bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular detection of pathogens from ticks collected from dogs and cats at veterinary clinics in Finland
Authors: Zakham Fathiah , Korhonen Essi M. , Puonti Petteri T. , Castrén Robert S. , Uusitalo Ruut , Smura Teemu , Kant Ravi , Vapalahti Olli , Sironen Tarja , Kinnunen Paula M. 
Published: September 2023

Abstract
Background
Ticks carry microbes, some of which are pathogenic for humans and animals. To assess this One Health challenge, 342 ticks were collected from pet dogs and cats at 10 veterinary clinics in Finland as part of the European project “Protect Our Future Too”.

Methods
The tick species were identified, and ticks were screened with quantitative PCR (qPCR) for tick-borne pathogens, including Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Ehrlichia canis, Anaplasma spp., Candidatus Neoehrlichia mikurensis, tick-borne encephalitis virus (TBEV), and Babesia spp. For comparison, a subset of tick DNA (20 qPCR-positive samples) was analysed with 16S next-generation sequencing (NGS).

Results
Most ticks were Ixodes ricinus (289, 84.5%), followed by Ixodes persulcatus (51, 14.9%). One hybrid tick (I. ricinus/I. persulcatus, 0.3%) and one Rhipicephalus sanguineus tick (0.3%) were identified. We found one or more of the analysed pathogens in 17% (59/342) of the ticks. The most prevalent pathogen was B. burgdorferi s.l. (36, 10.5%), followed by Anaplasma phagocytophilum (12, 3.5%), B. miyamotoi (5, 1.5%), Babesia venatorum (4, 1.2%), and TBEV (1, 0.3%). Candidatus Neoehrlichia mikurensis DNA was amplified from three (0.9%) ticks. Ehrlichia canis was not detected. In the 16S NGS, six samples produced enough reads for the analysis. In these six samples, we confirmed all the positive qPCR findings of Borrelia spp. and Ca. N. mikurensis.

Conclusions
The high prevalence of pathogenic microorganisms in the ticks of this study emphasizes the importance of awareness of ticks and tick-borne diseases and prevention. Furthermore, the results show that veterinary surveillance can facilitate early detection of tick-borne pathogens and new tick species and draw attention to possible co-infections that should be considered both in symptomatic humans and animals after tick bites.

Graphical Abstract
Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia
Authors: Humphries Sam , Bond Danielle R. , Germon Zacary P. , Keely Simon , Enjeti Anoop K. , Dun Matthew D. , Lee Heather J. 
Published: September 2023

Abstract
Background
Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment.

Main body
This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents.

Conclusion
Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.
The spatiotemporal heterogeneity of the biophysical microenvironment during hematopoietic stem cell development: from embryo to adult
Authors: Shi Guolin , Zhang Pan , Zhang Xi , Li Jing , Zheng Xinmin , Yan Jinxiao , Zhang Nu , Yang Hui 
Published: September 2023

AbstractHematopoietic stem cells (HSCs) with the ability to self-renew and differentiate are responsible for maintaining the supply of all types of blood cells. The complex and delicate microenvironment surrounding HSCs is called the HSC niche and can provide physical, chemical, and biological stimuli to regulate the survival, maintenance, proliferation, and differentiation of HSCs. Currently, the exploration of the biophysical regulation of HSCs remains in its infancy. There is evidence that HSCs are susceptible to biophysical stimuli, suggesting that the construction of engineered niche biophysical microenvironments is a promising way to regulate the fate of HSCs in vitro and ultimately contribute to clinical applications. In this review, we introduced the spatiotemporal heterogeneous biophysical microenvironment during HSC development, homeostasis, and malignancy. Furthermore, we illustrated how these biophysical cues contribute to HSC behaviors, as well as the possible mechanotransduction mechanisms from the extracellular microenvironment into cells. Comprehending the important functions of these biophysical regulatory factors will provide novel approaches to resolve clinical problems.
Loss of Dip2b leads to abnormal neural differentiation from mESCs
Authors: Yao Mingze , Pan Yuanqing , Ren Tinglin , Yang Caiting , Lei Yu , Xing Xiaoyu , Zhang Lei , Cui Xiaogang , Zheng Yaowu , Xing Li , Wu Changxin 
Published: September 2023

Abstract
Background
Disco-interacting protein 2 homolog B is a member of the Dip2 family encoded by the Dip2b gene. Dip2b is widely expressed in neuro-related tissues and is essential in axonal outgrowth during embryogenesis.

Methods
Dip2b knockout mouse embryonic stem cell line was established by CRISPR/Cas9 gene-editing technology. The commercial kits were utilized to detect cell cycle and growth rate. Flow cytometry, qRT-PCR, immunofluorescence, and RNA-seq were employed for phenotype and molecular mechanism assessment.

