tbuckley/cabot-search huggingface dataset:
Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions
Authors: Wei Lin, Pawan Noel, Erkut H. Borazanci, Jeeyun Lee, Albert Amini, In Woong Han, Jin Seok Heo, Gayle S. Jameson, Cory Fraser, Margaux Steinbach, Yanghee Woo, Yuman Fong, Derek Cridebring, Daniel D. Von Hoff, Joon Oh Park, Haiyong Han
Journal: Genome Medicine (2020)

Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC. However, almost all of those studies used primary tumor tissues.In this study, we employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with PDAC. Unsupervised clustering analysis as well as a new supervised classification algorithm, SuperCT, was used to identify the different cell types within the tumor tissues. The expression signatures of the different cell types were then compared between primary tumors and metastatic biopsies. The expressions of the cell type-specific signature genes were also correlated with patient survival using public datasets.Our single-cell RNA sequencing analysis revealed distinct cell types in primary and metastatic PDAC tissues including tumor cells, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. The cancer cells showed high inter-patient heterogeneity, whereas the stromal cells were more homogenous across patients. Immune infiltration varies significantly from patient to patient with majority of the immune cells being macrophages and exhausted lymphocytes. We found that the tumor cellular composition was an important factor in defining the PDAC subtypes. Furthermore, the expression levels of cell type-specific markers for EMT+ cancer cells, activated CAFs, and endothelial cells significantly associated with patient survival.Taken together, our work identifies significant heterogeneity in cellular compositions of PDAC tumors and between primary tumors and metastatic lesions. Furthermore, the cellular composition was an important factor in defining PDAC subtypes and significantly correlated with patient outcome. These findings provide valuable insights on the PDAC microenvironment and could potentially inform the management of PDAC patients.
Occupational dermatitis to facial personal protective equipment in health care workers: A systematic review
Authors: Jiade Yu, Jennifer K. Chen, Christen M. Mowad, Margo Reeder, Sara Hylwa, Sarah Chisolm, Cory A. Dunnick, Ari M. Goldminz, Sharon E. Jacob, Peggy A. Wu, Jonathan Zippin, Amber Reck Atwater
Journal: Journal of the American Academy of Dermatology (2020)

Prolonged wear of facial protective equipment can lead to occupational dermatoses.To identify important causes of occupational dermatoses from facial protective equipment.A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using PubMed and Embase databases. Articles were included if they reported occupational dermatoses caused by surgical/procedure masks or N95 respirators, or both.We identified 344 articles, and 16 were suitable for inclusion in this review. Selected articles focused on facial occupational dermatoses in health care workers. Allergic contact dermatitis to the elastic straps, glue, and formaldehyde released from the mask fabric was reported. Irritant contact dermatitis was common on the cheeks and nasal bridge due to pressure and friction. Irritant dermatitis was associated with personal history of atopic dermatitis and prolonged mask wear (>6 hours). Acneiform eruption was reported due to prolonged wear and occlusion. Contact urticaria was rare.Only publications listed in PubMed or Embase were included. Most publications were case reports and retrospective studies.This systematic review from members of the American Contact Dermatitis Society highlights cases of occupational dermatitis to facial protective equipment, including potential offending allergens. This work may help in the diagnosis and treatment of health care workers with facial occupational dermatitis.
Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble
Authors: Asaf Marco, Hiruy S. Meharena, Vishnu Dileep, Ravikiran M. Raju, Jose Davila-Velderrain, Amy Letao Zhang, Chinnakkaruppan Adaikkan, Jennie Z. Young, Fan Gao, Manolis Kellis, Li-Huei Tsai
Journal: Nature Neuroscience (2020)
Clinical development of CAR T cell therapy in China: 2020 update
Authors: Jianshu Wei, Yelei Guo, Yao Wang, Zhiqiang Wu, Jian Bo, Bin Zhang, Jun Zhu, Weidong Han
Journal: Cellular and Molecular Immunology (2020)

