bluuebunny/crossref_metadata_2025 huggingface dataset:
Hamstring Muscle Injury Prediction by Isokinetic Ratios Depends on the Method Used
Authors: Dauty Marc , Menu Pierre , Fouasson-Chailloux Alban
Published: April 2018

Objectives:

Hamstring muscle injury prediction by isokinetic strength ratios is low but could result from the method—depending either on the use of the limbs or of the sportsmen as references. We aimed to establish a predictive model including unilateral and bilateral ratios calculated from the dominant, nondominant, right, and left limb in injured and uninjured professional soccer players.

Design:

Cohort study.

Setting:

Soccer team of the French Professional Premier League.

Patients:

Ninety-one professional soccer players.

Interventions:

Isokinetic muscle strength was prospectively measured at the beginning of 5 consecutive seasons (2009-2014).

Main Outcome Measures:

Several bilateral, conventional, and functional ratios were calculated from isokinetic measurements at different angular speeds (60 and 240 degrees/s in concentric mode and 30 degrees/s in eccentric mode). Thirty-one soccer players had a hamstring injury during the seasons and were compared with 60 uninjured players. Four models were tested to predict the occurrence of hamstring injury from isokinetic ratios calculated in accordance with the dominant, nondominant, right, and left limb.

Results:

No predictive model was found when ratios were calculated from the dominant or the right limb. Two models of prediction were found when ratios were calculated from the nondominant or the left limb. In these 2 models, only the bilateral concentric hamstring-to-hamstring ratio at 60 degrees/s was predictive. The best prediction was found with the left limb.

Conclusions:

We identified 2 low predictive models for hamstring muscle injuries depending on the limbs studied. Because of a low prediction, the consensual method used to predict hamstring muscle injury must be defined in future studies.
Steps to Enhance Early Recovery After Hematopoietic Stem Cell Transplantation
Authors: Hacker Eileen Danaher , Peters Tara , Patel Pritesh , Rondelli Damiano
Published: April 2018

Aims:

This pilot study tested and refined a free-living physical activity intervention. The investigators evaluated the acceptability and feasibility of the intervention after hematopoietic stem cell transplantation and determined preliminary effects on physical activity, fatigue, muscle strength, functional ability, and quality of life.

Design:

This pilot study used a 1-group, pretest-posttest design.

Methods:

The free-living physical activity intervention consisted of an education component and 6 weeks of gradually increasing physical activity after discharge from the hospital. The intervention was designed to increase steps by 10% weekly. Subjects were assessed before transplantation and during the seventh week after discharge from the hospital after completing the intervention. Pretest-posttest scores were analyzed with paired t tests.

Results:

Subject wore the physical activity tracker for an average of 38 of 42 days and met their physical activity goals 57% of the time. Subjects reported significantly less physical fatigue after the free-living physical activity intervention compared with baseline (P = .05). Improvements in quality of life approached significance (P = .06).

Conclusion:

The findings demonstrate that the free-living physical activity intervention implemented during the very early recovery period after transplantation is feasible and acceptable. The intervention potentially reduces fatigue and improves quality of life. The positive results must be interpreted cautiously given the pilot nature of the study. The evidence supports continued investigation.
Sexual Behaviors of Human Immunodeficiency Virus–Infected Pregnant Women and Factors Associated With Sexually Transmitted Infection in South Africa
Authors: Joseph Davey Dvora , Peters Remco P.H. , Kojima Noah , Mudau Maanda , De Vos Lindsey , Olivier Dawie , McIntyre James A. , Klausner Jeffrey D. , Medina-Marino Andrew
Published: April 2018

Background

Sexual behaviors in human immunodeficiency virus (HIV)-infected pregnant women in South Africa are not well understood.

Methods

Human immunodeficiency virus–infected pregnant women were recruited into a prospective cohort at first antenatal care visit. Sociodemographic information and self-collected vulvovaginal swab samples were collected from participants. Vulvovaginal swab samples were tested for Chlamydia trachomatis, Neisseria gonorrhoea, and Trichomonas vaginalis using GeneXpert. We investigated sexual behaviors, alcohol use, factors associated with condomless sex during pregnancy, and prevalent sexually transmitted infection (STI) among our cohort. We report descriptive, univariate and multivariable logistic regression results of sexual behaviors and alcohol use, factors associated with condomless sex at last sex, and having any STI during pregnancy adjusting for a priori confounders.

Results

We recruited and enrolled 430 HIV-infected pregnant women. Median age was 30 years; median gestational age was 20 weeks. Eighty-nine percent of women reported sex during pregnancy. At last sex, 68% reported condomless sex; 18% reported having more than 1 sex partner in the past 12 months. Adjusting for age, income and relationship status, condom use at last sex was associated with prior knowledge of HIV status (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.54–3.92) and being in a concordant HIV-positive (aOR, 3.17; 95% CI, 1.84–5.50), or serodiscordant relationship (aOR, 6.50; 95% CI, 3.59–11.80). The prevalence of any STI was 41% (95% CI, 36%–45%). Adjusting for mothers' age and employment, odds of having an STI increased if the woman reported alcohol use during pregnancy (aOR, 1.96; 95% CI, 1.06–3.64) or if the father of the child was a non-cohabiting or casual partner (aOR, 1.42; 95% CI, 0.97–2.03).

