bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of Parascaris species in three different Equus populations in China
Authors: Zhou Mengchao , Lu Yaxian , Han Lei , Lu Maolin , Guan Chunyu , Yu Jie , Liu Hetong , Chen Denghui , Li Hongjia , Yang Yuling , Zhang Lu , Tian Lihong , Liu Quan , Hou Zhijun 
Published: June 2023

Abstract
Background
The roundworms, Parascaris spp., are important nematode parasites of foals and were historically model organisms in the field of cell biology, leading to many important discoveries. According to karyotype, ascarids in Equus are commonly divided into Parascaris univalens (2n = 2) and Parascaris equorum (2n = 4).

Methods
Here, we performed morphological identification, karyotyping and sequencing of roundworms from three different hosts (horses, zebras and donkeys). Phylogenetic analysis was performed to study the divergence of these ascarids based on cytochrome c oxidase subunit I (COI) and internal transcribed spacer (ITS) sequences.

Results
Karyotyping, performed on eggs recovered from worms of three different Equus hosts in China, showed two different karyotypes (2n = 2 in P. univalens collected from horses and zebras; 2n = 6 in Parascaris sp. collected from donkeys). There are some differences in the terminal part of the spicula between P. univalens (concave) and Parascaris sp. (rounded). Additionally, it was found that the egg’s chitinous layer was significantly thicker in Parascaris sp. (> 5 μm) than P. univalens (< 5 μm) (F(2537) = 1967, P < 0.01). Phylogenetic trees showed that the sequences of Parascaris from Equus hosts were divided into two distinct lineages based on sequences of the COI and ITS.

Conclusions
Comparing the differences in roundworms collected from three different Equus hosts, this study describes a Parascaris species (Parascaris sp.) with six chromosomes in donkeys. It is worth noting that the thickness of the chitinous layer in the Parascaris egg may serve as a diagnostic indicator to distinguish the two roundworms (P. univalens and Parascaris sp.). The Parascaris sp. with six chromosomes in donkeys in the present study may be a species of P. trivalens described in 1934, but the possibility that it is a new Parascaris species cannot be ruled out. Both karyotyping and molecular analysis are necessary to solve the taxonomic problems in Parascaris species.
Influence of time factor and albuminuria on characteristics of patients with type 2 diabetes Mellitus before, during and 1 year after COVID-19 recovery
Authors: Gameil Mohammed Ali , Marzouk Rehab Elsayed , El-Sebaie Ahmed Hassan , Ahmed Eldeeb Ahmed Ahmed 
Published: June 2023

Abstract
Background
The potential effects of time factor and albuminuria on the morbid alterations in patients with type 2 diabetes (T2D) and COVID-19 are still unclear. We aimed to address the morbid alterations and the potential effects of time factor and albuminuria on the patients’ characteristics before, during, and 1 year after COVID-19 recovery.

Methods
83 patients with T2D were included, at Mansoura University Hospital, Egypt (July 2021-December 2021). Data of detailed history, physical examination, laboratory tests were recruited from files of the patients. Diagnosis and resolution of COVID-19 were established by Real time polymerase chain reaction (RT-PCR) test of SARS-CoV2. Complete blood count (CBC), renal and hepatic function tests, multiple measures of morning spot urine albumin to creatinine ratio (urine ACR), glycosylated hemoglobin (HBA1c), lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ferritin, neutrophil to lymphocyte ratio (NLR), vitamin D3, intact parathyroid hormone (intact PTH), serum calcium were applied to all participants.

Results
Our participants had a mean age of 45 years, 60.2% male, 56.6% were hospitalized, and 25.3% were admitted to ICU for severe COVID-19. Albuminuria was prevalent in 71.1% before, 98.8% during, and 92.8% after COVID-19 recovery. Patients with albuminuria showed older age, longer duration of T2D, more frequent severe COVID-19 and hospitalization (p = 0.03, p < 0.001, p = 0.023& p = 0.025) respectively. Body mass index (BMI), mean arterial blood pressure, ESR, CRP, ferritin, NLR, HBA1c, triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio, vitamin D3, serum calcium, alkaline phosphatase (ALP), hepatic aminotransferases, and urine ACR showed significant alterations throughout the study (p < 0.001 for all). Although the interaction between time and albuminuria showed non-significant effect on all studied parameters, we noticed relevant main effects of time factor on Body mass index (BMI), HBA1c, glomerular filtration rate (eGFR), TG/HDL ratio, NLR, vitamin D3, (p < 0.001 for all). Moreover, albuminuria showed main effects on BMI, serum creatinine, and intact PTH (p = 0.019, 0.005 & <0.001), respectively.

