tbuckley/cabot-search huggingface dataset:
AB0190 Is bone mass and bone loss related to long-term glucocorticosteroids in rheumatoid arthritis and lupus erythematosus patients?
Authors: P Leszczynski, I Korczowska, JK Lacki
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The purpose of this study was to determine the correlation between chronic active inflammatory process and long-term glucocorticosteroids theraphy (GCS) and bone loss in patients (pts) with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). <h3>Methods</h3> We have studied a sample of 128 women (90 RA pts and 38 SLE pts). All SLE pts and 44 RA pts were on chronic GCS (disease duration and duration of GCS therapy was: 108 ± 82 months and 122 ± 102 months, respectively). Total dose of GCS was 25.3 ± 28.19 g in SLE group and 7.4 ± 8.3 g in RA group. BMD of the forearm was measured by DXA using DTX-200 and QUS parameters by DTU-ONE. BMD of lumbar spine and the hip were measured by DXA using ECLIPSE densitometer. Disease activity was assessed by measuring serum levels of proinflammatory cytokines (IL-1a, IL-6, TNF-alpha, GM-CSF) and acute phase markers (ESR, CRP, AGP, AGP-RC, ACT). <h3>Results</h3> In RA pts on GSC therapy the disease activity was lower and also bone turnover was decreased. Moreover, in SLE pts with the highest dosage of GCS and the longest duration of the therapy the decrease in bone mass and the bone loss was the lowest. <h3>Conclusion</h3> Our results show questionable correlation between bone mass and bone loss in patients with chronic connective tissue diseases on long-term and low-dose corticosteroids therapy. Nevertheless, in long-term GCS treatment of RA pts and SLE pts bone decomposition is probably higher than anti-inflammatory effect.
Abstract B43: The c-Myc/AKT1/TBX3 axis is important to target in the treatment of embryonal rhabdomyosarcoma
Authors: Danica Anne Sims, Hapiloe Mabaruti Maranyane, Jade Peres, Sharon Prince
Journal: Cancer Research (2020)

Abstract Rhabdomyosarcoma (RMS), a pediatric cancer of the skeletal muscle, is the most common malignant soft-tissue sarcoma in children and adolescents. There are two main subtypes: embryonal RMS (ERMS), which is more prevalent in children and accounts for approximately 75% of RMS cases, and alveolar RMS (ARMS), which presents in adolescents and young adults and accounts for the remaining 25% of cases. Little is known about the molecular mechanisms underpinning ERMS, and there is a need for new and effective therapeutic approaches. Here we investigate the status and role of the T-Box transcription factor 3 (TBX3), which has been well characterized for its function in development and, in particular,r the congenital disorder ulnar mammary syndrome that results from its haploinsufficiency. Conversely, TBX3 has been reported to be overexpressed in numerous cancers including a range of sarcoma subtypes and shown to contribute to oncogenic processes such as cell proliferation, migration, and invasion, in vitro and in vivo tumor-forming ability. To determine the status of TBX3 in ERMS, immunohistochemistry was performed using RMS patient tissue and Western blotting on a panel of RMS cell lines compared to normal myoblast cells. Cell culture models in which TBX3 was either stably knocked down or overexpressed were established, and in vitro and in vivo assays were performed to determine the impact of TBX3 on key hallmarks of cancer including cell proliferation (growth curves), migration (scratch motility assay), as well as tumor formation and invasion in nude mice. Our data showed high TBX3 levels in RMS patient tumor tissue sections as well as in ERMS cell lines tested. Preliminary data reveal that the mechanisms involved in upregulating TBX3 in ERMS involve c-Myc at a transcriptional level and AKT1 at a post-translational level. Importantly, TBX3 was found to promote ERMS cell proliferation and migration, anchorage-independent growth, tumor formation, and metastasis. This study describes for the first time that TBX3 is an oncogene in ERMS and identifies c-Myc/AKT1/TBX3 as an important axis that could be targeted as novel therapeutic approaches for the treatment of this cancer. Citation Format: Danica Anne Sims, Hapiloe Mabaruti Maranyane, Jade Peres, Sharon Prince. The c-Myc/AKT1/TBX3 axis is important to target in the treatment of embryonal rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B43.
Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
Authors: Daniele Corridoni, Agne Antanaviciute, Tarun Gupta, David Fawkner-Corbett, Anna Aulicino, Marta Jagielowicz, Kaushal Parikh, Emmanouela Repapi, Steve Taylor, Dai Ishikawa, Ryo Hatano, Taketo Yamada, Wei Xin, Hubert Slawinski, Rory Bowden, Giorgio Napolitani, Oliver Brain, Chikao Morimoto, Hashem Koohy, Alison Simmons
Journal: Nature Medicine (2020)
Genetic manipulation of immortalized normal human bronchial epithelial cells
Authors: Mitsuo Sato, Luc Girard, Michael Peyton, Ruben D. Ramirez, Noriaki Sunaga, Adi F. Gazdar, Jerry W. Shay, John D. Minna
Journal: Cancer Research (2005)

