-based cohort study using the South London Stroke Register
Authors: Amanda Clery, Ajay Bhalla, Anthony G. Rudd, Charles D. A. Wolfe, Yanzhong Wang
Journal: PLoS Medicine (2020)

Background Acute stroke impairments often result in poor long-term outcome for stroke survivors. The aim of this study was to estimate the trends over time in the prevalence of these acute stroke impairments. Methods and findings All first-ever stroke patients recorded in the South London Stroke Register (SLSR) between 2001 and 2018 were included in this cohort study. Multivariable Poisson regression models with robust error variance were used to estimate the adjusted prevalence of 8 acute impairments, across six 3-year time cohorts. Prevalence ratios comparing impairments over time were also calculated, stratified by age, sex, ethnicity, and aetiological classification (Trial of Org 10172 in Acute Stroke Treatment [TOAST]). A total of 4,683 patients had a stroke between 2001 and 2018. Mean age was 68.9 years, 48% were female, and 64% were White. After adjustment for demographic factors, pre-stroke risk factors, and stroke subtype, the prevalence of 3 out of the 8 acute impairments declined during the 18-year period, including limb motor deficit (from 77% [95% CI 74%–81%] to 62% [56%–68%], p < 0.001), dysphagia (37% [33%–41%] to 15% [12%–20%], p < 0.001), and urinary incontinence (43% [39%–47%) to 29% [24%–35%], p < 0.001). Declines in limb impairment over time were 2 times greater in men than women (prevalence ratio 0.73 [95% CI 0.64–0.84] and 0.87 [95% CI 0.77–0.98], respectively). Declines also tended to be greater in younger patients. Stratified by TOAST classification, the prevalence of all impairments was high for large artery atherosclerosis (LAA), cardioembolism (CE), and stroke of undetermined aetiology. Conversely, small vessel occlusions (SVOs) had low levels of all impairments except for limb motor impairment and dysarthria. While we have assessed 8 key acute stroke impairments, this study is limited by a focus on physical impairments, although cognitive impairments are equally important to understand. In addition, this is an inner-city cohort, which has unique characteristics compared to other populations. Conclusions In this study, we found that stroke patients in the SLSR had a complexity of acute impairments, of which limb motor deficit, dysphagia, and incontinence have declined between 2001 and 2018. These reductions have not been uniform across all patient groups, with women and the older population, in particular, seeing fewer reductions.
A new endoscopic fixation method using the commercially available Multi-Clamp: the “clamp technique”
Authors: Satoshi Abiko, Shuichi Miyamoto, Ryo Sugiura, Kenji Kinoshita, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse
Journal: Endoscopy (2020)

When endoscopic submucosal dissection (ESD) is performed in an unstable setting, removing one’s right hand from the endoscope to manipulate the ESD knife can make it difficult to maintain visibility during the surgery. Various tools and methods have been developed to overcome this challenge [1] [2] [3]; however, in many cases, the assistant is asked to fix the endoscope owing to issues such as difficulty in performing the complicated technique and limitations of the ESD knife available for use. We report our newly devised endoscopic fixation method using the commercially available Multi-Clamp (Taiyo Electric Ind. Co., Ltd., Tokyo, Japan).
Effects of PCB126 on Adipose-to-Muscle Communication in an <i>in Vitro</i> Model
Authors: Audrey Caron, Fozia Ahmed, Vian Peshdary, Léa Garneau, Ella Atlas, Céline Aguer
Journal: Environmental Health Perspectives (2020)

Exposure to coplanar polychlorinated biphenyls (PCBs) is linked to the development of insulin resistance. Previous studies suggested PCB126 alters muscle mitochondrial function through an indirect mechanism. Given that PCBs are stored in fat, we hypothesized that PCB126 alters adipokine secretion, which in turn affects muscle metabolism.We determined a) the impacts of PCB126 exposure on adipocyte cytokine/adipokine secretion in vitro; b) whether adipocyte-derived factors alter glucose metabolism and mitochondrial function in myotubes when exposed to PCB126; and c) whether preestablished insulin resistance alters the metabolic responses of adipocytes exposed to PCB126 and the communication between adipocytes and myotubes.3T3-L1 adipocytes were exposed to PCB126 (1-100 nM) in two insulin sensitivity conditions [insulin sensitive (IS) and insulin resistant (IR) adipocytes], followed by the measurement of secreted adipokines, mitochondrial function, and insulin-stimulated glucose uptake. Communication between adipocytes and myotubes was reproduced by exposing C2C12 myotubes or mouse primary myotubes to conditioned medium (CM) derived from IS or IR 3T3-L1 adipocytes exposed to PCB126. Mitochondrial function and insulin-stimulated glucose uptake were then determined in myotubes.IR 3T3-L1 adipocytes treated with PCB126 had significantly higher adipokine (adiponectin, IL-6, MCP-1, TNF-α) secretion and lower mitochondrial function, glucose uptake, and glycolysis. However, PCB126 did not significantly alter these parameters in IS adipocytes. Altered energy metabolism in IR 3T3-L1 adipocytes was linked to lower phosphorylation of AMP-activated protein kinase (p-AMPK) and higher superoxide dismutase 2 levels, an enzyme involved in reactive oxygen species detoxification. Myotubes exposed to the CM from PCB126-treated IR adipocytes had lower glucose uptake, with no alteration in glycolysis or mitochondrial function. Interestingly, p-AMPK levels were higher in myotubes exposed to the CM of PCB126-treated IR adipocytes.Taken together, these data suggest that increased adipokine secretion from IR adipocytes exposed to PCB126 might explain impaired glucose uptake in myotubes. https://doi.org/10.1289/EHP7058.
Is inpatient chemotherapy overutilized?
Authors: Natalie S Berger, Giulia Petrone, Chrystal Ann Landry, Hsin-hui Huang, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2020)

