bluuebunny/crossref_metadata_2025_split huggingface dataset:
A community-based peer-support group intervention “Paths to EvERyday life” (PEER) added to service as usual for adults with vulnerability to mental health difficulties – a study protocol for a randomized controlled trial
Authors: Poulsen Chalotte Heinsvig , Egmose Cecilie Høgh , Ebersbach Bea Kolbe , Hjorthøj Carsten , Eplov Lene Falgaard 
Published: September 2022

Abstract
Background
The number of people struggling with vulnerability to mental health difficulties is increasing worldwide, and there is a need for new interventions, to prevent more people from developing serious mental illnesses. In recent years, peer support has been suggested as a key element in creating person-centered interventions in mental health services. However, the evidence for peer support is not yet established. We aim to investigate the effect of a 10-week peer-support intervention “Paths to EvERyday life” (PEER) added to service as usual (SAU) versus SAU alone in a Danish municipality setting.

Methods
A two-armed, investigator-initiated, multi-municipal, parallel-group superiority trial to investigate the effectiveness of the PEER intervention added to SAU compared to SAU alone. A total of 284 participants will be recruited from the municipal social services in the participating municipalities and by self-referrals and randomly assigned to (1) the PEER intervention added to SAU or (2) SAU. The primary outcome is a self-assessed personal recovery (Questionnaire about the process of recovery (QPR-15)) at end of the intervention. The secondary outcomes are self-assessed empowerment (Empowerment Scale Rogers (ESR)), quality of life (The Manchester Short Assessment of Quality of life (MANSA)), and functioning (Work and Social Adjustment Scale (WSAS)).

Discussion
This trial will test a new community-based peer-support intervention, and if the intervention proves to be effective, the goal is that future integration of this intervention will improve individual recovery and mental health and reduce the societal burden of individuals seeking municipal social support and/or mental health services.

Trial registration
ClinicalTrials.gov NCT04639167. Registered on Nov. 19, 2020.
Preoperative oral diazepam for intraoperative blood pressure stabilisation in hypertensive patients undergoing vitrectomy under retrobulbar nerve block anaesthesia: study protocol for a randomised controlled trial
Authors: Qian Tianwei , Gong Qiaoyun , Chen Chong , Wu Xia , Xue Lin , Fan Ying , Wang Weijun , Zhang Zhihua , Cao Hui , Xu Xun 
Published: September 2022

Abstract
Background
As a type of local anaesthesia, retrobulbar nerve block is often used in vitrectomy, with patients remaining conscious during the operation. The increase in systolic blood pressure (SBP) caused by tension and fear during the operation—especially in patients with a history of hypertension—can negatively impact the safety of the procedure, resulting in suprachoroidal haemorrhage or retinal haemorrhage. Diazepam has a sedative effect and can relieve tension during surgery. This study aims to evaluate the efficacy and safety of diazepam for intraoperative BP stabilisation in hypertensive patients under retrobulbar anaesthesia during surgery.

Methods
This single-centre, double-blind, randomised controlled and parallel clinical trial will include 180 hypertensive patients who will undergo vitrectomy with nerve block anaesthesia. Study participants will be randomly allocated in a 1:1 ratio to intervention (patients receiving oral diazepam before the operation) and control (patients receiving oral placebo before the operation) groups. The primary outcome is the effective rate of intraoperative BP control (systolic BP during operation maintained at <160mmHg at all timepoints). The secondary outcomes are the proportion of patients with SBP ≥180 mmHg at any timepoint from operation to 1 h post-operation, the change of mean systolic blood pressure and mean heart rate during operation from baseline, as well as the number of patients with intraoperative and post-operative adverse reactions within 12 weeks of surgery. The logistic regression model will be performed to compare the outcomes.

Discussion
This study will evaluate the efficacy and safety of diazepam for intraoperative BP stabilisation in hypertensive patients under nerve block anaesthesia during surgery. The results of this trial will reveal whether diazepam has a significant effect on intraoperative BP stability in patients with a history of hypertension who require vitrectomy. If the results of this trial are significant, a large-scale multi-centre clinical trial can be designed.

