tbuckley/cabot-search huggingface dataset:
Maternal and Neonatal Morbidity for Women Who Would Be Added to the Diagnosis of GDM Using IADPSG Criteria: A Secondary Analysis of the Hyperglycemia and Adverse Pregnancy Outcome Study
Authors: Thaddeus P. Waters, Alan R. Dyer, Denise M. Scholtens, Sharon L. Dooley, Elaine Herer, Lynn P. Lowe, Jeremy J.N. Oats, Bengt Persson, David A. Sacks, Boyd E. Metzger, Patrick M. Catalano
Journal: Diabetes Care (2016)

OBJECTIVE To assess the frequency of adverse outcomes for women who are diagnosed with gestational diabetes mellitus (GDM) by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. RESEARCH DESIGN AND METHODS This is a secondary analysis from the North American HAPO study centers. Glucose measurements from a 75-g oral glucose tolerance test were used to group participants into three nonoverlapping categories: GDM based on Carpenter-Coustan (CC) criteria (also GDM based on IADPSG criteria), GDM diagnosed based on IADPSG criteria but not CC criteria, and no GDM. Newborn outcomes included birth weight, cord C-peptide, and newborn percentage fat above the 90th percentile; maternal outcomes included primary cesarean delivery and preeclampsia. Outcome frequencies were compared using multiple logistic regression, adjusting for predefined covariates. RESULTS Among 25,505 HAPO study participants, 6,159 blinded participants from North American centers were included. Of these, 81% had normal glucose testing, 4.2% had GDM based on CC criteria, and 14.3% had GDM based on IADPSG criteria but not CC criteria. Compared with women with no GDM, those diagnosed with GDM based on IADPSG criteria had adjusted odds ratios (95% CIs) for birth weight, cord C-peptide, and newborn percentage fat above the 90th percentile, as well as primary cesarean delivery and preeclampsia, of 1.87 (1.50–2.34), 2.00 (1.54–2.58), 1.73 (1.35–2.23), 1.31 (1.07–1.60), and 1.73 (1.32–2.27), respectively. CONCLUSIONS Women diagnosed with GDM based on IADPSG criteria had higher adverse outcome frequencies compared with women with no GDM. These data underscore the need for research to assess the effect of treatment to improve outcomes in such women.
Quantitative and Qualitative Analysis Of Regulatory T Cells (Tregs) Derived From The Peripheral Blood Of Chronic Lymphocytic Leukemia Patients
Authors: Eleni Dikaia Ioannidou, Vassiliki Mpakou, Myrofora Vikentiou, Eugenia Konsta, Frieda Kontsioti, Christos K Kontos, Sotiris Papageorgiou, Maria Atta, Nikos Papanikolaou, Anthi Bouhla, Christoforos Roubakis, George Dimitriadis, Vassiliki Pappa
Journal: Blood (2013)
Bone Marrow Biopsy May Be Required During the Initial Evaluation of Individuals with Asymptomatic Monoclonal Gammopathy
Authors: Meletios Athanasios Dimopoulos, Evangelos Terpos, Maria Gkotzamanidou, Evangelos Eleutherakis-Papaiakovou, Magdalini Migkou, Maria Gavriatopoulou, Dimitrios Christoulas, Maria Roussou, Efstathios Kastritis
Journal: Blood (2011)
Abstract 857: Diagnostic test system for sensitive, specific and reproducible detection of EML4-ALK RNA fusion transcripts in the blood of patients with NSCLC
Authors: Hestia Mellert, Leisa Jackson, Dianna Maar, Dawne Shelton, Gary Pestano
Journal: Cancer Research (2016)

