bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical significance of duration of untreated psychosis: an umbrella review and random‐effects meta‐analysis
Authors: Howes Oliver D. , Whitehurst Thomas , Shatalina Ekaterina , Townsend Leigh , Onwordi Ellis Chika , Mak Tsz Lun Allenis , Arumuham Atheeshaan , O’Brien Oisín , Lobo Maria , Vano Luke , Zahid Uzma , Butler Emma , Osugo Martin 
Published: January 2021

The idea that a longer duration of untreated psychosis (DUP) leads to poorer outcomes has contributed to extensive changes in mental health ser­vices worldwide and has attracted considerable research interest over the past 30 years. However, the strength of the evidence underlying this notion is unclear. To address this issue, we conducted an umbrella review of available meta‐analyses and performed a random‐effects meta‐analysis of primary studies. MEDLINE, Web of Science, PsycINFO and EMBASE were searched from inception to September 3, 2020 to identify relevant meta‐analyses of studies including patients with schizophrenia spectrum disorders, first‐episode psychosis, or affective and non‐affective psychosis. Thirteen meta‐analyses were included, corresponding to 129 individual studies with a total sample size of 25,657 patients. We detected potential violations of statistical assumptions in some of these meta‐analyses. We therefore conducted a new random‐effects meta‐analysis of primary studies. The association between DUP and each outcome was graded according to a standardized classification into convincing, highly suggestive, suggestive, weak, or non‐significant. At first presentation, there was suggestive evidence for a relationship between longer DUP and more severe negative symptoms (beta=–0.07, p=3.6×10–5) and higher chance of previous self‐harm (odds ratio, OR=1.89, p=1.1×10–5). At follow‐up, there was highly suggestive evidence for a relationship between longer DUP and more severe positive symptoms (beta=–0.16, p=4.5×10–8), more severe negative symptoms (beta=–0.11, p=3.5×10–10) and lower chance of remission (OR=2.16, p=3.0×10–10), and suggestive evidence for a relationship between longer DUP and poorer overall functioning (beta=–0.11, p=2.2×10–6) and more severe global psychopathology (beta=–0.16, p=4.7×10–6). Results were unchanged when analysis was restricted to prospective studies. These effect sizes are clinically meaningful, with a DUP of four weeks predicting >20% more severe symptoms at follow‐up relative to a DUP of one week. We conclude that DUP is an important prognostic factor at first presentation and predicts clinically relevant outcomes over the course of illness. We discuss conceptual issues in DUP research and methodological limitations of current evidence, and provide recommendations for future research.
Hierarchical models of psychopathology: empirical support, implications, and remaining issues
Authors: Lahey Benjamin B. , Moore Tyler M. , Kaczkurkin Antonia N. , Zald David H. 
Published: January 2021

There is an ongoing revolution in psychology and psychiatry that will likely change how we conceptualize, study and treat psychological problems.­ Many theorists now support viewing psychopathology as consisting of continuous dimensions rather than discrete diagnostic categories. Indeed, recent papers have proposed comprehensive taxonomies of psychopathology dimensions to replace the DSM and ICD taxonomies of categories. The proposed dimensional taxonomies, which portray psychopathology as hierarchically organized correlated dimensions, are now well supported at phenotypic levels. Multiple studies show that both a general factor of psychopathology at the top of the hierarchy and specific factors at lower levels predict different functional outcomes. Our analyses of data on a large representative sample of child and adolescent twins suggested the causal hypothesis that phenotypic correlations among dimensions of psychopathology are the result of many familial influences being pleiotropic. That is, most genetic variants and shared environmental factors are hypothesized to non‐specifically influence risk for multiple rather than individual dimensions of psychopathology. In contrast, person‐specific experiences tend to be related to individual dimensions. This hierarchical causal hypothesis has been supported by both large‐scale family and molecular genetic studies. Current research focuses on three issues. First, the field has not settled on a preferred statistical model for studying the hierarchy of causes and phenotypes. Second, in spite of encouraging progress, the neurobiological correlates of the hierarchy of dimensions of psychopathology are only partially described. Third, although there are potentially important clinical implications of the hierarchical model, insufficient research has been conducted to date to rec­ommend evidence‐based clinical practices.
Identification of proteins responsive to heterologous protein production in thermotolerant methylotrophic yeast Ogataea thermomethanolica TBRC656
Authors: Phithakrotchanakoon Chitwadee , Puseenam Aekkachai , Kruasuwan Worarat , Likhitrattanapisal Somsak , Phaonakrop Narumon , Roytrakul Sittiruk , Ingsriswang Supawadee , Tanapongpipat Sutipa , Roongsawang Niran 
Published: January 2021

