tbuckley/cabot-search huggingface dataset:
Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice
Authors: Zhenglin Yang, Yali Chen, Concepcion Lillo, Jeremy Chien, Zhengya Yu, Michel Michaelides, Martin Klein, Kim A. Howes, Yang Li, Yuuki Kaminoh, Haoyu Chen, Chao Zhao, Yuhong Chen, Youssef Tawfik Al-Sheikh, Goutam Karan, Denis Corbeil, Pascal Escher, Shin Kamaya, Chunmei Li, Samantha Johnson, Jeanne M. Frederick, Yu Zhao, Changguan Wang, D. Joshua Cameron, Wieland B. Huttner, Daniel F. Schorderet, Frances L. Munier, Anthony T. Moore, David G. Birch, Wolfgang Baehr, David M. Hunt, David S. Williams, Kang Zhang
Journal: Journal of Clinical Investigation (2009)

During the preparation of the manuscript, the mice in Figure 2 were incorrectly identified as having been infected with S. mansoni.The correct legend for Figure 2A appears below.(A) Mice received 1 or more egg injections.Repeat egg injections were 5 d apart, such that mice for the 20-d time point had received 4 injections prior to sacrifice.At 5, 10, 15, and 20 d after the first immunization, CD4 + T cells from draining popliteal LNs were analyzed ex vivo for the expression of IL-4/GFP by flow cytometry.Numbers within plots indicate mean ± SD percent of CD4 + cells that were IL-4/GFP + (3 mice per group).The JCI regrets the error.
Survival and quality of life in the randomized, multicenter GLARIUS trial investigating bevacizumab/irinotecan versus standard temozolomide in newly diagnosed, MGMT-non-methylated glioblastoma patients.
Authors: Ulrich Herrlinger, Niklas Schaefer, Joachim Peter Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Franziska Friedrich, Veit Rohde, Florian Ringel, Christian Braun, Ralf Kohnen, Barbara Leutgeb, Claus Belka, Horst Urbach, Walter Stummer, Martin Glas
Journal: Journal of Clinical Oncology (2014)

2042^ Background: There is a need for more effective therapies in newly diagnosed glioblastoma (GBM) patients with an MGMT-non-methylated tumor. The GLARIUS trial explored the efficacy of bevacizumab (BEV) + Irinotecan (IRI) as compared to standard TMZ in the first-line therapy of MGMT-non-methylated GBM. The primary endpoint progression-free survival after 6 months (PFS-6) has already been reported as being markedly increased in the BEV/IRI arm (Herrlinger et al., ASCO 2013, LBA 2000). The present report focuses on progression-free survival, overall survival (OS) and quality of life (QoL). OS and QoL are particularly important parameters since previous randomized trials investigating BEV in primary therapy of GBM have not been able to demonstrate an OS benefit and have yielded conflicting results regarding QoL. Methods: Patients (n=170) with newly diagnosed, MGMT-non-methylated glioblastoma received local radiotherapy (RT, 30 x 2 Gy) and were randomized (2:1) for experimental therapy with BEV (10 mg/kg q2w) during RT followed by maintenance BEV (10 mg/kg q2w) + IRI (125 mg/m² q2w) or standard therapy with daily TMZ (75 mg/m2) during RT followed by 6 courses of TMZ (150-200 mg/m2/day for 5 days q4w). For 5 prespecified domaines of the EORTC-QLQ C30 and BN20 questionnaires (global health status, physical functioning, social functioning, motor dysfunction, communication deficit as prespecified domaines), the time to deterioration by at least 10 points was analyzed using Kaplan-Meier statistics. Results: With BEV/IRI, PFS was significantly prolonged from a median of 5.9 months (95%CI 2.7-6.2 months) to 9.7 months (95%CI 8.7-10.5 months, p=0.0004; hazard ratio 0.56, 95%CI 0.4-0.79). At progression, the crossover rate was similar in both arms (60.8 and 61.9%). Final OS results will be presented. In all prespecified dimensions of QoL, the time to deterioration was not significantly different between the treatment arms. Data of post-progression QoL will be presented. Conclusions: BEV/IRI therapy was superior to TMZ regarding PFS. BEV/IRI therapy did not alter QoL as compared to TMZ therapy. Clinical trial information: No.: 2009-010390-21.
Health4Families: An intervention to improve weight and health behaviors in families with hereditary breast/ovarian cancer or Lynch syndrome.
Authors: Susan K. Peterson, Larkin Strong, Susan Schembre, Matthew Cox, Liang Li, Courtney Karam, Jaejoon Song, Banu Arun, Mala Pande, Y. Nancy You, Miguel A. Rodriguez-Bigas, Karen H. Lu, Patrick M. Lynch, Karen Basen-Engquist
Journal: Journal of Clinical Oncology (2017)