Conclusions

Almost all HIV-infected pregnant women were sexually active during pregnancy and most women reported condomless sex at last sex. Condom use was associated with knowledge of serostatus and/or partner's serostatus before first antenatal care visit. Factors associated with having STIs included: alcohol use during pregnancy and father of child being a non-cohabiting partner.
Optimizing a Positive Psychology Intervention to Promote Health Behaviors After an Acute Coronary Syndrome: The Positive Emotions After Acute Coronary Events III (PEACE-III) Randomized Factorial Trial
Authors: Celano Christopher M. , Albanese Ariana M. , Millstein Rachel A. , Mastromauro Carol A. , Chung Wei-Jean , Campbell Kirsti A. , Legler Sean R. , Park Elyse R. , Healy Brian C. , Collins Linda M. , Januzzi James L. , Huffman Jeff C.
Published: April 2018

Objective

Despite the clear benefits of physical activity and related behaviors on prognosis, most patients experiencing an acute coronary syndrome (ACS) remain nonadherent to these behaviors. Deficits in positive psychological constructs (e.g., optimism) are linked to reduced participation in health behaviors, supporting the potential utility of a positive psychology (PP)-based intervention in post-ACS patients. Accordingly, we aimed to identify optimal components of a PP-based intervention to promote post-ACS physical activity.

Methods

As part of a multiphase optimization strategy, we completed a randomized factorial trial with eight conditions in 128 post-ACS patients to efficiently identify best-performing intervention components. All participants received a PP-based intervention, with conditions varying in duration (presence/absence of booster sessions), intensity (weekly/daily PP exercises), and content (PP alone or combined with motivational interviewing), allowing three concurrent comparisons within the trial. The study aims included assessments of the overall feasibility, acceptability, and impact of the intervention, along with the primary aim of determining which components were associated with objectively measured physical activity and self-reported health behavior adherence at 16 weeks, assessed using longitudinal models.

Results

The intervention was well accepted and associated with substantial improvements in behavioral and psychological outcomes. Booster sessions were associated with greater activity to a nearly significant degree (β = 8.58, 95% confidence interval = −0.49–17.65, effect size difference = .43, p = .064), motivational interviewing was associated with overall adherence (β = 0.95, 95% confidence interval = 0.02–1.87, effect size difference = .39, p = .044), and weekly exercise completion was generally superior to daily.

Conclusions

These findings will enable optimization of the PP-based intervention in preparation for a well-powered controlled trial.

Clinical Trial Registration

Clinicaltrials.gov, NCT02754895.
HIV Infection Is Associated With Abnormal Bone Microarchitecture: Measurement of Trabecular Bone Score in the Women's Interagency HIV Study
Authors: Sharma Anjali , Ma Yifei , Tien Phyllis C. , Scherzer Rebecca , Anastos Kathryn , Cohen Mardge H. , Hans Didier , Yin Michael T.
Published: April 2018

Objectives:

We compared skeletal microarchitecture using trabecular bone score (TBS) and evaluated relationships between change in TBS and lumbar spine (LS) bone mineral density (BMD) in women with and without HIV.

Methods:

Dual-energy X-ray absorptiometry was performed on 319 women with HIV and 118 without HIV in the Women's Interagency HIV Study at baseline and 2 and 5 years, to measure regional BMD and lean and fat mass. TBS was extracted from LS dual-energy X-ray absorptiometry images and examined continuously and categorically [normal (≥1.35), intermediate (1.20–1.35), or degraded (≤1.20) microarchitecture]. Pearson correlation and linear regression examined associations of TBS with regional BMD at baseline and over time.

Results:

Women with HIV were older (43 vs. 37 years), more likely to be postmenopausal (27% vs. 4%), have lower baseline total fat mass, trunk fat, and leg fat than uninfected women, degraded microarchitecture (27% vs. 9%, P = 0.001), and lower baseline mean TBS (1.3 ± 0.1 vs. 1.4 ± 0.1, P < 0.001). After adjusting for age, race, menopause status, and body mass index, TBS remained lower in women with HIV (P < 0.0001). Annual change in TBS correlated with LS BMD change among women with HIV (r = 0.36, P < 0.0001) and without HIV (r = 0.26, P = 0.02); however, mean % annual TBS change did not differ by HIV status (−1.0%/yr ± 2.9% for HIV+ vs. −0.8%/yr ± 1.7% for HIV−, P = 0.42).

Conclusions:

Women with HIV have worse bone microarchitecture than uninfected women, but annual percent change in LS BMD or TBS was similar. Use of TBS as an adjunct to BMD to improve prediction of fragility fractures in women with HIV merits further study.
Effect of Lactobacillus rhamnosus GG Supplementation on Intestinal Inflammation Assessed by PET/MRI Scans and Gut Microbiota Composition in HIV-Infected Individuals
Authors: Arnbjerg Caroline J. , Vestad Beate , Hov Johannes R. , Pedersen Karin K. , Jespersen Sofie , Johannesen Helle H. , Holm Kristian , Halvorsen Bente , Fallentin Eva , Hansen Adam E. , Lange Theis , Kjær Andreas , Trøseid Marius , Fischer Barbara M. , Nielsen Susanne D.
Published: April 2018

Background:

Alterations in the gut microbiome have been associated with inflammation and increased cardiovascular risk in HIV-infected individuals. The aim of this study was to investigate the effects of the probiotic strainLactobacillus rhamnosus GG(LGG) on intestinal inflammation, gut microbiota composition, and systemic markers of microbial translocation and inflammation in HIV-infected individuals.

