tbuckley/cabot-search huggingface dataset:
Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment
Authors: Can Ni, Jing Zhou, Na Kong, Tianying Bian, Yangheng Zhang, Xiaofeng Huang, Yin Xiao, Wenrong Yang, Fuhua Yan
Journal: Biomaterials (2019)

The regeneration of lost periodontal apparatus in periodontitis treatment remains a clinical challenge due to the limited regenerative capacity of cementum, periodontal ligament and alveolar bone in periodontitis condition. For periodontal tissue regeneration, it is essential to regulate the inflammatory response and the subsequent differentiation of periodontal cells under the condition due to the infectious nature of the disease. In this study, it was noted that 45 nm gold nanoparticles (AuNPs) could exhibit significant anti-inflammatory effect and improve the periodontal inflammatory microenvironment via regulating inflammatory and regenerative cytokine production and modulating macrophage polarization, subsequently affect the differentiation of human periodontal ligament cells (hPDLCs). With the addition of direct effects of AuNPs on hPDLCs, the periodontal tissue differentiation capacity of hPDLCs in LPS-activated inflammatory macrophage-hPDLCs coculture system was significantly enhanced by the interaction between AuNPs-conditioned macrophage and AuNPs-stimulated hPDLCs. The potential therapeutic application of AuNPs in periodontal tissue regeneration and periodontitis treatment was investigated using both rat fenestration and ligature-induced periodontitis models. It was found that the treatment of 45 AuNPs showed significantly increased newly-formed periodontal attachment, bone and cementum in periodontal defect and less tissue destruction in the progression of periodontitis. This study demonstrated that 45 nm AuNPs could not only directly modulate hPDLCs, but also regulate the early inflammatory response of periodontal tissues via the regulation of macrophage phenotypes, therefore, generate a microenvironment with constraint inflammatory cytokine levels and reparative cytokines such as bone morphogenetic protein-2 (BMP-2), leading to PDLC differentiation, periodontal tissue regeneration and the prevention of periodontitis progression.
Abstract 15111: Genome-Wide Association Study Links Variants With Occurrence of Cardiovascular Events in People Taking the COX-2 Inhibitor Celecoxib: Identification of NCKX2 as a Novel Protective Pathway in Renal Vessels
Authors: Nicholas S Kirkby, Andrew P Morris, Jonathan Lytton, Je K Seong, Yun S Bae, Jen H Chu, Monica M Bertagnolli, Munir Pirmohamed, Jane A Mitchell
Journal: Circulation (2017)

Nonsteroidal anti-inflammatory analgesic drugs (NSAIDs) work by blocking cyclooxygenase(COX)-2 and are amongst the most commonly taken drugs worldwide. However they cause cardiovascular adverse eve...
Comment on Lacy et al. Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes. Diabetes Care 2018;41:2339–2345
Authors: Carolina Medrano-De-Ávila, Carolina Castillo-Castro, Fernando J. Lavalle-González
Journal: Diabetes Care (2019)

We read with great interest the recent article by Lacy et al. (1), who investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes. They reported that those with majority exposure to HbA1c 8–8.9% and ≥9% had increased dementia risk (1). We agree that intensive diabetes therapy, aimed at achieving glycemic control as close to the nondiabetic range as safely as possible, decreases the risk for developing multiple micro- and macrovascular complications.

However, tight glycemic control can expose the patient to hypoglycemia. Multiple studies have found an association …
Abstract 17333: Can Pre-Admission Medication Adherence Predict Post-Discharge P2Y12 Inhibitor Adherence Among Patients With Myocardial Infarction?
Authors: Jacob A Doll, Anne Hellkamp, Laine Thomas, Gregg Fonarow, Eric Peterson, Tracy Wang
Journal: Circulation (2017)

