tbuckley/cabot-search huggingface dataset:
Neutrophil expansion defines an immunoinhibitory peripheral and intratumoral inflammatory milieu in resected non-small cell lung cancer: a descriptive analysis of a prospectively immunoprofiled cohort
Authors: Kyle G Mitchell, Lixia Diao, Tatiana Karpinets, Marcelo V Negrao, Hai T Tran, Edwin R Parra, Erin M Corsini, Alexandre Reuben, Lorenzo Federico, Chantale Bernatchez, Hitoshi Dejima, Alejandro Francisco-Cruz, Jing Wang, Mara B Antonoff, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone, Ignacio I Wistuba, John V Heymach, Don L Gibbons, Jianjun Zhang, Cara L Haymaker, Boris Sepesi
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The biological underpinnings of the prognostic and predictive significance of a relative neutrophilia in patients with non-small lung cancer (NSCLC) are undefined. We sought to comprehensively examine the relationships between circulating and intratumoral neutrophil populations and features of the immune contexture in patients undergoing NSCLC resection. Methods Preoperative soluble cytokine and angiogenic factors; tumor multiplex immunofluorescence; RNA, whole exome, and T-cell receptor sequencing; and flow cytometry were analyzed for relationships with populations of circulating (from complete blood counts) and intratumoral neutrophils (transcriptional signatures) in a prospectively enrolled resected NSCLC cohort (n=66). In a historical cohort (n=1524), preoperative circulating neutrophil and lymphocyte counts were analyzed for associations with overall survival (OS). Results Circulating neutrophil populations were positively correlated with increased tumor burden, and surgical tumor resection was followed by a subsequent reduction in peripheral neutrophil counts. Expansion of the circulating neutrophil compartment was associated with increased levels of pro-granulopoietic (IL-1β, IL-17A, TNFα, IL-6) and T H 2-associated (IL-5, IL-13) cytokines. Tumors with high intratumoral neutrophil burden were marked by a blunted T-cell response characterized by reduced expression of cytotoxic T-cell genes ( CD8A , CD8B , GZMA , GZMB ), decreased CD3 + CD8 + cell infiltration, and diminished expression of IFNγ-related genes. The associations between increased intratumoral neutrophil burden and reduced CD3 + CD8 + infiltration persisted after adjustment for tumor size, histology, mutational burden, and PD-L1 expression. In 1524 patients, elevated preoperative circulating neutrophil count was independently associated with worse OS (main effect HR 1.82, 95% CI 1.24 to 2.68, p=0.002). Conclusions Our findings demonstrate that neutrophil expansion reflects protumorigenic and immunosuppressive processes that manifest as worse OS in patients undergoing NSCLC resection. These results justify further investigation of therapeutic strategies targeting neutrophil-associated immune evasion.
Periodontal disease as a possible cause for Alzheimer's disease
Authors: Angela R. Kamer, Ronald G. Craig, Richard Niederman, Juan Fortea, Mony J. de Leon
Journal: Periodontology 2000 (2020)

Approximately 47 million people worldwide have been diagnosed with dementia, 60%-80% of whom have dementia of the Alzheimer's disease type. Unfortunately, there is no cure in sight. Defining modifiable risk factors for Alzheimer's disease may have a significant impact on its prevalence. An increasing body of evidence suggests that chronic inflammation and microbial dysbiosis are risk factors for Alzheimer's disease. Periodontal disease is a chronic inflammatory disease that develops in response to response to microbial dysbiosis. Many studies have shown an association between periodontal disease and Alzheimer's disease. The intent of this paper was to review the existing literature and determine, using the Bradford Hill criteria, whether periodontal disease is causally related to Alzheimer's disease.
Impact of chemotherapy and external beam radiation therapy on outcomes among patients with resected gallbladder cancer: A multi-institutional analysis.
Authors: Yuhree Kim, Neda Amini, Ana Wilson, Cecilia Grace Ethun, George A. Poultsides, Thuy Tran, Kamran Idrees, Chelsea A Isom, Ryan C. Fields, Sharon M. Weber, Ahmed I. Salem, Robert C. G. Martin, Charles Raben Scoggins, Perry Shen, Harveshp Mogal, Carl Richard Schmidt, Ioannis Hatzaras, Rivfka Shenoy, Shishir Kumar Maithel, Timothy M. Pawlik
Journal: Journal of Clinical Oncology (2016)

