bluuebunny/crossref_metadata_2025_split huggingface dataset:
Valproic acid inhibits cell growth in both MCF-7 and MDA-MB231 cells by triggering different responses in a cell type-specific manner
Authors: Giordano Francesca , Paolì Alessandro , Forastiero Martina , Marsico Stefania , De Amicis Francesca , Marrelli Mariangela , Naimo Giuseppina Daniela , Mauro Loredana , Panno Maria Luisa 
Published: March 2023

Abstract
Background
Breast cancer is the second leading cause of death among women after lung cancer. Despite the improvement in prevention and in therapy, breast cancer still remains a threat, both for pre- and postmenopausal women, due to the development of drug resistance. To counteract that, novel agents regulating gene expression have been studied in both hematologic and solid tumors. The Histone Deacetylase (HDAC) inhibitor Valproic Acid (VA), used for epilepsy and other neuropsychiatric diseases, has been demonstrated a strong antitumoral and cytostatic activity. In this study, we tested the effects of Valproic Acid on the signaling pathways involved in breast cancer cells viability, apoptosis and in Reactive Oxygen Species (ROS) production using ER-α positive MCF-7 and triple negative MDA-MB-231 cells.

Methods
Cell proliferation assay was performed by MTT Cell cycle, ROS levels and apoptosis were analyzed by flow cytometry, protein levels were detected by Western Blotting.

Results
Cell treatment with Valproic Acid reduced cell proliferation and induced G0/G1 cell cycle arrest in MCF-7 and G2/M block in MDA-MB-231 cells. In addition, in both cells the drug enhanced the generation of ROS by the mitochondria. In MCF-7 treated cells, it has been observed a reduction in mitochondrial membrane potential, a down regulation of the anti-apoptotic marker Bcl-2 and an increase of Bax and Bad, leading to release of cytochrome C and PARP cleavage. Less consistent effects are recorded in MDA-MB-231 cells, in which the greater production of ROS, compared to MCF-7cells, involves an inflammatory response (activation of p-STAT3, increased levels of COX2).

Conclusions
Our results have demonstrated that in MCF-7 cells the Valproic Acid is a suitable drug to arrest cell growth, to address apoptosis and mitochondrial perturbations, all factors that are important in determining cell fate and health. In a triple negative MDA-MB 231 cells, valproate directs the cells towards the inflammatory response with a sustained expression of antioxidant enzymes. Overall, the not always unequivocal data between the two cellular phenotypes indicate that further studies are needed to better define the use of the drug, also in combination with other chemotherapy, in the treatment of breast tumors.
Immunogenic cell death in cancer: concept and therapeutic implications
Authors: Galluzzi Lorenzo , Kepp Oliver , Hett Erik , Kroemer Guido , Marincola Francesco M. 
Published: March 2023

AbstractMammalian cells responding to specific perturbations of homeostasis can undergo a regulated variant of cell death that elicits adaptive immune responses. As immunogenic cell death (ICD) can only occur in a precise cellular and organismal context, it should be conceptually differentiated from instances of immunostimulation or inflammatory responses that do not mechanistically depend on cellular demise. Here, we critically discuss key conceptual and mechanistic aspects of ICD and its implications for cancer (immuno)therapy.
Outcome of adalimumab monotherapy in paediatric non-infectious uveitis
Authors: Al-Julandani DA , Bagri NK , Tsang N , Clarke S , Upadhyay A , Guly C , Ramanan AV 
Published: March 2023

Abstract
Background
Adalimumab in combination with other disease-modifying antirheumatic drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric non-infectious uveitis. However, many children experience significant intolerance to methotrexate while on this combination, leaving a dilemma for clinicians for choosing the subsequent therapeutic roadmap. Continuation of adalimumab monotherapy might be an alternative feasible option under such settings. This study aims to investigate the efficacy of adalimumab monotherapy in paediatric non-infectious uveitis.

