tbuckley/cabot-search huggingface dataset:
Glucose Self-monitoring in Non–Insulin-Treated Patients With Type 2 Diabetes in Primary Care Settings
Authors: Laura A. Young, John B. Buse, Mark A. Weaver, Maihan B. Vu, C. Madeline Mitchell, Tamara Blakeney, Kimberlea Grimm, Jennifer Rees, Franklin Niblock, Katrina E. Donahue
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> The value of self-monitoring of blood glucose (SMBG) levels in patients with non–insulin-treated type 2 diabetes has been debated. <h3>Objective</h3> To compare 3 approaches of SMBG for effects on hemoglobin A<sub>1c</sub>levels and health-related quality of life (HRQOL) among people with non–insulin-treated type 2 diabetes in primary care practice. <h3>Design, Setting, and Participants</h3> The Monitor Trial study was a pragmatic, open-label randomized trial conducted in 15 primary care practices in central North Carolina. Participants were randomized between January 2014 and July 2015. Eligible patients with type 2 non–insulin-treated diabetes were: older than 30 years, established with a primary care physician at a participating practice, had glycemic control (hemoglobin A<sub>1c</sub>) levels higher than 6.5% but lower than 9.5% within the 6 months preceding screening, as obtained from the electronic medical record, and willing to comply with the results of random assignment into a study group. Of the 1032 assessed for eligibility, 450 were randomized. <h3>Interventions</h3> No SMBG, once-daily SMBG, and once-daily SMBG with enhanced patient feedback including automatic tailored messages delivered via the meter. <h3>Main Outcomes and Measures</h3> Coprimary outcomes included hemoglobin A<sub>1c</sub>levels and HRQOL at 52 weeks. <h3>Results</h3> A total of 450 patients were randomized and 418 (92.9%) completed the final visit. There were no significant differences in hemoglobin A<sub>1c</sub>levels across all 3 groups (<i>P</i> = .74; estimated adjusted mean hemoglobin A<sub>1c</sub>difference, SMBG with messaging vs no SMBG, −0.09%; 95% CI, −0.31% to 0.14%; SMBG vs no SMBG, −0.05%; 95% CI, −0.27% to 0.17%). There were also no significant differences found in HRQOL. There were no notable differences in key adverse events including hypoglycemia frequency, health care utilization, or insulin initiation. <h3>Conclusions and Relevance</h3> In patients with non–insulin-treated type 2 diabetes, we observed no clinically or statistically significant differences at 1 year in glycemic control or HRQOL between patients who performed SMBG compared with those who did not perform SMBG. The addition of this type of tailored feedback provided through messaging via a meter did not provide any advantage in glycemic control. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02033499
Abstract 12709: Addition of Depression Severity Indices to the Intermountain Risk Score for Predicting 3-Year Risk of Chronic Disease: The Mental Health Integration Risk Score
Authors: Heidi T May, Brenda Reiss-Brennan, Kimberly D Brunisholz, Benjamin D Horne
Journal: Circulation (2016)

Introduction: Depression (DPN) is a common illness that imposes a disproportionately large health burden. DPN is generally associated with higher prevalence of chronic disease (ChrD) risk factors and may contribute higher ChrD risk. Previously, the Intermountain Mortality Risk Score (IMRS) was shown to predict DPN incidence and post-diagnosis outcomes. Hypothesis: Sex-specific Mental Health Integration risk scores (MHIRS) can be developed based on the principles underlying IMRS and adding DPN severity indices to predict 3 year ChrD diagnosis. Methods: MHIRS was created to predict the first diagnosis of any of 10 ChrD (diabetes, renal failure, CAD, MI, HF, PVD, AF, stroke, dementia, or COPD) in patients completing a PHQ-9 DPN survey and were free at baseline from those 10 ChrD diagnoses. MHIRS used sex-specific weightings of PHQ-9 results, age, and components of the comprehensive metabolic panel and complete blood count in randomly-chosen derivation (70%) and validation (30%) groups. Results: Females (N=10,162; age: 48±16) and males (N=4615, age: 48±15) were studied. Among females, c-statistics for the composite ChrD endpoint were 0.746 (0.725, 0.767) for the derivation group and 0.717 (0.682, 0.753) for the validation group, while males had 0.755 (0.727, 0.783) and 0.742 (0.702, 0.782). See Table for MHIRS prediction of each ChrD. In the validation group, MHIRS strata of low, moderate, and high risk had hazard ratios (HR) for any 3-year ChrD diagnosis among females of HR=3.42 for moderate vs. low and HR=9.75 for high vs low, while males had HR=4.80 and HR=10.68, respectively (all p&lt;0.0001). Conclusion: A clinical decision tool composed of DPN severity and common lab tests, MHIRS provided very good discrimination of a 3 year ChrD diagnosis. Designed to be calculated electronically by an electronic health record, MHIRS can be efficiently obtained by clinicians to identify patients at higher ChrD risk who require further evaluation and more precise clinical management.
The Fogarty International Center, a National Treasure for Global Health
Authors: Lawrence O. Gostin
Journal: JAMA (2017)

