tbuckley/cabot-search huggingface dataset:
Recent updates on the resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors and resistance reversion strategies in lung cancer
Authors: Surya K. Tripathi, Kamal Pandey, Kannan R. R. Rengasamy, Bijesh K. Biswal
Journal: Medicinal Research Reviews (2020)

Abstract Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have led to a substantial improvement in the prognosis of lung cancer patients by explicitly targeting the activating mutations within the EGFR. Initially, patients harboring tumors with EGFR mutations show progression‐free survival and improvement in the response rates toward all‐generation EGFR‐TKIs; however, these agents fail to deliver the intended results in the long‐term due to drug resistance. Therefore, it is necessary to recognize specific cardinal mechanisms that regulate the resistance phenomenon. Understanding the intricate mechanisms underlying EGFR‐TKIs resistance in lung cancer could provide cognizance for more advanced targeted therapeutics. The present review features insights into current updates on the discrete mechanisms, including secondary or tertiary mutations, parallel and downstream signaling pathways, acquiring an epithelial‐to‐mesenchymal transition (EMT) signature, microRNAs (miRNAs), and epigenetic alterations, which lead to intrinsic and acquired resistance against EGFR‐TKIs in lung cancer. In addition, this paper also reviews current possible strategies to overcome this issue using combination treatment of recently developed MET inhibitors, allosteric inhibitors or immunotherapies, transformation of EMT, targeting miRNAs, and epigenetic alterations in intrinsic and acquired EGFR‐TKIs resistant lung cancer. In conclusion, multiple factors are responsible for intrinsic and acquired resistance to EGFR‐TKIs and understanding of the detailed molecular mechanisms, and recent advancements in pharmacological studies are needed to develop new strategies to overcome intrinsic and acquired EGFR‐TKIs resistance in lung cancer.
Thrombin Bionsensors: A Rapid and Ultrasensitive Thrombin Biosensor Based on a Rationally Designed Trifunctional Protein (Adv. Healthcare Mater. 12/2020)
Authors: Huayue Zhang, Lu Yang, Xiaqing Zhu, Yanyan Wang, Haitao Yang, Zefang Wang
Journal: Advanced Healthcare Materials (2020)

In article number 2000364 by Yanyan Wang, Zefang Wang, and co-workers, an ultrasensitive and rapid thrombin biosensor is developed based on rationally designed trifunctional protein HTs, comprising three functional units, including a far-red fluorescent protein smURFP, hydrophobin HGFI, and a thrombin cleavage site (TCS). smURFP is used as a detection signal to eliminate any interference from the autofluorescence of sample matrix to increase detection sensitivity. HGFI serves as an adhesive unit to allow rapid immobilization of HTs on a multiwall plate. The TCS linking HGFI and smURFP functions as a sensing element to recognize and detect thrombin. As a result, the intensity of the fluorescent signal on the surface of multiwall plates changes depending on the concentration of thrombin. The sensing mechanism of this biosensor relies on the ability of active thrombin in samples to specifically recognize and hydrolyze its cleavage site in the fusion protein, resulting in a subsequent decrease in the fluorescence intensity of the sample.
Familial Clustering of Aortic Size, Aneurysms, and Dissections in the Community
Authors: Jakob Raunsø, Rebecca J. Song, Ramachandran S. Vasan, Maximillian T. Bourdillon, Betina Nørager, Christian Torp-Pedersen, Gunnar H. Gislason, Vanessa Xanthakis, Charlotte Andersson
Journal: Circulation (2020)