Methods
Children with non-infectious uveitis on adalimumab monotherapy (from August 2015 to June 2022) following intolerance to accompanying methotrexate or mycophenolate mofetil were included in this retrospective study. Data were collected at the initiation of adalimumab monotherapy and at three monthly intervals until the last visit. The primary outcome was to evaluate disease control on adalimumab monotherapy as determined by the proportion of patients who had less than a 2-step worsening in uveitis (as per SUN score) and no additional systemic immunosuppression during follow-up. Secondary outcome measures were visual outcome, complications and side-effect profile of adalimumab monotherapy.

Results
Data was collected for 28 patients (56 eyes). The most common uveitis type and course were anterior and chronic uveitis respectively. Juvenile idiopathic arthritis-associated uveitis was the most common underlying diagnosis. During the study period, 23 (82.14%) of the study subjects met the primary outcome. On Kaplan–Meier survival analysis 81.25% (95% CI; 60.6–91.7%) children maintained remission at 12 months on adalimumab monotherapy.

Conclusion
Continuation of adalimumab monotherapy is an effective therapeutic option for the treatment of non-infectious uveitis in children who are intolerant to the combination of adalimumab and methotrexate or mycophenolate mofetil.
Opposing effects of β-2 and β-1 adrenergic receptor signaling on neuroinflammation and dopaminergic neuron survival in α-synuclein-mediated neurotoxicity
Authors: Torrente Daniel , Su Enming J. , Schielke Gerald P. , Warnock Mark , Mann Kris , Lawrence Daniel A. 
Published: March 2023

Abstract
Background
Noradrenergic neurons in the locus coeruleus (LC) are the primary source of norepinephrine (NE) in the brain and degeneration of these neurons is reported in the early stages of Parkinson’s disease (PD), even prior to dopaminergic neuron degeneration in the substantia nigra (SN), which is a hallmark of PD pathology. NE depletion is generally associated with increased PD pathology in neurotoxin-based PD models. The effect of NE depletion in other models of PD-like α-synuclein-based models is largely unexplored. In PD models and in human patients, β-adrenergic receptors’ (AR) signaling is associated with a reduction of neuroinflammation and PD pathology. However, the effect of NE depletion in the brain and the extent of NE and β-ARs signaling involvement in neuroinflammation, and dopaminergic neuron survival is poorly understood.

Methods
Two mouse models of PD, a 6OHDA neurotoxin-based model and a human α-synuclein (hα-SYN) virus-based model of PD, were used. DSP-4 was used to deplete NE levels in the brain and its effect was confirmed by HPLC with electrochemical detection. A pharmacological approach was used to mechanistically understand the impact of DSP-4 in the hα-SYN model of PD using a norepinephrine transporter (NET) and a β-AR blocker. Epifluorescence and confocal imaging were used to study changes in microglia activation and T-cell infiltration after β1-AR and β2-AR agonist treatment in the hα-SYN virus-based model of PD.

Results
Consistent with previous studies, we found that DSP-4 pretreatment increased dopaminergic neuron loss after 6OHDA injection. In contrast, DSP-4 pretreatment protected dopaminergic neurons after hα-SYN overexpression. DSP-4-mediated protection of dopaminergic neurons after hα-SYN overexpression was dependent on β-AR signaling since using a β-AR blocker prevented DSP-4-mediated dopaminergic neuron protection in this model of PD. Finally, we found that the β-2AR agonist, clenbuterol, reduced microglia activation, T-cell infiltration, and dopaminergic neuron degeneration, whereas xamoterol a β-1AR agonist showed increased neuroinflammation, blood brain barrier permeability (BBB), and dopaminergic neuron degeneration in the context of hα-SYN-mediated neurotoxicity.