Methods:

This prospective, clinical interventional trial included 45 individuals [15 combination antiretroviral treatment (cART) naive and 30 cART treated] who ingestedLGGtwice daily at a dosage of 6 × 109 colony-forming units per capsule for a period of 8 weeks. Intestinal inflammation was assessed using18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) scans in 15 individuals. Gut microbiota composition (V3–V4 region of the 16s rRNA gene) and markers of microbial translocation and inflammation (lipopolysaccharide, sCD14, sCD163, sCD25, high-sensitive CRP, IL-6, and tumor necrosis factor-alpha) were analyzed at baseline and after intervention.

Results:

At baseline, evidence of intestinal inflammation was found in 75% of the participants, with no significant differences between cART-naive and cART-treated individuals. AfterLGGsupplementation, a decrease in intestinal inflammation was detected on PET/MRI (−0.3 mean difference in the combined activity grade score from 6 regions,P= 0.006), along with a reduction of Enterobacteriaceae (P= 0.018) and Erysipelotrichaceae (P= 0.037) in the gut microbiome, with reduced Enterobacteriaceae among individuals with decreased18F-FDG uptake on PET/MRI (P= 0.048). No changes were observed for soluble markers of microbial translocation and inflammation.

Conclusions:

A decrease in intestinal inflammation was found in HIV-infected individuals after ingestion ofLGGalong with a reduced abundance of Enterobacteriaceae, which may explain the local anti-inflammatory effect in the gut.
Factors Associated With Initiation of Biologics in Patients With Axial Spondyloarthritis in an Urban Asian City
Authors: Png Wan Yu , Kwan Yu Heng , Lee Yi Xuan , Lim Ka Keat , Chew Eng Hui , Lui Nai Lee , Tan Chuen Seng , Thumboo Julian , Østbye Truls , Fong Warren
Published: April 2018

Objective

The aim of this study was to examine if patients' sociodemographic, clinical characteristics, and patient-reported outcomes were associated with biologics initiation in patients with axial spondyloarthritis in Singapore.

Methods

Data from a dedicated registry from a tertiary referral center in Singapore from January 2011 to July 2016 were used. Initiation of first biologics was the main outcome of interest. Logistic regression analyses were used to explore the association of various factors on biologics initiation.

Results

Of 189 eligible patients (aged 37.7 ± 13.3 years; 76.2% were males), 30 (15.9 %) were started on biologics during follow-up. In the multivariable analysis model, age (odds ratio [OR]; 0.93; 95% confidence interval [CI], 0.89–0.98; p < 0.01), mental component summary score of Short-Form 36 Health Survey (OR, 0.18; 95% CI, 0.03–0.89; p = 0.04), erythrocyte sedimentation rate (OR, 1.02; 95% CI, 1.00–1.04; p = 0.02), presence of peptic ulcer disease (OR, 10.4; 95% CI, 2.21–48.8; p < 0.01), and lack of good response to nonsteroidal anti-inflammatory drugs (OR, 4.44; 95% CI, 1.63–12.1; p < 0.01) were found to be associated with biologics initiation.

Conclusions

Age, erythrocyte sedimentation rate, mental component summary score, comorbidities of peptic ulcer disease, and responsiveness to nonsteroidal anti-inflammatory drugs were associated with biologics initiation. It is essential that clinicians recognize these factors in order to optimize therapy.
Factors Associated With the Complexity of Facial Trauma
Authors: Pita Neto Ivo Cavalcante , Franco Jéferson Martins Pereira Lucena , Junior Júlio Leite de Araujo , Santana Milana Drumond Ramos , de Abreu Luiz Carlos , Bezerra Ítalla Maria Pinheiro , Soares Eduardo Costa Studart , de Alencar Gondim David Gomes , Rodrigues Luciano Miller Reis
Published: April 2018

Introduction:

Facial fractures have their incidence, etiology, clinical presentation, and features influenced by variables such as economic, cultural, and demographic factors. A large number of these fractures require simple or more complex approaches, and it becomes important to understand their clinical and epidemiological profile and factors associated with the fracture event and surgical indication.

Objective:

The objective of this research is to analyze the clinical and epidemiological profile of surgical fractures and their associations with causal factors such as alcohol consumption, day of the incident, and nonuse of helmet for motorcycle accidents.

Method:

A retrospective study was conducted with collection of data from medical records of patients operated for facial fractures at the Hospital Regional of Cariri, state of Ceara, the Northeast of Brazil. Records from 2012 to 2014 were acquired highlighting sex, age, occupation, etiology, anatomical sites of fractures, and surgeries of varying complexities for single or multiple fractures. The day of the event, report or signs of alcohol consumption, and the use of helmets in motorcycle accidents were named associated factors.

Results:

As a result the authors had a total of 624 cases of surgical facial fractures. Out of these, 546 (87.5%) were male and the majority of them presented between 20 and 30 years of age (40.5%). It was also observed that as an etiological factor motorcycle accidents led to more cases of surgical facial fractures, with 357 cases (62.1%), followed by physical aggression with 72 cases (12.5%).

