tbuckley/cabot-search huggingface dataset:
Neurocognitive changes as measured by impact and the scat3 in women’s soccer players without diagnosed concussion
Authors: Thomas G Bowman, Katherine M Breedlove, Theresa E Leahy
Journal: British Journal of Sports Medicine (2017)

Objective Neurocognitive changes have been found in football players without documented concussion raising concerns regarding the long term consequences of subconcussive head impacts in sport. It remains unknown if similar neurocognitive changes are found in female soccer athletes without concussion. Females have been found to have higher concussion rates compared to males and soccer is the most popular sport internationally providing a compelling area of study. Design Observational study. Setting American collegiate women’s soccer team. Participants 16 National Collegiate Athletic Association Division III women’s soccer athletes (19.88±1.1 years old, 163.7±4.9 cm, 61.2±4.9 kg) volunteered and provided consent for the study. Assessment of risk factors We measured head impacts during practices and games throughout the 15 week season with the xPatch (X2 Biosystems, Seattle, WA, USA). All participants completed ImPACT and the Sport Concussion Assessment Tool – 3 rd Edition (SCAT3) prior to the season’s start and at the end of the season. Outcome measures The xPatch stored location, frequency, and magnitude (linear and rotational accelerations) of head impacts. Event film was used to verify each head impact. Changes in neurocognitive function were determined by comparing the baseline ImPACT and SCAT3 scores with the post-season scores. Main results A stepwise regression found a significant relationship between weekly head impact frequency during practices and the ImPACT measures of Visual Motor Speed ( P =0.03) and Symptom Score ( P =0.03). Conclusions Soccer activity may lead to lower visual motor speed and higher symptom scores. Future studies should use additional screening tools to verify these preliminary findings. Competing interests None.
The Perk-eIF2α -ATF4 arm of the Unfolded Protein Response (UPR) contributes to tumor progression and is a target for therapeutic intervention.
Authors: Constantinos Koumenis, Meixia Bi, Jiangbin Ye, Diane Fels, Joy Little, Steven Kridel
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4579 

Hypoxia/anoxia in the tumor microenvironment promotes tumor aggressiveness and negatively impacts response to therapy. We previously demonstrated that tumor cells under hypoxia activate the endoplasmic reticulum (ER) kinase Perk, thereby inducing phosphorylation of the translation initiation factor eIF2α and translational upregulation of the transcription factor ATF4. The Perk-eIF2α-ATF4 pathway constitutes one component of the Unfolded Protein Response (UPR), a coordinated cellular program that promotes survival under conditions of ER stress. Inactivation of Perk or eIF2α phosphorylation or expression of a dominant-negative Perk in transformed cells, result in significant inhibition of tumor growth due to higher levels of apoptosis inn hypoxic areas and defective angiogenesis compared to tumors with an intact UPR. Notably, we and others found expression of ATF4 in hypoxic areas of clinical samples of human tumors. To gain further insight into the role of ATF4 in tumor progression, we performed microarray gene expression analysis on ATF4+/+ and ATF4-/- Mouse Embryonic Fibroblasts (MEFs), exposed to anoxia or normoxia for 10h. We have identified a number of genes whose expression was significantly changed in both an ATF4-dependent and hypoxia-dependent manner. The mRNA levels of TRB3, a protein induced under nutrient deprivation and of Pyruvate dehydrogenase kinase 1 (PDK1), which inhibits mitochondrial respiration to protect cells in low-oxygen conditions, were induced by anoxia to significantly higher levels in ATF4+/+ compared to ATF4-/- MEFs (22-fold vs. 4-fold for TRB3 and 17-fold vs. 4-fold for PDK1). We are currently investigating the role of ATF4 and its targets in hypoxia tolerance and in tumor progression by knock-down experiments. Interestingly, using MTT and clonogenic survival assays, we also found that hypoxic HeLa and PC-3 cells were significantly more sensitive to the known ER stressors thapsigargin and the FDA-approved proteasome-inhibitor PS-341, compared to normoxic tumor cells. This increased cytotoxicity correlated with increased levels of the UPR effectors ATF4 and Chop, suggesting treatment of hypoxic tumor cells with ER stress-inducing agents produces levels of ER stress that are not compatible with cell survival. More importantly, xenograft tumors from HeLa cells treated with PS-341 showed increased levels of apoptosis in hypoxic areas compared to tumors treated with vehicle alone. Taken together, our results and those of other groups indicate that the UPR is activated by the tumor microenvironment and contributes to tumor progression; however, UPR activation may also provide a unique opportunity to selectively target hypoxic cells with ER stress-inducing agents. This work was supported by NCI grant CA-94214 to CK.
Prescribing patterns of rasburicase and glucose-6-phosphate-dehydrogenase (G6PD) testing in a large community health system.
Authors: Omar Alhalabi, Siddhartha Yadav, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2016)

