bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo
Authors: Wakasugi Daiki , Kondo Shinji , Ferdousi Farhana , Mizuno Seiya , Yada Akira , Tominaga Kenichi , Takahashi Satoru , Isoda Hiroko 
Published: June 2024

Abstract
Background
Neuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- and anxiety-like disorders. In recent years, there has been significant attention on natural compounds with potent anti-inflammatory effects due to their potential in mitigating neuroinflammation and neuroplasticity.

Methods
In the present study, we aimed to evaluate the neuroprotective effects of oleacein (OC), a rare secoiridoid derivative found in extra virgin olive oil. Our goal was to explore the BDNF/TrkB neurotrophic activity of OC and subsequently assess its potential for modulating neuroinflammatory response using human neuroblastoma cells (SH-SY5Y cells) and an in vivo model of depression induced by lipopolysaccharide (LPS)-mediated inflammation.

Results
In SH-SY5Y cells, OC exhibited a significant dose-dependent increase in BDNF expression. This enhancement was absent when cells were co-treated with inhibitors of BDNF's receptor TrkB, as well as downstream molecules PI3K and MEK. Whole-transcriptomics analysis revealed that OC upregulated cell cycle-related genes under normal conditions, while downregulating inflammation-associated genes in LPS-induced conditions. Furthermore, surface plasmon resonance (SPR) assays demonstrated that OC exhibited a stronger and more stable binding affinity to TrkB compared to the positive control, 7,8-dihydroxyflavone.
Importantly, bioluminescence imaging revealed that a single oral dose of OC significantly increased BDNF expression in the brains of Bdnf-IRES-AkaLuc mice. Furthermore, oral administration of OC at a dosage of 10 mg/kg body weight for 10 days significantly reduced immobility time in the tail suspension test compared to the LPS-treated group. RT-qPCR analysis revealed that OC significantly decreased the expression of pro-inflammatory cytokines Tnfα, Il6, and Il1β, while simultaneously enhancing Bdnf expression, as well as both pro and mature BDNF protein levels in mice hippocampus. These changes were comparable to those induced by the positive control antidepressant drug fluoxetine. Additionally, microarray analysis of mouse brains confirmed that OC could counteract LPS-induced inflammatory biological events.

Conclusion
Altogether, our study represents the first report on the potential antineuroinflammatory and antidepressant properties of OC via modulation of BDNF/TrkB neurotrophic activity. This finding underscores the potential of OC as a natural therapeutic agent for depression- and anxiety-related disorders.
Effects of temporal IFNγ exposure on macrophage phenotype and secretory profile: exploring GMP-Compliant production of a novel subtype of regulatory macrophages (MregIFNγ0) for potential cell therapeutic applications
Authors: Zitta Karina , Hummitzsch Lars , Lichte Frank , Fändrich Fred , Steinfath Markus , Eimer Christine , Kapahnke Sebastian , Buerger Matthias , Hess Katharina , Rusch Melanie , Rusch Rene , Berndt Rouven , Albrecht Martin 
Published: June 2024

Abstract
Background
Macrophages are involved in tissue homeostasis, angiogenesis and immunomodulation. Proangiogenic and anti-inflammatory macrophages (regulatory macrophages, Mreg) can be differentiated in-vitro from CD14+ monocytes by using a defined cell culture medium and a stimulus of IFNγ.

Aim of the study
To scrutinize the potential impact of temporal IFNγ exposure on macrophage differentiation as such exposure may lead to the emergence of a distinct and novel macrophage subtype.

Methods
Differentiation of human CD14+ monocytes to Mreg was performed using a GMP compliant protocol and administration of IFNγ on day 6. Monocytes from the same donor were in parallel differentiated to MregIFNγ0 using the identical protocol but with administration of IFNγ on day 0. Cell characterization was performed using brightfield microscopy, automated and metabolic cell analysis, transmission electron microscopy, flow cytometry, qPCR and secretome profiling.

Results
Mreg and MregIFNγ0 showed no differences in cell size and volume. However, phenotypically MregIFNγ0 exhibited fewer intracellular vesicles/vacuoles but larger pseudopodia-like extensions. MregIFNγ0 revealed reduced expression of IDO and PD-L1 (P < 0.01 for both). They were positive for CD80, CD14, CD16 and CD38 (P < 0.0001vs. Mreg for all), while the majority of MregIFNγ0 did not express CD206, CD56, and CD103 on their cell surface (P < 0.01 vs. Mreg for all). In terms of their secretomes, MregIFNγ0 differed significantly from Mreg. MregIFNγ0 media exhibited reduced levels of ENA-78, Osteopontin and Serpin E1, while the amounts of MIG (CXCL9) and IP10 were increased.