Conclusions:

It can be concluded that there is a high prevalence of surgical facial fractures in male patients between 20 and 30 years of age, caused by motorcycle accidents, and that there was a strong association between the consumption of alcohol, failure to wear a helmet, and the presence of surgical facial multiple fractures.
Primary and Secondary Stability of Single Short Implants
Authors: Alonso Fernando R. , Triches Diego F. , Mezzomo Luis A.M. , Teixeira Eduardo R. , Shinkai Rosemary S.A.
Published: April 2018

Purpose:

This prospective cohort study assessed the effect of bone quality on the primary and secondary stability of single short implants placed in the posterior region.

Materials and Methods:

A total of 39 short implants (4.1 × 6-mm long) were placed in the posterior region of the maxilla or mandible in 18 patients. Bone quality was classified into type I, II, III, or IV as assessed intrasurgically. Primary implant stability was measured with insertion torque, damping capacity (PTV values), and resonance frequency analysis (ISQ values). Secondary stability was measured by ISQ and PTV at abutment installation. Data were analyzed by using repeated-measures ANOVA and Tukey's test, Kruskall–Wallis test, and Spearman correlation tests.

Results:

Implants placed in bone type IV had significant lower insertion torque and ISQ values as well as higher PTV values than in bone types I to II (P< 0.05). The mean ISQ values were higher at abutment installation than at implant placement (P < 0.05), regardless the bone type. The assessment methods of implant stability showed a moderate correlation.

Conclusions:

Bone quality influences both the primary and secondary stability of single short implants in the posterior region.
Total nephrectomy following Corynebacterium coyleae urinary tract infection
Authors: Barberis Claudia M. , Montalvo Eduardo , Imas Soledad , Traglia Germán , Almuzara Marisa N. , Rodriguez Carlos Hernán , Famiglietti Angela , Mazzocchi Octavio , Vay Carlos
Published: April 2018

Introduction.
Corynebacterium coyleae is a Gram-stain-positive non-lipophilic coryneform rod first described in blood samples and pleural fluid. There is scarce information about the clinical relevance of C. coyleae and none on complicated urinary tract infections has been described so far.

Case presentation. A 36-year-old woman with a history of chronic kidney failure, under thrice-weekly haemodialysis since 2014 due to polycystic kidney disease, presented with hypogastric pain, lower left quadrant pain and nausea. Since 1997, the patient had developed several episodes of urinary tract infection. On admission, the patient presented tenderness in the lower abdomen and fist positive lumbar percussion. Urine culture showed significant bacterial growth (>105 c.f.u. ml−1). Slightly glistening colonies of 1 mm in diameter were observed after a 24 h incubation. Gram staining showed coryneform Gram-stain-positive rods. The patient was diagnosed as having a complicated urinary tract infection. A bilateral nephrectomy was performed on the fourth day of hospitalization. Two samples of kidney tissue were sent for culture. Direct examination of the material revealed the presence of abundant inflammatory reaction and Gram-positive diphtheroid rods. The organism was identified using MALDI–TOF and conventional biochemical tests; in both isolates further identification was performed by PCR amplification and sequence analysis of the rpoB gene as Corynebacterium coyleae.

Conclusions.
C. coyleae is an infrequent species among the genus Corynebacterium that should be considered as an emerging pathogen that can be involved in nosocomial infections and complicated urinary tract infections
Long-read whole genome sequencing and comparative analysis of six strains of the human pathogenOrientia tsutsugamushi
Authors: Batty Elizabeth M. , Chaemchuen Suwittra , Blacksell Stuart D. , Paris Daniel , Bowden Rory , Chan Caroline , Lachumanan Ramkumar , Day Nicholas , Donnelly Peter , Chen Swaine L. , Salje Jeanne
Published: April 2018

Background

Orientia tsutsugamushiis a clinically important but neglected obligate intracellular bacterial pathogen of the Rickettsiaceae family that causes the potentially life-threatening human disease scrub typhus. In contrast to the genome reduction seen in many obligate intracellular bacteria, early genetic studies ofOrientiahave revealed one of the most repetitive bacterial genomes sequenced to date. The dramatic expansion of mobile elements has hampered efforts to generate complete genome sequences using short read sequencing methodologies, and consequently there have been few studies of the comparative genomics of this neglected species.

Results

We report new high-quality genomes ofOrientia tsutsugamushi,generated using PacBio single molecule long read sequencing, for six strains: Karp, Kato, Gilliam, TA686, UT76 and UT176. In comparative genomics analyses of these strains together with existing reference genomes from Ikeda and Boryong strains, we identify a relatively small core genome of 657 genes, grouped into core gene ‘islands’ and separated by repeat regions, and use the core genes to infer the first whole-genome phylogeny ofOrientia.