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in the treatment of hematological malignancies. In recent years, fast-growing CAR T clinical trials have actively explored their potential application scenarios. According to the data from the clinicaltrials.gov website, China became the country with the most registered CAR T trials in September 2017. As of June 30, 2020, the number of registered CAR T trials in China has reached 357. In addition, as many as 150 other CAR T trials have been registered on ChiCTR. Although CAR T therapy is flourishing in China, there are still some problems that cannot be ignored. In this review, we aim to systematically summarize the clinical practice of CAR T-cell therapy in China. This review will provide an informative reference for colleagues in the field, and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation.
Hypertensive Exposure Markers by MRI in Relation to Cerebral Small Vessel Disease and Cognitive Impairment
Authors: Raquel P. Amier, Nick Marcks, Astrid M. Hooghiemstra, Robin Nijveldt, Mark A. van Buchem, Albert de Roos, Geert Jan Biessels, L. Jaap Kappelle, Robert J. van Oostenbrugge, Rob J. van der Geest, Michiel L. Bots, Jacoba P. Greving, Wiro J. Niessen, Matthias J.P. van Osch, Jeroen de Bresser, Peter M. van de Ven, Wiesje M. van der Flier, Hans-Peter Brunner-La Rocca, Albert C. van Rossum
Journal: JACC. Cardiovascular imaging (2020)
FREQUENCY OF MYCOBACTERIUM TUBERCULOSIS ANTIGEN-SPECIFIC IFN-Gamma-SECRETING T CELLS CORRELATES WITH PRESENCE OF PATHOLOGY IN TUBERCULOSIS
Authors: Hinks Tsc., Dosanjh Dps., J A Innes, G Pasvol, S Hackforth, H Varia, K A Millington, R Gunatheesan, J J Deeks, A Lalvani
Journal: Thorax (2008)
Determinants associated with uncontrolled asthma in Portugal: A national population-based study
Authors: C. Camarinha, M. Fernandes, V. Alarc.úo, J. Franco, M.E. Mana.ºas, C. B.írbara, P.J. Nicola
Journal: Pulmonology (2020)

Asthma is a chronic and heterogeneous disease that affects people of all ages and has a high estimated increase in prevalence worldwide. Asthma control represents a main goal in the disease management. International studies revealed low levels of disease control resulting in a significant burden for healthcare systems, not only in terms of quality of life, but also in terms of health costs. Modifiable and non-modifiable factors have been identified as relating to poor asthma control level. In this study we evaluated the distribution of asthma control levels in Portuguese adult population and examine the determinants associated with uncontrolled asthma.Using a similar methodology to the one employed in the Asthma Insights and Reality in Europe (AIRE) survey, 327 active asthmatic patients were identified by random phone number and completed a questionnaire during 2011 to 2012. Asthma control was assessed by the evaluation of GINA based symptom control, by Asthma Control Test.äó (ACT) and by self-perception of control. To examine the relationship between uncontrolled asthma and its determinants, univariate logistic regression analysis, sequential multivariable regression and population attributable risk percentage were determinate.35.2% active asthmatic patients had uncontrolled asthma, 64.8% partially controlled and none of the individuals had total control of asthma assessed by ACT test. Factors significantly associated with poor asthma control scores were: age (OR 1.02 per year of age; 95% CI: 1.01.Çô1.03), female sex (OR 1.87; 95% CI: 1.15.Çô3.04), educational level (OR 0.5; 95% CI: 0.28.Çô0.89 at high school level or over), occupation (OR 4.92; 95% CI: 2.12.Çô11.42 if looking for a first job or unemployed) (OR 2.51; 95% CI: 1.35.Çô4.65 if being retired), income (OR 0.23; 95% CI: 0.07.Çô0.72 if >619 euros), BMI (OR 1.09 per BMI unit; 95% CI: 1.03.Çô1.14), having rhinitis symptoms (OR 4.40; 95% CI: 2.56.Çô7.58) and using inhaled corticosteroids (OR 0.44; 95%CI: 0.24.Çô0.82 if used in the past or never used). Looking for a first job or being unemployed, BMI and having rhinitis symptoms remained significant after multivariate adjustments.Uncontrolled asthma was associated with several determinants. Their identification can contribute to improve asthma care both from clinical and from public health perspectives.
Risk of immunotherapy-related narcolepsy in genetically predisposed patients: a case report of narcolepsy after administration of pembrolizumab
Authors: Yutaka Natori, Eisaku Sasaki, Shu Soeda, Shigenori Furukawa, Yusuke Azami, Emi Tokuda, Takashi Kanbayashi, Shigehira Saji
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immune-related adverse events associated with immune checkpoint therapy cause autoimmune disease-like symptoms. People who carry specific genotypes or haplotypes of human leucocyte antigen (HLA) are known to be predisposed to develop autoimmune diseases including narcolepsy. Immunotherapy could be a trigger to develop narcolepsy in predisposing HLA positive patients. Case presentation A 66-year-old woman with stage IVB endometrial carcinosarcoma experienced daytime sleepiness and temporary muscle weakness 14 days after the administration of an immune checkpoint inhibitor, pembrolizumab. These were consistent with the main symptoms of narcolepsy with cataplexy. This patient carried a highly predisposing HLA haplotype for narcolepsy; HLA-DQB1*06:02, DRB1*15:01, DQA1*01:02 and DRB5*01:01:01. A hypocretin-1/orexin-A concentration in the patient’s cerebrospinal fluid was low at 9.6 pg/mL in ELISA, and 155.5 pg/mL in radioimmunoassay that was below the normal level of 200 pg/mL. Therefore, she was diagnosed with narcolepsy tentatively according to the International Classification of Sleep Disorders, third edition diagnostic criteria for narcolepsy. The onset of narcolepsy in the 60s is very rare, and narcoleptic symptoms in our patient were likely to be caused by pembrolizumab. Conclusions This case suggests that treatment with immune checkpoint inhibitors potentially causes narcolepsy in genetically predisposed patients.
Helen Salisbury: Clutching at straws (and sticky tape)
Authors: Helen Salisbury
Journal: BMJ (2020)