Ruptured aortic aneurysm and aortic dissections are potentially preventable disorders associated with high mortality. Screening of individuals at risk may translate into elective surgical interventions and lowered mortality. It is uncertain if the risk of aortic dilation of varying degrees aggregates within families.We investigated the risk of having thoracic and abdominal aortic sizes in the highest quartile (measured by computed tomography scans and indexed for body size) if at least 1 parent did so in the Framingham Heart Study cohorts, and estimated the incidence rates and hazard ratios of developing aortic aneurysm or dissection among first-degree relatives of those with aortic aneurysm or dissection, in comparison with age- and sex-matched controls (1:10 for aortic aneurysm and 1:100 for aortic dissection) using the Danish nationwide administrative registries.In the Framingham Heart Study, offspring (n=235) whose parent(s) had a sex- and age-standardized aortic size in the upper quartile had a multivariable-adjusted ≈3-fold increased odds ratio of belonging to the upper quartile themselves. In Denmark, a total of 68 939 individuals (mean age, 42 years) had a first-degree relative with aortic aneurysm and 7209 persons (mean age, 39 years) had a first-degree relative with aortic dissection. During an average follow-up of 7 years, first-degree relatives of patients with aortic aneurysm and dissection had a hazard ratio of 6.70 (95% CI, 5.96-7.52) for developing aortic aneurysm and a hazard ratio of 9.24 (95% CI, 5.53-15.44) for dissection in comparison with matched controls. These estimates remained unchanged on adjusting for several comorbidities, including prevalent hypertension, bicuspid aortic valve, and the Marfan syndrome. For both aortic aneurysm and dissections, the absolute event rates approached 1 per 1000 person-years for first-degree relatives versus 11 to 13 (aortic aneurysm) and 2 to 3 (aortic dissections) per 100 000 person-years among controls.Increased aortic size, a precursor of aortic aneurysm and a risk factor for dissection, clusters in families. The incidence rates of aortic aneurysm and dissections approach the incidence rates of other common cardiovascular conditions in first-degree relatives, supporting the use of systematic screening for these conditions.
Inhalational Indocyanine Green to Visualize Lung Tumors—Defining the Margin of Error
Authors: Joseph D. Phillips, David J. Finley
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Lymph node fibroblastic reticular cells deposit fibrosis-associated collagen following organ transplantation
Authors: Xiaofei Li, Jing Zhao, Vivek Kasinath, Mayuko Uehara, Liwei Jiang, Naima Banouni, Martina M. McGrath, Takaharu Ichimura, Paolo Fiorina, Dario R. Lemos, Su Ryon Shin, Carl F. Ware, Jonathan S. Bromberg, Reza Abdi
Journal: Journal of Clinical Investigation (2020)

Although the immune response within draining lymph nodes (DLNs) has been studied for decades, how their stromal compartment contributes to this process remains to be fully explored. Here, we show that donor mast cells were prominent activators of collagen I deposition by fibroblastic reticular cells (FRCs) in DLNs shortly following transplantation. Serial analysis of the DLN indicated that the LN stroma did not return to its baseline microarchitecture following organ rejection and that the DLN contained significant fibrosis following repetitive organ transplants. Using several FRC conditional-knockout mice, we show that induction of senescence in the FRCs of the DLN resulted in massive production of collagen I and a proinflammatory milieu within the DLN. Stimulation of herpes virus entry mediator (HVEM) on FRCs by its ligand LIGHT contributed chiefly to the induction of senescence in FRCs and overproduction of collagen I. Systemic administration of ex vivo-expanded FRCs to mice decreased DLN fibrosis and strengthened the effect of anti-CD40L in prolonging heart allograft survival. These data demonstrate that the transformation of FRCs into proinflammatory myofibroblasts is critically important for the maintenance of a proinflammatory milieu within a fibrotic DLN.
Childhood COVID-19: a multicentre retrospective study
Authors: Z. Chen, L. Tong, Y. Zhou, C. Hua, W. Wang, J. Fu, Q. Shu, L. Hong, H. Xu, Z. Xu, Y. Chen, Y. Mao, S. Ye, X. Wu, L. Wang, Y. Luo, X. Zou, X. Tao, Y. Zhang
Journal: Clinical Microbiology and Infection (2020)

To investigate the clinical and epidemiological characteristics of paediatric patients with coronavirus disease-19 (COVID-19). Paediatric patients diagnosed with COVID-19 between January 15 and March 15, 2020, from seven hospitals in Zhejiang Province, China, were collected retrospectively and analysed. Thirty-two children with COVID-19, ranging in age from 3 months to 18 years, were enrolled. Family aggregation occurred in 87.5% of infant and preschool-aged children (7/8), and also school-aged children (14/16), but in only 12.5% (1/8) of adolescents (p < 0.05, p < 0.001). Most of these patients had mild symptoms: mainly fever (20/32) followed by cough (10/32) and fatigue (4/32). The average durations of viral RNA in respiratory samples and gastrointestinal samples were 15.8 d and 28.9 d, respectively. Detox duration in faeces decreased with age: 39.8 d, 27.5 d and 20.4 d in infants and preschool children, school children, and adolescents respectively (p0-6, -18 <0.01, p0-6, -14 <0.05). Pneumonia was found in 14 children, but there was no statistical significance in the incidence of pneumonia between different age groups. Thirty patients were treated with antiviral drugs, and all patients were stable and gradually improved after admission. Most children with COVID-19 had a mild process and a good prognosis. More attention should be paid to investigation of household contact history in the diagnosis of COVID-19 in young children. Viral RNA lasts longer in the gastrointestinal system than in the respiratory tract, especially in younger children.
Experience of telemedicine use in a big cohort of patients with rheumatoid arthritis during COVID-19 pandemic
Authors: Pedro Santos-Moreno, Josefina Chavez-Chavez, Sandra Milena Hernández-Zambrano, Diana Patricia Rivera-Triana, Ruth Alexandra Castiblanco-Montañez, Anggie Aza, Diana Buitrago-Garcia, Laura Villarreal, Adriana Rojas-Villarraga
Journal: Annals of the Rheumatic Diseases (2020)