Conclusions

Complete assemblies of multiple Orientia genomes verify initial suggestions that these are remarkable organisms. They have large genomes with widespread amplification of repeat elements and massive chromosomal rearrangements between strains. At the gene level, Orientia has a relatively small set of universally conserved genes, similar to other obligate intracellular bacteria, and the relative expansion in genome size can be accounted for by gene duplication and repeat amplification. Our study demonstrates the utility of long read sequencing to investigate complex bacterial genomes and characterise genomic variation.
Isolation and sequencing of AGO-bound RNAs reveals characteristics of mammalian stem-loop processing in vivo
Authors: Silverman Ian M. , Gosai Sager J. , Vrettos Nicholas , Foley Shawn W. , Berkowitz Nathan D. , Mourelatos Zissimos , Gregory Brian D.
Published: April 2018

MicroRNA precursors (pre-miRNAs) are short hairpin RNAs that are rapidly processed into mature microRNAs (miRNAs) in the cytoplasm. Due to their low abundance in cells, sequencing-based studies of pre-miRNAs have been limited. We successfully enriched for and deep sequenced pre-miRNAs in human cells by capturing these RNAs during their interaction with Argonaute (AGO) proteins. Using this approach, we detected > 350 pre-miRNAs in human cells and > 250 pre-miRNAs in a reanalysis of a similar study in mouse cells. We uncovered widespread trimming and non-templated additions to the 3’ ends of pre- and mature miRNAs. Additionally, we created an index for microRNA precursor processing efficiency. This analysis revealed a subset of pre-miRNAs that produce low levels of mature miRNAs despite abundant precursors, including an annotated miRNA in the 5’ UTR of the DiGeorge syndrome critical region 8 mRNA transcript. This led us to search for AGO-associated stem-loops originating from other mRNA species, which identified hundreds of putative pre-miRNAs derived from human and mouse mRNAs. In summary, we provide a wealth of information on mammalian pre-miRNAs, and identify novel microRNA and microRNA-like elements localized in mRNAs.
Machine-Learning prognostic models from the 2014-16 Ebola outbreak: data-harmonization challenges, validation strategies, and mHealth applications
Authors: Colubri Andres , Hartley Mary-Anne , Siakor Mathew , Wolfman Vanessa , Sesay Tom , Felix August , Levine Adam C. , Sabeti Pardis C.
Published: April 2018

Background

We created a family of prognostic models for Ebola virus disease from the largest dataset of EVD patients published to date. We incorporated these models into an app, “Ebola Care Guidelines”, that provides access to recommended, evidence-based supportive care guidelines and highlights the signs/symptoms with the largest contribution to prognosis.

Methods

We applied multivariate logistic regression on 470 patients admitted to five Ebola treatment units in Liberia and Sierra Leone during the 2014-16 outbreak. We validated the models with two independent datasets from Sierra Leone.

Findings

Viral load and age were the most important predictors of death. We generated a parsimonious model including viral load, age, body temperature, bleeding, jaundice, dyspnea, dysphagia, and referral time recorded at triage. We also constructed fallback models for when variables in the parsimonious model are unavailable. The performance of the parsimonious model approached the predictive power of observational wellness assessments by experienced health workers, with Area Under the Curve (AUC) ranging from 0.7 to 0.8 and overall accuracy of 64% to 74%.

Interpretation

Machine-learning models and mHealth tools have the potential for improving the standard of care in low-resource settings and emergency scenarios, but data incompleteness and lack of generalizable models are major obstacles. We showed how harmonization of multiple datasets yields prognostic models that can be validated across different cohorts. Similar performance between the parsimonious model and those incorporating expert wellness assessments suggests that clinically-guided machine learning approaches can recapitulate clinical expertise, and thus be useful when such expertise is unavailable. We also demonstrated with our guidelines app how integration of those models with mobile technologies enables deployable clinical management support tools that facilitate access to comprehensive bodies of medical knowledge.

Funding

Howard Hughes Medical Institute, US National Institutes of Health
The 100-plus Study of cognitively healthy centenarians: rationale, design and cohort description
Authors: Holstege Henne , Beker Nina , Dijkstra Tjitske , Pieterse Karlijn , Wemmenhove Elizabeth , Schouten Kimja , Thiessens Linette , Horsten Debbie , Rechtuijt Sterre , Sikkes Sietske , van Poppel Frans W.A. , Meijers-Heijboer Hanne , Hulsman Marc , Scheltens Philip
Published: April 2018

RATIONALE

Although the incidence of dementia increases exponentially with age, some individuals reach >100 years with fully retained cognitive abilities. To identify the characteristics associated with the escape or delay of cognitive decline, we initiated the 100-plus Study (www.100plus.nl).

DESIGN

The 100-plus Study is an on-going prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. We collect demographics, life history, medical history, genealogy, neuropsychological data and blood samples. Centenarians are followed annually until death. PET-MRI scans and feces donation are optional. Almost 30% of the centenarians agreed to post-mortem brain donation.

COHORT DESCRIPTION

To date (September 2018), 332 centenarians were included in the study. We analyzed demographic statistics of the first 300 centenarians (25% males) included in the cohort. Centenarians came from higher socio-economic classes and had higher levels of education compared to their birth cohort; alcohol consumption of centenarians was similar, and most males smoked during their lifetime. At baseline, the centenarians had a median MMSE score of 25 points (IQR: 22.0-27.5); the large majority lived independently, retained hearing and vision abilities and was independently mobile. Mortality was associated with cognitive functioning: centenarians with a baseline MMSE score ≥26 and <26 points had a mortality percentage of respectively 17% and 42% per annual year in the second year after baseline (p=0.003). The cohort was 2.1-fold enriched with the neuroprotective APOE-ε2 allele relative to 60-80 year-old population controls (p=4.8×10-7), APOE-ε3 was unchanged and the APOE-ε4 allele was 2.3-fold depleted (p=6.3×10-7).

