tbuckley/cabot-search huggingface dataset:
Association of Clinical Markers With Disease Progression in Patients With Vitiligo From China
Authors: Li Zhang, Shujun Chen, Yuli Kang, Xiuxiu Wang, Fang Yan, Min Jiang, Qianqian Wang, Ziqi Liu, Chengfeng Zhang, Leihong Xiang
Journal: JAMA Dermatology (2020)

It is necessary to determine whether established clinical markers of vitiligo are associated with disease progression, severity, and patient prognosis.To evaluate the utility of trichrome sign, confetti-like depigmentation, and Koebner phenomenon in assessing disease progression, severity, and prognosis in patients with vitiligo.In this prospective cohort study, 425 patients with vitiligo were recruited from the outpatient department of Huashan Hospital, Fudan University in Shanghai, China, from September 1, 2016, to May 13, 2019.Disease progression, severity, and prognosis during a 12-month period. The active stage of vitiligo was defined as Vitiligo European Task Force spreading score of at least 1 or more lesions appearing as hypomelanotic with poorly defined borders using a Wood light. Progression was assessed using the Vitiligo Area Scoring Index (VASI) and serum CXCL10 level measurement.Of the 458 enrolled patients, 425 (235 female [55.3%]; mean [SD] age, 30.9 [10.2] years) completed the 12-month follow-up. Of the 425 patients (224 with no clinical marker and 201 with at least 1 clinical marker) included in this analysis, the proportion in the active stage of the disease was significantly higher in the cohort with at least 1 clinical marker compared with the cohort without any clinical marker at the first visit (196 of 201 [97.5%] vs 159 of 224 [71.0%]; P < .001) and at 3-month follow up (91 of 201 [45.3%] vs 52 of 224 [23.2%]; P < .001). The proportion of patients with rapid disease progression was also higher in the group with at least 1 clinical marker at 1-month follow-up (142 of 201 [70.6%] vs 60 of 224 [26.8%]; P < .001) and 3-month follow-up (63 of 201 [31.3%] vs 9 of 224 [4.0%]; P < .001). The improvement in VASI score (SD) was significantly smaller among patients with at least 1 clinical marker compared with those without any clinical marker at 6 months (mean [SD], 0.14 [0.12] vs 0.23 [0.21]; P = .02), at 9 months (mean [SD], 0.29 [0.19] vs 0.44 [0.25]; P = .03), and at 12 months (mean [SD], 0.47 [0.21] vs 0.63 [0.23]; P = .03).The presence of a clinical marker in patients with vitiligo may be associated with worse prognosis and rapid disease progression. Patients with multiple clinical markers may require more intensive treatment.
The protein C activator AB002 rapidly interrupts thrombus development in baboons
Authors: Erik I. Tucker, Norah G. Verbout, Brandon D. Markway, Michael Wallisch, Christina U. Lorentz, Monica T. Hinds, Joseph J. Shatzel, Leslie A. Pelc, David C. Wood, Owen J. T. McCarty, Enrico Di Cera, András Gruber
Journal: Blood (2020)
SWI/SNF Complex Mutations in Gynecologic Cancers: Molecular Mechanisms and Models
Authors: Yemin Wang, Lien Hoang, Jennifer X. Ji, David G. Huntsman
Journal: Annual Review of Pathology Mechanisms of Disease (2020)

The SWI/SNF (mating type SWItch/Sucrose NonFermentable) chromatin remodeling complexes interact with histones and transcription factors to modulate chromatin structure and control gene expression. These evolutionarily conserved multisubunit protein complexes are involved in regulating many biological functions, such as differentiation and cell proliferation. Genomic studies have revealed frequent mutations of genes encoding multiple subunits of the SWI/SNF complexes in a wide spectrum of cancer types, including gynecologic cancers. These SWI/SNF mutations occur at different stages of tumor development and are restricted to unique histologic types of gynecologic cancers. Thus, SWI/SNF mutations have to function in the appropriate tissue and cell context to promote gynecologic cancer initiation and progression. In this review, we summarize the current knowledge of SWI/SNF mutations in the development of gynecologic cancers to provide insights into both molecular pathogenesis and possible treatment implications for these diseases.
Abstract 16: Dispatched Citizen Responders Perform Three Out of Four of all Bystander Defibrillated Out-Of-Hospital Cardiac Arrests in Residential Areas
Authors: Linn Andelius, Carolina Malta Hansen, Freddy Lippert, Christian Torp-pedersen, Lena Karlsson, Gunnar H Gislason, Fredrik Folke
Journal: Circulation (2019)