Conclusion
Exposing CD14+ monocytes to an alternatively timed IFNγ stimulation results in a novel macrophage subtype which possess additional M1-like features (MregIFNγ0). MregIFNγ0 may therefore have the potential to serve as cellular therapeutics for clinical applications beyond those covered by M2-like Mreg, including immunomodulation and tumor treatment.
Implementation of shared decision-making about rooming-in: A before and after an audit of breastfeeding in Taiwan
Authors: Hung Hsiao-Ying , Wen Chun-Che , Su Pei-Fang , Man Shek-Yip , Chang Ying-Ju 
Published: June 2024

Abstract
Background
The 24-h rooming-in policy is crucial to the Baby-Friendly Hospital Initiative (BFHI) for promoting breastfeeding. However, this policy may restrict maternal autonomy. In 2018, to integrate women’s preferences into care decisions, Taiwan’s Baby-Friendly certification included prenatal shared decision-making (SDM) for rooming-in. Prior to 2018, maternal knowledge, considerations, and intentions regarding rooming-in and the impact of prenatal SDM were unknown.

Methods
A retrospective electronic medical record cohort study was conducted in southern Taiwan. Data on healthy postpartum women eligible for rooming-in and breastfeeding for the years 2017 and 2019, reflecting the periods before and after prenatal SDM was introduced, were gathered. Maternal and newborn characteristics, maternal knowledge, considerations, and prenatal intentions for postpartum rooming-in and breastfeeding during hospitalization were collected. Additionally, data on actual postpartum rooming-in practices during hospitalization and exclusive breastfeeding (EBF) practices from birth to hospital discharge, to 1 month, and to 2 months postpartum were collected. Descriptive and non-parametric statistics were applied to analyze the data.

Results
A total of 621 women in 2017 and 311 women in 2019 were included. After prenatal SDM was introduced, the rooming-in rate during hospitalization fell from 42.2% in 2017 to 25.6% in 2019 (p < 0.001), and the EBF rate declined from 45.9% to 35.7% (p = 0.01). Additionally, the 1-month postpartum EBF rate decreased from 46.4% in 2017 (n = 571) to 44.3% in 2019 (n = 264), and the 2-month postpartum EBF rate dropped from 45.5% in 2017 (n = 591) to 40.2% (n = 308). According to the 2019 Patient Decision Aids responses (n = 236), women demonstrated limited understanding of rooming-in, with only 40.7% expressing an intention toward 24-h rooming-in. Women of older maternal age (p < 0.001), with a graduate degree (p = 0.02), full-time employment (p = 0.04), and concerns about rest disruption (p < 0.001), were more likely to prefer non-24-h rooming-in.

Conclusions
Initiatives must promote prenatal SDM to enable healthcare providers to address misconceptions and tailor education, thereby increasing women’s intention toward 24-h rooming-in and EBF. Future research should explore women’s experiences and unmet needs at BFHI facilities to inform the construction of a baby- and mother-friendly environment.
How effective is proximal fibular osteotomy in redistributing joint pressures? Insights from an HTO comparative in-silico study
Authors: Morales Avalos Jorge Eduardo , Morales-Avalos Rodolfo , Martínez-Guajardo Karla V. , Pacheco-García Luis Miguel , Perelli Simone , Monllau Joan Carles , Sánchez Egea Antonio J. , Serrancoli Gil 
Published: June 2024

Abstract
Background
Knee osteoarthritis (KOA) represents a widespread degenerative condition among adults that significantly affects quality of life. This study aims to elucidate the biomechanical implications of proximal fibular osteotomy (PFO), a proposed cost-effective and straightforward intervention for KOA, comparing its effects against traditional high tibial osteotomy (HTO) through in-silico analysis.

Methods
Using medical imaging and finite element analysis (FEA), this research quantitatively evaluates the biomechanical outcomes of a simulated PFO procedure in patients with severe medial compartment genu-varum, who have undergone surgical correction with HTO. The study focused on evaluating changes in knee joint contact pressures, stress distribution, and anatomical positioning of the center of pressure (CoP). Three models are generated for each of the five patients investigated in this study, a preoperative original condition model, an in-silico PFO based on the same original condition data, and a reversed-engineered HTO in-silico model.

Results
The novel contribution of this investigation is the quantitative analysis of the impact of PFO on the biomechanics of the knee joint. The results provide mechanical evidence that PFO can effectively redistribute and homogenize joint stresses, while also repositioning the CoP towards the center of the knee, similar to what is observed post HTO. The findings propose PFO as a potentially viable and simpler alternative to conventional surgical methods for managing severe KOA, specifically in patients with medial compartment genu-varum.

