bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic and evolutionary basis of gene expression variation in East Africans
Authors: Kelly Derek E. , Ramdas Shweta , Ma Rong , Rawlings-Goss Renata A. , Grant Gregory R. , Ranciaro Alessia , Hirbo Jibril B. , Beggs William , Yeager Meredith , Chanock Stephen , Nyambo Thomas B. , Omar Sabah A. , Woldemeskel Dawit , Belay Gurja , Li Hongzhe , Brown Christopher D. , Tishkoff Sarah A. 
Published: February 2023

Abstract
Background
Mapping of quantitative trait loci (QTL) associated with molecular phenotypes is a powerful approach for identifying the genes and molecular mechanisms underlying human traits and diseases, though most studies have focused on individuals of European descent. While important progress has been made to study a greater diversity of human populations, many groups remain unstudied, particularly among indigenous populations within Africa. To better understand the genetics of gene regulation in East Africans, we perform expression and splicing QTL mapping in whole blood from a cohort of 162 diverse Africans from Ethiopia and Tanzania. We assess replication of these QTLs in cohorts of predominantly European ancestry and identify candidate genes under selection in human populations.

Results
We find the gene regulatory architecture of African and non-African populations is broadly shared, though there is a considerable amount of variation at individual loci across populations. Comparing our analyses to an equivalently sized cohort of European Americans, we find that QTL mapping in Africans improves the detection of expression QTLs and fine-mapping of causal variation. Integrating our QTL scans with signatures of natural selection, we find several genes related to immunity and metabolism that are highly differentiated between Africans and non-Africans, as well as a gene associated with pigmentation.

Conclusion
Extending QTL mapping studies beyond European ancestry, particularly to diverse indigenous populations, is vital for a complete understanding of the genetic architecture of human traits and can reveal novel functional variation underlying human traits and disease.
Mir-421 and mir-550a-1 are potential prognostic markers in esophageal adenocarcinoma
Authors: Ji Yun , Wang Lulu , Chang Guanglei , Yan Juan , Dai Liping , Ji Zhenyu , Liu Jingjing , He Meixia , Xu Hongliang , Zhang Liguo 
Published: February 2023

Abstract
Objective
To identify the prognostic indicators of esophageal adenocarcinoma (EAC) for future EAC diagnosis and treatment.

Methods
The EAC dataset from The Cancer Genome Atlas was screened for differentially expressed microRNAs (miRNAs) and mRNAs associated with EAC. Weighted gene coexpression network analysis was performed to cluster miRNAs or mRNA with similar expression patterns to identify the miRNAs or mRNA that are highly associated with EAC. Prognostic miRNAs for overall survival (OS) were identified using Cox proportional-hazards regression analysis and least absolute shrinkage and selection operator based on survival duration and status. Two types of miRNAs were selected to develop a prognostic signature model for EAC using multiple Cox regression analysis. Furthermore, the signature was validated using internal validation sets 1 and 2. The receiver operating characteristic curve and concordance index were used to evaluate the accuracy of the signature and validation sets. The expression of miR-421, miR-550a-3p, and miR-550a-5p was assessed using quantitative polymerase chain reaction (qPCR). The proliferation, invasion, and migration of EAC cells were assessed using CCK8 and transwell assays. The OS of target mRNAs was assessed using Kaplan–Meier analysis. Functional enrichment analysis of the target mRNAs was performed using Metascape.

Results
The prognostic signature and validation sets comprising mir-421 and mir-550a-1 had favorable predictive power in OS. Compared with the patients with EAC in the high-expression group, those assigned to the low-expression group displayed increased OS according to survival analysis. Differential and qPCR analysis showed that miR-421, miR-550a-3p, and miR-550a-5p were highly expressed in the EAC tissues and cell lines. Moreover, the downregulation of miR-421 and miR-550a-3p with inhibitor markedly suppressed the proliferation, invasion, and migration in OE33 cells compared with the negative control. A total of 20 target mRNAs of three miRNAs were predicted, among which seven target mRNAs—ASAP3, BCL2L2, LMF1, PPM1L, PTPN21, SLC18A2, and NR3C2—had prognostic value; PRKACB, PDCD4, RPS6KA5, and BCL2L2 were enriched in the miRNA cancer pathway.

Conclusion
Prognostic indicators of EAC may be useful in future EAC diagnosis and treatment.
Comparison of antimicrobial resistant Escherichia coli isolated from Irish commercial pig farms with and without zinc oxide and antimicrobial usage
Authors: Ekhlas Daniel , Sanjuán Juan M. Ortiz , Manzanilla Edgar G. , Leonard Finola C. , Argüello Héctor , Burgess Catherine M. 
Published: February 2023

Abstract
Background
The prophylactic use of antimicrobials and zinc oxide (ZnO) in pig production was prohibited by the European Union in 2022 due to potential associations between antimicrobial and heavy metal usage with antimicrobial resistance (AMR) and concerns regarding environmental pollution. However, the effects of their usage on the bacterial AMR profiles on commercial pig farms are still not fully understood and previous studies examining the effect of ZnO have reported contrasting findings. The objective of this study was to examine the effects of antimicrobial and ZnO usage on AMR on commercial pig farms. Faecal and environmental samples were taken on 10 Irish commercial farms, of which 5 farms regularly used ZnO and antimicrobials (amoxicillin or sulphadiazine-trimethoprim) for the prevention of disease. The other 5 farms did not use ZnO or any other form of prophylaxis. Escherichia coli numbers were quantified from all samples using non-supplemented and supplemented Tryptone Bile X-glucuronide agar.

