bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between Wolbachia pipientis and Leishmania infantum in heartworm infected dogs
Authors: Latrofa Maria Stefania , Varotto-Boccazzi Ilaria , Louzada-Flores Viviane Noll , Iatta Roberta , Mendoza-Roldan Jairo Alfonso , Roura Xavier , Zatelli Andrea , Epis Sara , Bandi Claudio , Otranto Domenico 
Published: February 2023

Abstract
Background
Wolbachia is a Gram-negative endosymbiont associated with several species of arthropods and filarioid nematodes, including Dirofilaria immitis. This endosymbiont may elicit a Th1 response, which is a component of the immunity against Leishmania infantum.

Methods
To investigate the interactions between Wolbachia of D. immitis and L. infantum in naturally infected dogs and cytokine circulation, dogs without clinical signs (n = 187) were selected. Dogs were tested for microfilariae (mfs) by Knott, for female antigens of D. immitis by SNAP, and for anti-L. infantum antibodies by IFAT and assigned to four groups. Dogs of group 1 (G1) and 2 (G2) were positive for D. immitis and positive or negative to L. infantum, respectively. Dogs of group 3 (G3) and 4 (G4) were negative to D. immitis and positive or negative to L. infantum, respectively. Wolbachia and L. infantum DNA was quantified by real-time PCR (qPCR) in dog blood samples. A subset of dogs (n = 65) was examined to assess pro- and anti-inflammatory cytokine production using an ELISA test.

Results
Of 93 dogs positive to D. immitis with circulating mfs, 85% were positive to Wolbachia, with the highest amount of DNA detected in G1 and the lowest in dogs with low mfs load in G1 and G2. Among dogs positive to L. infantum, 66% from G1 showed low antibody titer, while 48.9% from G3 had the highest antibody titer. Of 37 dogs positive to Wolbachia from G1, 26 (70.3%) had low antibody titers to L. infantum (1:160). Among cytokines, TNFα showed the highest mean concentration in G1 (246.5 pg/ml), IFNγ being the one most represented (64.3%). IL-10 (1809.5 pg/ml) and IL-6 (123.5 pg/ml) showed the highest mean concentration in dogs from G1. A lower percentage of dogs producing IL-4 was observed in all groups examined, with the highest mean concentration (2794 pg/ml) recorded in G2.

Conclusion
Results show the association of D. immitis and Wolbachia with the lower antibody titers of L. infantum in co-infected dogs, suggesting the hypothesis that the endosymbiont may affect the development of the patent leishmaniosis. However, due to the limitations associated with the heterogeneity of naturally infected dogs in field conditions, results should be validated by investigation on experimental models.

Graphical Abstract
Regulatory networks driving expression of genes critical for glioblastoma are controlled by the transcription factor c-Jun and the pre-existing epigenetic modifications
Authors: Roura Adria-Jaume , Szadkowska Paulina , Poleszak Katarzyna , Dabrowski Michal J. , Ellert-Miklaszewska Aleksandra , Wojnicki Kamil , Ciechomska Iwona A. , Stepniak Karolina , Kaminska Bozena , Wojtas Bartosz 
Published: February 2023

Abstract
Background
Glioblastoma (GBM, WHO grade IV) is an aggressive, primary brain tumor. Despite extensive tumor resection followed by radio- and chemotherapy, life expectancy of GBM patients did not improve over decades. Several studies reported transcription deregulation in GBMs, but regulatory mechanisms driving overexpression of GBM-specific genes remain largely unknown. Transcription in open chromatin regions is directed by transcription factors (TFs) that bind to specific motifs, recruit co-activators/repressors and the transcriptional machinery. Identification of GBM-related TFs-gene regulatory networks may reveal new and targetable mechanisms of gliomagenesis.

Results
We predicted TFs-regulated networks in GBMs in silico and intersected them with putative TF binding sites identified in the accessible chromatin in human glioma cells and GBM patient samples. The Cancer Genome Atlas and Glioma Atlas datasets (DNA methylation, H3K27 acetylation, transcriptomic profiles) were explored to elucidate TFs-gene regulatory networks and effects of the epigenetic background. In contrast to the majority of tumors, c-Jun expression was higher in GBMs than in normal brain and c-Jun binding sites were found in multiple genes overexpressed in GBMs, including VIM, FOSL2 or UPP1. Binding of c-Jun to the VIM gene promoter was stronger in GBM-derived cells than in cells derived from benign glioma as evidenced by gel shift and supershift assays. Regulatory regions of the majority of c-Jun targets have distinct DNA methylation patterns in GBMs as compared to benign gliomas, suggesting the contribution of DNA methylation to the c-Jun-dependent gene expression.