Abstract Clinical testing for the detection of RNA fusions in tissue currently include FISH, IHC, PCR and NGS. However, approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) are not candidates for tissue biopsies and in some cases where tissue is obtained, it is not always of sufficient quantity for molecular testing. For these reasons, the detection of nucleic acids in circulation has become increasingly relevant to clinical testing. In this study, we have focused on the development of an EML4-ALK diagnostic test system that includes the prospective collection of whole blood and the reproducible detection of mRNA fusion transcripts by a PCR-based technology. The focus was on the detection of EML4-ALK transcripts from donors with and without previously diagnosed NSCLC. Pre-analytic complexity was reduced by restricting the handling of samples to 72 hours from time of sample receipt to test result. Recovery methods for RNA extraction from donor plasma were then optimized to enrich for RNA recovered from both circulating-free, and RNA within blood vesicles, including platelets and exosomes. A two-step reverse transcription and Droplet Digital™ PCR (RT-ddPCR) method was evaluated in detection testing using a multiplexed EML4-ALK assay that includes variants 1, 2 and 3. Analytic assay specificity and sensitivity was examined for RT-ddPCR efficiency using a cell-line positive for EML4-ALK variant 1 and in vitro RNA designed to mimic variants 1, 2, and 3. Analytic sensitivity was determined to be 0.2% of fusion RNA spiked into a background of normal plasma. Precision studies were conducted with two different amounts of input RNA (high and low), over three consecutive days, three runs in one day and with two operators. The SD of detected fusion transcripts in this study did not exceed 25%. Finally, normal (n = 10) and FISH positive NSCLC donor (n = 9) plasma samples were processed for the recovery of RNA and tested for EML4-ALK fusions. All FISH positive cases were accurately detected by the RT-ddPCR test with EML4-ALK variant copies ranging from 13 to 150 copies. EML4-ALK fusion transcripts were not identified in normal donor plasma. We conclude that the developed test system is highly suited for a 72 hour test to result turnaround, reproducible and sensitive detection of diagnostic fusion RNA variants, including EML4-ALK in blood in the clinical laboratory. Citation Format: Hestia Mellert, Leisa Jackson, Dianna Maar, Dawne Shelton, Gary Pestano. Diagnostic test system for sensitive, specific and reproducible detection of EML4-ALK RNA fusion transcripts in the blood of patients with NSCLC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 857.
Mylotarg 9 mg/m² Combined with Intermediate Dose Aracytin and Mitoxantrone (MIDAM) in Relapsed/Refractory CD33+ Acute Myeloid Leukemia: A Single Center Phase II Experience.
Authors: Patrice Chevallier, Virginie Rolland, Richard Garand, Herve Avet-Loiseau, Beatrice Mahe, Philippe Moreau, Noel Milpied, Jean-Luc Harousseau
Journal: Blood (2004)
Abstract 845A: Novel twin method estimates genetic prevalence of breast cancer
Authors: Stuart G. Baker
Journal: Cancer Research (2016)

Abstract The standard twin method of the last one hundred years uses data from fraternal and identical twins to estimate heritability, which is the fraction of the variance attributed to genetic effects under an additive genetic model. Using the same data, the latent class twin method estimates a more easily interpretable quantity, the genetic prevalence, which is the fraction persons with an outcome who are in a genetic susceptibility latent class. A key assumption is that the genetic susceptibility latent class has relatively large independent probabilities of outcome as compared with an environmental susceptibility latent class with smaller and possibly dependent probabilities of outcome. Unlike the standard twin method which assumes additive genetic inheritance, the latent class twin method also allows for autosomal recessive, autosomal dominant inheritance. The method handles survival data by treating loss-to-follow up and death from competing risk as non-informative censoring. Applying this methodology to registry data from 45,000 pairs of Nordic twins, we estimated a genetic prevalence for breast cancer of only 1%. Because BRCA1 and BRAC2 have a combined prevalence of around 1%, there are likely no other high-penetrance genes contributing to breast cancer Citation Format: Stuart G. Baker. Novel twin method estimates genetic prevalence of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 845A.
Obamacare’s Skyrocketing Premiums? Why the Sky Isn’t Falling
Authors: Benjamin D. Sommers
Journal: New England Journal of Medicine (2016)

