bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness and reliability of cell free fetal DNA screening for main trisomies in case of atypical profile on first trimester maternal serum screening
Authors: Carrara Julie , Vivanti Alexandre , Jani Jacques C. , Demain Adèle , Costa Jean-Marc , Benachi Alexandra 
Published: November 2019

AbstractBackgroundPatients with atypical values of HCG and/or PAPP-A are at higher risk of chromosomal abnormality and vascular complications of pregnancy. The performance of cfDNA in this particular population has not yet been evaluated.ObjectivesThe primary objective was to evaluate the usefulness and reliability of cfDNA in screening for trisomy 21, 18 and 13 for patients with HCG < 0.25 multiple of median (MoM), HCG > 5.0 MoM and/or PAPP-A < 0.25 MoM, PAPP-A > 2.5 MoM. The secondary objective was to evaluate the contribution of cfDNA assay for the prediction of pregnancy’s vascular complications.MethodBetween June 2016 and July 2017, we analysed a women cohort from all over France who had at least one first trimester serum biomarker outside of normal range, in a retrospective, observational and multicentre study. Patients were included if they had a single pregnancy, normal first trimester ultrasound examination, whatever the result of the combined first trimester screening test was. The cfDNA was analysed by massive parallel sequencing technique. The accuracy of cfDNA assay was evaluated by calculation of sensitivity and specificity, and multivariate regression analysis was used to search for predictive factors for pregnancy’s vascular complications.ResultsAmong the 498 patients who underwent a cfDNA assay in this context, twenty-one (4.2%) were excluded because of loss to follow-up. Out of 477, test failure occurred for four patients initially, reduced to two patients (0.4%) after redrawn. CfDNA was positive for Trisomy 21 (n = 19), Trisomy 18 (n = 6) and Trisomy 13 (n = 1) and negative in 449. The sensitivity of cfDNA assay for trisomy 21 screening was 100% (19/19) (IC 95% 82.4–100) and specificity 100% (458/458) (IC 95% 99.2–100). Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was identified. Intra Uterine growth restriction under 5th percentile (n = 44, 9.8%) was significantly associated with a low fetal fraction (OR = 0.87, IC 95% 0.79–0.96, p = 0.006).ConclusioncfDNA assay is an effective and reliable tool for women with atypical profile of first trimester serum biomarkers.
21st-century capitalism: structural challenges for universal health care
Authors: Sell Susan K. 
Published: November 2019

AbstractThe structural perspective outlined here sheds light on some of the fundamental challenges involved in achieving Universal Health Care (UHC) in this twenty-first-century era of trade and financialized capitalism. This commentary explores connections between the structure of twenty-first-century capitalism and challenges to achieving UHC, discussing three features of today’s capitalism: financialized capitalism; trade, intangibles and global value chains; and inequality (as exacerbated by the first two features). The final section discusses the various opportunities for reform to facilitate UHC—from tinkering with the status quo, to deeper regulatory reform and fundamental structural change.
A mindfulness and compassion-based program applied to pregnant women and their partners to decrease depression symptoms during pregnancy and postpartum: study protocol for a randomized controlled trial
Authors: Sacristan-Martin Olga , Santed Miguel A. , Garcia-Campayo Javier , Duncan Larissa G. , Bardacke Nancy , Fernandez-Alonso Carmen , Garcia-Sacristan Gloria , Garcia-Sacristan Diana , Barcelo-Soler Alberto , Montero-Marin Jesus 
Published: November 2019

Abstract
Background
Pregnancy and the postpartum period are times of great change for women and their partners, often bringing substantial challenges and stress. Approximately 10%–20% of women suffer from mood disorders such as depression in the perinatal period. There are risks involved in using psychopharmacological interventions to treat perinatal depression. Mindfulness and compassion-based educational programs could be efficacious and cost-effective options for the prevention and treatment of perinatal mood disorders. The aim of this study is to assess the efficacy of an adapted Mindfulness-Based Childbirth and Parenting (MBCP) program that includes compassion training for pregnant women in primary care (PC) settings in the Spanish National Health System to decrease perinatal depression.