Since our initial tetrahedral design, we have by now progressed to several other protein origami shapes with different chemical properties," said Jerala."We plan to use these as cages to encapsulate different types of molecular cargo and guide the delivery of those cages to different cell types."Opening and closingofcagesmightberegulatedbymechanisms that respond to different chemical conditions, such as pH, salt concentration, or the presence of certain enzymes.Jerala's team also sees these cages, which resemble viral capsids, as potentially useful for vaccine design or for replacing aberrant enzymes or other dysfunctional cellular components that cause disease.
Abstract 67: A Rare Variant in <i>Myh11,</i> R247C, Affects Smooth Muscle Cell Phenotype and Acts as a Modifier for Aortic Disease
Authors: Callie Kwartler, Shao-Qing Kuang, Siddharth Prakash, Katerina Byanova, John Pham, Jian Huang, Kristine Kamm, James Stull, H Lee Sweeney, Dianna Milewicz
Journal: Circulation Research (2012)

Thoracic aortic aneurysms and dissections (TAAD) affect more than 30,000 Americans annually. One-fifth of TAAD patients have a first-degree relative with the disease, suggesting a genetic component to its pathogenesis. Missense mutations in a number of genes lead to TAAD, including MYH11 ,which encodes the smooth muscle isoform of myosin heavy chain. However, potential genetic contributors in the four-fifths of patients without affected relatives have not been explored. Variants of unknown significance in MYH11 are prevalent in the population, and are enriched in patients with TAAD and other vascular diseases. The goal of this study was to evaluate one of these variants as a potential contributor to TAAD. A knock-in mouse model of the Myh11 R247C rare variant was generated, and these mice survive and reproduce normally. They have no structural abnormalities of the aorta or signs of aortic disease, but do have decreased aortic contractility. Myh11 R247C/R247C mice also have increased neointimal proliferation following carotid ligation and increased proliferation of vascular smooth muscle cells (SMCs) in vitro. Myh11 R247C/R247C SMCs have decreased contractile gene and protein expression and are dedifferentiated. In fibroblasts, myosin force generation is required for maturation of focal adhesions, and enhancers of RhoA activity replace enhancers of Rac1 activity as maturation occurs. Consistent with these previous findings, adhesions are smaller in Myh11 R247C/R247C SMCs, and there is increased Rac1 and focal adhesion kinase (FAK) activation with decreased RhoA activation. A RhoA activator (CN03) rescues the dedifferentiated phenotype of Myh11 R247C/R247C SMCs, and FAK inhibition reduces proliferation. Since this rare variant occurs in the general population, we sought to determine if it acts as a modifier gene for aortic disease. The Myh11 R247C allele was bred into Acta2 -/- mice, which develop aortic aneurysms, and into Acta2 +/- mice, which do not. In both cases, the presence of the R247C allele increases aortic diameter. These preliminary data suggest that the MYH11 R247C rare variant may be a genetic contributor to TAAD in patients without an inherited mutation, or may affect the clinical presentation of TAAD in patients with Mendelian disease.
Detection of sentinel lymph node in patients with breast cancer: Application of 3D contrast enhanced ultrasound (3D-CEUS).
Authors: Man Lu, Ziyue Hu, Juan Li
Journal: Journal of Clinical Oncology (2017)

