tbuckley/cabot-search huggingface dataset:
COL7A1 Editing via CRISPR/Cas9 in Recessive Dystrophic Epidermolysis Bullosa
Authors: Stefan Hainzl, Patricia Peking, Thomas Kocher, Eva M. Murauer, Fernando Larcher, Marcela Del Rio, Blanca Duarte, Markus Steiner, Alfred Klausegger, Johann W. Bauer, Julia Reichelt, Ulrich Koller
Journal: Molecular Therapy (2017)

Designer nucleases allow specific and precise genomic modifications and represent versatile molecular tools for the correction of disease-associated mutations. In this study, we have exploited an ex vivo CRISPR/Cas9-mediated homology-directed repair approach for the correction of a frequent inherited mutation in exon 80 of COL7A1, which impairs type VII collagen expression, causing the severe blistering skin disease recessive dystrophic epidermolysis bullosa. Upon CRISPR/Cas9 treatment of patient-derived keratinocytes, using either the wild-type Cas9 or D10A nickase, corrected single-cell clones expressed and secreted similar levels of type VII collagen as control keratinocytes. Transplantation of skin equivalents grown from corrected keratinocytes onto immunodeficient mice showed phenotypic reversion with normal localization of type VII collagen at the basement membrane zone, compared with uncorrected keratinocytes, as well as fully stratified and differentiated skin layers without indication of blister development. Next-generation sequencing revealed on-target efficiency of up to 30%, whereas nuclease-mediated off-target site modifications at predicted genomic loci were not detected. These data demonstrate the potential of the CRISPR/Cas9 technology as a possible ex vivo treatment option for genetic skin diseases in the future.
Invasive cervical cancer after treatment for cervical intraepithelial neoplasia (multiple letters) [8]
Authors: F. Gardeil, O. McNally, J. Skinner, M. J. Turner, W. P. Soutter, A. De Barros Lopes, E. Paraskevaidis, H. C. Kitchener, E. Vaccher, U. Tirelli, A. E. Raffle
Journal: The Lancet (1997)
Total-Body PET Scanner Prototype Due Next Year
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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
Non-invasive <i>in vivo</i> imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin
Authors: Lovro Kramer, Miha Renko, Janja Završnik, Dušan Turk, Markus A. Seeger, Olga Vasiljeva, Markus G. Grütter, Vito Turk, Boris Turk
Journal: Theranostics (2017)

Cysteine cathepsins often contribute to cancer progression due to their overexpression in the tumour microenvironment and therefore present attractive targets for non-invasive diagnostic imaging.However, the development of highly selective and versatile small molecule probes for cathepsins has been challenging.Here, we targeted tumour-associated cathepsin B using designed ankyrin repeat proteins (DARPins).The selective DARPin 8h6 inhibited cathepsin B with picomolar affinity (Ki = 35 pM) by binding to a site with low structural conservation in cathepsins, as revealed by the X-ray structure of the complex.DARPin 8h6 blocked cathepsin B activity in tumours ex vivo and was successfully applied in in vivo optical imaging in two mouse breast cancer models, in which cathepsin B was bound to the cell membrane or secreted to the extracellular milieu by tumour and stromal cells.Our approach validates cathepsin B as a promising diagnostic and theranostic target in cancer and other inflammation-associated diseases.
Expanding the Baveno VI criteria for the screening of varices in patients with compensated advanced chronic liver disease
Authors: Salvador Augustin, Mònica Pons, James B. Maurice, Christophe Bureau, Horia Stefanescu, Michel Ney, Hélène Blasco, Bogdan Procopet, Emmanuel Tsochatzis, Rachel H. Westbrook, Jaime Bosch, Annalisa Berzigotti, Juan G. Abraldes, Joan Genescà
Journal: Hepatology (2017)

