tbuckley/cabot-search huggingface dataset:
In Situ Deployment of Engineered Extracellular Vesicles into the Tumor Niche via Myeloid‐Derived Suppressor Cells
Authors: Silvia Duarte‐Sanmiguel, Ana Panic, Daniel J. Dodd, Ana Salazar‐Puerta, Jordan T. Moore, William R. Lawrence, Kylie Nairon, Carlie Francis, Natalie Zachariah, William McCoy, Rithvik Turaga, Aleksander Skardal, William E. Carson, Natalia Higuita‐Castro, Daniel Gallego‐Perez
Journal: Advanced Healthcare Materials (2021)

Extracellular vesicles (EVs) have emerged as a promising carrier system for the delivery of therapeutic payloads in multiple disease models, including cancer. However, effective targeting of EVs to cancerous tissue remains a challenge. Here, it is shown that nonviral transfection of myeloid-derived suppressor cells (MDSCs) can be leveraged to drive targeted release of engineered EVs that can modulate transfer and overexpression of therapeutic anticancer genes in tumor cells and tissue. MDSCs are immature immune cells that exhibit enhanced tropism toward tumor tissue and play a role in modulating tumor progression. Current MDSC research has been mostly focused on mitigating immunosuppression in the tumor niche; however, the tumor homing abilities of these cells present untapped potential to deliver EV therapeutics directly to cancerous tissue. In vivo and ex vivo studies with murine models of breast cancer show that nonviral transfection of MDSCs does not hinder their ability to home to cancerous tissue. Moreover, transfected MDSCs can release engineered EVs and mediate antitumoral responses via paracrine signaling, including decreased invasion/metastatic activity and increased apoptosis/necrosis. Altogether, these findings indicate that MDSCs can be a powerful tool for the deployment of EV-based therapeutics to tumor tissue.
No Strong Evidence on Liver Transplant for Colorectal Cancer Liver Metastasis Over Portal Vein Embolization Associated With Liver Resection
Authors: Abudusalamu Aini, Qian Lu, Jiahong Dong
Journal: JAMA Surgery (2021)

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 Journals 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
Pyronaridine–artesunate or dihydroartemisinin–piperaquine combined with single low-dose primaquine to prevent Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a four-arm, single-blind, phase 2/3, randomised trial
Authors: William Stone, Almahamoudou Mahamar, Koualy Sanogo, Youssouf Sinaba, Sidi M Niambele, Adama Sacko, Sekouba Keita, Ahamadou Youssouf, Makonon Diallo, Harouna M Soumare, Harparkash Kaur, Kjerstin Lanke, Rob ter Heine, John Bradley, Djibrilla Issiaka, Halimatou Diawara, Sekou F Traore, Teun Bousema, Chris Drakeley, Alassane Dicko
Journal: The Lancet Microbe (2021)

Pyronaridine-artesunate is the most recently licensed artemisinin-based combination therapy. WHO has recommended that a single low dose of primaquine could be added to artemisinin-based combination therapies to reduce
NLRP3 inflammasome activation triggers gasdermin D–independent inflammation
Authors: Chun Wang, Tong Yang, Jianqiu Xiao, Canxin Xu, Yael Alippe, Kai Sun, Thirumala-Devi Kanneganti, Joseph B. Monahan, Yousef Abu-Amer, Judy Lieberman, Gabriel Mbalaviele
Journal: Science Immunology (2021)

Sustained stimulation of the NLRP3 inflammasome causes inflammation in the absence of GSDMD.
Covid-19: UK needs more doctors to support post-pandemic recovery, say leaders
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The UK must train more doctors to support the post-pandemic recovery of services, England’s national medical director has told MPs.

Giving evidence to the Health and Social Care Committee on 19 October, Stephen Powis highlighted that the UK had fewer doctors per head of population than many comparable nations and that increasing this number was fundamental to tackling the treatment backlog.