We have read with interest the work of Bozzalla-Cassione et al 1 published recently in your journal regarding the implementation of a telemedicine programme for patients with lupus in northern Italy. It is logical to suppose that the risk of patients with rheumatic diseases of having a more severe clinical course if they become infected with the COVID-19 infection is very high; however, although some of the reports show that there seems to be a low incidence of COVID-19 infection in patients with rheumatic disease, collaborative work with large cohorts is needed, which could show us the real incidence of COVID-19 infection in these patients and what happens with the establishment of telemedicine programmes.2–6 

We show an experience in a specialised centre in Bogota, Colombia; currently, we have a cohort of 5597 patients with rheumatoid arthritis (RA) in exclusively ambulatory care. On 12 March 2020, in Colombia, the health emergency by COVID-19 was established and a week later the Ministry of Health ordered the outpatient care procedure for the population in isolation. From that moment on, our …
Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation
Authors: Paul Tsoukas, Emily Rapp, Lauren Van Der Kraak, Eric S. Weiss, Vinh Dang, Corinne Schneider, Edwin Klein, Jennifer Picarsic, Rosalba Salcedo, C. Andrew Stewart, Scott W. Canna
Journal: Blood (2020)
Outcomes of anterior versus posterior peroral endoscopic myotomy 2 years post-procedure: prospective follow-up results from a randomized clinical trial
Authors: Yervant Ichkhanian, Jad P. Abimansour, Mathieu Pioche, Kia Vosoughi, Nicholas Eleftheriadis, Philip Wai Yan Chiu, Hitomi Minami, Kumi Ogihara, Omid Sanaei, Manol Jovani, Mouen A. Khashab
Journal: Endoscopy (2020)

Abstract Background Peroral endoscopic myotomy (POEM) is considered a primary treatment modality for achalasia. It can be performed using either the anterior or posterior approach. A previous randomized clinical trial (RCT) showed that the posterior approach was noninferior to the anterior approach at 1 year post-POEM in terms of clinical success, rate of adverse event, and risk of gastroesophageal reflux disease (GERD). The aim of this post-RCT study was to compare outcomes at ≥ 2 years post-POEM. Methods Patients who previously completed the 1-year follow-up were contacted and their Eckardt, dysphagia, and GERD questionnaire (GERDQ) scores and frequency of proton pump inhibitor use were recorded. Clinical success was defined as an Eckardt score &lt; 3. Results 150 patients were initially randomized and 138 completed the 1-year follow-up. Of the 138, 111 (anterior group 54, posterior group 57) also completed ≥ 2 years of follow-up, with an overall clinical success decrease from 89 % to 82 %. At ≥ 2 years post-POEM, clinical success was achieved in 46/54 (85 %) and 45/57 (79 %) in the anterior and posterior groups, respectively (P = 0.43). A similar decrease in clinical success was noted in both groups at ≥ 2 years (anterior: 90 % to 85 %; posterior 89 % to 79 %; P = 0.47). GERDQ score was 6 (interquartile range 6 – 8; P = 0.08) in both treatment groups. Conclusions The anterior and posterior POEM techniques remained equally effective at 2 years and decreases in efficacy were similar between the two approaches over time. GERD outcomes were also similar in both groups during medium-term follow-up.
Tumor Mutational Burden, Toxicity, and Response of Immune Checkpoint Inhibitors Targeting PD(L)1, CTLA-4, and Combination: A Meta-regression Analysis
Authors: Arsen Osipov, Su Jin Lim, Aleksandra Popovic, Nilofer S. Azad, Daniel A. Laheru, Lei Zheng, Elizabeth M. Jaffee, Hao Wang, Mark Yarchoan
Journal: Clinical Cancer Research (2020)

Tumor mutational burden (TMB) has emerged as a potential predictive biomarker for clinical response to ICI therapy, but whether TMB also predicts toxicity remains unknown. We investigated the relationship between TMB, objective response rate (ORR), overall survival (OS), and toxicity for ICI therapy across multiple cancer types.
Digital approaches for mental health in the age of covid-19
Authors: Bernard P Chang, Ronald C Kessler, Harold A Pincus, Matthew K Nock
Journal: BMJ (2020)

Gold’s editorial on psychological first aid interventions recognises the major psychological consequences arising in the covid-19 pandemic.1 In this current climate, mounting effective mental health responses faces challenges, including the widespread reduction of available in-person mental health services and broad limitations in mobility as a result of the public health measures enacted.

