tbuckley/cabot-search huggingface dataset:
Microbial taxonomic and metabolic alterations during faecal microbiota transplantation to treat infection
Authors: Lee Kellingray, Gwénaëlle Le Gall, Marianne Defernez, Ian L.P. Beales, Ngozi Franslem-Elumogo, Arjan Narbad
Journal: Journal of Infection (2018)

This study aimed to examine changes to the microbiota composition and metabolic profiles of seven patients with recurrent Clostridium difficile infection (rCDI), following treatment with faecal microbiota transplant (FMT).16S rDNA sequencing and 1H NMR were performed on faecal samples from the patients (pre-, post-FMT, and follow-up) and the associated donor samples. Sparse partial-least-square analysis was used to identify correlations between the two datasets.The patients' microbiota post-FMT tended to shift towards the donor microbiota, specifically through proportional increases of Bacteroides, Blautia, and Ruminococcus, and proportional decreases of Enterococcus, Escherichia, and Klebsiella. However, although cured of infection, one patient, who suffers from chronic alcohol abuse, retained the compositional characteristics of the pre-FMT microbiota. Following FMT, increased levels of short-chain fatty acids, particularly butyrate and acetate, were observed in all patients. Sparse partial-least-square analysis confirmed a positive correlation between butyrate and Bacteroides, Blautia, and Ruminococcus, with a negative correlation between butyrate and Klebsiella and Enterococcus.Clear differences were observed in the microbiota composition and metabolic profiles between donors and rCDI patients, which were largely resolved in patients following FMT. Increased levels of butyrate appear to be a factor associated with resolution of rCDI.
Abstract 19797: Enhanced Engraftment of Mesenchymal Stem Cells With Pro-survival Factors Improves Outcome in the Infarcted Heart
Authors: Pablo G Sanchez, Saman Eghtesad, Xiaoyan Liu, Ling Chen, Mark F Pittenger, Bartley P Griffith
Journal: Circulation (2015)

Mesenchymal stem cells are under study as exemplary adult progenitor cells for repair of heart tissue injury. Many clinical studies utilizing MSCs are underway, however the ideal approach to prepare these cells in vitro, and deliver them to injury sites in vivo with maximal effectiveness is still under study. In this report, MSCs from rat bone marrow were used to examine the 1) effect of anti-apoptotic factors on the cells’ viability when challenged in vitro and 2) effect on in vivo cardiac infarct physiologic parameters. Methods: Lewis rats underwent myocardial ischemia and reperfusion by temporary ligation (45 min) of the left anterior descending coronary. The periinfarct area then received five myocardial injections with either untreated or anti-apoptotic factor treated MSCs. Animals underwent transthoracic echocardiography over 8 weeks. Results: The treated MSCs had reduced in vitro apoptosis (Figure A). The MSCs treated with anti-apoptotic factors were tested in vivo to examine if the survival of MSCs was enhanced and could improve infarct physiologic parameters. The anti-apoptotic factor treated MSCs improved the injured hearts more than untreated MSCs by echocardiographic measurements: improved ejection fraction (58.4 ± 6.5 vs. 46.6 ± 8.6 respectively, p =0.01) and greater fractional shortening (32.2 ± 4.6 vs. 24.3 ± 5.3 respectively, p =0.009). Both were better than medium alone infarct controls (Figure B). The treated MSCs were detected in the hearts in greater abundance and at later interval than the untreated MSCs. Conclusions: MSCs that were treated to resist apoptosis survived longer in vitro and in vivo, and improved heart function more than untreated MSCs. Injury recovery improved to a far greater extent than differentiation of the limited number of surviving cells could provide; this is consistent with the MSCs providing growth factors and cytokines to reduce inflammation and aid recovery of the endogenous cells in the region of injury.
Regulatory T-cell deficiency leads to pathogenic bullous pemphigoid antigen 230 autoantibody and autoimmune bullous disease
Authors: Stefanie Haeberle, Xiaoying Wei, Katja Bieber, Stephanie Goletz, Ralf J. Ludwig, Enno Schmidt, Alexander H. Enk, Eva N. Hadaschik
Journal: Journal of Allergy and Clinical Immunology (2018)
Subcutaneous infiltration of carbon dioxide (carboxytherapy) for abdominal fat reduction: A randomized clinical trial
Authors: Murad Alam, Divya Sadhwani, Amelia Geisler, Imran Aslam, Inder Raj S. Makin, Daniel I. Schlessinger, Wareeporn Disphanurat, Marisa Pongprutthipan, Nataya Voravutinon, Alexandra Weil, Brian R. Chen, Dennis P. West, Emir Veledar, Emily Poon
Journal: Journal of the American Academy of Dermatology (2018)
From surviving to thriving: What evidence is needed to move early child-development interventions to scale?
Authors: Mark Tomlinson
Journal: PLoS Medicine (2018)