Results
Our results suggested that Dip2b is dispensable for the pluripotency maintenance of mESCs. Dip2b knockout could not alter the cell cycle and proliferation of mECSs, or the ability to differentiate into three germ layers in vitro. Furthermore, genes associated with axon guidance, channel activity, and synaptic membrane were significantly downregulated during neural differentiation upon Dip2b knockout.

Conclusions
Our results suggest that Dip2b plays an important role in neural differentiation, which will provide a valuable model for studying the exact mechanisms of Dip2b during neural differentiation.
Sox11 is enriched in myogenic progenitors but dispensable for development and regeneration of the skeletal muscle
Authors: Oprescu Stephanie N. , Baumann Nick , Chen Xiyue , Sun Qiang , Zhao Yu , Yue Feng , Wang Huating , Kuang Shihuan 
Published: September 2023

AbstractTranscription factors (TFs) play key roles in regulating differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment of Sox11 mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data, Sox11 levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate that Sox11 expression is reduced in aged MuSCs. Age-related decline of Sox11 expression is associated with reduced chromatin contacts within the topologically associating domains. Unexpectedly, Myod1Cre-driven deletion of Sox11 in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreER- or Rosa26CreER- driven (MuSC-specific or global) deletion of Sox11 in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remains to be elucidated.
Optimization and characterization of antileukemic l-asparaginase produced by Fusarium solani endophyte
Authors: Osama Sarah , El-Sherei Moshera M. , Al-Mahdy Dalia A. , Bishr Mokhtar , Salama Osama , Raafat Marwa M. 
Published: September 2023

Abstractl-asparaginase is an antileukemic enzyme that hydrolyzes l-asparagine into l-aspartic acid and ammonia, causing cell starvation and apoptosis in susceptible leukemic cell populations. Currently, l-asparaginase obtained from bacterial sources is constrained by several issues, including lesser productivity, stability, selectivity, and higher toxicity. The goal of this study is to provide fungal l-asparaginase with in-vitro effectiveness towards different human carcinomas. l-asparaginase from endophytic Fusarium solani (Gene Bank accession number MW209717) isolated from the roots of the medicinal plant Hedera helix L. was characterized and optimized experimentally for maximum l-asparaginase production in addition to evaluating its subsequent cytotoxicity towards acute monocytic leukemia and human skin fibroblast cell lines. The enzyme production was maximized using potato dextrose media (15.44 IU/ml/hr) at the 5th and 6th days of fermentation with incubation temperature 30 °C, 3% asparagine, 150–180 rpm agitation rate and a 250 ml flask. Enzyme characterization studies revealed that the enzyme maintained its thermal stability with temperatures up to 60 °C. However, its optimal activity was achieved at 35 °C. On measuring the enzymatic activity at various temperatures and different pH, maximum enzyme activity was recorded at 40 °C and pH 8 using 0.1 M asparagine concentration. Results also revealed promising cytotoxic activity against acute monocytic leukemia with IC50 = 3.66 µg/ml and low cytotoxicity against tested normal human skin fibroblast cell line which suggested that it might have selective toxicity, and consequently it could be used as a less toxic alternative to the current formulations.
A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1G93A model of ALS
Authors: Gerovska Daniela , Noer Julie B. , Qin Yating , Ain Quratul , Januzi Donjetë , Schwab Matthias , Witte Otto W. , Araúzo-Bravo Marcos J. , Kretz Alexandra 
Published: September 2023

Abstract
Background
Numerous genes, including SOD1, mutated in familial and sporadic amyotrophic lateral sclerosis (f/sALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. One possible outcome of chromosomal instability and repair processes is extrachromosomal circular DNA (eccDNA) formation. Therefore, eccDNA might accumulate in f/sALS with yet unknown function.

Methods
We combined rolling circle amplification with linear DNA digestion to purify eccDNA from the cervical spinal cord of 9 co-isogenic symptomatic hSOD1G93A mutants and 10 controls, followed by deep short-read sequencing. We mapped the eccDNAs and performed differential analysis based on the split read signal of the eccDNAs, referred as DifCir, between the ALS and control specimens, to find differentially produced per gene circles (DPpGC) in the two groups. Compared were eccDNA abundances, length distributions and genic profiles. We further assessed proteome alterations in ALS by mass spectrometry, and matched the DPpGCs with differentially expressed proteins (DEPs) in ALS. Additionally, we aligned the ALS-specific DPpGCs to ALS risk gene databases.

