Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Characteristics and Anticoagulant Property In Vitro and In Vivo of a Seaweed Sulfated Rhamnan

Great diversity and metabolite complexity of seaweeds offer a unique and exclusive source of renewable drug molecules. Polysaccharide from seaweed has potential as a promising candidate for marine drug development. In the present study, seaweed polysaccharide (SPm) was isolated from Monostroma angicava, the polymeric repeat units and anticoagulant property in vitro and in vivo of SPm were investigated. SPm was a sulfated polysaccharide which was mainly constituted by 3-linked, 2-linked-α-l-rhamnose residues with partially sulfate groups at C-2 of 3-linked α-l-rhamnose residues and C-3 of 2-linked α-l-rhamnose residues. Small amounts of xylose and glucuronic acid exist in the forms of β-d-Xylp(4SO4)-(1→ and β-d-GlcA-(1→. SPm effectively prolonged clotting time as evaluated by the activated partial thromboplastin time and thrombin time assays, and exhibited strong anticoagulant activity in vitro and in vivo. The fibrin(ogen)olytic and thrombolytic properties of SPm were evaluated by plasminogen activator inhibitior-1, fibrin degradation products, D-dimer and clot lytic rate assays using rats plasma, and the results showed that SPm possessed high fibrin(ogen)olytic and thrombolytic properties. These results suggested that SPm has potential as a novel anticoagulant agent.
Analysis and Correction of Inappropriate Image Duplication: the Molecular and Cellular Biology Experience

We analyzed 960 papers published in Molecular and Cellular Biology (MCB) from 2009 to 2016 and found 59 (6.1%) to contain inappropriately duplicated images. The 59 instances of inappropriate image duplication led to 41 corrections, 5 retractions, and 13 instances in which no action was taken. ABSTRACT We analyzed 960 papers published in Molecular and Cellular Biology (MCB) from 2009 to 2016 and found 59 (6.1%) to contain inappropriately duplicated images. The 59 instances of inappropriate image duplication led to 41 corrections, 5 retractions, and 13 instances in which no action was taken. Our experience suggests that the majority of inappropriate image duplications result from errors during figure preparation that can be remedied by correction. Nevertheless, ∼10% of papers with inappropriate image duplications in MCB were retracted (∼0.5% of total). If this proportion is representative, then as many as 35,000 papers in the literature are candidates for retraction due to inappropriate image duplication. The resolution of inappropriate image duplication concerns after publication required an average of 6 h of journal staff time per published paper. MCB instituted a pilot program to screen images of accepted papers prior to publication that identified 12 manuscripts (14.5% out of 83) with image concerns in 2 months. The screening and correction of papers before publication required an average of 30 min of staff time per problematic paper. Image screening can identify papers with problematic images prior to publication, reduces postpublication problems, and requires less staff time than the correction of problems after publication.
WHO hemoglobin thresholds for altitude increase the prevalence of anemia among Ethiopian highlanders

ANCA specificity among cocaine users and a diagnostic marker differentiating cocaine-induced midline destructive lesions from primary ANCA-associated vasculitis, particularly granulomatosis with polyangiitis. However, the association of cocaine-induced AGC with HNEANCA has not been described to date. We observed HNE-ANCA in 3 patients with cyclical AGC after cocaine exposure, with the target of this ANCA subtype being neutrophil elastase. A heterozygous mutation in the ELANE gene that encodes for neutrophil elastase causes CyN, leading to cycling AGC by a mechanism that is still partially unclear. In our study, all patients showed a cycling recurrence of AGC distant in time from the previous cocaine exposure, and all were positive for HNE-ANCA, suggesting a potential pathogenetic link between HNE-ANCA and acquired cyclic neutropenia. Since HNE-ANCA were demonstrated also during clinical remission, it may be hypothesized that cocaine exposure, rather than being directly toxic on myeloid precursors, stimulates the immune system to produce HNE-ANCA in predisposed individuals. This hypothesis is also suggested by the clinical benefit our patients obtained from immune-suppressive therapy. To the best of our knowledge, this study provides the first evidence of an association between cocaine-induced AGC and HNEANCA. The longer follow-up of the exposed patients allowed the demonstration of the self-sustained recurrence of AGC showing a clinical picture suggestive of acquired cyclic neutropenia, in spite of abstention from cocaine exposure. The present study highlights the need for clinical awareness of the potential link between cocaine abuse, the development of HNE-ANCA and a severe disease like cyclic neutropenia.
Mucor circinelloides: Growth, Maintenance, and Genetic Manipulation

