tbuckley/cabot-search huggingface dataset:
Exogenous Pigmentation Presenting as Longitudinal Melanonychia in a Child
Authors: Yuan Liang, Xiao Feng Han, Lin Ma
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Loss of Lkb1 impairs Treg function and stability to aggravate graft-versus-host disease after bone marrow transplantation
Authors: Xiuhua Su, Qianqian Wang, Wei Guo, Xiaolei Pei, Qing Niu, Maolan Liu, Yuanyuan Liu, Song Chen, Sizhou Feng, Yi He, Donglin Yang, Rongli Zhang, Qiaoling Ma, Weihua Zhai, Aiming Pang, Jialin Wei, Yong Huang, Yuechen Luo, Mingzhe Han, Xiaoming Feng, Erlie Jiang
Journal: Cellular and Molecular Immunology (2019)

Abstract Accumulating evidence suggests that a reduction in the number of Foxp3 + regulatory T cells (Tregs) contributes to the pathogenesis of acute graft-versus-host disease (aGVHD), which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the precise features and mechanism underlying the defects in Tregs remain largely unknown. In this study, we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution. Tregs from aGVHD patients exhibited multiple defects, including the instability of Foxp3 expression, especially in response to IL-12, impaired suppressor function, decreased migratory capacity, and increased apoptosis. Transcriptional profiling revealed the downregulation of Lkb1, a previously identified critical regulator of murine Treg identity and metabolism, and murine Lkb1-regulated genes in Tregs from aGVHD patients. Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene, respectively. Furthermore, a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity. These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.
Electrical impedance tomography for chest imaging in acute respiratory failure
Authors: Davide Chiumello, Giuseppe Francesco Sferrazza Papa
Journal: European Respiratory Journal (2019)

We read with interest the letter from Frerichs and Zhao regarding our recently published European Respiratory Society (ERS) statement [1]. Frerichs and Zhao noted that, although in the task force electrical impedance tomography (EIT) was considered among the imaging techniques used in acute respiratory failure, no related articles were reported in the final paper. In the report, task force members supported by two methodologists performed a systematic search of the literature on five lung imaging techniques ( i.e. chest radiography, lung ultrasound, computed tomography, position emission tomography and EIT) using the same search terms for all the techniques (refer to tables S1–S4 in the ERS statement); according to these criteria we did not report any articles related to the EIT. Is electrical impedance tomography ready for clinical use in acute respiratory failure? <http://bit.ly/30Gjvlt>
A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors
Authors: Xiaomin Qian, Zhendong Shi, Hongzhao Qi, Ming Zhao, Kai Huang, Donglin Han, Junhu Zhou, Chaoyong Liu, Yang Liu, Yunfeng Lu, Xubo Yuan, Jin Zhao, Chunsheng Kang
Journal: Theranostics (2019)

Cell-based immunotherapy for the treatment of hematologic malignancies, such as leukemia and lymphoma, has seen much success and played an increasingly important role in clinical studies.Nevertheless, the efficacy of immunotherapy in solid tumors still needs improvements due to the immunosuppressive properties of tumor cells and the microenvironment.To overcome these limitations, we prepared a novel tumor-targeting delivery system based on the underlying mechanism of immune-targeted cell death that encapsulated granzyme B protein within a porous polymeric nanocapsule.Methods: A cell-penetrating peptide TAT was attached onto granzyme B (GrB) to enhance its transmembrane transport efficiency and potency to induce cell apoptosis.The endocytosis and internalization pathways of GrB-TAT (GrB-T) were analyzed in comparison with perforin by confocal microscopy and flow cytometry.Furthermore, the positively charged GrB-T was wrapped into nanoparticles by p-2-methacryloyloxy ethyl phosphorylcholine (PMPC)-modified HA (hyaluronic acid).The nanoparticles (called TCiGNPs) were characterized in terms of zeta potential and by transmission electron microscopy (TEM).The in vitro anti-tumor effects of GrB-T were examined by cell apoptosis assay and Western blotting analysis.The in vivo anti-tumor therapeutic efficacy of TCiGNPs was evaluated in a mouse tumor model. Results:The TAT peptide could play a role similar to perforin to mediate direct transmembrane transfer of GrB and improve GrB-induced cell apoptosis.The TCiGNPs were successfully synthesized and accumulated in the solid tumor through enhanced permeability and retention (EPR) effect.In the tumor microenvironment, TCiGNPs could be degraded by hyaluronidase and triggered the release of GrB-T.The TAT peptide enabled the translocation of GrB across the plasma membrane to induce tumor cell apoptosis in vivo. Conclusion:We successfully developed a granzyme B delivery system with a GrB-T core and a PMPC/HA shell that simulated CTL/NK cell-mediated cancer immunotherapy mechanism.The GrB delivery system holds great promise for cancer treatment analogous to the CTL/NK cell-induced immunotherapy.
HIV: doctor who reused needles is blamed as nearly 900 children test positive in Pakistani city
Authors: Owen Dyer
Journal: BMJ (2019)

