tbuckley/cabot-search huggingface dataset:
Effect of low-level laser therapy on tooth-related pain and somatosensory function evoked by orthodontic treatment
Authors: Song Wu, Yinan Chen, Jinglu Zhang, Wenjing Chen, Sheng Shao, Huijie Shen, Ling Zhu, Ping Ye, Peter Svensson, Kelun Wang
Journal: International Journal of Oral Science (2018)

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12-33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm-2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.
Abstract 5234: Transcriptome profiling of single prostate cancer cells following androgen deprivation
Authors: Ashlee K. Clark, Mitchell Lawrence, Hieu Nim, Natalie Lister, Mark Frydengerg, Gail Risbridger, Renea Taylor
Journal: Cancer Research (2018)

Abstract Androgen withdrawal is the standard of care for men with metastatic prostate cancer. While all patients initially respond, resistance is inevitable and lethal castration-resistant prostate cancer ensues. Using patient-derived xenografts (PDX) of localized tumors, we have identified a subpopulation of castration-tolerant prostate cancer cells that survive following castration. Identifying the unique biologic characteristics of these cells is essential in determining their role in tumor progression and potential to be targeted by therapeutic agents. To study the genomic features of castrate-tolerant cells, we enriched for prostate cancer cells from PDXs using FACS and subjected them to single-cell isolation and RNA seq. We efficiently captured and sequenced &amp;gt;50 cells from pre- and post-castration PDXs using the Fluidigm C1 platform. Sequencing of isolated single cells was performed using the Illumina HiSeq in rapid mode with 50 bp fragment sequencing chemistry (3 million reads/cell). Multidimensional scaling showed that the response to castration is not uniform in all human cells. A unique gene set was identified in intact versus castrate-tolerant cells; we identified distinct changes in energy metabolism, including suppression of ATP production to aid cell survival. We also detected consistent upregulation of the retinoic acid signaling pathway, involving upregulation of CRABP2 and RARRES3 expression in castrate-tolerant cells. This is the first study to report on gene expression in single human prostate cells and revealed novel endocrine-related changes prior to and following androgen deprivation. Our data suggest that further and/or alternative hormone suppression may be effective in targeting castration-tolerant prostate cancer cells. Citation Format: Ashlee K. Clark, Mitchell Lawrence, Hieu Nim, Natalie Lister, Mark Frydengerg, Gail Risbridger, Renea Taylor. Transcriptome profiling of single prostate cancer cells following androgen deprivation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5234.
Abstract 4151: Fucoidan reduced radiation-induced fibrosis and secondary primary cancers
Authors: Szu-yuan Wu
Journal: Cancer Research (2018)

Abstract Radiotherapy (RT) causes tissue fibrosis and secondary cancers. Fucoidan is a sulfated polysaccharide that is mainly found in brown algae and brown seaweed. In this study, we assessed the radioprotective effect of oligo-fucoidan on zebrafish. Embryos were exposed to RT (5, 10, or 20 Gy) at 4 hours post-fertilization and compared with an oligo-fucoidan pretreatment group. We found that oligo-fucoidan protects embryos from death and embryonic defects. Using oligo-fucoidan oral feeding adult zebrafish prior radiation, we found that oligo-fucoidan treatment of wild-type fish yields much lower expression of apoptosis and fibrosis marker genes in liver compared to RT (40 Gy) only. Liver fibrosis was diagnosed from Sirius stain, proved oligo-fucoidan reduce fibrosis caused by high dose of radiation. Using a diet-induced obesity HBx,src(p53-) triple transgenic fish liver cancer model, we found that oligo-fucoidan can lower the expression of cell cycle/proliferation markers, as well as fibrosis markers and lipogenic enzymes, compared with that in fish with radiation exposure only. Furthermore, oligo-fucoidan can effectively decrease liver cancer formation, as observed by hematoxylin and eosin (H&amp;E) staining and immunohistochemistry (IHC) staining of PCNA proliferation marker. Genomic transcriptome profiling by GeneTitan reveals the main genes/pathways activated by oligo-fucoidan pre-treatment which have protection effect for the radiation-induced fibrosis and secondary primary cancers. Our results provide evidence for the ability of oligo-fucoidan to prevent steatosis, hepatocellular carcinoma and secondary cancers induced by radiation in zebrafish model. Citation Format: Szu-yuan Wu. Fucoidan reduced radiation-induced fibrosis and secondary primary cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4151.
Doctor who hid his HIV status for fear of stigma gets suspended sentence
Authors: Clare Dyer
Journal: BMJ (2018)

A doctor who faked blood tests to hide that he was HIV positive from his employers has received a suspended sentence after a court heard that he could not face the stigma of admitting his homosexuality.

