tbuckley/cabot-search huggingface dataset:
Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study
Authors: Hannah Chung, Siyi He, Sharifa Nasreen, Maria E Sundaram, Sarah A Buchan, Sarah E Wilson, Branson Chen, Andrew Calzavara, Deshayne B Fell, Peter C Austin, Kumanan Wilson, Kevin L Schwartz, Kevin A Brown, Jonathan B Gubbay, Nicole E Basta, Salaheddin M Mahmud, Christiaan H Righolt, Lawrence W Svenson, Shannon E MacDonald, Naveed Z Janjua, Mina Tadrous, Jeffrey C Kwong
Journal: BMJ (2021)

Abstract Objective To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). Design Test negative design study. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. Interventions BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Main outcome measures Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. Results Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. Conclusions Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.
Two-stage degradation and novel functional endothelium characteristics of a 3-D printed bioresorbable scaffold
Authors: Tieying Yin, Ruolin Du, Yang Wang, Junyang Huang, Shuang Ge, Yuhua Huang, Youhua Tan, Qing Liu, Zhong Chen, Hanqing Feng, Jie Du, Yazhou Wang, Guixue Wang
Journal: Bioactive Materials (2021)

Bioresorbable scaffolds have emerged as a new generation of vascular implants for the treatment of atherosclerosis, and designed to provide a temporary scaffold that is subsequently absorbed by blood vessels over time. Presently, there is insufficient data on the biological and mechanical responses of blood vessels accompanied by bioresorbable scaffolds (BRS) degradation. Therefore, it is necessary to investigate the inflexion point of degradation, the response of blood vessels, and the pathophysiological process of vascular, as results of such studies will be of great value for the design of next generation of BRS. In this study, abdominal aortas of SD rats were received 3-D printed poly-l-actide vascular scaffolds (PLS) for various durations up to 12 months. The response of PLS implanted aorta went through two distinct processes: (1) the neointima with desirable barrier function was obtained in 1 month, accompanied with slow degradation, inflammation, and intimal hyperplasia; (2) significant degradation occurred from 6 months, accompanied with decreasing inflammation and intimal hyperplasia, while the extracellular matrix recovered to normal vessels which indicate the positive remodeling. These in vivo results indicate that 6 months is a key turning point. This "two-stage degradation and vascular characteristics" is proposed to elucidate the long-term effects of PLS on vascular repair and demonstrated the potential of PLS in promoting endothelium function and positive remodeling, which highlights the benefits of PLS and shed some light in the future researches, such as drug combination coatings design.
CysLT1 receptor signaling induces transcriptional upregulation of proprotein convertase furin expression: Potential implications in airway remodeling
Authors: M. R. la-Pleszczynski, C. T. ompson, S. M. Mahon, Y. B. ssé, C. M. D. bois, J. S. ankova
Journal: Journal of Allergy and Clinical Immunology (2007)
Nanovaccines silencing IL-10 production at priming phase for boosting immune responses to melanoma
Authors: Cao Dai Phung, Tuan Hiep Tran, Hanh Thuy Nguyen, Tien Tiep Nguyen, Jee-Heon Jeong, Sae Kwang Ku, Chul Soon Yong, Han-Gon Choi, Jong Oh Kim
Journal: Journal of Controlled Release (2021)
Targeting the EP4 receptor for prostaglandin E2 increases natural killer cell lytic activity and inhibits metastasis
Authors: Dawn Holt, Xinrong Ma, Namita Kundu, Amy Fulton
Journal: Cancer Research (2007)