CONCLUSIONS

Comprehensive characterization of the 100-plus cohort of cognitively healthy centenarians might reveal protective factors that explain the physiology of long-term preserved cognitive health.
The impact of endogenous retroviruses on nuclear organization and gene expression
Authors: Raviram Ramya , Rocha Pedro P , Luo Vincent M , Swanzey Emily , Miraldi Emily R , Chuong Edward B , Feschotte Cédric , Bonneau Richard , Skok Jane A
Published: April 2018

Background

The organization of chromatin in the nucleus plays an essential role in gene regulation. When considering the mammalian genome it is important to take into account that about half of the DNA is comprised of transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses. Thus, it is challenging to identify the activities and properties of individual transposons. As a result, we only have a partial understanding of how transposons contribute to chromatin folding and how they impact gene regulation.

Results

Using adapted PCR and Capture-based chromosome conformation capture (3C) approaches, collectively called 4Tran, we take advantage of the repetitive nature of transposons to capture interactions from multiple copies of endogenous retrovirus (ERVs) in the human and mouse genomes. With 4Tran-PCR, reads are selectively mapped to unique regions in the genome. This enables the identification of TE interaction profiles for individual ERV families and integration events specific to particular genomes. With this approach we demonstrate that transposons engage in long-range intra-chromosomal interactions guided by the separation of chromosomes into A and B compartments as well as topologically associated domains (TADs). In contrast to 4Tran-PCR, Capture-4Tran can uniquely identify both ends of an interaction that involve retroviral repeat sequences, providing a powerful tool for uncovering the individual TE insertions that interact with, and potentially regulate target genes.

Conclusions

4Tran provides new insight into the manner in which transposons contribute to chromosome architecture and identifies target genes that transposable elements can potentially control.
Role of the default mode network in cognitive transitions
Authors: Smith Verity , Mitchell Daniel J , Duncan John
Published: April 2018

A frequently repeated finding is that the default mode network (DMN) shows activation decreases during externally-focused tasks. This finding has led to an emphasis in DMN research on internally-focused self-relevant thought processes. A recent study, in contrast, implicates the DMN in substantial externally-focused task switches. Using functional magnetic resonance imaging, we scanned 24 participants performing a task switch experiment. Whilst replicating previous DMN task switch effects, we also found large DMN increases for brief rests as well as task restarts after rest. Our findings are difficult to explain using theories strictly linked to internal or self-directed cognition. In line with principal results from the literature, we suggest that the DMN encodes scene, episode or context, by integrating spatial, self-referential and temporal information. Context representations are strong at rest, but re-reference to context also occurs at major cognitive transitions.
An intrinsic cell cycle timer terminates limb bud outgrowth
Authors: Pickering Joseph , Chinnaiya Kavitha , Rich Constance A. , Saiz-Lopez Patricia , Ros Maria A. , Towers Matthew
Published: April 2018

The longstanding view of how proliferative outgrowth terminates following the patterning phase of limb development involves the breakdown of reciprocal extrinsic signalling between the mesenchyme and the overlying epithelium (e-m signalling). However, by grafting mesenchyme cells from late stage chick wing buds to an early epithelial environment we show that this mechanism is not required. RNA sequencing reveals that mesenchyme cells terminate growth by an intrinsic cell cycle timer in the presence of e-m signalling. In this process, e-m signalling is required permissively to allow the intrinsic cell cycle timer to run its course. We provide evidence that a temporal switch from BMP antagonism to BMP signalling controls the intrinsic cell cycle timer during limb outgrowth. Our findings have general implications for other patterning systems in which extrinsic signals and intrinsic timers are integrated.
Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis
Authors: Kim Soo-Hyun , Redvers Richard P. , Chi Lap Hing , Ling Xiawei , Lucke Andrew J. , Reid Robert C. , Fairlie David P. , Baptista Moreno Martin Ana Carolina , Anderson Robin L. , Denoyer Delphine , Pouliot Normand
Published: April 2018

Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours. By immunohistochemistry, 4T1Br4 tumours and brain metastases display a triple negative phenotype, consistent with the high propensity of this breast cancer subtype to spread to brain.In vitroassays indicate that 4T1Br4 cells have an enhanced ability to adhere to or migrate across a brain-derived endothelial monolayer and greater invasive response to brain-derived soluble factors compared to 4T1 cells. These properties are likely to contribute to the brain-selectivity of 4T1Br4 tumours. Expression profiling and gene set enrichment analyses demonstrate the clinical relevance of the 4T1Br4 model at the transcriptomic level. Pathway analyses implicate tumour-intrinsic immune regulation and vascular interactions in successful brain colonisation, revealing potential therapeutic targets. Evaluation of two histone deacetylase inhibitors, SB939 and 1179.4b, shows partial efficacy against 4T1Br4 metastasis to brain and other sitesin vivoand potent radio-sensitising propertiesin vitro. The 4T1Br4 model provides a clinically relevant tool for mechanistic studies and to evaluate novel therapies against brain metastasis.