Results
We found a six-fold enrichment in the number of unique eccDNAs in the genotoxic ALS-model relative to controls. We uncovered a distinct genic circulome profile characterized by 225 up-DPpGCs, i.e., genes that produced more eccDNAs from distinct gene sequences in ALS than under control conditions. The inter-sample recurrence rate was at least 89% for the top 6 up-DPpGCs. ALS proteome analyses revealed 42 corresponding DEPs, of which 19 underlying genes were itemized for an ALS risk in GWAS databases. The up-DPpGCs and their DEP tandems mainly impart neuron-specific functions, and gene set enrichment analyses indicated an overrepresentation of the adenylate cyclase modulating G protein pathway.

Conclusions
We prove, for the first time, a significant enrichment of eccDNA in the ALS-affected spinal cord. Our triple circulome, proteome and genome approach provide indication for a potential importance of certain eccDNAs in ALS neurodegeneration and a yet unconsidered role as ALS biomarkers. The related functional pathways might open up new targets for therapeutic intervention.

Graphical Abstract
Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol
Authors: Rudajev Vladimir , Novotny Jiri 
Published: September 2023

AbstractAmyloid β is considered a key player in the development and progression of Alzheimer’s disease (AD). Many studies investigating the effect of statins on lowering cholesterol suggest that there may be a link between cholesterol levels and AD pathology. Since cholesterol is one of the most abundant lipid molecules, especially in brain tissue, it affects most membrane-related processes, including the formation of the most dangerous form of amyloid β, Aβ42. The entire Aβ production system, which includes the amyloid precursor protein (APP), β-secretase, and the complex of γ-secretase, is highly dependent on membrane cholesterol content. Moreover, cholesterol can affect amyloidogenesis in many ways. Cholesterol influences the stability and activity of secretases, but also dictates their partitioning into specific cellular compartments and cholesterol-enriched lipid rafts, where the amyloidogenic machinery is predominantly localized. The most complicated relationships have been found in the interaction between cholesterol and APP, where cholesterol affects not only APP localization but also the precise character of APP dimerization and APP processing by γ-secretase, which is important for the production of Aβ of different lengths. In this review, we describe the intricate web of interdependence between cellular cholesterol levels, cholesterol membrane distribution, and cholesterol-dependent production of Aβ, the major player in AD.
Early COVID-Related pandemic impacts and subsequent opioid outcomes among persons receiving medication for opioid use disorder: a secondary data analysis of a Type-3 hybrid trial
Authors: Janssen Tim , Garner Bryan R. , Yermash Julia , Yap Kimberly R. , Becker Sara J. 
Published: September 2023

Abstract
Background
Opioid overdoses have continued to increase since the start of the COVID-19 pandemic. The pathways through which the COVID-19 pandemic has affected trajectories of opioid use and opioid-related problems are largely unknown. Using the Epidemic-Pandemic Impacts Inventory (EPII), a novel instrument that assess pandemic-related impacts across multiple life domains, we tested the hypothesis that COVID-related impacts (on e.g., interpersonal conflict, employment, infection exposure, and emotional health) experienced in the early months of the pandemic would predict changes in opioid use and opioid-related problems at follow-up.

Methods
This analysis was embedded within a cluster randomized type 3 implementation-effectiveness hybrid trial that had enrolled 188 patients across eight opioid treatments prior to the start of the pandemic. Participants had all been recently inducted on medication for opioid use disorder and were actively receiving treatment. Participants reported on their opioid use and opioid-related problems at baseline and 3-, 6-, and 9-month post-baseline assessments. Between May and August 2020, participants were sent an optional invitation to complete the EPII.

Results
One hundred thirty-three respondents completed the EPII and 129 had sufficient data to analyze the EPII and at least one subsequent follow-up. In logistic and zero-inflated negative binomial analyses adjusting for covariates, each endorsed pandemic impact in the interpersonal conflict domain was associated with 67% increased odds of endorsement of any opioid use, and each impact in the employment and infection exposure-domains was associated with 25% and 75% increases in number of endorsed opioid-related problems, respectively.

Conclusions
Mitigating the effect of the pandemic on patients’ interpersonal relationships and employment, and promoting greater infection control in opioid treatment programs, could be protective against negative opioid-related outcomes.
Trial registration The present study describes secondary data analysis on a previously registered clinical trial: clinicaltrials.gov/ct2/show/NCT03931174.
Cholesterol reprograms glucose and lipid metabolism to promote proliferation in colon cancer cells
Authors: Mayengbam Shyamananda Singh , Singh Abhijeet , Yaduvanshi Himanshi , Bhati Firoz Khan , Deshmukh Bhavana , Athavale Dipti , Ramteke Pranay L. , Bhat Manoj Kumar 
Published: September 2023

