bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-synchronized immune-guided SBRT partial bulky tumor irradiation targeting hypoxic segment while sparing the peritumoral immune microenvironment
Authors: Tubin Slavisa , Ashdown Martin , Jeremic Branislav 
Published: December 2019

Abstract
Background
A novel unconventional SBRT-based PArtial Tumor irradiation targeting HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal bystander (BE) and abscopal effects (AE) was developed by translating our preclinical findings to a clinic in 2016. In order to further improve BE/AE response rate, SBRT-PATHY was upgraded in 2018 by the sparing of peritumoral immune microenvironment as a new OAR, defined by its own dose-constraints. Considering the anti-tumor immune response homeostatic fluctuation, which is cyclically suppressed and incited (“switched off and on”), we synchronized SBRT-PATHY with its most excitable phase, in order to overcome tumor tolerance locally and systemically. The aim of this study, therefore, was to report on the initial results of our latest innovation aimed to further improve BE/AE response rate by testing the effectiveness of the time-synchronized immune-guided SBRT-PATHY.

Materials and methods
In order to serially map the homeostatic anti-tumor immune response-fluctuations, High Sensitive C-Reactive Protein (HS-CRP), Lactate Dehydrogenase (LDH) and Lymphocyte/Monocyte Ratio (LMR) were analyzed using high-order polynomial trend analysis as surrogate of immune system response. After the biomarker data analysis detected the immune fluctuations and related idiosyncratic immune cycle periodicity, we determined the “most favourable” and “least favourable” treatment time-positions in the immune cycle. In order to evaluate the impact of an idiosyncratic immune cycle on treatment outcomes, our first consecutive four patients were treated on the “most favourable” while the remaining four on the “least favourable” day.

Results
The median follow-up was 11.8 months. The biomarker data analysis showed periodic immune response fluctuations of regular frequency. The “right” synchronization of SBRT-PATHY with the “most favorable day” of anti-tumor immune response was accompanied with improved clinical outcomes in terms of BE/AE-response rate.

Conclusion
We believe the right synchronization of radiotherapy with the homeostatically oscillating immune response may improve the probability of inducing BE/AE.
Present study has been retrospectively registered on 18th of October 2019 by the ethic committee for Austrian region „Kärnten “in Klagenfurt (AUT), under study number A 37/19.
Combination of mTORC1/2 inhibitor vistusertib plus fulvestrant in vitro and in vivo targets oestrogen receptor-positive endocrine-resistant breast cancer
Authors: Pancholi Sunil , Leal Mariana Ferreira , Ribas Ricardo , Simigdala Nikiana , Schuster Eugene , Chateau-Joubert Sophie , Zabaglo Lila , Hills Margaret , Dodson Andrew , Gao Qiong , Johnston Stephen R. , Dowsett Mitch , Cosulich Sabina C. , Maragoni Elisabetta , Martin Lesley-Ann 
Published: December 2019

Abstract
Background
Endocrine therapies are still the main strategy for the treatment of oestrogen receptor-positive (ER+) breast cancers (BC), but resistance remains problematic. Cross-talk between ER and PI3K/AKT/mTORC has been associated with ligand-independent transcription of ER. We have previously reported the anti-proliferative effects of the combination of everolimus (an mTORC1 inhibitor) with endocrine therapy in resistance models, but potential routes of escape via AKT signalling can lead to resistance; therefore, the use of dual mTORC1/2 inhibitors has met with significant interest.

Methods
To address this, we tested the effect of vistusertib, a dual mTORC1 and mTORC2 inhibitor, in a panel of endocrine-resistant and endocrine-sensitive ER+ BC cell lines, with varying PTEN, PIK3CA and ESR1 mutation status. End-points included proliferation, cell signalling, cell cycle and effect on ER-mediated transcription. Two patient-derived xenografts (PDX) modelling endocrine resistance were used to assess the efficacy of vistusertib, fulvestrant or the combination on tumour progression, and biomarker studies were conducted using immunohistochemistry and RNA-seq technologies.

