tbuckley/cabot-search huggingface dataset:
CircPVT1: a pivotal circular node intersecting Long Non-Coding-PVT1 and c-MYC oncogenic signals
Authors: Alina Catalina Palcau, Valeria Canu, Sara Donzelli, Sabrina Strano, Claudio Pulito, Giovanni Blandino
Journal: Molecular Cancer (2022)

Abstract The role of circular RNAs in oncogenesis has begun to be widely studied in recent years, due to the significant impact that these molecules have in disease pathogenesis, as well as their potential for the future of innovative therapies. Moreover, due to their characteristically circular shape, circular RNAs are very resistant molecules to RNA degradation whose levels are easily assessed in body fluids. Accordingly, they represent an opportunity for the discovery of new diagnostic and prognostic markers in a wide range of diseases. Among circular RNAs, circPVT1 is a rather peculiar one that originates from the circularization of the exon 2 of the PVT1 gene that encodes a pro-tumorigenic long non-coding RNA named lncPVT1. There are a few examples of circular RNAs that derive from a locus producing another non-coding RNA. Despite their apparent transcriptional independence, which occurs using two different promoters, a possible synergistic effect in tumorigenesis cannot be excluded considering that both have been reported to correlate with the oncogenic phenotype. This complex mechanism of regulation appears to also be controlled by c-MYC. Indeed, the PVT1 locus is located only 53 Kb downstream c-MYC gene, a well-known oncogene that regulates the expression levels of about 15% of all genes. Here, we review circPVT1 origin and biogenesis highlighting the most important mechanisms through which it plays a fundamental role in oncogenesis, such as the well-known sponge activity on microRNAs, as well as its paradigmatic interactome link with lncPVT1 and c-MYC expression.
Hotspot<i>ESR1</i>Mutations Are Multimodal and Contextual Modulators of Breast Cancer Metastasis
Authors: Zheqi Li, Yang Wu, Megan E. Yates, Nilgun Tasdemir, Amir Bahreini, Jian Chen, Kevin M. Levine, Nolan M. Priedigkeit, Azadeh Nasrazadani, Simak Ali, Laki Buluwela, Spencer Arnesen, Jason Gertz, Jennifer K. Richer, Benjamin Troness, Dorraya El-Ashry, Qiang Zhang, Lorenzo Gerratana, Youbin Zhang, Massimo Cristofanilli, Maritza A. Montanez, Prithu Sundd, Callen T. Wallace, Simon C. Watkins, Caterina Fumagalli, Elena Guerini-Rocco, Li Zhu, George C. Tseng, Nikhil Wagle, Jason S. Carroll, Paul Jank, Carsten Denkert, Maria M. Karsten, Jens-Uwe Blohmer, Ben H. Park, Peter C. Lucas, Jennifer M. Atkinson, Adrian V. Lee, Steffi Oesterreich
Journal: Cancer Research (2022)

Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these mutations are known as mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of ESR1 mutations exclusively in distant but not local recurrences in five independent breast cancer cohorts. In concordance with transcriptomic profiling of ESR1-mutant tumors, genome-edited ESR1 Y537S and D538G-mutant cell models exhibited a reprogrammed cell adhesive gene network via alterations in desmosome/gap junction genes and the TIMP3/MMP axis, which functionally conferred enhanced cell-cell contacts while decreasing cell-extracellular matrix adhesion. In vivo studies showed ESR1-mutant cells were associated with larger multicellular circulating tumor cell (CTC) clusters with increased compactness compared with ESR1 wild-type CTCs. These preclinical findings translated to clinical observations, where CTC clusters were enriched in patients with ESR1-mutated metastatic breast cancer. Conversely, context-dependent migratory phenotypes revealed cotargeting of Wnt and ER as a vulnerability in a D538G cell model. Mechanistically, mutant ESR1 exhibited noncanonical regulation of several metastatic pathways, including secondary transcriptional regulation and de novo FOXA1-driven chromatin remodeling. Collectively, these data provide evidence for ESR1 mutation-modulated metastasis and suggest future therapeutic strategies for targeting ESR1-mutant breast cancer.
Measuring the Effect of Local Control From Radiotherapy in Patients With Pancreatic Adenocarcinoma
Authors: Nina N. Sanford, Beow Y. Yeap, Theodore S. Hong
Journal: JAMA Oncology (2022)

