bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effectiveness of a problem-solving intervention with workplace involvement on self-reported sick leave, psychological symptoms and work ability: a cluster randomised clinical trial
Authors: Eklund Andreas , Karlsson Ida , Bergström Gunnar , Lisa Holmlund , Elisabeth Björk Brämberg 
Published: November 2024

Abstract
Background
Problem-solving interventions with workplace involvement (PSI-WPI) have been shown to reduce sick leave and increase return to work in an occupational health services context. However, many employees struggle with reduced work functioning, anxiety-, and depressive symptoms up to 12 months after a sick leave episode, and it is unclear if the intervention affects outcomes other than sick leave. The aim of this study is to investigate if a PSI-WPI added to care as usual (CAU) is superior to CAU with respect to self-reported sick leave, psychological symptoms, work ability, work performance, and health after RTW when provided in primary care.

Methods
Employed individuals aged 18–59 years on sick leave (2 to 12 weeks) diagnosed by a physician at a primary care center with mild to moderate depression, anxiety, or adjustment disorder were enrolled in a two-armed cluster-randomised trial evaluating the effectiveness of a PSI-WPI. Multiple outcomes were recorded at baseline, six months, 12 months, and every fourth week during the study period. Outcomes were categorised into psychological symptoms, health, work ability, work performance, and self-reported sick leave. Data were analysed using MANOVA, GEE (Generalized Estimating Equations), and cox regression.

Results
One hundred ninety-nine individuals responded to the invitation to participate; one participant withdrew, one was excluded as the employment ended, nine did not answer the baseline survey, and three were removed from the analysis due to missing data. The analysis included 81 subjects who received the intervention and 104 subjects who received the control. Baseline characteristics were similar across both groups. No differences between the groups were found among either variables except one. There was a significant difference between the groups in self-rated health (EQ5D) in favour of the CAU group from baseline to six-month follow-up, with a mean difference of -8.44 (-14.84, -2.04).

Conclusions
A problem-solving intervention with workplace involvement added to CAU did not result in statistically significant reductions in outcomes. Further research is needed to understand why problem-solving interventions appear to have an effect on sick leave in an occupational health services context and not in a primary care context.

Trial registration
NCT3346395, registration date 2017–11-17.
Coenzyme A fueling with pantethine limits autoreactive T cell pathogenicity in experimental neuroinflammation
Authors: Angiari Stefano , Carlucci Tommaso , Budui Simona L. , Bach Simone D. , Dusi Silvia , Walter Julia , Ellmeier Elena , Schnabl Alyssa , Stracke Anika , Bordag Natalie , Tafrali Cansu , Demjaha Rina , Khalil Michael , Angelini Gabriele , Terrabuio Eleonora , Pietronigro Enrica C. , Zenaro Elena , Laudanna Carlo , Rossi Barbara , Constantin Gabriela 
Published: November 2024

Abstract
Background
Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation.

Methods
We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells. Metabolomics, phosphoproteomics, in vitro functional assays, and in vivo studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), were then implemented to evaluate the effect of metabolic targeting on autoreactive T cell pathogenicity. Finally, we confirmed the translational potential of our targeting approach in human pro-inflammatory T helper cell subsets and in T cells from MS patients.

Results
We found that autoreactive encephalitogenic T cells display an altered coenzyme A (CoA) synthesis pathway, compared to resting T cells. CoA fueling with the CoA precursor pantethine (PTTH) affected essential immune-related processes of myelin-specific T cells, such as cell proliferation, cytokine production, and cell adhesion, both in vitro and in vivo. Accordingly, pre-clinical treatment with PTTH before disease onset inhibited the development of EAE by limiting T cell pro-inflammatory potential in vivo. Importantly, PTTH also significantly ameliorated the disease course when administered after disease onset in a therapeutic setting. Finally, PTTH reduced pro-inflammatory cytokine production by human T helper 1 (Th1) and Th17 cells and by T cells from MS patients, confirming its translational potential.