SUMMARY STATEMENT

We introduce a new syngeneic mouse model of spontaneous breast cancer brain metastasis, demonstrate its phenotypic, functional and transcriptomic relevance to human TNBC brain metastasis and test novel therapies.
Connectivity Patterns in Cognitive Control Networks Predict Naturalistic Multitasking Ability
Authors: Wen Tanya , Liu De-Cyuan , Hsieh Shulan
Published: April 2018

Multitasking is a fundamental aspect of everyday life activities. To achieve a complex, multi-component goal, the tasks must be subdivided into sub-tasks and component steps, a critical function of prefrontal networks. The prefrontal cortex is considered to be organized in a cascade of executive processes from the sensorimotor to anterior prefrontal cortex, which includes execution of specific goal-directed action, to encoding and maintaining task rules, and finally monitoring distal goals. In the current study, we used a virtual multitasking paradigm to tap into real-world performance and relate it to each individual’s resting-state functional connectivity in fMRI. While did not find any correlation between global connectivity of any of the major networks with multitasking ability, global connectivity of the lateral prefrontal cortex (LPFC) was predictive of EVET score. Further analysis showed that multivariate connectivity patterns within the sensorimotor network (SMN), and between-network connectivity of the frontopartietal network (FPN) and dorsal attention network (DAN), predicted individual multitasking ability and could be generalized to novel individuals. Together, these results support previous research that prefrontal networks underlie multitasking abilities and show that connectivity patterns in the cascade of prefrontal networks may explain individual differences in performance.
New tools for carbohydrate sulphation analysis: Heparan Sulphate 2-O-sulphotranserase (HS2ST) is a target for small molecule protein kinase inhibitors
Authors: Byrne Dominic P , Li Yong , Ramakrishnan Krithika , Barsukov Igor L , Yates Edwin A , Eyers Claire E , Papy-Garcia Dulcé , Chantepie Sandrine , Pagadala Vijayakanth , Liu Jian , Wells Carrow , Drewry David H , Zuercher William J , Berry Neil G , Fernig David G , Eyers Patrick A
Published: April 2018

Sulphation of carbohydrate residues occurs on a variety of glycans destined for secretion, and this modification is essential for efficient matrix-based signal transduction. Heparan sulphate (HS) glycosaminoglycans control physiological functions ranging from blood coagulation to cell proliferation. HS biosynthesis involves membrane-bound Golgi sulphotransferases, including heparan sulphate 2-O-sulphotransferase (HS2ST), which transfers sulphate from the co-factor PAPS (3’-phosphoadenosine 5’-phosphosulphate) to the 2-Oposition of α-L-iduronate in the maturing oligosaccharide chain. The current lack of simple non-radioactive enzyme assays that can be used to quantify the levels of carbohydrate sulphation hampers kinetic analysis of this process and the discovery of HS2ST inhibitors. In this paper, we describe a new procedure for thermal shift analysis of purified HS2ST. Using this approach, we quantify HS2ST-catalyzed oligosaccharide sulphation using a novel synthetic fluorescent substrate and screen the Published Kinase Inhibitor Set (PKIS), to evaluate compounds that inhibit catalysis. We report the susceptibility of HS2ST to a variety of cell permeable compoundsin vitro, including polyanionic polar molecules, the protein kinase inhibitor rottlerin and oxindole-based RAF kinase inhibitors. In a related study, published back-to-back with this article, we demonstrate that Tyrosyl Protein Sulpho Tranferases (TPSTs) are also inhibited by a variety of protein kinase inhibitors. We propose that appropriately validated small molecule compounds could become new tools for rapid inhibition of glycan (and protein) sulphation in cells, and that protein kinase inhibitors might be repurposed or redesigned for the specific inhibition of HS2ST.

SUMMARY STATEMENT

We report that HS2ST, which is a PAPS-dependent glycan sulphotransferase, can be assayed using a variety of novel biochemical procedures, including a non-radioactive enzyme-based assay that detects glycan substrate sulphation in real time. HS2ST activity can be inhibited by different classes of compounds, including known protein kinase inhibitors, suggesting new approaches to evaluate the roles of HS2ST-dependent sulphation with small molecules in cells.
Cluster Failure Revisited: Impact of First Level Design and Data Quality on Cluster False Positive Rates
Authors: Eklund Anders , Knutsson Hans , Nichols Thomas E.
Published: April 2018

Methodological research rarely generates a broad interest, yet our work on the validity of cluster inference methods for functional magnetic resonance imaging (fMRI) created intense discussion on both the minutia of our approach and its implications for the discipline. In the present work, we take on various critiques of our work and further explore the limitations of our original work. We address issues about the particular event-related designs we used, considering multiple event types and randomisation of events between subjects. We consider the lack of validity found with onesample permutation (sign ipping) tests, investigating a number of approaches to improve the false positive control of this widely used procedure. We found that the combination of a two-sided test and cleaning the data using ICA FIX resulted in nominal false positive rates for all datasets, meaning that data cleaning is not only important for resting state fMRI, but also for task fMRI. Finally, we discuss the implications of our work on the fMRI literature as a whole, estimating that at least 10% of the fMRI studies have used the most problematic cluster inference method (P = 0.01 cluster defining threshold), and how individual studies can be interpreted in light of our findings. These additional results underscore our original conclusions, on the importance of data sharing and thorough evaluation of statistical methods on realistic null data.
Crystal structure of (E)-1,2-diferrocenyl-1,2-bis(furan-2-yl)ethene
Authors: Linden Anthony , Hamera-Fałdyga Róża , Mlostoń Grzegorz , Heimgartner Heinz
Published: April 2018