Covid-19 is occurring in an age of unprecedented adoption of digital technology, creating opportunities for data driven testing and dissemination …
Rapid spread of OXA-244-producing Escherichia coli ST38 in Germany: insights from an integrated molecular surveillance approach; 2017 to January 2020
Authors: Katrin Kremer, Rolf Kramer, Bernd Neumann, Sebastian Haller, Niels Pfennigwerth, Guido Werner, Sören Gatermann, Horst Schroten, Tim Eckmanns, Jörg B Hans
Journal: Eurosurveillance (2020)

Annually, increasing numbers of OXA-244-producing Escherichia coli in 13 German federal states prompted us to initiate an outbreak investigation. Whole genome sequencing revealed that among 148 isolates analysed, most belonged to sequence type 38 with 62 isolates forming a genetically distinct cluster. Although no epidemiological link could be identified between cases, ongoing investigations suggest non-healthcare associated transmission. A screening-PCR was developed facilitating early detection of ST38 cluster isolates to identify the source and transmission route.
Diagnostic yield of early repeat colonoscopy after suboptimal bowel preparation in a fecal immunochemical test-based screening program
Authors: Sandra Baile-Maxía, Carolina Mangas-Sanjuan, Lucía Medina-Prado, Juan Martínez-Sempere, Oscar Murcia, Francisco Ruíz-Gómez, Juan A. Casellas, Pedro Zapater, Rodrigo Jover
Journal: Endoscopy (2020)

Abstract Background Current guidelines regarding surveillance after screening colonoscopy assume adequate bowel preparation. However, follow-up intervals after suboptimal cleansing are highly heterogeneous. We aimed to determine the diagnostic yield of early repeat colonoscopy in patients with suboptimal bowel preparation in fecal immunochemical test (FIT)-based screening colonoscopy. Methods An observational study including patients who underwent colonoscopy with suboptimal bowel preparation after positive FIT screening and then repeat colonoscopy within 1 year. Suboptimal preparation was defined as a Boston Bowel Preparation Scale (BBPS) score of 1 in any segment. Patients with a BBPS score of 0 in any segment or incomplete examination were excluded. The adenoma detection rate (ADR), advanced ADR (AADR), and colorectal cancer rate were calculated for the index and repeat colonoscopies. Results Of the 2474 patients with FIT-positive colonoscopy at our center during this period, 314 (12.7 %) had suboptimal preparation. Of the 259 (82.5 %) patients who underwent repeat colonoscopy, suboptimal cleansing persisted in 22 (9 %). On repeat colonoscopy, the ADR was 38.7 % (95 %CI 32.6 % to 44.8 %) and the AADR was 14.9 % (95 %CI 10.5 % to 19.4 %). The per-adenoma miss rate was 27.7 % (95 %CI 24.0 % to 31.6 %), and the per-advanced adenoma miss rate was 17.6 % (95 %CI 13.3 % to 22.7 %). After repeat colonoscopy, the post-polypectomy surveillance recommendation changed from 10 to 3 years in 14.7 % of the patients with previous 10-year surveillance recommendation. Conclusions Patients with suboptimal bowel preparation on FIT-positive colonoscopy present a high rate of advanced adenomas in repeat colonoscopy, with major changes in post-polypectomy surveillance recommendations.
Changing Epidemiology of Hepatitis A in China: Evidence From Three National Serological Surveys and the National Notifiable Disease Reporting System
Authors: Fuzhen Wang, Xiaojin Sun, Feng Wang, Hui Zheng, Zhiyuan Jia, Guomin Zhang, Shengli Bi, Ning Miao, Shuang Zhang, Fuqiang Cui, Li Li, Huaqing Wang, Xiaofeng Liang, Lance E. Rodewald, Zijian Feng, Zundong Yin, Liping Shen
Journal: Hepatology (2020)

