bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative stress-mediated TXNIP loss causes RPE dysfunction
Authors: Ji Cho Min , Yoon Sung-Jin , Kim Wooil , Park Jongjin , Lee Jangwook , Park Jong-Gil , Cho Young-Lai , Hun Kim Jeong , Jang Hyejin , Park Young-Jun , Lee Sang-Hyun , Min Jeong-Ki 
Published: October 2019

Abstract
The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood–retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.
A population-based family clustering study of tic-related obsessive-compulsive disorder
Authors: Brander Gustaf , Kuja-Halkola Ralf , Rosenqvist Mina A. , Rück Christian , Serlachius Eva , Fernández de la Cruz Lorena , Lichtenstein Paul , Crowley James J. , Larsson Henrik , Mataix-Cols David 
Published: October 2019

AbstractIn the latest edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), obsessive-compulsive disorder (OCD) included a new “tic-related” specifier. However, strong evidence supporting tic-related OCD as a distinct subtype of OCD is lacking. This study investigated whether, at the population level, tic-related OCD has a stronger familial load than non-tic-related OCD. From a cohort of individuals born in Sweden between 1967 and 2007 (n = 4,085,367; 1257 with tic-related OCD and 20,975 with non-tic-related OCD), we identified all twins, full siblings, maternal and paternal half siblings, and cousins. Sex- and birth year-adjusted hazard ratios (aHR) were calculated to estimate the risk of OCD in relatives of individuals with OCD with and without comorbid tics, compared with relatives of unaffected individuals. We found that OCD is a familial disorder, regardless of comorbid tic disorder status. However, the risk of OCD in relatives of individuals with tic-related OCD was considerably greater than the risk of OCD in relatives of individuals with non-tic-related OCD (e.g., risk for full siblings: aHR = 10.63 [95% CI, 7.92–14.27] and aHR = 4.52 [95% CI, 4.06–5.02], respectively;pvalue for the difference < 0.0001). These differences remained when the groups were matched by age at first OCD diagnosis and after various sensitivity analyses. The observed familial patterns of OCD in relation to tics were not seen in relation to other neuropsychiatric comorbidities. Tic-related OCD is a particularly familial subtype of OCD. The results have important implications for ongoing gene-searching efforts.
Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis
Authors: Kelly Helen , Benavente Yolanda , Pavon Miquel Angel , De Sanjose Silvia , Mayaud Philippe , Lorincz Attila Tibor 
Published: October 2019

Abstract

Background
To conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+).

Methods
Medline and Embase databases were searched for studies of methylation markers versus histological endpoints. Pooled sensitivity, specificity and positive predictive value (PPV) for CIN2+ were derived from bivariate models. Relative sensitivity and specificity for CIN2+ compared to cytology and HPV16/18 genotyping were pooled using random-effects models.

Results
Sixteen thousand three hundred thirty-six women in 43 studies provided data on human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV16 (L1/L2). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. Pooled CIN2+ and CIN3+ prevalence was 36.7% and 21.5%. For a set specificity of 70%, methylation sensitivity for CIN2+ and CIN3+ were 68.6% (95% CI: 62.9–73.8) and 71.1% (95% CI: 65.7–76.0) and PPV were 53.4% (95% CI: 44.4–62.1) and 35.0% (95% CI: 28.9–41.6). Among HR-HPV+ women, the relative sensitivity of methylation for CIN2+ was 0.81 (95% CI: 0.63–1.04) and 1.22 (95% CI: 1.05–1.42) compared to cytology of atypical squamous cells of undetermined significance, or greater (ASCUS+) and HPV16/18 genotyping, respectively, while relative specificity was 1.25 (95% CI: 0.99–1.59) and 1.03 (95% CI: 0.94–1.13), respectively.