387 Background: Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) in the treatment of resectable gallbladder cancer remains varied. We sought to define the utilization and effect of adjuvant therapy on patients having undergone curative-intent resection for gallbladder cancer. Methods: Using a multi-institutional national database, 291 patients with gallbladder cancer who underwent curative-intent resection between 2000 and 2015. Patients with metastasis or an R2 margin were excluded. The impact of adjuvant therapy on survival was analyzed among patients who received surgery alone versus CTx versus cXRT. Results: Median patient age was 66 years. Most patients had a T2 (41.9%) or T3 (35.1%) lesion and 37.8% of patients had lymph node (LN) metastasis. A total of 186 (63.9%) patients underwent surgery alone, 61 (21.0%) received CTx, whereas the remaining 44 (15.1%) patients received cXRT. At a median follow-up of 16.3 months, median and 5-year overall survival (OS) was 28.3 months and 33.0%, respectively. On multivariable analysis, factors associated with worse OS included AJCC T3/T4 (hazard ratio [HR] 2.97), LN metastasis (HR 1.75) and lymphovascular invasion (HR 1.98; all P&lt;0.05). In contrast, receipt of CTx or cXRT was associated with improved long-term OS (CTx, HR 0.33; cXRT, HR 0.27; P&lt;0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS)(CTx, HR 0.53; cXRT, HR 0.45; P&lt;0.01). Of note, the OS benefit for CTx or cXRT was observed among patients with high risk features such as AJCC T3/T4 disease (HR 0.61; HR 0.31), LN-metastasis (HR 0.45; HR 0.46), and R1 disease (HR 0.33; HR 0.11) (all P&lt;0.05). In contrast, the OS benefit of CTx and cXRT was not noted among patients with T1/T2 or N0 disease, or among those with an R0 margin (all P&gt;0.05). Conclusions: Adjuvant CTx and cXRT were utilized in 36% of patients undergoing curative-intent resection for gallbladder cancer. After adjusted analysis, CTx and cXRT were independent factors associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.
Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19
Authors: Louise Bowles, Sean Platton, Nada Yartey, Minal Dave, Kurtis Lee, Daniel P. Hart, Vickie MacDonald, Laura Green, Suthesh Sivapalaratnam, K. John Pasi, Peter MacCallum
Journal: New England Journal of Medicine (2020)

Prolonged aPTT in Patients with Covid-19 In this study, 20% of patients with Covid-19 had a prolonged activated partial-thromboplastin time. In 90% of these cases, the cause was lupus anticoagulant...
Bioprinting of radiopaque constructs for tissue engineering and understanding degradation behavior by use of Micro-CT
Authors: Sudipto Datta, Shuvodeep Jana, Ankita Das, Arindam Chakraborty, Amit Roy Chowdhury, Pallab Datta
Journal: Bioactive Materials (2020)

Bioprinting has emerged as a potential technique to fabricate tissue engineering constructs and in vitro models directly using living cells as a raw material for fabrication, conforming to the heterogeneity and architectural complexity of the tissues. In several of tissue engineering and in vitro disease modelling or surgical planning applications, it is desirable to have radiopaque constructs for monitoring and evaluation. In the present work, enhanced radiopaque constructs are generated by substituting Calcium ions with Barium ions for crosslinking of alginate hydrogels. The constructs are characterized for their structural integrity and followed by cell culture studies to evaluate their biocompatibility. This was followed by the radiopacity evaluation. The radiological images obtained by micro-CT technique was further applied to investigate the degradation behavior of the scaffolds. In conclusion, it is observed that barium crosslinking can provide a convenient means to obtain radiopaque constructs with potential for multi-faceted applications.
TCT-522 Outcomes of Laser-Assisted Balloon Angioplasty versus Balloon Angioplasty Alone for Below Knee Peripheral Arterial Disease
Authors: Chatchawan Piyaskulkaew, Kesav Parvataneni, Hussein Ballout, Tarun Sharma, Thomas LaLonde, Rajendra H. Mehta, Hiroshi Yamasaki
Journal: Journal of the American College of Cardiology (2014)
Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope
Authors: Paul D. Varosy, Lin Y. Chen, Amy L. Miller, Peter A. Noseworthy, David J. Slotwiner, Venkatesh Thiruganasambandamoorthy
Journal: Journal of the American College of Cardiology (2017)
A prospective study of cigarette smoking and age-related macular degeneration in women
Authors: J. M. Seddon
Journal: JAMA (1996)