Nearly 900 children under 12 are among 1112 cases of HIV infection now confirmed in an outbreak linked to a paediatrician in Ratodero, Pakistan, who reused syringes and IV drips.

Authorities fear that the true number of people infected could be much higher, as only 36 000 of the town’s population of roughly 225 000 have been tested to date.

The cluster of HIV cases was first discovered in May, when children around the city started coming down with a fever. A local journalist, Gulbahar Shaikh, revealed the cause to be HIV, sparking a rush to get tested.

Investigators interviewed the families of children who had tested positive and discovered that many had visited a paediatrician named Muzaffar Ghanghro. Ghanghro was one of the cheapest doctors in the city, where …
A Novel Standardized Quantitative Suppression Assay Reveals a Diversity of Human Immune-Regulatory Cell Potency
Authors: Samantha Miner, Nancy F. Hensel, Bahey Salem, Neil Dunavin, Kazushi Tanimoto, Minoo Battiwalla, Kit Lu, Keyvan Keyvanfar, Marianna Sabatino, David Stroncek, Patrick J Hanley, Catherine M. Bollard, Katayoun Rezvani, Marcin Kortylewski, Pawel Muranski, John Barrett, Sawa Ito
Journal: Blood (2014)
Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage
Authors: Marie-Louise Frémond, Marie Legendre, Michael Fayon, Annick Clement, Emilie Filhol-Blin, Nicolas Richard, Laura Berdah, Sylvie Roullaud, Gillian I Rice, Vincent Bondet, Darragh Duffy, Chiara Sileo, Hubert Ducou le Pointe, Hugues Begueret, Aurore Coulomb, Bénédicte Neven, Serge Amselem, Yanick Crow, Nadia Nathan
Journal: Thorax (2019)

COPA (coatomer subunit α) syndrome is a newly recognised cause of interstitial lung disease in children and adults, frequently associated with arthritis and renal dysfunction. We report a 11-year-old girl with disease limited to major pulmonary haemosiderosis manifesting at the age of 2 years, due to a heterozygous p.(Arg233His) mutation in COPA . Her interferon (IFN) signature was elevated (10.312 and 12.429, healthy &lt;2.466), as was the level of serum IFNα (211 fg/mL, healthy &lt;10 fg/mL). STAT1 phosphorylation in T lymphocytes and monocytes was increased as compared with healthy controls. Based on these results she was treated with the JAK1/2 inhibitor ruxolitinib, which resulted in reduction in IFN signalling and appeared to be associated with partial though incomplete decrease in the severity of her pulmonary disease. Patients with alveolar haemorrhage of unknown origin should be considered for COPA screening. Functional tests can help to personalise patient therapy.
A Microfluidic Platform for Single Cell Fluorometric Granzyme B Profiling
Authors: Jonathan C. Briones, Wilfred V. Espulgar, Shohei Koyama, Hiroyuki Yoshikawa, JeongHoon Park, Yujiro Naito, Atsushi Kumanogoh, Eiichi Tamiya, Hyota Takamatsu, Masato Saito
Journal: Theranostics (2019)