Trial registration
Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100041772. Registered on 5 January 2021.
Researcher perspectives on ethics considerations in epigenetics: an international survey
Authors: Dupras Charles , Knoppers Terese , Palmour Nicole , Beauchamp Elisabeth , Liosi Stamatina , Siebert Reiner , Berner Alison May , Beck Stephan , Charest Ian , Joly Yann 
Published: September 2022

AbstractOver the past decade, bioethicists, legal scholars and social scientists have started to investigate the potential implications of epigenetic research and technologies on medicine and society. There is growing literature discussing the most promising opportunities, as well as arising ethical, legal and social issues (ELSI). This paper explores the views of epigenetic researchers about some of these discussions. From January to March 2020, we conducted an online survey of 189 epigenetic researchers working in 31 countries. We questioned them about the scope of their field, opportunities in different areas of specialization, and ELSI in the conduct of research and knowledge translation. We also assessed their level of concern regarding four emerging non-medical applications of epigenetic testing—i.e., in life insurance, forensics, immigration and direct-to-consumer testing. Although there was strong agreement on DNA methylation, histone modifications, 3D structure of chromatin and nucleosomes being integral elements of the field, there was considerable disagreement on transcription factors, RNA interference, RNA splicing and prions. The most prevalent ELSI experienced or witnessed by respondents were in obtaining timely access to epigenetic data in existing databases, and in the communication of epigenetic findings by the media. They expressed high levels of concern regarding non-medical applications of epigenetics, echoing cautionary appraisals in the social sciences and humanities literature.
The absence of AhR in CD4+ T cells in patients with acute graft-versus-host disease may be related to insufficient CTCF expression
Authors: Zeng Cong , Cheng Ting-ting , Ma Xia , Liu Yi , Hua Juan , Chen Xu , Wang Shi-yu , Xu Ya-jing 
Published: September 2022

Abstract
Background
Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Accumulating evidence suggests that imbalanced Treg/Th17 ratio accelerates the progression of aGVHD. The aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix transcription factor activated through cognate ligand binding. Current evidence supports that AhR plays a critical regulatory role in the differentiation of Treg and Th17 cells. However, the relationship between AhR and aGVHD remains unclear.

Results
Our results showed that AhR expression was downregulated significantly in CD4+ T cells from patients with aGVHD compared with the non-aGVHD group. We also discovered that after activating AhR deficient CD4+ T cells, the expression levels of the activation markers-CD40L, CD134 and CD137 and cell proliferation activity were significantly higher than those of AhR-expressing CD4+ T cells. Restoring the expression of AhR in aGVHD CD4+ T cells resulted in significantly increased percentage of Tregs and associated gene transcripts, including Foxp3, IL-10 and CD39. In contrast, Th17 cell amounts and the transcription of related genes, including RORγt, IL-17A and IL-17F, were significantly reduced. We confirmed that CTCF recruited EP300 and TET2 to bind to the AhR promoter region and promoted AhR expression by mediating histone H3K9/K14 hyperacetylation and DNA demethylation in this region. The low expression of CTCF caused histone hypoacetylation and DNA hypermethylation of the AhR promoter, resulting in insufficient expression in aGVHD CD4+ T cells.

Conclusions
CTCF is an important inducer of AhR transcription. Insufficient expression of CTCF leads to excessive AhR downregulation, resulting in substantial CD4+ T cell activation and Th17/Treg ratio increase, thereby mediating the occurrence of aGVHD.
Dynamic network model reveals distinct tau spreading patterns in early- and late-onset Alzheimer disease
Authors: Lee Wha Jin , Cho Hanna , Baek Min Seok , Kim Han-Kyeol , Lee Jae Hoon , Ryu Young Hoon , Lyoo Chul Hyoung , Seong Joon-Kyung 
Published: September 2022

Abstract
Background
The clinical features of Alzheimer’s disease (AD) vary substantially depending on whether the onset of cognitive deficits is early or late. The amount and distribution patterns of tau pathology are thought to play a key role in the clinical characteristics of AD, which spreads throughout the large-scale brain network. Here, we describe the differences between tau-spreading processes in early- and late-onset symptomatic individuals on the AD spectrum.