Objective.-To evaluate the relationship between cigarette smoking and incidence of age-related macular degeneration (AMD) among women. Design.-Prospective cohort study with 12 years of follow-up (1980 to 1992), in which information on smoking habits was updated every 2 years. Setting.-Eleven states throughout the United States. Participants.-A total of 31 843 registered nurses enrolled in the Nurses' Health Study who were aged 50 to 59 years in 1980 and did not report a diagnosis of cancer or AMD at the beginning of the study. Additional women entered the analytic cohort as they reached 50 years of age. Main Outcome Measure.-Incidence of AMD with visual loss. Results.-During 556338 person-years of follow-up, 215 women were newly diagnosed as having AMD. After adjusting for other risk factors for AMD, women who currently smoked 25 or more cigarettes per day had a relative risk (RR) of AMD of 2.4 (95% confidence interval [Cl], 1.4-4.0) compared with women who never smoked. Past smokers of this amount also had a 2-fold increased risk (RR=2.0 ; 95% Cl, 1.2-3.4) relative to never smokers. Compared with current smokers, little reduction in risk was suggested even after quitting smoking for 15 or more years. Risk of AMD also increased with an increasing number of pack-years smoked (P for trend <.001) ; among women who smoked for 65 or more pack-years, the risk was 2.4 times the risk of never smokers (95% Cl, 1.5-3.8). Analyses of dry and exudative types of AMD and other altemative definitions of AMD revealed similar results. Conclusions.-Cigarette smoking is an independent and avoidable risk factor for AMD among women. Because AMD is the most common cause of severe visual impairment among the elderly and treatment is not available or is ineffective for most patients, reducing the risk of this disease is another important reason to avoid smoking.
Navigating the Pandemic Response Life Cycle: Molecular Diagnostics and Immunoassays in the Context of COVID-19 Management
Authors: Baback Gharizadeh, Junqiu Yue, Mingxia Yu, Yue Liu, Meiying Zhou, Daru Lu, Jingwei Zhang
Journal: IEEE Reviews in Biomedical Engineering (2020)

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To counter COVID-19 spreading, an infrastructure to provide rapid and thorough molecular diagnostics and serology testing is the cornerstone of outbreak and pandemic management. We hereby review the clinical insights with regard to using molecular tests and immunoassays in the context of COVID-19 management life cycle: the preventive phase, the preparedness phase, the response phase and the recovery phase. The spatial and temporal distribution of viral RNA, antigens and antibodies during human infection is summarized to provide a biological foundation for accurate detection of the disease. We shared the lessons learned and the obstacles encountered during real world high-volume screening programs. Clinical needs are discussed to identify existing technology gaps in these tests. Leverage technologies, such as engineered polymerases, isothermal amplification, and direct amplification from complex matrices may improve the productivity of current infrastructure, while emerging technologies like CRISPR diagnostics, visual end point detection, and PCR free methods for nucleic acid sensing may lead to at-home tests. The lessons learned, and innovations spurred from the COVID-19 pandemic could upgrade our global public health infrastructure to better combat potential outbreaks in the future.
Covid-19: Hong Kong government supplies reusable face masks to all residents
Authors: Jane Parry
Journal: BMJ (2020)

The Hong Kong government has begun to distribute reusable face masks to all residents, as part of its strategy to protect the city's 7.5 million people from covid-19.[1][1] In addition, all households will be supplied with 10 single use surgical masks, 30 million in total, in late June. The
A PREDICTIVE MODEL IDENTIFIES PATIENTS LESS LIKELY TO HAVE ADENOMAS AFTER A COLON CANCER
Authors: L Frazzoni, M Scagliarini, L Laterza, C Trovato, A Mussetto, M De Bellis, S Paggi, C Spada, L Petrella, V Smania, N De Bortoli, F Bazzoli, L Ricciardiello, F Radaelli, C Hassan, L Fuccio
Journal: Endoscopy (2019)