7  Natural Killer (NK) cells are important to the control of tumor metastasis. NK function is compromised, however, by prostaglandin E2 (PGE2) synthesized by cyclooxygenase-2 (COX-2) which is highly expressed in breast cancer. PGE2 contributes to the high metastatic capacity of breast tumors. Our published data indicates that inhibiting prostaglandin production with either selective or non-selective COX inhibitors prevents metastasis. We then targeted downstream signaling of PGE2 via prostaglandin E (EP) receptors. The pharmacological antagonism of the EP4 receptor inhibits metastasis to the same degree as the COX inhibitors. The ability of COX inhibitors and EP4 receptor antagonists to limit tumor dissemination is highly dependent on functional NK cells. Inhibiting either PGE2 synthesis or signaling increases NK lytic activity against murine mammary tumor targets in vitro. Blockade of PGE2 also decreases the expression of MHC class I, an inhibitory NK ligand. Furthermore, the protective capability of COX inhibitors and EP receptor antagonist on metastasis is compromised in mice depleted of functioning NK cells. To further examine signaling through PGE2 receptors, we then silenced EP4 gene expression in our mammary tumor cells. We confirmed that EP4 shRNA inhibited EP4 agonist stimulated adenyl cyclase activation. Intravenous injection of EP4 shRNA mammary tumor cells into syngeneic mice inhibited metastasis. This anti-metastatic effect was consistent with our results using pharmacologic EP4 antagonists. These results support a mechanism whereby decreasing PGE2 synthesis using COX inhibitors or preventing PGE2 signaling through its EP4 receptor inhibits metastatic disease and contributes to the therapeutic outcome. These studies support further investigation of the role of EP4 in tumor behavior.
Inhibiting collagen I production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles
Authors: Yan Yan, Cancan Du, Xixi Duan, Xiaohan Yao, Jiajia Wan, Ziming Jiang, Zhongyu Qin, Wenqing Li, Longze Pan, Zhuoyu Gu, Fazhan Wang, Ming Wang, Zhihai Qin
Journal: Acta Pharmaceutica Sinica B (2021)

The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.
Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile
Authors: Hege Marie Vedeld, Marit M. Grimsrud, Kim Andresen, Heidi D. Pharo, Erik von Seth, Tom H. Karlsen, Hilde Honne, Vemund Paulsen, Martti A. Färkkilä, Annika Bergquist, Marine Jeanmougin, Lars Aabakken, Kirsten M. Boberg, Trine Folseraas, Guro E. Lind
Journal: Hepatology (2021)

Abstract Background and Aims Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Approach and Results Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC‐associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77–0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA ≤ 12 months following bile collection increased the accuracy for cancer detection, with a combined sensitivity of 100% (28/28) and a specificity of 90% (20/203). The specificity increased to 93% when only including patients with PSC with longtime follow‐up (&gt; 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls ( n = 23). Importantly, the bile samples from the CCA‐PSC ≤ 12 patients, all positive for the biomarkers, included both early‐stage and late‐stage CCA, different tumor growth patterns, anatomical locations, and carbohydrate antigen 19‐9 levels. Conclusions Using highly sensitive ddPCR to analyze robust epigenetic biomarkers, CCA in PSC was accurately detected in bile, irrespective of clinical and molecular features, up to 12 months before CCA diagnosis. The findings suggest a potential for these biomarkers to complement current detection and screening methods for CCA in patients with PSC.
A therapeutic cancer vaccine delivers antigens and adjuvants to lymphoid tissues using genetically modified T cells
Authors: Joshua R. Veatch, Naina Singhi, Shivani Srivastava, Julia L. Szeto, Brenda Jesernig, Sylvia M. Stull, Matthew Fitzgibbon, Megha Sarvothama, Sushma Yechan-Gunja, Scott E. James, Stanley R. Riddell
Journal: Journal of Clinical Investigation (2021)