Conclusion
The characteristics of patients with T2D significantly altered throughout the study. Time factor and albuminuria exerted relevant main effects on the patients’ characteristics without significant effect of their interaction.
Predicting the effect of different folate doses on [68Ga]Ga-PSMA-11 organ and tumor uptake using physiologically based pharmacokinetic modeling
Authors: Siebinga Hinke , Hendrikx Jeroen J. M. A. , Huitema Alwin D. R. , de Wit-van der Veen Berlinda J. 
Published: June 2023

Abstract
Background
Folate intake might reduce [68Ga]Ga-PSMA-11 uptake in tissues due to a competitive binding to the PSMA receptor. For diagnostic imaging, this could impact decision making, while during radioligand therapy this could affect treatment efficacy. The relationship between folate dose, timing of dosing and tumor and organ uptake is not well established. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict the effect of folates on [68Ga]Ga-PSMA-11 PET/CT uptake in salivary glands, kidneys and tumors.

Methods
A PBPK model was developed for [68Ga]Ga-PSMA-11 and folates (folic acid and its metabolite 5-MTHF), with compartments added that represent salivary glands and tumor. Reactions describing receptor binding, internalization and intracellular degradation were included. Model evaluation for [68Ga]Ga-PSMA-11 was performed by using patient scan data from two different studies (static and dynamic), while for folates data from the literature were used for evaluation. Simulations were performed to assess the effect of different folate doses (150 µg, 400 µg, 5 mg and 10 mg) on accumulation in salivary glands, kidney and tumor, also for patients with different tumor volumes (10, 100, 500 and 1000 mL).

Results
Final model evaluation showed that predictions adequately described data for both [68Ga]Ga-PSMA-11 and folates. Predictions of a 5-MTFH dose of 150 µg and folic acid dose of 400 µg (in case of administration at the same time as [68Ga]Ga-PSMA-11 (t = 0)) showed no clinically relevant effect on salivary glands and kidney uptake. However, the effect of a decrease in salivary glands and kidney uptake was determined to be clinically relevant for doses of 5 mg (34% decrease for salivary glands and 32% decrease for kidney) and 10 mg (36% decrease for salivary glands and 34% decrease for kidney). Predictions showed that tumor uptake was not relevantly affected by the co-administration of folate for all different folate doses (range 150 µg–10 mg). Lastly, different tumor volumes did not impact the folate effect on [68Ga]Ga-PSMA-11 biodistribution.

Conclusion
Using a PBPK model approach, high doses of folate (5 and 10 mg) were predicted to show a decrease of [68Ga]Ga-PSMA-11 salivary glands and kidney uptake, while intake by means of folate containing food or vitamin supplements showed no relevant effects. In addition, tumor uptake was not affected by folate administration in the simulated dose ranges (150 µg–10 mg). Differences in tumor volume are not expected to impact folate effects on [68Ga]Ga-PSMA-11 organ uptake.
Out-of-pocket expenditure on community healthcare services at end-of-life among decedents from cardiovascular disease in six European countries and Israel
Authors: Tur-Sinai Aviad , Bentur Netta 
Published: June 2023

Abstract
Objectives
Most people who develop chronic diseases, including cardiovascular disease (CVD), live in their homes in the community in their last year of life. Since cost-sharing is common in most countries, including those with universal health insurance, these people incur out of pocket expenditure (OOPE).
The study aims to identify the prevalence and measure the size of OOPE among CVD decedents at end-of-life (EOL) explore differences among countries in OOPE, and examine whether the decedents’ characteristics or their countries’ health policy affects OOPE more.

Methods
SHARE data among people aged 50 + from seven European countries (including Israel) who died from CVD are analyzed. Decedents’ family members are interviewed to learn about OOPE on their relatives’ account.