Conclusions
Our data demonstrate that the effects of DSP-4 on dopaminergic neuron degeneration are model specific, and suggest that in the context of α-SYN-driven neuropathology, β2-AR specific agonists may have therapeutic benefit in PD.
Practical approaches of PULSE Racing in training their athlete for the Cybathlon Global Edition Functional Electrical Stimulation bike race: a case report
Authors: Docter Heleen , Podvinšek Katja , Koomen Sander ,   PULSE Racing III, Kaman Birgit E , Visser Ilona , Klunder Niek , van den Berg Anneloes , Bellens Laurien , Wijnbelt Chrétine , Groot Sterre 
Published: March 2023

AbstractDuring the Cybathlon Global Edition 2020, athletes compete in a Functional Electrical Stimulation (FES) bike race. In this event, athletes with a spinal cord injury cover a distance of 1200 m on an adapted bike by using electrostimulation to activate their leg muscles in order to evoke a pedalling movement. This report reviews the training regimen, as designed by the PULSE Racing team, and the experience of one athlete in preparation for the Cybathlon Global Edition 2020. The training plan was designed to vary exercise modes in order to optimize physiological adaptations and minimize monotony for the athlete. Additional constraints due to coronavirus pandemic, e.g., postponement of the Cybathon Global Edition and modification from a live cycling track to a virtual stationary race, along with the health concerns of the athlete, e.g. unwanted effects from the FES and bladder infection, required creativity to ensure an effective and safe training protocol. The individual needs of the athlete and task requirements for the FES bike race made the design of a suitable training programme challenging, emphasizing the importance of monitoring. Several objective and subjective measures to assess the athlete’s health and progress are presented, all with their own advantages and disadvantages. Despite these limitations, the athlete achieved a gold medal in the FES bike race Cybathlon Global Edition 2020 through discipline, team collaboration and the athlete’s own motivation.
Virtual reality-based interventions for the rehabilitation of vestibular and balance impairments post-concussion: a scoping review
Authors: LeMarshall Soraya J. , Stevens Lachlan M. , Ragg Nicholas P. , Barnes Leia , Foster Jacinta , Canetti Elisa F. D. 
Published: March 2023

Abstract
Background
Concussions and mild traumatic brain injuries are the most common causes of physical and cognitive disability worldwide. Concussion can result in post-injury vestibular and balance impairments that can present up to five years post initial concussion event, ultimately affecting many daily and functional activities. While current clinical treatment aims to reduce symptoms, the developing use of technology in everyday life has seen the emergence of virtual reality. Current literature has failed to identify substantial evidence regarding the use of virtual reality in rehabilitation. The primary aim of this scoping review is to identify, synthesise, and assess the quality of studies reporting on the effectiveness of virtual reality for the rehabilitation of vestibular and balance impairments post-concussion. Additionally, this review aims to summarise the volume of scientific literature and identify the knowledge gaps in current research pertaining to this topic.

Methods
A scoping review of six databases (PubMed, Embase, CINAHL, ProQuest, SportDiscus, Scopus) and a grey literature (Google Scholar) was conducted using three key concepts (virtual reality, vestibular symptoms, and post-concussion). Data was charted from studies and outcomes were categorised into one of three categories: (1) balance; (2) gait; or (3) functional outcome measures. Critical appraisal of each study was conducted using the Joanna Briggs Institute checklists. A critical appraisal of each outcome measure was also completed utilising a modified GRADE appraisal tool to summarise the quality of evidence. Effectiveness was assessed using calculations of change in performance and change per exposure time.

Results
Three randomised controlled trials, three quasi-experimental studies, three case studies, and one retrospective cohort study were ultimately included, using a thorough eligibility criteria. All studies were inclusive of different virtual reality interventions. The ten studies had a 10-year range and identified 19 different outcome measures.

Conclusion
The findings from this review suggests that virtual reality is an effective tool for the rehabilitation of vestibular and balance impairments post-concussion. Current literature shows sufficient but low level of evidence, and more research is necessary to develop a quantitative standard and to better understand appropriate dosage of virtual reality intervention.
RT-PCR-based assessment of the SD Bioline Rota/Adeno Antigen-based test in infants with and without diarrhea
Authors: Manouana Gédéon Prince , Nguema-Moure Paul Alvyn , Tomazatos Alexandru , Maloum Moustapha Nzamba , Bock C.-Thomas , Kremsner Peter G. , Velavan Thirumalaisamy P. , Adegnika Akim Ayola , Niendorf Sandra 
Published: March 2023

Abstract
Background
Rotavirus A (RVA) infections remain a major cause of severe acute diarrhea affecting children worldwide. To date, rapid diagnostic tests (RDT) are widely used to detect RVA. However, paediatricians question whether the RDT can still detect the virus accurately. Therefore, this study aimed to evaluate the performance of the rapid rotavirus test in comparison to the one-step RT-qPCR method.