Conclusion
DNA methylation is significantly higher in CIN2+ and CIN3+ compared to ≤CIN1. As triage test, DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping.
5 year incidence of YAG capsulotomy and PCO after cataract surgery with single-piece monofocal intraocular lenses: a real-world evidence study of 20,763 eyes
Authors: Ursell Paul G. , Dhariwal Mukesh , O’Boyle Derek , Khan Javeed , Venerus Alessandra 
Published: October 2019

AbstractObjectivesTo evaluate the 3- and 5-year incidence of posterior capsule opacification (PCO) and neodymium-doped yttrium aluminium garnet (Nd:YAG) capsulotomy in patients following cataract surgery, comparing results for different single-piece acrylic hydrophilic and hydrophobic monofocal intraocular lens (IOL) models and other patient factors.Patients and methodsElectronic medical record data collected from seven United Kingdom (UK) National Health Service (NHS) ophthalmology clinics for routine, age-related (≥65 years) cataract surgeries that implanted single-piece acrylic monofocal IOLs during 2010–2013 were used to calculate 3- and 5-year incidence of Nd:YAG and PCO. IOL models of Alcon Acrysof, AMO Tecnis, Bausch & Lomb (B & L) Akreos, LenStec Softec, and Rayner Flex were analyzed. Pairwise comparisons were conducted between AcrySof IOLs and other IOLs using Bonferroni adjustment for multiplicity. Multivariate analyses were conducted adjusting for known confounders.ResultsThe incidence of Nd:YAG capsulotomy ranged between 2.4–12.6% at 3 years and 5.8–19.3% at 5 years post-cataract surgery. Similarly, the incidence of PCO ranged between 4.7–18.6% at 3 years and 7.1–22.6% at 5 years. When comparing all of the single-piece IOLs, AcrySof demonstrated the lowest incidence rates for both PCO and Nd:YAG (P < 0.001 for each comparison). From adjusted logistic regression analysis, AcrySof were associated with lower 3- and 5-year odds of Nd:YAG and PCO incidence.ConclusionsFollowing cataract surgery with single-piece monofocal IOLs different incidence rates of PCO were observed with different IOLs. AcrySof IOLs were associated with significantly lower incidence of PCO requiring Nd:YAG treatment over periods of 3 and 5 years.
Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism
Authors: Göppner Corinna , Orozco Ian J. , Hoegg-Beiler Maja B. , Soria Audrey H. , Hübner Christian A. , Fernandes-Rosa Fabio L. , Boulkroun Sheerazed , Zennaro Maria-Christina , Jentsch Thomas J. 
Published: October 2019

AbstractHuman primary aldosteronism (PA) can be caused by mutations in several ion channel genes but mouse models replicating this condition are lacking. We now show that almost all known PA-associated CLCN2 mutations markedly increase ClC-2 chloride currents and generate knock-in mice expressing a constitutively open ClC-2 Cl− channel as mouse model for PA. The Clcn2op allele strongly increases the chloride conductance of zona glomerulosa cells, provoking a strong depolarization and increasing cytoplasmic Ca2+ concentration. Clcn2op mice display typical features of human PA, including high serum aldosterone in the presence of low renin activity, marked hypertension and hypokalemia. These symptoms are more pronounced in homozygous Clcn2op/op than in heterozygous Clcn2+/op mice. This difference is attributed to the unexpected finding that only ~50 % of Clcn2+/op zona glomerulosa cells are depolarized. By reproducing essential features of human PA, Clcn2op mice are a valuable model to study the pathological mechanisms underlying this disease.
Genome-wide association mapping of date palm fruit traits
Authors: Hazzouri Khaled M. , Gros-Balthazard Muriel , Flowers Jonathan M. , Copetti Dario , Lemansour Alain , Lebrun Marc , Masmoudi Khaled , Ferrand Sylvie , Dhar Michael I. , Fresquez Zoë A. , Rosas Ulises , Zhang Jianwei , Talag Jayson , Lee Seunghee , Kudrna David , Powell Robyn F. , Leitch Ilia J. , Krueger Robert R. , Wing Rod A. , Amiri Khaled M. A. , Purugganan Michael D. 
Published: October 2019

AbstractDate palms (Phoenix dactylifera) are an important fruit crop of arid regions of the Middle East and North Africa. Despite its importance, few genomic resources exist for date palms, hampering evolutionary genomic studies of this perennial species. Here we report an improved long-read genome assembly for P. dactylifera that is 772.3 Mb in length, with contig N50 of 897.2 Kb, and use this to perform genome-wide association studies (GWAS) of the sex determining region and 21 fruit traits. We find a fruit color GWAS at the R2R3-MYB transcription factor VIRESCENS gene and identify functional alleles that include a retrotransposon insertion and start codon mutation. We also find a GWAS peak for sugar composition spanning deletion polymorphisms in multiple linked invertase genes. MYB transcription factors and invertase are implicated in fruit color and sugar composition in other crops, demonstrating the importance of parallel evolution in the evolutionary diversification of domesticated species.
Prognostic value of 18F-FDG brain PET as an early indicator of neurological outcomes in a rat model of post-cardiac arrest syndrome
Authors: Kim Daehee , Yoon Hai-Jeon , Lee Woon Jeong , Woo Seon Hee , Kim Bom Sahn 
Published: October 2019