Results
Vistusertib caused a dose-dependent decrease in proliferation of all the cell lines tested and reduced abundance of mTORC1, mTORC2 and cell cycle markers, but caused an increase in abundance of EGFR, IGF1R and ERBB3 in a context-dependent manner. ER-mediated transcription showed minimal effect of vistusertib. Combined therapy of vistusertib with fulvestrant showed synergy in two ER+ PDX models of resistance to endocrine therapy and delayed tumour progression after cessation of therapy.

Conclusions
These data support the notion that models of acquired endocrine resistance may have a different sensitivity to mTOR inhibitor/endocrine therapy combinations.
Dashing: fast and accurate genomic distances with HyperLogLog
Authors: Baker Daniel N. , Langmead Ben 
Published: December 2019

AbstractDashing is a fast and accurate software tool for estimating similarities of genomes or sequencing datasets. It uses the HyperLogLog sketch together with cardinality estimation methods that are specialized for set unions and intersections. Dashing summarizes genomes more rapidly than previous MinHash-based methods while providing greater accuracy across a wide range of input sizes and sketch sizes. It can sketch and calculate pairwise distances for over 87K genomes in 6 minutes. Dashing is open source and available athttps://github.com/dnbaker/dashing.
Fire needle acupuncture or moxibustion for chronic plaque psoriasis: study protocol for a randomized controlled trial
Authors: Chen Zhaoxia , Zhou Dongmei , Wang Yan , Lan Haibing , Duan Xingwu , Li Bohua , Zhao Jingxia , Li Wei , Liu Zhengrong , Di Tingting , Guo Xinwei , Zhang Jinchao , Li Bo , Feng Shuo , Li Ping 
Published: December 2019

Abstract
Background
Psoriasis is a chronic, immune-mediated disorder with chronic plaque psoriasis being the primary manifestation during the remission stage. Patients often have a slow course and long history of the disease. The refractory type of psoriasis is a stubborn rash that does not subside easily. We designed this randomized controlled trial to compare the effectiveness and relapse rates of plaque psoriasis in patients treated with either acupuncture, moxibustion or calcipotriol ointment. The ultimate aim of the study is to select an effective traditional Chinese medicine therapy for patients with plaque psoriasis.

Methods
The study will be a multicenter, prospective, randomized controlled trial that compares the effectiveness of fire needle therapy, moxibustion and calcipotriol ointment. In total, 160 patients with plaque psoriasis who meet the inclusion criteria will be recruited from three hospitals in Beijing and then randomly assigned to receive either fire needle therapy (group A1), moxibustion (group A2) or calcipotriol ointment (group B). All participants will receive an 8-week treatment and will then be followed up for another 24 weeks, with time points at weeks 12 and 24 after treatment completion. The primary outcomes to be measured are relapse rates and psoriasis area and severity index score of the target lesions. In addition, the target lesion onset time, dermatology life quality index, traditional Chinese medicine syndrome score, and the relapse interval of the target lesion will be measured. Adverse events will be recorded for safety assessment.

Discussion
The aim of this study is to determine whether fire needle therapy or moxibustion could improve the clinical effectiveness for psoriasis lesions and reduce the relapse rate. Once completed, it will provide information regarding therapeutic evaluation on fire needle therapy or moxibustion for plaque psoriasis, which will assist clinicians in selecting the most effective treatment options for patients.

Trial registration
International Clinical Trials Registry Platform (ICTRP), ChiCTR1800019588. Registered on 19 November 2018.
Effectiveness of upgraded maternity waiting homes and local leader training in improving institutional births among women in the Jimma zone, Ethiopia: study protocol for a cluster-randomized controlled trial
Authors: Kurji Jaameeta , Kulkarni Manisha A. , Gebretsadik Lakew Abebe , Wordofa Muluemebet Abera , Morankar Sudhakar , Bedru Kunuz Haji , Bulcha Gebeyehu , Thavorn Kednapa , Labonte Ronald , Taljaard Monica 
Published: December 2019

Abstract
Background
Ethiopia is one of the ten countries in the world that together account for almost 60% of all maternal deaths. Recent reductions in maternal mortality have been seen, yet just 26% of women who gave birth in Ethiopia in 2016 reported doing so at a health facility. Maternity waiting homes (MWHs) have been introduced to overcome geographical and financial barriers to institutional births but there is no conclusive evidence as to their effectiveness. We aim to evaluate the effects of upgraded MWHs and local leader training in increasing institutional births in the Jimma zone of Ethiopia.