Patients with prior colorectal cancer (CRC) are at slightly increased risk of metachronous colorectal neoplasms, therefore endoscopic surveillance is indicated. Current recommendations of repeating examinations at 1, 3 and 5 years after surgery, are not tailored according to risk stratification. Our aim was to find predictive factors of colorectal neoplasms to build a predictive model, to spare colonoscopies for low-risk patients.
SURG-27. STEREOTACTIC LASER ABLATION (SLA) AS TREATMENT FOR BRAIN METASTASES THAT RECUR AFTER STEREOTACTIC RADIOSURGERY: A MULTI-INSTITUTIONAL EXPERIENCE
Authors: Clark Chen, Mir Amaan, Robert Rennert, Kate Carroll, Mayur Sharma, Jill Barnholtz-sloan, Charlotte Myers, Gene Barnett, Kris Smith, Alireza Mohammadi, Andrew Sloan
Journal: Neuro-Oncology (2016)

Therapeutic options for brain metastases (BMs) that recur after stereotactic radiosurgery (SRS) remain limited. Here we provide the collective experience of four institutions treatment of BMs that recurred after SRS with stereotactic laser ablation (SLA). Twenty-six BMs (in 23 patients) that recurred after SRS were treated with SLA (two patients underwent two SLAs for independent lesions, and a third underwent two serial SLAs for independent BMs). Histology of the BM treated included: breast (n=8), lung (n=6), melanoma (n=5), colon (n=2), ovarian (n=2), bladder (n=1), esophageal (n=1), and sarcoma (n=1). With a median follow-up of 145 days (range 64 to 794 days), nine of the SLA treated-BMs progressed despite treatment (35%). All cases of progression occurred in BMs where <80% ablation was achieved, while no disease progression was observed in BMs where >80% ablation was achieved. Five BMs were treated with SLA followed one month later by adjuvant SRS (5 Gy x 5 regimen). No disease progression was observed in these patients despite ablation efficiency of <80%, suggesting that adjuvant hypo-fractionated SRS enhances the efficacy of SLA. Of the 23 SLA-treated patients, three patients suffered transient hemiparesis (12%), one patient developed hydrocephalus requiring temporary ventricular drainage (4%), and one patient who underwent SLA of a 16.9cc lesion suffered neurologic deficit requiring an emergent hemicraniectomy (4%). While there is significant heterogeneity in corticosteroid treatment post-SLA, most patients underwent a two-week taper. SLA is an effective treatment option for BMs that fail SRS. Ablation of >80% of BMs is associated with decreased risk of disease progression. The efficacy of SLA in this setting may be augmented by adjuvant hypo-fractionated SRS.
Clinical Development of Novel Drug–Radiotherapy Combinations
Authors: Saif S. Ahmad, Marka R. Crittenden, Phuoc T. Tran, Paul G. Kluetz, Gideon M. Blumenthal, Helen Bulbeck, Richard D. Baird, Kaye J. Williams, Tim Illidge, Stephen M. Hahn, Theodore S. Lawrence, Patricia A. Spears, Amanda J. Walker, Ricky A. Sharma
Journal: Clinical Cancer Research (2018)

Abstract Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized. In view of this lack of progress, the FDA–AACR–ASTRO Clinical Development of Drug–Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups, and the FDA to discuss challenges to introducing new drug–radiotherapy combinations to the clinic. This Perspectives in Regulatory Science and Policy article summarizes the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies that efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation, and patient-reported outcomes. Novel approaches including immune-oncology or DNA-repair inhibitor agents combined with radiotherapy should be prioritized. In this article, we focus on how the regulatory challenges associated with defining a new drug–radiotherapy combination can be overcome to improve clinical outcomes for patients with cancer.
Bleomycin Pulmonary Toxicity in Adult Saudi Patients with Hodgkin’s Lymphoma
Authors: Mubarak M Al-Mansour, Wafa A Al-jizani, Turki Al-fayea, Shafi Ruaa, Ghieth A Kazkaz, Ali M Bayer, Meteb AL-Foheidi, Ezzeldin M Ibrahim
Journal: Blood (2014)
Image-guided chemotherapy with specifically tuned blood brain barrier permeability in glioma margins
Authors: Xihui Gao, Qi Yue, Yikang Liu, Dandan Fan, Kun Fan, Sihan Li, Jun Qian, Limei Han, Fang Fang, Fulin Xu, Daoying Geng, Liang Chen, Xin Zhou, Ying Mao, Cong Li
Journal: Theranostics (2018)

