bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different interventions for post-ischaemic stroke depression in different time periods: a single-blind randomized controlled trial with stratification by time after stroke
Authors: Gao Jie , Lin Meiqing , Zhao Jiuhan , Bi Siwei , Ni Ziyan , Shang Xiuli 
Published: January 2016

Objective: To determine the appropriate treatments for post-ischaemic stroke depression at different times after stroke. Design: A single-blind, randomized, controlled trial that compared three intervention groups, with subgroups stratified by time after stroke. Setting: Outpatient clinic. Subjects: Eligible patients were recruited at discharge ( n = 73) and three ( n = 67), six ( n = 65), and nine months ( n = 69) after discharge, and patients completed mood questionnaires. Interventions: Patients were randomly distributed into three groups: Group A received placebos and participated in general discussions; Group B, received citalopram and participated in general discussions; and Group C, received placebos and underwent cognitive behavioural therapy. All three groups participated in rehabilitation during three months of follow-up. Main measures: Outcome was assessed three months after baseline using the 17-item Hamilton Depression Scale (HAMD17) and the Bech–Rafaelsen Melancholia Scale (MES). During treatment, the Udvalg for Kliniske Undersogelser side-effect scale was also administered. Results: When stratification was not considered, the scores of Group B on the Melancholia Scale were lower than those of Group A ( P = 0.02); when the four time-based subgroups were analysed, significant differences were observed between Groups A and B (PMES = 0.02, PHAMD17 = 0.02) in the group recruited six months after discharge and between Groups A and C (PMES = 0.01) in the last time period nine months after discharge. Conclusions: The effects of citalopram or cognitive behavioural therapy is similar to the effect of rehabilitation alone for early-onset post-ischaemic depression; rehabilitation and citalopram for delayed-onset post-ischaemic depression; and rehabilitation and cognitive behavioural therapy for late-onset post-ischaemic depression are more effective than rehabilitation alone.
Biomechanical Effects of a Horizontal Medial Meniscal Tear and Subsequent Leaflet Resection
Authors: Brown Matthew J. , Farrell James P. , Kluczynski Melissa A. , Marzo John M. 
Published: January 2016

Background: Horizontal, degenerative tears of the medial meniscus and subsequent meniscectomy can compromise the biomechanical function of the meniscus in load transmission and weightbearing, leading to the development of radiographic and symptomatic tibiofemoral arthritis. Hypothesis: Resection of both leaflets of a horizontal medial meniscal tear will increase peak contact pressures and decrease contact areas in comparison with resection of only the inferior leaflet. Study Design: Controlled laboratory study. Methods: Twelve fresh-frozen human cadaveric knees had tibiofemoral peak contact pressures and contact areas under an 1800-N axial load measured by Tekscan in the control state. A horizontal tear was created in the posterior horn of the medial meniscus, and the knees were retested. The knees were tested a third time after resection of the inferior leaflet (single leaflet) and a final time after resection of the superior leaflet (both leaflets). The Friedman test was used to test for group differences in peak pressure (psi) and contact area (mm2) between test conditions (native, tear, inferior leaflet resection, and resection of both leaflets). Results: For the medial compartment, there was a statistically significant difference in peak pressure ( P = .03) but not in contact area ( P = .70) between testing conditions. Median peak pressure in the medial compartment was significantly greater for resection of both leaflets compared with the tear (406.5 vs 294.7 psi, respectively; P = .002). Median contact area in the medial compartment was greatest for resection of both leaflets (602.7 mm2), but there were no statistically significant differences between test conditions ( P = .70). For the lateral compartment, there were no statistically significant differences in peak pressure ( P = .99) or contact area ( P = .77) between test conditions. Conclusion: Resection of a single inferior leaflet after a horizontal medial meniscal tear preserves much of the original biomechanical function of the meniscus. Resection of both leaflets leads to a significant increase in contact pressure dispersed over the same contact area, which results in an undesirable biomechanical environment. Clinical Relevance: Arthroscopic inferior leaflet resection is a viable option for providing symptomatic relief of horizontal medial meniscal tears and preserves the ability of the meniscus to absorb axial loading on the knee joint, theoretically decreasing the risk of subsequent osteoarthritis.
Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis
Authors: Zhou Yuan , Zhu Gu , Charlesworth Jac C , Simpson Steve , Rubicz Rohina , Göring Harald HH , Patsopoulos Nikolaos A , Laverty Caroline , Wu Feitong , Henders Anjali , Ellis Jonathan J , van der Mei Ingrid , Montgomery Grant W , Blangero John , Curran Joanne E , Johnson Matthew P , Martin Nicholas G , Nyholt Dale R , Taylor Bruce V ,   ANZgene consortium
Published: January 2016