Introduction: Bystander defibrillation has increased in public locations but remained stagnated around 2% in private homes, where most out-of-hospital cardiac arrests (OHCAs) occur. Hypothesis: Dispatching citizen responders through a smartphone application can increase bystander defibrillation in residential OHCAs. Methods: From September 2017-2018, a total of 23,117 (1,284/100,000) citizen responders and 5,225 (290/100,000) automated external defibrillators (AEDs) were registered in the Capital Region of Denmark (1.8 mil. inhabitants). In case of suspected OHCA, up to 20 citizen responders &lt;1.8 km (1.1 miles) from the OHCA were alerted and dispatched to either start cardiopulmonary resuscitation (CPR) or to retrieve an AED. Activated citizen responders received a survey where they reported whether they arrived before Emergency Medical Services (EMS) and defibrillated the patient. Results: Of 433 consecutive OHCAs included, 354 (81.8%) were residential OHCAs. Compared with citizen responders in public locations, those in residential areas were a median of 100m further away from OHCAs but were equally likely to arrive before EMS (~40% of both residential and public OHCAs). A total of 9.3% (33 of 354) of all residential OHCAs were bystander defibrillated. Citizen responders were responsible for 75.8% (25 out of 33) of all bystander defibrillated OHCAs in residential areas compared to 50.0% (13 out of 26) of all bystander defibrillated OHCAs in public areas (Table 1). Conclusions: Dispatched citizen responders arrived before EMS in 40.1% (142 of 354) of all residential OHCAs and performed three out of four of all bystander defibrillated OHCAs in residential areas.
CHAOS Challenge - combined (CT-MR) healthy abdominal organ segmentation
Authors: A. Emre Kavur, N. Sinem Gezer, Mustafa Barış, Sinem Aslan, Pierre-Henri Conze, Vladimir Groza, Duc Duy Pham, Soumick Chatterjee, Philipp Ernst, Savaş Özkan, Bora Baydar, Dmitry Lachinov, Shuo Han, Josef Pauli, Fabian Isensee, Matthias Perkonigg, Rachana Sathish, Ronnie Rajan, Debdoot Sheet, Gurbandurdy Dovletov, Oliver Speck, Andreas Nürnberger, Klaus H. Maier-Hein, Gözde Bozdağı Akar, Gözde Ünal, Oğuz Dicle, M. Alper Selver
Journal: Medical Image Analysis (2020)
Contribution of diet to gut microbiota and related host cardiometabolic health: diet-gut interaction in human health
Authors: Yi Wan, Jun Tang, Jiaomei Li, Jie Li, Jihong Yuan, Fenglei Wang, Duo Li
Journal: Gut Microbes (2020)

Obesity and cardiometabolic diseases in both developed and developing counties in a state of nutrition transition are often related to diet, which also play a major role in shaping human gut microbiota. The human gut harbors diverse microbes that play an essential role in the well-being of their host. Complex interactions between diet and microorganisms may lead to beneficial or detrimental outcomes to host cardiometabolic health. Despite numerous studies using rodent models indicated that high-fat diet may disrupt protective functions of the intestinal barrier and contribute to inflammatory processes, evidence from population-based study is still limited. In our recent study of a 6-month randomized controlled-feeding trial, we showed that high-fat, low-carbohydrate diet was associated with unfavorable changes in gut microbiota, fecal microbial metabolites, and plasma proinflammatory factors in healthy young adults. Here, we provide an overview and extended discussion of our key findings, and outline important future directions.
The pathogenic role of coronary microvascular dysfunction in the setting of other cardiac or systemic conditions
Authors: Regina E Konst, Tomasz J Guzik, Juan-Carlos Kaski, Angela H E M Maas, Suzette E Elias-Smale
Journal: Cardiovascular Research (2020)