e18206 Background: Rasburicase is a recombinant urate-oxidase used in prevention and treatment of tumor lysis syndrome (TLS.) Since conversion of uric acid to allantoin leads to the production of hydrogen peroxide as a by-product, Rasburicase is contraindicated in patients with G6PD deficiency. Rasburicase-induced hemolysis occurs in < 1% of recipients. It is recommended that physicians screen for G6PD deficiency in patients at risk prior to administration of Rasburicase. This study assesses adherence to this recommendation and evaluates the incidence of Rasburicase-induced hemolysis. Methods: A retrospective analysis of 361 adult patients who received Rasburicase at Beaumont Health between 2009 and 2015 was conducted. These patients were identified by query of the electronic medication administration record. Cairo-Bishop criteria were used to define TLS. Data on demographics, presence of TLS, G6PD testing and level, and hemolytic reaction post administration was collected. Statistical analysis was performed using RStudio. Chi-square and Wilcoxon rank-sum tests were used to compare categorical and continuous variables, accordingly. Results: Rasburicase was used emergently for treatment of TLS in only 94 (26%) patients. On average, G6PD test resulted 35.6 hours after administration of Rasburicase. 59 (16%) of the recipients were identified as high risk race/ethnicity for G6PD deficiency. African Americans and Middle Easterns were more likely to be G6PD tested, (OR 2.82, 95% CI 1.33 to 6.01, p = 0.007). However, only 12 (20.3%) of these at-risk patients were tested. 5 (13.5%) of G6PD tested subjects were found to be deficient. Of these, 4 (80%) developed hemolysis post Rasburicase administration. Conclusions: Only a minority of at-risk patients were tested for G6PD deficiency prior to receiving Rasburicase. Perhaps, the delayed G6PD result timing or the urgency in giving Rasburicase lead to this shortcoming. Nonetheless, in light of the relatively common incidence of G6PD deficiency among tested individuals, further interventions beside blackbox warning are needed to improve adherence. Knowing the G6PD status is important to predict and promptly manage adverse events.
Successive governments are responsible for GP crisis
Authors: Patrick Lush
Journal: BMJ (2017)

I was shocked by the findings of the House of Lords Committee on NHS sustainability.1 I looked at the members of the committee. It comprised two surgeons, a professor of medicine, an obstetrician, a former Minister of Health, former politicians, a former headmaster, and retired administrators, among others; there were no general practitioners. Yet they concluded that “the traditional small business …
Promoter Module Detection as a Tool for Gene Identifcation in Colon Carcinoma
Authors: A Moss, P Doran, P MacMathuna
Journal: Endoscopy (2004)

Background: Promoter modules, consisting of at least two transcription factor binding sites at defined distances along a gene, are an integral part of the regulation of gene expression. These modules can be responsible for the control of genes sharing common functions i.e. proliferation
Trusts boost ratings by engaging staff and including clinicians in management
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Trusts that have managed to improve their bad ratings from the Care Quality Commission (CQC) have done so by better engagement with staff and ensuring that clinicians are more involved in organising and managing care, claims a new report.1

A CQC report published on 14 June details case studies from eight NHS trusts around England and looks at how they significantly improved quality of care and their CQC rating.

The report is based on interviews with staff, patients, and patient groups. All steps towards improvement by the trusts involved reviewing the organisation’s culture and tackling any “disconnect” between clinicians and managers, between medical and nursing teams, or between different hospitals at …
Correction to: MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway
Authors: Chun-Hua Wei, Gang Wu, Qian Cai, Xi-Can Gao, Fan Tong, Rui Zhou, Rui-Guang Zhang, Ji-Hua Dong, Yu Hu, Xiao-Rong Dong
Journal: Journal of Hematology & Oncology (2018)

The original article [1] contained incorrect affiliations for the authors.
Integrating molecular profiling into cancer treatment decision making: Experience with over 35,000 cases.
Authors: Zoran Gatalica, Sherri Millis, Sting Chen, Gargi Dan Basu, Wenhsiang Wen, Les Paul, Ryan P. Bender, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2013)