Methods
A parallel, three-arm, stratified, cluster-randomized controlled trial design is being employed to evaluate intervention effects on institutional births, which is the primary outcome. Trial arms are: (1) upgraded MWH + religious/community leader training; (2) leader training alone; and (3) standard care. Twenty-four primary health care unit catchment areas (clusters) have been randomized and 3840 women of reproductive age who had a pregnancy outcome (livebirth, stillbirth or abortion) are being randomly recruited for each survey round. Outcome assessments will be made using repeat cross-sectional surveys at baseline and 24 months postintervention. An intention to treat approach will be used and the primary outcome analysed using generalized linear mixed models with a random effect for cluster and time. A cost-effectiveness analysis will also be conducted from a societal perspective.

Discussion
This is one of the first trials to evaluate the effectiveness of upgraded MWHs and will provide much needed evidence to policy makers about aspects of functionality and the community engagement required as they scale-up this programme in Ethiopia.

Trial registration
ClinicalTrial.gov, NCT03299491. Retrospectively registered on 3 October 2017.
Arthritis sensory and motor scale: predicting functional deficits from the clinical score in collagen-induced arthritis
Authors: Mausset-Bonnefont Anne-Laure , Cren Maïlys , Vicente Rita , Quentin Julie , Jorgensen Christian , Apparailly Florence , Louis-Plence Pascale 
Published: December 2019

Abstract
Background
In the collagen-induced arthritis (CIA) mouse model, inflammation readouts are usually quantified using operator-dependent clinical scoring systems, and no systematic relationship with functional deficits has been detected. In this study, we extensively quantified sensory and motor deficits in CIA mice during natural disease progression and therapeutic treatment. Then, we used these data to build a scale to predict functional deficits on the basis of the classical clinical score.

Methods
Using the CIA mouse model, we longitudinally screened multiple approaches to assess locomotion (open field test, Catwalk™), sensitivity (Von Frey, Hargreaves, static weight-bearing tests), and inflammation (skin temperature), and identified the most accurate tests to correlate sensory and motor deficits with disease severity, measured by clinical score. We then used these tests to characterize functional deficits in control (naïve and mice injected with complete Freund’s adjuvant) and CIA mice, either untreated or treated with methotrexate to prevent functional deficits. By mathematical approaches, we finally investigated the relationship between functional deficits and clinical score.

Results
We found that the functional disability scores obtained with the open field, Catwalk™, Hargreaves, and skin temperature tests significantly correlated with the clinical score in CIA mice, either untreated or treated with methotrexate. Mathematical correlation showed that motor deficits, robustly characterized by two different tests, were twice more responsive than thermal sensitivity deficits.

Conclusion
We propose the arthritis sensory and motor (ArthriSM) scale as a new theranostic tool to predict motor and sensory deficit based on the clinical score, in the experimental mouse model of CIA. This ArthriSM scale may facilitate the transfer of knowledge between preclinical and clinical studies.
Epigenome-wide base-resolution profiling of DNA methylation in chorionic villi of fetuses with Down syndrome by methyl-capture sequencing
Authors: Lim Ji Hyae , Kang Yu-Jung , Lee Bom Yi , Han You Jung , Chung Jin Hoon , Kim Moon Young , Kim Min Hyoung , Kim Jin Woo , Cho Youl-Hee , Ryu Hyun Mee 
Published: December 2019

Abstract
Background
Epigenetic mechanisms provide an interface between environmental factors and the genome and are influential in various diseases. These mechanisms, including DNA methylation, influence the regulation of development, differentiation, and establishment of cellular identity. Here, we performed high-throughput methylome profiling to determine whether differential patterns of DNA methylation correlate with Down syndrome (DS).

