tbuckley/cabot-search huggingface dataset:
Practical precursors to reconsidering objective for physical activity in physical education
Authors: Susan Giblin, David John Collins, Chris Button, Aine MacNamara
Journal: British Journal of Sports Medicine (2017)

We enjoyed and concur with the recently published editorial ‘Reconsidering current objectives for physical activity within physical education’,1  although that much of this has been said already, both by ourselves and others.2–5 However, we do feel that the editorial missed the opportunity to consider why the balance between physical activity (PA) and physical literacy (PL) may have swung to a negative extreme. In simple terms, we suggest that this has a lot to do with the …
Authors’ reply to Wicks
Authors: Michèle Bally, James M Brophy
Journal: BMJ (2017)

We thank Wicks for his insightful comments.12 For the individual participant data meta-analysis of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of acute myocardial infarction we accessed de-identified data that were coded to prevent a person’s identity from being connected with their personal health information.

Permission to access data …
Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy
Authors: Tabitha Turner-Stokes, Hannah R. Wilson, Massimiliano Morreale, Ana Nunes, Tom Cairns, H. Terence Cook, Charles D. Pusey, Ruth M. Tarzi, Liz Lightstone
Journal: Kidney International (2017)
Chemoprevention of colorectal carcinogenesis with newly synthesized curcumin analogues
Authors: Hiroyuki Shibata, Atsuko Sato, Hiroyuki Yamakoshi, Hisatsugu Ohori, Chieko Kudo, Yuichi Kakudo, Yoshiharu Iwabuchi, Chikashi Ishioka
Journal: Clinical Cancer Research (2007)

A12   We have developed a series of curcumin analogues bearing a monoketon strucure. Among as many as 90 compounds, two analogues named GO-Y030 and GO-Y031 showed the highest tumor suppressive potential (about 30 times higher than curcumin) against various cancer cell lines. They can induce the down-regulation of critical oncogene for colorectal carcinogenesis, I²-catenin.  Their chemopreventive effects on colorectal carcinogenesis were examined by using familial adenomatous polyposis (FAP) mouse,  Apc 580D. This FAP mouse line developes several hundreds adenomas mainly in its intestine and has very short average life span as long as 20 weeks of age due to its polyposis phenotype, such as intestinal bleeding and mechanical obstruction. In  Apc 580D mice fed with GO-Y030 or GO-Y031 (5mg oral administration, daily), each tumor incidence was suppressed to 42 and 51 % of basic diet group, respectively. The values of the median survival time (MST) were prolonged over 200 days in both cases, compared with the basic diet group (in this case, MST was around 130 days). The prolongation of MST was statistically apparent in case of GO-Y030, even compared with curcumin trearment. These effects were thought to be exerted in part from the ability to down-regulate the expression of I²-catenin and its related molecules including c-Myc, cyclinD1, which were shown  in vitro .The expression of these target molecules were analyzed immunohistchemically  in vivo . These findings indicate that GO-Y030 and GO-Y031 have enhansed potential of chemoprevention for colorectal carcinogenesis.
Adaptation of the pathological tendon: you cannot trade in for a new one, but perhaps you don’t need to?
Authors: Ebonie Rio, Sean Iain Docking
Journal: British Journal of Sports Medicine (2017)

You can pick up any recent issue of BJSM and a consistent theme arises: exercise is good. Whether we are talking rehabilitation, performance or prevention, exercise is medicine. Mechanotransduction is central to adaptation where local cells detect mechanical stimuli and respond positively to increase the load capacity of the tissue.1 However, our understanding of adaptation and how certain tissues increase their load capacity is incomplete. Furthermore, when discussing adaptation and load capacity of the pathological and painful tendon, research has primarily focused on the local tissue, with little appreciation for the involvement of multiple systems involved in adaptation.

