tbuckley/cabot-search huggingface dataset:
CD69 Plays a Beneficial Role in Ischemic Stroke by Dampening Endothelial Activation
Authors: Vanessa H. Brait, Francesc Miró-Mur, Isabel Pérez-de-Puig, Laura Notario, Begoña Hurtado, Jordi Pedragosa, Mattia Gallizioli, Francesc Jiménez-Altayó, Maria Arbaizar-Rovirosa, Amaia Otxoa-de-Amezaga, Juan Monteagudo, Maura Ferrer-Ferrer, Xavier de la Rosa, Ester Bonfill-Teixidor, Angélica Salas-Perdomo, Alba Hernández-Vidal, Pablo Garcia-de-Frutos, Pilar Lauzurica, Anna M. Planas
Journal: Circulation Research (2019)

CD69 is an immunomodulatory molecule induced during lymphocyte activation. Following stroke, T-lymphocytes upregulate CD69 but its function is unknown.We investigated whether CD69 was involved in brain damage following an ischemic stroke.We used adult male mice on the C57BL/6 or BALB/c backgrounds, including wild-type mice and CD69-/- mice, and CD69+/+ and CD69-/- lymphocyte-deficient Rag2-/- mice, and generated chimeric mice. We induced ischemia by transient or permanent middle cerebral artery occlusion. We measured infarct volume, assessed neurological function, and studied CD69 expression, as well as platelet function, fibrin(ogen) deposition, and VWF (von Willebrand factor) expression in brain vessels and VWF content and activity in plasma, and performed the tail-vein bleeding test and the carotid artery ferric chloride-induced thrombosis model. We also performed primary glial cell cultures and sorted brain CD45-CD11b-CD31+ endothelial cells for mRNA expression studies. We blocked VWF by intravenous administration of anti-VWF antibodies. CD69-/- mice showed larger infarct volumes and worse neurological deficits than the wild-type mice after ischemia. This worsening effect was not attributable to lymphocytes or other hematopoietic cells. CD69 deficiency lowered the time to thrombosis in the carotid artery despite platelet function not being affected. Ischemia upregulated Cd69 mRNA expression in brain endothelial cells. CD69-deficiency increased fibrin(ogen) accumulation in the ischemic tissue, and plasma VWF content and activity, and VWF expression in brain vessels. Blocking VWF reduced infarct volume and reverted the detrimental effect of CD69-/- deficiency.CD69 deficiency promotes a prothrombotic phenotype characterized by increased VWF and worse brain damage after ischemic stroke. The results suggest that CD69 acts as a downregulator of endothelial activation.
Human islets expressing HNF1A variant have defective β cell transcriptional regulatory networks
Authors: Rachana Haliyur, Xin Tong, May Sanyoura, Shristi Shrestha, Jill Lindner, Diane C. Saunders, Radhika Aramandla, Greg Poffenberger, Sambra D. Redick, Rita Bottino, Nripesh Prasad, Shawn E. Levy, Raymond D. Blind, David M. Harlan, Louis H. Philipson, Roland W. Stein, Marcela Brissova, Alvin C. Powers
Journal: Journal of Clinical Investigation (2018)

Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained β cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1α (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.
Abstract 15599: Saline Induced Pd/Pa Ratio Can Accurately Predict Functional Significance of Coronary Stenosis Assessed by Fractional Flow Reserve - a Novel Concept Based on Low Viscosity Effect
Authors: Yoshiharu Fujimori, Kyohei Yamazaki, Satoshi Hashimoto, Kenichirou Ebisuda, Kazuto Kurihara, Tomoko Baba, Yasushi Yamanaka, Nao Takeuchi, Hirohisa Fujikawa, Shigeru Nishiyama, Yuya Terasawa, Tadamasa Wakabayashi, Taku Imai
Journal: Circulation (2017)