Conclusion
This research also marks the first application of FEA that may support one of the underlying biomechanical theories of PFO, providing a foundation for future clinical and in-silico studies.
Current and future immunotherapeutic approaches in pancreatic cancer treatment
Authors: Farhangnia Pooya , Khorramdelazad Hossein , Nickho Hamid , Delbandi Ali-Akbar 
Published: June 2024

AbstractPancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type of tumor have remained grim for a long time. Currently, it is extremely challenging to prevent or detect it early enough for effective treatment because patients rarely exhibit symptoms and there are no reliable indicators for detection. Most patients have advanced or spreading cancer that is difficult to treat, and treatments like chemotherapy and radiotherapy can only slightly prolong their life by a few months. Immunotherapy has revolutionized the treatment of pancreatic cancer, yet its effectiveness is limited by the tumor's immunosuppressive and hard-to-reach microenvironment. First, this article explains the immunosuppressive microenvironment of pancreatic cancer and highlights a wide range of immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered and chimeric antigen receptor [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced killer cells, immune checkpoint inhibitors, immunomodulators, cancer vaccines, and strategies targeting myeloid cells in the context of contemporary knowledge and future trends. Lastly, it discusses the main challenges ahead of pancreatic cancer immunotherapy.
Understanding the processes underpinning IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) in primary care: study protocol for a process evaluation within a cluster randomised controlled implementation trial
Authors: Sheringham J. , Steed L. , McClatchey K. , Delaney B. , Barat A. , Hammersley V. , Marsh V. , Fulop N. J. , Taylor S. J. C. , Pinnock H. 
Published: June 2024

Abstract
Background
Providing supported self-management for people with asthma can reduce the burden on patients, health services and wider society. Implementation, however, remains poor in routine clinical practice. IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) is a UK-wide cluster randomised implementation trial that aims to test the impact of a whole-systems implementation strategy, embedding supported asthma self-management in primary care compared with usual care. To maximise opportunities for sustainable implementation beyond the trial, it is necessary to understand how and why the IMP2ART trial achieved its clinical and implementation outcomes.

Methods
A mixed-methods process evaluation nested within the IMP2ART trial will be undertaken to understand how supported self-management was implemented (or not) by primary care practices, to aid interpretation of trial findings and to inform scaling up and sustainability. Data and analysis strategies have been informed by mid-range and programme-level theory. Quantitative data will be collected across all practices to describe practice context, IMP2ART delivery (including fidelity and adaption) and practice response. Case studies undertaken in three to six sites, supplemented by additional interviews with practice staff and stakeholders, will be undertaken to gain an in-depth understanding of the interaction of practice context, delivery, and response. Synthesis, informed by theory, will combine analyses of both qualitative and quantitative data. Finally, implications for the scale up of asthma self-management implementation strategies to other practices in the UK will be explored through workshops with stakeholders.

Discussion
This mixed-methods, theoretically informed, process evaluation seeks to provide insights into the delivery and response to a whole-systems approach to the implementation of supported self-management in asthma care in primary care. It is underway at a time of significant change in primary care in the UK. The methods have, therefore, been developed to be adaptable to this changing context and to capture the impact of these changes on the delivery and response to research and implementation processes.
Effects of robot-assisted upper limb training combined with functional electrical stimulation in stroke patients: study protocol for a randomized controlled trial
Authors: Yang Xu , Fengyi Wang , Yi Chen , Lin Qiu , Yang Lin , Xize Li , Shaxin Liu , Yonghong Yang 
Published: June 2024

Abstract
Introduction
About 17–80% stroke survivors experience the deficit of upper limb function, which strongly influences their independence and quality of life. Robot-assisted training and functional electrical stimulation are commonly used interventions in the rehabilitation of hemiplegia upper extremities, while the effect of their combination remains unclear. The aim of this trial is to explore the effect of robot-assisted upper limb training combined with functional electrical stimulation, in terms of neuromuscular rehabilitation, compared with robot-assisted upper limb training alone.

Methods
Individuals (n = 60) with the first onset of stroke (more than 1 week and less than 1 year after stroke onset) will be considered in the recruitment of this single-blinded, three-arm randomized controlled trial. Participants will be allocated into three groups (robot-assisted training combined with functional electrical stimulation group, robot-assisted training group, and conventional rehabilitation therapies group) with a ratio of 1:1:1. All interventions will be executed for 45 min per session, one session per day, 5 sessions per week for 6 weeks. The neuromuscular function of the upper limb (Fugl-Meyer Assessment of upper extremity), ability of daily life (modified Barthel Index), pain (visual analogue scale), and quality of life (EQ-5D-5L) will be assessed at the baseline, at the end of this trial and after 3 months follow-up. Two-way repeated measures analysis of variance will be used to compare the outcomes if the data are normally distributed. Simple effects tests will be used for the further exploration of interaction effects by time and group. Scheirer-Ray-Hare test will be used if the data are not satisfied with normal distribution.