Previous research has established that delivering interventions in the first 1,000 days of life improves mother-child attachment [1], contributes to the reduction of health inequities [2], has a significant impact on adult health [3], and is cost-effective [4].At the global level, the importance of the early years of a child's life is reflected in high-level World Health Organization (WHO) and United Nations Children's Fund (UNICEF) support [5], the Global Strategy for Women's, Children's and Adolescents' Health (with its focus on not only survival but also children's ability to thrive and progress successfully into adolescence) [6], and the Nurturing Care Framework to be launched at the WHO World Health Assembly in May 2018.In this week's PLOS Medicine, 2 Research Articles present findings from trials conducted in Zambia and Colombia that add to the burgeoning evidence base on the implementation of early interventions designed to improve early child development (ECD) in low-and middle-income countries (LMICs). Child development interventions: Mechanism of impactPeter Rockers and colleagues [7] assessed the impact on ECD of community-based home visiting incorporating health screening and parenting groups.The study was a 2-year follow-up of a cluster-randomised controlled trial conducted in Zambia with the caregivers of children between the ages of 6 and 12 months.The study included fortnightly home visits conducted by child development agents (CDAs) for the first year as well as parenting groups every 2 weeks for 2 years.The intervention significantly reduced stunting (odds ratio [OR] 0.45, 95% CI 0.22-0.92;p = 0.028) and was associated with an improvement in child language (β 0.14, 95% CI 0.01-0.27;p = 0.039), but there was no impact on other child-development outcomes.While Rockers and colleagues' study is important and speaks to the difficulties of improving child development in low-resource contexts, one of the key conclusions of the paper is that parenting groups may be a promising avenue for improving physical growth and child development.This of course may be true, but it is more likely that the improvements in stunting were a result of the home visits of the CDAs, and not the parenting groups, given that their visits focused on screening for infections and acute malnutrition and encouraging caregivers to attend routine health services.Without an understanding of the mechanisms involved, drawing conclusions about what component of a complex intervention is the likely agent of change is difficult.Alison Andrew and colleagues [8] describe the medium-term impacts of an ECD intervention in Colombia.They followed up a cohort that had previously received a psychosocial
High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides
Authors: Adele de Masson, John T. O’Malley, Christopher P. Elco, Sarah S. Garcia, Sherrie J. Divito, Elizabeth L. Lowry, Marianne Tawa, David C. Fisher, Phillip M. Devlin, Jessica E. Teague, Nicole R. Leboeuf, Ilan R. Kirsch, Harlan Robins, Rachael A. Clark, Thomas S. Kupper
Journal: Science Translational Medicine (2018)

The malignant T cell clone frequency in cutaneous T cell lymphoma lesions is an independent prognostic indicator for early disease progression and death.
Role of sentinel lymph node harboring 4T1 tumor metastases in the development of systemic antitumor immune response
Authors: Katsuya Deguchi, Satoshi Watanabe, Terrence Johnson, Suyu Shu
Journal: Cancer Research (2008)