“We do need more doctors,” he said. “The UK has 2.8 doctors per 100 000 of the population including GPs; the European average is 3.7, [the] OECD average is 3.5. Having said that, it’s a long time from medical school to becoming …
Why healthcare needs rebels
Authors: Fiona Godlee
Journal: BMJ (2021)

Members of the Independent Scientific and Advisory Group for Emergencies may be surprised to find themselves portrayed as rebel scientists (doi:10.1136/bmj.n2504),1 and critics may see this as yet another reason to distrust or dismiss this self-appointed group. But rebels they have been, and we need rebels if things are to change. Opinions differ as to whether iSAGE has made a positive difference in the UK’s response to the covid-19 pandemic, but it has definitely achieved one thing. Through its frequent and open engagement with the …
MA08.05 Integrating Genomic and Transcriptomic Features Predict the Recurrence Risk of Stage IA Non-Small Cell Lung Cancer
Authors: S. Zhang, H. Jiang, X. Chen, X. Zhu, J. Bai, Q. Wu, R. Hu, J. Zheng, X. Xia, Y. Xun, J. Zhang, S. Ma
Journal: Journal of Thoracic Oncology (2021)
Congenital X‐linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in <scp>SEPT6</scp>
Authors: Raffaele Renella, Katelyn Gagne, Ellen Beauchamp, Jonathan Fogel, Aleksej Perlov, Mireia Sola, Thorsten Schlaeger, Inga Hofmann, Akiko Shimamura, Benjamin L. Ebert, Klaus Schmitz‐Abe, Kyriacos Markianos, Kristi Murphy, Liang Sun, Shira Rockowitz, Piotr Sliz, Dean R. Campagna, Timothy A. Springer, Christopher Bahl, Suneet Agarwal, Mark D. Fleming, David A. Williams
Journal: American Journal of Hematology (2021)

Septins play key roles in mammalian cell division and cytokinesis but have not previously been implicated in a germline human disorder. A male infant with severe neutropenia and progressive dysmyelopoiesis with tetraploid myeloid precursors was identified. No known genetic etiologies for neutropenia or bone marrow failure were found. However, next-generation sequencing of germline samples from the patient revealed a novel, de novo germline stop-loss mutation in the X-linked gene SEPT6 that resulted in reduced SEPT6 staining in bone marrow granulocyte precursors and megakaryocytes. Patient skin fibroblast-derived induced pluripotent stem cells (iPSCs) produced reduced myeloid colonies, particularly of the granulocyte lineage. CRISPR/Cas9 knock-in of the patient's mutation or complete knock-out of SEPT6 was not tolerated in non-patient-derived iPSCs or human myeloid cell lines, but SEPT6 knock-out was successful in an erythroid cell line and resulting clones revealed a propensity to multinucleation. In silico analysis predicts that the mutated protein hinders the dimerization of SEPT6 coiled-coils in both parallel and antiparallel arrangements, which could in turn impair filament formation. These data demonstrate a critical role for SEPT6 in chromosomal segregation in myeloid progenitors that can account for the unusual predisposition to aneuploidy and dysmyelopoiesis.
Targeting Vascular Risk Factors to Reduce Dementia Incidence in Old Age
Authors: Marieke P. Hoevenaar-Blom, Edo Richard, Eric P. Moll van Charante, Lennard L. van Wanrooij, Wim B. Busschers, Jan W. van Dalen, Wim A. van Gool
Journal: JAMA Neurology (2021)

This follow-up analysis of a randomized clinical trial investigates the association of multidomain interventions targeting vascular risk factors with dementia incidence among community-dwelling older adults.
FP14.03 Diagnostic Accuracy in Central Pulmonary Carcinoid tumors is Dependent of Biopsy Size
Authors: E. Reuling, D. Naves, J. Daniels, C. Dickhoff, P. Kortman, P. Plaisier, E. Thunnissen, T. Radonic
Journal: Journal of Thoracic Oncology (2021)
Receptor binding domain‐IgG levels correlate with protection in residents facing SARS‐CoV‐2 B.1.1.7 outbreaks
Authors: Hubert Blain, Edouard Tuaillon, Lucie Gamon, Amandine Pisoni, Stéphanie Miot, Valentin Delpui, Nejm Si‐Mohamed, Clémence Niel, Yves Rolland, Brigitte Montes, Soraya Groc, Sophia Rafasse, Anne‐Marie Dupuy, Nathalie Gros, Delphine Muriaux, Marie‐Christine Picot, Jean Bousquet
Journal: Allergy (2021)