Conclusion
Our data demonstrate that CoA fueling with PTTH in pro-inflammatory and autoreactive T cells may represent a novel therapeutic approach for the treatment of autoimmune neuroinflammation.
PHARC syndrome: an overview
Authors: Harutyunyan Lusine , Callaerts Patrick , Vermeer Sascha 
Published: November 2024

AbstractPHARC, polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa and cataracts, or PHARC is a very rare progressive neurodegenerative autosomal recessive disease caused by biallelic mutations in the ABHD12 (a/b-hydrolase domain containing 12) gene, which encodes a lyso-phosphatidylserine (lyso-PS) lipase. The Orpha number for PHARC is ORPHA171848. The clinical picture of PHARC syndrome is very heterogeneous with a wide range of age at onset for each symptom, making a clinical diagnosis very challenging. Differential diagnoses of the disease include Refsum disease, Charcot–Marie–Tooth disease, and Usher syndrome. Many aspects of the disease, such as the biochemistry and pathophysiology, are still not fully understood. We generated a clinical overview of all PHARC patients, including their mutations, described in literature so far. Furthermore, we give an outline of the most recent developments in research on the pathophysiology of PHARC syndrome in an attempt to gain more insight into and increase awareness of the heterogeneity of the disease. We included 58 patients with PHARC from 37 different families with 27 known ABHD12 mutations. The age at onset (from early childhood to late thirties) and the severity of each feature of PHARC varied widely among patients. Demyelinating polyneuropathy was reported in 91% of the patients. In 86% of patients, hearing loss was present and 74% had cerebellar ataxia, the most variable symptom of PHARC. Retinitis pigmentosa and cataracts occurred in 82% and 86% of patients, respectively. Due to the rareness of the disease and the variable clinical phenotype, a diagnosis of PHARC is often delayed and mostly only made after an extensive genetic work-up. Therefore, we recommend adding the ABHD12 gene to diagnostic gene panels for polyneuropathy, cerebellar ataxia, hearing loss, retinal dystrophy, and cataracts. In addition, a full clinical work-up, neurological (with EMG and neuroimaging of the brain) and ophthalmological (with ERG) examination and audiological tests are indispensable to obtain a comprehensive overview of the clinical phenotype as some symptoms in PHARC may be very subtle and easily overlooked if not tested for. In conclusion, we strongly recommend that patients with (suspected) PHARC should be evaluated in a multidisciplinary setting involving ophthalmologists, audiologists, neurologists, and geneticists to ensure the best possible care. Furthermore, we discuss whether PHARC is a spectrum with various incomplete phenotypes even later in life, or whether it is a syndrome in which the clinical symptoms are variable in severity and age of onset.
Low nucleotide diversity of the Plasmodium falciparum AP2-EXP2 gene among clinical samples from Ghana
Authors: Quansah Elvis , Zhao Ji , Eduful Kenneth Kofi , Amoako Enock Kofi , Amenga-Etego Lucas , Halm-Lai Faustina , Luo Qingli , Shen Jilong , Zhang Chao , Yu Li 
Published: November 2024

Abstract
Background
PfAP2-EXP2 is located within chromosome 6 of Plasmodium falciparum recently identified to be undergoing an extensive selective sweep in West African isolates. The gene encoding this transcription factor, PfAP2-EXP2, is essential and thus likely subject to purifying selection that limits variants in the parasite population despite its genomic location.

Methods
72 Plasmodium falciparum field samples and 801 clinical sequences from the Pf6 MalariaGEN dataset of Ghanaian origin, were integrated and analysed.

Results
A total of 14 single nucleotide variants of which 5 were missense variants, were identified after quality checks and filtering. Except for one, all identified variants were rare among the clinical samples obtained in this study (Minor allelic frequency < 0.01). Further results revealed a considerably low dN/dS value (0.208) suggesting the presence of purifying selection. Further, all the mutant amino acids were wildtype residues in AP2-EXP2 orthologous proteins—tentatively suggesting a genus-level conservation of amino acid residues. Computational analysis and predictions corroborated these findings.

