bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy
Authors: Moschny Nicole , Zindler Tristan , Jahn Kirsten , Dorda Marie , Davenport Colin F. , Wiehlmann Lutz , Maier Hannah B. , Eberle Franziska , Bleich Stefan , Neyazi Alexandra , Frieling Helge 
Published: July 2020

AbstractBackgroundMajor depressive disorder (MDD) represents a serious global health concern. The urge for efficient MDD treatment strategies is presently hindered by the incomplete knowledge of its underlying pathomechanism. Despite recent progress (highlighting both genetics and the environment, and thus DNA methylation, to be relevant for its development), 30–50% of MDD patients still fail to reach remission with standard treatment approaches. Electroconvulsive therapy (ECT) is one of the most powerful options for the treatment of pharmacoresistant depression; nevertheless, ECT remission rates barely reach 50% in large-scale naturalistic population-based studies. To optimize MDD treatment strategies and enable personalized medicine in the long- term, prospective indicators of ECT response are thus in great need. Because recent target-driven analyses revealed DNA methylation baseline differences between ECT responder groups, we analyzed the DNA methylome of depressed ECT patients using next-generation sequencing. In this pilot study, we did not only aim to find novel targets for ECT response prediction but also to get a deeper insight into its possible mechanism of action.ResultsLongitudinal DNA methylation analysis of peripheral blood mononuclear cells isolated from a cohort of treatment-resistant MDD patients (n= 12; time points: before and after 1st and last ECT, respectively) using a TruSeq-Methyl Capture EPIC Kit for library preparation, led to the following results: (1) The global DNA methylation differed neither between the four measured time points nor between ECT responders (n= 8) and non-responders (n= 4). (2) Analyzing the DNA methylation variance for every probe (=1476812 single CpG sites) revealed eight novel candidate genes to be implicated in ECT response (protein-coding genes:RNF175,RNF213,TBC1D14,TMC5,WSCD1; genes encoding for putative long non-coding RNA transcripts:AC018685.2,AC098617.1,CLCN3P1). (3) In addition, DNA methylation of two CpG sites (located withinAQP10andTRERF1) was found to change during the treatment course.ConclusionsWe suggest ten novel candidate genes to be implicated in either ECT response or its possible mechanism. Because of the small sample size of our pilot study, our findings must be regarded as preliminary.
The effect of electronic monitoring combined with weekly feedback and reminders on adherence to inhaled corticosteroids in infants and younger children with asthma: a randomized controlled trial
Authors: Chen Jiande , Xu Juan , Zhao Liebin , Zhang Jing , Yin Yong , Zhang Fen 
Published: July 2020

Abstract
Background
Adherence to asthma treatment among children is usually poor. We sought to explore whether electronic adherence monitoring combined with weekly feedback regarding adherence along with a reminder to use inhaled corticosteroids (ICS) would lead to improved compliance with ICS in infants and younger children with asthma.

Methods
96 recruited children (aged 6 months to 3 years) with mild or moderate persistent asthma who were on regular inhaled corticosteroids were randomly allocated to receive electronic monitoring combined with instant messaging software (IMS)-based weekly feedback regarding adherence along with a reminder to keep taking the ICS (intervention group) and to receive electronic monitoring only (control group).

Results
The mean device-monitored adherence was significantly higher in the intervention group (80%) than in the control group (45.9%), with a difference of 34.0% (95% confidence interval [CI], 26.8–41.3%; P < 0.001). No difference in the mean caregiver-reported adherence between the interventional group (89.7%) and the control group (92.7%) was observed (P = 0.452).

Conclusions
Electronic monitoring combined with IMS-based weekly feedback regarding adherence along with a reminder to keep taking the ICS significantly improved the treatment compliance of infants and younger children with asthma. Caregiver-reported adherence is an unreliable monitoring indicator.
Trial registration ClinicalTrials.gov, NCT03277664. Registered 11 September 2017—Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=NCT03277664
Intermittent parathyroid hormone (1–34) supplementation of bone marrow stromal cell cultures may inhibit hypertrophy, but at the expense of chondrogenesis
Authors: Music Ena , Futrega Kathryn , Palmer James S. , Kinney Mackenzie , Lott Bill , Klein Travis J. , Doran Michael R. 
Published: July 2020

Abstract
Background
Bone marrow stromal cells (BMSC) have promise in cartilage tissue engineering, but for their potential to be fully realised, the propensity to undergo hypertrophy must be mitigated. The literature contains diverging reports on the effect of parathyroid hormone (PTH) on BMSC differentiation. Cartilage tissue models can be heterogeneous, confounding efforts to improve media formulations.