Patients with compensated advanced chronic liver disease (cACLD) can safely avoid screening endoscopy with a platelet count >150 × 109 cells/L and a liver stiffness measurement (LSM) <20 kPa (Baveno VI criteria). However, the total number of avoided endoscopies using this rule is relatively low. We aimed at expanding the Baveno VI criteria and validating them in additional cohorts. Patients from the Anticipate cohort (499 patients with cACLD of different etiologies) were used to study the performance of different thresholds of platelets and LSM for the identification of patients at very low risk (<5%) of having varices needing treatment (VNT). The new criteria (Expanded-Baveno VI) were validated in two additional cohorts from London (309 patients) and Barcelona (117 patients). The performance of the new criteria by etiology of cACLD was also assessed. The best new expanded classification rule was platelet count >110 × 109 cells/L and LSM <25 kPa. This was validated in the two additional cohorts. Overall, the Expanded-Baveno VI criteria would potentially spare 367 (40%) endoscopies (21% with Baveno VI criteria) with a risk of missing VNT of 1.6% (95% confidence interval, 0.7%-3.5%) in patients within the criteria and 0.6% (95% confidence interval, 0.3%-1.4%) in the overall population of 925 patients evaluated. The Expanded-Baveno VI criteria performed well in patients with cACLD with hepatitis C virus and alcoholic and nonalcoholic steatohepatitis.The new Expanded-Baveno VI criteria spare more endoscopies than the original criteria with a minimal risk of missing VNT in most of the main etiologies of cACLD. (Hepatology 2017;66:1980-1988).
Abstract 73: Aberrant Activation of γ2-AMPK Increases Cardiac Growth Through Cellular Hypertrophy and Hyperplasia
Authors: Maengjo Kim, Roger Hunter, Kei Sakamoto, Stephen Kolwicz, Lorena Menendez, Guohua Gong, Wang Wang, Christine Seidman, Jonathan Seidman, Rong Tian
Journal: Circulation Research (2012)

AMP-activated protein kinase (AMPK) is an energy sensor and a key regulator of cell metabolism, hence a promising drug target. Point mutations in the regulatory γ2-subunit (encoded by PRKAG2 gene) have been shown to cause a unique form of cardiomyopathy in humans characterized by cardiac growth, arrhythmias and glycogen storage. In previous studies, we demonstrated that the mutation of prkag2 (N488I) caused aberrant activation of AMPK leading to glycogen storage. However, elimination of glycogen storage by inhibiting glycogen synthase activity failed to normalize heart weight (HW) of the mutant mice. Here, we aimed to determine whether cardiac growth in PRKAG2 ardiomyopathy was dueto cellular hypertrophy or hyperplasia. We used transgenic mice expressing a mutant PRKAG2 (N488I) in the heart (TGγ2 N488I ) that faithfully recapitulated PRKAG2 cardiomyopathy. We determined HW and cardiac myocyte size in adult (2 months) and postnatal (2 weeks) hearts in WT and TGγ2 N488I . At 2 months, TGγ2 N488I hearts show a 2.4-fold increase in HW/BW (body weight) (10.3 ± 1.44 vs. 4.3± 0.17 mg/g) as well as cross-sectional cell surface area compared WT hearts (325 ± 13 vs. 155 ± 5.4 μm 2 ,p&lt;0.01), suggesting cellular hypertrophy in adult TGγ2 N488I heart. Furthermore, we observed increased mTOR activity evidenced by enhanced phosphorylation of mTOR (Ser2448) as well as its downstream targets S6 and 4E-BP. The HW of TGγ2 N488I was partially inhibited by treatment with rapamycin, an inhibitor of mTOR. Interestingly, the length and width of isolated cardiomyocytes from 2 weeks old mice were not different between the WT and TGγ2 N488I heart in spite of a 50% increase of HW of TGγ2 N488I mice. We observed a 2- fold increase in the expression of a proliferation marker, proliferating cell nuclear antigen (PCNA) during postnatal cardiac growth. Expression of Cyclin genes including cyclin D1, D2 and E1 was greatly increased in TGγ2 N488I hearts (2.4 - 4 fold, p&lt;0.01 vs. WT). Taken together, these data indicate that aberrant γ2-AMPK activation stimulates cardiac growth through increased cell number during postnatal growth period and increased cell size at adulthood. These results suggest a novel role of γ2-AMPK in the growth of cardiac myocytes.
Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging
Authors: Michelle M. Mielke, Clinton E. Hagen, Alexandra M. V. Wennberg, David C. Airey, Rodolfo Savica, David S. Knopman, Mary M. Machulda, Rosebud O. Roberts, Clifford R. Jack, Ronald C. Petersen, Jeffrey L. Dage
Journal: JAMA Neurology (2017)