Conclusions
Despite the recent extensive selective sweep within chromosome 6 of West African isolates, PfAP2-EXP2 of Ghanaian origin exhibits low nucleotide diversity and very low dN/dS consistent with purifying selection acting to maintain the function of an essential gene. The conservation of AP2-EXP2 is an important factor that makes it a potential drug target.

Graphical Abstract
The assembly and activation of the PANoptosome promote porcine granulosa cell programmed cell death during follicular atresia
Authors: Wu Hao , Han Yingxue , Liu Jikang , Zhao Rong , Dai Shizhen , Guo Yajun , Li Nan , Yang Feng , Zeng Shenming 
Published: November 2024

Abstract
Background
Follicular atresia significantly impairs female fertility and hastens reproductive senescence. Apoptosis of granulosa cells is the primary cause of follicular atresia. Pyroptosis and necroptosis, as additional forms of programmed cell death, have been reported in mammalian cells. However, the understanding of pyroptosis and necroptosis pathways in granulosa cells during follicular atresia remains unclear. This study explored the effects of programmed cell death in granulosa cells on follicular atresia and the underlying mechanisms.

Results
The results revealed that granulosa cells undergo programmed cell death including apoptosis, pyroptosis, and necroptosis during follicular atresia. For the first time, we identified the formation of a PANoptosome complex in porcine granulosa cells. This complex was initially identified as being composed of ZBP1, RIPK3, and RIPK1, and is recruited through the RHIM domain. Additionally, we demonstrated that caspase-6 is activated and cleaved, interacting with RIPK3 as a component of the PANoptosome. Heat stress may exacerbate the activation of the PANoptosome, leading to programmed cell death in granulosa cells.

Conclusions
Our data identified the formation of a PANoptosome complex that promoted programmed cell death in granulosa cells during the process of follicular atresia. These findings provide new insights into the molecular mechanisms underlying follicular atresia.
Effectiveness of a multi-component sleep-mood group intervention on improving insomnia in university students – a pilot randomized controlled trial
Authors: Pape Laura M. , Jonker Sophie , Kivelä Liia M.M. , van Straten Annemieke , Antypa Niki 
Published: November 2024

Abstract
Background
Sleep and mental health problems are very common in university students. The objective of this study was to assess the effectiveness of a multi-component sleep-mood intervention on improving sleep and mental health in university students with clinically significant insomnia symptoms, and to investigate possible mediators.

Methods
Thirty-five participants were randomized to the Sleep Mood Intervention: Live Effectively (SMILE) intervention (n = 23), or wait-list group (n = 12). SMILE is a multi-component group therapy and includes elements of cognitive behavioral therapy for insomnia (CBT-I), mindfulness, and lifestyle modifications, in four weekly two-hour sessions. The primary outcome was insomnia severity. Secondary outcomes were severity of depression and anxiety, and quality of life (QoL). Dysfunctional beliefs and attitudes about sleep and pre-sleep arousal were assessed as mediators.

Results
Intention-to-treat analysis showed significant time x treatment interaction on insomnia symptoms p = .02, partial η²= 0.15, d = 0.84 [95% CI: 0.63 to 1.14], with significantly lower insomnia severity for SMILE compared to waitlist at post-test. No significant effects were found on depression d = 0.02 [95% CI: -0.35 to 0.37], anxiety d = 0.15 [95% CI: -0.16 to 0.53], and QoL d = 0.09 [95% CI: -0.25 to 0.42]. Dysfunctional beliefs mediated the effect on insomnia severity, but pre-sleep arousal did not.

Conclusions
This integrated group intervention is associated with reductions in insomnia symptoms in university students. Since no significant effects were detected on mood and QoL, future studies with larger sample size may explore the effects of this intervention on these outcomes.