AbstractThe thermotolerant methylotrophic yeast Ogataea thermomethanolica TBRC656 is a potential host for heterologous protein production. However, overproduction of heterologous protein can induce cellular stress and limit the level of its secretion. To improve the secretion of heterologous protein, we identified the candidate proteins with altered production during production of heterologous protein in O. thermomethanolica by using a label‐free comparative proteomic approach. Four hundred sixty‐four proteins with various biological functions showed differential abundance between O. thermomethanolica expressing fungal xylanase (OT + Xyl) and a control strain. The induction of proteins in transport and proteasomal proteolysis was prominently observed. Eight candidate proteins involved in cell wall biosynthesis (Chs3, Gas4), chaperone (Sgt2, Pex19), glycan metabolism (Csf1), protein transport (Ypt35), and vacuole and protein sorting (Cof1, Npr2) were mutated by a CRISPR/Cas9 approach. An Sgt2 mutant showed higher phytase and xylanase activity compared with the control strain (13%–20%), whereas mutants of other genes including Cof1, Pex19, Gas4, and Ypt35 showed lower xylanase activity compared with the control strain (15%–25%). In addition, an Npr2 mutant showed defective growth, while overproduction of Npr2 enhanced xylanase activity. These results reveal genes that can be mutated to modulate heterologous protein production and growth of O. thermomethanolica TBRC656.
Gravitational memory effects and Bondi-Metzner-Sachs symmetries in scalar-tensor theories
Authors: Hou Shaoqi , Zhu Zong-Hong 
Published: January 2021

Abstract
The relation between gravitational memory effects and Bondi-Metzner-Sachs symmetries of the asymptotically flat spacetimes is studied in the scalar-tensor theory. For this purpose, the solutions to the equations of motion near the future null infinity are obtained in the generalized Bondi-Sachs coordinates with a suitable determinant condition. It turns out that the Bondi-Metzner-Sachs group is also a semi-direct product of an infinite dimensional supertranslation group and the Lorentz group as in general relativity. There are also degenerate vacua in both the tensor and the scalar sectors in the scalar-tensor theory. The supertranslation relates the vacua in the tensor sector, while in the scalar sector, it is the Lorentz transformation that transforms the vacua to each other. So there are the tensor memory effects similar to the ones in general relativity, and the scalar memory effect, which is new. The evolution equations for the Bondi mass and angular momentum aspects suggest that the null energy fluxes and the angular momentum fluxes across the null infinity induce the transition among the vacua in the tensor and the scalar sectors, respectively.
Transformed tissue of Dionaea muscipula J. Ellis as a source of biologically active phenolic compounds with bactericidal properties
Authors: Makowski Wojciech , Królicka Aleksandra , Nowicka Anna , Zwyrtková Jana , Tokarz Barbara , Pecinka Ales , Banasiuk Rafał , Tokarz Krzysztof Michał 
Published: January 2021

Abstract
The Venus flytrap (Dionaea muscipula J. Ellis) is a carnivorous plant able to synthesize large amounts of phenolic compounds, such as phenylpropanoids, flavonoids, phenolic acids, and 1,4-naphtoquinones. In this study, the first genetic transformation of D. muscipula tissues is presented. Two wild-type Rhizobium rhizogenes strains (LBA 9402 and ATCC 15834) were suitable vector organisms in the transformation process. Transformation led to the formation of teratoma (transformed shoot) cultures with the bacterial rolB gene incorporated into the plant genome in a single copy. Using high-pressure liquid chromatography, we demonstrated that transgenic plants were characterized by an increased quantity of phenolic compounds, including 1,4-naphtoquinone derivative, plumbagin (up to 106.63 mg × g−1 DW), and phenolic acids (including salicylic, caffeic, and ellagic acid), in comparison to non-transformed plants. Moreover, Rhizobium-mediated transformation highly increased the bactericidal properties of teratoma-derived extracts. The antibacterial properties of transformed plants were increased up to 33% against Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli and up to 7% against Pseudomonas aeruginosa. For the first time, we prove the possibility of D. muscipula transformation. Moreover, we propose that transformation may be a valuable tool for enhancing secondary metabolite production in D. muscipula tissue and to increase bactericidal properties against human antibiotic-resistant bacteria.