AbstractPredicting neurological outcomes in patients with post-cardiac arrest syndrome (PCAS) is crucial for identifying those who will benefit from intensive care. We evaluated the predictive value of 18F-FDG PET. PCAS was induced in Sprague Dawley rats. Baseline and post-3-hour images were acquired. Standardized uptake value (SUV) changes before and after PCAS induction (SUVdelta) and SUV ratios (SUVR) of regional SUV normalized to the whole brain SUV were obtained. The Morris water maze (MWM) test was performed after 2 weeks to evaluate neurological outcomes and rats were classified into two groups based on the result. Of 18 PCAS rats, 8 were classified into the good outcome group. The SUVdelta of forebrain regions were significantly decreased in good outcome group (p < 0.05), while the SUVdelta of hindbrain regions were not significantly different according to outcomes. The SUVR of forebrain regions were significantly higher and the SUVR of hindbrain regions were significantly lower in good outcome group (p < 0.05). Forebrain-to-hindbrain ratio predicted a good neurological outcome with a sensitivity of 90% and specificity of 100% using an optimal cutoff value of 1.22 (AUC 0.969, p < 0.05). These results suggest the potential utility of 18F-FDG PET in the early prediction of neurological outcomes in PCAS.
Soluble guanylyl cyclase α1 subunit is a key mediator of proliferation, survival, and migration in ECC-1 and HeLa cell lines
Authors: Ronchetti Sonia A. , Pino María Teresa L. , Cordeiro Georgina , Bollani Sabrina N. , Ricci Analía G. , Duvilanski Beatriz H. , Cabilla Jimena P. 
Published: October 2019

AbstractSoluble guanylyl cyclase (sGC) is a heterodimeric enzyme constituted by two subunits, α1 and β1. Previously we have shown that 17β-estradiol (E2) exerts opposite effects on these subunits by increasing α1 and decreasing both β1 expression and enzymatic activity. To date, the physiological relevance of E2-induced sGC subunits’ imbalance has not been addressed. Also, increased levels strongly correlate with E2-induced proliferation in E2-dependent tissues. The aim of the present study was to investigate the role of sGCα1 in proliferation, survival, and migration in two E2-responsive and non-responsive tumour cell lines. Here we showed that E2 stimulated sGCα1 expression in ECC-1 endometrial cancer cells. sGCα1 knock-down significantly reduced E2-dependent cell proliferation. Moreover, sGCα1 silencing caused G1 arrest together with an increase in cell death and dramatically inhibited cell migration. Surprisingly, disruption of sGCα1 expression caused a similar effect even in absence of E2. Confirming this effect, sGCα1 knock-down also augmented cell death and decreased proliferation and migration in E2-unresponsive HeLa cervical cancer cells. Our results show that sGCα1 mediated cell proliferation, survival, and migration in ECC-1 and HeLa cells and suggest that sGCα1 can not only mediate E2-tumour promoting effects but can also be involved in hormone-independent tumour progression.
Radiation-related Adverse Effects of CT-guided Implantation of 125I Seeds for Thoracic Recurrent and/or Metastatic Malignancy
Authors: Ji Zhe , Jiang Yuliang , Guo Fuxin , Peng Ran , Sun Haitao , Wang Panfeng , Fan Jinghong , Wang Junjie 
Published: October 2019