Trial registration
Registry: Overzicht van Medisch-wetenschappelijk Onderzoek. Registration number: NL-OMON46359. Date of registration: September 18th, 2018.
Linking past insights with contemporary understanding: an ontological and knowledge graph approach to the transmission of ancient Chinese classics
Authors: Cui Yu , Yao Shenjun , Wu Jianping , Lv Muhan 
Published: November 2024

Abstract
Ancient Chinese classics embody and transmit the intellectual heritage of China across generations. These texts, rich in enduring ideas, narratives, and insights, have been passed down through a lengthy historical process. While digital modeling of cultural heritage has advanced, research that integrates both the unique characteristics of these classics and their transmission processes remains limited. This study introduces ClaOnto, an ontology specifically designed for ancient Chinese classics. It captures the various versions of these texts and their interrelations, contents, related individuals, locations, periods, and languages. It also emphasizes the processes and evaluations involved in their transmission. This contributes to a more nuanced understanding and increased awareness of preserving ancient classics. ClaOnto comprises three modules: Basic Information, Transmission Information, and Evaluation Information. Its development involved adapting and enhancing existing mature ontologies, as well as designing new concepts and relationships to articulate the knowledge and intangible values transmitted through these classics across generations. Additionally, by employing methods such as data mining, text analysis, and data visualization, this study outlines a workflow for implementing this ontology-based knowledge graph, demonstrated using the Tao Te Ching as a case study. The methodological enhancement enriches the analysis of how the intangible value in classics manifests through transmission.
Increased national critical care demands were associated with a higher mortality of intubated COVID-19 patients in Japan: a retrospective observational study
Authors: Kikutani Kazuya , Nishikimi Mitsuaki , Emoto Ryo , Matsui Shigeyuki , Ohbe Hiroyuki , Ogura Takayuki , Hashimoto Satoru , Kushimoto Shigeki , Takeda Shinhiro , Ohshimo Shinichiro , Shime Nobuaki 
Published: November 2024

Abstract
Background
There was no study to investigate the association between the national surge of Coronavirus disease 2019 (COVID-19) patients and the mortality of mechanically ventilated COVID-19 patients. The aim of this study was to assess the association between mortality in mechanically ventilated COVID-19 patients and two distinct national COVID-19 surge indices: (1) the daily number of newly confirmed COVID-19 cases, representing overall medical demands and (2) the total number of critically ill COVID-19 patients, reflecting critical care demands.

Methods
We analyzed the patient data registered in a national database of mechanically ventilated COVID-19 patients between February 6, 2020, and May 16, 2023, combined with the data officially published by the Japanese government. Multivariable logistic regression analysis was performed to evaluate the association of these two indices with COVID-19 mortality. A generalized linear mixed effect model was used to examine the relationships between the variation in the impact of critical care demands across hospitals and the variation in baseline risk across hospitals.

Results
The data of 8327 patients from 264 centers in Japan were analyzed. The overall mortality rate was 24% (1990/8327). The critical care demands, but not overall medical demands, were independently associated with the mortality (OR, 1.11; 95% CI 1.07–1.16; p < 0.001). This effect of critical care demands on the mortality was more pronounced in hospitals with higher baseline risk (r = 0.67).

Conclusions
The national critical care demands were independently associated with the mortality of COVID-19 patients requiring mechanical ventilation. This effect was more pronounced in hospitals with higher baseline risk.
Precise regulating the specific oxygen consumption rate to strengthen the CoQ10 biosynthesis by Rhodobater sphaeroides
Authors: Li Bo , Ge Yan , Liang Jianguang , Zhu Zhichun , Chen Biqin , Li Dan , Zhuang Yingping , Wang Zejian 
Published: November 2024