Background: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). Objective: We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. Methods: We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective sample size ( Neff) = 5555) and a large MS GWAS ( Neff = 15,231). Results: We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 ( p = 4.11 × 10−9). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP ( p = 3.32 × 10−20). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance ( p < 5 × 10−8). Conclusions: Our results suggest that apart from the confirmed HLA region, the association of anti-EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS.
Do on-demand irrigation warmers provide an adequate intraoperative rate of irrigation for holmium enucleation of the prostate?
Authors: Chapman Richard Alexander , Halliday Paul 
Published: January 2016

Introduction: On-demand irrigation warmers are widely used to provide a convenient way of irrigating warmed fluids for endoscopic procedure. However, concern has been raised that flow rates via these devices are inadequate for safe operating. Holmium enucleation of prostate (HoLEP) requires significant volume and flow rate of irrigation. Poiseuille’s Law states the resistance of a tube will result in reduced flow and a reduction in pressure across the tube. The aim was to compare the irrigation rates provided by one such warming device compared to a standard giving set whilst simulating HoLEP and to monitor intravesical pressure. Methods: A simulated apparatus was set up to replicate HoLEP surgery. Simulated design rather than ‘real-life’ apparatus was used to allow for repeated testing in a more controlled environment and to avoid other variables due to operative differences. Comparison of irrigation rate and pressure difference was measured whilst using a standard irrigation set (Fresenius Kabi) with pre-warmed fluid and the Ranger irrigation warming system (3M). Pressure was measured using a pressure line passed via the working channel of the laser resectoscope. Results: The standard giving set demonstrated lower resistance and higher irrigation rates. The irrigation rate was 31% higher (7.2 vs 5.5 ml/s). A lower change in pressure across the standard giving set was found (20 vs 38 cm H2O). The resistance therefore is much higher in the Ranger irrigation system, which gave a much slower flow and greater drop in pressure. Conclusion: This unique demonstration has led to a quantitative assessment of commonly used giving sets and has shown irrigation rates via a standard giving set are 31% greater than through the Ranger irrigation warming system. On-demand fluid warmers are felt to result in poor intraoperative vision and pose a potential risk to patient safety during HoLEP and other urological procedures requiring high fluid volumes.
Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms
Authors: Araki Marito , Yang Yinjie , Masubuchi Nami , Hironaka Yumi , Takei Hiraku , Morishita Soji , Mizukami Yoshihisa , Kan Shin , Shirane Shuichi , Edahiro Yoko , Sunami Yoshitaka , Ohsaka Akimichi , Komatsu Norio 
Published: January 2016

Key Points
Mutant CALR induces TPO-independent growth in the human megakaryocytic cell line UT-7/TPO. Mutant CALR binds to the TPO receptor, inducing phosphorylation of JAK2 and activating downstream signaling.
Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia
Authors: Bellon Marcia , Lu Ling , Nicot Christophe 
Published: January 2016

Key Points
Epigenetic silencing of miR-124a leads to constitutive STAT3 and activation of downstream Pim1. Pim1 kinase signaling is constitutively activated in ATL cells and represents a novel therapeutic target.
Inter-Strain Differences of Serotonergic Inhibitory Pain Control in Inbred Mice
Authors: Wijnvoord Nina , Albuquerque Boris , Häussler Annett , Myrczek Thekla , Popp Laura , Tegeder Irmgard 
Published: January 2016

Background: Descending inhibitory pain control contributes to the endogenous defense against chronic pain and involves noradrenergic and serotonergic systems. The clinical efficacy of antidepressants suggests that serotonin may be particularly relevant for neuropathic pain conditions. Serotonergic signaling is regulated by synthesis, metabolisms, reuptake and receptors. Results: To address the complexity, we used inbred mouse strains, C57BL/6J, 129 Sv, DBA/2J and Balb/c, which differ in brain serotonin levels. Serotonin analysis after nerve injury revealed inter-strain differences in the adaptation of descending serotonergic fibers. Upregulation of spinal cord and midbrain serotonin was apparent only in 129 Sv mice and was associated with attenuated nerve injury evoked hyperalgesia and allodynia in this strain. The increase of dorsal horn serotonin was blocked by hemisectioning of descending fibers but not by rhizotomy of primary afferents indicating a midbrain source. Para-chlorophenylalanine-mediated serotonin depletion in spinal cord and midbrain intensified pain hypersensitivity in the nerve injury model. In contrast, chronic inflammation of the hindpaw did not evoke equivalent changes in serotonin levels in the spinal cord and midbrain and nociceptive thresholds dropped in a parallel manner in all strains. Conclusion: The results suggest that chronic nerve injury evoked hypernociception may be contributed by genetic differences of descending serotonergic inhibitory control.
Identification of molecular signatures specific for distinct cranial sensory ganglia in the developing chick
Authors: Patthey Cedric , Clifford Harry , Haerty Wilfried , Ponting Chris P. , Shimeld Sebastian M. , Begbie Jo 
Published: January 2016

Abstract

Background
The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process.