Discussion
We expect this three-arm randomized controlled trial to explore the effectiveness of robot-assisted training combined with functional electrical stimulation in improving post-stroke upper limb function compared with robot-assisted training alone.

Trial registration
Effect of upper limb robot on improving upper limb function after stroke, identifier: ChiCTR2300073279. Registered on 5 July 2023.
Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial
Authors: Anandavadivelan Poorna , Cardinale Daniele , Blomhoff Rune , Sunde Berit , Lassen Kristoffer , Kleive Dyre , Sturesson Christian , Gilg Stefan , Raastad Truls , Mijwel Sara 
Published: June 2024

Abstract
Background
Patients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer.

Methods
The PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6–10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients’ medical records; (v) explorative outcomes of patients’ experience of the exercise program which will be evaluated using focus group/individual interviews.

Discussion
It is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs.

Trial registration
ClinicalTrials.gov NCT05044065. Registered on September 14, 2021.
A DRL-based resource allocation for IRS-enhanced semantic spectrum sharing networks
Authors: Zhang Yingzheng , Li Jufang , Mu Guangchen , Chen Xiaoyu 
Published: June 2024

AbstractSemantic communication and spectrum sharing are pivotal technologies in addressing the perennial challenge of scarce spectrum resources for the sixth-generation (6G) communication networks. Notably, scant attention has been devoted to investigating semantic resource allocation within spectrum sharing semantic communication networks, thereby constraining the full exploitation of spectrum efficiency. To mitigate interference issues between primary users and secondary users while augmenting legitimate signal strength, the introduction of Intelligent Reflective Surfaces (IRS) emerges as a salient solution. In this study, we delve into the intricacies of resource allocation for IRS-enhanced semantic spectrum sharing networks. Our focal point is the maximization of semantic spectral efficiency (S-SE) for the secondary semantic network while upholding the minimum quality of service standards for the primary semantic network. This entails the joint optimization of parameters such as semantic symbol allocation, subchannel allocation, reflective coefficients of IRS elements, and beamforming adjustment of secondary base station. Recognizing computational intricacies and interdependence of variables in the non-convex optimization problem formulated, we present a judicious approach: a hybrid intelligent resource allocation approach leveraging dueling double-deep Q networks coupled with the twin-delayed deep deterministic policy. Simulation results unequivocally affirm the efficacy of our proposed resource allocation approach, showcasing its superior performance relative to baseline schemes. Our approach markedly enhances the S-SE of the secondary network, thereby establishing its prowess in advancing the frontiers of semantic spectrum sharing (S-SE).
Long non-coding RNA Small Nucleolar RNA Host Gene 4 ameliorates cigarette smoke-induced proliferation, apoptosis, inflammation, and airway remodeling in alveolar epithelial cells through the modulation of the mitogen-activated protein kinase signaling pathway via the microRNA-409-3p/Four and a Half LIM Domains 1 axis
Authors: Liu Meng , Meng JiGuang , Chen XuXin , Wang Fan , Han ZhiHai 
Published: June 2024

AbstractThe long non-coding RNA (lncRNA) Small Nucleolar RNA Host Gene 4 (SNHG4) has been demonstrated to be significantly downregulated in various inflammatory conditions, yet its role in chronic obstructive pulmonary disease (COPD) remains elusive. This study aims to elucidate the biological function of SNHG4 in COPD and to unveil its potential molecular targets. Our findings reveal that both SNHG4 and Four and a Half LIM Domains 1 (FHL1) were markedly downregulated in COPD, whereas microRNA-409-3p (miR-409-3p) was upregulated. Importantly, SNHG4 exhibited a negative correlation with inflammatory markers in patients with COPD, but a positive correlation with forced expiratory volume in 1s percentage (FEV1%). SNHG4 distinguished COPD patients from non-smokers with high sensitivity, specificity, and accuracy. Overexpression of SNHG4 ameliorated cigarette smoke extract (CSE)-mediated inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE bronchial epithelial cells. These beneficial effects of SNHG4 overexpression were reversed by the overexpression of miR-409-3p or the silencing of FHL1. Mechanistically, SNHG4 competitively bound to miR-409-3p, mediating the expression of FHL1, and consequently improving inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE cells. Additionally, SNHG4 regulated the miR-409-3p/FHL1 axis to inhibit the activation of the mitogen-activated protein kinase (MAPK) pathway induced by CSE. In a murine model of COPD, knockdown of SNHG4 exacerbated CSE-induced pulmonary inflammation, apoptosis, and oxidative stress. In summary, our data affirm that SNHG4 mitigates pulmonary inflammation, apoptosis, and oxidative damage mediated by COPD through the regulation of the miR-409-3p/FHL1 axis.
Graphical Abstract