Methods
Herein, we use a novel microwell platform (the Microwell-mesh) to manufacture hundreds of small-diameter homogeneous micro-pellets and use this high-resolution assay to quantify the influence of constant or intermittent PTH(1–34) medium supplementation on BMSC chondrogenesis and hypertrophy. Micro-pellets were manufactured from 5000 BMSC each and cultured in standard chondrogenic media supplemented with (1) no PTH, (2) intermittent PTH, or (3) constant PTH.

Results
Relative to control chondrogenic cultures, BMSC micro-pellets exposed to intermittent PTH had reduced hypertrophic gene expression following 1 week of culture, but this was accompanied by a loss in chondrogenesis by the second week of culture. Constant PTH treatment was detrimental to chondrogenic culture.

Conclusions
This study provides further clarity on the role of PTH on chondrogenic differentiation in vitro and suggests that while PTH may mitigate BMSC hypertrophy, it does so at the expense of chondrogenesis.
Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures
Authors: Hingert Daphne , Ekström Karin , Aldridge Jonathan , Crescitelli Rosella , Brisby Helena 
Published: July 2020

Abstract
Background
Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and have been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences, there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSC-derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model.

Methods
hMSCs were isolated from bone marrow aspirate, and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the sEVs at 5 × 1010 vesicles/ml concentration for 28 days and compared to control. The pellets were harvested at days 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis, and cytokine secretions.

Results
The findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEV-treated DC pellets compared to control cultures. Further, sEV treatment suppressed secretion of MMP-1 in the DCs.

Conclusion
hMSC-derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.
Pathophysiological effects of androgens on the female vascular system
Authors: Stone Tori , Stachenfeld Nina S. 
Published: July 2020

AbstractSex hormones and their respective receptors affect vascular function differently in men and women, so it is reasonable to assume they play a role in the sex differences in cardiovascular disease states. This review focuses on how the effects of testosterone on arterial vessels impact the female vasculature. In women with androgen-excess polycystic ovary syndrome, and in transgender men, testosterone exposure is associated with high blood pressure, endothelial dysfunction, and dyslipidemia. These relationships suggest that androgens may exert pathophysiological effects on the female vasculature, and these effects on the female vasculature appear to be independent from other co-morbidities of cardiovascular disease. There is evidence that the engagement of androgens with androgen receptor induces detrimental outcomes in the female cardiovascular system, thereby representing a potential causative link with sex differences and cardiovascular regulation. Gender affirming hormone therapy is the primary medical intervention sought by transgender people to reduce the characteristics of their natal sex and induce those of their desired sex. Transgender men, and women with androgen-excess polycystic ovary syndrome both represent patient groups that experience chronic hyperandrogenism and thus lifelong exposure to significant medical risk. The study of testosterone effects on the female vasculature is relatively new, and a complex picture has begun to emerge. Long-term research in this area is needed for the development of more consistent models and controlled experimental designs that will provide insights into the impact of endogenous androgen concentrations, testosterone doses for hormone therapy, and specific hormone types on function of the female cardiovascular system.
Subjective working memory predicts objective memory in cognitively normal aging: a HUNT study
Authors: Bosnes Ole , Almkvist Ove , Bosnes Ingunn , Stordal Eystein 
Published: July 2020

Abstract
Background
Recent studies have shown that subjective memory is multi-, rather than uni-dimensional, in line with the results of objective memory tests. The purpose of this study was to investigate whether there is an association between aspects of memory measured by the subjective Meta-Memory Questionnaire (MMQ) and aspects of memory measured by the objective Wechsler Memory Scale-III (WMS-III) and Wechsler Adult Intelligence Scale-III (WAIS-III) tests in cognitively normal older adults.