Granzyme B (GrB) is an essential cytotoxic effector in cancer immunotherapy as it can be a potential biomarker to predict the efficacy of immunotherapies including checkpoint inhibitors.Monitoring the Granzyme B activity in cells would help determine a patient's clinical response to treatment and lead to better treatment strategies by preventing administration of ineffective therapies and avoid adverse events resulting in a delay in subsequent treatment.Methods: A microfluidic device with hydrodynamic traps and pneumatic valving system was fabricated using photo and soft lithography.Single cell Granzyme B (GrB) activity was detected and measured fluorometrically using a commercial assay kit with a peptide substrate containing GrB recognition sequence (Ac-IEPD-AFC) and AFC (7-Amino-4-trifluoromethylcoumarin) label.Fluorescence was observed and measured using a confocal microscope with CSU-W1 scanner unit and CCD camera as well as an inverted microscope with photodetector.Model cells (NK-92, GrB-transduced Jurkat, and THP1 cells) and human PBMCs from healthy donor and lung cancer patients including an anti-PD-1 antibody treated patient were profiled of its GrB activity as proof of concept.Results: GrB expression from the model cells was found to be markedly different.NK-92 cells were found to have higher GrB activity than the GrB-transduced Jurkat cells.THP-1 was found to have relatively no significant activity.A marked increase in GrB expression was also observed in anti-PD-1 treated lung cancer patient sample in comparison to PBMC from a healthy donor.TCR+ Ig-G4+ PBMC cells were found to have high activity which signifies a clear response to PD-1 blockade. Conclusion:As proof of concept, we have shown the capability of a microfluidic platform to measure GrB production through a single cell enzymatic activity assay.Our platform might be a promising tool for evaluating the sensitivity of immunotherapies and identifying specific T cell subset responsible for the anti-tumor response.
Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene–Driven Myeloid Leukemia
Authors: Cécile K. Lopez, Esteve Noguera, Vaia Stavropoulou, Elie Robert, Zakia Aid, Paola Ballerini, Chrystèle Bilhou-Nabera, Hélène Lapillonne, Fabien Boudia, Cécile Thirant, Alexandre Fagnan, Marie-Laure Arcangeli, Sarah J. Kinston, M'Boyba Diop, Bastien Job, Yann Lecluse, Erika Brunet, Loélia Babin, Jean Luc Villeval, Eric Delabesse, Antoine H.F.M. Peters, William Vainchenker, Muriel Gaudry, Riccardo Masetti, Franco Locatelli, Sébastien Malinge, Claus Nerlov, Nathalie Droin, Camille Lobry, Isabelle Godin, Olivier A. Bernard, Berthold Göttgens, Arnaud Petit, Françoise Pflumio, Juerg Schwaller, Thomas Mercher
Journal: Cancer Discovery (2019)

Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2-GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2-GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2-GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.See related commentary by Cruz Hernandez and Vyas, p. 1653.This article is highlighted in the In This Issue feature, p. 1631.
Effectiveness of a Question Prompt List Intervention for Older Patients Considering Major Surgery
Authors: Margaret L. Schwarze, Anne Buffington, Jennifer L. Tucholka, Bret Hanlon, Paul J. Rathouz, Nicholas Marka, Lauren J. Taylor, Christopher J. Zimmermann, Anna Kata, Nathan D. Baggett, Daniel A. Fox, Andrea E. Schmick, Ana Berlin, Nina E. Glass, Anne C. Mosenthal, Emily Finlayson, Zara Cooper, Karen J. Brasel
Journal: JAMA Surgery (2019)