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 Oncology 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 Oncology journal
Instead of gimmicks, the NHS needs a workforce plan
Authors: Richard Vize
Journal: BMJ (2022)

The reported plan by health and social care secretary Sajid Javid to introduce "academy" style hospitals risks triggering organisational chaos in the NHS while failing to address any of its underlying problems. 1 According to the Times, barely six months after returning to the cabinet Javid is planning to force failing hospitals to become "reform trusts," similar to academy schools, to address wide variations in performance across the health service. 2 It is possible that chains of hospitals will be run by leading NHS managers, or even outside sponsors.
Decoding the annulus fibrosus cell atlas by scRNA-seq to develop an inducible composite hydrogel: A novel strategy for disc reconstruction
Authors: Han Wang, Di Wang, Beier Luo, Dong Wang, Haoruo Jia, Pandi Peng, Qiliang Shang, Jianxin Mao, Chu Gao, Ye Peng, Lu Gan, Junjie Du, Zhuojing Luo, Liu Yang
Journal: Bioactive Materials (2022)

Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The key pathological change during IVDD is dysfunction of the annulus fibrosus (AF). However, due to the lack of an in-depth understanding of AF biology, the methods to reconstruct the AF are very limited. In this study, the mice AF cell atlas were decoded by single-cell RNA sequencing to provide a guide for AF reconstruction. The results first identify a new population of AF cells, fibrochondrocyte-like AF cells, which synthesize both collagen I and collagen II and are potential functional cells for AF reconstruction. According to the dual features of the AF extracellular matrix, a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was produced. To obtain the ability to stimulate differentiation, the composite hydrogels were combined with a fibrochondrocyte-inducing supplement. Finally, reconstruction of the AF defects, by the novel AF stem cell-loaded composite hydrogel, could be observed, its amount of chondroid matrices recovered to 31.7% of AF aera which is significantly higher than that in other control groups. In summary, this study decodes the AF cell atlas, based on which a novel strategy for AF reconstruction is proposed.
list of contributors
Authors: Mitsuru Adachi, Sarah Austin, Leonard Bielory, Stephan C Bischoff, Attilio L Boner, Larry Borish, Piera Boschetto, David H Broide, William W Busse, Virginia L Calder, Thomas B Casale, Martin K Church, Jonathan Corren, Peter S Creticos, Adnan Custovic, Charles W DeBrosse, Pascal Demoly, Stephen R Durham, Mark S Dykewicz, Pamela W Ewan, Clive EH Grattan, Rebecca S Gruchalla, Melanie Hingorani, Stephen T Holgate, John W Holloway, Patrick G Holt, Alexander Kapp, Phil Lieberman, Susan Lightman, Martha Ludwig, Piero Maestrelli, Hans-Jorgen Malling, Fernando D Martinez, Marcus Maurer, Dean D Metcalfe, Dean J Naisbitt, Hans Oettgen, B Kevin Park, David B Peden, R Stokes Peebles, Thomas AE Platts-Mills, Susan Prescott, Marc E Rothenberg, Hugh A Sampson, Glenis K Scadding, Peter D Sly, Geoffrey A Stewart, Philip J Thompson, Peter Valent, Erika von Mutius, John O Warner, Thomas Werfel, Bruce L Zuraw
Journal: Allergy (2012)
Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies
Authors: Karim Taha, Feddo P. Kirkels, Arco J. Teske, Folkert W. Asselbergs, J. Peter van Tintelen, Pieter A. Doevendans, Shelby Kutty, Kristina H. Haugaa, Maarten J. Cramer
Journal: Journal of the American College of Cardiology (2022)
Exosome-mediated delivery of RBP-J decoy oligodeoxynucleotides ameliorates hepatic fibrosis in mice
Authors: Fei He, Wei-Na Li, Xin-Xin Li, Kang-Yi Yue, Juan-Li Duan, Bai Ruan, Jing-Jing Liu, Ping Song, Zhen-Sheng Yue, Kai-Shan Tao, Lin Wang
Journal: Theranostics (2022)