Abstract Coronary microvascular dysfunction (CMD) plays a pathogenic role in cardiac and systemic conditions other than microvascular angina. In this review, we provide an overview of the pathogenic role of CMD in the setting of diabetes mellitus, obesity, hypertensive pregnancy disorders, chronic inflammatory and autoimmune rheumatic disorders, chronic kidney disease, hypertrophic cardiomyopathy, and aortic valve stenosis. In these various conditions, CMD results from different structural, functional, and/or dynamic alterations in the coronary microcirculation associated with the primary disease process. CMD is often detectable very early in the course of the primary disease, before clinical symptoms or signs of myocardial ischaemia are present, and it portrays an increased risk for cardiovascular events.
Efficacy of Immune Checkpoint Inhibitors in Lung Sarcomatoid Carcinoma
Authors: Charlotte Domblides, Karen Leroy, Isabelle Monnet, Julien Mazières, Fabrice Barlesi, Valérie Gounant, Simon Baldacci, Bertrand Mennecier, Anne-Claire Toffart, Clarisse Audigier-Valette, Ludovic Doucet, Etienne Giroux-Leprieur, Florian Guisier, Charles Ricordel, Olivier Molinier, Maurice Perol, Eric Pichon, Gilles Robinet, Dorine Templement-Grangerat, Anne-Marie Ruppert, Nathalie Rabbe, Martine Antoine, Marie Wislez
Journal: Journal of Thoracic Oncology (2020)
B02 The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma
Authors: M. Momcilovic, J.T. Lee, D. Braas, T.G. Graeber, F. Parlati, S. Demo, R. Li, M. Gricowski, R. Shuman, J. Ibarra, D. Fridman, M. St.John, N. Bernthal, N. Federman, J. Yanagawa, S.M. Dubinett, S. Sadeghi, H.R. Christofk, D.B. Shackelford
Journal: Journal of Thoracic Oncology (2020)
Lack of Availability and Efficacy of Phase I and Basket Trials for Patients With Gastrointestinal Cancers
Authors: Rajiv Agarwal, Nicholas A Cangemi, Andrew S Epstein, James Harding, Diane Reidy-Lagunes, Leonard B Saltz
Journal: JNCI Journal of the National Cancer Institute (2019)

In the modern era of targeted and immune-based therapies, investigator and patient expectations of availability and efficacy in phase I trials have increased. We assessed availability of, and benefit from, early drug development trials, specifically in patients with gastrointestinal cancers. We reviewed computerized referral records of the Early Drug Development Service at our institution to identify patients internally referred from our Gastrointestinal Oncology Service in calendar year 2018. End points were treatment on a trial, 3- and 6-month progression-free survival (PFS), and any tumor shrinkage. Of 394 gastrointestinal cancer patients referred in 2018, 54 enrolled on a trial and 53 (13.5%) were treated (1 withdrew before treatment): 34 on immune-based and 19 on targeted (3 to phase II basket) studies. None of the 52 patients who had exhausted standard therapy achieved 6-month PFS, two (3.8%) met 3-month PFS with tumor growth below Response Evaluation Criteria in Solid Tumors progression at 3 months, and both came off study for progression at 4 months. One patient who was to receive an irinotecan-based regimen as standard therapy instead received irinotecan plus an investigational targeted agent and remained stable for 8 months. No patients achieved any degree of tumor shrinkage. The most common reasons for nonaccrual were lack of available protocol treatment openings and failure to meet eligibility criteria for specific trials. Thus, availability and benefit from investigational treatment in this treatment-refractory gastrointestinal cancer patient population was extremely modest. Expectations regarding both availability and efficacy of phase I investigational therapy in gastrointestinal cancer patients likely exceed what our experience suggests.
Abstract 10000: Mutation in CELA2A Derives Early-onset Cardiovascular Diseases
Authors: Sahar Esteghamat, J S Broughton, E Smith, Rebecca Cardone, T Tyagi, M Guerra, A Szabó, N Ugwu, M V Mani, B Azari, G Kayingo, S Chung, Jeffery Bender, S Mane, Rick P Lifton, A Adeniran, M H Nathanson, F S Gorelick, John Hwa, M Sahin-Tóth, R Belfort-DeAguiar, Richard G Kibbey, Arya Mani
Journal: Circulation (2019)

