tbuckley/cabot-search huggingface dataset:
Abstract 13218: Remodeling of High Density Lipoprotein Induced by CSL112: Structure and Function of the Remodeled Lipoproteins
Authors: Svetlana A Didichenko, Alexei V Navdaev, Martin O Spycher, Samuel D Wright
Journal: Circulation (2016)

Introduction: CSL112 is a novel formulation of human apolipoprotein A-I (apoA-I) suitable for intravenous infusion, currently in development for reducing the high rate of early recurrent events after acute myocardial infarction. Infusion of CSL112 into healthy volunteers causes HDL remodeling, with an immediate rise in lipid-poor apoA-I and a strong and immediate increase in the ABCA1-dependent cholesterol efflux capacity of plasma. Interaction of CSL112 with whole plasma or purified HDL gives rise to three new remodeled HDL species: large (L-HDL rem ) and small (S-HDL rem ) species, and lipid-poor apoA-I. Here we characterized the composition and morphology of remodeled HDL species and compared their ability to efflux cholesterol via different transporters. Methods and Results: CSL112 and HDL3, fluorescently labeled on protein or lipid, were incubated together for varying periods of time at 37°C. Resultant HDL particle size distribution was assessed by native gel electrophoresis followed by fluorescence imaging. Morphology of the individual purified products of HDL remodeling was examined by negative stain electron microscopy. We show that L-HDL rem is a large, spherical species composed of apoA-I and phospholipid from both native HDL and CSL112. S-HDL rem is a small, disc-shaped species composed of apoA-I from CSL112 that is smaller due to the loss of phospholipids. The smallest species, lipid-poor apoA-I, is composed of apoA-I from HDL and CSL112. Lipid-poor apoA-I and S-HDL rem were found to have the greatest ability to efflux cholesterol via ABCA1. While S-HDL rem and L-HDL rem showed comparable ability to efflux cholesterol via ABCG1, L-HDL rem mediated additional efflux via SR-B1 and by an aqueous diffusion process. Conclusion: The generation of these remodeled HDL species can account for the strong and immediate increase in cholesterol efflux capacity observed upon infusion of CSL112, and make CSL112 a promising approach for rapidly removing cholesterol from atherosclerotic plaque.
Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence
Authors: Jian Yuan Goh, Min Feng, Wenyu Wang, Gokce Oguz, Siti Maryam J M Yatim, Puay Leng Lee, Yi Bao, Tse Hui Lim, Panpan Wang, Wai Leong Tam, Annette R Kodahl, Maria B Lyng, Suman Sarma, Selena Y Lin, Alexander Lezhava, Yoon Sim Yap, Alvin S T Lim, Dave S B Hoon, Henrik J Ditzel, Soo Chin Lee, Ern Yu Tan, Qiang Yu
Journal: Nature Medicine (2017)
Regular nicotine intake increased tooth movement velocity, osteoclastogenesis and orthodontically induced dental root resorptions in a rat model
Authors: Christian Kirschneck, Michael Maurer, Michael Wolf, Claudia Reicheneder, Peter Proff
Journal: International Journal of Oral Science (2017)

Orthodontic forces have been reported to significantly increase nicotine-induced periodontal bone loss. At present, however, it is unknown, which further (side) effects can be expected during orthodontic treatment at a nicotine exposure corresponding to that of an average European smoker. 63 male Fischer344 rats were randomized in three consecutive experiments of 21 animals each (A/B/C) to 3 experimental groups (7 rats, 1/2/3): (A) cone-beam-computed tomography (CBCT); (B) histology/serology; (C) reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR)/cotinine serology—(1) control; (2) orthodontic tooth movement (OTM) of the first and second upper left molar (NiTi closed coil spring, 0.25 N); (3) OTM with 1.89 mg·kg−1 per day s.c. of L(−)-nicotine. After 14 days of OTM, serum cotinine and IL-6 concentration as well as orthodontically induced inflammatory root resorption (OIIRR), osteoclast activity (histology), orthodontic tooth movement velocity (CBCT, within 14 and 28 days of OTM) and relative gene expression of known inflammatory and osteoclast markers were quantified in the dental-periodontal tissue (RT–qPCR). Animals exposed to nicotine showed significantly heightened serum cotinine and IL-6 levels corresponding to those of regular European smokers. Both the extent of root resorption, osteoclast activity, orthodontic tooth movement and gene expression of inflammatory and osteoclast markers were significantly increased compared to controls with and without OTM under the influence of nicotine. We conclude that apart from increased periodontal bone loss, a progression of dental root resorption and accelerated orthodontic tooth movement are to be anticipated during orthodontic therapy, if nicotine consumption is present. Thus patients should be informed about these risks and the necessity of nicotine abstinence during treatment. Exposure to nicotine can strongly affect both the movement of teeth and the surrounding bone over the course of an orthodontic procedure. The deleterious dental effects of smoking are well understood, but little is known about how nicotine affects the changes that take place when wearing an orthodontic appliance. Researchers led by Christian Kirschneck at Germany's University Medical Centre of Regensburg have now determined that regular nicotine exposure exerts both positive and negative influences in rats during a multi-week orthodontic treatment. On the one hand, nicotine markedly accelerated the intended goal of tooth movement and reorganization. However, it was also associated with inflammation and bone loss at the roots of the teeth. Accordingly, the researchers conclude that orthodontists should caution their patients regarding the added risks of using tobacco during treatment.
Absence of Hypervitaminosis D in Mice Subjected to Ultraviolet Radiation
Authors: Blum, Harold F., Lippincott, Stuart W.
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Absence of Hypervitaminosis D in Mice Subjected to Ultraviolet Radiation Get access Harold F. Blum, Harold F. Blum senior pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Stuart W. Lippincott Stuart W. Lippincott passed assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 6, June 1942, Pages 623–624, https://doi.org/10.1093/jnci/2.6.623 Published: 01 June 1942
Modeling Cytostatic and Cytotoxic Responses to New Treatment Regimens for Ovarian Cancer
Authors: Francesca Falcetta, Francesca Bizzaro, Elisa D'Agostini, Maria Rosa Bani, Raffaella Giavazzi, Paolo Ubezio
Journal: Cancer Research (2017)