1555 Background: Physical activity, diet, and healthy weight may reduce cancer risk in hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) families. Evidence-based programs to help affected families make these behavioral changes are lacking. We evaluated data from a 16-week family-centered lifestyle intervention trial for individuals with HBOC or LS germline gene mutations and their relatives. Methods: Index cases with HBOC- or LS-associated mutations were recruited from an institutional registry and advocacy organizations, and identified relatives to participate with them in the study. Those eligible had BMI&gt;25 and/or did not meet recommendations for exercise or fruit/vegetable consumption. Participants were randomized to multiple conditions including text messaging, online weight/diet monitoring, an online social network, and E-mail or telephone coaching. All monitored activity using Fitbits. Behavioral outcomes were assessed online at baseline and 8 weeks. Results: 65 HBOC index cases with 63 family members, and 35 LS index cases with 36 family members participated in the study. At 8 weeks, participants lost 3.2 pounds on average (p&lt;.0001) and increased weekly physical activity from 126 to 172 minutes (p=.0012). LS participants decreased self-reported sedentary time (p=.0126). Program effects did not differ between index cases and family members. Participants reported high program satisfaction; 78% would recommend it to a family member. Conclusions: Hereditary cancer families can benefit from behavioral interventions to improve weight and physical activity. Data show that distance-based methods are effective, and are ideally suited for families with a hereditary predisposition to cancer but who are often geographically dispersed. Clinical trial information: NCT02194387. [Table: see text]
Abstract 261: G3bp1-Gas5 Axis Regulates Glucocorticoid Receptor Signaling During Cardiac Hypertrophy
Authors: Zhi Yang, Minzhen He, Danish Sayed
Journal: Circulation Research (2016)

Congestive heart failure is one of the leading causes of mortality in US. With persistent work overload, pathological hypertrophy progresses into an irreversible state of dysfunction and failure. Understanding the mechanisms involved in these advances is crucial to prevent adverse changes in the heart. Studies show that Glucocorticoid (Gc) signaling and -dependent gene transcription promotes cardiac hypertrophy and fibrosis. High serum cortisol levels have been shown as independent risk factor for increased mortality in patients with cardiac failure. Gc activates cytosolic Glucocorticoid receptor (GR) that translocates to nucleus and regulates gene transcription by binding to genomic GR-response element (GRE). We confirmed nuclear translocation of GR in hypertrophing cardiac myocytes in vitro and in vivo . Our aim was to examine GR signaling in cardiac myocytes. Using in vitro biotin labeling and RNA immunoprecipitation we show that a non-coding RNA Gas5, which harbors decoy GRE sequence associates with GR in cardiac myocytes and competes with genomic GRE for DNA binding domain of GR, thus inhibiting the transcriptional effects of activated GR. Interestingly, this association decreases with hypertrophy or Gc agonist (dexamethasone) stimulation. Conversely, Gas5 association with G3bp1, a RNA binding protein increases in cardiac myocytes with similar stimulations, suggesting that increase in G3bp1-Gas5 binding might play a role in release of activated GR from Gas5. In accordance, expression of exogenous Gas5 in vitro and in vivo restricted hypertrophy, suggesting critical role in progression of hypertrophy. We recently reported that G3bp1 is required for development of cardiac hypertrophy. Moreover, in situ hybridization revealed sequestration of Gas5 transcripts to perinuclear focal regions with growth stimulus, which resemble cytoplasmic protein-RNA aggregates seen with hypertrophic stimulation or G3bp1 over expression in cardiac myocytes. These results suggest that G3bp1 regulates Gas5 cellular compartmental dynamics and hence its GR-repressor function in cardiac myocytes. Thus, we conclude that G3bp1-Gas5 axis regulates GR -dependent gene transcription and progression of pathological cardiac hypertrophy and onset of failure
A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons
Authors: Marina Vidaki, Frauke Drees, Tanvi Saxena, Erwin Lanslots, Matthew J. Taliaferro, Antonios Tatarakis, Christopher B. Burge, Eric T. Wang, Frank B. Gertler
Journal: Neuron (2017)
Patients cry “whitewash” as NHS refuses to halt use of mesh implants
Authors: Rebecca Coombes
Journal: BMJ (2017)