Tamas Nyary, 45, worked at 24 hospitals across England between 2010 and 2016. When his infected status became known, authorities had to contact 397 of his former patients and offer them a blood test. All came back negative, but two former patients told the court of their fear on being told of their potential exposure while waiting for test results.

Nyary’s first offence came as he was about to take up a post as an orthopaedic fellow at Nottingham …
<i>BCL3</i> expression promotes resistance to alkylating chemotherapy in gliomas
Authors: Longtao Wu, Giovanna M. Bernal, Kirk E. Cahill, Peter Pytel, Carrie A. Fitzpatrick, Heather Mashek, Ralph R. Weichselbaum, Bakhtiar Yamini
Journal: Science Translational Medicine (2018)

The carbonic anhydrase inhibitor acetazolamide sensitizes gliomas to the chemotherapeutic temozolomide in mice.
Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation
Authors: Benjamin G. Wu, Imran Sulaiman, Jing Wang, Nan Shen, Jose C. Clemente, Yonghua Li, Robert J. Laumbach, Shou-En Lu, Iris Udasin, Oanh Le-Hoang, Alan Perez, Shahnaz Alimokhtari, Kathleen Black, Michael Plietz, Akosua Twumasi, Haley Sanders, Patrick Malecha, Bianca Kapoor, Benjamin D. Scaglione, Anbang Wang, Cameron Blazoski, Michael D. Weiden, David M. Rapoport, Denise Harrison, Nishay Chitkara, Eugenio Vicente, José M. Marin, Jag Sunderram, Indu Ayappa, Leopoldo N. Segal
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome.To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers.Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated.In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota.We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.
Helping smokers to quit
Authors: John P Pierce
Journal: BMJ (2018)

New report proposes a radical change for the NHS

On 26 June 2018, 56 years after their landmark report calling for public health action on smoking, the Royal College of Physicians (RCP) published a new report calling for a change in how smoking cessation services are handled.1 This report details the health consequences and societal costs of smoking. It documents the evidence that patients who continue to smoke compromise the effectiveness of many medical and surgical treatment interventions. Clearly, all public health professionals have a critical interest in doing whatever is possible to reduce cigarette smoking, and this has fuelled many jurisdictions to take action to promote a smoke-free society.

The UK focused on testing the hypothesis, championed by Michael Russell, that the best way to reduce lung cancer mortality quickly was to provide treatment services to as many smokers as possible.2 By 2010-11, the NHS was providing smoking cessation treatment to more than 800 000 smokers.1 On a per population basis, this volume of treatment was many …
Relationship between enteric pathogens and acute gastroenteritis disease severity: a prospective cohort study
Authors: J. Xie, A. Nettel-Aguirre, B.E. Lee, L. Chui, X.L. Pang, R. Zhuo, B. Parsons, O.G. Vanderkooi, P.I. Tarr, S. Ali, J.A. Dickinson, E. Hagen, L.W. Svenson, S.E. MacDonald, S.J. Drews, R. Tellier, T. Graham, M. Lavoie, J. MacDonald, S.B. Freedman
Journal: Clinical Microbiology and Infection (2018)
The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria
Authors: T. Zuberbier, W. Aberer, R. Asero, A. H. Abdul Latiff, D. Baker, B. Ballmer‐Weber, J. A. Bernstein, C. Bindslev‐Jensen, Z. Brzoza, R. Buense Bedrikow, G. W. Canonica, M. K. Church, T. Craig, I. V. Danilycheva, C. Dressler, L. F. Ensina, A. Giménez‐Arnau, K. Godse, M. Gonçalo, C. Grattan, J. Hebert, M. Hide, A. Kaplan, A. Kapp, C. H. Katelaris, E. Kocatürk, K. Kulthanan, D. Larenas‐Linnemann, T. A. Leslie, M. Magerl, P. Mathelier‐Fusade, R. Y. Meshkova, M. Metz, A. Nast, E. Nettis, H. Oude‐Elberink, S. Rosumeck, S. S. Saini, M. Sánchez‐Borges, P. Schmid‐Grendelmeier, P. Staubach, G. Sussman, E. Toubi, G. A. Vena, C. Vestergaard, B. Wedi, R. N. Werner, Z. Zhao, M. Maurer
Journal: Allergy (2018)

