tbuckley/cabot-search huggingface dataset:
Nephrectomy After Complete Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma: A New Surgical Challenge?
Authors: Geraldine Pignot, Antoine Thiery-Vuillemin, Jochen Walz, Hervé Lang, Pierre Bigot, Pierre Werle, Loïc Balssa, Lionnel Geoffrois, Louis Leblanc, Laurence Albigès, Vincenzo di Nunno, Karim Bensalah, Sylvain Ladoire, Gwenaelle Gravis, Philippe Barthélémy
Journal: European Urology (2020)
More Explorations Needed on Association of Electronic Cigarette Use and Smoking Reduction—Reply
Authors: Ramchandar Gomajee, Fabienne El-Khoury, Maria Melchior
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
Human Fetal Lungs Harbor a Microbiome Signature
Authors: Denise Al Alam, Soula Danopoulos, Brendan Grubbs, Nur A’tikah Binte Mohamed Ali, Micheal MacAogain, Sanjay H. Chotirmall, David Warburton, Amit Gaggar, Namasivayam Ambalavanan, Charitharth Vivek Lal
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

COPD (11,12). RARB is expressed in human lung tissue, bronchial epithelial cells, and airway smooth muscle cells (10), and knockout of this gene could lead to premature alveolar septation in mice (13), suggesting its fundamental function in lung development, normal physiology, and capacity.In this study, we observed the positive association between PAH exposure and hypermethylation in RARB promoter; a putative effect may exist on decreasing expression of RARB caused by PAHs.There was also a suggestive association of rs1529672-A allele with reduced RARB expression.Considering the important biological roles of RARB in lung development, we speculated that the decreased expression of RARB may act as the common target for PAH exposure and rs1529672, suggesting a possible mechanism underlying the statistical gene-environment interaction.Strengths of this study were the prospective design and results validation by two independent cohorts of populations with a wide range of PAH exposure.The limitations of this study included not investigating the SNPs reported after March 2017, along with variants in genes involved in PAH metabolism and related biological pathways.Future longitudinal studies in other ethnic populations and the well-designed functional studies are warranted to validate these associations and elucidate putative mechanisms for the PAH-RARB interaction in lung function impairment.In conclusion, the GWAS reported RARB rs1529672 may modify the effect of PAH exposure on annual FEV 1 /FVC decline.The results emphasize the urgency of reducing environmental PAH levels and the importance of lung function monitoring in the routine physical examination, especially for high-risk populations.
A dual-action peptide-containing hydrogel targets wound infection and inflammation
Authors: Manoj Puthia, Marta Butrym, Jitka Petrlova, Ann-Charlotte Strömdahl, Madelene Å. Andersson, Sven Kjellström, Artur Schmidtchen
Journal: Science Translational Medicine (2020)