AbstractDuring radioactive Iodine-125 seed implantation (RISI), Iodine-125 radionuclide is implanted directly into a lesion and kills tumor cells by steadily emitting radiation. In our study, we analyzed the adverse effects of RISI for thoracic malignancy, and investigated the safety, dosage, and adverse effects of RISI for these cases. Between June 2007 and January 2018, 77 patients with thoracic recurrent and/or metastatic tumors who underwent CT-guided RISI were enrolled. Radiation-related adverse effects were analyzed, including pneumonia, esophagitis, hemorrhage, fistula, skin injury, heart injury, and spinal cord injury. We used the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 to evaluate adverse effects and analyzed the relationship between adverse effects and dosimetric parameters of organs at risk (OAR), including D0.1cc, D2cc, Dmean, and V20. The results of the study were as follows: The median follow-up period was 11 months. The median postoperative dose (D90) was 122 Gy (45.7–241.8 Gy). Three patients (3.9%) showed radiation pneumonitis of grade ≥2. Two patients (2.6%) showed radiation-induced esophagitis of grade ≥2. One patient (1.3%) showed an esophageal fistula. Two patients (2.6%) had a tracheal fistula. Five patients (6.5%) had radiation-related skin reactions. One patient (1.3%) reported chest wall pain, while three (3.9%) showed hemoptysis. No patients showed radiation myelitis or cardiotoxicity. The mean D2cc of organs at risk were 165.7 Gy (lung), 10.61 Gy (esophagus), 10.25 Gy (trachea), 18.07 Gy (blood vessel), 12.64 Gy (heart), 14.77 Gy (spinal cord), 17.47 Gy (skin). Dosimetric parameters, such as D0.1cc, D2cc and Dmean, were higher in patients with toxic reactions (above the upper limit of 95% confidence interval among the overall data). Chi-square test showed that skin D0.1cc > 600 Gy, D2cc > 500 Gy, and Dmean >90 Gy were associated with grade ≥2 radiation dermatitis (p < 0.05), but no clear dose-toxicity correlation was found in other OARs. So, we concluded that the overall incidence of toxicity and adverse effects from RISI for the treatment of thoracic tumors is low. The dose-toxicity characteristics have not been fully defined. Doses within the upper limit of the 95% confidence interval may be considered safe. This was a retrospective analysis, and follow-up period was minimal, indicating possible limitations of this study.
Effects of the MAML2 genetic variants in glioma susceptibility and prognosis
Authors: Zhang Ming , Zhao Yonglin , Zhao Junjie , Huang Tingqin , Guo Xiaoye , Ma Xudong , Wu Yuan 
Published: October 2019

Abstract
Background: Abnormal expression of the mastermind-like transcriptional co-activator 2 (MAML2) gene is oncogenic in several human cancers, including glioma. However, the relevance of MAML2 variants with glioma remains unknown. We aimed to investigate the role of MAML2 polymorphisms in glioma risk and prognosis among the Chinese Han population. Methods: Seven MAML2 single-nucleotide polymorphisms (SNPs) were genotyped using Agena MassARRAY system among 575 patients with glioma and 500 age- and gender-matched healthy controls. Logistic regression was used to estimate the association between MAML2 polymorphisms and glioma risk by calculating odds ratios (ORs) and 95% confidence intervals (CI). Kaplan–Meier survival analysis and univariate, multivariate Cox proportional hazard regression analyses for hazard ratios (HRs) and 95% CIs were performed to evaluate the contribution of MAML2 polymorphisms to glioma prognosis. Results:MAML2 rs7938889 and rs485842 polymorphisms were associated with the reduced risk of glioma (OR = 0.69, P=0.023; and OR = 0.81, P=0.032, respectively). Rs7115578 polymorphism had a lower susceptibility to glioma in males (OR = 0.68, P=0.034), while rs4598633 variant with a higher risk in females (OR = 1.66, P=0.016). Additionally, rs7115578 AG genotype represented a poorer prognosis of glioma (HR = 1.24, P=0.033) and astrocytoma (log-rank P=0.037, HR = 1.31, P=0.036). Furthermore, rs11021499 polymorphism had lower overall survival (OS) and progression-free survival (PFS) in patients with low-grade glioma. Conclusion: We provided some novel data suggesting MAML2 polymorphisms might contribute to glioma risk and prognosis. Future studies are warranted to validate these findings and characterize mechanisms underlying these associations.
Charting nearby dust clouds usingGaiadata only
Authors: Leike R. H. , Enßlin T. A. 
Published: October 2019