Mucor circinelloides is a fungus that belongs to the order Mucorales. It grows as mold in the environment and can cause mucormycosis, a potentially fatal infection in immunocompromised patients. M. circinelloides is a biodiesel producer and serves as a model organism for studying several biological processes, such as light responses and RNA interference–mediated gene silencing. Over the past decade, the increasing number of molecular tools has also allowed us to manipulate the genome of this fungus. This article outlines the fundamental protocols for the in vitro growth, maintenance, and genetic manipulation of M. circinelloides in the laboratory. © 2018 by John Wiley & Sons, Inc.
Dietary Protein and Muscle in Aging People: The Potential Role of the Gut Microbiome

Muscle mass, strength, and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. Dietary protein is essential for skeletal muscle function. Resistance exercise appears to be the most beneficial form of physical activity for preserving skeletal muscle and a synergistic effect has been noted when this is combined with dietary protein. However, older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis, and response is variable. Thus, the recommended daily amount of protein is greater for older people. The aetiologies and mechanisms responsible for anabolic resistance are not fully understood. The gut microbiota is implicated in many of the postulated mechanisms for anabolic resistance, either directly or indirectly. The gut microbiota change with age, and are influenced by dietary protein. Research also implies a role for the gut microbiome in skeletal muscle function. This leads to the hypothesis that the gut microbiome might modulate individual response to protein in the diet. We summarise the existing evidence for the role of the gut microbiota in anabolic resistance and skeletal muscle in aging people, and introduce the metabolome as a tool to probe this relationship in the future.
Over a Thousand Years of Evolutionary History of Domestic Geese from Russian Archaeological Sites, Analysed Using Ancient DNA

The European domestic goose is a widely farmed species known to have descended from the wild greylag goose (Anser anser). However, the evolutionary history of this domesticate is still poorly known. Ancient DNA studies have been useful for many species, but there has been little such work on geese. We have studied temporal genetic variation among domestic goose specimens excavated from Russian archaeological sites (4th–18th centuries) using a 204 base pair fragment of the mitochondrial control region. Specimens fell into three different genetic clades: the domestic D-haplogroup, the F-haplogroup that includes both wild and domestic geese, and a clade comprising another species, the taiga bean goose. Most of the subfossil geese carried typical domestic D-haplotypes. The domestication status of the geese carrying F-haplotypes is less certain, as the haplotypes identified were not present among modern domestic geese and could represent wild geese (misclassified as domestics), introgression from wild geese, or local domestication events. The bones of taiga bean goose were most probably misidentified as domestic goose but the domestication of bean goose or hybridization with domestic goose is also possible. Samples from the 4th to 10th century were clearly differentiated from the later time periods due to a haplotype that was found only in this early period, but otherwise no temporal or geographical variation in haplotype frequencies was apparent.
In Vitro Methods to Characterize the Effects of Tobacco and Nontobacco Products on Human Platelet Function

In this document, we describe methods for the isolation, treatment, and functional testing of human blood platelets in vitro. Functional assays for inflammatory function include flow cytometry and immunoassays for platelet release of platelet factor 4, soluble CD40L, prostaglandin E2, and thromboxane. Assays for platelet hemostatic function described here examine platelet spreading, aggregation using platelet‐rich plasma, and thromboelastography. Also described here are methods for testing cigarette smoke on primary human platelets in vitro, which our lab developed to address a major knowledge gap regarding how cigarette smoke dysregulates platelets and how this platelet dysregulation contributes to cardiovascular disease. Some of these protocols may be repurposed for investigation of the toxicity potential of other tobacco products and environmental insults. © 2018 by John Wiley & Sons, Inc.
Analysis of the Relationship between the Referral and Evolution of Patients with Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM) is a chronic disease that has risen in prominence in recent years and can cause serious complications. Several studies show that the level of adherence to different types of treatment has a direct correlation with the positive evolution of chronic diseases. While such studies relate to patient adherence to medication, those that concern adherence to medical appointments do not distinguish between the different disciplines that attend to or refer patients. This study analyses the relationship between adherence to referrals made by three distinct disciplines (doctors, nurses, and nutritionists) and the results of HbA1c tests from a sample of 2290 patients with T2DM. The aim is to determine whether a relationship exists between patient improvement and the frequency with which they attend scheduled appointments in a timely manner, having been previously referred from or to a particular discipline. Results showed that patients tended to be more adherent when their next appointment is with a doctor, and less adherent when it is with a nurse or nutritionist. Furthermore, patients that remained stable had higher rates of adherence, whereas those with lower adherence tended to be more decompensated. The results can enable healthcare professionals to monitor patients and place particular emphasis on those who do not attend their scheduled appointments in a timely manner.
On the Anonymization of Differentially Private Location Obfuscation