Methods
A cross-sectional study was conducted in Lambaréné, Gabon, from April 2018 to November 2019. Stool samples were collected from children under 5 years of age with diarrhoea or a history of diarrhoea within the last 24 h, and from asymptomatic children from the same communities. All stool samples were processed and analysed using the SD BIOLINE Rota/Adeno Ag RDT against a quantitative reverse transcription PCR (RT-qPCR), which is considered the gold standard.

Results
For a total of 218 collected stool samples, the overall sensitivity of the RDT was 46.46% (confidence interval (CI) 36.38–56.77), with a specificity of 96.64% (CI 91.62–99.08) compared to one-step RT-qPCR. After confirming the presence or absence of RVA gastroenteritis, the RDT showed suitable results in detecting rotavirus A-associated disease, with a 91% concordance with the RT-qPCR. Furthermore, the performance of this test varied when correlated with seasonality, symptoms, and rotavirus genotype.

Conclusion
This RDT showed high sensitivity and was suitable for the detection of RVA in patients with RVA gastroenteritis, although some asymptomatic RVA shedding was missed by RT-qPCR. It could be a useful diagnostic tool, especially in low-income countries.
CeDAR: incorporating cell type hierarchy improves cell type-specific differential analyses in bulk omics data
Authors: Chen Luxiao , Li Ziyi , Wu Hao 
Published: March 2023

AbstractBulk high-throughput omics data contain signals from a mixture of cell types. Recent developments of deconvolution methods facilitate cell type-specific inferences from bulk data. Our real data exploration suggests that differential expression or methylation status is often correlated among cell types. Based on this observation, we develop a novel statistical method named CeDAR to incorporate the cell type hierarchy in cell type-specific differential analyses of bulk data. Extensive simulation and real data analyses demonstrate that this approach significantly improves the accuracy and power in detecting cell type-specific differential signals compared with existing methods, especially in low-abundance cell types.
Challenges and opportunities for conducting pre-hospital trauma trials: a behavioural investigation
Authors: Lawrie Louisa , Duncan Eilidh M. , Lendrum Robert , Lebrec Victoria , Gillies Katie 
Published: March 2023

Abstract

Background
Trials in pre-hospital trauma care are relatively uncommon. There are logistical and methodological challenges related to designing and delivering trials in this setting. Previous studies have assessed challenges reported in individual trials rather than across the pre-hospital trial landscape to identify over-arching factors. The aim of this study was to investigate the challenges and opportunities related to the set-up, design and conduct of pre-hospital trauma trials from across the pre-hospital trial landscape and a specific pre-hospital trauma feasibility study.

Methods
Semi-structured interviews were conducted with two cohorts of participants: research personnel who had experience of pre-hospital trials, either through direct involvement in conduct or through strategic oversight of national initiatives (n = 7), and clinical staff (n = 16) involved in recruitment to a pre-hospital trauma feasibility study. Thematic analyses were used to assess the barriers and enablers of conducting pre-hospital trauma trials. Two frameworks (The Capability Opportunity Motivation—Behaviour and the Theoretical Domains Framework) were used to guide analyses.

Results
The barriers and enablers reported were relevant to several TDF domains and COM-B components. Across both cohorts, challenges associated with opportunities were reported and included the lack of research experience amongst pre-hospital staff, team dynamics within a rotating shift schedule, and the involvement of external organisations with diverse institutional priorities and infrastructures (e.g. Air Ambulances). The infrequency of eligible cases was also reported to affect the trial design, set-up, and conduct. Other barriers reported related to clinical equipoise amongst staff and institutional pressures, which affected motivation.