Introduction: Non-adherence to P2Y12 inhibitors after myocardial infarction (MI) has been associated with adverse clinical outcomes such as stent thrombosis or death. Pre-admission pharmacy fill da...
Tumorigenesis as the Paradigm of Quasi-neutral Molecular Evolution
Authors: Bingjie Chen, Zongkun Shi, Qingjian Chen, Xu Shen, Darryl Shibata, Haijun Wen, Chung-I Wu
Journal: Molecular Biology and Evolution (2019)

In the absence of both positive and negative selections, coding sequences evolve at a neutral rate (R = 1). Such a high genomic rate is generally not achievable due to the prevalence of negative selection against codon substitutions. Remarkably, somatic evolution exhibits the seemingly neutral rate R ∼ 1 across normal and cancerous tissues. Nevertheless, R ∼ 1 may also mean that positive and negative selections are both strong, but equal in intensity. We refer to this regime as quasi-neutral. Indeed, individual genes in cancer cells often evolve at a much higher, or lower, rate than R ∼ 1. Here, we show that 1) quasi-neutrality is much more likely when populations are small (N < 50); 2) stem-cell populations in single normal tissue niches, from which tumors likely emerge, have a small N (usually <50) but selection at this stage is measurable and strong; 3) when N dips below 50, selection efficacy decreases precipitously; and 4) notably, N is smaller in the stem-cell niche of the small intestine than in the colon. Hence, the ∼70-fold higher rate of phenotypic evolution (observed as cancer risk) in the latter can be explained by the greater efficacy of selection, which then leads to the fixation of more advantageous and fewer deleterious mutations in colon cancers. In conclusion, quasi-neutral evolution sheds a new light on a general evolutionary principle that helps to explain aspects of cancer evolution.
Treatment of patients with multiple myeloma progressing on frontline-therapy with lenalidomide
Authors: Philippe Moreau, Elena Zamagni, Maria-Victoria Mateos
Journal: Blood Cancer Journal (2019)

Abstract Over the last years, there has been great progress in the treatment of multiple myeloma with many new agents and combinations having been approved and being now routinely incorporated into treatment strategies. As a result, patients are experiencing benefits in terms of survival and better tolerance. However, the multitude of treatment options also presents a challenge to select the best options tailored to the specific patient situation. Lenalidomide is increasingly being used as part of frontline therapy in newly diagnosed multiple myeloma. This agent is typically administered until disease progression. It is currently unclear, how to best manage patients, who relapse while receiving lenalidomide as part of their frontline treatment. We conducted a review to summarize the available evidence in this setting. Our summary shows that there are very few data from current trials testing new combinations based on carfilzomib, pomalidomide, or daratumumab that address this specific patient population. Our review is aimed to summarize the available evidence to assist treatment decision making and to raise awareness of this lack of data to encourage further analyses and the incorporation of sequencing questions in future trial designs.
QIM19-122: Quality Improvement Initiatives in the Second Year of an Adolescent and Young Adult Oncology Clinic
Authors: Heather Bowers, Kerri Susko, Aniket Saha, Elizabeth Cull
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Adolescent and young adult (AYA) oncology patients have a distinctive set of needs that are often not addressed by primary providers in busy clinical practices. Genetic counseling, fertility preservation, clinical trial enrollment, and individualized psychosocial support are a few key issues to address in this group. The AYA Oncology Program was created in August 2016 to specifically address these issues and mitigate the disparity in care and outcomes often seen in the AYA population. After the first year, we identified several areas in our program that required improvement. These included increasing referrals to our clinic, increasing appropriate referrals to genetics and fertility specialists, and improving clinical trial enrollment. Several quality improvement initiatives were created to address these issues. Methods: The study assessed patients actively under treatment between ages 15–39 from September 1, 2016 to September 1, 2018 that were seen in the AYA clinic. Starting in year 2, patients seen in the AYA clinic as well as AYAs not seen in the AYA clinic were screened weekly by the AYA team for clinical trial eligibility. Additionally, a weekly email was sent to all physicians and nurse practitioners listing patients for the week that were eligible for AYA referral as well as the clinical trials they were eligible for. The research staff was also included on these emails to facilitate communication and enrollment. Results: In year 2 of the program, 66 patients were seen in the AYA clinic, a 16% increase from the prior year. 65% of patients were referred to genetics, increased from 61% the prior year. 39% of patients were referred to fertility, increased from 37% the prior year. Of patients seen in the AYA clinic, 22% were on a clinical trial in year 1, which increased to 28% in year 2. The AYA team screened all patients at the cancer center regardless of whether they were referred to AYA starting in year 2, and over this year, 17% of AYA patients throughout the cancer center were enrolled on a clinical trial. Conclusion: In our quality improvement initiative in year 2, we increased referrals to the AYA clinic, referrals to specialist services, and clinical trial enrollment. Screening AYA patients on a weekly basis is productive in increasing clinical trial referrals and enrollment. The use of a weekly reminder email to providers also increased AYA clinic referrals.
Publisher Correction: Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers
Authors: Conan G. Kinsey, Soledad A. Camolotto, Amelie M. Boespflug, Katrin P. Guillen, Mona Foth, Amanda Truong, Sophia S. Schuman, Jill E. Shea, Michael T. Seipp, Jeffrey T. Yap, Lance D. Burrell, David H. Lum, Jonathan R. Whisenant, G. Weldon Gilcrease, Courtney C. Cavalieri, Kaitrin M. Rehbein, Stephanie L. Cutler, Kajsa E. Affolter, Alana L. Welm, Bryan E. Welm, Courtney L. Scaife, Eric L. Snyder, Martin McMahon
Journal: Nature Medicine (2019)
AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma
Authors: John P. Leonard, Marek Trneny, Koji Izutsu, Nathan H. Fowler, Xiaonan Hong, Jun Zhu, Huilai Zhang, Fritz Offner, Adriana Scheliga, Grzegorz S. Nowakowski, Antonio Pinto, Francesca Re, Laura Maria Fogliatto, Phillip Scheinberg, Ian W. Flinn, Claudia Moreira, José Cabeçadas, David Liu, Stacey Kalambakas, Pierre Fustier, Chengqing Wu, John G. Gribben
Journal: Journal of Clinical Oncology (2019)