Pathology and pain in musculoskeletal medicine are poorly linked. A large proportion of the asymptomatic population exhibit pathology on imaging.2 3 This highlights several things (that are not new):

1.  we have no gold standard of diagnosis (it cannot be imaging for most tissues, as pathology on imaging is evident in people without symptoms);

2.  pain is complex, and not always linked to nociception;

3.  lastly, and the focus of this piece—that the body is capable of achieving pain-free function due to adaptation in response …
Repression of BET activity sensitizes homologous recombination–proficient cancers to PARP inhibition
Authors: Lu Yang, Youyou Zhang, Weiwei Shan, Zhongyi Hu, Jiao Yuan, Jingjiang Pi, Yueying Wang, Lingling Fan, Zhaoqing Tang, Chunsheng Li, Xiaowen Hu, Janos L. Tanyi, Yi Fan, Qihong Huang, Kathleen Montone, Chi V. Dang, Lin Zhang
Journal: Science Translational Medicine (2017)

PARP inhibitors can be combined with BET inhibitors to treat cancers with de novo or acquired resistance to PARP inhibition.
Ian R D Proctor
Authors: Stuart Yuill Proctor, Martyn C D Proctor
Journal: BMJ (2017)

In his final year as a medical student, Ian R D Proctor volunteered to go to Belsen to care for the surviving prisoners. After a month, the death rate halved from 1200 to 600 with better food, pain relief, and symptom control. In 1947 Ian married a Barts …
Role for academic institutions and think tanks in speeding progress on sustainable development goals
Authors: Ilona Kickbusch, Johanna Hanefeld
Journal: BMJ (2017)

Academic institutions and think tanks are uniquely placed to broker links between different sectors and assist with cross cutting approaches to achieving the health related sustainable development goals, say <b>Ilona Kickbusch</b> and <b>Johanna Hanefeld</b>
Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy
Authors: Rajeev Kumar Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E. Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N. Khleif
Journal: Journal for ImmunoTherapy of Cancer (2017)

Background: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4 + and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment.Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment.Methods: Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model.We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations. Results:We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model.We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals.We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4 + and CD8 + T cells along with a decrease of inhibitory cells. Conclusion:To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy.We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall efficacy of cancer immunotherapy.
John Crispin Townsend
Authors: Elaine Carter, Mary Macintosh
Journal: BMJ (2017)

John Crispin Townsend (“Cris”) was born in Rutland, a special place to him all his life. He started work as a laboratory technician, serving Northampton, but realised his future lay in medicine. As a mature student he entered the 1st MB year at Sheffield University …
Investigating Regional Differences in Short-Term Effects of Air Pollution on Daily Mortality in the APHEA Project: A Sensitivity Analysis for Controlling Long-Term Trends and Seasonality
Authors: Evangelia Samoli, Joel Schwartz, Bogdan Wojtyniak, Giota Touloumi, Claudia Spix, Frank Balducci, Sylvia Medina, Giuseppe Rossi, Jordi Sunyer, Ljuba Bacharova, Hugh Ross Anderson, Klea Katsouyanni
Journal: Environmental Health Perspectives (2001)

Short-term effects of air pollution on daily mortality in eight western and five central-eastern European countries have been reported previously, as part of the APHEA project. One intriguing finding was that the effects were lower in central-eastern European cities. The analysis used sinusoidal terms for seasonal control and polynomial terms for meteorologic variables, but this is a more rigid approach than the currently accepted method, which uses generalized additive models (GAM). We therefore reanalyzed the original data to examine the sensitivity of the results to the statistical model. The data were identical to those used in the earlier analyses. The outcome was the daily total number of deaths, and the pollutants analyzed were black smoke (BS) and sulfur dioxide (SO(2)). The analyses were restricted to days with pollutant concentration < 200 microg/m(3) and < 150 microg/m(3) alternately. We used Poisson regression in a GAM model, and combined individual city regression coefficients using fixed and random-effect models. An increase in BS by 50 microg/m(3) was associated with a 2.2% and 3.1% increase in mortality when analysis was restricted to days < 200 microg/m(3) and < 150 microg/m(3), respectively. The corresponding figures were 5.0% and 5.6% for a similar increase in SO(2). These estimates are larger than the ones published previously: by 69% for BS and 55% for SO(2). The increase occurred only in central-eastern European cities. The ratio of western to central-eastern cities for estimates was reduced to 1.3 for BS (previously 4.8) and 2.6 for SO(2) (previously 4.4). We conclude that part of the heterogeneity in the estimates of air pollution effects between western and central-eastern cities reported in previous publications was caused by the statistical approach used and the inclusion of days with pollutant levels above 150 microg/m(3). However, these results must be investigated further.
Biosimilars in Oncology in the United States
Authors: Chadi Nabhan, Sandeep Parsad, Anthony R. Mato, Bruce A. Feinberg
Journal: JAMA Oncology (2017)