The margin for optimizing polychemotherapy is wide, but a quantitative comparison of current and new protocols is rare even in preclinical settings. In silico reconstruction of the proliferation process and the main perturbations induced by treatment provides insight into the complexity of drug response and grounds for a more objective rationale to treatment schemes. We analyzed 12 treatment groups in trial on an ovarian cancer xenograft, reproducing current therapeutic options for this cancer including one-, two-, and three-drug schemes of cisplatin (DDP), bevacizumab (BEV), and paclitaxel (PTX) with conventional and two levels ("equi" and "high") of dose-dense schedules. All individual tumor growth curves were decoded via separate measurements of cell death and other antiproliferative effects, gaining fresh insight into the differences between treatment options. Single drug treatments were cytostatic, but only DDP and PTX were also cytotoxic. After treatment, regrowth stabilized with increased propensity to quiescence, particularly with BEV. More cells were killed by PTX dose-dense-equi than with PTX conventional, but with the addition of DDP, cytotoxicity was similar and considerably less than expected from that of individual drugs. In the DDP/PTX dose-dense-high scheme, both cell death and regrowth impairment were intensified enough to achieve complete remission, and addition of BEV increased cell death in all schemes. The results support the option for dose-dense PTX chemotherapy with active single doses, showing the relative additional contribution of BEV, but also indicate negative drug interactions in concomitant DDP/PTX treatments, suggesting that sequential schedules could improve antitumor efficacy. Cancer Res; 77(23); 6759-69. ©2017 AACR.
NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-lymphocyte Responses in Patients with Myelodysplastic Syndrome
Authors: Elizabeth A. Griffiths, Pragya Srivastava, Junko Matsuzaki, Zachary Brumberger, Eunice S. Wang, Justin Kocent, Austin Miller, Gregory W. Roloff, Hong Yuen Wong, Benjamin E. Paluch, Linda G. Lutgen-Dunckley, Brandon L. Martens, Kunle Odunsi, Adam R. Karpf, Christopher S. Hourigan, Michael J. Nemeth
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are first-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that patients with acute myeloid leukemia (AML) receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in patients with MDS receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1–specific MDS-directed cytotoxic T-cell immune response. Experimental Design: In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine (CDX-1401 + poly-ICLC) in a nonoverlapping schedule every four weeks with standard-dose decitabine. Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 patients and NY-ESO-1–specific CD4+ and CD8+ T-lymphocyte responses in 6 of 7 and 4 of 7 of the vaccinated patients, respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1–specific T lymphocytes. Vaccine responses were associated with a detectable population of CD141Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses. Conclusions: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options. Clin Cancer Res; 24(5); 1019–29. ©2017 AACR. See related commentary by Fuchs, p. 991
Abstract 12162: Changes in Renal Function Following Left Ventricular Assist Device Placement in Pediatric Patients: A PediMACS Analysis
Authors: Joshua M Friedland-Little, Borah J Hong, Jeffrey G Gossett, Shriprasad R Deshpande, Sabrina Law, Kathryn A Hollifield, Ryan S Cantor, Steven J Kindel, Mark W Turrentine, Ryan R Davies
Journal: Circulation (2016)