An NHS review of transvaginal mesh implants released this week has been branded a “whitewash” after failing to order a safety review of the devices, which patients say carry unacceptable risks of severe and life altering side effects.

The review, led by NHS England, looked at the use of implants to treat stress urinary incontinence (SUI) and pelvic organ prolapse (POP)—surgery carried out in about 15 000 women every year in England.1

An emotionally charged meeting in parliament last week heard testimonies from a dozen women on how mesh had left them disabled, in chronic and debilitating pain, needing bladders and bowels removed where the mesh had shrunk and sliced into them, unable to have sex, or with psychological problems.2

The implants are subject to an ongoing inquiry in Scotland, where …
Safety and initial clinical efficacy of a dendritic cell (DC) vaccine in locally advanced, triple-negative breast cancer (TNBC) patients (pts).
Authors: Joyce O'Shaughnessy, Lee K Roberts, Jennifer L Smith, Maren K Levin, Roxana Timis, Jennifer P Finholt, Susan B Burkeholder, Jessica Tarnowski, Luz Stella Muniz, Melissa G Melton, Karolina Palucka
Journal: Journal of Clinical Oncology (2016)

1086 Background: Women with TNBC who do not achieve a pathologic complete response (pCR) with preoperative (preop) chemotherapy have a high risk of recurrence and death from breast cancer (BC). A high priority for clinical research is to increase the pCR rate in breast and axilla with preop therapy. Immunotherapy is an attractive strategy as human BCs can be immunogenic, and enhancing the immune effector function may augment the cytotoxic effects of standard therapies. Methods: Following IRB-approved informed consent, 10 pts with locally advanced TNBC received standard preop dose-dense doxorubicin/cyclophosphamide (AC) followed by paclitaxel and carboplatin (TCb) chemotherapy, combined with antigen-loaded (antigens found to be overexpressed in TNBC plus control viral antigens: cyclin B1, WT1, CEF) autologous monocyte-derived DC vaccinations administered intratumorally and subcutaneously. Vaccines were given at 4 time points prior to definitive surgery, and 3 times post-surgery, pre- and post-radiation therapy. Safety is the primary study endpoint, and pCR rate in breast and axilla is a secondary endpoint. Blood was collected at baseline, prior to each vaccination, and at the end of treatment for immunologic studies. BC tissue was collected at 3 intervals during the study for biomarker evaluation. Results: All pts received the 4 vaccines during preop chemotherapy, and 4/10 have received all 7 vaccines. 9/10 pts experienced Grade 1-2 injection site reactions. Incidence and grade of chemotherapy-related AEs were not greater than would be expected with chemotherapy alone. At the time of definitive surgery, 5 pts achieved a pCR, 3 pts had macroscopic residual disease in the breast and axillary lymph nodes, and 2 pts had residual cancer burden scores of 1. Updated clinical and immunologic biomarker evaluation is underway and data will be presented. Conclusions: Vaccine preparation per GMP, quality control, and administration were feasible in the outpatient oncology setting. Intratumoral and subcutaneous autologous DC vaccine administration given during preop chemotherapy is safe in TNBC pts. Clinical trial information: NCT02018458.
A Comparison of Socioeconomic Factors in Patients Continuing Warfarin Versus Those Transitioning to Direct Oral Anticoagulants (DOACs) for Venous Thromboembolic Disease or Atrial Fibrillation
Authors: Jordan K. Schaefer, Suman L. Sood, Brian Haymart, Xiaokui Gu, Eva Kline-Rogers, Steven L. Almany, Jay H. Kozlowski, Gregory D. Krol, Scott Kaatz, James B. Froehlich, Geoffrey D. Barnes
Journal: Blood (2016)
New Medical Officer at Indian Health Service
Authors: Jeff Lyon
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
The extensive glycosylation of the ACPA variable domain observed for ACPA-IgG is absent from ACPA-IgM
Authors: Ayla C Kempers, Lise Hafkenscheid, Annemarie L Dorjée, Eleni Moutousidou, Fleur S van de Bovenkamp, Theo Rispens, Leendert A Trouw, Maikel van Oosterhout, Tom WJ Huizinga, René Toes, Hans Ulrich Scherer
Journal: Annals of the Rheumatic Diseases (2017)