Biosimilars are biological medicines that contain a highly similar version of the active substance of an already approved biologic reference product. The availability of biosimilars might provide an opportunity to lower health care expenditures as a result of the inherent price competition with their reference product. Understanding how biosimilar cancer drugs are regulated, approved, and paid for, as well as their impact in a value-based care environment, is essential for physicians and other stakeholders in oncology.Important structural and regulatory differences exist between biosimilar and generic medications. Minor differences in clinically inactive components with no clinically meaningful differences between biosimilars and their reference biologic are allowed. A biosimilar uses the same mechanism of action as the reference biologic, and its condition of use is the same as the approved indication, although extrapolation is permitted across indications under regulatory guidance. A biosimilar has to have a similar route of administration, dosage, and strength as the reference biologic. As patent expiration of multiple cancer biologics will occur in the next few years, more biosimilars might enter the market. Whether the approval and use of biosmilars as replacements for these heavily prescribed reference biologics will ultimately lead to cost savings is unknown and requires longer follow-up. Two biosimilars with an oncology supportive care indication are currently approved in the United States; both are myeloid growth factors.The financial impact of generic drug competition can be dramatic, but significant differences in regulatory and development processes between generics and biosimilars limit such comparisons and likely present significant challenges for biosimilar approval and adoption in the US market. However, a value-based care environment and their cost-savings potential make biosimilars an attractive option for the therapeutic arsenal. Oncologists' understanding of biosimilars is critical to moving forward.
Tropomodulin 1 controls erythroblast enucleation via regulation of F-actin in the enucleosome
Authors: Roberta B. Nowak, Julien Papoin, David S. Gokhin, Carla Casu, Stefano Rivella, Jeffrey M. Lipton, Lionel Blanc, Velia M. Fowler
Journal: Blood (2017)
The Enduring Challenge of Advanced HIV Infection
Authors: Nathan Ford, Meg Doherty
Journal: New England Journal of Medicine (2017)

Until recently, progress in the fight against human immunodeficiency virus (HIV) infection was primarily measured in terms of the number of patients who were started on antiretroviral therapy (ART). Major efforts to increase access to ART in the low- and middle-income countries that are most affected by HIV infection began in 2000, and over the following 15 years, an estimated 8 million HIV-related deaths were averted. In countries with a high burden of disease, this decline translated into important increases in life expectancy.1 Notwithstanding these gains, the decrease in HIV-associated deaths appears to have plateaued in recent years. HIV still . . .
Thyroid Functional Abnormalities in Newly Diagnosed AL Amyloidosis: Frequency and Influence By Type of Organ Involvement and Disease Burden
Authors: Eli Muchtar, Diana Dean, Angela Dispenzieri, David Dingli, Francis K Buadi, Martha Q. Lacy, Wilson I. Gonsalves, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Stephen J. Russell, John A Lust, Ronald S. Go, Yi Lin, Rajshekhar Chakraborty, Steven R. Zeldenrust, Shaji Kumar, Robert A. Kyle, S. Vincent Rajkumar, Morie A. Gertz
Journal: Blood (2016)
Survival following segmentectomy and lobectomy for stage I non-small cell lung cancer.
Authors: Cardinale B. Smith, Juan P. Wisnivesky
Journal: Journal of Clinical Oncology (2012)