Conclusions
GBM-specific TFs-gene networks identified in GBMs differ from regulatory pathways attributed to benign brain tumors and imply a decisive role of c-Jun in controlling genes that drive glioma growth and invasion as well as a modulatory role of DNA methylation.
Association between Cystic Fibrosis exacerbations, lung function, T2 inflammation and microbiological colonization
Authors: Albon Dana , Zhang Lijia , Patrie James , Jones Marieke , Li Z. Galvin , Noonan Emily , Borish Larry 
Published: February 2023

Abstract
Background
The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients.

Research question
This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data.

Study design and methods
We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL.

Results
Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization.

Interpretation
This study has shown that in CF patients, T2 inflammation based on serum AEC and IgE correlated with pulmonary exacerbations requiring hospitalizations and/or intravenous antibiotics, independent of bacterial airway colonization. In addition, lung function decline correlated with increased IgE and AEC. Further studies are needed to explore these correlations and potential impact on treatment.
Implementing organized colorectal cancer screening programs in Europe—protocol for a systematic review of determinants and strategies
Authors: Albers Bianca , Auer Reto , Caci Laura , Nyantakyi Emanuela , Plys Ekaterina , Podmore Clara , Riegel Franziska , Selby Kevin , Walder Joel , Clack Lauren 
Published: February 2023

Abstract
Background
With a high mortality of 12.6% of all cancer cases, colorectal cancer (CRC) accounts for substantial burden of disease in Europe. In the past decade, more and more countries have introduced organized colorectal cancer screening programs, making systematic screening available to entire segments of a population, typically based on routine stool tests and/or colonoscopy. While the effectiveness of organized screening in reducing CRC incidence and mortality has been confirmed, studies continuously report persistent program implementation challenges. This systematic review will synthesize the literature on organized CRC screening programs. Its aim is to understand what is currently known about the barriers and facilitators that influence the implementation of these programs and about the implementation strategies used to navigate these determinants.

Methods
A systematic review of primary studies of any research design will be conducted. CENTRAL, CINAHL, EMBASE, International Clinical Trials Registry Platform, MEDLINE, PsycINFO, and Scopus will be searched. Websites of (non-)government health care organizations and websites of organizations affiliated with authors of included studies will be screened for unpublished evaluation reports. Existing organized CRC screening programs will be contacted with a request to share program-specific grey literature. Two researchers will independently screen each publication in two rounds for eligibility. Included studies will focus on adult populations involved in the implementation of organized CRC screening programs and contain information about implementation determinants/ strategies. Publications will be assessed for their risk of bias. Data extraction will include study aim, design, location, setting, sample, methods, and measures; program characteristics; implementation stage, framework, determinants, strategies, and outcomes; and service and other outcome information. Findings will be synthesized narratively using the three stages of thematic synthesis.

Discussion
With its sole focus on the implementation of organized CRC screening programs, this review will help to fill a central knowledge gap in the literature on colorectal cancer screening. Its findings can inform the decision-making in policy and practice needed to prioritize resources for establishing new and maintaining existing programs in the future.

Systematic review registration
PROSPERO (CRD42022306580).
Stabilization of hybrid stochastic systems with time-varying delay by discrete-time state feedback control
Authors: Mao Wei , Xiao Xiao , Miao Liangliang , Hu Liangjian 
Published: February 2023

AbstractIn this paper, we are concerned with the stabilization of hybrid stochastic systems with variable delay by discrete-time state feedback control. By using Lyapunov functionals, we obtain an upper bound $\tau ^{*}$

τ
∗

on the duration τ between two consecutive state observations. Meantime, we show that hybrid stochastic systems with variable delay can be stabilized by discrete-time state feedback control as long as $\tau <\tau ^{*}$
τ
<

τ
∗

. Finally, two examples are given to demonstrate the applicability of our work.
Ecological niche modelling of a critically endangered species Commiphora wightii (Arn.) Bhandari using bioclimatic and non-bioclimatic variables
Authors: Mathur Manish , Mathur Preet , Purohit Harshit 
Published: February 2023