Introduction: Metabolic syndrome (MetS) is a cluster of inherited metabolic risk factors that increase the predisposition to Coronary artery disease (CAD). Genetic factors that underlie the associa...
Association of Blood Pressure Patterns in Young Adulthood With Cardiovascular Disease and Mortality in Middle Age
Authors: Yuichiro Yano, Jared P. Reis, Cora E. Lewis, Stephen Sidney, Mark J. Pletcher, Kirsten Bibbins-Domingo, Ann Marie Navar, Eric D. Peterson, Michael P. Bancks, Hiroshi Kanegae, Samuel S. Gidding, Paul Muntner, Donald M. Lloyd-Jones
Journal: JAMA Cardiology (2020)

Determining blood pressure (BP) patterns in young adulthood that are associated with cardiovascular disease (CVD) events in later life may help to identify young adults who have an increased risk for CVD.To determine whether the long-term variability of BP across clinical visits and the rate of change in BP from young adulthood to midlife are associated with CVD and all-cause mortality by middle age, independently of mean BP during young adulthood and a single BP in midlife.This prospective cohort study included a community-based sample of 3394 African American and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, enrolled from March 1985 through June 1986. Patterns of systolic BP (SBP) were evaluated with measurements at year 0 (baseline) and 2, 5, 7, and 10 years after baseline. Visit-to-visit SBP variability was estimated as BP variability independent of the mean (VIM). Data were collected from March 1985 through August 2015 and analyzed from June through October 2019.Cardiovascular disease and all-cause mortality experienced through August 2015 were adjudicated. The associations of each SBP pattern with CVD events and all-cause mortality were determined using Cox proportional hazards regression models.At year 10, the mean (SD) age of the 3394 participants was 35.1 (3.6) years; 1557 (45.9%) were African American; 1892 (55.7%) were women; and 103 (3.0%) were taking antihypertensive medication. During a median follow-up of 20.0 (interquartile range, 19.4-20.2) years, 162 CVD events and 181 deaths occurred. When all BP pattern measurements were entered into the same model including a single SBP measurement at the year 10 examination, the hazard ratios for CVD events for each 1-SD increase in SBP measures were 1.25 (95% CI, 0.90-1.74) for mean SBP, 1.23 (95% CI, 1.07-1.43) for VIM SBP, and 0.99 (95% CI, 0.81-1.26) for annual change of SBP. The VIM for SBP was the only BP pattern associated with all-cause mortality (hazard ratio, 1.24; 95% CI, 1.09-1.41).The results of this study suggest that the assessment of visit-to-visit SBP variability may help identify young adults at increased risk for CVD and all-cause mortality later in life.
Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets
Authors: Carsten Deppermann, Rachel M. Kratofil, Moritz Peiseler, Bruna A. David, Joel Zindel, Fernanda Vargas E Silva Castanheira, Fardau van der Wal, Agostina Carestia, Craig N. Jenne, Jamey D. Marth, Paul Kubes
Journal: The Journal of Experimental Medicine (2020)