Patients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab.A phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review.A total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively.Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.
Geographical distribution and prevalence of podoconiosis in Rwanda: a cross-sectional country-wide survey
Authors: Kebede Deribe, Aimable Mbituyumuremyi, Jorge Cano, Mbonigaba Jean Bosco, Emanuele Giorgi, Eugene Ruberanziza, Ursin Bayisenge, Uwayezu Leonard, Jean Paul Bikorimana, Aniceth Rucogoza, Innocent Turate, Andre Rusanganwa, David M Pigott, Rachel L Pullan, Abdisalan M Noor, Fikre Enquselassie, Jeanine U Condo, Christopher J L Murray, Simon J Brooker, Simon I Hay, Melanie J Newport, Gail Davey
Journal: The Lancet Global Health (2019)

Podoconiosis is a type of tropical lymphoedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. Reliable and detailed data on the prevalence and distribution of podoconiosis are scarce. We aimed to fill this data gap by doing a nationwide community-based study to estimate the number of cases throughout Rwanda.
Nitrogen-doped graphene quantum dots (N-GQDs) perturb redox-sensitive system via the selective inhibition of antioxidant enzyme activities in zebrafish
Authors: Shun Deng, Ailing Fu, Muhammad Junaid, Yan Wang, Qian Yin, Chen Fu, Li Liu, Dong-Sheng Su, Wan-Ping Bian, De-Sheng Pei
Journal: Biomaterials (2019)
Poor teamwork among surgeons is affecting patient care, finds college
Authors: Abi Rimmer
Journal: BMJ (2019)

Where problems occur in surgery, poor teamwork between surgeons is often a major factor, a review by the Royal College of Surgeons has found.

The college carried out 240 reviews of surgeons or surgical services across the UK between 2008 and the end of 2017 after being invited by hospitals to investigate. Of these, it analysed 100 consecutive reviews, comprising 58 reviews of a service, 25 of a surgeon, and 17 reviews of clinical records.