Poor preoperative communication can have serious consequences, including unwanted treatment and postoperative conflict.To compare the effectiveness of a question prompt list (QPL) intervention vs usual care on patient engagement and well-being among older patients considering major surgery.This randomized clinical trial used a stepped-wedge design to randomly assign patients to a QPL intervention (n = 223) or usual care (n = 223) based on the timing of their visit with 1 of 40 surgeons at 5 US study sites. Patients were 60 years or older with at least 1 comorbidity and an oncologic or vascular (cardiac, neurosurgical, or peripheral vascular) problem that could be treated with major surgery. Family members were also enrolled (n = 263). The study dates were June 2016 to November 2018. Data analysis was by intent-to-treat.A brochure of 11 questions to ask a surgeon developed by patient and family stakeholders plus an endorsement letter from the surgeon were sent to patients before their outpatient visit.Primary patient engagement outcomes included the number and type of questions asked during the surgical visit and patient-reported Perceived Efficacy in Patient-Physician Interactions scale assessed after the surgical visit. Primary well-being outcomes included (1) the difference between patient's Measure Yourself Concerns and Well-being (MYCaW) scores reported after surgery and scores reported after the surgical visit and (2) treatment-associated regret at 6 to 8 weeks after surgery.Of 1319 patients eligible for participation, 223 were randomized to the QPL intervention and 223 to usual care. Among 446 patients, the mean (SD) age was 71.8 (7.1) years, and 249 (55.8%) were male. On intent-to-treat analysis, there was no significant difference between the QPL intervention and usual care for all patient-reported primary outcomes. The difference in MYCaW scores for family members was greater in usual care (effect estimate, 1.51; 95% CI, 0.28-2.74; P = .008). When the QPL intervention group was restricted to patients with clear evidence they reviewed the QPL, a nonsignificant increase in the effect size was observed for questions about options (odds ratio, 1.88; 95% CI, 0.81-4.35; P = .16), expectations (odds ratio, 1.59; 95% CI, 0.67-3.80; P = .29), and risks (odds ratio, 2.41; 95% CI, 1.04-5.59; P = .04) (nominal α = .01).The results of this study were null related to primary patient engagement and well-being outcomes. Changing patient-physician communication may be difficult without addressing clinician communication directly.ClinicalTrials.gov identifier: NCT02623335.
Application of machine learning to determine top predictors of noncalcified coronary burden in psoriasis: An observational cohort study
Authors: Eric Munger, Harry Choi, Amit K. Dey, Youssef A. Elnabawi, Jacob W. Groenendyk, Justin Rodante, Andrew Keel, Milena Aksentijevich, Aarthi S. Reddy, Noor Khalil, Jenis Argueta-Amaya, Martin P. Playford, Julie Erb-Alvarez, Xin Tian, Colin Wu, Johann E. Gudjonsson, Lam C. Tsoi, Mohsin Saleet Jafri, Veit Sandfort, Marcus Y. Chen, Sanjiv J. Shah, David A. Bluemke, Benjamin Lockshin, Ahmed Hasan, Joel M. Gelfand, Nehal N. Mehta
Journal: Journal of the American Academy of Dermatology (2019)
Influenza-associated mortality in hospital care: a retrospective cohort study of risk factors and impact of oseltamivir in an English teaching hospital, 2016 to 2017
Authors: Mark Reacher, Ben Warne, Lucy Reeve, Neville Q. Verlander, Nicholas K. Jones, Kyriaki Ranellou, Silvana Christou, Callum Wright, Saher Choudhry, Maria Zambon, Clare Sander, Hongyi Zhang, Hamid Jalal
Journal: Eurosurveillance (2019)