Results
We identified 1,335 individuals who had died from CVD (average age 80.8 years, 54% men). More than half of CVD-decedent people spend OOPE on community services at EOL and their expenditure varies widely among countries. About one-third of people in France and Spain had OOPE, rising to around two-thirds in Israel and Italy and almost all in Greece. The average OOPE is 391.9 PPT, with wide variance across countries. Significant odds of OOPE exist in the country variable only, and significant differences exist in the amount of OOPE among countries and duration of illness preceding death.

Conclusions
Since improving CVD care efficiency and effectiveness are key aims, healthcare policymakers should broaden the investigation into expanding public funding for community services in order to mitigate OOPE, alleviate the economic burden on households, mitigate forgoing of community services due to price, and reduce rehospitalization.
Revisiting generalized Caputo derivatives in the context of two-point boundary value problems with the p-Laplacian operator at resonance
Authors: Adjabi Yassine , Jarad Fahd , Bouloudene Mokhtar , Panda Sumati Kumari 
Published: June 2023

AbstractThe novelty of this paper is that, based on Mawhin’s continuation theorem, we present some sufficient conditions that ensure that there is at least one solution to a particular kind of a boundary value problem with the p-Laplacian and generalized fractional Caputo derivative.
Effect of epigenetics on vitamin D levels: a systematic review until December 2020
Authors: Forouhari Ali , Heidari-Beni Motahar , Veisi Shaahin , Poursafa Parnian , Kelishadi Roya 
Published: June 2023

Abstract
Background
The association between epigenetic modification of the genes involved in the vitamin D metabolic pathway and vitamin D metabolites’ status has been elucidated incompletely. This study aims to review the studies on the mentioned association and create a brighter view of this topic.

Methods
A systematic literature search was conducted in Medline database (PubMed), Scopus, and Web of Science up to the end of November 2020. Original articles which reported the effect of epigenetic alteration—methylation level or its changes—of genes involved in vitamin D regulation on the vitamin D metabolites serum level or its changes were included. The National Institutes of Health (NIH) checklist was used to assess the quality of included articles.

Results
Among 2566 records, nine reports were included in the systematic review according to the inclusion and exclusion criteria. Studies discussed the contribution of methylation status of members of the cytochrome P450 family (CYP2R1, CYP27B1, CYP24A1), and Vitamin D Receptor (VDR) genes to vitamin D level variance. CYP2R1 methylation status could regulate the contributing factors affecting the vitamin D serum level and predict response to vitamin D supplementation. Studies revealed that impaired methylation of CYP24A1 occurs in response to an increase in serum level of 25-hydroxyvitamin D (25(OH)D). It is reported that the association between methylation levels of CYP2R1, CYP24A1, and VDR genes and 25(OH)D level is not affected by the methyl-donors bioavailability.

Conclusions
The epigenetic modification of the vitamin D-related genes could explain the vitamin D levels variation among populations. Large-scale clinical trials in various ethnicities are suggested to find the effect of epigenetics on vitamin D response variation.

Registration
The systematic review protocol was registered on PROSPERO (registration number: CRD42022306327).
In search of factors related to migration affecting children’s health – an analysis of documents guiding health visits within the Swedish school health services
Authors: Wahlström Emmie , Golsäter Marie , Holmström Inger K. , Larm Peter , Harder Maria 
Published: June 2023

Abstract
Background
Migration affects the health of children worldwide. Therefore, school nurses who encounter these children as part of their everyday practice need support from guidelines on how to promote the health of children who have migrated or whose parents have migrated. Yet knowledge regarding such content in guidelines of school nursing practice is sparse. Therefore, this study aims to investigate how municipal and regional guidelines and health questionnaires used in health visits in the Swedish school health services include factors related to migration that affect children’s health.

Methods
A document analysis of municipal and regional guidelines and health questionnaires guiding school nurses’ practice in health visits was conducted during the autumn of 2020. In total, 687 guidelines and health questionnaires were analyzed using deductive content analysis.

Results
The results show that municipal and regional guidelines and health questionnaires used in health visits in the Swedish school health services include content on many factors related to migration that affect children’s health. Yet the content was limited, and none was found on factors related to discrimination based on ethnicity or origin.