Problems with team working were highlighted in 76 out of 100 reviews, a report on the analysis said.1 A number of behaviours …
Immune Reconstitution Is a Predictive Biomarker of Chronic Graft-Versus-Host Disease: Analysis of 307 Consecutive Patients
Authors: Fabio Serpenti, Francesca Lorentino, Raffaella Milani, Raffaella Greco, Andrea Assanelli, Carlo Messina, Sara Mastaglio, Fabio Giglio, Francesca Pavesi, Francesca Farina, Sarah Marktel, Magda Marcatti, Francesca Lunghi, Elena Guggiari, Matteo Giovanni Carrabba, Consuelo Corti, Massimo Bernardi, Jacopo Peccatori, Chiara Bonini, Fabio Ciceri, Maria Teresa Lupo Stanghellini
Journal: Blood (2018)
Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL–USP2 fusions
Authors: Claus Meyer, Bruno A. Lopes, Aurélie Caye-Eude, Hélène Cavé, Chloé Arfeuille, Wendy Cuccuini, Rosemary Sutton, Nicola C. Venn, Seung Hwan Oh, Grigory Tsaur, Gabriele Escherich, Tobias Feuchtinger, Hansen J. Kosasih, Seong L. Khaw, Paul G. Ekert, Maria S. Pombo-de-Oliveira, Audrey Bidet, Bardya Djahanschiri, Ingo Ebersberger, Marketa Zaliova, Jan Zuna, Zuzana Zermanova, Vesa Juvonen, Renate Panzer Grümayer, Grazia Fazio, Gianni Cazzaniga, Patrizia Larghero, Mariana Emerenciano, Rolf Marschalek
Journal: Leukemia (2019)
Enhancing the Content of the EORTC QLQ-C30 to Maximize the Detection of Treatment Benefit in Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Low-Blast Acute Myeloid Leukemia Using the EORTC Item Bank
Authors: Jill A Bell, Aaron Galaznik, Farrah A Pompilus, Sara Strzok, Rafael Bejar, Robert J. Fram, Douglas V. Faller, Patrick Marquis
Journal: Blood (2017)
CSF-oma Identification With Nuclear Medicine Shunt-o-Gram
Authors: Stephanie Schmieder, Frank Schraml
Journal: Clinical Nuclear Medicine (2019)

A nuclear medicine shunt-o-gram is used to evaluate ventriculoperitoneal shunt patency and dispersion of radiotracer into the peritoneal cavity. A 73-year-old man presented with worsening memory, gait disturbance, and urinary incontinence. Shunt-o-gram revealed antegrade flow through the tubing and spillage into the peritoneal cavity without dispersion. CT confirmed a CSF-oma. Symptoms resolved after CSF-oma resection. Normal passage of radiotracer through the shunt without normal dispersion into the peritoneal cavity along with CT imaging correctly identified a CSF-oma. This is an unexpected complication of a shunt. Correct diagnosis on imaging likely saved this patient from unnecessary complete shunt revision.
Elizabeth Barrett-Connor: Instrumental Contributor to the Understanding of Midlife Well-being and Health in Both Women and Men
Authors: Kay-Tee Khaw
Journal: Diabetes Care (2019)

When asked what her motto or philosophy of life was in an interview for her local newspaper, La Jolla Light , Elizabeth Barrett-Connor’s response was that she did not have any one particular philosophy so much as an attitude: “My defining principle is that I am a pathological optimist.” Boundlessly curious, fearless, challenging, inspiring, and great fun to be with are some of the words her colleagues and mentees might use to describe her. Elizabeth Barrett-Connor, MD, FACP, FAHA, is internationally acclaimed with a stellar record of research accomplishments (over one thousand original research publications), is on all the highly cited researcher lists, has been a principal investigator on numerous major population studies and multicenter clinical trials, and has received extensive grants and awards. Her immense impact is not just in research but is also reflected through her teaching, encouragement, and mentorship of generations of physicians and scientists.