Methods
A multicenter randomized controlled trial (RCT) will be conducted. Participants will be pregnant women (n = 122) and their partners who wish to participate. They will be enrolled and assessed in PC settings and randomly assigned to either: (1) an adapted MBCP educational program tailored to the Spanish National Health System + treatment as usual (TAU); or (2) TAU only. The main outcome to be assessed will be depression, evaluated with the Edinburgh Postnatal Depression Scale (EPDS). Secondary outcomes will include self-reported measures of perceived stress, affects, mindfulness, self-compassion, maternal self-efficacy, and use of health and social services. Patients will be assessed at four timepoints: baseline; post-treatment; and at three and six months after childbirth. Intention-to-treat and per-protocol analyses will be carried out using linear regression mixed models. Effect sizes will be estimated using Cohen’s d.

Discussion
Perinatal depression is a significant health problem. An effective and low-cost childbirth education program that incorporates mindfulness and compassion practices may be a beneficial preventive complementary healthcare modality for expectant women and their partners. This study will be the first multicenter RCT in Spanish PC settings using adapted MBCP and compassion practices to reduce symptoms of depression during pregnancy and the postpartum period.

Trial registration
ClinicalTrials.gov, NCT03247491. Registered on 31 July 2017.
Risk stratification and clinical course of hepatitis B virus reactivation in rheumatoid arthritis patients with resolved infection: final report of a multicenter prospective observational study at Japanese Red Cross Hospital
Authors: Fukuda Wataru , Hanyu Tadamasa , Katayama Masaki , Mizuki Shinichi , Okada Akitomo , Miyata Masayuki , Handa Yuichi , Hayashi Masatoshi , Koyama Yoshinobu , Arii Kaoru , Kitaori Toshiyuki , Hagiyama Hiroyuki , Urushidani Yoshinori , Yamasaki Takahito , Ikeno Yoshihiko , Suzuki Takeshi , Omoto Atsushi , Sugitani Toshifumi , Morita Satoshi , Inokuma Shigeko 
Published: November 2019

Abstract
Background
The prophylaxis for hepatitis B virus (HBV) reactivation assumes that hepatic injury after reactivation is often rapidly progressive and can evoke fulminant hepatitis. The incidence and prognosis of reactivation in patients with rheumatoid arthritis (RA) may be different from those receiving organ transplantation and cancer chemotherapy. This study aimed to investigate the incidence, risk factors, and clinical course of HBV reactivation and develop a scoring system for risk stratification in RA patients with resolved infection.

Methods
HBV DNA was measured using real-time polymerase chain reaction, and patient data were collected for 4 years in RA patients with resolved HBV infection who were treated with steroids or synthetic or biologic immunosuppressive drugs.

Results
Among 1127 patients, HBV DNA was detected in 57 patients (1.65/100 person-years); none of the reactivated patients exhibited worsening of hepatic function. Multivariate logistical analysis revealed that age > 70 years and HB core antibody (HBcAb) positivity alone were independent risk factors for HBV reactivation. HBV DNA ≥ 2.1 log copies/mL was observed in 15 patients (0.43/100 person-years); seven patients were treated with nucleic acid analogs (NAAs), whereas the remaining eight were observed without treatment. Among reactivated cases, 15 cases changed to HBV DNA-negative status spontaneously, whereas 24 cases remained HBV DNA positive < 2.1 log copies/mL during the observation period. We designed the following scoring system: HBV reactivation risk score = 1 × (age > 70 years) + 2 × (HBcAb positivity alone) + 1 × (treatment other than methotrexate monotherapy). This revealed that patients with the highest score had an odds ratio of 13.01 for HBV reactivation, compared to those with the lowest score.

Conclusions
Rapid progression and poor outcomes after HBV reactivation were not frequent in RA patients with resolved infection. Our new risk scoring system might be useful for screening and optimization of prophylactic treatment by distinguishing patients with significantly lower reactivation risk.
An exploration of the gut and environmental resistome in a community in northern Vietnam in relation to antibiotic use
Authors: Bich Vu Thi Ngoc , Thanh Le Viet , Thai Pham Duy , Van Phuong Tran Thi , Oomen Melissa , Driessen Christel , Beuken Erik , Hoang Tran Huy , van Doorn H. Rogier , Penders John , Wertheim Heiman F. L. 
Published: November 2019

Abstract
Background
Antibiotic resistance is a major global public health threat. Antibiotic use can directly impact the antibiotic resistant genes (ARGs) profile of the human intestinal microbiome and consequently the environment through shedding.