AbstractHypercholesterolemia is often correlated with obesity which is considered a risk factor for various cancers. With the growing population of hypercholesterolemic individuals, there is a need to understand the role of increased circulatory cholesterol or dietary cholesterol intake towards cancer etiology and pathology. Recently, abnormality in the blood cholesterol level of colon cancer patients has been reported. In the present study, we demonstrate that alteration in cholesterol levels (through a high-cholesterol or high-fat diet) increases the incidence of chemical carcinogen-induced colon polyp occurrence and tumor progression in mice. At the cellular level, low-density lipoprotein cholesterol (LDLc) and high-density lipoprotein cholesterol (HDLc) promote colon cancer cell proliferation by tuning the cellular glucose and lipid metabolism. Mechanistically, supplementation of LDLc or HDLc promotes cellular glucose uptake, and utilization, thereby, causing an increase in lactate production by colon cancer cells. Moreover, LDLc or HDLc upregulates aerobic glycolysis, causing an increase in total ATP production through glycolysis, and a decrease in ATP generation by OXPHOS. Interestingly, the shift in the metabolic status towards a more glycolytic phenotype upon the availability of cholesterol supports rapid cell proliferation. Additionally, an alteration in the expression of the molecules involved in cholesterol uptake along with the increase in lipid and cholesterol accumulation was observed in cells supplemented with LDLc or HDLc. These results indicate that colon cancer cells directly utilize the cholesterol associated with LDLc or HDLc. Moreover, targeting glucose metabolism through LDH inhibitor (oxamate) drastically abrogates the cellular proliferation induced by LDLc or HDLc. Collectively, we illustrate the vital role of cholesterol in regulating the cellular glucose and lipid metabolism of cancer cells and its direct effect on the colon tumorigenesis.
Graphical Abstract
Sub-threshold or full-syndrome borderline personality disorder in adolescents with recurrent self-harm – distinctly or dimensionally different?
Authors: Brager-Larsen Anne , Zeiner Pål , Mehlum Lars 
Published: September 2023

Abstract
Background
Borderline personality disorder (BPD) is a severe mental disorder frequently seen in individuals with recurrent self-harm behaviour. To what extent there are distinguishing characteristics between self-harming adolescents who meet the criteria for a full diagnosis of BPD, a sub-threshold number of BPD criteria and those who don’t have BPD, with respect to clinical characteristics, is still uncertain and could have important clinical implications.

Methods
Data from 103 adolescents with recurrent self-harm behaviour recruited from child and adolescent psychiatric outpatient clinics were collected through clinical interviews and self-reports. Bivariate analyses comparing participants with or without a diagnosis of BPD were performed. Group differences based on the number of BPD criteria fulfilled (few-if-any BPD: 0–2 criteria, sub-threshold BPD: 3–4 criteria, full-syndrome BPD: 5 or more criteria) were tested and regression analyses performed.

Results
Adolescents with a diagnosis of BPD (28.2%) had significantly higher numbers of co-morbid DSM-5 disorders, suicide attempts and self-harm methods. They also reported significantly higher levels of suicidal ideation, depression, anxiety and impulsivity, compared with adolescents without BPD. Adolescents with sub-threshold BPD (20.4%) place themselves in the intermediate position between participants with full-syndrome BPD and participants with few-if-any BPD, in terms of these symptoms. Higher levels of emotional regulation difficulties and a lower level of global functioning were significantly associated with fulfilling a higher number of BPD criteria.

Conclusion
Adolescents with recurrent self-harm who meet diagnostic criteria for a full-syndrome BPD or sub-threshold BPD seem to have difficulties within the same spectrum. They seem dimensionally, but not categorically, different with respect to the severity of their difficulties. These adolescents need interventions aimed at their dysfunctional self-harm behaviour, emotional regulation difficulties and BPD symptoms at an earlier, rather than at a later stage of symptom development.
Fabrication and evaluation of a flexible temperature sensor array using multi-layer ceramic capacitors for spatial temperature mapping
Authors: Yoon Ji-Sung , Yun Kwang-Seok 
Published: September 2023

AbstractThis paper presents the development of a flexible temperature sensor array using multi-layer ceramic capacitors. By integrating the capacitors into a 5 × 5 array on a polydimethylsiloxane (PDMS) substrate, we exploit the principle of changing dielectric constant with temperature, which results in a change in capacitance. Our sensor array demonstrates a consistent decrease in capacitance with increasing temperature, with a sensitivity ranging from 1.42 to 1.62 pF/°C. This sensitivity range is maintained even when measurements are taken using a capacitance-to-voltage conversion circuit, with a sensitivity of 1.1 to 1.5 mV/°C. The repeatability and hysteresis of the sensors were also investigated, with the latter revealing a maximum error of 12.7%. Our findings provide valuable insights for the development of efficient, flexible, and reliable temperature sensor arrays using ceramic capacitors.