Dr. Benjamin Sommers on the future cost of insurance coverage under the Affordable Care Act. (07:21)Download Predictions of major increases in premiums for health insurance plans offered on the exchanges are overblown. Given the rate review, competition, and tax credits built into the ACA, consumers are not likely to be paying vastly more for their coverage in 2017.
Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate
Authors: Elise S. Eerenberg, Pieter W. Kamphuisen, Meertien K. Sijpkens, Joost C. Meijers, Harry R. Buller, Marcel Levi
Journal: Circulation (2011)

Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs.In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus 12.3±0.7 seconds at baseline; P<0.001) that was immediately and completely reversed by PCC (12.8±1.0; P<0.001). The endogenous thrombin potential was inhibited by rivaroxaban (51±22%; baseline, 92±22%; P=0.002) and normalized with PCC (114±26%; P<0.001), whereas saline had no effect. Dabigatran increased the activated partial thromboplastin time, ecarin clotting time (ECT), and thrombin time. Administration of PCC did not restore these coagulation tests.Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study. Clinical Trial Registration- URL: http://www.trialregister.nl. Unique identifier: NTR2272.
Abstract 1087: Circulating microRNAs as metastasis biomarkers in oral cavity and oropharyngeal squamous cell carcinomas
Authors: Flavia Maziero Andreghetto, Mariana Barbosa de Souza, Raquel Ajub Moyses, Tatiana Natasha Toporcov, Fabio Daumas Nunes, Marcos Brasilino de Carvalho, Patricia Severino
Journal: Cancer Research (2016)

Abstract MicroRNAs are small non-coding RNA molecules with roles in gene expression regulation and implications in cancer initiation and progression. Cell-free microRNAs detected in body fluids, and in particular in plasma, are of clinical interest due to their possible use as biomarkers. Despite the fact that their reliable quantification depends on several technical parameters, there is great clinical interest in this approach due to its simplicity and low risk to the patient. Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide, with survival rates of about 50% in 5 years. Tobacco and alcohol consumption are the most important risk factors and, currently, the presence of cervical lymph node metastases remain the strongest prognostic factor for this cancer type. In this study we identified plasma microRNAs associated with squamous cell carcinomas of the oral cavity and oropharynx as well as with the presence of cervical lymph node metastases. We evaluated the expression of 179 microRNAs in plasma from 45 patients (28 presenting cervical lymph node metastases at diagnosis and 17 with no lymph node metastasis) and 15 healthy controls. Samples were matched according to age, sex, drinking and smoking habits. Among microRNAs mostly expressed in tumor samples, some had been already detected in oral squamous cell carcinoma tissues, such as miR-210, while others, such as miR-573, are still poorly studied. Comparisons between oral and oropharyngeal carcinomas yielded several differences, in accordance with molecular distinctions between these cancer types. MicroRNAs possibly involved in the metastatic process were identified when comparing plasma samples from individuals presenting lymph node metastasis at diagnosis and plasma from patients who were metastasis-free. Among these molecules, miR-192 and miR-574 were identified as more expressed in plasma from individuals with metastatic oropharyngeal cancer. We conclude that plasma microRNAs associated with specific clinical conditions or cancer sub-sites may help in the diagnosis and prognosis assessment of head and neck squamous cell carcinomas. Citation Format: Flavia Maziero Andreghetto, Mariana Barbosa de Souza, Raquel Ajub Moyses, Tatiana Natasha Toporcov, Fabio Daumas Nunes, Marcos Brasilino de Carvalho, Patricia Severino. Circulating microRNAs as metastasis biomarkers in oral cavity and oropharyngeal squamous cell carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1087.
A phase I/II study of TKM-080301, a <i>PLK1</i>-targeted RNAi in patients with adrenocortical cancer (ACC).
Authors: Michael J Demeure, Tannaz Armaghany, Samuel Ejadi, Ramesh K. Ramanathan, Aymen Elfiky, Jonathan R. Strosberg, David C. Smith, Timothy Whitsett, Winnie S. Liang, Shobana Sekar, John D. Carpten, Paul Fredlund, Demi Niforos, Andrew Dye, Sarabjit Gahir, Sean C. Semple, Mark Marion Kowalski
Journal: Journal of Clinical Oncology (2016)