Conclusions
This study has highlighted that pre-hospital trials face many context-specific but also generic challenges. Pre-hospital trauma trial teams could consider the findings to develop targeted, behaviourally focused, solutions to the challenges identified in order to enhance the set-up and conduct of trials in this setting.

Trial registration
NCT04145271. Trial registration date: October 30, 2019. Note that this paper does not report results from a specific trial but does include participants who were involved in the conduct of a registered pre-hospital feasibility study.
Development of environmental loop-mediated isothermal amplification (eLAMP) diagnostic tool for Bulinus truncatus field detection
Authors: Blin Manon , Senghor Bruno , Boissier Jérôme , Mulero Stephen , Rey Olivier , Portela Julien 
Published: March 2023

Abstract
Background
Global changes are reshaping the distribution of vector-borne diseases by spreading vectors to previously non-endemic areas. Since 2013, urogenital schistosomiasis has emerged in Corsica and threatens European countries. Gastropod vectors release schistosome larvae that can infect humans who come into contact with freshwater bodies. Monitoring schistosomiasis host vectors is a prerequisite to understand and subsequently to control this pathogen transmission. Because malacological surveys are time consuming and require special expertise, the use of a simple molecular method is desirable.

Methods
The aim of this study is to develop a ready-to-use protocol using the LAMP (loop-mediated isothermal amplification) method to detect environmental DNA of Bulinus truncatus, vector of Schistosoma haematobium. Interestingly, LAMP method possesses all the characteristics required for adaptability to field conditions particularly in low-income countries: speed, simplicity, lyophilized reagents, low cost and robustness against DNA amplification inhibitors. We have tested this new method on Corsican water samples previously analysed by qPCR and ddPCR.

Results
We demonstrate that our diagnostic tool B. truncatus eLAMP (Bt-eLAMP) can detect the eDNA of Bulinus truncatus as effectively as the two other methods. Bt-eLAMP can even detect 1/4 of positive samples not detectable by qPCR. Moreover, the complete Bt-eLAMP protocol (sampling, sample pre-process, amplification and revelation) does not require sophisticated equipment and can be done in 1 ½ h.

Conclusions
LAMP detection of environmental DNA provides large-scale sensitive surveillance of urogenital schistosomiasis possible by identifying potentially threatened areas. More generally, eLAMP method has great potential in vector-borne diseases and ecology.

Graphical Abstract
Cerebrospinal fluid biomarkers of axonal and synaptic degeneration in a population-based sample
Authors: Arvidsson Rådestig Maya , Skoog Ingmar , Skillbäck Tobias , Zetterberg Henrik , Kern Jürgen , Zettergren Anna , Andreasson Ulf , Wetterberg Hanna , Kern Silke , Blennow Kaj 
Published: March 2023

Abstract
Background
Neurofilament light (NfL) and neurogranin (Ng) are promising candidate AD biomarkers, reflecting axonal and synaptic damage, respectively. Since there is a need to understand the synaptic and axonal damage in preclinical Alzheimer’s disease (AD), we aimed to determine the cerebrospinal fluid (CSF) levels of NfL and Ng in cognitively unimpaired elderly from the Gothenburg H70 Birth Cohort Studies classified according to the amyloid/tau/neurodegeneration (A/T/N) system.

Methods
The sample consisted of 258 cognitively unimpaired older adults (age 70, 129 women and 129 men) from the Gothenburg Birth Cohort Studies. We compared CSF NfL and Ng concentrations in A/T/N groups using Student’s T-test and ANCOVA.

Results
CSF NfL concentration was higher in the A−T−N+ group (p=0.001) and the A−T+N+ group (p=0.006) compared with A−T−N−. CSF Ng concentration was higher in the A−T−N+, A−T+N+, A+T−N+, and A+T+N+ groups (p<0.0001) compared with A−T−N−. We found no difference in NfL or Ng concentration in A+ compared with A− (disregarding T− and N− status), whereas those with N+ had higher concentrations of NfL and Ng compared with N− (p<0.0001) (disregarding A− and T− status).

Conclusions
CSF NfL and Ng concentrations are increased in cognitively normal older adults with biomarker evidence of tau pathology and neurodegeneration.