Doctors like to have answers: it makes us feel useful. GPs take pride in our tolerance of uncertainty, but even we are being pushed beyond our comfort zone by current circumstances, and many of us are very apprehensive. Having lost patients and colleagues during the first wave of the covid-19 pandemic, I now fear—despite voices raised in dismay, then and now—that some of the mistakes from March are about to be repeated.

We were told in June that a functioning test, track, and trace system was the key to getting England safely back to work, but it’s still lacking.1 As schools go back …
Glioblastoma TCGA Mesenchymal and IGS 23 Tumors are Identifiable by IHC and have an Immune-phenotype Indicating a Potential Benefit from Immunotherapy
Authors: Cristina Carrato, Francesc Alameda, Anna Esteve-Codina, Estela Pineda, Oriol Arpí, Maria Martinez-García, Mar Mallo, Marta Gut, Raquel Lopez-Martos, Sonia Del Barco, Teresa Ribalta, Jaume Capellades, Josep Puig, Oscar Gallego, Carlos Mesia, Ana M Muñoz-Marmol, Ivan Archilla, Montserrat Arumí, Julie Marie Blanc, Beatriz Bellosillo, Silvia Menendez, Anna Esteve, Silvia Bagué, Ainhoa Hernandez, Jordi Craven-Bartle, Rafael Fuentes, Noemí Vidal, Iban Aldecoa, Nuria de la Iglesia, Carmen Balana
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice. Experimental Design: Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities. Results: We detected high molecular and IHC overlapping of the The Cancer Genome Atlas (TCGA) mesenchymal subtype with instrinsic glioma subtypes (IGS) cluster 23 and of the TCGA classical subtype with IGS cluster 18. IHC patterns, gene fusion profiles, and immune-phenotypes varied across subtypes. IHC revealed that the TCGA classical subtype was identified by high expression of EGFR and low expression of PTEN, while the mesenchymal subtype was identified by low expression of SOX2 and high expression of two antibodies, SHC1 and TCIRG1, selected on the basis of RNA differential transcriptomic expression. The proneural subtype was identified by frequent positive IDH1 expression and high Olig2 and Ki67 expression. Immune-phenotyping showed that mesenchymal and IGS 23 tumors exhibited a higher positive effector cell score, a higher negative suppressor cell score, and lower levels of immune checkpoint molecules. The cell-type deconvolution analysis revealed that these tumors are highly enriched in M2 macrophages, resting memory CD4+ T cells, and activated dendritic cells, indicating that they may be ideal candidates for immunotherapy, especially with anti-M2 and/or dendritic cell vaccination. Conclusions: There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with IHC and could well be optimal candidates for immunotherapy.
Road Map to Safe and Well-Designed De-escalation Trials of Systemic Adjuvant Therapy for Solid Tumors
Authors: Martine J. Piccart, Florentine S. Hilbers, Judith M. Bliss, Carmela Caballero, Elizabeth S. Frank, Patrick Renault, Rachida Naït Kaoudjt, Eva Schumacher, Patricia A. Spears, Meredith M. Regan, Richard D. Gelber, Nancy E. Davidson, Larry Norton, Eric P. Winer
Journal: Journal of Clinical Oncology (2020)