Limited information exists on nursing home (NH) residents regarding BNT162b2 vaccine efficacy in preventing SARS-CoV-2 and severe COVID-19, and its association with post-vaccine humoral response.396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-qPCR). SARS-CoV-2 receptor-binding domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-qPCR-positive residents and serum neutralizing antibodies in vaccinated residents from one NH.The incidence of positive RT-qPCR was lower in residents vaccinated by two doses (72/317; 22.7%) vs one dose (10/31; 32.3%) or non-vaccinated residents (21/48; 43.7%; p < .01). COVID-19-induced deaths were observed in 5 of the 48 non-vaccinated residents (10.4%), in 2 of the 31 who had received one dose (6.4%), and in 3 of the 317 (0.9%) who had received two doses (p = .0007). Severe symptoms were more common in infected non-vaccinated residents (10/21; 47.6%) than in infected vaccinated residents (15/72; 21.0%; p = .002). Higher levels of RBD-IgG (n = 325) were associated with a lower SARS-CoV-2 incidence. No in vitro serum neutralization activity was found for RBD-IgG levels below 1050 AU/ml. RBD-IgG levels were inversely associated with N-Ag levels, found as a risk factor of severe COVID-19.Two BNT162b2 doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. Post-vaccine RBD-IgG levels correlate with BNT162b2 protection against SARS-CoV-2 B.1.1.7.
FP12.08 Lung Adenocarcinomas with ROS1 Rearrangement show Diffuse Strong ROS1 Immunohistochemical Staining
Authors: T. Fielder, J. Butler, G. Tierney, M. Holmes, K.Y. Lam, L. Satgunaseelan, A. Colebatch, A. Mahar, R. Gupta, S. O'Toole, W. Cooper
Journal: Journal of Thoracic Oncology (2021)
P53.03 The Characteristics of FGFR Genetic Aberrations in Chinese Lung Cancer Patients
Authors: X. Zhang, Z. Yu, C. Li, J. Shi, B. Ni, D. Jiang, L. Yang, X. Shen, M. Zhang, D. Gu, R. Chen, X. Xia
Journal: Journal of Thoracic Oncology (2021)
Self-Assembly of DNA Molecules: Towards DNA Nanorobots for Biomedical Applications
Authors: Yong Hu
Journal: Cyborg and Bionic Systems (2021)

DNA nanotechnology takes DNA molecule out of its biological context to build nanostructures that have entered the realm of robots and thus added a dimension to cyborg and bionic systems. Spurred by spring-like properties of DNA molecule, the assembled nanorobots can be tuned to enable restricted, mechanical motion by deliberate design. DNA nanorobots can be programmed with a combination of several unique features, such as tissue penetration, site-targeting, stimuli responsiveness, and cargo-loading, which makes them ideal candidates as biomedical robots for precision medicine. Even though DNA nanorobots are capable of detecting target molecule and determining cell fate via a variety of DNA-based interactions both in vitro and in vivo, major obstacles remain on the path to real-world applications of DNA nanorobots. Control over nanorobot’s stability, cargo loading and release, analyte binding, and dynamic switching both independently and simultaneously represents the most eminent challenge that biomedical DNA nanorobots currently face. Meanwhile, scaling up DNA nanorobots with low-cost under CMC and GMP standards represents other pertinent challenges regarding the clinical translation. Nevertheless, DNA nanorobots will undoubtedly be a powerful toolbox to improve human health once those remained challenges are addressed by using a scalable and cost-efficient method.
The missing role of diagnosis of confined placental mosaicism in the management of fetal growth restriction
Authors: Sedigheh Hantoushzadeh, Maasoumeh Saleh, Behnaz Nouri, Farzaneh Nazari, Tayyebali Salmani
Journal: Human Reproduction Update (2021)

Dear Sir, We have read the study by Eggenhuizen et al. (2021) and wanted to congratulate the authors for this prosperous article and make some minor contributions. In this article, the relationship between confined placental mosaicism (CPM) and fetal growth restriction (FGR), fetal structural anomalies, premature birth and low birth weight is analyzed. These adverse outcomes were more distinct in CPM trisomy 16 (T16) cases and FGR was reported in 81.5% of cases. After confirming the diagnosis of FGR, the next step is to determine the cause. Obstetric imaging and laboratory evaluations are performed to look for fetal and placental etiologies. A detailed fetal anatomic survey should be done due to the 10% risk of fetal anomalies. Fetal genetic studies are indicated in the cases of FGR with major fetal structural abnormalities, ultrasound markers of aneuploidy, polyhydramnios, partial molar pregnancy and also in early-onset severe symmetrical FGR. CPM refers to...
Temporal manipulation of Cdkl5 reveals essential postdevelopmental functions and reversible CDKL5 deficiency disorder–related deficits
Authors: Barbara Terzic, M. Felicia Davatolhagh, Yugong Ho, Sheng Tang, Yu-Ting Liu, Zijie Xia, Yue Cui, Marc V. Fuccillo, Zhaolan Zhou
Journal: Journal of Clinical Investigation (2021)

