bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical staging and the differential risks for clinical and functional outcomes in young people presenting for youth mental health care
Authors: Capon William , Hickie Ian B. , Varidel Mathew , Prodan Ante , Crouse Jacob J. , Carpenter Joanne S. , Cross Shane P. , Nichles Alissa , Zmicerevska Natalia , Guastella Adam J. , Scott Elizabeth M. , Scott Jan , Shah Jai , Iorfino Frank 
Published: December 2022

Abstract
Background
Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care.

Methods
Demographic and clinical information of 2901 young people who accessed mental health care at age 12–25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: ‘non-specific anxious or depressive symptoms’, 1b: ‘attenuated mood or psychotic syndromes’, 2+: ‘full-threshold mood or psychotic syndromes’). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care.

Results
Of the entire cohort, 2093 young people aged 12–25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60–4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36–3.28), develop suicidal ideations (OR=1.92; CI 1.30–2.84) and circadian disturbances (OR=1.94, CI 1.31–2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity.

Conclusions
The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages.
Construction and experimental validation of an acetylation-related gene signature to evaluate the recurrence and immunotherapeutic response in early-stage lung adenocarcinoma
Authors: Wang Haiqiang , Lu Xiyan , Chen Jiakuan 
Published: December 2022

Abstract
Background
Acetylation is a reversible epigenetic process, playing an important role in the initiation and progression of malignant tumors. However, the prognosis value of acetylation-related genes in the early-stage lung adenocarcinoma (LUAD) remains obscure.

Materials and methods
The acetylation-related genes were collected and clustered based on transcriptome sequencing of the patients with early-stage LUAD from the Cancer Genome Atlas. The genomic divergence analysis, protein–protein interaction network construction, Lasso regression, and univariate Cox regression were used to identify the significant biomarkers for the recurrence of the early-stage LUAD. The multivariate Cox regression was used to establish the predictive model. Gene Expression Omnibus was systemically retrieved and four independent datasets were used for external validation. 23 early-stage LUAD samples were collected from the local hospital to detect the expression difference of the genes in the model. Transfection assays were performed to verify the regulatory ability of the screened gene to the proliferation of LUAD cell lines. The single-cell RNA sequencing of the early-stage LUAD patients and two lung cancer cohorts receiving immunotherapy were utilized to explore the predictive ability of the established model to immunotherapeutic sensitivity.

Results
The clustering based on acetylation-related genes was significantly associated with the recurrence (P < 0.01) and immune infiltration statuses. Through a series of bioinformatical and machine learning methods, RBBP7 and YEATS2 were ultimately identified. Accordingly, a novel gene signature containing RBBP7 and YEATS2 was developed to evaluate the recurrence-free survival of early-stage LUAD, which was then validated in five independent cohorts (pooled hazard ratio = 1.88, 95% confidence interval = 1.49–2.37) and 23 local clinical samples (P < 0.01). The knock-down of YEATS2 obviously suppressed proliferation of H1975 and HCC-827 cells. Single-cell RNA sequencing analyses indicated that RBBP7 and YEATS2 were both associated with the tumor immune response, and the prognosis signature could predict the immunotherapeutic response in two cohorts receiving immunotherapy (P < 0.05; P < 0.01).

Conclusions
Totally, an acetylation-related gene signature is constructed, helping to evaluate the recurrence and immunotherapeutic effectiveness of early-stage LUAD patients.
A novel structurally identified epitope delivered by macrophage membrane-coated PLGA nanoparticles elicits protection against Pseudomonas aeruginosa
Authors: Gao Chen , Chen Yin , Cheng Xin , Zhang Yi , Zhang Yueyue , Wang Ying , Cui Zhiyuan , Liao Yaling , Luo Ping , Wu Weihui , Wang Cheng , Zeng Hao , Zou Quanming , Gu Jiang 
Published: December 2022