11001 Background: Molecular profiling of both common and rare cancer types provides for the identification of actionable targets for chemotherapy with many unexpected associations. Methods: Caris Life Sciences database of &gt;35,000 profiled cancers was reviewed for well-established driver gene mutations and copy number alterations, and protein expression patterns that are relevant for selection of targeted therapy. Based on the published literature, these tumor characteristics were then associated with potential benefit or no benefit to the specific therapeutic agents. All relevant published studies were evaluated using the USPSTF grading scheme for study design and validity. Assay methodologies included sequencing (Sanger, pyrosequencing), PCR, FISH, CISH, and immunohistochemistry. Results: All common malignancies (10 most common cancer types in men and women) and 10 rare cancer types were well represented (minimum of 100 cases in each individual cancer type). Well established driver mutations and protein expression in common cancers were all identified with expected frequencies (e.g. HER2 amplification in breast, PIK3CA mutations in ER+ breast cancer, EGFR mutations in NSCLC, etc.). Importantly, unexpected new and potentially actionable targets were identified in common (e.g., 6.7% HER2 amplification in NSCLC, 1.6% KRAS mutation in prostatic adenocarcinoma) and rare cancers (e.g., 8.3% ALK alteration in soft tissue sarcomas, 10.5% c-MET and 26.4% EGFR gene amplification in melanomas, 16.3% KRAS mutation in cholangiocarcinomas, 10% AR expression in STS), as well in cancers of unknown primary site (approximately 4% of all tested cases). Conclusions: This review of the large referral cancer profiling database provided an unparalleled insight in the distribution of common and rare genetic and protein alterations with direct and potential treatment implications. Numerous targets were discovered that had a potential to be treated by the conventional chemotherapy as well as targeted therapy not usually considered for the cancer type. Comparison between an individual patient tumor profile and database for the matched cancer type provides additional level of support for targeted treatment choices.
A non-synonymous SNP in an autophagy-related gene is associated with Crohn's disease
Authors: Natalie Prescott, Sheila Fisher, A Franke, Clive Onnie, J Hampe, CE Todhunter, D Soars, Jeremy Sanderson, A Forbes, J Mansfield, Cathryn Lewis, S Schreiber, Christopher Mathew
Journal: Gut (2007)
Deprivation Indices and Gastro-Oesophageal Cancers in Westmidlands (England) over 15 Years – A Study
Authors: S Dutta Roy, A Jibawi, D Corless, M Deakin
Journal: Endoscopy (2004)

Background: For most major cancers there is good evidence that patients from affluent neighbourhoods survive better than deprived patients. We decided to look at the incidence, mortality and survival trends of gastro-oesophageal cancers in West Midlands, England from 1984 to 1999 and analyse the results in terms of socio-economic deprivation.
Assessment of Human Leukocyte Antigen (HLA) Type on Outcomes of Allogeneic Transplant for Chronic Lymphocytic Leukemia (CLL)
Authors: Brian T. Hill, Kwang Woo Ahn, Zhen-Huan Hu, Matt Kalaycio, Richard T. Maziarz, Jorge E. Cortes, Edwin Alyea, Uday R. Popat, Ronald M. Sobecks, Wael Saber
Journal: Blood (2016)
Autologous Cell Therapy for Peripheral Arterial Disease
Authors: Mauro Rigato, Matteo Monami, Gian Paolo Fadini
Journal: Circulation Research (2017)

Rationale: Critical limb ischemia is a life-threatening complication of peripheral arterial disease. In patients who are ineligible for revascularization procedures, there are few therapeutic alternatives, leading to amputations and death. Objective: To provide a systematic review of the literature and a meta-analysis of studies evaluating safety and efficacy of autologous cell therapy for intractable peripheral arterial disease/critical limb ischemia. Methods and Results: We retrieved 19 randomized controlled trials (837 patients), 7 nonrandomized trials (338 patients), and 41 noncontrolled studies (1177 patients). The primary outcome was major amputation. Heterogeneity was high, and publication bias could not be excluded. Despite these limitations, the primary analysis (all randomized controlled trials) showed that cell therapy reduced the risk of amputation by 37%, improved amputation-free survival by 18%, and improved wound healing by 59%, without affecting mortality. Cell therapy significantly increased ankle brachial index, increased transcutaneous oxygen tension, and reduced rest pain. The secondary analysis (all controlled trials; n=1175 patients) shows that there may be potential to avoid ≈1 amputation/year for every 2 patients successfully treated. The tertiary analysis (all studies; n=2332 patients) precisely estimated the changes in ankle brachial index, transcutaneous oxygen tension, rest pain, and walking capacity after cell therapy. Intramuscular implantation appeared more effective than intra-arterial infusion, and mobilized peripheral blood mononuclear cells may outperform bone marrow–mononuclear cells and mesenchymal stem cells. Amputation rate was improved more in trials wherein the prevalence of diabetes mellitus was high. Cell therapy was not associated with severe adverse events. Remarkably, efficacy of cell therapy on all end points was no longer significant in placebo-controlled randomized controlled trials and disappeared in randomized controlled trials with a low risk of bias. Conclusions: Although this meta-analysis highlights the need for more high-quality placebo-controlled trials, equipoise may no longer be guaranteed because autologous cell therapy has the potential to modify the natural history of intractable critical limb ischemia.
Targeting VEGFR-3/-2 signaling pathways with AD0157: a potential strategy against tumor-associated lymphangiogenesis and lymphatic metastases
Authors: Melissa García-Caballero, Jenny Paupert, Silvia Blacher, Maureen Van de Velde, Ana Rodríguez Quesada, Miguel Angel Medina, Agnès Noël
Journal: Journal of Hematology & Oncology (2017)