CDKL5 deficiency disorder (CDD) is an early onset, neurodevelopmental syndrome associated with pathogenic variants in the X-linked gene encoding cyclin-dependent kinase-like 5 (CDKL5). CDKL5 has been implicated in neuronal synapse maturation, yet its postdevelopmental necessity and the reversibility of CDD-associated impairments remain unknown. We temporally manipulated endogenous Cdkl5 expression in male mice and found that postdevelopmental loss of CDKL5 disrupts numerous behavioral domains, hippocampal circuit communication, and dendritic spine morphology, demonstrating an indispensable role for CDKL5 in the adult brain. Accordingly, restoration of Cdkl5 after the early stages of brain development using a conditional rescue mouse model ameliorated CDD-related behavioral impairments and aberrant NMDA receptor signaling. These findings highlight the requirement of CDKL5 beyond early development, underscore the potential for disease reversal in CDD, and suggest that a broad therapeutic time window exists for potential treatment of CDD-related deficits.
Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma
Authors: Daniel J. Gross, Navin K. Chintala, Raj G. Vaghjiani, Rachel Grosser, Kay See Tan, Xiaoyu Li, Jennie Choe, Yan Li, Rania G. Aly, Katsura Emoto, Hua Zheng, Joseph Dux, Waseem Cheema, Matthew J. Bott, William D. Travis, James M. Isbell, Bob T. Li, David R. Jones, Prasad S. Adusumilli
Journal: Journal of Thoracic Oncology (2021)
The impact of the COVID-19 pandemic on paediatric glioma patients in low, middle, and high-income countries: a multicentre, international, observational cohort study
Authors: Soham Bandyopadhyay
Journal: Neuro-Oncology (2021)

Abstract Aims Paediatric cancer is a leading cause of non-communicable disease deaths for children worldwide, with more than 90% of deaths occurring in low-and-middle-income countries (LMICs). The COVID-19 pandemic may have exacerbated disparities in paediatric cancer outcomes between LMICs and HICs. The World Health Organization (WHO) Global Initiative for Childhood Cancer has identified gliomas as a common cancer that can act as a benchmark for assessing global paediatric cancer care. This study aims to ascertain the short and medium-term outcome across 17 countries during the COVID-19 pandemic by determining 30- and 90-day all-cause mortality rates for paediatric glioma patients who underwent treatment. Method A multicentre, international, mixed- (retrospective and prospective), collaborative cohort study in 17 countries. Patients were recruited between March 12th 2020 and July 12th 2020. Results 129 patients were recruited with the majority being histologically diagnosed as low-grade gliomas (n = 86/118, 72.9%). Seven children had a change to their planned chemotherapy treatment because of the COVID-19 pandemic. Similarly, seven children and eleven children had a change to their planned radiotherapy treatment and surgical treatment respectively because of the COVID-19 pandemic. Five patients died within the 30-day follow-up period, with all five patients being in LMICs. A sixth child, also in a LMIC, died within the 90-day follow-up period. This significant difference in mortality between LMICs and HICs was present when controlling for confounding for factors such as grade, ASA status, sex, weight, and age. Conclusion There has been relatively minimal change to the treatment of paediatric gliomas worldwide compared to their initial planned care. There was a significant difference in mortality for childhood gliomas between LMICS and high-income countries during the COVID-19 pandemic. There needs to be a concerted effort to improve equity in health outcomes globally.
The Gut–Brain Axis
Authors: Emeran A. Mayer, Karina Nance, Shelley Chen
Journal: Annual Review of Medicine (2021)

Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels. Alterations in gut-brain-microbiome interactions have been identified in rodent models of several digestive, psychiatric, and neurological disorders. While alterations in gut-brain interactions have clearly been established in irritable bowel syndrome, a causative role of the microbiome in irritable bowel syndrome remains to be determined. In the absence of specific microbial targets for more effective therapies, current approaches are limited to dietary interventions and centrally targeted pharmacological and behavioral approaches. A more comprehensive understanding of causative influences within the gut-brain-microbiome system and well-designed randomized controlled trials are needed to translate these exciting preclinical findings into effective therapies.
P59.14 Concordance and Performance of ddPCR Compared to NGS for The Detection of KRAS G12C Mutation
Authors: A. Ruiz-Patiño, J.K. Rodriguez, J. Avila Coy, P. Archila, A. Cardona Zorrilla, C. Sotelo, H. Carranza, C. Vargas, J. Otero, M. Bermudez, T. Gamez, O. Arrieta, L.L. Rojas Puentes, L. Corrales, C. Martin, J.E. Garcia-Robledo, N.D. Santoyo Sarmiento, C. Rolfo, R. Rosell
Journal: Journal of Thoracic Oncology (2021)
An interferon-inducible signature of airway disease from blood gene expression profiling
Authors: Jeong H. Yun, Sool Lee, Pooja Srinivasa, Jarrett Morrow, Robert Chase, Aadbida Saferali, Zhonghui Xu, Michael Cho, Peter Castaldi, Craig P. Hersh
Journal: European Respiratory Journal (2021)

Background The molecular basis of airway remodelling in chronic obstructive pulmonary disease (COPD) remains poorly understood. We identified gene expression signatures associated with chest computed tomography (CT) scan airway measures to understand molecular pathways associated with airway disease. Methods In 2396 subjects in the COPDGene Study, we examined the relationship between quantitative CT airway phenotypes and blood transcriptomes to identify airway disease-specific genes and to define an airway wall thickness (AWT) gene set score. Multivariable regression analyses were performed to identify associations of the AWT score with clinical phenotypes, bronchial gene expression and genetic variants. Results Type 1 interferon (IFN)-induced genes were consistently associated with AWT, square root wall area of a hypothetical airway with 10 mm internal perimeter (Pi10) and wall area percentage, with the strongest enrichment in AWT. A score derived from 18 genes whose expression was associated with AWT was associated with COPD-related phenotypes including reduced lung function (forced expiratory volume in 1 s percentage predicted β= −3.4; p&lt;0.05) and increased exacerbations (incidence rate ratio 1.7; p&lt;0.05). The AWT score was reproducibly associated with AWT in bronchial samples from 23 subjects (β=3.22; p&lt;0.05). The blood AWT score was associated with genetic variant rs876039, an expression quantitative trait locus for IKZF1 , a gene that regulates IFN signalling and is associated with inflammatory diseases. Conclusions A gene expression signature with IFN-stimulated genes from peripheral blood and bronchial brushings is associated with CT AWT, lung function and exacerbations. Shared genes and genetic associations suggest viral responses and/or autoimmune dysregulation as potential underlying mechanisms of airway disease in COPD.
Abstract 12821: Admission Cortisol Levels Are Associated to Risk Factors and Mortality in Acute Coronary Syndrome
Authors: Jose M Aladio, Diego Costa, Maia Matsudo, Sandra P Swieszkowski, Alejandra Scazziota, Diego Gonzalez, Alejandra Brignoli, Ricardo Perez de la Hoz
Journal: Circulation (2019)

Introduction: Acute coronary syndrome (ACS) is a stress-inducing situation, and cortisol (Cor) is a key stress response hormone. We aimed to study Cor′s behavior and prognostic value in ACS. Method...
The immunology of asymptomatic SARS-CoV-2 infection: what are the key questions?
Authors: Rosemary J. Boyton, Daniel M. Altmann
Journal: Nature reviews. Immunology (2021)

An important challenge during the COVID-19 pandemic has been to understand asymptomatic disease and the extent to which this may be a source of transmission. As asymptomatic disease is by definition hard to screen for, there is a lack of clarity about this aspect of the COVID-19 spectrum. Studies have considered whether the prevalence of asymptomatic disease is determined by differences in age, demographics, viral load, duration of shedding, and magnitude or durability of immunity. It is clear that adaptive immunity is strongly activated during asymptomatic infection, but some features of the T cell and antibody response may differ from those in symptomatic disease. Areas that need greater clarity include the extent to which asymptomatic disease leads to persistent symptoms (long COVID), and the quality, quantity and durability of immune priming required to confer subsequent protection. Individuals with asymptomatic COVID-19 can transmit the virus and may be at risk of long-term disease. In this Progress article, Boyton and Altman present current insights into immune responses in asymptomatic SARS-CoV-2 infection and discuss the relevance of asymptomatic disease for public health strategies.