Methods
We divided 74 cognitively unimpaired (CU) and 68 cognitively impaired (CI) patients receiving 18F-flortaucipir positron emission tomography scans into two groups by age and age at onset. Members of each group were arranged in a pseudo-longitudinal order based on baseline tau pathology severity, and potential interregional tau-spreading pathways were defined following the order using longitudinal tau uptake. We detected a multilayer community structure through consecutive tau-spreading networks to identify spatio-temporal changes in the propagation hubs.

Results
In each group, ordered tau-spreading networks revealed the stage-dependent dynamics of tau propagation, supporting distinct tau accumulation patterns. In the young CU/early-onset CI group, tau appears to spread through a combination of three independent communities with partially overlapped territories, whose specific driving regions were the basal temporal regions, left medial and lateral temporal regions, and left parietal regions. For the old CU/late-onset CI group, however, continuation of major communities occurs in line with the appearance of hub regions in the order of bilateral entorhinal cortices, parahippocampal and fusiform gyri, and lateral temporal regions.

Conclusion
Longitudinal tau propagation depicts distinct spreading pathways of the early- and late-onset AD spectrum characterized by the specific location and appearance period of several hub regions that dominantly provide tau.
Extracellular vesicle therapy for traumatic central nervous system disorders
Authors: Zhang Jing , Shi Weipeng , Qu Di , Yu Tengbo , Qi Chao , Fu Haitao 
Published: September 2022

AbstractTraumatic central nervous system (CNS) disorders have catastrophic effects on patients, and, currently, there is no effective clinical treatment. Cell transplantation is a common treatment for traumatic CNS injury in animals. In recent years, an increasing number of studies have reported that the beneficial effect of transplanted cells for CNS repair is mediated primarily through the extracellular vesicles (EVs) secreted by the cells, in which microRNAs play a major role. Accordingly, numerous studies have evaluated the roles and applications of EVs secreted by different cell types in neurological diseases. Furthermore, due to their unique biological features, EVs are used as disease biomarkers and drug delivery systems for disease prevention and treatment. We discuss current knowledge related to EVs, focusing on the mechanism underlying their effects on traumatic CNS diseases, and summarize existing research on the potential clinical utility of EVs as disease biomarkers and drug delivery systems.
Challenges and perspectives of tendon-derived cell therapy for tendinopathy: from bench to bedside
Authors: Chen Ziming , Chen Peilin , Zheng Monica , Gao Junjie , Liu Delin , Wang Allan , Zheng Qiujian , Leys Toby , Tai Andrew , Zheng Minghao 
Published: September 2022

AbstractTendon is composed of dense fibrous connective tissues, connecting muscle at the myotendinous junction (MTJ) to bone at the enthesis and allowing mechanical force to transmit from muscle to bone. Tendon diseases occur at different zones of the tendon, including enthesis, MTJ and midsubstance of the tendon, due to a variety of environmental and genetic factors which consequently result in different frequencies and recovery rates. Self-healing properties of tendons are limited, and cell therapeutic approaches in which injured tendon tissues are renewed by cell replenishment are highly sought after. Homologous use of individual’s tendon-derived cells, predominantly differentiated tenocytes and tendon-derived stem cells, is emerging as a treatment for tendinopathy through achieving minimal cell manipulation for clinical use. This is the first review summarizing the progress of tendon-derived cell therapy in clinical use and its challenges due to the structural complexity of tendons, heterogeneous composition of extracellular cell matrix and cells and unsuitable cell sources. Further to that, novel future perspectives to improve therapeutic effect in tendon-derived cell therapy based on current basic knowledge are discussed.
Human pluripotent stem cell-derived macrophages and macrophage-derived exosomes: therapeutic potential in pulmonary fibrosis
Authors: Rasaei Roya , Tyagi Apoorvi , Rasaei Shima , Lee Seung-Joon , Yang Se-Ran , Kim Kye-Seong , Ramakrishna Suresh , Hong Seok-Ho 
Published: September 2022

