https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0040297&type=printable

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration

As methods for determining protein three-dimensional (3D) structure develop, a continuing problem is how to verify that the final protein model is correct. The revision of several protein models to correct errors has prompted the development of new criteria for judging the validity of X-ray and NMR structures, as well as the formation of energetic and empirical methods to evaluate the correctness of protein models. The challenge is to distinguish between a mistraced or wrongly folded model, and one that is basically correct, but not adequately refined. We show that an effective test of the accuracy of a 3D protein model is a comparison of the model to its own amino-acid sequence, using a 3D profile, computed from the atomic coordinates of the structure 3D profiles of correct protein structures match their own sequences with high scores. In contrast, 3D profiles for protein models known to be wrong score poorly. An incorrectly modelled segment in an otherwise correct structure can be identified by examining the profile score in a moving-window scan. The accuracy of a protein model can be assessed by its 3D profile, regardless of whether the model has been derived by X-ray, NMR or computational procedures.

Assessment of protein models with three-dimensional profiles.

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies, and cross-sectional studies, and 4 are specific to each of the 3 study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors, and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, 1 or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (www.strobe-statement.org) should be helpful resources to improve reporting of observational research.

/pdf/strengthening-the-reporting-of-observational-studies-in-2coc5huwto.pdf

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration

Publisher Summary This chapter discusses the role of plasminogen activators in various biological processes. In specific, it describes two types of plasminogen activators—namely, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA), which are essentially different gene products. The amino acid sequences of these activators and nucleotide sequences of the corresponding cDNAs have largely been determined, and the cDNAs have been cloned using recombinant techniques. A variety of enzymatic as well as immunological assay and detection methods have also been developed that allows a precise quantification of the activators, a distinction between u-PA and t-PA, determination of whether an activator is present in its active or zymogen form, analysis of the kinetics of different steps of the cascade reaction, and immunocytochemical identification of u-PA and t-PA in tissue sections. Much of the studies on plasminogen activators and cancer has been guided by the hypothesis that proteolysis of the components of extracellular matrix, initiated by the release of plasminogen activator from the cancer cells, plays a decisive role for the degradation of normal tissue, and thereby for invasive growth and metastases.

Plasminogen activators, tissue degradation, and cancer.

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers.This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated web site (http://www.strobe-statement.org) should be helpful resources to improve reporting of observational research.

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.

Background Factor XI, a component of the intrinsic pathway of coagulation, contributes to the generation of thrombin, which is involved in both the formation of fibrin and protection against fibrinolysis. A deficiency of factor XI is associated with bleeding, but a role of high factor XI levels in thrombosis has not been investigated. Methods We determined factor XI antigen levels in the patients enrolled in the Leiden Thrombophilia Study, a large population-based, case–control study (with a total of 474 patients and 474 controls) designed to estimate the contributions of genetic and acquired factors to the risk of deep venous thrombosis. Odds ratios were calculated as a measure of relative risk. Results The age- and sex-adjusted odds ratio for deep venous thrombosis in subjects who had factor XI levels above the 90th percentile, as compared with those who had factor XI levels at or below that value, was 2.2 (95 percent confidence interval, 1.5 to 3.2). There was a dose–response relation between the facto...

https://www.nejm.org/doi/pdf/10.1056/NEJM200003093421004

High levels of coagulation factor XI as a risk factor for venous thrombosis.

In the early 1960s, shortly after the introduction of oral contraceptives, the first case reports appeared describing venous thrombosis and pulmonary emboli in women using this method of birth control. Later, myocardial infarction and stroke were also found to be associated with the use of oral contraceptives. These observations led to numerous epidemiologic and clinical studies of oral-contraceptive pills and thrombosis and subsequently to the development of new oral contraceptives with a lower estrogen content. These lower-estrogen contraceptives were considered safer: changes in hemostatic factors remained small, inconsistent in direction, and mostly within the normal range.1–4 Recent studies have . . .

/pdf/oral-contraceptives-and-the-risk-of-venous-thrombosis-3hdsqrbpxj.pdf

Oral contraceptives and the risk of venous thrombosis

Human blood coagulation factor XI. Purification, properties, and mechanism of activation by activated factor XII.

Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis

https://www.gastrojournal.org/article/S0016-5085(01)80205-5/pdf

Bonno N. Bouma

Papers

High levels of coagulation factor XI as a risk factor for venous thrombosis.

Oral contraceptives and the risk of venous thrombosis

Human blood coagulation factor XI. Purification, properties, and mechanism of activation by activated factor XII.

Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis

Thrombin-Activatable Fibrinolysis Inhibitor Deficiency in Cirrhosis Is Not Associated With Increased Plasma Fibrinolysis