Introduction: Fractional flow reserve (FFR), assessed by distal coronary pressure (Pd)/aortic pressure (Pa) ratio, has been developed to evaluate functional significance of coronary stenosis. Nevertheless, the need of adenosine to achieve maximal hyperemia is considered as one of limiting factors for widespread application of FFR. A single intracoronary bolus of saline also decreases Pd due to its low viscosity. Hypothesis: We hypothesized that saline induced Pd/Pa ratio (SPR) could assess the coronary stenosis as an alternative to FFR. Methods: Among patients with coronary stenosis over 50% diameter stenosis, SPR was assessed by intracoronary saline injection (2 ml/sec) for 5 heart beats (SPR-5) and 3 heart beats (SPR-3). FFR value was obtained after intravenous adenosine infusion (140μg/kg/min). In order to test how low viscosity effect differs depending on arteriolar diameters, we added an intracoronary bolus of saline during recording FFR (FFR+saline). Results: We enrolled 88 patients with 108 coronar...
A Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2–Positive Metastatic Breast Cancer
Authors: Sheau W. Lok, James R. Whittle, François Vaillant, Charis E. Teh, Louisa L. Lo, Antonia N. Policheni, Alice R.T. Bergin, Jayesh Desai, Sarah Ftouni, Luke C. Gandolfo, Danny Liew, He K. Liu, G. Bruce Mann, Kate Moodie, Anand Murugasu, Bhupinder Pal, Andrew W. Roberts, Mark A. Rosenthal, Kylie Shackleton, Maria João Silva, Zhen R. Siow, Gordon K. Smyth, Leanne Taylor, Avraham Travers, Belinda Yeo, Miriam M. Yeung, Andjelija Zivanovic Bujak, Sarah-Jane Dawson, Daniel H.D. Gray, Jane E. Visvader, Geoffrey J. Lindeman
Journal: Cancer Discovery (2019)

Abstract Venetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using a phase Ib 3 + 3 dose-escalation and expansion study design, 33 patients with ER and BCL2-positive metastatic disease (mean prior regimens, 2; range, 0–8) were treated with daily tamoxifen (20 mg) and venetoclax (200–800 mg). Apart from uncomplicated “on-target” lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase II dose (RP2D). In the expansion phase (18 patients), few high-grade treatment-related adverse events were observed. For 24 patients treated at the RP2D, the confirmed radiologic response rate was 54% and the clinical benefit rate was 75%. Treatment responses were preempted by metabolic responses (FDG-PET) at 4 weeks and correlated with serial changes in circulating tumor DNA. Radiologic responses (40%) and clinical benefit (70%) were observed in 10 patients with plasma-detected ESR1 mutations. Significance: In the first clinical study to evaluate venetoclax in a solid tumor, we demonstrate that combining venetoclax with endocrine therapy has a tolerable safety profile and elicits notable activity in ER and BCL2-positive metastatic breast cancer. These findings support further investigation of combination therapy for patients with BCL2-positive tumors. See related commentary by Drago et al., p. 323. This article is highlighted in the In This Issue feature, p. 305
Surgeon who concealed removal of wrong tooth is struck off
Authors: Clare Dyer
Journal: BMJ (2018)

A specialist registrar in maxillofacial surgery has been struck off the UK medical register after a tribunal found that he lied repeatedly to cover up his removal of the wrong tooth during an operation.

Panagiotis Stathopoulos, who qualified in Greece, was working at the Royal Derby Hospital in January 2017 when he removed a patient’s lower right molar 7 and 8 teeth, instead of 6 and 7 as requested by the referring dentist.

The patient, who was particularly troubled by his LR6 tooth, realised the mistake within hours and wrote an email of complaint.

Stathopoulos told the hospital trust—and, later, General Medical Council (GMC) investigators and his medical practitioners’ tribunal hearing—that …
A Phase 1b Study of Oprozomib with Dexamethasone or Pomalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma
Authors: Parameswaran Hari, Mark A. Schroeder, James R Berenson, Andrzej Jakubowiak, Jonathan L Kaufman, Peter M. Voorhees, Hisaki Fujii, Zhao Yang, Francesco Galimi, Kenneth H. Shain
Journal: Blood (2018)
Pooled extracellular receptor-ligand interaction screening using CRISPR activation
Authors: Zheng-Shan Chong, Shuhei Ohnishi, Kosuke Yusa, Gavin J. Wright
Journal: Genome biology (2018)