Therapeutic vaccines that augment T cell responses to tumor antigens have been limited by poor potency in clinical trials. In contrast, the transfer of T cells modified with foreign transgenes frequently induces potent endogenous T cell responses to epitopes in the transgene product, and these responses are undesirable, because they lead to rejection of the transferred T cells. We sought to harness gene-modified T cells as a vaccine platform and developed cancer vaccines composed of autologous T cells modified with tumor antigens and additional adjuvant signals (Tvax). T cells expressing model antigens and a broad range of tumor neoantigens induced robust and durable T cell responses through cross-presentation of antigens by host DCs. Providing Tvax with signals such as CD80, CD137L, IFN-β, IL-12, GM-CSF, and FLT3L enhanced T cell priming. Coexpression of IL-12 and GM-CSF induced the strongest CD4+ and CD8+ T cell responses through complimentary effects on the recruitment and activation of DCs, mediated by autocrine IL-12 receptor signaling in the Tvax. Therapeutic vaccination with Tvax and adjuvants showed antitumor activity in subcutaneous and metastatic preclinical mouse models. Human T cells modified with neoantigens readily activated specific T cells derived from patients, providing a path for clinical translation of this therapeutic platform in cancer.
Antibody formation against SARS-CoV-2 in imatinib-treated COVID-19 patients
Authors: Alejandro Morales-Ortega, Ana Isabel Farfán-Sedano, Aida Izquierdo-Martínez, Cristina Llarena-Barroso, Beatriz Jaenes-Barrios, Nieves Mesa-Plaza, María Toledano-Macías, Guillermo Soria Fernández-Llamazares, Laura Molina-Esteban, Jaime García de Tena, Santiago Prieto-Menchero, Sonia Gonzalo-Pascua, Juan Víctor San Martín-López, David Bernal-Bello
Journal: Journal of Infection (2021)
26780 Patient experiences with teledermatology during the COVID-19 pandemic: A survey
Authors: Samuel Yeroushalmi, Sarah Hannah Millan, Kamaria Nelson, Andrew Sparks, Adam Friedman
Journal: Journal of the American Academy of Dermatology (2021)

Background: The COVID-19 pandemic has drastically changed the practice of dermatology as social distancing guidelines have led to a shift from in-office care to virtual telehealth (teledermatology). We aimed to determine patient satisfaction, perceived barriers, as well as indications for teledermatology appointments during the COVID-19 pandemic. Methods: A survey was sent out via SurveyMonkey's online platform to patients of the George Washington Medical Faculty Associates' Dermatology department who attended telehealth appointments during the COVID-19 pandemic. Results: Out of 894 invitations sent, 168 patients completed our survey. The most common reasons for making a telehealth appointment were for a new rash (11.6%), eczema (9.8%), and psoriasis (9.1%). The most common reasons respondents liked telehealth were because of time efficiency (81.1%), not requiring transportation (74.2%), and maintaining social distancing (73.6%). The most common reasons respondents did not like telehealth were due to lack of physical touch (26.8%) and feeling they received an inadequate assessment (15.7%). Very few patients reported that they were unlikely to undertake another telehealth visit (9.9%) or recommend a telehealth visit to others (6.9%). Conclusion: Dermatology patients likely perceive telehealth visits as a convenient and safe method for quality care during the COVID-19 pandemic. The lack of physical touch, inability to provide close inspection and/or procedural intervention can be frustrating for patients and therefore meaningful selection of appropriate cases for telehealth visits can optimize the patient experience. Overall, telemedicine represents an effective and safe vehicle for delivering care, especially during a global pandemic.
Discovery and validation of a three-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations: a case-control and observational cohort study
Authors: Ho Kwong Li, Myrsini Kaforou, Jesus Rodriguez-Manzano, Samuel Channon-Wells, Ahmad Moniri, Dominic Habgood-Coote, Rishi K Gupta, Ewurabena A Mills, Dominique Arancon, Jessica Lin, Yueh-Ho Chiu, Ivana Pennisi, Luca Miglietta, Ravi Mehta, Nelofar Obaray, Jethro A Herberg, Victoria J Wright, Pantelis Georgiou, Laura J Shallcross, Alexander J Mentzer, Michael Levin, Graham S Cooke, Mahdad Noursadeghi, Shiranee Sriskandan
Journal: The Lancet Microbe (2021)

Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department.
Low-count whole-body PET with deep learning in a multicenter and externally validated study
Authors: Akshay S. Chaudhari, Erik Mittra, Guido A. Davidzon, Praveen Gulaka, Harsh Gandhi, Adam Brown, Tao Zhang, Shyam Srinivas, Enhao Gong, Greg Zaharchuk, Hossein Jadvar
Journal: npj Digital Medicine (2021)

More widespread use of positron emission tomography (PET) imaging is limited by its high cost and radiation dose. Reductions in PET scan time or radiotracer dosage typically degrade diagnostic image quality (DIQ). Deep-learning-based reconstruction may improve DIQ, but such methods have not been clinically evaluated in a realistic multicenter, multivendor environment. In this study, we evaluated the performance and generalizability of a deep-learning-based image-quality enhancement algorithm applied to fourfold reduced-count whole-body PET in a realistic clinical oncologic imaging environment with multiple blinded readers, institutions, and scanner types. We demonstrate that the low-count-enhanced scans were noninferior to the standard scans in DIQ (p < 0.05) and overall diagnostic confidence (p < 0.001) independent of the underlying PET scanner used. Lesion detection for the low-count-enhanced scans had a high patient-level sensitivity of 0.94 (0.83-0.99) and specificity of 0.98 (0.95-0.99). Interscan kappa agreement of 0.85 was comparable to intrareader (0.88) and pairwise inter-reader agreements (maximum of 0.72). SUV quantification was comparable in the reference regions and lesions (lowest p-value=0.59) and had high correlation (lowest CCC = 0.94). Thus, we demonstrated that deep learning can be used to restore diagnostic image quality and maintain SUV accuracy for fourfold reduced-count PET scans, with interscan variations in lesion depiction, lower than intra- and interreader variations. This method generalized to an external validation set of clinical patients from multiple institutions and scanner types. Overall, this method may enable either dose or exam-duration reduction, increasing safety and lowering the cost of PET imaging.
PEG‐Polymer Encapsulated Aggregation‐Induced Emission Nanoparticles for Tumor Theranostics
Authors: Jun Dai, Xiaoqi Dong, Quan Wang, Xiaoding Lou, Fan Xia, Shixuan Wang
Journal: Advanced Healthcare Materials (2021)

Abstract In the field of tumor imaging and therapy, the aggregation‐caused quenching (ACQ) effect of fluorescent dyes at high concentration is a great challenge. In this regard, the aggregation‐induced emission luminogens (AIEgens) show great potential, since AIEgens effectively overcome the ACQ effect and have better fluorescence quantum yield, photobleaching resistance, and photosensitivity. Polyethylene glycol (PEG)‐polymer is the most commonly used carrier to prepare nanoparticles (NPs). The advantage of PEGylation is that it can greatly prolong the metabolic half‐life and reduce immunogenicity and toxicity. Considering that the hydrophobicity of most AIEgens hinders their application in organisms, the use of PEG‐polymer encapsulation is an effective strategy to overcome this obstacle. Importantly, bioactive functional groups can be modified on PEG‐polymers to enhance the biological effect of NPs. The combination of powerful AIEgens and PEG‐polymers provides a new strategy for tumor imaging and therapy, which is promising for clinical application.
Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study
Authors: J William L Brown, Nick G Cunniffe, Ferran Prados, Baris Kanber, Joanne L Jones, Edward Needham, Zoya Georgieva, David Rog, Owen R Pearson, James Overell, David MacManus, Rebecca S Samson, Jonathan Stutters, Charles ffrench-Constant, Claudia A M Gandini Wheeler-Kingshott, Carla Moran, Paul D Flynn, Andrew W Michell, Robin J M Franklin, Siddharthan Chandran, Daniel R Altmann, Declan T Chard, Peter Connick, Alasdair J Coles
Journal: The Lancet Neurology (2021)
LBA-5 Phase Ib study of the anti-TIGIT antibody tiragolumab in combination with atezolizumab in patients with metastatic esophageal cancer
Authors: Z. Wainberg, I. Matos, J. Delord, P. Cassier, M. Gil-Martin, T. Kim, P. LoRusso, R. Bahleda, A. Italiano, D. Mendus, T. Hoang, C. Xue, X. Wen, O. Carvalho, T. Pham, N. Patil, R. Meng, J. Bendell, A. Cervantes, B. Cho
Journal: Annals of Oncology (2021)
18F-FDG PET/CT Findings in a Rare Case of Paraneoplastic Vestibulocerebellar Syndrome Associated With Isolated Antiamphiphysin Antibodies
Authors: Shivaram Rao Komandla, Kousik Vankadari, Milap Milap, Hemanth V., Rukmini Mridula Kandadai
Journal: Clinical Nuclear Medicine (2021)