Results
Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq. Whole transcriptome analysis confirmed the division into somato- versus viscerosensory neurons, with additional evidence for subdivision of the somatic class into general and special somatosensory neurons. Cross-comparison of distinct ganglia transcriptomes identified a total of 134 markers, 113 of which are novel, which can be used to distinguish trigeminal, vestibulo-acoustic and epibranchial neuronal populations. In situ hybridisation analysis provided validation for 20/26 tested markers, and showed related expression in the target region of the hindbrain in many cases.

Conclusions
One hundred thirty-four high-confidence markers have been identified for placode-derived cranial sensory ganglia which can now be used to address the acquisition of specific cranial sensory modalities.
Double-blind, placebo-controlled, proof-of-concept trial of bexarotene in moderate Alzheimer’s disease
Authors: Cummings Jeffrey L. , Zhong Kate , Kinney Jefferson W. , Heaney Chelcie , Moll-Tudla Joanne , Joshi Abhinay , Pontecorvo Michael , Devous Michael , Tang Anne , Bena James 
Published: January 2016

Abstract
Background
We assessed the impact of retinoid X receptor (RXR) agonist bexarotene on brain amyloid measured by amyloid imaging in patients with Alzheimer’s disease (AD) in a proof-of-concept trial.

Methods
Twenty patients with AD [Mini Mental State Examination (MMSE) score 10–20 inclusive] with positive florbetapir scans were randomized to receive 300 mg of bexarotene or placebo for 4 weeks. The amyloid imaging result was the primary outcome. Whole-population analyses and prespecified analyses by genotype [apolipoprotein E ε4 (ApoE4) carriers and ApoE4 noncarriers] were conducted. Secondary outcomes included scores on the Alzheimer’s Disease Assessment Scale–Cognitive subscale, Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale, MMSE, Clinical Dementia Rating scale, and Neuropsychiatric Inventory. Serum amyloid-β (Aβ) peptide sequences Aβ1–40 and Aβ1–42 measurements were collected as biomarker outcomes.

Results
There was no change in the composite or regional amyloid burden when all patients were included in the analysis. ApoE4 noncarriers showed a significant reduction in brain amyloid on the composite measure in five of six regional measurements. No change in amyloid burden was observed in ApoE4 carriers. There was a significant association between increased serum Aβ1–42 and reductions in brain amyloid in ApoE4 noncarriers (not in carriers). There were significant elevations in serum triglycerides in bexarotene-treated patients. There was no consistent change in any clinical measure.

Conclusions
The primary outcome of this trial was negative. The data suggest that bexarotene reduced brain amyloid and increased serum Aβ1–42 in ApoE4 noncarriers. Elevated triglycerides could represent a cardiovascular risk, and bexarotene should not be administered outside a research setting. RXR agonists warrant further investigations as AD therapies.

Trial registration
ClinicalTrials.gov identifier NCT01782742. Registered 29 January 2013.
Species-level resolution of 16S rRNA gene amplicons sequenced through the MinION™ portable nanopore sequencer
Authors: Benítez-Páez Alfonso , Portune Kevin J , Sanz Yolanda 
Published: January 2016

Abstract

Background
The miniaturised and portable DNA sequencer MinION™ has been released to the scientific community within the framework of an early access programme to evaluate its application for a wide variety of genetic approaches. This technology has demonstrated great potential, especially in genome-wide analyses. In this study, we tested the ability of the MinION™ system to perform amplicon sequencing in order to design new approaches to study microbial diversity using nearly full-length 16S rDNA sequences.

Results
Using R7.3 chemistry, we generated more than 3.8 million events (nt) during a single sequencing run. These data were sufficient to reconstruct more than 90 % of the 16S rRNA gene sequences for 20 different species present in a mock reference community. After read mapping and 16S rRNA gene assembly, consensus sequences and 2d reads were recovered to assign taxonomic classification down to the species level. Additionally, we were able to measure the relative abundance of all the species present in a mock community and detected a biased species distribution originating from the PCR reaction using ‘universal' primers.