Key points
• Rhizobium-mediated transformation created Dionaea muscipula teratomas.
• Transformed plants had highly increased synthesis of phenolic compounds.
• The MBC value was connected with plumbagin and phenolic acid concentrations.
Trends, insights and effects of the Urban Wastewater Treatment Directive (91/271/EEC) implementation in the light of the Polish coastal zone eutrophication
Authors: Preisner Michał , Smol Marzena , Szołdrowska Dominika 
Published: January 2021

AbstractThe intensification of the Baltic Sea eutrophication is associated with the increase of anthropogenic nutrients loads, mainly nitrogen and phosphorus introduced into surface waters from a diffuse, point and natural background sources. Despite the observed decreasing trends in nutrient concentrations in some parts of the Baltic Sea, eutrophication-related indicators continue to deteriorate. This accelerates harmful algal blooms and dissolved oxygen deficits resulting in severe ecosystem disturbance. The paper presents trends, insights and effects of the Urban Wastewater Treatment Directive 91/271/EEC implementation in Poland based on the nutrient riverine loads from Polish territory with particular attention given to the development of municipal wastewater treatment plants under the National Wastewater Treatment Programme 2003–2016. Environmental effects of wastewater infrastructure modernisation are investigated by using available data on the changing nutrient concentrations in the coastal water in 3 basins (Gdansk Basin, Bornholm Basin and Eastern Gotland Basin) belonging to the Polish Exclusive Economic Zone within the Baltic Sea. The results show that the decreasing trend regarding phosphorus loads reduction from municipal effluents was achieved while a stable trend with temporary increases was achieved in terms of nitrogen loads. Moreover, the investigation provides information about the potential bioavailability of discharged effluents before and after the Directive implementation by including total and inorganic forms of nitrogen and phosphorus in the analysis.
DGK and DZHK position paper on genome editing: basic science applications and future perspective
Authors: Brandes Ralf P. , Dueck Anne , Engelhardt Stefan , Kaulich Manuel , Kupatt Christian , De Angelis Maria Teresa , Leisegang Matthias S. , le Noble Ferdinand , Moretti Alessandra , Müller Oliver J. , Skryabin Boris V. , Thum Thomas , Wurst Wolfgang 
Published: January 2021

AbstractFor a long time, gene editing had been a scientific concept, which was limited to a few applications. With recent developments, following the discovery of TALEN zinc-finger endonucleases and in particular the CRISPR/Cas system, gene editing has become a technique applicable in most laboratories. The current gain- and loss-of function models in basic science are revolutionary as they allow unbiased screens of unprecedented depth and complexity and rapid development of transgenic animals. Modifications of CRISPR/Cas have been developed to precisely interrogate epigenetic regulation or to visualize DNA complexes. Moreover, gene editing as a clinical treatment option is rapidly developing with first trials on the way. This article reviews the most recent progress in the field, covering expert opinions gathered during joint conferences on genome editing of the German Cardiac Society (DGK) and the German Center for Cardiovascular Research (DZHK). Particularly focusing on the translational aspect and the combination of cellular and animal applications, the authors aim to provide direction for the development of the field and the most frequent applications with their problems.
Factors contributing to clinically important health utility gains in cochlear implant recipients
Authors: Müller Lida , Graham Petra , Kaur Jasmin , Wyss Josie , Greenham Paula , James Chris J. 
Published: January 2021

Abstract
Purpose
Cochlear implantation can restore access to sound and speech understanding in subjects with substantial hearing loss. The Health Utilities Index Mark III (HUI3) measures the impact of an intervention on the patient’s quality of life and is sensitive to changes in hearing. In the current study we used factor analysis to predict a clinically important gain in HUI3 scores in adult cochlear implant recipients.