Abstract Paraneoplastic cerebellar degeneration (PCD) is an immune-mediated neurological disease characterized by adaptive immune response against onconeural antigens physiologically expressed in the cerebellum. It is characterized by presence of highly specific onconeural autoantibodies such as anti-Yo, anti-Hu, anti-Ri, and anti-Ma2 in the serum and cerebrospinal fluid as diagnostic biomarkers. Antiamphiphysin autoantibody–related paraneoplastic encephalitis is a less commonly seen autoimmune neurological disorder usually presenting as stiff person syndrome. We present an unusual case of isolated antiamphiphysin antibody–related PCD presenting as vestibulocerebellar syndrome with associated sensorineural hearing loss and sensory neuropathy. FDG PET helped in topographical localization of brain lesion along with early detection of extragonadal germ cell tumor in the retroperitoneum.
Relationship between obesity and structural brain abnormality: Accumulated evidence from observational studies
Authors: Yi-Peng Han, Xingyao Tang, Min Han, Jinkui Yang, Marly Augusto Cardoso, Jianbo Zhou, Rafael Simó
Journal: Ageing Research Reviews (2021)

We aimed to evaluate the relationship between obesity and structural brain abnormalities assessed by magnetic resonance imaging using data from 45 observational epidemiological studies, where five articles reported prospective longitudinal results. In cross-sectional studies' analyses, the pooled weighted mean difference for total brain volume (TBV) and gray matter volume (GMV) in obese/overweight participants was -11.59 (95 % CI: -23.17 to -0.02) and -10.98 (95 % CI: -20.78 to -1.18), respectively. TBV was adversely associated with BMI and WC, GMV with BMI, and hippocampal volume with BMI, WC, and WHR. WC/WHR are associated with a risk of lacunar and white matter hyperintensity (WMH). In longitudinal studies' analyses, BMI was not statistically associated with the overall structural brain abnormalities (for continuous BMI: RR = 1.02, 95 % CI: 0.94-1.12; for categorial BMI: RR = 1.18, 95 % CI: 0.75-1.85). Small sample size of prospective longitudinal studies limited the power of its pooled estimates. A higher BMI is associated with lower brain volume while greater WC/WHR, but not BMI, is related to a risk of lacunar infarct and WMH. Future longitudinal research is needed to further elucidate the specific causal relationships and explore preventive measures.
Interventions to Improve Communication at Hospital Discharge and Rates of Readmission
Authors: Christoph Becker, Samuel Zumbrunn, Katharina Beck, Alessia Vincent, Nina Loretz, Jonas Müller, Simon A. Amacher, Rainer Schaefert, Sabina Hunziker
Journal: JAMA Network Open (2021)

Shortcomings in the education of patients at hospital discharge are associated with higher risks for treatment failure and hospital readmission. Whether improving communication at discharge through specific interventions has an association with patient-relevant outcomes remains unclear.