There is a clinical need for improved wound treatments that prevent both infection and excessive inflammation. TCP-25, a thrombin-derived peptide, is antibacterial and scavenges pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide, thereby preventing CD14 interaction and Toll-like receptor dimerization, leading to reduced downstream immune activation. Here, we describe the development of a hydrogel formulation that was functionalized with TCP-25 to target bacteria and associated PAMP-induced inflammation. In vitro studies determined the polymer prerequisites for such TCP-25-mediated dual action, favoring the use of noncharged hydrophilic hydrogels, which enabled peptide conformational changes and LPS binding. The TCP-25-functionalized hydrogels killed Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacteria in vitro, as well as in experimental mouse models of subcutaneous infection. The TCP-25 hydrogel also mediated reduction of LPS-induced local inflammatory responses, as demonstrated by analysis of local cytokine production and in vivo bioimaging using nuclear factor κB (NF-κB) reporter mice. In porcine partial thickness wound models, TCP-25 prevented infection with S. aureus and reduced concentrations of proinflammatory cytokines. Proteolytic fragmentation of TCP-25 in vitro yielded a series of bioactive TCP fragments that were identical or similar to those present in wounds in vivo. Together, the results demonstrate the therapeutic potential of TCP-25 hydrogel, a wound treatment based on the body's peptide defense, for prevention of both bacterial infection and the accompanying inflammation.
NCOG-03. COGNITIVE CONCERNS AND PERFORMANCE IN PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (mNSCLC)
Authors: Annemarie Eggen, Nadine Richard, Gerald Shen, David Shultz, Natasha Leighl, Geoffrey Liu, Alexander Sun, Ingeborg Bosma, Anna Reyners, Mathilde Jalving, Gary Rodin, Kim Edelstein
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Cognitive concerns and objective cognitive impairment are both common in cancer patients, although the relationship between these variables is uncertain. Brain metastases have the potential to affect both outcomes. We examined the relationships between cognitive concerns, cognitive performance, and psychological disturbance in mNSCLC patients with and without brain metastases. METHODS mNSCLC patients completed standardized neuropsychological tests (HVLT-R, TMTA/B, COWA) and questionnaires measuring cognitive and neurobehavioral concerns, depression, demoralization, self-esteem, illness intrusiveness, and physical symptoms. Perceived cognitive impairment was defined as FACT-Cog scores ≤1.5 SD below the normative mean. Impaired cognitive performance was defined as ≥2 test scores ≤1.5 SD or one test score ≤2.0 SD below normative means. Multivariate analyses used the mean composite of neuropsychological test z-scores (COG-comp). Progressive disease (extra- and/or intracranial) was defined as radiological progression or clinical deterioration within one month before the study. RESULTS 74 patients participated (53% female; median age 62 (37–82); 30% EGFR mutated). Time since mNSCLC diagnosis was 11 months (median; 0–89). 50% had brain metastases, 21 of whom received cranial radiation (11 SRS, 10 WBRT±SRS). 27% reported cognitive concerns and 42% were impaired on objective testing (HVLT-R:34%, TMT:27%, COWA:16%). Neither was more common in patients with brain metastases. COG-comp (mean±SD: –0.39±0.91) was unrelated to cognitive concerns. In multivariate analyses, less depression (p&amp;lt; 0.01) and illness intrusiveness (p=0.03), and absence of disease progression (p=0.03) were related to better perceived cognitive function. No significant associations were found between cognitive performance and demographic, disease, or psychological variables. CONCLUSION Cognitive impairment is common in mNSCLC patients with or without brain metastases, but is independent of cognitive concerns. Cognitive concerns which are linked to depression, illness intrusiveness and disease progression, may be more likely to reflect the impact of cognitive changes in daily life. Both merit further clinical and research attention.
Stress Testing and Risk Prediction in People With Known Symptomatic Multivessel Coronary Artery Disease—Reply
Authors: Cibele Larrosa Garzillo, Paulo Cury Rezende, Whady Hueb
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
In vivo isolation of circulating tumor cells in prostate cancer patients by a medical device.
Authors: Gerit Theil, M.Raschid Hoda, Kersten Fischer, Andre Schumann, Kathrin Haubold, Catrin Boehm, Thomas Krahn, Klaus Luecke, Nils G. Morgenthaler, Paolo Fornara
Journal: Journal of Clinical Oncology (2013)

e22055 Background: CTCs are discussed as a prognostic and stratification biomarker, and may help to assess the treatment efficacy. The aim was to demonstrate proof of concept of in vivo CTC isolation in Prostate cancer patients (PCa). Methods: A medical device (CellCollector) was inserted in a cubital vein for 30 minutes. The interaction of target CTCs with the CellCollector was mediated by antibodies to the epithelial cell adhesion molecule (EpCAM). To confirm binding of CTCs to the wire, immunohistochemical staining against Cytokeratin and CD45 was performed. There were 226 applications of the device in 16 metastasized PCa (PCa-m) with up to 8 wire applications per patient, 24 localized PCa (PCa-l) with up to 3 wire applications per patient as well as 19 men with benign prostate hypertrophy (BPH) and 21 women as control group with only one wire application. CTC counts from 22 PCa patients with 58 applications were directly compared to the CellSearch technology. Results: We obtained in vivo isolation of CTCs in 73 of 98 applications to PCa patients (74.5 %). The sensitivity for metastasized PCa was (86.2%) and for local PCa (57.5%), respectively. Follow up data of one patient with PCa-m: 2009 diagnosed PCa with multiple metastases. 2 years later PSA of 11.2ng/mL and 25 CTCs. After transurethral resection and removal of a brain metastasis, CTCs decreased to 20 cells with no effect on PSA levels. 4 months later we observed 187 CTCs and a PSA level of 76ng/mL, which was correlated with the patient condition. In PCa-l patients we observed prior radical prostatectomy (n=18) and 6 (n=15) and 12 (n=7) months after surgery CTC numbers on average of 18.2, 2.8 and 1.4, respectively. In the direct comparison of the CellCollector and CellSearch we showed detection rates of 65% (13/20) and 20% (4/20). Conclusions: We demonstrate the use of CTCs besides PSA during therapy adjustment in PCa patients In summary the CTC detection rate of the CellCollector in PCa-m and PCa-l in comparison to the CellSearch method increased by 26% and 45%. Further molecular genetic CTC characterization as well as multiple antibody coating at the CellCollector will assume crucial information for therapy decisions. Clinical trial information: ISRCTN10403616.
Development of a new class of PSMA radioligands comprising ibuprofen as an albumin-binding entity
Authors: Luisa M. Deberle, Martina Benešová, Christoph A. Umbricht, Francesca Borgna, Manuel Büchler, Konstantin Zhernosekov, Roger Schibli, Cristina Müller
Journal: Theranostics (2020)