1038   The standard treatment of early breast cancer is surgical removal of primary tumors along with regional lymph-nodes (LN) if positive sentinel LN are detected. In the absence of positive sentinel LN, only primary tumors are removed. These procedures are generally believed to be curative if cancer cells have not metastasized to distant visceral organs. We developed an animal model using 4T1 mammary carcinoma to study the role of tumor-draining LN (TDLN) that harbored metastases in the development of an antitumor immune response. BALB/c mice were inoculated with 1x10 6  4T1 tumor cells subdermally on the right hind leg and primary tumors were surgically removed on day7 or day10. To detect the presence of 4T1 cells in the draining inguinal LN and other visceral organs such the lung and liver, we prepared single cell suspensions and cultured them in the presence of 60 μM 6-thioguanine. This method allows the detection of a single viable tumor cell, thus provided evidence of early metastases. Analyses of metastases on day7 revealed that 98% (43/44), 80% (8/10), of TDLN and lungs had metastases, respectively, with no evidence of metastases (0/10) in the liver. Metastases were detected on day10 in 100% (16/16), 100% (9/9), and 80% (4/5) of TDLN, lung and liver, respectively. Surgical removal of primary tumors alone on day7 cured 91% (20/22) of mice despite the presence of metastases in the TDLN and lung. Similarly, removal of primary tumors on day10 cured 73% (11/15) of mice. By contrast, resection of both primary tumors and TDLN on day7 cured 68% (27/40), and resection of primary tumors and TDLN on day10 cured only 27% (4/15) of mice. Preliminary experiments also showed that 89% (8/9) of survival mice after removal of primary tumors with intact TDLN resisted a secondary subdermal challenge of 4T1 tumor cells. Sublethal whole body irradiation (500 rad) of mice on the day of the removal of primary tumors on day7 or day10 reduced survival rates from 80% (8/10) to 43% (6/14). Our results suggest that despite the presence of tumor metastases, sentinel TDLN played an important role in the development of a systemic antitumor immunity. Surgical removal of the TDLN at the time of primary tumor surgery could interfere with the immune response mounted against the growing tumor metastases.
Gold Nanoparticles in Radiotherapy and Recent Progress in Nanobrachytherapy
Authors: Myriam Laprise‐Pelletier, Teresa Simão, Marc‐André Fortin
Journal: Advanced Healthcare Materials (2018)

Abstract Over the last few decades, gold nanoparticles (GNPs) have emerged as “radiosensitizers” in oncology. Radiosensitizers are additives that can enhance the effects of radiation on biological tissues treated with radiotherapy. The interaction of photons with GNPs leads to the emission of low‐energy and short‐range secondary electrons, which in turn increase the dose deposited in tissues. In this context, GNPs are the subject of intensive theoretical and experimental studies aiming at optimizing the parameters leading to greater dose enhancement and highest therapeutic effect. This review describes the main mechanisms occurring between photons and GNPs that lead to dose enhancement. The outcome of theoretical simulations of the interactions between GNPs and photons is presented. Finally, the findings of the most recent in vivo studies about interactions between GNPs and photon sources (e.g., external beams, brachytherapy sources, and molecules labeled with radioisotopes) are described. The advantages and challenges inherent to each of these approaches are discussed. Future directions, providing new guidelines for the successful translation of GNPs into clinical applications, are also highlighted.
MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease
Authors: Raj R. Bhanvadia, Calvin VanOpstall, Hannah Brechka, Nimrod S. Barashi, Marc Gillard, Erin M. McAuley, Juan Manuel Vasquez, Gladell Paner, Wen-Ching Chan, Jorge Andrade, Angelo M. De Marzo, Misop Han, Russell Z. Szmulewitz, Donald J. Vander Griend
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS–HOX interactions in prostate cancer etiology and progression. The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. Experimental Design: Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression. Results: These analyses demonstrate a stepwise decrease in the expression of both MEIS1 and MEIS2 from benign epithelia, to primary tumor, to metastatic tissues. Positive expression of MEIS proteins in primary tumors, however, is associated with a lower hazard of clinical metastasis (HR = 0.28) after multivariable analysis. Pathway and gene set enrichment analyses identified MEIS-associated networks involved in cMYC signaling, cellular proliferation, motility, and local tumor environment. Depletion of MEIS1 and MEIS2 resulted in increased tumor growth over time in vivo, and decreased MEIS expression in both patient-derived tumors and MEIS-depleted cell lines was associated with increased expression of the protumorigenic genes cMYC and CD142, and decreased expression of AXIN2, FN1, ROCK1, SERPINE2, SNAI2, and TGFβ2. Conclusions: These data implicate a functional role for MEIS proteins in regulating cancer progression, and support a hypothesis whereby tumor expression of MEIS1 and MEIS2 expression confers a more indolent prostate cancer phenotype, with a decreased propensity for metastatic progression. Clin Cancer Res; 24(15); 3668–80. ©2018 AACR.
Divergent adaptation in thyroid cancers
Authors: A. Sottoriva
Journal: Annals of Oncology (2018)