Abstract This evidence‐ and consensus‐based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation ( GRADE ) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology ( EAACI ), the EU ‐founded network of excellence, the Global Allergy and Asthma European Network ( GA ² LEN ), the European Dermatology Forum ( EDF ) and the World Allergy Organization ( WAO ) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists ( UEMS ). Urticaria is a frequent, mast cell‐driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.
Trends in Weight Loss Efforts Among US Adolescents With Overweight and Obesity
Authors: Daneisha R. Hawkins, Kathryn Kazmierski, Andrew Hansen, Cathony Reid, Alicia Brown, Samuel T. Opoku, Jian Zhang
Journal: JAMA Pediatrics (2018)

norms, is unclear.We assessed the trend in weight loss efforts among adolescents with overweight and obesity aged 16 to 19 years.
Cognitive and visual diagnostic errors in dermatology: part 1
Authors: E.J. Lowenstein, R. Sidlow
Journal: British Journal of Dermatology (2018)

Sir William Osler famously, and ironically, stated that 'Medicine is a science of uncertainty and an art of probability'. The processes by which each physician metes out diagnostic uncertainty and navigates probabilities in dermatology is far from uniform. While certain ubiquitous cognitive and visual heuristics can enhance diagnostic speed, they also create pitfalls and thinking traps that introduce significant variation in the diagnostic process. Discussed in this part of a two‐part article are various cognitive and visual heuristics as they pertain to skin disease, with an introduction and special attention paid to the heuristic methods classically applied by dermatologists. How to best address error and improve our thought processes will be addressed in part 2.
Abstract 17598: Inflammatory Effect of Fasting and Postprandial Triglycerides by Leukocyte Activation
Authors: Benjamin Burggraaf, Marijke A de Vries, Boudewijn Klop, Arash Alipour, Anho Liem, Peter de Man, Gert-Jan M van de Geijn, Manuel Castro Cabezas
Journal: Circulation (2016)

Introduction:  Atherosclerosis is characterized by systemic inflammation in which the activation of leukocytes plays a crucial role. While hypertriglyceridemia is an atherogenic condition, the underlying mechanisms have not been well defined. We aimed to evaluate the effect of triglycerides (TGs) on leukocyte activation.   Methods:  Volunteers (n=196) attended the outpatient clinic for fasting blood tests. Oral fat loading tests (n=36) were carried out to evaluate postprandial inflammation. For in vitro experiments, freshly drawn blood samples from 9 healthy volunteers were incubated with different TG emulsions: Lipoplus, Lipofundin and Intralipid and compared to LPS as positive control. Leukocyte activation markers were measured using the flow cytometer.   Results:  The mean age of the total cohort was 56.7±16.5 years, 49.5% was male. Mean fasting TGs were 1.58±0.96 mmol/L. Fasting TGs were associated with monocyte CD11b (Spearman’s rho:0.29), granulocyte CD11b (r:0.30) and granulocyte CD66b (r:0.29). Significant associations were also found with HDLC (r:-0.38) and apoB (r:0.28; p   Conclusions:  This study provides evidence for a role of TGs in leukocyte activation, most likely depending on the composition of the TG-rich particles. These inflammatory effects may be blunted by statins. Our data contribute to the understanding of the atherogenicity of TG-rich lipoproteins.
Early-drug development in the era of immuno-oncology: are we ready to face the challenges?
Authors: M. Ochoa de Olza, M. Oliva, C. Hierro, I. Matos, J. Martin-Liberal, E. Garralda
Journal: Annals of Oncology (2018)