Every day, megakaryocytes produce billions of platelets that circulate for several days and eventually are cleared by the liver. The exact removal mechanism, however, remains unclear. Loss of sialic acid residues is thought to feature in the aging and clearance of platelets. Using state-of-the-art spinning disk intravital microscopy to delineate the different compartments and cells of the mouse liver, we observed rapid accumulation of desialylated platelets predominantly on Kupffer cells, with only a few on endothelial cells and none on hepatocytes. Kupffer cell depletion prevented the removal of aged platelets from circulation. Ashwell-Morell receptor (AMR) deficiency alone had little effect on platelet uptake. Macrophage galactose lectin (MGL) together with AMR mediated clearance of desialylated or cold-stored platelets by Kupffer cells. Effective clearance is critical, as mice with an aged platelet population displayed a bleeding phenotype. Our data provide evidence that the MGL of Kupffer cells plays a significant role in the removal of desialylated platelets through a collaboration with the AMR, thereby maintaining a healthy and functional platelet compartment.
Aberrant B cell repertoire selection associated with HIV neutralizing antibody breadth
Authors: Krishna M. Roskin, Katherine J. L. Jackson, Ji-Yeun Lee, Ramona A. Hoh, Shilpa A. Joshi, Kwan-Ki Hwang, Mattia Bonsignori, Isabela Pedroza-Pacheco, Hua-Xin Liao, M. Anthony Moody, Andrew Z. Fire, Persephone Borrow, Barton F. Haynes, Scott D. Boyd
Journal: Nature Immunology (2020)
Gene therapy delivering a paraoxonase 1 variant offers long-term prophylactic protection against nerve agents in mice
Authors: Venkaiah Betapudi, Reena Goswami, Liliya Silayeva, Deborah M. Doctor, Nageswararao Chilukuri
Journal: Science Translational Medicine (2020)

Paraoxonase 1 variant IF-11 offers long-term prophylactic protection against chemical warfare nerve agents in mice.
Functional and Computational Genomics Reveal Unprecedented Flexibility in Stage-Specific Toxoplasma Metabolism
Authors: Aarti Krishnan, Joachim Kloehn, Matteo Lunghi, Anush Chiappino-Pepe, Benjamin S. Waldman, Damien Nicolas, Emmanuel Varesio, Adrian Hehl, Sebastian Lourido, Vassily Hatzimanikatis, Dominique Soldati-Favre
Journal: Cell Host & Microbe (2020)
Collagen‐Elastin‐Like Polypeptide‐Bioglass Scaffolds for Guided Bone Regeneration
Authors: Bhuvaneswari Gurumurthy, Michelle A. Tucci, Lir‐Wan Fan, Hamed A. Benghuzzi, Pallabi Pal, Gene L. Bidwell, Susana M. Salazar Marocho, Zelma Cason, David Gordy, Amol V. Janorkar
Journal: Advanced Healthcare Materials (2020)

Abstract The goals of this study are to evaluate the ability of the multicomponent collagen‐elastin‐like polypeptide (ELP)‐Bioglass scaffolds to support osteogenesis of rat mesenchymal stem cells (rMSCs), demonstrate in vivo biocompatibility by subcutaneous implantation in Sprague‐Dawley rats, monitor degradation noninvasively, and finally assess the scaffold's ability in healing critical‐sized cranial bone defects. The collagen‐ELP‐Bioglass scaffold supports the in vitro osteogenic differentiation of rMSCs over a 3 week culture period. The cellular (rMSC‐containing) or acellular scaffolds implanted in the subcutaneous pockets of rats do not cause any local or systemic toxic effects or tumors. The real‐time monitoring of the fluorescently labeled scaffolds by IVIS reveals that the scaffolds remain at the site of implantation for up to three weeks, during which they degrade gradually. Micro‐CT analysis shows that the bilateral cranial critical‐sized defects created in rats lead to greater bone regeneration when filled with cellular scaffolds. Bone mineral density and bone microarchitectural parameters are comparable among different scaffold groups, but the histological analysis reveals increased formation of high‐quality mature bone in the cellular group, while the acellular group has immature bone and organized connective tissue. These results suggest that the rMSC‐seeded collagen‐ELP‐Bioglass composite scaffolds can aid in better bone healing process.
Figures show big increase in emergency admissions for dementia patients
Authors: Ingrid Torjesen
Journal: BMJ (2020)

There has been a large rise in the number of emergency hospital admissions for people with dementia in England, with many having to remain in hospital for months because of a lack of social care support in the community, an analysis by the Alzheimer’s Society has shown.