215 Background: Inpatient palliative chemotherapy has been associated with more aggressive end of life care, reduced utilization of hospice services and decreased quality of life. The decision to administer chemotherapy in the inpatient setting is not always standardized which may lead to overutilization. Methods: We performed a retrospective chart review of all patients who received inpatient chemotherapy at an Academic center during the year 2016. Patients were stratified by solid tumor (ST) versus hematologic malignancies (HM) and assessed for the urgency of chemotherapy. We also evaluated response to treatment, death within 30 days of chemotherapy administration, and other qualitative and quantitative variables. We used descriptive statistics and odds ratios (OR) were estimated from logistic regression models. Results: We identified 141 patients; 47% HM. Select significant patient outcomes (p-value ≤0.05) are summarized in Table. At the time of admission, the majority of ST patients had stage 4 cancer (71%) with a poorer performance status (p= 0.0005) and were more often admitted due to symptoms related to their cancer (p&lt;0.0001). HM patients were more likely to be directly admitted for chemotherapy (p&lt;0.0001). Among ST patients, 29% received chemotherapy because the admission coincided with a non-urgent planned cycle compared to 11% of HM. Reason for inpatient chemotherapy was documented as urgent for 94% HM and 67% ST patients. ST patients were more likely to receive a palliative care consult (65% vs 24%; p&lt;0.001) and to die within 30 days of index admission (15.8% vs 6.2%; p=0.019). In the adjusted analysis, the most important factor associated with urgent chemotherapy was the cancer type (OR: 8.25, 95% CI 2.13-31.97, p=0.002). Conclusions: Our study indicates that there is an overutilization of inpatient chemotherapy in ST patients as well as increased mortality within 30 days of inpatient chemotherapy administration compared to HM. The administration of inpatient chemotherapy can be avoided in many cases which can lead to improved quality of life and cost savings. Creation of a standardized algorithm on the appropriateness of inpatient chemotherapy may be a useful tool to guide decision making. [Table: see text]
Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy
Authors: Guofeng Ji, Lushun Ma, Haochen Yao, Sheng Ma, Xinghui Si, Yalin Wang, Xin Bao, Lili Ma, Fangfang Chen, Chong Ma, Leaf Huang, Xuedong Fang, Wantong Song
Journal: Acta Pharmaceutica Sinica B (2020)