Rationale: Macrophages play multi-dimensional roles in hepatic fibrosis.Studies have implicated Notch signaling mediated by the transcription factor RBP-J in macrophage activation and plasticity.Additionally, we have previously shown that myeloid-specific disruption of RBP-J can ameliorate hepatic fibrosis in mice.Accordingly, we next asked whether blocking Notch signaling in macrophages could serve as a therapeutic strategy to treat hepatic fibrosis.In this study, we used a combination of transcription factor decoy oligodeoxynucleotides (ODNs) and exosomes to test this possibility.Methods: Hairpin-type decoy oligodeoxynucleotides (ODNs) were designed for the transcription factor RBP-J.The effects of RBP-J decoy ODNs on Notch signaling were evaluated by western blot, quantitative RT-PCR, luciferase reporter assays, and electrophoretic mobility shift assays.ODNs were loaded into HEK293T-derived exosomes by electroporation.A hepatic fibrosis mouse model was established by the intraperitoneal injection of carbon tetrachloride or bile duct ligation.Mice with hepatic fibrosis were administered exosomes loaded with RBP-J decoy ODNs via tail vein injection.The in vivo distribution of exosomes was analyzed by fluorescence labeling and imaging.Liver histology was examined using hematoxylin and eosin, Sirius red, and Masson staining, as well as immunohistochemical staining for Col1α1 and αSMA.Results: We found that RBP-J decoy ODNs could be efficiently loaded into exosomes and inhibit the activation of Notch signaling.Furthermore, exosomes administered via the tail vein were found to be primarily taken up by hepatic macrophages in mice with liver fibrosis.Importantly, RBP-J decoy ODNs delivered by exosomes could efficiently inhibit Notch signaling in macrophages and ameliorate hepatic fibrosis in mice.Conclusions: Combined, our data showed that the infusion of exosomes loaded with RBP-J decoy ODNs represents a promising therapeutic strategy for the treatment of hepatic fibrosis.
Characterization Of Alcohol Induced Respiratory Symptoms In Aspirin Exacerbated Respiratory Disease (AERD): The Happy Hour Study
Authors: Courtney Ramos, Justin Babbel, Hiral Thakrar, Kathleen Luskin, kristen Walters, Jeremy Waldram, Jeffrey Bulva, Ronald Simon, Katharine Woessner, Andrew White
Journal: Journal of Allergy and Clinical Immunology (2022)
Pairs of Mutually Compensatory Frameshifting Mutations Contribute to Protein Evolution
Authors: Dmitry Biba, Galya Klink, Georgii A Bazykin
Journal: Molecular Biology and Evolution (2022)

Insertions and deletions of lengths not divisible by 3 in protein-coding sequences cause frameshifts that usually induce premature stop codons and may carry a high fitness cost. However, this cost can be partially offset by a second compensatory indel restoring the reading frame. The role of such pairs of compensatory frameshifting mutations (pCFMs) in evolution has not been studied systematically. Here, we use whole-genome alignments of protein-coding genes of 100 vertebrate species, and of 122 insect species, studying the prevalence of pCFMs in their divergence. We detect a total of 624 candidate pCFM genes; six of them pass stringent quality filtering, including three human genes: RAB36, ARHGAP6, and NCR3LG1. In some instances, amino acid substitutions closely predating or following pCFMs restored the biochemical similarity of the frameshifted segment to the ancestral amino acid sequence, possibly reducing or negating the fitness cost of the pCFM. Typically, however, the biochemical similarity of the frameshifted sequence to the ancestral one was not higher than the similarity of a random sequence of a protein-coding gene to its frameshifted version, indicating that pCFMs can uncover radically novel regions of protein space. In total, pCFMs represent an appreciable and previously overlooked source of novel variation in amino acid sequences.
Bran reduces cholesterol saturation of bile
Journal: JAMA (1979)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Sustained Reductions in Hereditary Angioedema (HAE) Attack Rates Observed over 96 Weeks of Oral Berotralstat Treatment Regardless of Initial Response
Authors: H. James Wedner, Raffi Tachdjian, Timothy Craig, Philip Collis, Bhavisha Desai, Dianne Tomita, Teresa Caballero
Journal: Journal of Allergy and Clinical Immunology (2022)
A Single-Center, Randomized, 3-Way, Crossover Study to Evaluate the Effect of an Exhalation Delivery System on Nasal Nitric Oxide Concentrations in Patients with Chronic Rhinosinusitis Compared with Healthy Participants
Authors: Claudia Eisenlohr, Miguel Lanz, Kim Koob, Eric Zaccone, John McGinnis, John Messina
Journal: Journal of Allergy and Clinical Immunology (2022)
P137: WHAT’S IN A NAME? PATIENTS WANT US TO RETHINK ‘SICKLE CELL DISEASE’
Authors: C Otasowie, A Pearse, C Gilmour-Hamilton, F Dasaolu, K Fordwor, M Sinclair, N Igbineweka, S Njoku, S Hayes, W Atoyebi, N Roy
Journal: HemaSphere (2022)