BackgroundEvidence of an oseltamivir treatment effect on influenza A(H3N2) virus infections in hospitalised patients is incomplete.AimsThis cohort study aimed to evaluate risk factors for death among PCR-confirmed hospitalised cases of seasonal influenza A(H3N2) of all ages and the impact of oseltamivir.MethodsParticipants included all 332 PCR-confirmed influenza A(H3N2) cases diagnosed between 30 August 2016 and 17 March 2017 in an English university teaching Hospital. Oseltamivir treatment effect on odds of inpatient death was assessed by backward stepwise multivariable logistic regression analysis.ResultsThe odds of death were reduced by two thirds (odds ratio (OR): 0.32; 95% confidence interval (CI): 0.11-0.93), in inpatients treated with a standard course of oseltamivir 75 mg two times daily for 5 days - compared with those untreated with oseltamivir, after adjustment for age, sex, current excess alcohol intake, receipt of 2016/17 seasonal influenza vaccine, serum haemoglobin and hospital vs community attribution of acquisition of influenza.ConclusionsOseltamivir treatment given according to National Institutes of Clinical Excellence (NICE); United States Centres for Disease Control and Prevention (CDC); Infectious Diseases Society of America (IDSA) and World Health Organization (WHO) guidelines was shown to be effective in reducing the odds of mortality in inpatients with PCR-confirmed seasonal influenza A(H3N2) after adjustment in a busy routine English hospital setting. Our results highlight the importance of hospitals complying with relevant guidelines for prompt seasonal influenza PCR testing and ensuring standard oseltamivir treatment to all PCR-confirmed cases of seasonal influenza.
Advances in nanomedicine for cancer starvation therapy
Authors: Shuangjiang Yu, Zhaowei Chen, Xuan Zeng, Xuesi Chen, Zhen Gu
Journal: Theranostics (2019)

Abnormal cell metabolism with vigorous nutrition consumption is one of the major physiological characteristics of cancers. As such, the strategy of cancer starvation therapy through blocking the blood supply, depleting glucose/oxygen and other critical nutrients of tumors has been widely studied to be an attractive way for cancer treatment. However, several undesirable properties of these agents, such as low targeting efficacy, undesired systemic side effects, elevated tumor hypoxia, induced drug resistance, and increased tumor metastasis risk, limit their future applications. The recent development of starving-nanotherapeutics combined with other therapeutic methods displayed the promising potential for overcoming the above drawbacks. This review highlights the recent advances of nanotherapeutic-based cancer starvation therapy and discusses the challenges and future prospects of these anticancer strategies.
Integrin α<sub>v</sub>β<sub>3</sub>-targeted radionuclide therapy combined with immune checkpoint blockade immunotherapy synergistically enhances anti-tumor efficacy
Authors: Haojun Chen, Liang Zhao, Kaili Fu, Qiuming Lin, Xuejun Wen, Orit Jacobson, Long Sun, Hua Wu, Xianzhong Zhang, Zhide Guo, Qin Lin, Xiaoyuan Chen
Journal: Theranostics (2019)

Radiotherapy combined with immunotherapy has revealed promising outcomes in both preclinical studies and ongoing clinical trials. Targeted radionuclide therapy (TRT) is a branch of radiotherapy concerned with the use of radioisotopes, radiolabeled molecules or nanoparticles that deliver particulate radiation to cancer cells. TRT is a promising approach in cases of metastatic disease where conventional treatments are no longer effective. The increasing use of TRT raises the question of how to best integrate TRT with immunotherapy. In this study, we proposed a novel therapeutic regimen that combined programmed death ligand 1 (PD-L1)-based immunotherapy with peptide-based TRT (177Lu as the radionuclide) in the murine colon cancer model.To explore the most appropriate timing of immunotherapy after radionuclide therapy, the anti-PD-L1 antibody (αPD-L1 mAb) was delivered in a concurrent or sequential manner when 177Lu TRT was given.The results demonstrated that TRT led to an acute increase in PD-L1 expression on T cells, and TRT in combination with αPD-L1 mAb stimulated the infiltration of CD8+ T cells, which improved local tumor control, overall survival and protection against tumor rechallenge. Moreover, our data revealed that the time window for this combination therapy may be critical to outcome.This therapeutic combination may be a promising approach to treating metastatic tumors in which TRT can be used. Clinical translation of the result would suggest that concurrent rather than sequential blockade of the PD-1/PD-L1 axis combined with TRT improves overall survival and long-term tumor control.