7064 Background: Although lobectomy is considered the standard surgical treatment forstage IA non–small cell lung cancer (NSCLC), limited resections are frequently performed for patients with poor lung function or high operative risk. Recent studies suggest that segmentectomy may be the superior limited resection procedure. The objective of this study was to compare survival among patients with stage IA (≤3cm) NSCLC undergoing lobectomy vs. segmentectomy. Methods: Using the Surveillance, Epidemiology and End Results registry we identified 15,180 cases of stage IA NSCLC that underwent lobectomy or segmentectomy. We used logistic regression to determine propensity scores for patients undergoing segmentectomy based on the patient’s preoperative characteristics. Overall and lung cancer-specific survival of patients treated with lobectomy versus segmentectomy was compared after adjusting, stratifying, or matching patients based on their propensity score. We also performed secondary analyses in subgroups of age (≤70 vs. &gt;70 years) and tumor size ≤2 cm. Results: Overall, 1,200 (8%) patients underwent segmentectomy. Among the entire cohort, analyses adjusting for propensity scores did not demonstrate a difference in outcomes among patients treated with lobectomy versus segmentectomy, (adjusted hazard ratio [HR] for overall survival 1.11, 95% confidence interval [CI]: 0.94 – 1.30 and lung cancer-specific survival 1.11, 95% CI: 0.98 – 1.25). Similarly, secondary analyses showed no difference in overall (HR: 1.12, 95% CI: 0.90 – 1.40) and lung cancer-specific survival (HR: 1.04, 95% CI: 0.88 – 1.24) among patients with tumors ≤2 cm (T1a tumors). For patients ≤70 years of age, no difference in overall survival was observed (HR: 0.97, 95% CI: 0.73 – 1.28); however, a lung cancer-specific survival advantage of lobectomy was observed (HR: 1.19, 95% CI: 1.00 – 1.40). Finally, among those &gt;70 years overall survival (HR: 1.03, 95% CI: 0.87 – 1.22) and lung cancer-specific survival (HR: 1.18, 95% CI: 0. 97 – 1.44) showed equivalence of the two surgical groups. Conclusions: Segmentectomy and lobectomy may lead to equivalent survival rates among patients with stage IA NSCLC. These study findings should be confirmed in prospective studies.
Detection of Osteomyelitis in the Diabetic Foot by Imaging Techniques: A Systematic Review and Meta-analysis Comparing MRI, White Blood Cell Scintigraphy, and FDG-PET
Authors: Chiara Lauri, Menno Tamminga, Andor W.J.M. Glaudemans, Luis Eduardo Juárez Orozco, Paola A. Erba, Paul C. Jutte, Benjamin A. Lipsky, Maarten J. IJzerman, Alberto Signore, Riemer H.J.A. Slart
Journal: Diabetes Care (2017)

OBJECTIVE Diagnosing bone infection in the diabetic foot is challenging and often requires several diagnostic procedures, including advanced imaging. We compared the diagnostic performances of MRI, radiolabeled white blood cell (WBC) scintigraphy (either with 99mTc-hexamethylpropyleneamineoxime [HMPAO] or 111In-oxine), and [18F]fluorodeoxyglucose positron emission tomography (18F-FDG–PET)/computed tomography. RESEARCH DESIGN AND METHODS We searched Medline and Embase as of August 2016 for studies of diagnostic tests on patients known or suspected to have diabetes and a foot infection. We performed a systematic review using criteria recommended by the Cochrane Review of a database that included prospective and retrospective diagnostic studies performed on patients with diabetes in whom there was a clinical suspicion of osteomyelitis of the foot. The preferred reference standard was bone biopsy and subsequent pathological (or microbiological) examination. RESULTS Our review found 6,649 articles; 3,894 in Medline and 2,755 in Embase. A total of 27 full articles and 2 posters was selected for inclusion in the analysis. The performance characteristics for the 18F-FDG–PET were: sensitivity, 89%; specificity, 92%; diagnostic odds ratio (DOR), 95; positive likelihood ratio (LR), 11; and negative LR, 0.11. For WBC scan with 111In-oxine, the values were: sensitivity, 92%; specificity, 75%; DOR, 34; positive LR, 3.6; and negative LR, 0.1. For WBC scan with 99mTc-HMPAO, the values were: sensitivity, 91%; specificity, 92%; DOR, 118; positive LR, 12; and negative LR, 0.1. Finally, for MRI, the values were: sensitivity, 93%; specificity, 75%; DOR, 37; positive LR, 3.66, and negative LR, 0.10. CONCLUSIONS The various modalities have similar sensitivity, but 18F-FDG–PET and 99mTc-HMPAO–labeled WBC scintigraphy offer the highest specificity. Larger prospective studies with a direct comparison among the different imaging techniques are required.
18F-FDG PET/CT Scan Can Predate Clinical Presentation in Acute Appendicitis
Authors: Syed Zama Ali, Loi Hoi Yin, Khor Lih Kin, Arvind Kumar Sinha, Li Mei Poon
Journal: Clinical Nuclear Medicine (2017)