Racism impacts all aspects of patient care, not least for those with Sickle Cell Disease (SCD). Minimal research exists in this area, despite being long identified as a compelling issue for patients [1], and highlighted as a “Top 10” Priority in a workshop during ASCAT 2019. In response, we conducted a series of workshops to explore how race and racism impacts the quality of care in the SCD community and to identify actionable areas of change. This comprised three 90 minute sessions held over Zoom in May, June and July 2021. Attendees included people living with SCD, doctors, nurses, medical students, and members of the local community. Outcomes broadly centred around the themes of medical education; public education; and ways of better supporting the SCD patient community. However, we were struck by a rich discussion on how the name ‘Sickle Cell Disease’ may, in itself, influence the mindset of caregivers and perpetuate stigma in both clinical and social settings. The term ‘Sickle Cell Anaemia’ traditionally refers to HbSS only, though OMIM uses it to cover all genotypes [2]. Meanwhile the ICD-10 classification code D57 refers to ‘Sickle Cell Disorders’, with sub-categories using ‘Disease’ and divided by genotype [3].From the workshops, the patient group shared a strong consensus view that Sickle Cell Disorder, rather than ‘Disease’, would be preferable as a more neutral term of reference. To verify the results of the workshop in an independent sample, a questionnaire was circulated to a small SCD patient support group (12 individuals) to assess their preference for one or other label. 9/12 (75%) preferred ‘Disorder’, one preferred ‘Disease’ and two expressed no preference. Which label was used by patients themselves, their families and friends, and their medical teams was important to patients, with 67% expressing a wish that this issue be pursued further. Interestingly, the acceptability of Disorder/Disease showed some variation by the patient’s country of birth. These findings point towards a pressing need for increased sensitivity around the language used to talk about illness, particularly where the condition has been historically stigmatised. References 1. Igbineweka et al. Medical science must address health disparities amongst different ethnic groups. Nat Hum Behav. 2021. 2. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 603903: 03/08/2021:. World Wide Web URL: https://omim.org/ 3. World Health Organization (WHO). The ICD-10 Classification of Mental and Behavioural Disorders. World Health Organization. 1993.
Deaths Associated With Allergenic Extracts
Journal: JAMA (1994)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Souvenir Cinchona Tercentenary Celebration and Exhibition at the Wellcome Historical Medical Museum, 54, Wigmore Street, London, W. 1.
Journal: JAMA (1931)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Fabrication of channeled scaffolds through polyelectrolyte complex (PEC) printed sacrificial templates for tissue formation
Authors: Haoyu Wang, Xiaqing Zhou, Juan Wang, Xinping Zhang, Meifeng Zhu, Hongjun Wang
Journal: Bioactive Materials (2022)

One of the pivotal factors that limit the clinical translation of tissue engineering is the inability to create large volume and complex three-dimensional (3D) tissues, mainly due to the lack of long-range mass transport with many current scaffolds. Here we present a simple yet robust sacrificial strategy to create hierarchical and perfusable microchannel networks within versatile scaffolds via the combination of embedded 3D printing (EB3DP), tunable polyelectrolyte complexes (PEC), and casting methods. The sacrificial templates of PEC filaments (diameter from 120 to 500 μm) with arbitrary 3D configurations were fabricated by EB3DP and then incorporated into various castable matrices (e.g., hydrogels, organic solutions, meltable polymers, etc.). Rapid dissolution of PEC templates within a 2.00 M potassium bromide aqueous solution led to the high fidelity formation of interconnected channels for free mass exchange. The efficacy of such channeled scaffolds for in vitro tissue formation was demonstrated with mouse fibroblasts, showing continuous cell proliferation and ECM deposition. Subcutaneous implantation of channeled silk fibroin (SF) scaffolds with a porosity of 76% could lead to tissue ingrowth as high as 53% in contrast to 5% for those non-channeled controls after 4 weeks. Both histological and immunofluorescence analyses demonstrated that such channeled scaffolds promoted cellularization, vascularization, and host integration along with immunoregulation.