Recently, we described the presence of highly sialylated N -linked glycans in the antigen-binding fragment (Fab) of almost all anti-citrullinated protein antibody (ACPA) IgG molecules.1 2 These glycans could not be found on several other autoantibody systems analysed. Given the low affinity of ACPA,3 this observation raises the intriguing possibility that citrullinated antigen-specific B cells could be selected based on the presence of glycans in the variable domain, rather than on affinity for their cognate antigen. N -glycosylation requires the presence of specific consensus sequences in the amino acid backbone of proteins.4 However, only few human germline Ig variable region genes encode for such sequences.5 So far, we could identify several N -glycosylation sites in ACPA-IgG Fab-domains using mass spectrometry, but none of these were encoded in the germline sequence.1 This suggests that the extensive presence of N -glycans in ACPA-IgG Fab-domains results from somatic mutations. Moreover, it indicates that the ACPA response matures under the influence of T-cell help, presumably in germinal centres, and makes it conceivable that the introduction of N -glycosylation sites …
Tomo-Seq Identifies SOX9 as a Key Regulator of Cardiac Fibrosis During Ischemic Injury
Authors: Grégory P.A. Lacraz, Jan Philipp Junker, Monika M. Gladka, Bas Molenaar, Koen T. Scholman, Marta Vigil-Garcia, Danielle Versteeg, Hesther de Ruiter, Marit W. Vermunt, Menno P. Creyghton, Manon M.H. Huibers, Nicolaas de Jonge, Alexander van Oudenaarden, Eva van Rooij
Journal: Circulation (2017)

Cardiac ischemic injury induces a pathological remodeling response, which can ultimately lead to heart failure. Detailed mechanistic insights into molecular signaling pathways relevant for different aspects of cardiac remodeling will support the identification of novel therapeutic targets.Although genome-wide transcriptome analysis on diseased tissues has greatly advanced our understanding of the regulatory networks that drive pathological changes in the heart, this approach has been disadvantaged by the fact that the signals are derived from tissue homogenates. Here we used tomo-seq to obtain a genome-wide gene expression signature with high spatial resolution spanning from the infarcted area to the remote to identify new regulators of cardiac remodeling. Cardiac tissue samples from patients suffering from ischemic heart disease were used to validate our findings.Tracing transcriptional differences with a high spatial resolution across the infarcted heart enabled us to identify gene clusters that share a comparable expression profile. The spatial distribution patterns indicated a separation of expressional changes for genes involved in specific aspects of cardiac remodeling, such as fibrosis, cardiomyocyte hypertrophy, and calcium handling (Col1a2, Nppa, and Serca2). Subsequent correlation analysis allowed for the identification of novel factors that share a comparable transcriptional regulation pattern across the infarcted tissue. The strong correlation between the expression levels of these known marker genes and the expression of the coregulated genes could be confirmed in human ischemic cardiac tissue samples. Follow-up analysis identified SOX9 as common transcriptional regulator of a large portion of the fibrosis-related genes that become activated under conditions of ischemic injury. Lineage-tracing experiments indicated that the majority of COL1-positive fibroblasts stem from a pool of SOX9-expressing cells, and in vivo loss of Sox9 blunted the cardiac fibrotic response on ischemic injury. The colocalization between SOX9 and COL1 could also be confirmed in patients suffering from ischemic heart disease.Based on the exact local expression cues, tomo-seq can serve to reveal novel genes and key transcription factors involved in specific aspects of cardiac remodeling. Using tomo-seq, we were able to unveil the unknown relevance of SOX9 as a key regulator of cardiac fibrosis, pointing to SOX9 as a potential therapeutic target for cardiac fibrosis.
Human Nature in the Light of Psychopathology
Journal: JAMA (1941)