Method
The study subjects (n = 106) were cognitively normal, were aged 57–89 years and had participated in the third wave of the North-Trøndelag Health survey (HUNT3). All subjects had completed the MMQ, the WMS-III and the WAIS-III. Previous results from the MMQ (measured as the total MMQ score; the Component I score, related to long-term explicit declarative memory; and the Component II score, related to working/short-term memory) were compared with objective results from WMS-III (Logical Memory) and WAIS-III (Vocabulary and Letter-Number Sequencing) subtests. We conducted linear regression analyses with each objective memory test result as the dependent variable, and subjective memory measures and demographics as independent variables, as well as analyses of MMQ items vs. objective memory.

Results
Subjective working memory impairment (Component II) was significant related to poor performance in objective episodic memory, according to correlation and regression analyses with demographic covariates. In contrast, ratings of impaired subjective declarative memory (Component I) were not related to poor objective memory performance.

Conclusions
Specific aspects of subjective memory related differentially to performance in specific objective memory tests. Clinicians and researchers might consider targeting working memory aspects of subjective memory tests, when seeking an estimate of objective memory performance.
Euthanasia and assisted suicide in patients with personality disorders: a review of current practice and challenges
Authors: Mehlum Lars , Schmahl Christian , Berens Ann , Doering Stephan , Hutsebaut Joost , Kaera Andres , Kramer Ueli , Moran Paul Anthony , Renneberg Babette , Ribaudi Joaquim Soler , Simonsen Sebastian , Swales Michaela , Taubner Svenja , di Giacomo Ester 
Published: July 2020

Abstract
Background
Over the last two decades an increasing number of countries have legalized euthanasia and physician-assisted suicide (EAS) leading to considerable debate over the inherent ethical dilemmas. Increasing numbers of people with personality disorders, faced with unbearable suffering, have requested and received assistance in terminating their lives. EAS in people with personality disorders has, however, received very sparse attention from clinicians and researchers. In this paper, we examine the literature on the practice and prevalence of EAS in people with personality disorders to date and discuss the associated challenges for research and practice.

Methods
Narrative review of the literature combined with the authors’ collective experience and knowledge of personality disorders.

Results
In six of the eight countries where EAS is currently legal, mental disorders are accepted as disorders for which EAS may be granted. In four of these countries, EAS in minors with mental disorders is also accepted. Our literature search resulted in 9 papers on the subject of EAS in people with personality disorders. These studies suggest that most clinicians who grant EAS have indeed perceived their patients’ suffering as chronic, unbearable and untreatable without prospect of improvement. The majority of patients with personality disorders had tried some form of psychotherapy, but very few had received any of the relevant evidence-based treatments. The decision to grant EAS based on a perception of the patient’s illness as being untreatable with no prospect of improvement, could, thus, in many cases fail to meet the due care criteria listed in EAS laws. People with personality disorders more often wish for death for extended periods of time than people without these disorders. However, there is ample empirical data to show that suicidal tendencies and behaviour can be treated and that they fluctuate rapidly over time.

Conclusions
In light of our findings, we believe that the current legislation and practice of EAS for people with personality disorders is based on an inadequate understanding of underlying psychopathology and a lack of awareness about the contemporary treatment literature. Moreover, we assert that this practice neglects the individual’s potential for having a life worth living.
Assessing the effects of climate change on flood inundation in the lower Mekong Basin using high-resolution AGCM outputs
Authors: Try Sophal , Tanaka Shigenobu , Tanaka Kenji , Sayama Takahiro , Lee Giha , Oeurng Chantha 
Published: July 2020