There were 379 004 emergency admissions for people with dementia in England in 2017-18, compared with 279 265 in 2012-13 (a rise of 35%), the charity’s analysis of NHS England’s Hospital Episode Statistics dataset found.1

In 2017-18 there were 40 083 patients with dementia who remained in hospital for between a month and a year, including 412 who were in hospital for over six months.

More than half (237 881) of the 435 600 people …
Response to: ‘Regulatory T cell frequencies in patients with rheumatoid arthritis are increased by conventional and biological DMARDs but not by JAK inhibitors’ by Meyer et al
Authors: Michelle Rosenzwajg, Roberta Lorenzon, David Klatzmann
Journal: Annals of the Rheumatic Diseases (2020)

Commenting on Meyer et al 1 our recent publication2 ‘Immunological and clinical effects of low-dose interleukin-2 (IL-2) across 11 autoimmune diseases in a single, open clinical trial’, Dr Meyer and colleagues point to the issue of concomitant background therapies that could affect the effects of low-dose IL-2. They reported a significant increase of Treg cell frequencies in peripheral blood of patients with rheumatoid arthritis treated with methotrexate, adalimumab, etanercept, golimumab and tocilizumab, which they discuss could affect the increase expected after an IL-2 treatment.

Only four rheumatoid arthritis patients were included in our study, all being treated with low-dose corticosteroids and/or low doses of immunosuppressants. Their baseline Treg evaluation was similar to that of patients with other diseases treated with …
Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy
Authors: Xiaoming Zhong, Hangtian Zhang, Ying Zhu, Yuqing Liang, Zhuolin Yuan, Jiachen Li, Jing Li, Xin Li, Yifan Jia, Tian He, Jiangyuan Zhu, Yu Sun, Wengting Jiang, Hui Zhang, Cheng Wang, Zunfu Ke
Journal: Molecular Cancer (2020)

Abstract Cancer metastasis is the leading cause of cancer-related death. Circulating tumor cells (CTCs) are shed into the bloodstream from either primary or metastatic tumors during an intermediate stage of metastasis. In recent years, immunotherapy has also become an important focus of cancer research. Thus, to study the relationship between CTCs and immunotherapy is extremely necessary and valuable to improve the treatment of cancer. In this review, based on the advancements of CTC isolation technologies, we mainly discuss the clinical applications of CTCs in cancer immunotherapy and the related immune mechanisms of CTC formation. In order to fully understand CTC formation, sufficiently and completely understood molecular mechanism based on the different immune cells is critical. This understanding is a promising avenue for the development of effective immunotherapeutic strategies targeting CTCs.
Injectable biodegradable bi-layered capsule for sustained delivery of bevacizumab in treating wet age-related macular degeneration
Authors: Pengfei Jiang, Francisco J. Chaparro, Clayton T. Cuddington, Andre F. Palmer, Matthew P. Ohr, John J. Lannutti, Katelyn E. Swindle-Reilly
Journal: Journal of Controlled Release (2020)
A Prospective Head-to-Head Comparison of 18F-Fluciclovine With 68Ga-PSMA-11 in Biochemical Recurrence of Prostate Cancer in PET/CT: A Special Aspect in Imaging Local Recurrence: Reply
Authors: Birgit Pernthaler, Herbert Kvaternik, Reingard M. Aigner
Journal: Clinical Nuclear Medicine (2020)

Pernthaler, Birgit MD; Kvaternik, Herbert PhD; Aigner, Reingard M. MD Author Information
A dual-ligand fusion peptide improves the brain-neuron targeting of nanocarriers in Alzheimer's disease mice
Authors: Qian Guo, Shuting Xu, Peng Yang, Pengzhen Wang, Shuai Lu, Dongyu Sheng, Kang Qian, Jinxu Cao, Wei Lu, Qizhi Zhang
Journal: Journal of Controlled Release (2020)
Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study
Authors: Vaishali Sanchorawala, Shayna Sarosiek, Amanda Schulman, Meredith Mistark, Mary Ellen Migre, Ramon Cruz, J. Mark Sloan, Dina Brauneis, Anthony C. Shelton
Journal: Blood (2020)