AbstractThe increasing prevalence of antibiotic resistance by Pseudomonas aeruginosa (PA) raises an urgent need for an effective vaccine. The outer membrane proteins of PA, especially those that are upregulated during infection, are ideal vaccine targets. However, the strong hydrophobicity of these proteins hinders their application for this purpose. In this study, we selected eight outer membrane proteins from PA with the most significantly upregulated expression. Their extracellular loops were analyzed and screened by using sera from patients who had recovered from PA infection. As a result, a novel immunogenic epitope (Ep167-193) from PilY1 (PA4554) was found. Moreover, we constructed a macrophage membrane-coated PLGA (poly lactic-co-glycolic acid) nanoparticle vaccine carrying PilY1 Ep167-193 (PNPs@M-Ep167-193) that elicits a Th2 immune response and confers adequate protection in mice. Our data furnished the promising vaccine candidate PNPs@M-Ep167-193 while providing additional evidence for structure-based epitope identification and vaccine design.
Graphical Abstract
Chaihu-Guizhi-Ganjiang Decoction is more efficacious in treating irritable bowel syndrome than Dicetel according to metabolomics analysis
Authors: Li Mingming , Zhu Jiawei , Liu Xuan , Dong Zhiying , Tang Jigui , Zhang Cian , Jiao Jianpeng , Chen Jiani , Yin Fenghao , Qiu Shi , Zhang Feng , Gao Shouhong , Wang Zhipeng , Tao Xia , Yue Xiaoqiang , Sun Lianna , Chen Wansheng 
Published: December 2022

Abstract
Background
Chaihu-Guizhi-Ganjiang Decoction (CGGD) is a traditional Chinese medicine (TCM) prescription used to treat viral influenza. There is evidence that CGGD can be used to treat irritable bowel syndrome (IBS) but the potential mechanism of action and metabolites produced upon CGGD treatment remains elusive.

Methods
Patients with IBS were treated with pinaverium bromide (Dicetel™) and then CGGD after a washout period of 1 week. Both treatments lasted for 30 days. The efficacy and changes of metabolites in plasma after the two treatments were compared. Plasma samples were acquired before and after each treatment, and untargeted metabolics analysis was performed.

Results
Efficacy was measured according to the Rome IV criteria and TCM theory. Our results indicated that CGGD showed significantly better efficacy than Dicetel in the treatment of IBS utilizing each criterion. CGGD exerted greater effects on plasma metabolism than Dicetel. Dicetel treatment led to increased tryptophan metabolism (increased levels of 5-Hydroxyindoleacetaldehyde) and increased protein metabolism (increased levels of L-arginine). CGGD treatment significantly (p < 0.05) increased carnitine metabolism, with elevated levels of L-carnitine and acylcarnitine in plasma. Such changes in these metabolites could exert effects against IBS by improving gastrointestinal motility and suppressing pain, depression, and inflammation.

Conclusions
CGGD appeared to be more efficacious than Dicetel for treating patients with IBS. The findings provide a sound support for the underlying biomolecular mechanism of CGGD in the prevention and treatment of IBS.
Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells
Authors: Nikesjö Frida , Sayyab Shumaila , Karlsson Lovisa , Apostolou Eirini , Rosén Anders , Hedman Kristofer , Lerm Maria 
Published: December 2022

AbstractPost-acute COVID-19 syndrome (PACS) has been defined as symptoms persisting after clearance of a COVID-19 infection. We have previously demonstrated that alterations in DNA methylation (DNAm) status persist in individuals who recovered from a COVID-19 infection, but it is currently unknown if PACS is associated with epigenetic changes. We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein–protein interaction networks that have bearings on vesicle formation and mitochondrial function.
A biostatistical approach for augmenting rare bianthraquinone antibiotic production by Streptomyces sp. RA-WS2 using Taguchi design
Authors: Manhas Ravi Singh , Kumar Amit , Chaubey Asha 
Published: December 2022