Acute appendicitis is a clinical diagnosis typically presenting with right lower quadrant pain. We describe the case of an asymptomatic 53-year-old man with stage 2A diffuse large B-cell lymphoma, who underwent 18F-FDG PET/CT at the completion of chemotherapy. The scan showed complete lymphomatous disease remission. Incidentally, there was increased FDG uptake in a tubular structure adjacent to the cecum. Clinical examination was negative. Subsequently, the patient presented 6 days later with typical acute appendicitis symptoms. This case is interesting wherein increased FDG uptake in the appendix predated the appearance of clinical symptoms.
Abstract 188: Contractile Function and Myofilament Proteins of the Naked Mole-rat Heart Show Resistance to Oxidative Stress
Authors: Kelly M Grimes, David Barefield, David A Kramer, Sakthivel Sadayappan, Rochelle Buffenstein
Journal: Circulation Research (2015)

The naked mole-rat (NMR) is the longest-lived rodent, with a maximum lifespan of &gt;31 years. Unlike every other mammal studied to date, this species withstands cardiovascular structural and functional changes for at least 75% of its lifespan. Due to the intersection of oxidative stress, aging, and cardiovascular disease, we questioned if NMRs were more resistant to oxidative stress-induced cardiac dysfunction compared to short-lived mice. Echocardiography showed that 7 days after a 20 mg/kg dose of doxorubicin (DOX), mice had a 25% decline in fractional shortening (36 ± 1% to 27 ± 2%). In contrast, the fractional shortening of NMRs was unchanged with DOX treatment (27 ± 1%). Previously we observed that while basal cardiac function is low, NMRs have a robust cardiac reserve, displaying a 1.7 fold increase in fractional shortening under exercise-like conditions. DOX-treated NMRs had a significant reduction in their dobutamine response, signifying a diminished cardiac reserve. Intriguingly, we found no changes in phosphorylation or expression of myofilament proteins in the NMR heart with DOX treatment. Mice on the other hand, increased the phosphorylation of cardiac myosin binding protein-C and switched expression from predominantly α-myosin heavy chain to the β-isoform. Electron microscopy showed that DOX caused marked mitochondrial swelling and loss of cristae as well as massive cardiac myofibrillar disarray in mice. Conversely, DOX-treated NMRs had only slight alterations to myofilament structure. NMRs additionally had twofold higher levels of glutathione in their hearts, indicating a high antioxidant capacity. These findings reveal that long-lived NMRs are less susceptible to oxidative stress-induced cardiac dysfunction than mice. The NMR’s low basal cardiac function, unique regulation of myofilament proteins, and high glutathione levels may all be integral in the species’ ability to withstand oxidative damage and preserve cardiac function well into its third decade of life.
Secretory phospholipase A 2 responsive liposomes exhibit a potent anti-neoplastic effect in vitro , but induce unforeseen severe toxicity in vivo
Authors: Ragnhild Garborg Østrem, Ladan Parhamifar, Houman Pourhassan, Gael Clergeaud, Ole Lerberg Nielsen, Andreas Kjær, Anders Elias Hansen, Thomas Lars Andresen
Journal: Journal of Controlled Release (2017)