Obfuscation techniques in location-based services (LBSs) have been shown useful to hide the concrete locations of service users, whereas they do not necessarily provide the anonymity. We quantify the anonymity of the location data obfuscated by the planar Laplacian mechanism and that by the optimal geo-indistinguishable mechanism of Bordenabe et al. We empirically show that the latter provides stronger anonymity than the former in the sense that more users in the database satisfy k-anonymity. To formalize and analyze such approximate anonymity we introduce the notion of asymptotic anonymity. Then we show that the location data obfuscated by the optimal geo-indistinguishable mechanism can be anonymized by removing a smaller number of users from the database. Furthermore, we demonstrate that the optimal geo-indistinguishable mechanism has better utility both for users and for data analysts.
Tools to assess the measurement properties of quality of life instruments: a meta-review protocol

Introduction Using specific tools to assess the measurement properties of health status instruments is recommended both to standardise the review process and to improve the methodological quality of systematic reviews. However, depending on the measurement standards on which these tools are developed, the approach to appraise the measurement properties of instruments may vary. For this reason, the present meta-review aims to: (1) identify systematic reviews assessing the measurement properties of instruments evaluating health-related quality of life (HRQoL); (2) identify the tools applied to assess the measurement properties of HRQoL instruments; (3) describe the characteristics of the tools applied to assess the measurement properties of HRQoL instruments; (4) identify the measurement standards on which these tools were developed or conform to and (5) compare the similarities and differences among the identified measurement standards. Methods and analysis A systematic review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols Guidelines. Electronic search will be carried out on bibliographic databases, including PubMed, Cumulative Index to Nursing and Allied Health Literature, Psychological Information, SCOPUS, Web of Science, COSMIN database and ProQuest Dissertations & Theses Global, being limited by time (2008–2018) and language (English). Descriptive analyses of different aspects of tools applied to evaluate the measurement properties of HRQoL instruments will be presented; the different measurement standards will be described and some recommendations about the methodological and research applications will be made. Ethics and dissemination Ethical approval is not necessary for systematic review protocols. The results will be disseminated by its publication in a peer-reviewed journal and presented at a relevant conference. PROSPERO registration number CRD42017065232
Modeling the random effects covariance matrix for longitudinal data with covariates measurement error

Longitudinal data occur frequently in practice such as medical studies and life sciences. Generalized linear mixed models (GLMMs) are commonly used to analyze such data. It is typically assumed that the random effects covariance matrix is constant among subjects in these models. In many situations, however, the correlation structure may differ among subjects and ignoring this heterogeneity can lead to biases in model parameters estimate. Recently, Lee et al developed a heterogeneous random effects covariance matrix for GLMMs for error‐free covariates. Covariates measured with error also happen frequently in the longitudinal data set‐up (eg, blood pressure and cholesterol level). Ignoring this issue in the data may produce bias in model parameters estimate and lead to wrong conclusions. In this paper, we propose an approach to properly model the random effects covariance matrix based on covariates in the class of GLMMs, where we also have covariates measured with error. The resulting parameters from the decomposition of random effects covariance matrix have a sensible interpretation and can be easily modeled without the concern of positive definiteness of the resulting estimator. The performance of the proposed approach is evaluated through simulation studies, which show that the proposed method performs very well in terms of bias, mean squared error, and coverage rate. An application of the proposed method is also provided using a longitudinal data from Manitoba follow‐up study.
ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy

Background The development of new revascularization devices has improved recanalization rates and time, but not clinical outcomes. We report a prospectively collected clinical experience with a new technique utilizing a direct aspiration first pass technique with large bore aspiration catheter as the primary method for vessel recanalization. Methods 98 prospectively identified acute ischemic stroke patients with 100 occluded large cerebral vessels at six institutions were included in the study. The ADAPT technique was utilized in all patients. Procedural and clinical data were captured for analysis. Results The aspiration component of the ADAPT technique alone was successful in achieving Thrombolysis in Cerebral Infarction (TICI) 2b or 3 revascularization in 78% of cases. The additional use of stent retrievers improved the TICI 2b/3 revascularization rate to 95%. The average time from groin puncture to at least TICI 2b recanalization was 37 min. A 5MAX demonstrated similar success to a 5MAX ACE in achieving TICI 2b/3 revascularization alone (75% vs 82%, p=0.43). Patients presented with an admitting median National Institutes of Health Stroke Scale (NIHSS) score of 17.0 (12.0–21.0) and improved to a median NIHSS score at discharge of 7.3 (1.0–11.0). Ninety day functional outcomes were 40% (modified Rankin Scale (mRS) 0–2) and 20% (mRS 6). There were two procedural complications and no symptomatic intracerebral hemorrhages. Discussion The ADAPT technique is a fast, safe, simple, and effective method that has facilitated our approach to acute ischemic stroke thrombectomy by utilizing the latest generation of large bore aspiration catheters to achieve previously unparalleled angiographic outcomes.
Menstrual fluid factors facilitate tissue repair: identification and functional action in endometrial and skin repair