The title compound, [Fe2(C5H5)2(C20H14O2)], is the product of a new synthetic route towards tetraaryl/hetaryl-substituted ethenes that reduces the occurrence of side-products. In the crystal, the molecule is centrosymmetric and the cyclopentadienyl (Cp) rings are nearly coplanar and aligned slightly closer to a staggered conformation than to an eclipsed one. The ethene plane is tilted by 32.40 (18)° with respect to that of the substituted Cp ring and by 63.19 (19)° with respect to that of the furan ring. C—H...π interactions link the molecules into a three-dimensional supramolecular framework.
X-ray and UV radiation-damage-induced phasing using synchrotron serial crystallography
Authors: Foos Nicolas , Seuring Carolin , Schubert Robin , Burkhardt Anja , Svensson Olof , Meents Alke , Chapman Henry N. , Nanao Max H.
Published: April 2018

Specific radiation damage can be used to determine phasesde novofrom macromolecular crystals. This method is known as radiation-damage-induced phasing (RIP). One limitation of the method is that the dose of individual data sets must be minimized, which in turn leads to data sets with low multiplicity. A solution to this problem is to use data from multiple crystals. However, the resulting signal can be degraded by a lack of isomorphism between crystals. Here, it is shown that serial synchrotron crystallography in combination with selective merging of data sets can be used to determine high-quality phases for insulin and thaumatin, and that the increased multiplicity can greatly enhance the success rate of the experiment.
Projecting Canadian Prairie Runoff for 2041–2070 with North American Regional Climate Change Assessment Program (NARCCAP) Data
Authors: St‐Jacques Jeannine‐Marie , Andreichuk Yuliya , Sauchyn David J. , Barrow Elaine
Published: April 2018

The South Saskatchewan River Basin (SSRB) of Alberta, Canada, is semiarid and under severe water stress due to increasing human demands. We present the first examination of projected changes in SSRB runoff from a large set of North American Regional Climate Change Assessment Program regional climate models (RCMs) plus one Coordinated Regional Climate Downscaling Experiment RCM. We used six different runoff estimation methods: total surface and subsurface runoff (total runoff), surface runoff, and four estimations based on Budyko functions. Most RCM estimations showed substantial biases and distribution differences when compared to observed data; thus bias correction was necessary. Total runoff was the best of the six variables in modeling observed runoff for each of the four SSRB subbasins. Projected total runoff for 2041–2070 shows a geographic gradient in the SSRB, with possible drying in the southern Oldman River subbasin and possible increased runoff in the northernmost Red Deer River subbasin. A shift to an earlier spring peak in runoff and drier late summer, with a need for increased irrigation, should be expected. In a first examination of the important question of projected changes in interannual variability, we show increasing magnitude. This result further adds to adaptation challenges over the course of this century in this basin, which is already largely closed to further allocation.
Let's talk about sex: A rigorous statistical framework to assign the sex of individuals from reduced‐representation sequencing data
Authors: Moore Jean‐Sébastien , Benestan Laura
Published: April 2018

Molecular markers have been used to identify the sex of sampled individuals for several decades, but the time‐consuming development phase prevented their application in many systems. Recently, a growing number of papers have applied reduced‐representation sequencing (RRS) protocols to the identification of sex‐specific markers without the use of test crosses or prior genomic information. While such an approach has great advantages in terms of versatility and ease of use, the “shotgun sequencing” nature ofRRSdata sets leads to a high amount of missing data, which results in statistical challenges to the confident assignment of sex to individuals. In this issue of Molecular Ecology Resources, Stovall et al. (Molecular Ecology Resources, 18, 2018) provide a statistical framework to answer two questions: (1) how many individuals of one sex only must possess a genotype for this locus to be considered significantly sex‐specific? and (2) How many sex‐specific loci must an individual of unknown sex possess (in a given data set) to be confidently assigned a sex? The statistical pipeline introduced, and applied to samples of New Zealand fur seal (Arctocephalus forsteri) to identify 90 sex‐specific loci, should be broadly applicable to a large number of species and constitutes a nice addition to the molecular ecology toolkit in the genomics era.
Radiology and biomarkers in assessing disease activity in Takayasu arteritis
Authors: Sun Ying , Huang Qingrong , Jiang Lindi
Published: April 2018

Takayasu arteritis (TA) is a rare and chronic large‐vessel vasculitis that predominantly affects aorta and its main branches. It occurs mainly in females <40 years. Precise assessment of disease activity is one of the major difficulties in the long‐term management of TA. Until now, the accuracy of traditional activity index is still controversial. During these years, due to rapid development of radiological technology and researches of pathogenesis, new measurements and biomarkers have been applied to monitor disease activity for TA. Thus, in this review, we mainly discuss the benefits and limitations of recent developments of radiology and biomarkers for disease activity assessment in TA.
Takayasu arteritis and giant cell arteritis: are they a spectrum of the same disease?
Authors: Kermani Tanaz A.
Published: April 2018

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are forms of large‐vessel vasculitides that affect the aorta and its branches. There is ongoing debate about whether they are within a spectrum of the same disease or different diseases. Shared commonalities include clinical features, evidence of systemic inflammation, granulomatous inflammation on biopsy, role of T‐helper (Th)‐1 and Th17 in the pathogenesis, and, abnormalities of the aorta and its branches on imaging. However, there are also several differences in the geographic distribution, genetics, inflammatory cells and responses to treatment. This review highlights the similarities and differences in the epidemiology, pathogenesis, clinical manifestations, imaging findings and treatment responses in these conditions. Current data supports that they are two distinct conditions despite the numerous similarities.