Introduction: Renal dysfunction (RD) is prevalent among pediatric patients with advanced heart failure. Data are limited regarding changes in renal function following left ventricular assist device (LVAD) placement in this population. Hypothesis: Renal function will improve following pediatric LVAD placement, but degree and durability of improvement may vary based upon patient and device characteristics. Methods: Pediatric LVAD recipients enrolled in the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) between September 19, 2012 and December 31, 2015 were included. The Schwartz equation was used to calculate eGFR and longitudinal changes in renal function were analyzed for the entire cohort as well as subgroups stratified by patient and device characteristics. Results: Data from 218 patients from 39 centers were analyzed. Mean age at implant was 9.2 years and total follow up time was 768 patient-months. There were 117 (54%) durable continuous flow LVADs, 60 (27%) durable pulsatile flow LVADs, and 41 (19%) temporary LVADs. The underlying diagnosis was cardiomyopathy in 162 (74%) patients and congenital heart disease in 47 (22%) patients. Baseline RD (eGFR &lt; 90 mL/min/1.73 m 2 ) was present in 140 (64%) patients. Overall, eGFR improved post-LVAD, peaking at 1 month post-implant (Figure 1). There was an inverse relationship between baseline eGFR and the degree of improvement at 1 month (mean increase in eGFR of 45 +/- 16 for patients with baseline RD vs. mean increase of 16 +/- 58 for patients with normal eGFR pre-LVAD, p=0.001). Degree of improvement in eGFR at 1 month did not appear impacted by device type, age, or diagnosis. There was a downward trend in eGFR after 1 month, although eGFR remained over baseline for patients with pre-implant RD. Conclusions: Renal function improves post-LVAD placement in pediatric patients regardless of age, diagnosis or device type, with improvement most pronounced in patients with baseline RD.
The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study
Authors: Scott A Lear, Weihong Hu, Sumathy Rangarajan, Danijela Gasevic, Darryl Leong, Romaina Iqbal, Amparo Casanova, Sumathi Swaminathan, R M Anjana, Rajesh Kumar, Annika Rosengren, Li Wei, Wang Yang, Wang Chuangshi, Liu Huaxing, Sanjeev Nair, Rafael Diaz, Hany Swidon, Rajeev Gupta, Noushin Mohammadifard, Patricio Lopez-Jaramillo, Aytekin Oguz, Katarzyna Zatonska, Pamela Seron, Alvaro Avezum, Paul Poirier, Koon Teo, Salim Yusuf
Journal: The Lancet (2017)
Planned safety analysis of the ACTS-CC 02 trial: A randomized phase III trial of S-1/oxaliplatin (SOX) versus UFT/LV as adjuvant chemotherapy for high-risk stage III colon cancer.
Authors: Takuya Miura, Eiji Sunami, Tetsuya Kusumoto, Mitsuyoshi Ota, Kazuhiro Yoshida, Naohiro Tomita, Atsuyuki Maeda, Izumi Mochizuki, Michio Okabe, Katsuyuki Kunieda, Junichiro Yamauchi, Michio Itabashi, Kenjiro Kotake, Keiichi Takahashi, Hideo Baba, Narikazu Boku, Keisuke Aiba, Megumi Ishiguro, Satoshi Morita, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2016)

3622 Background: The ACTS-CC 02 trial was designed to verify the superiority of postoperative adjuvant chemotherapy with S-1/oxaliplatin (SOX) over Japanese standard treatment with UFT/LV in terms of disease-free survival in patients (pts) with high-risk stage III colon cancer. To date, no phase III trials evaluating SOX as postoperative adjuvant chemotherapy have been reported. We report the results of a planned safety analysis. Methods: Pts who underwent curative resection for high-risk stage III colon cancer were randomly assigned to either UFT/LV (300–600 mg/day of UFT according to body surface area [BSA] and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80–120 mg/day of S-1 according to BSA on days 1-14, every 21 days, 8 courses). The dose and adverse events (AEs) in each course were recorded. Results: From April 2010 through October 2014, a total of 966 pts were enrolled at 260 institutions. The safety analysis set (derived by excluding pts who received no protocol treatment from the full analysis set which excluded pts who withdrew informed consent) comprised 472 pts in UFT/LV and 460 in SOX. The median age was 65.0 years, with men accounting for 54.2%, an ECOG PS of 0 in 94.2%, and colon + rectosigmoid cancer in 86.4%.Demographic factors were well balanced. The population of pts who received the planned 6-month protocol treatment was 76.9% in UFT/LV and 65.8% in SOX. The overall incidences of any grade AEs in UFT/LV and SOX were 91.3% and 98.7%, respectively. The incidences of grade ≥ 3 AEs were 15.9% and 35.7% respectively, including neutropenia (1.5% v 17.2%), thrombocytopenia (0.6% v 2.8%), increased AST (2.1% v 0.7%), increased ALT (3.0% v 0.9%), anorexia (2.3% v 3.5%), nausea (0.8% v 2.0%), diarrhea (8.1% v 5.4%), fatigue (1.1% v 1.5%) and sensory neuropathy (0.2% v 4.6%). There was 1 treatment-related death (fulminant hepatitis) in UFT/LV. Conclusions: The incidence of AEs associated with SOX as postoperative adjuvant chemotherapy for colon cancer was considered acceptable, although slightly higher than that of UFT/LV. It was similar to that reported for adjuvant chemotherapy with FOLFOX or CapeOX. Clinical trial information: JapicCTI-101073.
An atypical, non-healing perioral lesion
Authors: Vinay Naresh Mistry, Mohamed Imran Suida, Deborah Kirkham, Michael Wing Sung Ho
Journal: BMJ (2017)