Thyroid cancer can be divided into several histological subtypes, the most common one being Papillary Thyroid Cancer (PTC). PTC has a good prognosis, whereas other subtypes such as Anaplastic Thyroid Cancer (ATC) have a dismal survival. Some patients with ATC have a previous history of PTC and in rare cases two tumours with distinct histology can coexist at the same time. This led to the hypothesis that ATC is the result of progression from PTC, generally through the accumulation of additional malignant traits driven by clonal selection, hence linear evolution from PTC to ATC. The hypothesis was sound and motivated by good histological data. However, as it happened with the advent of ancient genomics in archaeology [1.Callaway E. Divided by DNA: the uneasy relationship between archaeology and ancient genomics.Nature. 2018; 555: 573-576Crossref Scopus (23) Google Scholar], DNA data are often bound to shake previous assumptions. The field of cancer genomics is often driven by big numbers and large cohorts, but it is the analysis of rare and unusual cases that is often key to grasp the underlying cancer biology. Many cancer genes have indeed been identified by studying rare germline predispositions to cancer, from APC [2.Chasing down the APC bowel cancer gene—Cancer Research UK—Science blog. http://scienceblog.cancerresearchuk.org/2011/11/29/high-impact-science-chasing-down-the-apc-bowel-cancer-gene/.Google Scholar] to NF1 [3.Yap Y.-S. McPherson J.R. Ong C.-K. et al.The NF1 gene revisited – from bench to bedside.Oncotarget. 2014; 5: 5873-5892Crossref PubMed Scopus (74) Google Scholar]. In a study led by Ana Vivancos and Joan Seoane, from the Vall d'Hebron Institute of Oncology in Barcelona, Spain, Capdevila et al. [4.Capdevila J. Mayor R. Mancuso F.M. et al.Early evolutionary divergence between papillary and anaplastic thyroid cancers.Ann Oncol. 2018; 29: 1454-1460Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar] analyse the genomic profiles of a cohort of ATC and PTC tumours. Interestingly, they also examine a small set of rare cases with concomitant ATC and PTC neoplasms. The data are clear and indicate that ATC is unlikely to have linearly evolved from PTC. Instead, the two lesions seem to develop in parallel and are characterised by early evolutionary divergence. Hence, divergent adaptation, rather than linear evolution, drives tumourigenesis in these thyroid cancers, with the two phenotypes co-existing side by side. Although a larger study and additional data will be necessary to confirm this pattern, this study demonstrates how branched evolution is pervasive in cancer, supporting the idea that some tumours are born to be bad. AS is supported by the Wellcome Trust ( 202778/B/16/Z ), Cancer Research UK ( A22909 ) and the Chris Rokos Fellowship in Evolution and Cancer. We also acknowledge funding from the Wellcome Trust to the Centre for Evolution and Cancer ( 105104/Z/14 /Z).
Interventions to Prevent Falls in Older Adults
Authors: Janelle M. Guirguis-Blake, Yvonne L. Michael, Leslie A. Perdue, Erin L. Coppola, Tracy L. Beil
Journal: JAMA (2018)