e12095 Background: Sentinel lymph node biopsy (SLNB) has became widely accepted as the gold standard procedure for axilla nodal staging .The main methods for the detection of Sentinel lymph nodes (SLNs) are dye-guided and g-probe-guided method.Currently, studies suggest that 2D - Contrast Enhanced Ultrasound(2D-CEUS) may be as good as the accepted techniques for SLNs detection .But the 2D-CEUS can not image the spatial relationship of the lymph vessel and SLNs.The objective of this study was to explore whether three-dimensional contrast enhanced ultrasonography (3D-CEUS) poses higher diagnostic value of in SLNs and lymphatic drainage routes of breast cancer than conventional ultrasonography (US) or 2D-CEUS.To our knowledge, this is the first study to investigate the value of 3D-CEUS in the preoperative diagnosis of SLN metastases in patients with early breast cancer. Methods: By using postoperative pathological results as gold standard, the accuracy and sensitivity of conventional US, 2D-CEUS and 3D-CEUS for SLNs were retrospectively tested in 73 patients with early breast cancer confirmed by pathology between December 2015 and June 2016, all patients underwent US, 2D-CEUS and 3D-CEUS before operation. Injection of the Blue dye was performed half an hour before the operation. Results: According to the postoperative pathology, 25 of 73 patients were with lymphatic metastasis. The lymph nodes detection rate of 2D-US,2D-CEUS and 3D-CEUS was 35.2%, 73.4%, 79.4% ,respectively.The correct rate of 2D-US,2D-CEUS and 3D-CEUS was 74%,90.4%,91.8%, respectively(p&lt;0.05).The lymph drainage route of SLNs are divided into 7 types by 3D-CEUS and the enhancement modes of the lymphatic vessels and the lymph nodes are divided into six categories by 2D-CEUS. Conclusions: The 2D-CEUS and 3D-CEUS can clearly display the SLNs and the lymph drainage routes. 3D-CEUS possesses advantages over 2D-CEUS in displaying lesions with spatial relationship which is informative to preoperative assessment of the stage, the operative type and surgical prognosis in patients with breast cancer, and can contribute greatly to the easy detection of SLNs during SLNB. Clinical trial information: Approval NO,SCPPHEC-D-2015-75.
Adjustment Strategies in Studies of Therapy—Reply
Authors: Thomas Agoritsas, Arnaud Merglen, Gordon H. Guyatt
Journal: JAMA (2017)

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The impact of a novel lung gross dissection protocol on intrapulmonary lymph node (LN) retrieval from lung cancer (LC) resection specimens.
Authors: Raymond U. Osarogiagbon, Srishti Sareen, Ransome Eke, Cynthia D Leary, Nicholas Faris, Xinhua Yu, David Spencer
Journal: Journal of Clinical Oncology (2014)

7571 Background: Although thorough pathologic LN staging provides the greatest prognostic information in patients with potentially curable non-small cell LC, N1 nodal metastases are frequently missed. We tested the impact of corrective intervention with a novel gross dissection protocol on intrapulmonary LN retrieval. Methods: Retrospective review of consecutive lobectomy, or greater, LC specimens over a period of 15 months before and 15 months after training pathology technicians on the novel dissection protocol. Results: N= 152 specimens before, and 110 after introduction of the novel dissection protocol. The median number of intrapulmonary LN retrieved increased from 2 to 5 (p<.0001), and the 75th – 100th percentile range of detected intrapulmonary LN metastasis increased from 0 – 5 to 0 – 17 (p=.0003). In multivariate analysis (table), the extent of resection, examination period (pre- / post-intervention), and pathologic N1 (vs. N0) status were most strongly associated with increased intrapulmonary LN retrieval. Conclusions: A novel pathology dissection protocol is a feasible and effective means of improving intrapulmonary LN retrieval for examination. Dissemination and implementation studies of this novel pathology dissection protocol are warranted. Variables LN examined All N1 LN Intrapulmonary LN RR (95% C.I) p-value RR (95% C.I) p-value Intervention period 1.00 - 1.00 - Before 2.27 (2.09 – 2.46) < 0.0001 2.52 (2.32 – 2.75) < 0.0001 After Age Category 1.00 - 1.00 - < 65 1.00 (0.89 – 1.11) 0.922 0.91 (0.84 – 0.99) 0.030 65-74 1.06 (0.87 – 1.29) 0.558 0.93 (0.80 – 1.09) 0.373 >74 Race 1.00 - 1.00 - White 0.84 (0.60 – 1.17) 0.307 0.72 (0.50 – 1.03) 0.072 Black Sex 1.00 - 1.00 - Female 1.22 (1.09 – 1.36) 0.001 1.34 (1.14 – 1.59) 0.001 Male Histology 1.00 - 1.00 - Non-adeno 0.92 (0.81 – 1.04) 0.177 0.87 (0.79 – 0.95) 0.002 Adeno N-category 1.00 - 1.00 - N0 1.80 (1.40 – 2.32) < 0.0001 2.15 (1.57 – 2.93) < 0.0001 N1 1.10 (0.88 – 1.38) 0.419 0.97 (0.72 – 1.30) < 0.0001 N2 T-category 1.00 - 1.00 - 1 (Ref) 0.90 (0.80 – 1.01) 0.084 0.92 (0.074 – 1.14) 0.418 2 1.34 (1.12 – 1.58) 0.001 1.25 (1.01 – 1.55) 0.041 3 Extent of resection 1.00 - 1.00 - Greater than lobectomy 0.74 (0.66 – 0.83) < 0.0001 0.58 (0.51 – 0.65) < 0.0001 Lobectomy
Explanation model using pathological data for treatment outcome of patients with early-stage breast cancer with hormonal receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative.
Authors: Naiyarat Prasongsook
Journal: Journal of Clinical Oncology (2017)