Methods
Data were collected in an observational study for 137 adult recipients from a single center who had at least 1-year HUI3 follow-up. Demographic and other baseline parameters were retrospectively analyzed for their association with a clinically important HUI3 scale gain, defined as at least 0.1 points. Data were also collected for the speech spatial qualities (SSQ) scale.

Results
Baseline telephone use and HUI3 hearing, speech and emotion attribute levels were significantly associated with clinically important gains in HUI3 scores. However, SSQ scores increased significantly with or without clinically important HUI3 gains.

Conclusion
Those subjects who were unhappy or experienced difficulties communicating with strangers or in a group were twice as likely to obtain a clinically important gain in health utility compared to those who were happy or had less difficulty communicating. Subjects who were unable to use the telephone prior to cochlear implantation were one and a half times more likely to obtain a clinically important gain. The SSQ scale was more sensitive to hearing improvements due to cochlear implantation. An inability to use the telephone is an easy to assess biomarker for candidacy for cochlear implantation.
Validity of the LACE index for identifying frequent early readmissions after hospital discharge in children
Authors: Han Thang S , Fluck David , Fry Christopher H 
Published: January 2021

AbstractThe LACE index scoring tool has been designed to predict hospital readmissions in adults. We aimed to evaluate the ability of the LACE index to identify children at risk of frequent readmissions. We analysed data from alive-discharge episodes (1 April 2017 to 31 March 2019) for 6546 males and 5875 females from birth to 18 years. The LACE index predicted frequent all-cause readmissions within 28 days of hospital discharge with high accuracy: the area under the curve = 86.9% (95% confidence interval = 84.3–89.5%, p < 0.001). Two-graph receiver operating characteristic curve analysis revealed the LACE index cutoff to be 4.3, where sensitivity equals specificity, to predict frequent readmissions. Compared with those with a LACE index score = 0–4 (event rates, 0.3%), those with a score > 4 (event rates, 3.7%) were at increased risk of frequent readmissions: age- and sex-adjusted odds ratio = 12.4 (95% confidence interval = 8.0–19.2, p < 0.001) and death within 30 days of discharge: OR = 5.0 (95% CI = 1.5–16.7). The ORs for frequent readmissions were between 6 and 14 for children of different age categories (neonate, infant, young child and adolescent), except for patients in the child category (6–12 years) where odds ratio was 2.8.Conclusion: The LACE index can be used in healthcare services to identify children at risk of frequent readmissions. Focus should be directed at individuals with a LACE index score above 4 to help reduce risk of readmissions.

What is Known:• The LACE index scoring tool has been widely used to predict hospital readmissions in adults.

What is New:• Compared with children with a LACE index score of 0–4 (event rates, 0.3%), those with a score > 4 are at increased risk of frequent readmissions by 14-fold.• The cutoff of a LACE index of 4 may be a useful level to identify children at increased risk of frequent readmissions.
miR-146a-3p suppressed the differentiation of hAMSCs into Schwann cells via inhibiting the expression of ERBB2
Authors: Chen Wei , Ji Linlin , Wei Zairong , Yang Chenglan , Chang Shusen , Zhang Yucheng , Nie Kaiyu , Jiang Lingli , Deng Yurong 
Published: January 2021

AbstractHuman amniotic mesenchymal stem cells (hAMSCs) can be differentiated into Schwann-cell-like cells (SCLCs) in vitro. However, the underlying mechanism of cell differentiation remains unclear. In this study, we explored the phenotype and multipotency of hAMSCs, which were differentiated into SCLCs, and the expression of nerve repair-related Schwann markers, such as S100 calcium binding protein B (S-100), TNF receptor superfamily member 1B (P75), and glial fibrillary acidic protein (GFAP) were observed to be significantly increased. The secreted functional neurotrophic factors, like brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3), were determined and also increased with the differentiation time. Moreover, miR-146a-3p, which significantly decreased during the differentiation of hAMSCs into SCLCs, was selected by miRNA-sequence analysis. Further molecular mechanism studies showed that Erb-B2 receptor tyrosine kinase 2 (ERBB2) was an effective target of miR-146a-3p and that miR-146a-3p down-regulated ERBB2 expression by binding to the 3′-UTR of ERBB2. The expression of miR-146a-3p markedly decreased, while the mRNA levels of ERBB2 increased with the differentiation time. The results showed that down-regulating miR-146a-3p could promote SC lineage differentiation and suggested that miR-146a-3p negatively regulated the Schwann-like phenotype differentiation of hAMSCs by targeting ERBB2. The results will be helpful to establish a deeper understanding of the underlying mechanisms and find novel strategies for cell therapy.
Ex vivo glucocorticoid receptor-mediated IL-10 response predicts the course of depression severity
Authors: von Zimmermann Claudia , Böhm Lea , Richter-Schmidinger Tanja , Kornhuber Johannes , Lenz Bernd , Mühle Christiane 
Published: January 2021