Results
In total 351 isolates were phenotypically analysed, and the genomes of 44 AmpC/ESBL-producing E. coli isolates from 4 farms were characterised using whole-genome sequencing. Phenotypic analysis suggested higher numbers of multi-drug resistant (MDR) E. coli isolates on farms using prophylaxis. Furthermore, farms using prophylaxis were associated with higher numbers of isolates resistant to apramycin, trimethoprim, tetracycline, streptomycin, and chloramphenicol, while resistance to ciprofloxacin was more associated with farms not using any prophylaxis. Thirty-four of the 44 AmpC/ESBL-producing E. coli strains harboured the blaCTX-M-1 resistance gene and were multi drug resistant (MDR). Moreover, network analysis of plasmids and analysis of integrons showed that antimicrobial and biocide resistance genes were frequently co-located on mobile genetic elements, indicating the possibility for co-selection during antimicrobial or biocide usage as a contributor to AMR occurrence and persistence on farms.

Conclusions
The results of this study showed evidence that antimicrobial and ZnO treatment of pigs post-weaning can favour the selection and development of AMR and MDR E. coli. Co-location of resistance genes on mobile genetic elements was observed. This study demonstrated the usefulness of phenotypic and genotypic detection of antimicrobial resistance by combining sequencing and microbiological methods.
The prevalence of gastrointestinal symptoms and cobalamin deficiency in patients with chronic urticaria
Authors: Abadeh Armin , Herman Sari M. , Abdalian Rupert 
Published: February 2023

AbstractBackgroundThere is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population.ObjectiveTo report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria.MethodsA retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records.ResultsSeventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms.ConclusionsThis is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients.Trial registrationNot applicable
Diffusion tensor imaging discriminates focal cortical dysplasia from normal brain parenchyma and differentiates between focal cortical dysplasia types
Authors: Gennari Antonio Giulio , Cserpan Dorottya , Stefanos-Yakoub Ilona , Kottke Raimund , O’Gorman Tuura Ruth , Ramantani Georgia 
Published: February 2023

Abstract
Objectives
Although diffusion tensor imaging (DTI) may facilitate the identification of cytoarchitectural changes associated with focal cortical dysplasia (FCD), the predominant aetiology of paediatric structural epilepsy, its potential has thus far remained unexplored in this population. Here, we investigated whether DTI indices can differentiate FCD from contralateral brain parenchyma (CBP) and whether clinical features affect these indices.

Methods
In this single-centre, retrospective study, we considered children and adolescents with FCD-associated epilepsy who underwent brain magnetic resonance (MRI), including DTI. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity, were calculated in both FCD and CBP. The DTI indices best discriminating between FCD and CBP were subsequently used to assess the link between DTI and selected clinical and lesion-related parameters.

Results
We enrolled 32 patients (20 male; median age at MRI 4 years), including 15 with histologically confirmed FCD. FA values were lower (p = 0.03), whereas MD values were higher in FCD than in CBP (p = 0.04). The difference in FA values between FCD and CBP was more pronounced for a positive vs. negative history of status epilepticus (p = 0.004). Among histologically confirmed cases, the difference in FA values between FCD and CBP was more pronounced for type IIb versus type I FCD (p = 0.03).

Conclusions
FA and MD discriminate between FCD and CBP, while FA differentiates between FCD types. Status epilepticus increases differences in FA, potentially reflecting changes induced in the brain. Our findings support the potential of DTI to serve as a non-invasive biomarker to characterise FCD in the paediatric population.
Undergraduate radiology education in Europe in 2022: a survey from the European Society of Radiology (ESR)
Authors:   European Society of Radiology (ESR), Sendra-Portero Francisco , Souto Miguel , Becker Minerva , Goh Vicky ,   ESR Undergraduate Subcommittee
Published: February 2023

Abstract
Background
Education in radiology should be an integral aspect of undergraduate medical training given the essential role of imaging in patient management. Since the introduction of the European Society of Radiology undergraduate curriculum a decade ago, radiology education has evolved.

Objectives
This survey aimed to assess the current status of undergraduate radiology education in Europe.

Methods
An electronic survey on undergraduate teaching was distributed by the European Society of Radiology to delegates of the European Society of Radiology education committee and presidents of national radiological societies from April 1 to May 31, 2022. Data from the twenty questions were summarized using descriptive statistics.

Results
There were 72 respondents from 36 countries. Radiology was taught to undergraduates in 95% (68/72), with a national or local curriculum informing radiology education in 93% (67/72). Radiology teaching was delivered by radiologists in 98% (58/59), across all years of medical school but most commonly in the fourth year of medical training (63%, 44/70), through various means including lectures, workshops, radiology department placements, online resources and simulation. Teaching hours were variable, with a minimum of 10 h reported.