e12006 Background: The decision to initiate adjuvant chemotherapy for early-stage breast cancer patients with HR+ and HER2- is still unclear. Although the 21-gene Recurrence Score (RS) assay is a validated testing and becomes an emerging decision-making tool; it is still controversial guidance on adding adjuvant chemotherapy for patients with intermediate RS. This study aimed to develop the explanation model by using pathological information for prediction of the best outcome from adjuvant systemic treatment in these patients.Methods: Early-stage breast cancer patients with HR+, and HER2- who underwent complete resection registered within electronic medical record from 2003 to 2013 were included. Patient’s characteristics and pathological information were collected and analyzed. Univariate and multivariate analysis were conducted by using stepwise logistic regression. The explanation model was explored by using association between multivariate models and overall survival (OS).Results: 236 patients who underwent complete surgery treatment were included. 121 patients (51%) were treated with sequential adjuvant treatment, and 115 patients (48%) with anti-hormonal therapy alone. Clinicopathological parameters between two groups were demonstrated in Table1. Tumor size (≥2 – 5 cm), Estrogen receptor-negative/ Progesterone receptor-positive (ER-/PgR+), and Ki-67 expression were statistically significant multivariate independent prognostic factors for OS. When we adjusted for tumor size, HR status, and Ki-67 expression, the explanation model predicted 10-year OS was 99.2% for patients with sequential adjuvant treatment, whereas 89.5% for patients with adjuvant anti-hormonal alone (difference: 9.7%); p-value = 0.01.Conclusions: We found substantial discordance in 10-year OS benefit between early-breast cancer patients with HR+, HER2- with sequential adjuvant therapy and adjuvant hormonal therapy alone. Adjuvant chemotherapy should be considered in early-breast cancer patients with 2-3 cm in tumor size, ER-/PgR+, and Ki 67 expression.
FDG PET/CT Image of Seminoma in Androgen Insensitivity Syndrome
Authors: Eun Ji Han, Joo Hyun O, Gun Park, Junguee Lee
Journal: Clinical Nuclear Medicine (2017)

We report the FDG PET/CT findings of seminoma in a 21-year-old woman with androgen insensitivity syndrome. PET images showed focal FDG uptake in the left pelvic sidewall, and a hypodense lesion with calcifications was noted in the corresponding CT images. Another smaller hypodense lesion with calcifications was noted in the right pelvic sidewall, but faint FDG uptake. Laparoscopic surgery was performed, and both lesions were pathologically confirmed as seminomas.
Abstract TMEM-025: IMPACT OF MESOTHELIN EXPRESSION ON THE METASTATIC SUCCESS OF OVARIAN CANCER
Authors: Tyvette Hilliard, Kyle Iwamoto, Elizabeth Loughran, Marwa Asem, Yueying Liu, Jing Yang, Laura Tarwater, Yuliya Klymenko, Jeff Johnson, Zonggao Shi, M. Sharon Stack
Journal: Clinical Cancer Research (2017)