An important challenge in the field of cancer is finding the balance between delivering effective treatments and avoiding adverse effects and financial toxicity caused by innovative, yet expensive, drugs. To address this, several treatment de-escalation trials have been conducted, but only a few of these have provided clear answers. A few trials had poor accrual or had design flaws that led to conflicting results. Members of the Breast International Group (BIG) and North American Breast Cancer Group (NABCG) believe the way forward is to understand the lessons from these trials and listen more carefully to what truly matters to our patients. We reviewed several adjuvant trials of different cancer types and developed a road map for improving the design and implementation of future de-escalation trials. The road map incorporates patients' insights obtained through focused group discussions across the BIG-NABCG networks. Considerations for the development of de-escalation trials for systemic adjuvant treatment, including noninferiority trial design, choice of end points, and prioritization of a patient's perspectives, are presented in this consensus article.
Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents
Authors: Anna R. Docherty, Andrey A. Shabalin, Emily DiBlasi, Eric Monson, Niamh Mullins, Daniel E. Adkins, Silviu-Alin Bacanu, Amanda V. Bakian, Sheila Crowell, Danli Chen, Todd M. Darlington, William B. Callor, Erik D. Christensen, Douglas Gray, Brooks Keeshin, Michael Klein, John S. Anderson, Leslie Jerominski, Caroline Hayward, David J. Porteous, Andrew McIntosh, Qingqin Li, Hilary Coon
Journal: American Journal of Psychiatry (2020)

Death by suicide is a highly preventable yet growing worldwide health crisis. To date, there has been a lack of adequately powered genomic studies of suicide, with no sizable suicide death cohorts available for analysis. To address this limitation, the authors conducted the first comprehensive genomic analysis of suicide death using previously unpublished genotype data from a large population-ascertained cohort.
Rapid Enhancer Remodeling and Transcription Factor Repurposing Enable High Magnitude Gene Induction upon Acute Activation of NK Cells
Authors: Giuseppe Sciumè, Yohei Mikami, Dragana Jankovic, Hiroyuki Nagashima, Alejandro V. Villarino, Tasha Morrison, Chen Yao, Sadie Signorella, Hong-Wei Sun, Stephen R. Brooks, Difeng Fang, Vittorio Sartorelli, Shingo Nakayamada, Kiyoshi Hirahara, Beatrice Zitti, Fred P. Davis, Yuka Kanno, John J. O’Shea, Han-Yu Shih
Journal: Immunity (2020)
AB0036 Polymorphism of cholesterol crystalas in synovial fluid
Authors: IT Zimmermann-Górska, M Puszczewicz, G Bia³kowska-Puszczewicz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The aim of the study was to evaluate the frequency of cholesterol crystals occurrence in synovial fluid (SF) in rheumatic diseases as well as characteristics of crystals. <h3>Objectives</h3> We have studied 1000 synovial fluid samples from 854 patients. The most numerous was group of rheumatoid arthritis (RA) patients (573 cases) and osteoarthritis (OA). <h3>Methods</h3> Synovial fluids were taken on heparin as anticoagulant. SF sediments were examined under polarised microscope. <h3>Results</h3> Cholesterol crystals were demonstrated in 16 samples taken from 7 patients with RA only. Most of the crystals occurred as typical large flat rectangular or romboid plates. They ranged in size from 8 to 100 um and they showed strong birefringence with negative or positive elongation. Less often, they appeared as long rods or curved needle-shaped crystals. <h3>Conclusion</h3> The results showed rare occurrence of cholesterol crystals in synovial fluid samples. Polymorphism of cholesterol crystals under polarised microscope may be a cause of difficulties in synovial crystals differentiation.
THE BIOLOGICAL EFFECT OF TISSUE PLASMINOGEN (T-PA) ACTIVATOR AND DNASE INTRAPLEURAL DELIVERY IN PLEURAL INFECTION PATIENTS
Authors: N I Kanellakis, J W Wrightson, R Hallifax, R Mercer, M Fayed, R Asciak, E Hedley, M Dobson, I Psallidas, N M Rahman
Journal: Thorax (2018)
Suppression of Serum Interferon‐γ Levels as a Potential Measure of Response to Ustekinumab Treatment in Patients With Systemic Lupus Erythematosus
Authors: Matteo Cesaroni, Loqmane Seridi, Matthew J. Loza, Jessica Schreiter, Kristen Sweet, Carol Franks, Keying Ma, Ashley Orillion, Kim Campbell, Robert M. Gordon, Patrick Branigan, Peter Lipsky, Ronald van Vollenhoven, Bevra H. Hahn, George C. Tsokos, Marc Chevrier, Shawn Rose, Frédéric Baribaud, Jarrat Jordan
Journal: Arthritis & Rheumatology (2020)