AbstractDirectly measuring hypothalamic pituitary adrenal (HPA) axis function, an important player in affective disorders, is intensive and invasive. A crucial component of this system, the activity of the glucocorticoid receptor (GR), can be assessed ex vivo instead. Here, we investigated GR sensitivity in patients with major depressive disorder (MDD) to determine its predictive potential. Psychometric data and blood samples were collected from patients experiencing a major depressive episode (MDE, n = 87), healthy control subjects (n = 49), and patients with remitted MDD (n = 31) at baseline and (for patients) after median 20 days of follow-up after treatment as usual. Blood cells were stimulated ex vivo with lipopolysaccharide and the effect was suppressed by increasing dexamethasone (DEX) concentrations. The resultant cytokine secretion profile (for IL-6, IL-10, and TNF-α) was considered indicative of GR activity. Higher baseline scores of the Montgomery–Åsberg Depression Rating Scale (MADRS) were associated with a stronger decrease of logIC IL-6 (indicating an increase of GR sensitivity). Higher baseline logEC IL-10 (indicating a lower GR sensitivity) and a stronger reduction of logEC IL-10 (indicating a stronger increase in GR sensitivity) were associated with a stronger decrease in the MADRS score. Patients with remitted MDD showed higher logIC TNF-α values (indicating lower GR sensitivity) in comparison to patients with a current MDD at baseline and follow-up. Initially low GR sensitivity measured ex vivo in peripheral blood cells that increases over the course of treatment could serve as a predictive marker for stronger improvement in depression severity.
Promoting eco-driving behavior through multisensory stimulation: a preliminary study on the use of visual and haptic feedback in a virtual reality driving simulator
Authors: Pietra Andrea , Vazquez Rull Marina , Etzi Roberta , Gallace Alberto , Scurati Giulia Wally , Ferrise Francesco , Bordegoni Monica 
Published: January 2021

AbstractThis paper describes the design and preliminary test of a virtual reality driving simulator capable of conveying haptic and visual messages to promote eco-sustainable driving behavior. The driving simulator was implemented through the Unity game engine; a large street environment, including high-speed and urban sections, was created to examine different driving behaviors. The hardware setup included a gaming driving seat, equipped with a steering wheel and pedals; the virtual scenarios were displayed through an Oculus Rift headset to guarantee an immersive experience. Haptic stimulation (i.e., vibrations) was delivered to the driver through the accelerator pedal, while visual stimuli (i.e., icons and colors) were shown on a virtual head-up display. The sensory feedbacks were presented both alone and in combination, providing information about excessive acceleration and speed. Four different virtual scenarios, each one including a distracting element (i.e., navigator, rain, call, and traffic), were also created. Ten participants tested the simulator. Fuel consumption was evaluated by calculating a mean power index (MPI) in reference to the sensory feedback presentation; physiological reactions and responses to a usability survey were also collected. The results revealed that the haptic and visuo-haptic feedback were responsible for an MPI reduction, respectively, for 14% and 11% compared with a condition of no feedback presentation; while visual feedback alone resulted in an MPI increase of 11%. The efficacy of haptic feedback was also accompanied by a more relaxing physiological state of the users, compared with the visual stimulation. The system’s usability was adequate, although haptic stimuli were rated slightly more intrusive than the visual ones. Overall, these preliminary results highlight how promising the use of the haptic channel can be in communicating and guiding the driver toward a more eco-sustainable behavior.