Abstract Extracellular interactions between cell surface receptors are necessary for signaling and adhesion but identifying them remains technically challenging. We describe a cell-based genome-wide approach employing CRISPR activation to identify receptors for a defined ligand. We show receptors for high-affinity antibodies and low-affinity ligands can be unambiguously identified when used in pools or as individual binding probes. We apply this technique to identify ligands for the adhesion G-protein-coupled receptors and show that the Nogo myelin-associated inhibitory proteins are ligands for ADGRB1. This method will enable extracellular receptor-ligand identification on a genome-wide scale.
Uproleselan (GMI-1271), an E-Selectin Antagonist, Improves the Efficacy and Safety of Chemotherapy in Relapsed/Refractory (R/R) and Newly Diagnosed Older Patients with Acute Myeloid Leukemia: Final, Correlative, and Subgroup Analyses
Authors: Daniel J. DeAngelo, Brian A. Jonas, Jane L. Liesveld, Dale L. Bixby, Anjali S. Advani, Paula Marlton, Michael E O'Dwyer, William E Fogler, Curt D Wolfgang, John L Magnani, Helen M Thackray, Pamela S. Becker
Journal: Blood (2018)
Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase <scp>IV</scp> study
Authors: L.F. Eichenfield, J.Q. Del Rosso, J.K.L. Tan, A.A. Hebert, G.F. Webster, J. Harper, H.E. Baldwin, L.H. Kircik, L. Stein-Gold, A. Kaoukhov, N. Alvandi
Journal: British Journal of Dermatology (2018)

Once-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments.To evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed.In two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose.Among 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant.Assessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity.
MRSA decolonization of human skin via photodynamic treatment
Authors: M. Schreiner, W. Bäumler, D. Eckl, A. Späth, B. König, A. Eichner
Journal: British Journal of Dermatology (2018)

One of the sources of infections in hospitals is the presence of potentially harmful bacteria on the skin surface (carriage) of a patient without the development of an infection, but which can spread to other people under certain conditions. Bacteria living on the skin surface can also contribute to worsening of eczema. The current methods of ridding the skin of these microbes (bacteria) involves giving the patient either topical (on the skin) or oral (by mouth) antibiotics, a strategy which, over time, is thought to have caused antibiotic resistance, meaning the antibiotics can no longer kill the bacteria. The study described in this paper was carried out by a group from the University of Regensburg in Germany. They used excised pig and human skin samples to which they had added drug resistant bacteria, such as methicillin resistant staphylococci or MRSA, and then treated the skin with a chemical in solution that acts by increasing sensitivity to light. Skin samples were then exposed to a source of light, a process known as photodynamic activation. They found that this technique led to a large reduction in the numbers of bacteria, without damage to skin cells. The authors suggest that this process should now be investigated as a safer method of reducing surface bacterial carriage without increasing the risk of bacterial resistance and without damaging the skin.
Addressing Clinical Significance
Authors: Kristen L. W. Webster, Oluwafemi P. Owodunni, Elliott R. Haut
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Abstract 18682: Short-term Decrease in Home Blood Pressure: Implications of Waiting Few Minutes Between Measurements
Authors: Giorgio Quer, Nima Nikzad, Angela Chieh, Alexis Normand, Matthieu Vegreville, Erik J Topol, Steven R STeinhubl
Journal: Circulation (2017)

Introduction: Blood pressure (BP) measurement following 5-10 minutes of seated rest during an office visit is recommended to more accurately determine a person’s BP. Alternatively, home BP readings...
The Alleged Health-Protective Effects of Coffee
Authors: Jack E. James
Journal: JAMA Internal Medicine (2018)

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
RELAX: An immersion virtual reality relaxation intervention for quality of life improvement in cancer patients.
Authors: Erlinda Maria Gordon, Bryan M Li, Seiya Liu, Sant P Chawla, Seiji M Liu, Stephen M Liu
Journal: Journal of Clinical Oncology (2018)