Lymphatic metastasis is one of the leading causes of death in patients with different types of cancer and is the main prognostic factor for the disease survival. The formation of new lymphatic vessels (lymphangiogenesis) in primary tumors facilitates tumor cell dissemination to regional lymph nodes and correlates with distant metastases. Lymphangiogenesis has thus emerged as a suitable therapeutic target to block metastases, but no anti-lymphangiogenic compounds have been approved for clinical use to date. Therefore, new or improved therapies blocking lymphatic metastases are urgently required. We established murine breast tumors to assess the effect of AD0157 on tumor growth, lymphangiogenesis, and lymphatic dissemination. Then, a battery of in vivo (mouse corneal neovascularization and ear sponges), ex vivo (mouse lymphatic rings and rat mesentery explants), and in vitro (proliferation, tubulogenesis, wound-healing, Boyden chambers, and spheroids) assays was used to give insight into the lymphangiogenic steps affected by AD0157. Finally, we investigated the molecular pathways controlled by this drug. AD0157 was found to inhibit the growth of human breast cancer xenografts in mice, to strongly reduce tumor-associated lymphangiogenesis and to block metastatic dissemination to both lymph nodes and distant organs. The high anti-lymphangiogenic potency of AD0157 was further supported by its inhibitory activity at low micromolar range in two in vivo pathological models and in two ex vivo assays. In addition, AD0157 inhibited lymphatic endothelial cell proliferation, migration and invasion, cellular sprouting, and tube formation. Mechanistically, this compound induced apoptosis in lymphatic endothelial cells and decreased VEGFR-3/-2, ERK1/2, and Akt phosphorylations. These findings demonstrate the suitability of AD0157 to suppress tumor-associated lymphangiogenesis. Beyond discovering a new potent anti-lymphangiogenic drug that is worth considering in future clinical settings, our study supports the interest of designing anti-lymphangiogenic therapies to avoid distant metastatic processes.
Innovative financing instruments for global health 2002–15: a systematic analysis
Authors: Rifat Atun, Sachin Silva, Felicia M Knaul
Journal: The Lancet Global Health (2017)

Development assistance for health (DAH), the value of which peaked in 2013 and fell in 2015, is unlikely to rise substantially in the near future, increasing reliance on domestic and innovative financing sources to sustain health programmes in low-income and middle-income countries. We examined innovative financing instruments (IFIs)-financing schemes that generate and mobilise funds-to estimate the quantum of financing mobilised from 2002 to 2015. We identified ten IFIs, which mobilised US$8·9 billion (2·3% of overall DAH) in 2002-15. The funds generated by IFIs were channelled mostly through GAVI and the Global Fund, and used for programmes for new and underused vaccines, HIV/AIDS, malaria, tuberculosis, and maternal and child health. Vaccination programmes received the largest amount of funding ($2·6 billion), followed by HIV/AIDS ($1080·7 million) and malaria ($1028·9 million), with no discernible funding targeted to non-communicable diseases.
The Peptidase Activities of the Cathepsins of Normal Rat Tissue and of Jensen Rat Sarcoma
Authors: Maver, Mary E., Johnson, J. M., Thompson, J. W.
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article The Peptidase Activities of the Cathepsins of Normal Rat Tissue and of Jensen Rat Sarcoma Get access Mary E. Maver, Mary E. Maver biochemist 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 J. M. Johnson, J. M. Johnson senior chemist 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 J. W. Thompson J. W. Thompson associate 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 JNCI: Journal of the National Cancer Institute, Volume 1, Issue 5, April 1941, Pages 675–686, https://doi.org/10.1093/jnci/1.5.675 Published: 01 April 1941
Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis
Journal: New England Journal of Medicine (2017)

After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT.We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics.We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation.In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).
Talking to Patients About Cancer Screening Cessation
Authors: Alexia M. Torke
Journal: JAMA Internal Medicine (2017)

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