AbstractPulmonary fibrosis (PF) is a fatal chronic disease characterized by accumulation of extracellular matrix and thickening of the alveolar wall, ultimately leading to respiratory failure. PF is thought to be initiated by the dysfunction and aberrant activation of a variety of cell types in the lung. In particular, several studies have demonstrated that macrophages play a pivotal role in the development and progression of PF through secretion of inflammatory cytokines, growth factors, and chemokines, suggesting that they could be an alternative therapeutic source as well as therapeutic target for PF. In this review, we describe the characteristics, functions, and origins of subsets of macrophages involved in PF and summarize current data on the generation and therapeutic application of macrophages derived from pluripotent stem cells for the treatment of fibrotic diseases. Additionally, we discuss the use of macrophage-derived exosomes to repair fibrotic lung tissue.
A time-splitting local meshfree approach for time-fractional anisotropic diffusion equation: application in image denoising
Authors: Mazloum Jalil , Hadian Siahkal-Mahalle Behrang 
Published: September 2022

AbstractImage denoising approaches based on partial differential modeling have attracted a lot of attention in image processing due to their high performance. The nonlinear anisotropic diffusion equations, specially Perona–Malik model, are powerful tools that improve the quality of the image by removing noise while preserving details and edges. In this paper, we propose a powerful and accurate local meshless algorithm to solve the time-fractional Perona–Malik model which has an adjustable fractional derivative making the control of the diffusion process more convenient than the classical one. In order to overcome the complexities of the problem, a suitable combination of the compactly supported radial basis function method and operator splitting technique is proposed to convert a complex time-fractional partial differential equation into sparse linear algebraic systems that standard solvers can solve. The numerical results of classical and fractional models are explored in different metrics to demonstrate the proposed scheme’s effectiveness. The numerical experiments confirm that the method is suitable to denoise digital images and show that the fractional derivative increases the model’s ability to remove noise in images.
“Autonomous weapons” as a geopolitical signifier in a national power play: analysing AI imaginaries in Chinese and US military policies
Authors: Bächle Thomas Christian , Bareis Jascha 
Published: September 2022

Abstract“Autonomous weapon systems” (AWS) have been subject to intense discussions for years. Numerous political, academic and legal actors are debating their consequences, with many calling for strict regulation or even a global ban. Surprisingly, it often remains unclear which technologies the term AWS refers to and also in what sense these systems can be characterised as autonomous at all. Despite being feared by many, weapons that are completely self-governing and beyond human control are more of a conceptual possibility than an actual military reality.As will be argued, the conflicting interpretations of AWS are largely the result of the diverse meanings that are constructed in political discourses. These interpretations convert specific understandings of AI into strategic assets and consequently hinder the establishment of common ethical standards and legal regulations. In particular, this article looks at the publicly available military AI strategies and position papers by China and the USA. It analyses how AWS technologies, understood as evoking sociotechnical imaginaries, are politicised to serve particular national interests.The article presents the current theoretical debate, which has sought to find a functional definition of AWS that is sufficiently unambiguous for regulatory or military contexts. Approaching AWS as a phenomenon that is embedded in a particular sociotechnical imaginary, however, flags up the ways in which nation states portray themselves as part of a global AI race, competing over economic, military and geopolitical advantages. Nation states do not just enforce their geopolitical ambitions through a fierce realpolitik rhetoric but also play around with ambiguities in definitions. This especially holds true for China and the USA, since they are regarded and regard themselves as hegemonic antagonists, presenting competing self-conceptions that are apparent in their histories, political doctrines and identities. The way they showcase their AI-driven military prowess indicates an ambivalent rhetoric of legal sobriety, tech-regulation and aggressive national dominance. AWS take on the role of signifiers that are employed to foster political legitimacy or to spark deliberate confusion and deterrence.
Light-driven progesterone production by InP–(M. neoaurum) biohybrid system
Authors: Liu Kun , Wang Feng-Qing , Liu Ke , Zhao Yunqiu , Gao Bei , Tao Xinyi , Wei Dongzhi 
Published: September 2022