Methods
We determined the resistome of human feces, animal stools, human food and environmental (rain, well, and irrigative water) samples (n = 304) in 40 households within a community cohort and related the data to antibiotic consumption. Metagenomic DNA was isolated and qPCR was used to determine presence of mobile colistin resistance (mcr) genes, genes encoding extended-spectrum β-lactamases (ESBL), carbapenemases and quinolone resistance genes.

Results
Nearly 40 % (39.5%, 120/304) of samples contained ESBL genes (most frequent were CTX-M-9 (23.7% [72/304]), CTX-M-1 (18.8% [57/304]). Quinolone resistance genes (qnrS) were detected in all human and 91% (41/45) of animal stool samples. Mcr-1 and mcr-3 were predominantly detected in human feces at 88% (82/93) and 55% (51/93) and animal feces at 93% (42/45) and 51% (23/45), respectively. Mcr-2, mrc-4 and mcr-5 were not detected in human feces, and only sporadically (< 6%) in other samples. Carbapenemase-encoding genes were most common in water (15% [14/91]) and cooked food (13% [10/75]) samples, while their prevalence in human and animal stools was lower at 4% in both human (4/93) and animal (2/45) samples. We did not find an association between recent antibiotic consumption and ARGs in human stools. Principal component analysis showed that the resistome differs between ecosystems with a strong separation of ARGs profiles of human and animal stools on the one hand versus cooked food and water samples on the other.

Conclusions
Our study indicated that ARGs were abundant in human and animal stools in a rural Vietnamese community, including ARGs targeting last resort antibiotics. The resistomes of animal and human stools were similar as opposed to the resistomes from water and food sources. No association between antibiotic use and ARG profiles was found in a setting of high background rates of AMR.
Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms
Authors: Lorenz David R. , Misra Vikas , Gabuzda Dana 
Published: November 2019

AbstractBackgroundTobacco smoking induces immunomodulatory and pro-inflammatory effects associated with transcriptome changes in monocytes and other immune cell types. While smoking is prevalent in HIV-infected (HIV+) individuals, few studies have investigated its effects on gene expression in this population. Here, we report whole-transcriptome analyses of 125 peripheral blood monocyte samples from ART-treated HIV+ and uninfected (HIV−) men enrolled in the Multicenter AIDS Cohort Study (MACS) (n =25 HIV+ smokers,n= 60 HIV+ non-smokers,n= 40 HIV− non-smoking controls). Gene expression profiling was performed using Illumina HumanHT-12 Expression BeadChip microarrays. Differential expression analysis was performed with weighted linear regression models using the Rlimmapackage, followed by functional enrichment and Ingenuity Pathway analyses.ResultsA total of 286 genes were differentially expressed in monocytes from HIV+ smokers compared with HIV− non-smokers; upregulated genes (n= 180) were enriched for immune and interferon response, chemical/stress response, mitochondria, and extracellular vesicle gene ontology (GO) terms. Expression of genes related to immune/interferon responses (AIM2,FCGR1A-B,IFI16,SP100), stress/chemical responses (APAF1,HSPD1,KLF4), and mitochondrial function (CISD1,MTHFD2,SQOR) was upregulated in HIV+ non-smokers and further increased in HIV+ smokers. Gene expression changes associated with smoking in previous studies of human monocytes were also observed (SASH1,STAB1,PID1,MMP25). Depressive symptoms (CES-D scores ≥ 16) were more prevalent in HIV+ tobacco smokers compared with HIV+ and HIV− non-smokers (50% vs. 26% and 13%, respectively;p= 0.007), and upregulation of immune/interferon response genes, includingIFI35,IFNAR1,OAS1-2,STAT1, andSP100, was associated with depressive symptoms in logistic regression models adjusted for HIV status and smoking (p< 0.05). Network models linked the Stat1-mediated interferon pathway to transcriptional regulator Klf4 and smoking-associated toll-like receptor scaffolding protein Sash1, suggesting inter-relationships between smoking-associated genes, control of monocyte differentiation, and interferon-mediated inflammatory responses.ConclusionsThis study characterizes immune, interferon, stress response, and mitochondrial-associated gene expression changes in monocytes from HIV+ tobacco smokers, and identifies augmented interferon and stress responses associated with depressive symptoms. These findings help to explain complex interrelationships between pro-inflammatory effects of HIV and smoking, and their combined impact on comorbidities prevalent in HIV+ individuals.
The anterolateral ligament of the knee joint: a review of the anatomy, biomechanics, and anterolateral ligament surgery
Authors: Ahn Ji Hyun , Patel Nilay A. , Lin Charles C. , Lee Thay Q. 
Published: November 2019