2547 Background: Polo-like kinase 1 (PLK1) regulates critical aspects of tumor progression. High expression levels correlate with poor survival in ACC. TKM-080301 is a lipid nanoparticle formulation of a siRNA against PLK1. Methods: TKM-080301 was evaluated in an open-label study with dose escalation and expansion phases in patients with refractory ACC. TKM-080301 was infused IV over 30 minutes on days 1, 8, and 15 of a 28-day cycle. Primary study objectives included assessment of safety and anti-tumor activity by RECIST 1.1 after every 2 cycles. Results: Sixteen patients were treated at 0.6 or 0.75 mg/kg/week for up to 18 cycles. Eight received at least 2 cycles of study treatment and were evaluable for tumor response. Four had a best response of stable disease including one with a 13% reduction of target tumor diameter. One 51 yo man with metastatic intraperitoneal non-functional ACC had a partial response (target tumor reduction of 19% after cycle 2 and 49% after cycle 14). Residual tumor was resected and histopathology showed near-complete necrosis. Paired tumor/normal whole exome sequencing of this tumor revealed key somatic alterations including a missense mutation (Q331H) in TP53’s DNA binding domain, an NF1 nonsense mutation (S365*), and a missense ARID1A mutation (A438V). RNA sequencing showed elevated expression of PLK1 (FPKM = 13.5) in this tumor compared to a normal adrenal RNA control (FPKM = 0.95). Two subjects completed at least 6 cycles. Subjects were discontinued for progressive disease (7); infusion reactions (2); acute respiratory failure (1); elevated LFTs (1); or bowel obstruction (1). Most common AEs related to TKM-080301 were pyrexia (56%); chills (50%); back pain (31%); infusion reaction (31%); and nausea (25%). Serious AEs related to TKM-080301 were ECG T-wave inversion and musculoskeletal pain (1) and infusion reaction (1). Conclusions: TKM-080301 has been tolerated at a dose of 0.6 - 0.75 mg/kg for up to 18 cycles. Preliminary anti-tumor efficacy has been observed. A potential molecular therapeutic context of increased PLK1 expression with inactivation of p53 or NF1 was observed in a remarkable responder. Further evaluation of PLK1 as a therapeutic target of TKM-080301 in ACC is warranted. Clinical trial information: NCT01262235.
Abstract 1677: CLCA2 interaction with EVA1 promotes mammary epithelial differentiation
Authors: Grace N.T. Ramena, Yufang Yin, Yang Yu, Vijay Walia, Randolph C. Elble
Journal: Cancer Research (2016)

Abstract CLCA2 is a p53-, p63-inducible transmembrane protein that is frequently downregulated in breast cancer. It is induced during differentiation of human mammary epithelial cells, and its knockdown causes epithelial-to-mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with the cell junctional protein EVA1 (Epithelial V-like Antigen 1) and confirmed it by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 and p63. It is thought to mediate homophilic cell-cell adhesion in diverse epithelial tissues. We found that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype. Moreover, knockdown of EVA1 in immortalized HMEC caused EMT, implying that EVA1 is essential for epithelial differentiation. Both EVA1 and CLCA2 co-localized with E-cadherin at cell-cell junctions. The interacting domains were delimited by deletion analysis, revealing the site of interaction to be the transmembrane segment (TMS). The TMS primary sequence of CLCA2 was found to be conserved throughout mammals. Moreover, competitive inhibition of the interaction by ectopic expression of the TMS caused partial EMT, suggesting that the interaction is important for differentiation. A screen for other junctional interactors revealed that CLCA2 was involved in two different complexes, one with EVA1 and ZO-1, the other with beta catenin. Overexpression of CLCA2 caused downregulation of beta catenin and beta catenin-activated genes. Thus, CLCA2 links a junctional adhesion molecule to cytosolic signaling proteins that modulate proliferation and differentiation. These results may explain how attenuation of CLCA2 causes EMT and why CLCA2 and EVA1 are frequently downregulated in metastatic breast cancer cell lines. Citation Format: Grace N.T. Ramena, Yufang Yin, Yang Yu, Vijay Walia, Randolph C. Elble. CLCA2 interaction with EVA1 promotes mammary epithelial differentiation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1677.
Workforce gaps are result of reorganisations and “quick fixes,” Health Foundation says
Authors: Matthew Limb
Journal: BMJ (2016)