Repair after damage is essential for tissue homeostasis. Postmenstrual endometrial repair is a cyclical manifestation of rapid, scar‐free, tissue repair taking ∼3–5 d. Skin repair after wounding is slower (∼2 wk). In the case of chronic wounds, it takes months to years to restore integrity. Herein, the unique “rapid‐repair” endometrial environment is translated to the “slower repair” skin environment. Menstrual fluid (MF), the milieu of post‐menstrual endometrial repair, facilitates healing of endometrial and keratinocyte “wounds” in vitro, promoting cellular adhesion and migration, stimulates keratinocyte migration in an ex vivo human skin reconstruct model, and promotes re‐epithelialization in an in vivo porcine wound model. Proteomic analysis of MF identified a large number of proteins: migration inhibitory factor, neutrophil gelatinase–associated lipocalin, follistatin like‐1, chemokine ligand‐20, and secretory leukocyte protease inhibitor were selected for further investigation. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration. Translation of these and other MF factors into a migration‐inducing treatment paradigm could provide novel treatments for tissue repair. —Evans, J., Infusini, G. , McGovern, J., Cuttle, L. , Webb, A. , Nebl, T. , Milla, L. , Kimble, R. , Kempf, M. , Andrews, C. J., Leavesley, D. , Salamonsen, L. A. Menstrual fluid factors facilitate tissue repair: identification and functional action in endometrial and skin repair. FASEB J. 33, 584–605 (2019). www.fasebj. org
Variability in Characterizing Escherichia coli from Cattle Feces: A Cautionary Tale

Shiga toxin-producing Escherichia coli (STEC) are diverse bacteria, with seven serogroups (O26, O45, O103, O111, O121, O145, O157; “Top 7”) of interest due to their predominance in human disease. Confirmation of STEC relies on a combination of culturing, immunological and molecular assays, but no single gold standard for identification exists. In this study, we compared analysis of STEC between three independent laboratories (LAB) using different methodologies. In LAB A, colonies of Top 7 were picked after serogroup-specific immunomagnetic separation of feces from western-Canadian slaughter cattle. A fraction of each colony was tested by PCR (stx1, stx2, eae, O group), and Top 7 isolates were saved as glycerol stocks (n = 689). In LAB B, a subsample of isolates (n = 171) were evaluated for stx1 and stx2 using different primer sets. For this, approximately half of the PCR were performed using original DNA template provided by LAB A and half using DNA extracted from sub-cultured isolates. All Top 7 isolates were sub-cultured by LAB A and shipped to LAB C for traditional serotyping (TS) to determine O and H groups, with PCR-confirmation of virulence genes using a third set of primers. By TS, 76% of O groups (525/689) matched PCR-determined O groups. Lowest proportions (p < 0.05) of O group matches between PCR and TS (62.6% and 69.8%) occurred for O26 and O45 serogroups, respectively. PCR-detection of stx differed most between LAB A and LAB C. Excluding isolates where O groups by PCR and TS did not match, detection of stx1 was most consistent (p < 0.01) for O111 and O157:H7/NM. In contrast, for O45 and O103, stx1 was detected in >65% of isolates by LAB A and <5% by LAB C. Stx2 was only detected by LAB C in isolates of serogroups O121, O145, and O157:H7/NM. LAB B also detected stx2 in O26 and O157:H12/H29, while LAB A detected stx2 in all serogroups. Excluding O111 and O157:H7/NM, marked changes in stx detection were observed between initial isolation and sub-cultures of the same isolate. While multiple explanations exist for discordant O-typing between PCR and TS and for differences in stx detection across labs, these data suggest that assays for STEC classification may require re-evaluation and/or standardization.
Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss

Purpose: PI3K–Akt–mTOR and androgen receptor (AR) signaling are commonly aberrantly activated in metastatic castration-resistant prostate cancer (mCRPC), with PTEN loss associating with poor prognosis. We therefore conducted a phase Ib/II study of the combination of ipatasertib, an Akt inhibitor, with the CYP17 inhibitor abiraterone in patients with mCRPC. Patients and Methods: Patients were randomized 1:1:1 to ipatasertib 400 mg, ipatasertib 200 mg, or placebo, with abiraterone 1,000 mg orally. Coprimary efficacy endpoints were radiographic progression-free survival (rPFS) in the intent-to-treat population and in patients with PTEN-loss tumors. Results: rPFS was prolonged in the ipatasertib cohort versus placebo, with similar trends in overall survival and time-to-PSA progression. A larger rPFS prolongation for the combination was demonstrated in PTEN-loss tumors versus those without. The combination was well tolerated, with no treatment-related deaths. Conclusions: In mCRPC, combined blockade with abiraterone and ipatasertib showed superior antitumor activity to abiraterone alone, especially in patients with PTEN-loss tumors. See related commentary by Zhang et al., p. 901