Conclusion
Guidance related to promoting the health of children who have migrated or whose parents have migrated should include all factors affecting these children’s health. Therefore, to strengthen school nurses’ evidence-based practice, guideline development might be needed, although guidelines and health questionnaires exist and include content on many factors related to migration affecting the health of children in order to provide equitable healthcare for all children, regardless of country of origin.
Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models
Authors: Drobny Alice , Boros Fanni Annamária , Balta Denise , Prieto Huarcaya Susy , Caylioglu Deniz , Qazi Niyeti , Vandrey Julia , Schneider Yanni , Dobert Jan Philipp , Pitcairn Caleb , Mazzulli Joseph Robert , Zunke Friederike 
Published: June 2023

Abstract
Background
Lysosomal dysfunction has been implicated in a number of neurodegenerative diseases such as Parkinson’s disease (PD). Various molecular, clinical and genetic studies have highlighted a central role of lysosomal pathways and proteins in the pathogenesis of PD. Within PD pathology the synaptic protein alpha-synuclein (αSyn) converts from a soluble monomer to oligomeric structures and insoluble amyloid fibrils. The aim of this study was to unravel the effect of αSyn aggregates on lysosomal turnover, particularly focusing on lysosomal homeostasis and cathepsins. Since these enzymes have been shown to be directly involved in the lysosomal degradation of αSyn, impairment of their enzymatic capacity has extensive consequences.

Methods
We used patient-derived induced pluripotent stem cells and a transgenic mouse model of PD to examine the effect of intracellular αSyn conformers on cell homeostasis and lysosomal function in dopaminergic (DA) neurons by biochemical analyses.

Results
We found impaired lysosomal trafficking of cathepsins in patient-derived DA neurons and mouse models with αSyn aggregation, resulting in reduced proteolytic activity of cathepsins in the lysosome. Using a farnesyltransferase inhibitor, which boosts hydrolase transport via activation of the SNARE protein ykt6, we enhanced the maturation and proteolytic activity of cathepsins and thereby decreased αSyn protein levels.

Conclusions
Our findings demonstrate a strong interplay between αSyn aggregation pathways and function of lysosomal cathepsins. It appears that αSyn directly interferes with the enzymatic function of cathepsins, which might lead to a vicious cycle of impaired αSyn degradation.

Graphical abstract
Lysosomal trafficking of cathepsin D (CTSD), CTSL and CTSB is disrupted when alpha-synuclein (αSyn) is aggregated. This results in a decreased proteolytic activity of cathepsins, which directly mediate αSyn clearance. Boosting the transport of the cathepsins to the lysosome increases their activity and thus contributes to efficient αSyn degradation.
Domestic abuse in the Covid-19 pandemic: measures designed to overcome common limitations of trend measurement
Authors: Hodgkinson Sarah , Dixon Anthony , Halford Eric , Farrell Graham 
Published: June 2023

AbstractResearch on pandemic domestic abuse trends has produced inconsistent findings reflecting differences in definitions, data and method. This study analyses 43,488 domestic abuse crimes recorded by a UK police force. Metrics and analytic approaches are tailored to address key methodological issues in three key ways. First, it was hypothesised that reporting rates changed during lockdown, so natural language processing was used to interrogate untapped free-text information in police records to develop a novel indicator of change in reporting. Second, it was hypothesised that abuse would change differentially for those cohabiting (due to physical proximity) compared to non-cohabitees, which was assessed via a proxy measure. Third, the analytic approaches used were change-point analysis and anomaly detection: these are more independent than regression analysis for present purposes in gauging the timing and duration of significant change. However, the main findings were largely contrary to expectation: (1) domestic abuse did not increase during the first national lockdown in early 2020 but increased across a prolonged post-lockdown period, (2) the post-lockdown increase did not reflect change in reporting by victims, and; (3) the proportion of abuse between cohabiting partners, at around 40 percent of the total, did not increase significantly during or after the lockdown. The implications of these unanticipated findings are discussed.
Synthase-selected sorting approach identifies a beta-lactone synthase in a nudibranch symbiotic bacterium
Authors: Džunková Mária , La Clair James J. , Tyml Tomáš , Doud Devin , Schulz Frederik , Piquer-Esteban Samuel , Porcel Sanchis Dafne , Osborn Andrew , Robinson David , Louie Katherine B. , Bowen Ben P. , Bowers Robert M. , Lee Janey , Arnau Vicente , Díaz-Villanueva Wladimiro , Stepanauskas Ramunas , Gosliner Terrence , Date Shailesh V. , Northen Trent R. , Cheng Jan-Fang , Burkart Michael D. , Woyke Tanja 
Published: June 2023