The NHS workforce in England has swung from boom to bust because of repeated reorganisations and a reliance on “quick fixes” to solve deep systemic problems, independent healthcare charity the Health Foundation has said.

A study by the charity has concluded that “mismatches” between funding and staffing levels and top down system reforms have undermined any long term consistency in workforce planning. At the same time lower cost “quick fixes” have placed a “sticking plaster” on deep seated systemic difficulties, the study found. The Health Foundation has called for a more coherent, sustainable approach to tackling funding constraints and staff shortages. It said that these constraints and shortages posed the “greatest threats” to the delivery of the NHS Five Year …
Implementing HPV vaccine to reach young girls in Thailand.
Authors: Khunying Kobchitt Limpaphayom, Wachara Eamratsameekool, Enriquito Lu
Journal: Journal of Clinical Oncology (2014)

e16504 Background: Cytology and HPV test are complex and expensive even for Thailand.Since 2000, the cervical cancer screening program includes the use SVA through VIA and cryotherapy. SVA has been scaled up in 33 of 77 provinces utilizing trained and qualified nurse providers at primary health care level.The linkage opens up an opportunity of introducing human papilloma virus(HPV)vaccine for young girls between 9-13 years old. The mother-daughter initiative(MDI),an 18 months, 2 country project involving Thailand and the Philippines , was an operational study to explore the feasibility and acceptability of a strategy of linking primary and secondary prevention. This report will focus on the program components of MDI as implemented in Thailand. Methods: The HPV vaccination of young girls 9-13 years was implemented whilst providing SVA services to women, either their mothers or guardians, at primary care units where healthcare personnel work closely with village health volunteers.Since HPV vaccine is new to the community and the providers, advocacy,providers and supervisors training, community education and mobilization, and maintaining cold-chain are critical program components to set up. Monitoring and evaluation are also important to manage the program. Results: The project trained 18 nurses providers and prepared 4 supervisors in 10 facilities in two district of Nakornsri-Thammaraj province. Additionally 100 commmunity health workers were updated to include in their messaging HPV vaccination.A total of 3,997 from 4005(99.8%) girls completed all three doses of HPV vaccines. The knowledge of cervical cancer , HPV, and HPV vaccine were high among the mothers, fathers. and guardians.No severe adverse events were reported. Conclusions: MDI is potentially a feasible strategy to introduce HPV vaccines and ensure compliance to the 3 doses. Issues such as community perception and family concerns regarding the HPV vaccine can be addressed by the providers. Program using this approach need to consider investing in advocacy, community education, training of providers and setting up a supply mechanism that complies with the cold chain needs of the HPV vaccine.
Surveillance du paludisme en Italie : analyse des données de 1986 à 1996 et données provisoires de 1997
Authors: G Sabatinelli, G Majori
Journal: Eurosurveillance (1998)

Pendant des siecles le paludisme etait endemique dans les regions italiennes tres marecageuses. Des travaux hydrauliques ont reduit de facon importante la transmission du paludisme ; mais la maladie etait encore assez courante au debut de la deuxieme guerre mondiale dans certaines zones marecageuses situees a moins de 800 metres au dessus du niveau de la mer et les perturbations dues a la guerre ont entraine une forte augmentation de la transmission du paludisme.