AbstractClimate change currently affects the resilience and aquatic ecosystem. Climate change alters rainfall patterns which have a great impact on river flow. Annual flooding is an important hydrological characteristic of the Mekong River Basin (MRB) and it drives the high productivity of the ecosystem and biodiversity in the Tonle Sap floodplain and the Mekong Delta. This study aims to assess the impacts of climate change on river flow in the MRB and flood inundation in the Lower Mekong Basin (LMB). The changing impacts were assessed by a two-dimensional rainfall-runoff and inundation model (RRI model). The present climate (1979–2003) and future projected climate (2075–2099) datasets from MRI-AGCM3.2H and MRI-AGCM3.2S models were applied with a linear scaling bias correction method before input into the RRI model. The results of climate change suggested that flood magnitude in the LMB will be severer than the present climate by the end of the twenty-first century. The increment of precipitation between 6.6 and 14.2% could lead to increase extreme flow (Q5) 13–30%, peak inundation area 19–43%, and peak inundation volume 24–55% in the LMB for ranging of Representative Concentration Pathways (RCP) and sea surface temperature (SST) scenarios while there is no significant change on peak flood timing.
An in vivo multimodal feasibility study in a rat brain tumour model using flexible multinuclear MR and PET systems
Authors: Choi Chang-Hoon , Stegmayr Carina , Shymanskaya Aliaksandra , Worthoff Wieland A. , da Silva Nuno A. , Felder Jörg , Langen Karl-Josef , Shah N. Jon 
Published: July 2020

Abstract
Background
In addition to the structural information afforded by 1H MRI, the use of X-nuclei, such as sodium-23 (23Na) or phosphorus-31 (31P), offers important complementary information concerning physiological and biochemical parameters. By then combining this technique with PET, which provides valuable insight into a wide range of metabolic and molecular processes by using of a variety of radioactive tracers, the scope of medical imaging and diagnostics can be significantly increased. While the use of multimodal imaging is undoubtedly advantageous, identifying the optimal combination of these parameters to diagnose a specific dysfunction is very important and is advanced by the use of sophisticated imaging techniques in specific animal models.

Methods
In this pilot study, rats with intracerebral 9L gliosarcomas were used to explore a combination of sequential multinuclear MRI using a sophisticated switchable coil set in a small animal 9.4 T MRI scanner and, subsequently, a small animal PET with the tumour tracer O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). This made it possible for in vivo multinuclear MR-PET experiments to be conducted without compromising the performance of either multinuclear MR or PET.

Results
High-quality in vivo images and spectra including high-resolution 1H imaging, 23Na-weighted imaging, detection of 31P metabolites and [18F]FET uptake were obtained, allowing the characterisation of tumour tissues in comparison to a healthy brain. It has been reported in the literature that these parameters are useful in the identification of the genetic profile of gliomas, particularly concerning the mutation of the isocitrate hydrogenase gene, which is highly relevant for treatment strategy.

Conclusions
The combination of multinuclear MR and PET in, for example, brain tumour models with specific genetic mutations will enable the physiological background of signal alterations to be explored and the identification of the optimal combination of imaging parameters for the non-invasive characterisation of the molecular profile of tumours.
Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves’ disease
Authors: Sun Ying , Wang Wei , Tang Yuxiao , Wang Daping , Li Liang , Na Min , Jiang Guantong , Li Qian , Chen Shulin , Zhou Jin 
Published: July 2020

Abstract
Background
Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves’ disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses.

Methods
Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes.

Results
There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling.

Conclusions
hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves’ disease.
Long-term follow-up of full-arch immediate implant-supported restorations in edentulous jaws: a clinical study
Authors: Werbelow Laura , Weiss Michael , Schramm Alexander 
Published: July 2020

AbstractBackgroundThis study aims to show the long-time stability of straight and tilted implants loaded immediately with a provisional resin bridge followed by a definitive prosthodontic rehabilitation in edentulous jaws despite difficult hygiene conditions postoperatively.ResultsThis study included the participation of 23 patients and the restoration of 170 dental implants in 32 edentulous jaws. Patient data was analyzed from the start of treatment with a minimum follow-up period of 6 years in order to determine long-term implant success rates. However, the age of patients at time of surgery significantly affected the BOP to the detriment of younger patients (median 62 years old).ConclusionAlthough there was a higher risk of implant failure due to general disease, all the implants in this study survived successfully. As a replacement for a complete dental arch, the reduced number of implants in combination with the avoidance of augmentations reduces treatment costs. The immediate fixed prosthetic restoration of edentulous jaws thus represents a reliable therapeutic alternative to a two- to three-stage procedure. Optimized aftercare including professional teeth cleaning (PTC) (at least twice a year) can minimize the anamnestic effect of smoking, diabetes mellitus, and osteoporosis on BOP and possible bone loss.