The classical development of drugs has progressively faded away, and we are currently in an era of seamless drug-development, where first-in-human trials include unusually big expansion cohorts in the search for early signs of activity and rapid regulatory approval. The fierce competition between different pharmaceutical companies and the hype for immune combinations obliges us to question the current way in which we are evaluating these drugs. In this review, we discuss critical issues and caveats in immunotherapy development. A particular emphasis is put on the limitations of pre-clinical toxicology studies, where both murine models and cynomolgus monkeys have underpredicted toxicity in humans. Moreover, relevant issues surrounding dose determination during phase I trials, such as dose-escalation methods or flat versus body-weight dosing, are discussed. A proposal of how to face these different challenges is offered, in order to achieve maximum efficacy with minimum toxicity for our patients.
Safety and Efficacy of Atezolizumab in Combination with Obinutuzumab and Bendamustine in Patients with Previously Untreated Follicular Lymphoma: An Interim Analysis
Authors: Anas Younes, Burke M. John, Catherine S Diefenbach, Silvia Ferrari, Cyrus Kahn, Jeffrey P. Sharman, Monica Tani, Chaitra S. Ujjani, Umberto Vitolo, Sam Yuen, Paul Woodard, Kirsten Mundt, Günter Fingerle-Rowson, Surya Chitra, Gila Sellam, Rodica Morariu-Zamfir, Michael Gilbertson
Journal: Blood (2017)
Hierarchical Biomineralization: from Nature's Designs to Synthetic Materials for Regenerative Medicine and Dentistry
Authors: Sherif Elsharkawy, Alvaro Mata
Journal: Advanced Healthcare Materials (2018)

Abstract Biomineralization is a highly dynamic, yet controlled, process that many living creatures employ to develop functional tissues such as tooth enamel, bone, and others. A major goal in materials science is to create bioinspired functional structures based on the precise organization of building blocks across multiple length scales. Therefore, learning how nature has evolved to use biomineralization could inspire new ways to design and develop synthetic hierarchical materials with enhanced functionality. Toward this goal, this review dissects the current understanding of structure–function relationships of dental enamel and bone using a materials science perspective and discusses a wide range of synthetic technologies that aim to recreate their hierarchical organization and functionality. Insights into how these strategies could be applied for regenerative medicine and dentistry are also provided.
Migrant children in US were given range of psychotropic drugs to control behaviour, lawsuits allege
Authors: Owen Dyer
Journal: BMJ (2018)

Migrant children separated from their families in the United States are being given psychotropic drugs to control their behaviour—including antipsychotics not approved for paediatric use—without seeking consent from parents even when they can be easily reached, evidence presented and filed in a federal court has shown.

The allegations, backed up by medical records obtained from detention centres, appear in two lawsuits that demand an end to the practice. The lawsuits are part of a flurry of litigation surrounding the Trump administration’s policies of detaining almost all asylum seekers and separating migrant parents from their children.

Some children were told that the drugs were vitamins, the suits allege, while others were told to take pills if they wished to see their parents again, and some were held down and forcibly injected. One child had 10 different shots and pills prescribed, including lurasidone, ziprasidone, olanzapine, benztropine, clonazepam, divalproex, duloxetine, and guanfacine.

Some of the drugs are not approved by the Food and Drug Administration for use in children, while others have “black box” warnings about paediatric use. Side effects can include diabetes and weight gain, lethargy, and suicidality. …
CRISPR/Cas9-Mediated Knockout of DGK Improves Antitumor Activities of Human T Cells
Authors: In-Young Jung, Yoon-Young Kim, Ho-Sung Yu, Myoungsoo Lee, Seokjoong Kim, Jungmin Lee
Journal: Cancer Research (2018)

Abstract The efficacy of T-cell therapy is inhibited by various tumor-associated immunosuppressive ligands and soluble factors. Such inhibitory signals turn specific T-cell signaling pathways on or off, impeding the anticancer functions of T cells. Many studies have focused on PD-1 or CTLA-4 blockade to invigorate T-cell functions through CD28/B7 signaling, but obtaining robust clinical outcomes remains challenging. In this study, we use CRISPR/Cas9 to potentiate T-cell function by increasing CD3 signaling via knockout of diacylglycerol kinase (DGK), an enzyme that metabolizes diacylglycerol to phosphatidic acid. Knockout of DGK augmented the effector functions of CAR-T cells in vitro via increased TCR signaling. DGK knockout from CAR-T cells rendered them resistant to soluble immunosuppressive factors such as TGFβ and prostaglandin E2 and sustained effector functions under conditions of repeated tumor stimulation. Moreover, DGK knockout caused significant regression of U87MGvIII glioblastoma tumors through enhanced effector functions in a xenograft mouse model. Collectively, our study shows that knockout of DGK effectively enhances the effector functions of CAR-T cells, suggesting that CRISPR/Cas9-mediated knockout of DGK could be applicable as part of a multifaceted clinical strategy to treat solid cancers. Significance: This novel study demonstrates efficient ablation of diacylglycerol kinase in human CAR-T cells that leads to improved antitumor immunity and may have significant impact in human cancer immunotherapy. Cancer Res; 78(16); 4692–703. ©2018 AACR.