Materials and methods
We extracted DNA from the chorionic villi cells of five normal and five DS fetuses at the early developmental stage (12–13 weeks of gestation). Methyl-capture sequencing (MC-Seq) was used to investigate the methylation levels of CpG sites distributed across the whole genome to identify differentially methylated CpG sites (DMCs) and regions (DMRs) in DS. New functional annotations of DMR genes using bioinformatics tools were predicted.

Results
DNA hypermethylation was observed in DS fetal chorionic villi cells. Significant differences were evident for 4,439 DMCs, including hypermethylation (n = 4,261) and hypomethylation (n = 178). Among them, 140 hypermethylated DMRs and only 1 hypomethylated DMR were located on 121 genes and 1 gene, respectively. One hundred twenty-two genes, including 141 DMRs, were associated with heart morphogenesis and development of the ear, thyroid gland, and nervous systems. The genes were significantly associated with DS and various diseases, including hepatopulmonary syndrome, conductive hearing loss, holoprosencephaly, heart diseases, glaucoma, and musculoskeletal abnormalities.

Conclusions
This is the first study to compare the whole-epigenome DNA methylation pattern of the chorionic villi cells from normal and DS fetuses at the early developmental-stage using MC-seq. Overall, our results indicate that the chorionic villi cells of DS fetuses are hypermethylated in all autosomes and suggested that altered DNA methylation may be a recurrent and functionally relevant downstream response to DS in human cells. This study provides basic information for future research focused on the pathophysiology of the DS and its potential effects, as well as the role DNA methylation plays in the early developmental stage of DS fetuses.
Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity
Authors: Desiderio Antonella , Longo Michele , Parrillo Luca , Campitelli Michele , Cacace Giuseppe , de Simone Sonia , Spinelli Rosa , Zatterale Federica , Cabaro Serena , Dolce Pasquale , Formisano Pietro , Milone Marco , Miele Claudia , Beguinot Francesco , Raciti Gregory A. 
Published: December 2019

Abstract
Background
Obesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Ankyrin Repeat Domain 26 (Ankrd26) is involved in the development of both obesity and diabetes in mice and is modulated by environmentally induced epigenetic modifications. This study aims at investigating whether impaired ANKRD26 gene expression and methylation occur in human obesity and whether they correlate to the phenotype of these subjects.

Results
We found that downregulation of ANKRD26 mRNA and hyper-methylation of a specific region of the ANKRD26 promoter, embedding the CpG dinucleotides − 689, − 659, and − 651 bp, occur in peripheral blood leukocytes from obese compared with the lean subjects. ANKRD26 gene expression correlates inversely to the percentage of DNA methylation at these 3 CpG sites. Luciferase assays reveal a cause-effect relationship between DNA methylation at the 3 CpG sites and ANKRD26 gene expression. Finally, both ANKRD26 mRNA levels and CpG methylation correlate to body mass index and to the pro-inflammatory status and the increased cardio-metabolic risk factors of these same subjects.

Conclusion
Downregulation of the ANKRD26 gene and hyper-methylation at specific CpGs of its promoter are common abnormalities in obese patients. These changes correlate to the pro-inflammatory profile and the cardio-metabolic risk factors of the obese individuals, indicating that, in humans, they mark adverse health outcomes.
Mechanism(s) of prolonged attenuation of allergic responses after modulation of idiotypic regulatory network
Authors: Gorczynski R. M. , Maqbool T. , Hoffmann G. 
Published: December 2019

Abstract
Background
We showed previously that allergic reactivity to ovalbumin (OVA) could be regulated in mice following perturbation of immune networks using combinations of an immune Ig along with anti-idiotypic Ig. We have explored features of this regulation including: its persistence after cessation of administration of combined Igs; the ability of heterologous Igs to produce immunoregulation; a role for Treg induction in regulation; and the ability to attenuate responses in mice pre-sensitized to an allergic stimulus.