AbstractProgesterone is one of the classical hormone drugs used in medicine for maintaining pregnancy. However, its manufacturing process, coupled with organic reagents and poisonous catalysts, causes irreversible environmental pollution. Recent advances in synthetic biology have demonstrated that the microbial biosynthesis of natural products, especially difficult-to-synthesize compounds, from building blocks is a promising strategy. Herein, overcoming the heterologous cytochrome P450 enzyme interdependency in Mycolicibacterium neoaurum successfully constructed the CYP11A1 running module to realize metabolic conversion from waste phytosterols to progesterone. Subsequently, progesterone yield was improved through strategies involving electron transfer and NADPH regeneration. Mutant CYP11A1 (mCYP11A1) and adrenodoxin reductase (ADR) were connected by a flexible linker (L) to form the chimera mCYP11A1-L-ADR to enhance electron transfer. The chimera mCYP11A1-L-ADR, adrenodoxin (ADX), and ADR-related homolog ARH1 were expressed in M. neoaurum, showed positive activity and produced 45 mg/L progesterone. This electron transfer strategy increased progesterone production by 3.95-fold compared with M. neoaurum expressing mCYP11A1, ADR, and ADX. Significantly, a novel inorganic–biological hybrid system was assembled by combining engineered M. neoaurum and InP nanoparticles to regenerate NADPH, which was increased 84-fold from the initial progesterone titer to 235 ± 50 mg/L. In summary, this work highlights the green and sustainable potential of obtaining synthetic progesterone from sterols in M. neoaurum.
Graphical Abstract
Comment on “Soil salinity assessment by using near-infrared channel and Vegetation Soil Salinity Index derived from Landsat 8 OLI data: a case study in the Tra Vinh Province, Mekong Delta, Vietnam” by Kim-Anh Nguyen, Yuei-An Liou, Ha-Phuong Tran, Phi-Phung Hoang and Thanh-Hung Nguyen
Authors: Silvestri Sonia , Nguyen Diep Ngoc , Chiapponi Emilia 
Published: September 2022

AbstractNguyen et al. (Prog Earth Planet Sci 7:1, 2020. https://doi.org/10.1186/s40645-019-0311-0) suggest that Landsat 8 OLI can be used to map and monitor soil salinity in the coastal zone of the Mekong River Delta. The authors use empirical correlations between the near-infrared (NIR) band, or vegetation indexes containing the NIR band, and soil salinity. We show that within the coastal portion of the Mekong Delta, extensively ponded due to widespread shrimp farming, about 90% of Landsat 8 pixels are fully or partially covered by water. We then find that, due to strong NIR radiation absorption, NIR reflectance from ponded pixels decreases linearly with increasing water percentage cover, while no significant correlation is found between reflectance and soil salinity. Through detailed new analyses, we conclude that NIR reflectance attenuation cannot be ascribed to vegetation stress caused by soil salinity, but rather to the presence of water ponds. We also show that a similar behavior exists in ponded freshwater inland areas, confirming that the NIR absorption exerted by water is independent of salinity.
Masquelet technique in military practice: specificities and future directions for combat-related bone defect reconstruction
Authors: Mathieu Laurent , Mourtialon Romain , Durand Marjorie , de Rousiers Arnaud , de l’Escalopier Nicolas , Collombet Jean-Marc 
Published: September 2022

AbstractBecause of its simplicity, reliability, and replicability, the Masquelet induced membrane technique (IMT) has become one of the preferred methods for critical bone defect reconstruction in extremities. Although it is now used worldwide, few studies have been published about IMT in military practice. Bone reconstruction is particularly challenging in this context of care due to extensive soft-tissue injury, early wound infection, and even delayed management in austere conditions. Based on our clinical expertise, recent research, and a literature analysis, this narrative review provides an overview of the IMT application to combat-related bone defects. It presents technical specificities and future developments aiming to optimize IMT outcomes, including for the management of massive multi-tissue defects or bone reconstruction performed in the field with limited resources.