Abstract Ovarian cancer is the most lethal gynecological cancer in U.S. women. Poor 5-year survival rates (&amp;lt;30%) are due to presentation of most women at diagnosis with advanced stage disease with widely disseminated intraperitoneal metastasis. However, when diagnosed before metastatic propagation the overall 5-year survival rate is &amp;gt;90%. Metastasizing tumor cells grow rapidly and aggressively attach to the mesothelium of all organs within the peritoneal cavity, including the parietal peritoneum and the omentum, producing secondary lesions. Mesothelin (MSLN), a 40kDa glycoprotein that is over expressed in many cancers including ovarian and mesotheliomas is suggested to play a role in cell survival, proliferation, tumor progression and adherence. However, the biological function of mesothelin is not fully understood as MSLN knockout mice do not present with an abnormal phenotype. Conversely, MSLN has been shown to bind to the ovarian cancer antigen, CA-125, and thought to play a role in the peritoneal diffusion of ovarian tumor cells. Taking into consideration the potential importance of MSLN/CA-125 binding in ovarian tumor metastasis within the peritoneum, MSLN wild type (WT) and knockout (KO) mice were used to explore the role of mesothelin on the susceptibility of ovarian tumor cells to adhere to the mesothelium of the organs in the peritoneal cavity. An ex vivo peritoneal assay, using CA-125 positive human ovarian tumor cells OVCAR8-GFP and peritoneal explants from MSLN WT and KO mice demonstrated a decrease in OVCAR8-GFP cell adhesion to peritoneal tissues from MSLN KO mice compared to MSLN WT mice. Furthermore, allograft tumor studies using MSLN WT and KO mice injected intraperitoneally with fluorescently-tagged syngeneic murine ovarian cancer cells (ID8-RFP) was performed. Disease progression was evaluated post injection by fluorescent in vivo imaging prior to end point dissection (~8 weeks). Abdominal organs were dissected, imaged ex vivo and organ-specific tumor burden was quantified by tumor area. Tumor burden was significantly decreased in the liver and omentum of MSLN KO mice compared to MSLN WT mice. Together, the results demonstrate a loss of mesothelial cell-ovarian tumor cell adhesion in the omentum and peritoneum of mice that do not express MSLN. Citation Format: Tyvette Hilliard, Kyle Iwamoto, Elizabeth Loughran, Marwa Asem, Yueying Liu, Jing Yang, Laura Tarwater, Yuliya Klymenko, Jeff Johnson, Zonggao Shi, and M. Sharon Stack. IMPACT OF MESOTHELIN EXPRESSION ON THE METASTATIC SUCCESS OF OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-025.
Evolution of poor reporting and inadequate methods over time in 20 920 randomised controlled trials included in Cochrane reviews: research on research study
Authors: Agnes Dechartres, Ludovic Trinquart, Ignacio Atal, David Moher, Kay Dickersin, Isabelle Boutron, Elodie Perrodeau, Douglas G Altman, Philippe Ravaud
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To examine how poor reporting and inadequate methods for key methodological features in randomised controlled trials (RCTs) have changed over the past three decades. <b>Design</b>&nbsp;Mapping of trials included in Cochrane reviews. <b>Data sources</b>&nbsp;Data from RCTs included in all Cochrane reviews published between March 2011 and September 2014 reporting an evaluation of the Cochrane risk of bias items: sequence generation, allocation concealment, blinding, and incomplete outcome data. <b>Data extraction</b>&nbsp;For each RCT, we extracted consensus on risk of bias made by the review authors and identified the primary reference to extract publication year and journal. We matched journal names with <i>Journal Citation Reports</i> to get 2014 impact factors. <b>Main outcomes measures</b>&nbsp;We considered the proportions of trials rated by review authors at unclear and high risk of bias as surrogates for poor reporting and inadequate methods, respectively. <b>Results</b>&nbsp;We analysed 20 920 RCTs (from 2001 reviews) published in 3136 journals. The proportion of trials with unclear risk of bias was 48.7% for sequence generation and 57.5% for allocation concealment; the proportion of those with high risk of bias was 4.0% and 7.2%, respectively. For blinding and incomplete outcome data, 30.6% and 24.7% of trials were at unclear risk and 33.1% and 17.1% were at high risk, respectively. Higher journal impact factor was associated with a lower proportion of trials at unclear or high risk of bias. The proportion of trials at unclear risk of bias decreased over time, especially for sequence generation, which fell from 69.1% in 1986-1990 to 31.2% in 2011-14 and for allocation concealment (70.1% to 44.6%). After excluding trials at unclear risk of bias, use of inadequate methods also decreased over time: from 14.8% to 4.6% for sequence generation and from 32.7% to 11.6% for allocation concealment. <b>Conclusions</b>&nbsp;Poor reporting and inadequate methods have decreased over time, especially for sequence generation and allocation concealment. But more could be done, especially in lower impact factor journals.