Prostate-specific membrane antigen (PSMA)-targeted radioligands have been used for the treatment of metastatic castration-resistant prostate cancer (mCRPC).Recently, albumin-binding PSMA radioligands with enhanced blood circulation were developed to increase the tumor accumulation of activity.The present study aimed at the design, synthesis and preclinical evaluation of a novel class of PSMA-targeting radioligands equipped with ibuprofen as a weak albumin-binding entity in order to improve the pharmacokinetic properties.Methods: Four novel glutamate-urea-based PSMA ligands were synthesized with ibuprofen, conjugated via variable amino acid-based linker entities.The albumin-binding properties of the 177 Lu-labeled PSMA ligands were tested in vitro using mouse and human plasma.Affinity of the radioligands to PSMA and cellular uptake and internalization was investigated using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu tumor cells.The tissue distribution profile of the radioligands was assessed in biodistribution and imaging studies using PC-3 PIP/flu tumor-bearing nude mice.Results: The PSMA ligands were obtained in moderate yields at high purity (>99%). 177Lu-labeling of the ligands was achieved at up to 100 MBq/nmol with >96% radiochemical purity.In vitro assays confirmed high binding of all radioligands to mouse and human plasma proteins and specific uptake and internalization into PSMA-positive PC-3 PIP tumor cells.Biodistribution studies and SPECT/CT scans revealed high accumulation in PC-3 PIP tumors but negligible uptake in PC-3 flu tumor xenografts as well as rapid clearance of activity from background organs and tissues. 177Lu-Ibu-DAB-PSMA, in which ibuprofen was conjugated via a positively-charged diaminobutyric acid (DAB) entity, showed distinguished tumor uptake and the most favorable tumor-to-blood and tumor-to-kidney ratios. Conclusion:The high accumulation of activity in the tumor and fast clearance from background organs was a common favorable characteristic of PSMA radioligands modified with ibuprofen as albumin-binding entity. 177Lu-Ibu-DAB-PSMA emerged as the most promising candidate; hence, more detailed preclinical investigations with this radioligand are warranted in view of a clinical translation.
Bernard Fisher, MD: In Memoriam (1918–2019)
Authors: Nancy E. Davidson
Journal: Cancer Research (2020)

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With the death of Bernard Fisher, MD, on October 16, 2019, at the age of 101, we lost a visionary thinker and medical pioneer in cancer research and care. Fisher, a surgeon and clinical trialist, revolutionized breast cancer treatment, leading trials that transformed breast
Neurodevelopmental Abnormalities Associated With In Utero Zika Virus Infection in Infants and Children—The Unfolding Story
Authors: Margaret A. Honein, Kate R. Woodworth, Christopher J. Gregory
Journal: JAMA Pediatrics (2020)

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
Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma
Authors: Ayesha Noorani, Xiaodun Li, Martin Goddard, Jason Crawte, Ludmil B. Alexandrov, Maria Secrier, Matthew D. Eldridge, Lawrence Bower, Jamie Weaver, Pierre Lao-Sirieix, Inigo Martincorena, Irene Debiram-Beecham, Nicola Grehan, Shona MacRae, Shalini Malhotra, Ahmad Miremadi, Tabitha Thomas, Sarah Galbraith, Lorraine Petersen, Stephen D. Preston, David Gilligan, Andrew Hindmarsh, Richard H. Hardwick, Michael R. Stratton, David C. Wedge, Rebecca C. Fitzgerald
Journal: Nature Genetics (2020)
Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
Authors: Myriam Jaraíz-Rodríguez, Rocío Talaverón, Laura García-Vicente, Sara G Pelaz, Marta Domínguez-Prieto, Andrea Álvarez-Vázquez, Raquel Flores-Hernández, Wun Chey Sin, John Bechberger, José M Medina, Christian C Naus, Arantxa Tabernero
Journal: Neuro-Oncology (2019)

Malignant gliomas are the most frequent primary brain tumors and remain among the most incurable cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulate the tumor suppressor properties of this protein in in vivo glioma models.TAT-Cx43266-283 a cell-penetrating peptide which mimics the effect of Cx43 on c-Src inhibition, was studied in orthotopic immunocompetent and immunosuppressed models of glioma. The effects of this peptide in brain cells were also analyzed.While glioma stem cell malignant features were strongly affected by TAT-Cx43266-283, these properties were not significantly modified in neurons and astrocytes. Intraperitoneally administered TAT-Cx43266-283 decreased the invasion of intracranial tumors generated by GL261 mouse glioma cells in immunocompetent mice. When human glioma stem cells were intracranially injected with TAT-Cx43266-283 into immunodeficient mice, there was reduced expression of the stemness markers nestin and Sox2 in human glioma cells at 7 days post-implantation. Consistent with the role of Sox2 as a transcription factor required for tumorigenicity, TAT-Cx43266-283 reduced the number and stemness of human glioma cells at 30 days post-implantation. Furthermore, TAT-Cx43266-283 enhanced the survival of immunocompetent mice bearing gliomas derived from murine glioma stem cells.TAT-Cx43266-283 reduces the growth, invasion, and progression of malignant gliomas and enhances the survival of glioma-bearing mice without exerting toxicity in endogenous brain cells, which suggests that this peptide could be considered as a new clinical therapy for high-grade gliomas.
Promotion of mitochondrial fusion protects against developmental PBDE-47 neurotoxicity by restoring mitochondrial homeostasis and suppressing excessive apoptosis
Authors: Lixin Dong, Pei Li, Kaichao Yang, Luming Liu, Hui Gao, Guoyu Zhou, Qian Zhao, Tao Xia, Aiguo Wang, Shun Zhang
Journal: Theranostics (2020)