Aims.Highly resolved maps of the local Galactic dust are an important ingredient for sky emission models. Over almost the whole electromagnetic spectrum one can see imprints of dust, many of which originate from dust clouds within 300 pc. Having a detailed 3D reconstruction of these local dust clouds enables detailed studies, helps to quantify the impact on other observables, and is a necessary milestone of larger reconstructions, as every sightline for more distant objects will pass through the local dust.Methods.To infer the dust density we use parallax and extinction estimates published by theGaiacollaboration in their second data release (DR2). We model the dust as a log-normal process using a hierarchical Bayesian model. We also nonparametrically infer the kernel of the log-normal process, which corresponds to the physical spatial correlation power spectrum of the log-density.Results.Using only data fromGaiaDR2, we reconstruct the 3D dust density and its spatial correlation spectrum in a 600 pc cube centered on the Sun. We report a spectral index of the logarithmic dust density of 3.1 on Fourier scales with wavelengths between 2 and 125 pc. The resulting 3D dust map as well as the power spectrum and posterior samples are publicly available for download.
Scattering, absorption, and thermal emission by large cometary dust particles: Synoptic numerical solution
Authors: Markkanen Johannes , Agarwal Jessica 
Published: October 2019

Context.Remote light scattering and thermal infrared observations provide clues about the physical properties of cometary and interplanetary dust particles. Identifying these properties will lead to a better understanding of the formation and evolution of the Solar System.Aims.We present a numerical solution for the radiative and conductive heat transport in a random particulate medium enclosed by an arbitrarily shaped surface. The method will be applied to study thermal properties of cometary dust particles.Methods.The recently introduced incoherent Monte Carlo radiative transfer method developed for scattering, absorption, and propagation of electromagnetic waves in dense discrete random media is extended for radiative heat transfer and thermal emission. The solution is coupled with the conductive Fourier transport equation that is solved with the finite-element method.Results.The proposed method allows the synoptic analysis of light scattering and thermal emission by large cometary dust particles consisting of submicrometer-sized grains. In particular, we show that these particles can sustain significant temperature gradients resulting in the superheating factor phase function observed for the coma of comet 67P/Churyumov–Gerasimenko.
Pathophysiologie der Migräne
Authors: Ziegeler Christian , May Arne 
Published: October 2019

ZUSAMMENFASSUNGLange Zeit wurde das pathophysiologische Verständnis der Migräne von der Vorstellung geprägt, dass die Gefäße des Kopfes den Schmerz bedingen und die Migräne also ein vaskulärer Kopfschmerz sei. Diese Theorie kann als überholt, zumindest jedoch lückenhaft angesehen werden. Mittlerweile deutet vieles darauf hin, dass es sich bei der Migräne um eine oszillierende Schwellen-/Filterstörung des zentralen Nervensystems handelt, wobei der im Vordergrund stehende Kopfschmerz nur einen Teil des vielfältigen Symptomkomplexes darstellt. Neuere Befunde der funktionellen Bildgebung zeigen zyklische Veränderungen von Aktivitätsmustern im Hypothalamus, Thalamus und Hirnstamm, welche besser erklären können, wie der Kopfschmerz und die migränetypischen Begleitsymptome entstehen. Die zukünftige Grundlagenforschung wird sich auf Kerngebiete im Diencephalon als mögliche Ursprungsorte der Attackengenerierung bei Migräne fokussieren. Große Hoffnung ruhen auf der Erforschung der Wirkweisen neuer Antikörpertherapien, welche helfen werden, molekulare Mechanismen der Schmerzentstehung der Migräne zu entschlüsseln.
Kopfschmerzklassifikation in der Medizingeschichte
Authors: Evers Stefan 
Published: October 2019

ZUSAMMENFASSUNGKopfschmerzklassifikationen existieren seit der Spätantike und haben zuerst in einfacher Weise Kopfschmerzen semiologisch beschrieben. Durch die humoralpathologische Medizin kam es im Mittelalter aber auch zu ätiologisch orientierten Klassifikationen, die jedoch immer von der vorherrschenden Lehrmeinung ausgingen und sich immer wieder als nicht haltbar erwiesen. Im 20. Jahrhundert wurde als erstes 1962 eine ätiologische Klassifikation vorgelegt, die aber durch moderne Forschungsergebnisse überholt wurde. Die aktuelle Kopfschmerzklassifikation ist zwar phänomenologisch orientiert, wird sich aber durch moderne Feldforschung hin zu einer ätiologisch orientierten entwickeln.