Falls are the most common cause of injury-related morbidity and mortality among older adults.To systematically review literature on the effectiveness and harms of fall prevention interventions in community-dwelling older adults to inform the US Preventive Services Task Force.MEDLINE, PubMed, Cumulative Index for Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials for relevant English-language literature published through August 2016, with ongoing surveillance through February 7, 2018.Randomized clinical trials of interventions to prevent falls in community-dwelling adults 65 years and older.Independent critical appraisal and data abstraction by 2 reviewers. Random-effects meta-analyses using the method of DerSimonian and Laird.Number of falls (number of unexpected events in which a person comes to rest on the ground, floor, or lower level), people experiencing 1 or more falls, injurious falls, people experiencing injurious falls, fractures, people experiencing fractures, mortality, hospitalizations, institutionalizations, changes in disability, and treatment harms.Sixty-two randomized clinical trials (N = 35 058) examining 7 fall prevention intervention types were identified. This article focused on the 3 most commonly studied intervention types: multifactorial (customized interventions based on initial comprehensive individualized falls risk assessment) (26 trials [n = 15 506]), exercise (21 trials [n = 7297]), and vitamin D supplementation (7 trials [n = 7531]). Multifactorial intervention trials were associated with a reduction in falls (incidence rate ratio [IRR], 0.79 [95% CI, 0.68-0.91]) but were not associated with a reduction in other fall-related morbidity and mortality outcomes. Exercise trials were associated with statistically significant reductions in people experiencing a fall (relative risk, 0.89 [95% 13 CI, 0.81-0.97]) and injurious falls (IRR, 0.81 [95% CI, 0.73-0.90]) and with a statistically nonsignificant reduction in falls (IRR, 0.87 [95% CI, 0.75-1.00]) but showed no association with mortality. Few exercise trials reported fall-related fractures. Seven heterogeneous trials of vitamin D formulations (with or without calcium) showed mixed results. One trial of annual high-dose cholecalciferol (500 000 IU), which has not been replicated, showed an increase in falls, people experiencing a fall, and injuries, while 1 trial of calcitriol showed a reduction in falls and people experiencing a fall; the remaining 5 trials showed no significant difference in falls, people experiencing a fall, or injuries. Harms of multifactorial and exercise trials were rarely reported but generally included minor musculoskeletal injuries.Multifactorial and exercise interventions were associated with fall-related benefit, but evidence was most consistent across multiple fall-related outcomes for exercise. Vitamin D supplementation interventions had mixed results, with a high dose being associated with higher rates of fall-related outcomes.
Tau oligomers mediate α-synuclein toxicity and can be targeted by immunotherapy
Authors: Julia E. Gerson, Kathleen M. Farmer, Natalie Henson, Diana L. Castillo-Carranza, Mariana Carretero Murillo, Urmi Sengupta, Alan Barrett, Rakez Kayed
Journal: Molecular Neurodegeneration (2018)

We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson's disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target. We treated seven-month-old mice overexpressing mutated α-synuclein (A53T mice) with tau oligomer-specific monoclonal antibody (TOMA) and a control antibody and assessed both behavioral and pathological phenotypes. We found that A53T mice treated with TOMA were protected from cognitive and motor deficits two weeks after a single injection. Levels of toxic tau oligomers were specifically decreased in the brains of TOMA-treated mice. Tau oligomer depletion also protected against dopamine and synaptic protein loss. These results indicate that targeting tau oligomers is beneficial for a mouse model of synucleinopathy and may be a viable therapeutic strategy for treating diseases in which tau and α-synuclein have a synergistic toxicity.
Representation of obese participants in obesity-related cancer randomized trials
Authors: E. Pestine, A. Stokes, L. Trinquart
Journal: Annals of Oncology (2018)

Obesity is a risk factor for numerous cancer types, and may influence cancer treatment outcomes. Underrepresentation of obese patients in obesity-related cancer randomized controlled trials (RCTs) may affect generalizability of results. We aimed to assess the reporting of information about eligibility and enrollment of obese participants in obesity-related cancer RCTs.We conducted a systematic review of RCTs of 10 obesity-related cancer types (esophagus, colon/rectum, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, and thyroid cancer). We selected RCTs published between 2013 and 2016 in five major journals. For each trial, we examined the article, the protocol, and the registration record. We assessed if eligibility criteria limiting the enrollment of obese participants were reported, the proportion of obese participants that were enrolled, and if a subgroup analysis according to obesity status was reported. We systematically contacted corresponding authors and asked for information about eligibility of obese participants and the proportion of obese participants.We included 76 RCTs. Colon/rectum (n = 20), postmenopausal breast (n = 11), and kidney (n = 11) cancers were the most frequent types. Based on publicly available sources, information on the eligibility of obese participants was available in 5 (7%) trials. The proportion of obese participants could be estimated in 9 (12%) trials only. We found a subgroup analysis in only one RCT. When considering unpublished information, the eligibility of obese participants was explicitly stated in 31 (41%) trials but it was unclear if the remaining 59% trials considered obese participants as eligible and what proportion of obese participants was included. Across 22 trials, the median proportion of obese participants included was 18% (Q1-Q3 11-23).Information on the eligibility and enrollment of obese participants in cancer RCTs is dramatically underreported. More transparency is needed to understand the applicability of obesity-related cancer RCT results to obese patients with cancer.