AbstractConsistent production of bioactives from microbial sources remains a big challenge for fermentation based bio-processes. Setomimycin, a rare 9,9'-bianthrylanthracene antibiotic reported to be active against Gram positive bacteria i.e. Staphyloccocus aureus, Bacillus subtilis, Bacillus cereus, and Mycobacterium smegmatis, including mycobacteria is one of the least exploited antibiotic. Present work aims to enhance and maximize setomimycin production using One Factor at a Time (OFAT) approach, followed by Taguchi L9 orthogonal array (OA) design in 30L fermenter. Four most influential parameters, namely carbon source, nitrogen source, air and agitation were selected for optimization studies. The optimized production medium supplemented with 150 g/L glycerol and 7.5 g/L soyabean meal with an agitation rate of 100 RPM and air flow rate of 20 LPM (Liters Per Minute) resulted in 675 mg/L setomimycin production within 96–108 h of fermentation as compared to the initial production i.e. 40 mg/L. Thus, an overall enhancement of 16.8 folds was achieved in setomimycin production after optimization in 30L fermenter.
Graphical Abstract
Occupational physicians dealing with mental health: between employee and company interests: a qualitative study
Authors: Pößnecker Tim , Baxendale Maximilian , Braun Simone , Schwarz Elena , Hölzer Michael , Angerer Peter , Gündel Harald , Balint Elisabeth , Rothermund Eva 
Published: December 2022

Abstract
Background
Occupational health physicians are increasingly confronted with mental health issues at their workplace. Facing them, most of them feel insecure and not sufficiently trained. Employee’s mental well-being depends at the same time on individual and significantly on organizational variables. This complicates the physician’s position, since they have to serve many interests. The focus of the present study is to investigate what difficulties occupational health physicians face and how organizational culture and management influence their work.

Methods
Interviews were conducted with N = 25 physicians as part of a training for basic mental health care. Interviews were interpreted using qualitative content analysis.

Results
Working with mentally ill employees was difficult for the physicians interviewed. Many felt insecure managing and preventing mental health issues. A need for further education was observed. Environmental factors (organizational culture, management) have a strong impact on the work of an occupational health physician and highlight its systemic dimension. Even though many of our participants report a meanwhile more open attitude towards mental disorders at their workplace, on the level of direct contact to the management prevail descriptions of little acceptance and a high priority of economic outcomes.

Conclusions
More education on topics of mental health is needed for occupational health physicians. Future trainings should consider the intertwined nature of their work and enable them in dealing consciously with other actors in the company. For enhancing employee’s mental well-being occupational health physicians could be granted a strengthened position in companies or be supported through more exchange with colleagues in other companies.
SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex
Authors: Brown Jennifer L. , Hart Damyan W. , Boyle Gabriel E. , Brown Taylor G. , LaCroix Michael , Baraibar Andrés M. , Pelzel Ross , Kim Minwoo , Sherman Mathew A. , Boes Samuel , Sung Michelle , Cole Tracy , Lee Michael K. , Araque Alfonso , Lesné Sylvain E. 
Published: December 2022

AbstractAntisense oligonucleotide (ASO) therapy for neurological disease has been successful in clinical settings and its potential has generated hope for Alzheimer’s disease (AD). We previously described that ablating SNCA encoding for α-synuclein (αSyn) in a mouse model of AD was beneficial. Here, we sought to demonstrate whether transient reduction of αSyn expression using ASOSNCA could be therapeutic in a mouse model of AD. The efficacy of the ASOSNCA was measured via immunocytochemistry, RT-qPCR and western blotting. To assess spatial learning and memory, ASOSNCA or PBS-injected APP and non-transgenic (NTG) mice, and separate groups of SNCA-null mice, were tested on the Barnes circular maze. Hippocampal slice electrophysiology and transcriptomic profiling were used to explore synaptic function and differential gene expression between groups. Reduction of SNCA transcripts alleviated cognitive deficits in male transgenic animals, but surprisingly, not in females. To determine the functional cause of this differential effect, we assessed memory function in SNCA-null mice. Learning and memory were intact in male mice but impaired in female animals, revealing that the role of αSyn on cognitive function is sex-specific. Transcriptional analyses identified a differentially expressed gene network centered around EGR1, a central modulator of learning and memory, in the hippocampi of SNCA-null mice. Thus, these novel results demonstrate that the function of αSyn on memory differs between male and female brains.
Genomic, transcriptomic and RNA editing analysis of human MM1 and VV2 sporadic Creutzfeldt-Jakob disease
Authors: Tarozzi Martina , Baiardi Simone , Sala Claudia , Bartoletti-Stella Anna , Parchi Piero , Capellari Sabina , Castellani Gastone 
Published: December 2022