AbstractResidual knee instability and low rates of return to previous sport are major concerns after anterior cruciate ligament (ACL) reconstruction. To improve outcomes, surgical methods, such as the anatomical single-bundle technique or the double-bundle technique, were developed. However, these reconstruction techniques failed to adequately overcome these problems, and, therefore, new potential answers continue to be of great interest. Based on recent anatomical and biomechanical studies emphasizing the role of the anterolateral ligament (ALL) in rotational stability, novel surgical methods including ALL reconstruction and anterolateral tenodesis have been introduced with the possibility of resolving residual instability after ACL reconstruction. However, there is still little consensus on many aspects of the ALL, including: several anatomical issues, appropriate indications for ALL surgery, and the optimal surgical method and graft choice for reconstruction surgery. Therefore, further studies are necessary to advance our knowledge of the ALL and its contribution to knee stability.
Recruitment of ανβ3 integrin to α5β1 integrin-induced clusters enables focal adhesion maturation and cell spreading
Authors: Diaz Carolina , Neubauer Stefanie , Rechenmacher Florian , Kessler Horst , Missirlis Dimitris 
Published: November 2019

ABSTRACT
The major fibronectin (FN)-binding α5β1 and αvβ3 integrins exhibit cooperativity during cell adhesion, migration and mechanosensing, through mechanisms that are not yet fully resolved. Exploiting mechanically tunable nano-patterned substrates, and peptidomimetic ligands designed to selectively bind corresponding integrins, we report that focal adhesions (FAs) of endothelial cells assembled on α5β1 integrin-selective substrates rapidly recruit αvβ3 integrins, but not vice versa. Blocking of αvβ3 integrin hindered FA maturation and cell spreading on α5β1 integrin-selective substrates, indicating a mechanism dependent on extracellular ligand binding and highlighting the requirement of αvβ3 integrin engagement for efficient adhesion. Recruitment of αvβ3 integrins additionally occurred on hydrogel substrates of varying mechanical properties, above a threshold stiffness that supports FA formation. Mechanistic studies revealed the need for soluble factors present in serum to allow recruitment, and excluded exogenous, or endogenous, FN as the ligand responsible for αvβ3 integrin accumulation to adhesion clusters. Our findings highlight a novel mechanism of integrin cooperation and a critical role for αvβ3 integrins in promoting cell adhesion on α5β1 integrin-selective substrates.
B cells rapidly target antigen and surface-derived MHCII into peripheral degradative compartments
Authors: Hernández-Pérez Sara , Vainio Marika , Kuokkanen Elina , Šuštar Vid , Petrov Petar , Forstén Sofia , Paavola Vilma , Rajala Johanna , Awoniyi Luqman O. , Sarapulov Alexey V. , Vihinen Helena , Jokitalo Eija , Bruckbauer Andreas , Mattila Pieta K. 
Published: November 2019