Methods
BALB/c mice were sensitized to OVA. Mice also received 5 weekly injections of immune Ig or anti-idiotype Ig (at separate sites) from either homologous (mouse) or heterologous (human) sources. In the latter case pooled IVIG (given IM, hence hereafter IMIG) was used as a source of anti-idiotype Ig, and human anti-Tet as immune Ig. Injections of the Ig were given from the time of OVA sensitization (to attenuate development of immunity), or after pre-sensitization of mice (to attenuate existing allergic responses). All mice were assayed for development of OVA-specific serum IgE and IgG, as well as the production of OVA-induced IL-2, IL-4, IL-13, IL-31 and IL-33 in splenocytes cultured for 72 h. In studies examining possible mechanism(s) responsible for inhibition of immunity mice received, in addition to the Ig treatments described, infusion of depleting anti-CD4, and/or anti-CD8 antibodies, or a mAb to TNFSFR25, known to expand Tregs implicated in regulation of Allo immunity.

Results
Combinations of both heterologous and homologous immune Igs and anti-idiotype Igs attenuated OVA allergic responses in both naïve and pre-sensitized mice. This attenuation persisted in mice greater than 14 weeks after cessation of treatment with the Igs used. Finally, depletion of either CD4 or CD8 cells ameliorated the suppressive effect seen, while the combination of anti-CD4 and anti-CD8 essentially abolished suppression. Suppression was further enhanced by anti-TNFSFR25 mAb.

Conclusions
We conclude that the combine Ig treatment protocols used produced a long-lasting suppression of allergic immunity, even in pre-sensitized animals. The effects seem to depend upon induction and expansion of Tregs and represents a novel approach to treatment of allergic disease in humans and other animals.
Non-neoplastic pathology at the crossroads between neck imaging and cardiothoracic imaging
Authors: Nguyen Trinh T. , Melendez Patricia E. , Kaproth-Joslin Katherine , Bhatt Alok A. 
Published: December 2019

AbstractThe thoracic inlet is located at the crossroads between imaging of the neck and chest. It represents an important anatomic landmark, serving as the central conducting pathway for many vital structures extending from the neck into the chest and vice versa. Many important body systems are located within this region, including the enteric, respiratory, vascular, lymphatic, neurologic, and endocrine systems. A detailed examination of this region is essential when reviewing neck and thoracic imaging. This article will discuss the normal anatomic boundaries of the thoracic inlet and present an image-rich systematic discussion of the non-neoplastic pathology that can occur in this region. The neoplastic pathology of the thoracic inlet will be covered in a companion article.
Congenital systemic venous return anomalies to the right atrium review
Authors: Oliveira João Diogo , Martins Isa 
Published: December 2019

AbstractCongenital anomalies of the systemic venous return to the right atrium are rare and stem from variations in the embryogenesis of the venous system. They are usually asymptomatic, and such the major clinical significance of their recognition is to prevent misdiagnosis, in addition to some having technical implications on invasive procedures.Typically, the venous blood from the upper half of the body is carried by the right-sided, superior vena cava (SVC), and some common congenital abnormalities found are persistent left SVC, SVC duplication, anomalous drainage of the brachiocephalic veins, or interruption of the SVC. The venous blood from the lower body is carried by the right-sided, inferior vena cava (IVC), and some common congenital abnormalities found are left-sided IVC, IVC duplication, the absence of IVC (total or just the infrarenal segment), and azygos continuation of the IVC. The azygos system of veins, running up the side of the thoracic vertebral column, connects both systems and can provide an alternative path to the right atrium when either of thevenae cavaeis absent. Other associated azygos-hemiazygos system anomalies are the azygos lobe and variable configuration of the azygos and hemiazygos veins.Such anomalies are reviewed with particular respect to their embryology and imagiological presentation, as knowledge of the normal anatomy and the most common congenital anomalies of the systemic venous return by a radiologist is important, being incidentally found.