AbstractCreutzfeldt-Jakob disease (CJD) is characterized by a broad phenotypic spectrum regarding symptoms, progression, and molecular features. Current sporadic CJD (sCJD) classification recognizes six main clinical-pathological phenotypes. This work investigates the molecular basis of the phenotypic heterogeneity of prion diseases through a multi-omics analysis of the two most common sCJD subtypes: MM1 and VV2. We performed DNA target sequencing on 118 genes on a cohort of 48 CJD patients and full exome RNA sequencing on post-mortem frontal cortex tissue on a subset of this cohort. DNA target sequencing identified multiple potential genetic contributors to the disease onset and phenotype, both in terms of coding, damaging-predicted variants, and enriched groups of SNPs in the whole cohort and the two subtypes. The results highlight a different functional impairment, with VV2 associated with higher impairment of the pathways related to dopamine secretion, regulation of calcium release and GABA signaling, showing some similarities with Parkinson’s disease both on a genomic and a transcriptomic level. MM1 showed a gene expression profile with several traits shared with different neurodegenerative, without an apparent distinctive characteristic or similarities with a specific disease. In addition, integrating genomic and transcriptomic data led to the discovery of several sites of ADAR-mediated RNA editing events, confirming and expanding previous findings in animal models. On the transcriptomic level, this work represents the first application of RNA sequencing on CJD human brain samples. Here, a good clusterization of the transcriptomic profiles of the two subtypes was achieved, together with the finding of several differently impaired pathways between the two subtypes. The results add to the understanding of the molecular features associated with sporadic CJD and its most common subtypes, revealing strain-specific genetic signatures and functional similarities between VV2 and Parkinson’s disease and providing preliminary evidence of RNA editing modifications in human sCJD.
Feasibility and acceptability of novel functional electronic stimulated rehabilitation application for treatment in patients with cerebrovascular disorders: the FRAT study protocol
Authors: Mano Tomoo , Asada Kiyoshi , Suzuki Shota , Kasama Shu , Kinugawa Kaoru , Sugie Kazuma , Kasahara Masato , Kido Akira 
Published: December 2022

Abstract
Background
The prognosis of patients with cerebrovascular disorders is poor owing to their high residual rate of hemiplegia. Delayed withdrawal from synkinesis is a major cause of prolonged hemiplegia; however, effective rehabilitation has not been established. This single-arm, open-label study aims to evaluate the influence of a low-frequency treatment device on canceling synkinesis in patients with incomplete paralysis and cerebrovascular disorders.

Methods
Eligible participants will include patients aged 20 years or older with incomplete paralysis, defined as upper limb Brunnstrom stage (BRS) of 2–4, who are within 1 month of onset of a cerebrovascular disorder. Qualified patients will be assigned to the novel rehabilitation treatment with IVES+ for 4 weeks. The primary endpoint of the study is the change from baseline in the upper-limb Fugl-Meyer Assessment (FMA) 2 weeks after the start of treatment. The secondary endpoints are changes in the amount of Functional Independence Measure, changes in the amount of upper-limb BRS, and changes in the amount of Barthel Index (BI) compared to the pre-intervention value at weeks 2 and 4; changes in the upper-limb FMA scores at 1, 3, and 4 weeks; changes in grip strength compared to the pre-intervention values at 1, 2, 3, and 4 weeks; and changes in upper-limb strength (manual muscle test) compared to the pre-intervention values at 1, 2, 3, and 4 weeks.

Discussion
This study will explore the usefulness of IVES+ for recovery from motor paralysis in patients with cerebrovascular disorders.