ABSTRACT
In order to mount high-affinity antibody responses, B cells internalise specific antigens and process them into peptides loaded onto MHCII for presentation to T helper cells (TH cells). While the biochemical principles of antigen processing and MHCII loading have been well dissected, how the endosomal vesicle system is wired to enable these specific functions remains much less studied. Here, we performed a systematic microscopy-based analysis of antigen trafficking in B cells to reveal its route to the MHCII peptide-loading compartment (MIIC). Surprisingly, we detected fast targeting of internalised antigen into peripheral acidic compartments that possessed the hallmarks of the MIIC and also showed degradative capacity. In these vesicles, internalised antigen converged rapidly with membrane-derived MHCII and partially overlapped with cathepsin-S and H2-M, both required for peptide loading. These early compartments appeared heterogenous and atypical as they contained a mixture of both early and late endosomal markers, indicating a specialized endosomal route. Together, our data suggest that, in addition to in the previously reported perinuclear late endosomal MIICs, antigen processing and peptide loading could have already started in these specialized early peripheral acidic vesicles (eMIIC) to support fast peptide–MHCII presentation.
This article has an associated First Person interview with the first author of the paper.
Pan-SHIP1/2 inhibitors promote microglia effector functions essential for CNS homeostasis
Authors: Pedicone Chiara , Fernandes Sandra , Dungan Otto M. , Dormann Shawn M. , Viernes Dennis R. , Adhikari Arijit A. , Choi Lydia B. , De Jong Ebbing P. , Chisholm John D. , Kerr William G. 
Published: November 2019

ABSTRACT
We show here that both SHIP1 (Inpp5d) and its paralog SHIP2 (Inppl1) are expressed at protein level in microglia. To examine whether targeting of SHIP paralogs might influence microglial physiology and function, we tested the capacity of SHIP1-selective, SHIP2-selective and pan-SHIP1/2 inhibitors for their ability to impact on microglia proliferation, lysosomal compartment size and phagocytic function. We find that highly potent pan-SHIP1/2 inhibitors can significantly increase lysosomal compartment size, and phagocytosis of dead neurons and amyloid beta (Aβ)1−42 by microglia in vitro. We show that one of the more-potent and water-soluble pan-SHIP1/2 inhibitors, K161, can penetrate the blood-brain barrier. Consistent with this, K161 increases the capacity of CNS-resident microglia to phagocytose Aβ and apoptotic neurons following systemic administration. These findings provide the first demonstration that small molecule modulation of microglia function in vivo is feasible, and suggest that dual inhibition of the SHIP1 and 2 paralogs can provide a novel means to enhance basal microglial homeostatic functions for therapeutic purposes in Alzheimer's disease and, possibly, other types of dementia where increased microglial function could be beneficial.
Quantification of gas exchange-related upward motion of the liver during prolonged breathholding—potential reduction of motion artifacts in abdominal MRI
Authors: Khot Rachita , McGettigan Melissa , Patrie James T , Feuerlein Sebastian 
Published: November 2019

Objective:
To test the hypothesis that there is a measureable upward motion of the diaphragm during prolonged breath-holds that could have a detrimental effect on image quality in liver MRI and to identify factor that potentially influence the magnitude of this motion.

Methods:
15 healthy volunteers underwent MRI examination using prolonged breath-holds in the maximum inspiratory position and a moderate inspiratory position. Coronal T 1 weighted three-dimensional gradient echo sequences of the entire thorax were acquired every 6 s during breath-holding allowing the calculation of total lung volume and the measurement of the absolute position of the dome of the liver. The potential impact of subject’s gender, body mass index, and total lung capacity on the change in lung volume/diaphragmatic motion was assessed using random coefficient regression.

Results:
All volunteers demonstrated a slow reduction of the total lung volume during prolonged breath-holding up to 123 ml. There was a measurable associated upward shift of the diaphragm, measuring up to 5.6 mm after 24 s. There was a positive correlation with female gender (p = 0.037) and total lung volume (p = 0.005) and a negative association with BMI (p = 0.012) for the maximum inspiratory position only.

Conclusion:
There is a measureable reduction of lung volumes with consecutive upward shift of the diaphragm during prolonged breath-holding which likely contributes to motion artifacts in liver MRI.

Advances in knowledge:
There is a measureable gas exchange-related reduction of lung volumes with consecutive upward shift of the diaphragm during prolonged breath-holding which likely contributes to motion artifacts in liver MRI. Correcting for this predictable upward shift has potential to improve image quality.
The magnitude of this effect does not seem to be related to gender, BMI or total lung capacity if a moderate inspiratory position is used.