China has conducted surveillance for hepatitis A since 1990, and hepatitis A was highly-to-intermediately endemic in 1992 when a Chinese hepatitis A vaccine (HepA) was licensed and introduced as a family-pay vaccine. In 2008, HepA was introduced into the Expanded Program on Immunization as a free childhood vaccine.Three nationally representative surveys conducted in 1992, 2006, and 2014 assessed hepatitis B serology. The 1992 survey included hepatitis A virus (HAV) serology, and we tested sera from the 2006 and 2014 surveys for HAV antibodies. We used surveillance, seroprevalence, and vaccination status data to describe the changing epidemiology of hepatitis A in China from 1990 through 2014. Before HepA licensure, anti-HAV seroprevalence was 60% at 4 years of age, 70% at 10 years, and 90% at 59 years; incidence was 52/100,000 and peaked at 4 years. In 2006, after >10 years of private sector vaccination, HepA coverage was <30% among children <5 years, and incidence was 5.4/100,000 with a peak at 10 years. In 2014, coverage was >90% among children under 5 years; incidence was 1.9/100,000. Individuals born before the national introduction of HepA (1988-2004) had lower anti-HAV seroprevalence than earlier and later birth cohorts.The incidence of hepatitis A declined markedly following HepA introduction and improvement of sanitation and hygiene. The emerging epidemiology is consistent with disease-induced immunity having been replaced by vaccine-induced immunity, resulting in a low incidence of hepatitis A. Catch-up HepA campaigns to close the immunity gap among the 1998-2004 birth cohorts should be considered.
A multicenter, open-label, phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of JMT-101 in patients (pts) with advanced colorectal cancer (ACC).
Authors: Jian Li, Lin Shen, Jifang Gong, Zhi Peng, Dan Liu, Changsong QI, Jiajia Yuan, Rong Hu, Xiugao Yang, Tao Li, Dongxue Fu, Ruirui Yang, Li Feng, Peng Zhang, Xin Chen, Jing Yuan, Yuanyuan Liu, Zhufeng Wu, Ye Cao, Shulin Zhong
Journal: Journal of Clinical Oncology (2020)

e16025 Background: JMT101 is a fully human monoclonal IgG1 antibody targeting epidermal growth factor receptor (EGFR). This study aimed to evaluate the safety and tolerability of JMT101 alone or in combination with chemotherapy in ACC. Methods: This is an open label, dose-escalating, phase I clinical trial. The pts with ACC and naïve to systemic EGFR-targeted therapy were assigned to receive JMT101 monotherapy (JMT101 group, pts with wild-type RAS ACC and had experienced failure of at least one standard regimen) or JMT101 in combination with mFOLFOX6/FOLFIRI (combination group, pts with wild-type RAS/non-BRAF V600E mutant ACC). JMT101 was infused intravenously by accelerated titration and traditional "3+3" dose-escalation scheme. The initial dose of JMT101 monotherapy was 0.5 mg/kg (q1w), and sequentially escalated to 2.0, 4.0, 6.0, 8.0, and 10.0 mg/kg (q2w). Until the dose of JMT101 group was escalated to the higher dose and sufficient safety data were obtained, the dose of the combination group would be escalated sequentially from 6.0, 8.0, to 10.0 mg/kg (q2w). The primary endpoints were safety and tolerability. The secondary endpoints were clinical efficacy and pharmacokinetic parameters. Results: From April 2017 to December 2019, 16 enrolled pts in JMT101 group (13 males, 3 females, median age 59.5 [27-64] years) and 7 in combination group (4 males, 3 females, median age 49 [39-68] years) were evaluable. The dose of JMT101 was escalated to 10.0, 8.0, 6.0 mg/kg in JMT101 group, mFOLFOX6 group and FOLFIRI group, respectively. Dose-limiting toxicity was not observed, maximum tolerated dose was not reached, and treatment-related SAE was not reported so far. JMT101 monotherapy and combination therapy were associated with grade 1 (15 and 7 cases), grade 2 (10 and 7 cases), and grade 3 (5 and 5 cases) AEs. In all groups, the most common AEs were skin rash (81.3% [13/16] in JMT101 group, 100% [7/7] in combination group), proteinuria (62.5% [10/16] in JMT101 group, 28.6% [2/7] in combination group) and oral mucositis (86.0% [6/7] in combination group). JMT101 monotherapy and combination therapy resulted in partial response (2 and 4 pts), objective response rate (12.5% and 57.1%), disease control rate (56.2% and 100%), and disease control &gt; 24 weeks (4 and 3 pts). Conclusions: JMT101 shows good safety, tolerability, and antitumor activity in pts with ACC. Clinical trial information: 20160904 .