The utility of plasma total tau level as a prognostic marker for cognitive decline and dementia is not well understood.To determine (1) the association between plasma total tau level, cognitive decline, and risk of mild cognitive impairment (MCI) and dementia; (2) whether this association differs by the presence of elevated brain amyloid β (Aβ); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months.The present analyses included 458 participants who were enrolled in a population-based cohort study between October 2008 and June 2013. All included participants had available plasma total tau levels, Aβ positron emission tomography imaging, and a complete neuropsychological examine at the same visit, as well as at least 1 follow-up visit.Concentration of plasma total tau.Risk of MCI and dementia; global and domain-specific cognitive decline.Of the 458 participants, 287 (62.7%) were men; mean (SD) age was 80.6 (5.6) years. Among cognitively normal (CN) participants oversampled for elevated brain Aβ, both the middle (hazard ratio [HR], 2.43; 95% CI, 1.25-4.72) and highest (HR, 2.02; 95% CI, 1.01-4.06) tertiles of plasma total tau level, compared with the lowest, were associated with an increased risk of MCI. Among participants with MCI, higher plasma total tau levels were not significantly associated with risk of dementia (all-cause dementia or Alzheimer disease). Among all participants, higher levels of plasma total tau, examined as a continuous variable, were associated with significant (P < .05) declines in global cognition, memory, attention, and visuospatial ability over a median follow-up of 3.0 years (range, 1.1-4.9 years). In additional analyses restricting the follow-up to 15 months, plasma total tau did not predict decline among CN participants. However, among participants with MCI, higher plasma total tau levels were associated with greater decline in both visuospatial ability (regression coefficient [b] = -0.50 [0.15], P < .001) and global cognition (b = -0.27 [0.10], P = .009) at 15 months. Adjusting for elevated brain Aβ did not attenuate any association. There was no interaction between plasma total tau level and brain Aβ for prognosis with any outcome.These results suggest that elevated plasma total tau levels are associated with cognitive decline, but the results differ based on cognitive status and the duration of follow-up. The association between plasma total tau levels and cognition is independent of elevated brain Aβ.
Abstract 244: Characterization Of Endogenous C-kit Positive Cells From Right Atrial Appendage Of Neonate And Adult Heart Patients
Authors: Savitha Deshmukh, Rachana Mishra, Sudhish Sharma, David Simpson, Sunjay Kaushal
Journal: Circulation Research (2013)

Background: Stem cell therapy provides novel regenerative strategy for congenital heart patients. We have previously identified two distinct subpopulations (c-kit+ cells and cardiosphere derived cells (hCDCs)) from right atrial appendage (RAA) of neonate and adult heart patients. We have characterized hCDCs from neonate and adult heart patients and found strong regenerative capacity in hCDC derived from neonatal hearts. The aim of this study is to characterize c-kit+ cells derived from neonate and adult heart patients. Methods: C-kit+ cells were isolated and expanded from RAA heart samples, ranging in weight from 20 mg to 300 mgs of tissues using the standard protocol. The atrial tissue was minced and suspended in Ham’s F12 medium containing collagenase NB 6. After digestion, cells were plated in c-kit growing media. C-kit+ cells were isolated using MACS column with &gt;90% homogeneity. Cells were characterized using FACS and immunofluorescence techniques. Results: The characterization of c-kit+ cells showed that these cells were co-expressing nkx2.5, GATA4 and FLK1 and negative for CD45, Lin and tryptase. The growth potential of c-kit+ cells was determined by use of doubling times which was never greater than 36 hours, computed by use of linear regression of log2 value of cell number. We observed neonate derived c-kit+ cells have more (2x) proliferation capacity compared to adult derived c-kit+ cells. During subsequent passages, c-kit expression was lost more in adult derived c-kit+ cells when compared to neonate derived c-kit+ cells. Conclusion: Neonate derived c-kit+ cells retain their stemness and have more proliferative capacity compared to adult derived c-kit+ cells. Based on our previous study and present data we believe that neonate derived c-kit+ cells may have higher regenerative capacity compared to adult derived c-kit+ cells.
Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span
Authors: Alexander V. Misharin, Luisa Morales-Nebreda, Paul A. Reyfman, Carla M. Cuda, James M. Walter, Alexandra C. McQuattie-Pimentel, Ching-I Chen, Kishore R. Anekalla, Nikita Joshi, Kinola J.N. Williams, Hiam Abdala-Valencia, Tyrone J. Yacoub, Monica Chi, Stephen Chiu, Francisco J. Gonzalez-Gonzalez, Khalilah Gates, Anna P. Lam, Trevor T. Nicholson, Philip J. Homan, Saul Soberanes, Salina Dominguez, Vince K. Morgan, Rana Saber, Alexander Shaffer, Monique Hinchcliff, Stacy A. Marshall, Ankit Bharat, Sergejs Berdnikovs, Sangeeta M. Bhorade, Elizabeth T. Bartom, Richard I. Morimoto, William E. Balch, Jacob I. Sznajder, Navdeep S. Chandel, Gökhan M. Mutlu, Manu Jain, Cara J. Gottardi, Benjamin D. Singer, Karen M. Ridge, Neda Bagheri, Ali Shilatifard, G.R. Scott Budinger, Harris Perlman
Journal: The Journal of Experimental Medicine (2017)

Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
STAG2 Mutations Are an Independent Prognostic Factor in Patients with Myelodysplastic Syndromes
Authors: Guillermo Montalban-Bravo, Koichi Takahashi, Ana Alfonso Pierola, Feng Wang, Song Xingzhi, Elias J. Jabbour, Tapan M. Kadia, Farhad Ravandi, Jorge E. Cortes, Courtney D DiNardo, Naval Daver, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Graciela M. Nogueras-Gonzalez, Xuelin Huang, Carlos E. Bueso-Ramos, Andrew Futreal, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2016)
Ethical Considerations for Nutrition Counseling About Processed Food—Reply
Authors: Robert H. Lustig
Journal: JAMA Pediatrics (2017)

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 Pediatrics 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 Pediatrics journal
SAT0216 Juxtaarticular and general osteoporosis in rheumatoid arthritis – results of dxa-densitometry
Authors: M Welcker, J Gottwalt, K Wienands, H Franck
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Juxtaarticular osteoporosis is an early sign of inflammation in conventional radigraphy in Rheumatoid arthritis. <h3>Objectives</h3> It should be shown weather juxtaarticular osteoporosis can be analysed by dual x-ray adsorption (DXA) and if there is a correlation to general bone loss in inflammatory joint disease. <h3>Methods</h3> 20 patients with Rheumatoid arthritis and 10 patients with Fibromyalgia were analysed by DXA (Hologic 2000). Regions of interest (ROIs) were the spine, the hip, the forearm and juxtaarticular subregions of the fingers. <h3>Results</h3> Patients with Rheumatoid arthritis showed decreased bone densities of the spine, the hip, the forearm and the juxtaarticular joint region of the fingers. This was the case in late and early stages (Larsen 0–1) of the disease. The relative loss of juxtaarticular bone density was in these cases comparable to the relative loss of bone density of the spine and the hip. <h3>Conclusion</h3> DXA revealed loss of juxtaarticular bone density in patients suffering from Rheumatoid arthritis. This could be a method for objective estimation of juxtaarticular osteoporosis in the early course of Rheumatoid arthritis. Infection related rheumatic diseases
Fusion Stage of HIV-1 Entry Depends on Virus-Induced Cell Surface Exposure of Phosphatidylserine
Authors: Elena Zaitseva, Eugene Zaitsev, Kamran Melikov, Anush Arakelyan, Mariana Marin, Rafael Villasmil, Leonid B. Margolis, Gregory B. Melikyan, Leonid V. Chernomordik
Journal: Cell Host & Microbe (2017)
Bioprosthetic Total Artificial Heart Induces a Profile of Acquired Hemocompatibility With Membranes Recellularization
Authors: David M. Smadja, Bruno Saubaméa, Sophie Susen, Michel Kindo, Patrick Bruneval, Eric Van Belle, Piet Jansen, Jean-Christian Roussel, Christian Latrémouille, Alain Carpentier
Journal: Journal of the American College of Cardiology (2017)
Should we screen for cirrhosis?
Authors: Mark Hudson, Nick Sheron, Ian A Rowe, Gideon M Hirschfield
Journal: BMJ (2017)

Recent guidelines are right to recommend screening high risk patients for liver cirrhosis, say <b>Mark Hudson</b> and <b>Nick Sheron</b>. But <b>Ian Rowe</b> and <b>Gideon Hirschfield</b> worry about the lack of a suitable screening test
A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis
Authors: Sara L. Colpitts, Eli J. Kasper, Abigail Keever, Caleb Liljenberg, Trevor Kirby, Krisztian Magori, Lloyd H. Kasper, Javier Ochoa-Repáraz
Journal: Gut Microbes (2017)

The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive multiple sclerosis (SP-MS). This non-obese diabetic (NOD) model of EAE develops a biphasic pattern of disease that more closely resembles the human condition when transitioning from relapsing-remitting (RR)-MS to SP-MS. We compared the gut microbiome of NOD mice with either mild or severe disease to that of non-immunized control mice. We found that the mice which developed a severe secondary form of EAE harbored a dysbiotic gut microbiome when compared with the healthy control mice. Furthermore, we evaluated whether treatment with a cocktail of broad-spectrum antibiotics would modify the outcome of the progressive stage of EAE in the NOD model. Our results indicated reduced mortality and clinical disease severity in mice treated with antibiotics compared with untreated mice. Our findings support the hypothesis that there are reciprocal effects between experimental CNS inflammatory demyelination and modification of the microbiome providing a foundation for the establishment of early therapeutic interventions targeting the gut microbiome that could potentially limit disease progression.
Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p.Q575E)
Authors: Joonhee Park, Jingyi Yang, Alexander T. Wenzel, Akshaya Ramachandran, Wung J. Lee, Jay C. Daniels, Juhyun Kim, Estela Martinez-Escala, Nduka Amankulor, Barbara Pro, Joan Guitart, Marc L. Mendillo, Jeffrey N. Savas, Titus J. Boggon, Jaehyuk Choi
Journal: Blood (2017)