Elizabeth Barrett-Connor was born in Evanston, Illinois, to Florence (Hershey) and Willard Barrett. Her father was a Cornell University PhD chemist who worked for ammunition companies during the Second World War years, so the family moved quite a bit, ending up in the little town of Lee, Massachusetts. They spent frequent Sundays on the lawn listening to the Boston Pops at Tanglewood and seeing Leonard Bernstein on orchestra. “Glory days,” she says. Elizabeth was an only child who loved horses, the outdoors, and visiting grandparents. Her Grandmother Barrett was postmistress in a small western New York village. Elizabeth learned to read from the postcards with her grandmother prior to delivery. Her Grandmother Hershey was from Mount Joy, Pennsylvania, and helped run a dairy. Mrs. Barrett, who thought that being lead cheerleader was not sufficient, pulled Elizabeth out of public high school and enrolled her at Northfield Preparatory School. Following Northfield, Elizabeth went …
The FOXP3Δ2 isoform supports Treg cell development and protects against severe IPEX syndrome
Authors: Katie Frith, Anne-Laure Joly, Cindy S. Ma, Stuart G. Tangye, Zuzana Lohse, Christina Seitz, Charles F. Verge, John Andersson, Paul Gray
Journal: Journal of Allergy and Clinical Immunology (2019)
Preoperative exposure to anti-tumor necrosis factor therapy in ulcerative colitis patients undergoing ileal pouch-anal anastomosis (IPAA) is not associated with histological fibrosis: A case control study
Authors: Eran Zittan, Jennifer Muir, Raquel Milgrom, Marc Berns, Ian M. Gralnek, Zane Cohen, Robert Riddell, Mark S. Silverberg
Journal: International Journal of Surgery (2019)
Integrating spatial configuration into heatmap regression based CNNs for landmark localization
Authors: Christian Payer, Darko Štern, Horst Bischof, Martin Urschler
Journal: Medical Image Analysis (2019)

In many medical image analysis applications, only a limited amount of training data is available due to the costs of image acquisition and the large manual annotation effort required from experts. Training recent state-of-the-art machine learning methods like convolutional neural networks (CNNs) from small datasets is a challenging task. In this work on anatomical landmark localization, we propose a CNN architecture that learns to split the localization task into two simpler sub-problems, reducing the overall need for large training datasets. Our fully convolutional SpatialConfiguration-Net (SCN) learns this simplification due to multiplying the heatmap predictions of its two components and by training the network in an end-to-end manner. Thus, the SCN dedicates one component to locally accurate but ambiguous candidate predictions, while the other component improves robustness to ambiguities by incorporating the spatial configuration of landmarks. In our extensive experimental evaluation, we show that the proposed SCN outperforms related methods in terms of landmark localization error on a variety of size-limited 2D and 3D landmark localization datasets, i.e., hand radiographs, lateral cephalograms, hand MRIs, and spine CTs.
Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception
Authors: Rima K. Dhillon-Smith, Lee J. Middleton, Kirandeep K. Sunner, Versha Cheed, Krys Baker, Samantha Farrell-Carver, Ruth Bender-Atik, Rina Agrawal, Kalsang Bhatia, Edmond Edi-Osagie, Tarek Ghobara, Pratima Gupta, Davor Jurkovic, Yacoub Khalaf, Marjory MacLean, Christopher McCabe, Khashia Mulbagal, Natalie Nunes, Caroline Overton, Siobhan Quenby, Raj Rai, Nick Raine-Fenning, Lynne Robinson, Jackie Ross, Andrew Sizer, Rachel Small, Alex Tan, Martyn Underwood, Mark D. Kilby, Kristien Boelaert, Jane Daniels, Shakila Thangaratinam, Shiao Y. Chan, Arri Coomarasamy
Journal: New England Journal of Medicine (2019)

Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P = 0.74; absolute difference, -0.4 percentage points; 95% CI, -6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P = 0.14).The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.).