Conclusions
Although nanopore-based sequencing produces reads with lower per-base accuracy compared with other platforms, the MinION™ DNA sequencer is valuable for both high taxonomic resolution and microbial diversity analysis. Improvements in nanopore chemistry, such as minimising base-calling errors and the nucleotide bias reported here for 16S amplicon sequencing, will further deliver more reliable information that is useful for the specific detection of microbial species and strains in complex ecosystems.
Complete genome sequence and genomic characterization of Microcystis panniformis FACHB 1757 by third-generation sequencing
Authors: Zhang Jun-Yi , Guan Rui , Zhang Hu-Jun , Li Hua , Xiao Peng , Yu Gong-Liang , Du Lei , Cao De-Min , Zhu Bing-Chuan , Li Ren-Hui , Lu Zu-Hong 
Published: January 2016

AbstractThe cyanobacterial genus Microcystis is well known as the main group that forms harmful blooms in water. A strain of Microcystis, M. panniformis FACHB1757, was isolated from Meiliang Bay of Lake Taihu in August 2011. The whole genome was sequenced using PacBio RS II sequencer with 48-fold coverage. The complete genome sequence with no gaps contained a 5,686,839 bp chromosome and a 38,683 bp plasmid, which coded for 6,519 and 49 proteins, respectively. Comparison with strains of M. aeruginosa and some other water bloom-forming cyanobacterial species revealed large-scale structure rearrangement and length variation at the genome level along with 36 genomic islands annotated genome-wide, which demonstrates high plasticity of the M. panniformis FACHB1757 genome and reveals that Microcystis has a flexible genome evolution.
Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology
Authors: Zhang Cuilin , Shi Zhun , Zhang Lingzhi , Zhou Zehua , Zheng Xiaoyuan , Liu Guiying , Bu Guojun , Fraser Paul E. , Xu Huaxi , Zhang Yun-wu 
Published: January 2016

ABSTRACT
Mitochondrial morphology is regulated by fusion and fission machinery. Impaired mitochondria dynamics cause various diseases, including Alzheimer's disease. Appoptosin (encoded by SLC25A38) is a mitochondrial carrier protein that is located in the mitochondrial inner membrane. Appoptosin overexpression causes overproduction of reactive oxygen species (ROS) and caspase-dependent apoptosis, whereas appoptosin downregulation abolishes β-amyloid-induced mitochondrial fragmentation and neuronal death during Alzheimer's disease. Herein, we found that overexpression of appoptosin resulted in mitochondrial fragmentation in a manner independent of its carrier function, ROS production or caspase activation. Although appoptosin did not affect levels of mitochondrial outer-membrane fusion (MFN1 and MFN2), inner-membrane fusion (OPA1) and fission [DRP1 (also known as DNM1L) and FIS1] proteins, appoptosin interacted with MFN1 and MFN2, as well as with the mitochondrial ubiquitin ligase MITOL (also known as MARCH5) but not OPA1, FIS1 or DRP1. Appoptosin overexpression impaired the interaction between MFN1 and MFN2, and mitochondrial fusion. By contrast, co-expression of MFN1, MITOL and a dominant-negative form of DRP1, DRP1K38A, partially rescued appoptosin-induced mitochondrial fragmentation and apoptosis, whereas co-expression of FIS1 aggravated appoptosin-induced apoptosis. Together, our results demonstrate that appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.
Associations between joint effusion in the knee and gene expression levels in the circulation: a meta-analysis
Authors: Peters Marjolein J. , Ramos Yolande F.M. , den Hollander Wouter , Schiphof Dieuwke , Hofman Albert , Uitterlinden André G. , Oei Edwin H.G. , Slagboom P. Eline , Kloppenburg Margreet , Bloem Johan L. , Bierma-Zeinstra Sita M.A. , Meulenbelt Ingrid , van Meurs Joyce B.J. 
Published: January 2016

Objective: To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation.Materials and Methods: Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI. To investigate enriched pathways and protein-protein interactions, we used the DAVID and STRING webtools.Results: In a meta-analysis, we identified 257 probes mapping to 189 unique genes in blood that were nominally significantly associated with joint effusion grades in the knee. Several compelling genes were identified such as C1orf38 and NFATC1. Significantly enriched biological pathways were: response to stress, gene expression, negative regulation of intracellular signal transduction, and antigen processing and presentation of exogenous pathways.Conclusion: Meta-analyses and subsequent enriched biological pathways resulted in interesting candidate genes associated with joint effusion that require further characterization. Associations were not transcriptome-wide significant most likely due to limited power. Additional studies are required to replicate our findings in more samples, which will greatly help in understanding the pathophysiology of OA and its relation to inflammation, and may result in biomarkers urgently needed to diagnose OA at an early stage.