152 Background: Interventions that reduce symptom distress and enhance positive feelings are crucial for improving quality of life and, conceivably, overall survival of cancer patients. One remedy is the immersive virtual reality relaxation (VR-R) environment/s to inspire an emotion-focused coping mechanism in cancer patients. Herein, we report on our experience with the use of this VR-R intervention in normal volunteers and cancer patient volunteers. Methods: Fifty cancer patient volunteers underwent VR-R training and used the VR-R environment/s for 5 - 30 minutes. VR-R is a software-based simulation, which allows an individual to be placed inside an experience, hearing and interacting with stimuli that correspond with visual images of an artificial world. The VR equipment consists of the Oculus Rift Head Mounted Display (HMD) that enables play of an interactive scenario or game that patients can experience from a first-person perspective (i.e., upon entering the interactive scenario, participants are transported into a virtual, 3D world). After the immersion VR-R intervention, patients reported on their experience during the VR-R intervention by answering a QoL questionnaire created by IFGCURE/Cancer Center of Southern California/Sarcoma Oncology Center. Results: Eight of 50 (16%) patients experienced mild motion sickness as the only adverse event associated with its use. Table 1 shows the emotions that patients reportedly experienced during VR-R intervention. Conclusions: Taken together, the data support the premise that VR-R intervention is safe and may be efficacious in improving symptom distress and quality of life of cancer patients. A phase 1/2 study is planned to evaluate the safety and efficacy of the VR-R intervention in improving quality of life in a larger number of cancer patients. [Table: see text]
Airway Cells Make Trade-off When Fighting the Cold Virus
Authors: Tracy Hampton
Journal: JAMA (2018)

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
Longitudinal intravital imaging of transplanted mesenchymal stem cells elucidates their functional integration and therapeutic potency in an animal model of interstitial cystitis/bladder pain syndrome
Authors: Chae-Min Ryu, Hwan Yeul Yu, Hye-Yeon Lee, Jung-Hyun Shin, Seungun Lee, Hyein Ju, Bjorn Paulson, Sanghwa Lee, Sujin Kim, Jisun Lim, Jinbeom Heo, Ki-Sung Hong, Hyung-Min Chung, Jun Ki Kim, Dong-Myung Shin, Myung-Soo Choo
Journal: Theranostics (2018)

Rationale: Mesenchymal stem cell (MSC) therapy may be a novel approach to improve interstitial cystitis/bladder pain syndrome (IC/BPS), an intractable disease characterized by severe pelvic pain and urinary frequency.Unfortunately, the properties of transplanted stem cells have not been directly analyzed in vivo, which hampers elucidation of the therapeutic mechanisms of these cells and optimization of transplantation protocols.Here, we monitored the behaviors of multipotent stem cells (M-MSCs) derived from human embryonic stem cells (hESCs) in real time using a novel combination of in vivo confocal endoscopic and microscopic imaging and demonstrated their improved therapeutic potency in a chronic IC/BPS animal model.Methods: Ten-week-old female Sprague-Dawley rats were instilled with 10 mg of protamine sulfate followed by 750 µg of lipopolysaccharide weekly for 5 weeks.The sham group was instilled with phosphate-buffered saline (PBS).Thereafter, the indicated dose (0.1, 0.25, 0.5, and 1×10 6 cells) of M-MSCs or PBS was injected once into the outer layer of the bladder.The distribution, perivascular integration, and therapeutic effects of M-MSCs were monitored by in vivo endoscopic and confocal microscopic imaging, awake cystometry, and histological and gene expression analyses.Results: A novel combination of longitudinal intravital confocal fluorescence imaging and microcystoscopy in living animals, together with immunofluorescence analysis of bladder tissues, demonstrated that transplanted M-MSCs engrafted following differentiation into multiple cell types and gradually integrated into a perivascular-like structure until 30 days after transplantation.The beneficial effects of transplanted M-MSCs on bladder voiding function and the pathological characteristics of the bladder were efficient and long-lasting due to the stable engraftment of these cells. Ivyspring
Early Prediction of Moderate-Severe Chronic GvHD By Immunity Related Transcriptome
Authors: Amit Kalra, Poonam Dharmani-Khan, Stuti Patel, Rehan Mujeeb Faridi, Victor A. Lewis, Andrew Daly, Adnan Mansoor, Meer-Taher Shabani-Rad, Jan Storek, Faisal M Khan
Journal: Blood (2018)
Clindamycin versus clindamycin plus rifampicin in hidradenitis suppurativa treatment: Clinical and ultrasound observations
Authors: Raffaele Dante Caposiena Caro, Maria Vittoria Cannizzaro, Elisabetta Botti, Cosimo Di Raimondo, Eleonora Di Matteo, Roberta Gaziano, Luca Bianchi
Journal: Journal of the American Academy of Dermatology (2018)