3896  Purpose: To evaluate the oncogenic impact of p53 knockdown, mutant K-RASV12, mutant EGFR alone and their combination on tumorigenicity of a newly developed immortalized human bronchial epithelial cell line. Background: Molecular analysis of lung cancer has revealed several genetic and epigenetic alterations in the multistep pathogenesis of lung cancer. However, little is known about the relative importance of each individual alteration on the tumorigenic process. One approach is to use a model system in which the contribution of each genetic alteration to lung tumorigenesis can be assessed individually and combinatorially. We have developed an in vitro model system using normal human bronchial epithelial cells that overexpress Cyclin-dependent kinase 4 and human telomerase. Ectopic expression of these two genes enables the cells to bypass the growth inhibitory signals of the p16/Rb pathway and also replicative senescence induced by shortened telomeres. We manipulated this cell line (HBEC3), by stably knocking down p53 using RNA interference, by introducing a mutant form of K-RASV12, and by introducing a mutant epidermal growth factor receptor (EGFR), alone and in combination. Methods: pSuper.retro vector was used for p53 knockdown and a mutant K-RASV12 and mutant EGFRs (EGFRdel746-750 and EGFRL858R) were introduced using viral expression vectors. To test the genetically manipulated lines for changes in their malignant potential, growth in liquid culture, colony formation ability, growth factor dependence, and growth as xenografts in immuno-compromised mice were performed. To determine the effect of tyrosine kinase inhibitors (TKIs) (gefitinib and erlotinib) on manipulated HBEC3 cells and to assess their potential as chemopreventive agents, the cells were evaluated both in the presence or absence of these drugs for colony forming ability. Results: Stable knockdown of p53 and overexpression of mutant EGFR were confirmed by immunoblotting in manipulated cells. K-RASV12 expression was confirmed by RFLP analysis. p53 knockdown and K-RASV12 alone caused cells to be less sensitive to contact inhibition and to be capable of partial anchorage-independent growth. The combination of p53 knockdown and K-RASV12 further enhanced the tumorigenic phenotype by growth in soft agar but failed to cause cells to form tumors in nude mice. In addition, the ability of both anchorage-dependent and-independent cell growth of HBEC3 cells was highly dependent on epidermal growth factor (EGF) and this ability was completely inhibited with TKIs. Both types of mutant EGFRs enhanced the tumorigenic phenotype by growth in soft agar. Importantly, introduction of mutant EGFRL858R into the HBEC3-p53 knockdown cells abrogated EGF dependence as measured by anchorage-independent colony formation ability. These results demonstrate that this isogenic in vitro model system is a powerful approach for studying lung cancer development.
The role of gut microbiota in cancer treatment: friend or foe?
Authors: Wing Yin Cheng, Chun-Ying Wu, Jun Yu
Journal: Gut (2020)

The gut microbiota has been implicated in cancer and shown to modulate anticancer drug efficacy. Altered gut microbiota is associated with resistance to chemo drugs or immune checkpoint inhibitors (ICIs), whereas supplementation of distinct bacterial species restores responses to the anticancer drugs. Accumulating evidence has revealed the potential of modulating the gut microbiota to enhance the efficacy of anticancer drugs. Regardless of the valuable findings by preclinical models and clinical data of patients with cancer, a more thorough understanding of the interactions of the microbiota with cancer therapy helps researchers identify novel strategy for cancer prevention, stratify patients for more effective treatment and reduce treatment complication. In this review, we discuss the scientific evidence on the role of gut microbiota in cancer treatment, and highlight the latest knowledge and technologies leveraged to target specific bacteria that contribute to tumourigenesis. First, we provide an overview of the role of the gut microbiota in cancer, establishing the links between bacteria, inflammation and cancer treatment. Second, we highlight the mechanisms used by distinct bacterial species to modulate cancer growth, immune responses, as well as the efficacy of chemotherapeutic drugs and ICIs. Third, we demonstrate various approaches to modulate the gut microbiota and their potential in translational research. Finally, we discuss the limitations of current microbiome research in the context of cancer treatment, ongoing efforts to overcome these challenges and future perspectives.
Evaluation of four commercial real-time PCR assays for the detection of lymphogranuloma venereum in Chlamydia trachomatis-positive anorectal samples
Authors: Arabella Touati, Cécile Laurier-Nadalié, Cécile Bébéar, Olivia Peuchant, Bertille de Barbeyrac
Journal: Clinical Microbiology and Infection (2020)
Epidemiology of measles during the COVID-19 pandemic, a description of the surveillance data, 29 EU/EEA countries and the United Kingdom, January to May 2020
Authors: Nathalie Nicolay, Grazina Mirinaviciute, Thomas Mollet, Lucia Pastore Celentano, Sabrina Bacci
Journal: Eurosurveillance (2020)