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared via ultrasonic emulsification method, with a diameter of 184 nm and good stability. In vivo biodistribution studies confirmed that the injected OCA-NE mainly accumulated in the liver and especially in LSECs and Kupffer cells. As a result, OCA-NE treatment significantly suppressed hepatic tumor growth in a murine orthotopic H22 tumor model, which performed much better than oral medication of free OCA. Immunologic analysis revealed that the OCA-NE resulted in augmented secretion of CXCL16 and IFN-γ, as well as increased NKT cell populations inside the tumor. Overall, our research provides a new evidence for the antitumor effect of receptors for primary bile acids, and should inspire using nanotechnology for precisely manipulating LSECs for liver cancer therapy
Development and Validation of a Natural Language Processing Tool to Generate the CONSORT Reporting Checklist for Randomized Clinical Trials
Authors: Fan Wang, Richard L. Schilsky, David Page, Robert M. Califf, Kei Cheung, Xiaofei Wang, Herbert Pang
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Adherence to the Consolidated Standards of Reporting Trials (CONSORT) for randomized clinical trials is associated with improvingquality because inadequate reporting in randomized clinical trials may complicate the interpretation and the application of findings to clinical care. <h3>Objective</h3> To evaluate an automated reporting checklist generation tool that uses natural language processing (NLP), called CONSORT-NLP. <h3>Design, Setting, and Participants</h3> This study used published journal articles as training, testing, and validation sets to develop, refine, and evaluate the CONSORT-NLP tool. Articles reporting randomized clinical trials were selected from 25 high-impact-factor journals under the following categories: (1) general and internal medicine, (2) oncology, and (3) cardiac and cardiovascular systems. <h3>Main Outcomes and Measures</h3> For an evaluation of the performance of this tool, an accuracy metric defined as the number of correct assessments divided by all assessments was calculated. <h3>Results</h3> The CONSORT-NLP tool uses the widely used Portable Document Format as an input file. Of the 37 CONSORT reporting items, 34 (92%) were included in the tool. Of these 34 reporting items, 30 were fully implemented; 28 (93%) of the fully implemented CONSORT reporting items had an accuracy of more than 90% for the validation set. The remaining 2 (7%) had an accuracy between 80% and 90% for the validation set. Two to 5 articles were selected from each of these journals for a total of 158 articles to establish a training set of 111 articles to train CONSORT-NLP for CONSORT reporting items, a testing set of 25 articles to refine CONSORT-NLP, and a validation set of 22 articles to assess the performance of CONSORT-NLP. The CONSORT-NLP tool used the Portable Document Format of the articles as input files. A CONSORT-NLP graphical user interface was built using Java in 2019. The time required to complete the CONSORT checklist manually vs using the CONSORT-NLP tool was compared for 30 articles. Two case studies for randomized clinical trials are provided as an illustration for the CONSORT-NLP tool. For the 30 articles investigated, CONSORT-NLP required a mean (SD) 23.0 (4.1) seconds, whereas the manual reviewer required a mean (SD) 11.9 (2.2), 22.6 (4.6), and 57.6 (7.1) minutes, for 3 reviewers, respectively. <h3>Conclusions and Relevance</h3> The CONSORT-NLP tool is designed to assist in the reporting of randomized clinical trials. Potential users of CONSORT-NLP include clinicians, researchers, and scientists who plan to publish a randomized trial study in a peer-reviewed journal. The use of CONSORT-NLP may help them save substantial time when generating the CONSORT checklist. This tool may also be useful for manuscript reviewers and journal editors who review these articles.
Antithrombotic Strategies in Patients With Atrial Fibrillation and Percutaneous Coronary Intervention—Reply
Authors: Renato D. Lopes, Amit N. Vora, John H. Alexander
Journal: JAMA Cardiology (2020)

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Early detection of breast cancer during the Covid-19 pandemic using artificial intelligence neural networks
Authors: Subash Kumar
Journal: Clinical Cancer Research (2020)

Currently, as governments across the world attempt to halt the spread of COVID-19, many of their efforts are beinghampered by shortages of crucial testing kits  Even in many developed countries, the health system has come to thepoint of standstill due to the increasing demand for intensive care units  One study reveals that 40,000 women die ina year from breast cancer, which is one woman every 13 minutes dying from this disease every day  Breast cancerremains the number one form of cancer that women are diagnosed with around the world  Any hospital in the worldwill have a multidisciplinary team of experts including radiologists, oncologists, surgeons, and other respiratoryphysicians and consultants  This multidisciplinary team uses a wide variety of data taken from CT scans, x-rays, PET scans, biopsies, clinical examination, imaging mammography, ultrasound (sonography), pathology biopsy, andfine-needle aspiration to identify whether a patient has cancer  Individuals with cancer, particularly those who arereceiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19 Therefore, it is the need of an hour to implement an early detection of cancer that will prevent patients from COVID-19 and due treatment will be provided  Breast cancer that is detected early is far easier to cure, but at the same timeit is difficult to detect  An accurate breast cancer staging is an essential task performed by pathologists (experts whoexamine the laboratory samples) to inform clinical management for the appropriate treatment  For instance, evaluation of the extent of cancer spread by histopathologic analysis or microscopic examination is an importantpart of breast cancer staging, and the process involves the decision-making of human behavior with time-consumingand costly sample examination and a period of more than one month to have breast cancer type, stage, etc , todecide the appropriate therapy to patients by the time it can affect the results of therapeutic treatments and survivalof patients  The application of artificial intelligence (AI) machine learning technology with deep learning algorithms towhole-slide pathology images can potentially improve the diagnostic accuracy of breast cancer at a very early stage I have developed a simple machine-learning model using the Python programming language and neural network, inspired by the structure of the human brain, with 12 attributes, out of which 10 real-valued features from each cellnucleus obtained from the Wisconsin diagnostic breast cancer dataset available in public domain for the educationcapacity that explains about the stage of breast cancer M (Malignant) and B (Benign)  This model predicts thepresence of breast cancer with an accuracy of 98 8% at a very early stage  The continuous development oftechnology in the medical field will save countless lives and the overall quality of human life will continue to improveover time