A 57 year old man was referred urgently to the oral and maxillofacial surgery clinic. He described a three month history of fatigue, recurrent sore throats, and a persistent “cold sore.” An irregular and indurated ulcer was present on the right oral commissure (fig 1⇓), and an ipsilateral swelling was palpable in the submandibular triangle (fig 2⇓). He had no relevant medical history. He drank little alcohol and was a non-smoker.



Fig 1  Irregular and indurated ulcer present on the right oral commissure





Fig 2  Ipsilateral swelling palpable in the submandibular triangle





### 1. What are the most important differential diagnoses to consider?

#### Short answer

The most important differential diagnoses to consider include herpes labialis, primary syphilis, and squamous cell carcinoma.

#### Discussion

Primary syphilis should be considered alongside herpes simplex labialis if the symptoms do not resolve in 10-14 days.1 Association with other red flags such as induration, bleeding, and concurrent cervical lymphadenopathy should prompt fast track referral to the local head and neck oncology clinic. Malaise is a common feature of syphilis that would not normally be seen at an early stage of squamous cell carcinoma.

Cases of syphilis have risen dramatically in recent years. In the UK, USA, and other Western countries, this rise has been most marked in men who have sex with men, so taking a targeted sexual history is essential.2 Syphilis is classified …
Effectiveness of physical therapy interventions for pregnancy-related pelvic girdle pain (PEDro synthesis)
Authors: Hilde Stendal Robinson, Arun Prasad Balasundaram
Journal: British Journal of Sports Medicine (2017)

Ferreira CWS, Alburquerque-Sendi’n F. Effectiveness of physical therapy for pregnancy-related low back and/or pelvic pain after delivery: a systematic review. Physiother Theory Pract 2013; 29: 419–431.

Pelvic girdle pain (PGP) is often reported during and after pregnancy and the exact cause(s) is not clear. A wide variety of physical therapy interventions such as exercise/manual therapies, use of pelvic belts, electrotherapeutic agents and patient education are presently used for the treatment of pregnancy-related PGP1. These interventions are continuing to be used, whereby evidence-informed decisions may not be followed.

The aim of the systematic review was to investigate the effectiveness of physiotherapy interventions for the treatment of postpartum low back pain (LBP) and PGP.

The searches were conducted using eight electronic databases including PubMed, Medline, SciELO, LILACS, Cochrane Collaboration Database, SCIRUS, Scopus and the Physiotherapy Evidence Database (PEDro). The keywords used were obtained from the Medical Subject Headings, which included LBP, physiotherapy, postpartum period and pregnancy. Corresponding terms of these keywords in Portuguese and Spanish languages were also included. Studies published in peer-reviewed journals were only included with …
Magnifying chromoendoscopy does not seem helpful in avoiding unnecessary surgery once deep submucosal invasion is suspected
Authors: Yara Backes, Johannes Reitsma, Leon Moons
Journal: Endoscopy (2017)

We read with interest the article by Zhang et al. on the diagnostic accuracy of magnifying narrow-band imaging (M-NBI) for the optical diagnosis of T1 colorectal cancer (CRC) with deep submucosal invasion [1]. The authors claim that, although the specificity of M-NBI was comparable to magnifying chromoendoscopy (M-CE), the sensitivity was significantly lower (0.74, 95 % confidence interval [CI] 0.66 – 0.81 for M-NBI vs. 0.84, 95 %CI 0.76 – 0.89 for M-CE). This contradicts the conclusion of a recently published meta-analysis by our study group [2], in which no difference was observed. In this letter, we would like to discuss some concerns regarding the conclusion and recommendations proposed by Zhang et al.
Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample
Authors: Pedro Mario Pan, João R. Sato, Giovanni A. Salum, Luis A. Rohde, Ary Gadelha, Andre Zugman, Jair Mari, Andrea Jackowski, Felipe Picon, Eurípedes C. Miguel, Daniel S. Pine, Ellen Leibenluft, Rodrigo A. Bressan, Argyris Stringaris
Journal: American Journal of Psychiatry (2017)

Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents.A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction.Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use.Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.