Trial registration
Japanese Clinical Registry, jRCTs052180226. Date of registration: February 1, 2022
The use of technology in higher education teaching by academics during the COVID-19 emergency remote teaching period: a systematic review
Authors: Sum McQueen , Oancea Alis 
Published: December 2022

AbstractThis paper presents a systematic review of scholarly efforts that uniquely emerged at the onset of the COVID-19 pandemic and focused primarily on higher education teachers’ perspectives on technology use and on associated changes in the relationship between teachers and students amidst the transition to emergency remote teaching worldwide. Our narrative synthesis of 32 studies, the majority of which come from lower-and middle-income countries/regions, suggests that numerous factors interact to shape academics’ technology use in emergency remote teaching across higher education contexts. We report strong findings of teachers’ resilience and resourcefulness in their self-exploration of various technologies and teaching strategies in response to the continued severity of the pandemic. Ultimately, this review suggests directions for further research on engaging educational leaders and faculty in reimagining teaching as not only a core academic function of higher education, but also, and importantly, a humanising experience shaped by an ethics of care.
Intra-operative ultrasound (IOUS) value in cases of AVM and cavernoma excision: single-center experience
Authors: El-Tantawy Ibrahim M. S. , Kassem Mohammed A. , El-Badry Ashraf A. , AbdElwahab Khaled M. 
Published: December 2022

Abstract
Objective
The aim of the study is to use ultrasound to get maximal lesion resection without doing harm to the brain tissue in the absence of neuronavigation system in neurovascular cases as AVM and cavernoma.

Methods
The study is held in Mansoura University Hospitals, Department of Neurosurgery. Two different cases (AVM and cavernoma) were operated, and IOUS was used to assess its value during the surgery. Postoperatively the patients are followed up clinically and radiologically.

Results
In 2 different parenchymal lesions: AVM and cavernoma, IOUS was valuable in accurate localization of the lesions and the related vascularity specially in AVM case. It also helped to evaluate the extent of resection and confirm total excision. It also helped to determine the site of cortical incision and so to minimize brain tissue manipulation to prevent development of postoperative neurological deficit.

Conclusion
IOUS can be very helpful in cases of parenchymal neurovascular lesions such as AVM and cavernoma.
Endovascular treatment of haemorrhagic pancreatic serous cystadenoma
Authors: Le Tat Thomas , Carlier Robert , El Hajjam Mostafa , Sarrot Guillaume-Marie , Obadia Ilan , Tordjman Mickael , Zhou Jeffery 
Published: December 2022

Abstract
Background
Pancreatic microcystic serous cystadenoma are rare benign pancreatic tumors. No treatment is needed in most cases as this lesion is often discovered incidentally. Surgery is not required except in symptomatic cases.

Case presentation
We report herein a rare case of pancreatic serous cystadenoma complicated with a hemorrhage in a 95 years old patient treated with arterial embolization since surgery was not possible. The patient recovered without any adverse events or bleed recurrence in the 6 months following the procedure.

Conclusion
Hemorrhage secondary to a pancreatic serous cystadenoma was successfully treated with arterial embolization, which may represent an alternative therapeutic option to surgery.
Pareto optimality based PID controller design for vehicle active suspension system using grasshopper optimization algorithm
Authors: Gampa Srinivasa Rao , Mangipudi Siva Kumar , Jasthi Kiran , B. Mahesh Babu , Goli Preetham , Das D. , Balas Valentina E. 
Published: December 2022

AbstractIn this paper, a Pareto multiobjective and grasshopper optimization algorithm (GOA) based optimum proportional–integral–derivative (P–I–D) controller design is proposed for improving the vehicle active suspension system dynamics under road disturbance conditions. The Pareto objectives considered are minimization of sprung mass suspension deflection, tyre deflection, sprung mass acceleration minimization and eigenvalue-based objective function. State space model for quarter vehicle active suspension system with P–I–D controller is developed for analyzing the stability and dynamic performance of the system. The sinusoidal-based bump road disturbances are used for testing the robustness of the proposed control technique. Simulation results have been presented to show the advantage of the proposed Pareto multiobjective and GOA-based P–I–D controller over the weighted multiobjective and genetic algorithm-based P–I–D controller in terms of stability and dynamics of the active suspension system.