Blood-brain barrier (BBB) disruption is frequently observed in the glioma region.However, the tumor uptake of drugs is still too low to meet the threshold of therapeutic purpose.Method: A tumor vasculature-targeted nanoagonist was developed.Glioma targeting specificity of the nanoagonist was evaluated by in vivo optical imaging.BBB permeability at the glioma margin was quantitatively measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).Single-photon emission computed tomography imaging/computed tomography (SPECT/CT) quantitatively determined the glioma uptake of the radiolabeled model drug.T2-weighted MRI monitored the tumor volume.Results: Immunostaining studies demonstrated that the BBB remained partially intact in the invasive margin of patients' gliomas regardless of their malignancies.DCE-MRI showed that vascular permeability in the glioma margin reached its maximum at 45 min post nanoagonist administration.In vivo optical imaging indicated the high glioma targeting specificity of the nanoagonist.SPECT/CT showed the significantly enhanced glioma uptake of the model drug after pre-treatment with the nanoagonist.Image-guided paclitaxel injection after nanoagonist-mediated BBB modulation more efficiently attenuated tumor growth and extended survival than in animal models treated with paclitaxel or temozolomide alone.Conclusion: Thus, image-guided drug delivery following BBB permeability modulation holds promise to enhance the efficacy of chemotherapeutics to glioma.
Incidence and Factors Associated With HBV Relapse After Cessation of Entecavir or Tenofovir in Patients With HBsAg Below 100 IU/mL
Authors: Tzu-Ning Tseng, Tsung-Hui Hu, Jing-Houng Wang, Yuan-Hung Kuo, Chao-Hung Hung, Sheng-Nan Lu, Wen-Juei Jeng, Chien-Hung Chen
Journal: Clinical Gastroenterology and Hepatology (2020)
“Living Robots”: Ethical Questions About Xenobots
Authors: Simon Coghlan, Kobi Leins
Journal: The American Journal of Bioethics (2020)

Xenobots have been called “novel living machines” and “living robots” (Brown 2020). A coauthor of the paper (Kriegman et al. 2020) that recently introduced xenobots said, “They’re neither a traditi...
Endocarditis in Patients With Ascending Aortic Prosthetic Graft
Authors: Antonio Ramos-Martínez, Silvia Blanco-Alonso, Jorge Calderón-Parra, Begoña Rodríguez-Alfonso, Daniel Martínez-López, Marta Cobo-Marcos, Ana Fernández-Cruz, Elena Múñez-Rubio, Carlos Esteban Martín-López, Alberto Forteza-Gil
Journal: Journal of the American College of Cardiology (2020)
Best Practices for Preclinical In Vivo Testing of Cancer Nanomedicines
Authors: Danielle M. Valcourt, Chintan H. Kapadia, Mackenzie A. Scully, Megan N. Dang, Emily S. Day
Journal: Advanced Healthcare Materials (2020)

Significant advances have been made in the development of nanoparticles for cancer treatment in recent years. Despite promising results in preclinical animal models, cancer nanomedicines often fail in clinical trials. This failure rate could be reduced by defining stringent criteria for testing and quality control during the design and development stages, and by performing carefully planned preclinical studies in relevant animal models. This article discusses best practices for the evaluation of nanomedicines in murine tumor models. First, a recommended set of experiments to perform is introduced, including discussion of the types of data to collect during these studies. This is followed by an outline of various tumor models and their clinical relevance. Next, different routes of nanoparticle administration are overviewed, followed by a summary of important controls to include in in vivo studies of nanomedicine. Finally, animal welfare considerations are discussed, and an overview of the steps involved in achieving US Food and Drug Administration approval after animal studies are completed is provided. Researchers should use this report as a guideline for effective preclinical evaluation of cancer nanomedicine. As the community adopts best practices for in vivo testing, the rate of clinical translation of cancer nanomedicines is likely to improve.