Polybrominated diphenyl ethers (PBDEs)-induced neurotoxicity is closely associated with mitochondrial abnormalities. Mitochondrial fusion and fission dynamics are required for the maintenance of mitochondrial homeostasis. However, little is known about how PBDEs disrupt this dynamics and whether such disruption contributes to impaired neurodevelopment. Methods: We investigated the effects of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47), the dominant congener in human samples, on mitochondrial fusion and fission dynamics using PC12 cells, a well-defined in vitro neurodevelopmental model. We also evaluated the effects of perinatal low-dose PBDE-47 exposure on hippocampal mitochondrial dynamics and its association with neurobehavioral changes in adult Sprague-Dawley rats. Results: In vitro, PBDE-47 disrupted mitochondrial dynamics by inhibiting mitochondrial fusion and fission simultaneously, accompanied by mitochondrial fragmentation, membrane potential dissipation, ATP loss, and apoptosis activation. Specifically, enhancing mitochondrial fusion by the chemical promoter M1 or adenovirus-mediated mitofusin 2 (Mfn2) overexpression rescued PBDE-47-caused mitochondrial dynamic, morphological and functional impairments, prevented the resultant apoptosis and promoted neuronal survival. Unexpectedly, either stimulating mitochondrial fission by adenovirus-mediated fission protein 1 (Fis1) overexpression or suppressing mitochondrial fission by the mitochondrial division inhibitor-1 (Mdivi-1) failed to reverse whereas aggravated PBDE-47-induced mitochondrial damage and neuronal death. Importantly, promoting mitochondrial fusion by Mfn2 overexpression neutralized the detrimental effects elicited by Fis1 overexpression after PBDE-47 treatment. Finally, perinatal oral administration of PBDE-47 elicited neurobehavioral deficits and hippocampal neuronal loss via apoptosis in adult rats, which were associated with mitochondrial dynamics alterations manifested as a fragmented phenotype. Conclusion: Our results suggest that PBDE-47 disrupts mitochondrial dynamics to induce mitochondrial abnormalities, triggering apoptosis and thus contributing to neuronal loss and subsequent neurobehavioral deficits. Targeting mitochondrial fusion may be a promising therapeutic intervention against PBDE-47 neurotoxicity.
A comparison framework and guideline of clustering methods for mass cytometry data
Authors: Xiao Liu, Weichen Song, Brandon Y. Wong, Ting Zhang, Shunying Yu, Guan Ning Lin, Xianting Ding
Journal: Genome biology (2019)

Abstract Background With the expanding applications of mass cytometry in medical research, a wide variety of clustering methods, both semi-supervised and unsupervised, have been developed for data analysis. Selecting the optimal clustering method can accelerate the identification of meaningful cell populations. Result To address this issue, we compared three classes of performance measures, “precision” as external evaluation, “coherence” as internal evaluation, and stability, of nine methods based on six independent benchmark datasets. Seven unsupervised methods (Accense, Xshift, PhenoGraph, FlowSOM, flowMeans, DEPECHE, and kmeans) and two semi-supervised methods (Automated Cell-type Discovery and Classification and linear discriminant analysis (LDA)) are tested on six mass cytometry datasets. We compute and compare all defined performance measures against random subsampling, varying sample sizes, and the number of clusters for each method. LDA reproduces the manual labels most precisely but does not rank top in internal evaluation. PhenoGraph and FlowSOM perform better than other unsupervised tools in precision, coherence, and stability. PhenoGraph and Xshift are more robust when detecting refined sub-clusters, whereas DEPECHE and FlowSOM tend to group similar clusters into meta-clusters. The performances of PhenoGraph, Xshift, and flowMeans are impacted by increased sample size, but FlowSOM is relatively stable as sample size increases. Conclusion All the evaluations including precision, coherence, stability, and clustering resolution should be taken into synthetic consideration when choosing an appropriate tool for cytometry data analysis. Thus, we provide decision guidelines based on these characteristics for the general reader to more easily choose the most suitable clustering tools.