AbstractBackgroundThe aim of this study is to examine the effects of four different bioclimatic predictors (current, 2050, 2070, and 2090 under Shared Socioeconomic Pathways SSP2-4.5) and non-bioclimatic variables (soil, habitat heterogeneity index, land use, slope, and aspect) on the habitat suitability and niche dimensions of the critically endangered plant speciesCommiphora wightiiin India. We also evaluate how niche modelling affects its extent of occurrence (EOO) and area of occupancy (AOO).ResultsThe area under the receiver operating curve (AUC) values produced by the maximum entropy (Maxent) under various bioclimatic time frames were more than 0.94, indicating excellent model accuracy. Non-bioclimatic characteristics, with the exception of terrain slope and aspect, decreased the accuracy of our model. Additionally, Maxent accuracy was the lowest across all combinations of bioclimatic and non-bioclimatic variables (AUC = 0.75 to 0.78). With current, 2050, and 2070 bioclimatic projections, our modelling revealed the significance of water availability parameters (BC-12 to BC-19, i.e. annual and seasonal precipitation as well as precipitation of wettest, driest, and coldest months and quarters) on habitat suitability for this species. However, with 2090 projection, energy variables such as mean temperature of wettest quarter (BC-8) and isothermality (BC-3) were identified as governing factors. Excessive salt, rooting conditions, land use type (grassland), characteristics of the plant community, and slope were also noticed to have an impact on this species. Through distribution modelling of this species in both its native (western India) and exotic (North-east, Central Part of India, as well as northern and eastern Ghat) habitats, we were also able to simulate both its fundamental niche and its realized niche. Our EOO and AOO analysis reflects the possibility of many new areas in India where this species can be planted and grown.ConclusionAccording to the calculated area under the various suitability classes, we can conclude thatC. wightii's potentially suitable bioclimatic distribution under the optimum and moderate classes would increase under all future bioclimatic scenarios (2090 > 2050 ≈ current), with the exception of 2070, demonstrating that there are more suitable habitats available forC. wightiiartificial cultivation and will be available for future bioclimatic projections of 2050 and 2090. Predictive sites indicated that this species also favours various types of landforms outside rocky environments, such as sand dunes, sandy plains, young alluvial plains, saline areas, and so on. Our research also revealed crucial information regarding the community dispersion variable, notably the coefficient of variation that, when bioclimatic + non-bioclimatic variables were coupled, disguised the effects of bioclimatic factors across all time frames.
Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunction
Authors: Lu Yi , Bu Fa-Qian , Wang Fang , Liu Li , Zhang Shuai , Wang Guan , Hu Xiu-Ying 
Published: February 2023

AbstractPhysical exercise is of great significance for maintaining human health. Exercise can provide varying degrees of benefits to cognitive function at all stages of life cycle. Currently, with the aging of the world’s population and increase of life expectancy, cognitive dysfunction has gradually become a disease of high incidence, which is accompanied by neurodegenerative diseases in elderly individuals. Patients often exhibit memory loss, aphasia and weakening of orientation once diagnosed, and are unable to have a normal life. Cognitive dysfunction largely affects the physical and mental health, reduces the quality of life, and causes a great economic burden to the society. At present, most of the interventions are aimed to maintain the current cognitive level and delay deterioration of cognition. In contrast, exercise as a nonpharmacological therapy has great advantages in its nontoxicity, low cost and universal application. The molecular mechanisms underlying the effect of exercise on cognition are complex, and studies have been extensively centered on neural plasticity, the direct target of exercise in the brain. In addition, mitochondrial stability and energy metabolism are essential for brain status. Meanwhile, the organ-brain axis responds to exercise and induces release of cytokines related to cognition. In this review, we summarize the latest evidence on the molecular mechanisms underlying the effects of exercise on cognition, and point out directions for future research.
Synergistic effect of HDAC inhibitor Chidamide with Cladribine on cell cycle arrest and apoptosis by targeting HDAC2/c-Myc/RCC1 axis in acute myeloid leukemia
Authors: Gu Siyu , Hou Yue , Dovat Katarina , Dovat Sinisa , Song Chunhua , Ge Zheng 
Published: February 2023

Abstract
Background
More effective targeted therapy and new combination regimens are needed for Acute myeloid leukemia (AML), owing to the unsatisfactory long-term prognosis of the disease. Here, we investigated the synergistic effect and the mechanism of a histone deacetylase inhibitor, Chidamide in combination with Cladribine, a purine nucleoside antimetabolite analog in the disease.