The number of measles cases declined in European Union/European Economic Area countries and the United Kingdom in 2020. Reported cases to The European Centre for Disease Prevention and Control decreased from 710 to 54 between January and May. Epidemic intelligence screening observed a similar trend. Under-diagnoses and under-reporting during the coronavirus disease (COVID-19) pandemic should be ruled out before concluding reduced measles circulation is because of social distancing and any community control measures taken to control COVID-19.
Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models
Authors: Britta L Jewell, Edinah Mudimu, John Stover, Debra ten Brink, Andrew N Phillips, Jennifer A Smith, Rowan Martin-Hughes, Yu Teng, Robert Glaubius, Severin Guy Mahiane, Loveleen Bansi-Matharu, Isaac Taramusi, Newton Chagoma, Michelle Morrison, Meg Doherty, Kimberly Marsh, Anna Bershteyn, Timothy B Hallett, Sherrie L Kelly
Journal: The Lancet HIV (2020)

The COVID-19 pandemic could lead to disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimated that more than two-thirds of the approximately 38 million people living with HIV resided in 2018. We aimed to predict the potential effects of such disruptions on HIV-related deaths and new infections in sub-Saharan Africa.In this modelling study, we used five well described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, an Imperial College London model, and Epidemiological MODeling software [EMOD]) to estimate the effect of various potential disruptions to HIV prevention, testing, and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months over 1 year from April 1, 2020. We considered scenarios in which disruptions affected 20%, 50%, and 100% of the population.A 6-month interruption of supply of antiretroviral therapy (ART) drugs across 50% of the population of people living with HIV who are on treatment would be expected to lead to a 1·63 times (median across models; range 1·39-1·87) increase in HIV-related deaths over a 1-year period compared with no disruption. In sub-Saharan Africa, this increase amounts to a median excess of HIV deaths, across all model estimates, of 296 000 (range 229 023-420 000) if such a high level of disruption occurred. Interruption of ART would increase mother-to-child transmission of HIV by approximately 1·6 times. Although an interruption in the supply of ART drugs would have the largest impact of any potential disruptions, effects of poorer clinical care due to overstretched health facilities, interruptions of supply of other drugs such as co-trimoxazole, and suspension of HIV testing would all have a substantial effect on population-level mortality (up to a 1·06 times increase in HIV-related deaths over a 1-year period due to disruptions affecting 50% of the population compared with no disruption). Interruption to condom supplies and peer education would make populations more susceptible to increases in HIV incidence, although physical distancing measures could lead to reductions in risky sexual behaviour (up to 1·19 times increase in new HIV infections over a 1-year period if 50% of people are affected).During the COVID-19 pandemic, the primary priority for governments, donors, suppliers, and communities should focus on maintaining uninterrupted supply of ART drugs for people with HIV to avoid additional HIV-related deaths. The provision of other HIV prevention measures is also important to prevent any increase in HIV incidence.Bill & Melinda Gates Foundation.
Abstract 343: Chest Compression Compliance With Guidelines Declines Over the Course of Rescues
Authors: James K Russell, Digna González Otero, Sofia Ruiz de Gauna, Mikel Leturiondo, Jesus M Ruiz, Mohamud R DAYA
Journal: Circulation (2019)