In a previously reported phase II randomized, placebo-controlled, interventional trial, we demonstrated that treatment with ustekinumab, an anti-interleukin-12 (IL-12)/IL-23 p40 neutralizing monoclonal antibody, improved global and organ-specific measures of disease activity in patients with active systemic lupus erythematosus (SLE). Utilizing the biomarker data from this phase II clinical study, we sought to determine whether modulation of the expression of IL-12, IL-23, or both cytokines by ustekinumab is associated with clinical efficacy in patients with SLE.This phase II randomized, placebo-controlled study enrolled 102 patients with autoantibody-positive SLE whose disease remained active despite standard-of-care therapy. Patients were randomized at a 3:2 ratio to receive ~6 mg/kg ustekinumab intravenously or placebo at week 0, followed by subcutaneous injections of 90 mg ustekinumab or placebo every 8 weeks, with placebo crossover to 90 mg ustekinumab every 8 weeks. The SLE Responder Index 4 (SRI-4) at week 24 was used to determine which patients could be classified as ustekinumab responders and which could be classified as nonresponders. In addition to measurements of p40 and IL-23, serum levels of interferon-γ (IFNγ), IL-17A, IL-17F, and IL-22, as a proxy for the IL-12 and IL-23 pathways, were quantified by immunoassay.Changes in the serum levels of IL-17A, IL-17F, and IL-22 at different time points after treatment were not consistently significantly associated with an SRI-4 clinical response to ustekinumab in patients with SLE. In contrast, an SRI-4 response to ustekinumab was significantly associated (P < 0.01) with durable reductions in the serum IFNγ protein levels at several time points relative to baseline, which was not observed in ustekinumab nonresponders or patients who received placebo.While not diminishing a potential role of IL-23, these serum biomarker assessments indicate that IL-12 blockade has an important role in the mechanism of action of ustekinumab treatment in patients with SLE.
Treatment of Masked Hypertension with a Chinese Herbal Formula
Authors: Dong-Yan Zhang, Yi-Bang Cheng, Qian-Hui Guo, Xiao-Li Shan, Fang-Fei Wei, Feng Lu, Chang-Sheng Sheng, Qi-Fang Huang, Chuan-Hua Yang, Yan Li, Ji-Guang Wang
Journal: Circulation (2020)

Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)-lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension.Patients with an office BP of <140/90 mm Hg and daytime ambulatory BP of 135 to 150 mm Hg systolic or 85 to 95 mm Hg diastolic were randomly assigned 1:1 to the treatment of gastrodia-uncaria granules or placebo 5 to 10 g twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP.At baseline, office and daytime BP of the 251 participants (mean age, 50.4 years; 53.4% men; mean body mass index 24.5 kg/m2; and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes, and smoking, respectively) averaged 129/82 and 135/89 mm Hg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44/3.39 and 2.91/1.60 mm Hg in the gastrodia-uncaria granules and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mm Hg; P≤0.025) and 24-hour BP (2.33/1.49 mm Hg; P≤0.012), but not for the clinic and nighttime BPs (P≥0.162). The per-protocol analysis in 229 patients produced similar results. Only 1 adverse event (sleepiness during the day) was reported, and no serious adverse event occurred.BP-lowering treatment with Chinese traditional medicine gastrodia-uncaria granules is efficacious for patients with masked hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02156024.