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
Response to Comment on Niewczas et al. Circulating Modified Metabolites and a Risk of ESRD in Patients With Type 1 Diabetes and Chronic Kidney Disease. Diabetes Care 2017;40:383–390
Authors: Monika A. Niewczas, Andrzej S. Krolewski
Journal: Diabetes Care (2017)

We appreciate the invitation to respond to comments by Luo et al. (1) on our article (2). The clinical ascertainment of exposures and the outcome is crucial for epidemiological studies and we appreciate the given attention.

The goal of our study was to evaluate metabolomic determinants predicting development of end-stage renal disease (ESRD) 10 years in advance. Apparently, we were not explicit in explaining that our study design was prospective and not cross-sectional.

Luo et al. (1) mentioned limitations regarding the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to estimate glomerular filtration rate in the elderly and in subjects with certain CKD stages or to define ESRD. These might be valid diagnostic concerns relevant in the cross-sectional setting, but they are not applicable to our prospective study. We chose development of ESRD within 8–12 years, an …
Assessment of the Probability of Autochthonous Transmission of Chikungunya Virus in Canada under Recent and Projected Climate Change
Authors: Victoria Ng, Aamir Fazil, Philippe Gachon, Guillaume Deuymes, Milka Radojević, Mariola Mascarenhas, Sophiya Garasia, Michael A. Johansson, Nicholas H. Ogden
Journal: Environmental Health Perspectives (2017)

Chikungunya virus (CHIKV) is a reemerging pathogen transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The ongoing Caribbean outbreak is of concern due to the potential for infected travelers to spread the virus to countries where vectors are present and the population is susceptible. Although there has been no autochthonous transmission of CHIKV in Canada, there is concern that both Ae. albopictus and CHIKV will become established, particularly under projected climate change. We developed risk maps for autochthonous CHIKV transmission in Canada under recent (1981–2010) and projected climate (2011–2040 and 2041–2070).The risk for CHIKV transmission was the combination of the climatic suitability for CHIKV transmission potential and the climatic suitability for the presence of Ae. albopictus; the former was assessed using a stochastic model to calculate R0 and the latter was assessed by deriving a suitability indicator (SIG) that captures a set of climatic conditions known to influence the ecology of Ae. albopictus. R0 and SIG were calculated for each grid cell in Canada south of 60°N, for each time period and for two emission scenarios, and combined to produce overall risk categories that were mapped to identify areas suitable for transmission and the duration of transmissibility.The risk for autochthonous CHIKV transmission under recent climate is very low with all of Canada classified as unsuitable or rather unsuitable for transmission. Small parts of southern coastal British Columbia become progressively suitable with short-term and long-term projected climate; the duration of potential transmission is limited to 1–2 months of the year.Although the current risk for autochthonous CHIKV transmission in Canada is very low, our study could be further supported by the routine surveillance of Ae. albopictus in areas identified as potentially suitable for transmission given our uncertainty on the current distribution of this species in Canada. https://doi.org/10.1289/EHP669
Interleukin-7 Availability Is Maintained by a Hematopoietic Cytokine Sink Comprising Innate Lymphoid Cells and T Cells
Authors: Christopher E. Martin, Darina S. Spasova, Kwesi Frimpong-Boateng, Hee-Ok Kim, Minji Lee, Kwang Soon Kim, Charles D. Surh
Journal: Immunity (2017)