AbstractCoenzyme Q10 (CoQ10) is the most consumed dietary supplement and mainly biosynthesized by aerobic fermentation of Rhodobacter sphaeroides (R. sphaeroides). Oxygen supply was identified as a bottleneck for improving CoQ10 yield in R. sphaeroides. In this study, a precise regulation strategy based on dielectric spectroscopy (DS) was applied to further improve CoQ10 biosynthesis by R. sphaeroide. First, a quantitative response model among viable cells, cell morphology, and oxygen uptake rate (OUR) was established. DS could be used to detect viable R. sphaeroides cells, and the relationship among cell morphology, CoQ10 biosynthesis, and OUR was found to be significant. Based on this model, the online specific oxygen consumption rate (QO2) control strategy was successfully applied to the CoQ10 fermentation process. QO2 controlled at 0.07 ± 0.01 × 10− 7mmol/cell/h was most favorable for CoQ10 biosynthesis, resulting in a 28.3% increase in CoQ10 production. Based on the multi-parameters analysis and online QO2 control, a precise online nutrient feeding strategy was established using conductivity detected by DS. CoQ10 production was improved by 35%, reaching 3384 mg/L in 50 L bioreactors. This online control strategy would be effectively applied for improving industrial CoQ10 production, and the precise fermentation control strategy could also be applied to other fermentation process.
Development of a whole-cell SELEX process to select species-specific aptamers against Aspergillus niger
Authors: Ellena Valeria , Ioannou Alexandra , Kolm Claudia , Farnleiter Andreas H. , Steiger Matthias G. 
Published: November 2024

Abstract
Background
Spores produced by the filamentous fungus Aspergillus niger are abundant in a variety of environments. The proliferation of this fungus in indoor environments has been associated to health risks and its conidia can cause allergic reaction and severe invasive disease in animals and humans. Therefore, the detection and monitoring of Aspergillus conidia is of utmost importance to prevent serious fungal infections and contaminations. Among others, aptamers could serve as biosensors for the specific detection of fungal spores.

Results
In this study, DNA aptamers specific to conidia of A. niger were developed by optimizing a whole-cell SELEX approach. Three whole-cells SELEX experiments were performed in parallel with similar conditions. Quantification of recovered ssDNA and melting curve analyses were applied to monitor the ongoing SELEX process. Next-generation sequencing was performed on selected recovered ssDNA pools, allowing the identification of DNA aptamers which bind with high affinity to the target cells. The developed aptamers were shown to be species-specific, being able to bind to A. niger but not to A. tubingensis or to A. nidulans. The binding affinity of two aptamers (AN01-R9-006 and AN02-R9-185) was measured to be 58.97 nM and 138.71 nM, respectively, which is in the range of previously developed aptamers.

Conclusions
This study demonstrates that species-specific aptamers can be successfully developed via whole-cell SELEX to distinguish different Aspergillus species and opens up new opportunities in the field of diagnostics of fungal infections.
Migration experience and risky financial assets investments of county households: evidence from China
Authors: Zhang Yunliang , He Xiaobin , Liu Jiankun 
Published: November 2024

AbstractEnhancing the support for inclusive finance in county economies is crucial in achieving the strategic goal of building financial power. Drawing upon the theoretical lens of county-level inclusive financial accessibility, this study examines the effect of the migration experience (ME) of county socialites on their risky financial assets investment (FAI) and the underlying mechanisms. We utilize data sourced from the County Consumption Survey, a nationwide effort by the Department of Sociology of Tsinghua University and the 58 Tongzhen Research Group. Our findings reveal that the ME of county socialites significantly boosts their likelihood of engaging in financial markets. Furthermore, housing inequality factors, such as housing property rights and housing loans, play a moderating role in the impact of individual ME on their FAI. Additionally, the financial concept has a masking effect rather than a mediating effect on the path of the ME affecting FAI. Notably, the promotion effect of ME displays heterogeneity. Specifically, ME has a stronger positive effect on FAI among college-educated groups, members of the Communist Party of China (CPC), and urban hukou residents than on those who have not completed college education, non-CPC members and rural hukou households. In light of these findings, we propose policy recommendations to optimize the distribution of financial services, adjust the housing equality policy, and enhance inclusive financial literacy.