Methods
Cell counting kit-8 assays and Chou-Talalay’s combination index were used to examine the synergistic effect of Chidamide and Cladribine on AML cell lines (U937, THP-1, and MV4-11) and primary AML cells. PI and Annexin-V/PI assays were used to detect the cell cycle effect and apoptosis effect, respectively. Global transcriptome analysis, RT-qPCR, c-MYC Knockdown, western blotting, co-immunoprecipitation, and chromatin immunoprecipitation assays were employed to explore the molecule mechanisms.

Results
The combination of Chidamide with Cladribine showed a significant increase in cell proliferation arrest, the G0/G1 phase arrest, and apoptosis compared to the single drug control in AML cell lines along with upregulated p21Waf1/Cip1 expression and downregulated CDK2/Cyclin E2 complex, and elevated cleaved caspase-9, caspase-3, and PARP. The combination significantly suppresses the c-MYC expression in AML cells, and c-MYC knockdown significantly increased the sensitivity of U937 cells to the combination compared to single drug control. Moreover, we observed HDAC2 interacts with c-Myc in AML cells, and we further identified that c-Myc binds to the promoter region of RCC1 that also could be suppressed by the combination through c-Myc-dependent. Consistently, a positive correlation of RCC1 with c-MYC was observed in the AML patient cohort. Also, RCC1 and HDAC2 high expression are associated with poor survival in AML patients. Finally, we also observed the combination significantly suppresses cell growth and induces the apoptosis of primary cells in AML patients with AML1-ETO fusion, c-KIT mutation, MLL-AF6 fusion, FLT3-ITD mutation, and in a CMML-BP patient with complex karyotype.

Conclusions
Our results demonstrated the synergistic effect of Chidamide with Cladribine on cell growth arrest, cell cycle arrest, and apoptosis in AML and primary cells with genetic defects by targeting HDAC2/c-Myc/RCC1 signaling in AML. Our data provide experimental evidence for the undergoing clinical trial (Clinical Trial ID: NCT05330364) of Chidamide plus Cladribine as a new potential regimen in AML.
Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
Authors: Raggio Víctor , Graña Martín , Winiarski Erik , Mansilla Santiago , Simoes Camila , Rodríguez Soledad , Brandes Mariana , Tapié Alejandra , Rodríguez Laura , Cibils Lucía , Alonso Martina , Martínez Jennyfer , Fernández-Calero Tamara , Domínguez Fernanda , Mezquida Melania Rosas , Castro Laura , Cerisola Alfredo , Naya Hugo , Cassina Adriana , Quijano Celia , Spangenberg Lucía 
Published: February 2023

AbstractThe SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutations in SPATA5 gene to microcephaly, intellectual disability, seizures and hearing loss. This suggests a role of the SPATA5 gene also in neuronal development. Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsy. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using next generation sequencing. We found two novel compound heterozygous variants in SPATA5 that are most likely causative. To analyze the impact of SPATA5 mutations on mitochondrial functional studies directly on the patients' mononuclear cells and platelets were undertaken. Oxygen consumption rates in platelets and PBMCs were impaired in the patient when compared to a healthy control. Also, a decrease in mitochondrial mass was observed in the patient monocytes with respect to the control. This suggests a true pathogenic effect of the mutations in mitochondrial function, especially in energy production and possibly biogenesis, leading to the observed phenotype.
Collaborative dietetic and psychological care in Interprofessional Enhanced Cognitive Behaviour Therapy for adults with Anorexia Nervosa: a novel treatment approach
Authors: Bray Megan , Heruc Gabriella , Byrne Susan , Wright Olivia R. L. 
Published: February 2023

AbstractClinical practice guidelines for anorexia nervosa (AN) and atypical anorexia nervosa recommend treatment from a team including a mental health professional and a dietitian. To date, however, AN treatment models such as Enhanced Cognitive Behaviour Therapy (CBT-E) seldom include dietitians and have low to moderate treatment efficacy. Given interprofessional approaches to healthcare have been shown to improve treatment outcomes and enhance patient and clinician satisfaction, formalising collaborative dietetic and psychological treatment may be a feasible strategy to improve treatment outcomes and the patient and clinician experience of treatment. Moreover, malnutrition is a serious consequence of AN, and dietitians are considered experts in its diagnosis and treatment. This paper proposes a novel treatment approach, Interprofessional Enhanced Cognitive Behaviour Therapy (CBT-IE), an adaptation of CBT-E where dietitians deliver content related to malnutrition and dietary restraint and mental health professionals deliver content related to cognitive and behavioural change. The rationale for developing CBT-IE, treatment structure, and future research directions is discussed.