Introduction: CPR guidelines recommend limits for rate and depth, and release (avoidance of leaning). Simultaneous compliance with all three recommendations is challenging, sustained compliance more so. Hypothesis: Compliance with rate, depth and release guidelines is limited, and will decline over the course of rescues. Methods: Acceleration and force signals were extracted from monitor/defibrillators equipped with CPR monitors in 248 adult cases of manual CPR during out-of-hospital resuscitations treated by Tualatin Valley Fire &amp; Rescue (TVF&amp;R, Tigard, OR) during 2016 and 2017. TVF&amp;R personnel delivered continuous compression CPR with real-time feedback available for rate, depth and leaning. Depth was calculated from acceleration. Peak depth, release force, and rate were measured for each compression. Release with force exceeding 2.5 kg-f was counted as incomplete (leaning). Results: Cases included 1802 (1055-2683) (median, IQR) compressions (total 481,407 compressions). Compliance with all three recommendations was 25% initially, declining to 19% for the ends of the longest rescues (&gt; 3000 compressions from 48 cases). Depth compliance and complete release varied relatively little (31-36%, 93-95% respectively) and irregularly over the course of resuscitation. Early, 45% of compressions were too shallow (&lt; 50 mm), and 21% were too deep (&gt; 60 mm). Depth exceptions shifted over the course of resuscitation (to 36%, 28% respectively). Rate compliance declined from 73% to 54%. Rates below 100 cpm were 9% initially, declining to 5%. Rates exceeding 120 cpm were 18% early on, but climbed to 41% towards the end of long resuscitations, accounting for most of the decline in compliance with guidelines. Conclusions: Compliance with all 3 recommendations for CPR compressions is challenging, and becomes more so as the chest changes in response to compressions. Most problematic is a steady increase in compression rates above 120 cpm.
The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review
Authors: L F Perez-Garcia, R J E M Dolhain, S Vorstenbosch, W Bramer, E van Puijenbroek, J M W Hazes, B te Winkel
Journal: Human Reproduction Update (2020)

Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment.The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes.A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data.A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported.Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods.
Response to COVID-19 phenotyping correspondence
Authors: Lieuwe D.J. Bos, Pratik Sinha, Robert P. Dickson
Journal: European Respiratory Journal (2020)

In their letter, R. Cherian and co-workers take issue with our interpretation of the respiratory physiology of coronavirus disease 2019 (COVID-19), arguing that it is based merely on "small cohort studies", and instead declaring that "a high proportion of mechanically ventilated COVID-19 patients exhibit near-normal lung compliance". Yet the low respiratory compliance of COVID-19 patients has now been extensively demonstrated by studies totalling more than 800 COVID-19 patients [1–7], including a direct comparison with non-COVID-19 acute respiratory distress syndrome (ARDS) patients that revealed no difference in respiratory compliance [7]. In contrast, the three case series cited by R. Cherian and co-workers in support of their claim comprise cohorts of, respectively, 16, 10 and 26 patients [8–10]. Furthermore, even these case series report average respiratory compliance in COVID-19 of 40–45 mL·cmH2O−1, which is in fact abnormal and far from "near-normal compliance" [11, 12]. Phenotyping of COVID-19-related ARDS should be done using careful, data-driven approaches <https://bit.ly/3eX65Yu>
The conductive function of biopolymer corrects myocardial scar conduction blockage and resynchronizes contraction to prevent heart failure
Authors: Sheng He, Jun Wu, Shu-Hong Li, Li Wang, Yu Sun, Jun Xie, Daniel Ramnath, Richard D. Weisel, Terrence M. Yau, Hsing-Wen Sung, Ren-Ke Li
Journal: Biomaterials (2020)
Team sport in a COVID-19 world. A catastrophe in waiting, or an opportunity for community sport to evolve and further enhance population health?
Authors: Steffan A Griffin, Amy Mendham, Peter Krustrup, Andrew Murray, Nicholas Peirce, Jo Larkin, Rod Jaques, Charlotte M Cowie, Keith A Stokes, Simon PT Kemp
Journal: British Journal of Sports Medicine (2020)

While sporting governing bodies prepare guidelines and policies to comply with social distancing requirements and governmental guidelines, and some may feel that such changes threaten the very existence of their sport, is there a hidden opportunity to be found among the noise?

Elite team sports generate significant financial wealth and widespread media attention, but grass-roots participation rates in many traditional team sports have been decreasing, especially over the last 5 years.1 2 This contrasts with some data suggesting that physical activity levels actually may be increasing overall across the general population, especially among women and older people.1 This begs the question, are sports losing touch with the general population, and are people turning to non-traditional sports and individual activities for leisure-time physical activity?

First of all, why might people be turning away from traditional team sports? We know that some of the most frequently cited barriers to participating in sporting activities include: not feeling fit enough to participate; lack of time; poor accessibility; cost and fear of injury.3 4 However, as opposed to consigning these important findings to the pages of medical journals, could sports embrace these barriers as challenges to enhance participation, and secure their futures?

Positively, there are ‘bright-spots’ around the world, where these challenges have …