Abstract
Background
Nudibranchs comprise a group of > 6000 marine soft-bodied mollusk species known to use secondary metabolites (natural products) for chemical defense. The full diversity of these metabolites and whether symbiotic microbes are responsible for their synthesis remains unexplored. Another issue in searching for undiscovered natural products is that computational analysis of genomes of uncultured microbes can result in detection of novel biosynthetic gene clusters; however, their in vivo functionality is not guaranteed which limits further exploration of their pharmaceutical or industrial potential. To overcome these challenges, we used a fluorescent pantetheine probe, which produces a fluorescent CoA-analog employed in biosynthesis of secondary metabolites, to label and capture bacterial symbionts actively producing these compounds in the mantle of the nudibranch Doriopsilla fulva.

Results
We recovered the genome of Candidatus Doriopsillibacter californiensis from the Ca. Tethybacterales order, an uncultured lineage of sponge symbionts not found in nudibranchs previously. It forms part of the core skin microbiome of D. fulva and is nearly absent in its internal organs. We showed that crude extracts of D. fulva contained secondary metabolites that were consistent with the presence of a beta-lactone encoded in Ca. D. californiensis genome. Beta-lactones represent an underexplored group of secondary metabolites with pharmaceutical potential that have not been reported in nudibranchs previously.

Conclusions
Altogether, this study shows how probe-based, targeted sorting approaches can capture bacterial symbionts producing secondary metabolites in vivo.
A live attenuated RHΔompdcΔuprt mutant of Toxoplasma gondii induces strong protective immunity against toxoplasmosis in mice and cats
Authors: Shen Yu , Zheng Bin , Sun Hao , Wu Songrui , Fan Jiyuan , Ding Jianzu , Gao Meng , Kong Qingming , Lou Di , Ding Haojie , Zhuo Xunhui , Lu Shaohong 
Published: June 2023

AbstractBackgroundToxoplasma gondiiis an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis. It is essential to develop an effective anti-T. gondiivaccine for the control of toxoplasmosis, and this study is to explore the immunoprotective effects of a live attenuated vaccine in mice and cats.MethodsFirst, theompdcanduprtgenes ofT. gondiiwere deleted through the CRISPR-Cas9 system. Then, the intracellular proliferation and virulence of this mutant strain were evaluated. Subsequently, the immune responses induced by this mutant in mice and cats were detected, including antibody titers, cytokine levels, and subsets of T lymphocytes. Finally, the immunoprotective effects were evaluated by challenge with tachyzoites of different strains in mice or cysts of the ME49 strain in cats. Furthermore, to discover the effective immune element against toxoplasmosis, passive immunizations were carried out. GraphPad Prism software was used to conduct the log-rank (Mantel–Cox) test, Student’sttest and one-way ANOVA.ResultsThe RHΔompdcΔuprtwere constructed by the CRISPR-Cas9 system. Compared with the wild-type strain, the mutant notably reduced proliferation (P < 0.05). In addition, the mutant exhibited virulence attenuation in both murine (BALB/c and BALB/c-nu) and cat models. Notably, limited pathological changes were found in tissues from RHΔompdcΔuprt-injected mice. Furthermore, compared with nonimmunized group, high levels of IgG (IgG1 and IgG2a) antibodies and cytokines (IFN-γ, IL-4, IL-10, IL-2 and IL-12) in mice were detected by the mutant (P < 0.05). Remarkably, all RHΔompdcΔuprt-vaccinated mice survived a lethal challenge with RHΔku80and ME49 and WH6 strains. The immunized sera and splenocytes, especially CD8+T cells, could significantly extend (P < 0.05) the survival time of mice challenged with the RHΔku80strain compared with naïve mice. In addition, compared with nonimmunized cats, cats immunized with the mutant produced high levels of antibodies and cytokines (P < 0.05), and notably decreased the shedding numbers of oocysts in feces (95.3%).ConclusionsThe avirulent RHΔompdcΔuprtstrain can provide strong anti-T. gondiiimmune responses, and is a promising candidate for developing a safe and effective live attenuated vaccine.Graphical abstract