Conclusion
This survey’s findings suggest an improvement over the last decade in the engagement of radiologists in the delivery of undergraduate radiology education in European countries affiliated with the European Society of Radiology.
Sex differences in hearing impairment due to diet-induced obesity in CBA/Ca mice
Authors: Kim Soo Jeong , Gajbhiye Akanksha , Lyu Ah-Ra , Kim Tae Hwan , Shin Sun-Ae , Kwon Hyuk Chan , Park Yong-Ho , Park Min Jung 
Published: February 2023

Abstract
Background
Obesity is an independent risk factor for hearing loss. Although attention has focused on major obesity comorbidities such as cardiovascular disease, stroke, and type 2 diabetes, the impact of obesity on sensorineural organs, including the auditory system, is unclear. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impact of diet-induced obesity on sexual dimorphism in metabolic alterations and hearing sensitivity.

Methods
Male and female CBA/Ca mice were randomly assigned to three diet groups and fed, from weaning (at 28 days) to 14 weeks of age, a sucrose-matched control diet (10 kcal% fat content diet), or one of two HFDs (45 or 60 kcal% fat content diets). Auditory sensitivity was evaluated based on the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and ABR wave 1 amplitude at 14 weeks of age, followed by biochemical analyses.

Results
We found significant sexual dimorphism in HFD-induced metabolic alterations and obesity-related hearing loss. Male mice exhibited greater weight gain, hyperglycemia, increased ABR thresholds at low frequencies, elevated DPOAE, and lower ABR wave 1 amplitude compared to female mice. The hair cell (HC) ribbon synapse (CtBP2) puncta showed significant sex differences. The serum concentration of adiponectin, an otoprotective adipokine, was significantly higher in female than in male mice; cochlear adiponectin levels were elevated by HFD in female but not male mice. Adiponectin receptor 1 (AdipoR1) was widely expressed in the inner ear, and cochlear AdipoR1 protein levels were increased by HFD, in female but not male mice. Stress granules (G3BP1) were significantly induced by the HFD in both sexes; conversely, inflammatory (IL-1β) responses were observed only in the male liver and cochlea, consistent with phenotype HFD-induced obesity.

Conclusions
Female mice are more resistant to the negative effects of an HFD on body weight, metabolism, and hearing. Females showed increased peripheral and intra-cochlear adiponectin and AdipoR1 levels, and HC ribbon synapses. These changes may mediate resistance to HFD-induced hearing loss seen in female mice.
Predicting RP-LC retention indices of structurally unknown chemicals from mass spectrometry data
Authors: Boelrijk Jim , van Herwerden Denice , Ensing Bernd , Forré Patrick , Samanipour Saer 
Published: February 2023

AbstractNon-target analysis combined with liquid chromatography high resolution mass spectrometry is considered one of the most comprehensive strategies for the detection and identification of known and unknown chemicals in complex samples. However, many compounds remain unidentified due to data complexity and limited number structures in chemical databases. In this work, we have developed and validated a novel machine learning algorithm to predict the retention index (r$$_i$$

i

) values for structurally (un)known chemicals based on their measured fragmentation pattern. The developed model, for the first time, enabled the predication of r$$_i$$

i

values without the need for the exact structure of the chemicals, with an $$R^2$$

R
2

of 0.91 and 0.77 and root mean squared error (RMSE) of 47 and 67 r$$_i$$

i

units for the NORMAN ($$n=3131$$

n
=
3131

) and amide ($$n=604$$

n
=
604

) test sets, respectively. This fragment based model showed comparable accuracy in r$$_i$$

i

prediction compared to conventional descriptor-based models that rely on known chemical structure, which obtained an $$R^2$$

R
2

of 0.85 with an RMSE of 67.
The Environmental Conditions, Treatments, and Exposures Ontology (ECTO): connecting toxicology and exposure to human health and beyond
Authors: Chan Lauren E. , Thessen Anne E. , Duncan William D. , Matentzoglu Nicolas , Schmitt Charles , Grondin Cynthia J. , Vasilevsky Nicole , McMurry Julie A. , Robinson Peter N. , Mungall Christopher J. , Haendel Melissa A. 
Published: February 2023

Abstract
Background
Evaluating the impact of environmental exposures on organism health is a key goal of modern biomedicine and is critically important in an age of greater pollution and chemicals in our environment. Environmental health utilizes many different research methods and generates a variety of data types. However, to date, no comprehensive database represents the full spectrum of environmental health data. Due to a lack of interoperability between databases, tools for integrating these resources are needed. In this manuscript we present the Environmental Conditions, Treatments, and Exposures Ontology (ECTO), a species-agnostic ontology focused on exposure events that occur as a result of natural and experimental processes, such as diet, work, or research activities. ECTO is intended for use in harmonizing environmental health data resources to support cross-study integration and inference for mechanism discovery.

Methods and findings
ECTO is an ontology designed for describing organismal exposures such as toxicological research, environmental variables, dietary features, and patient-reported data from surveys. ECTO utilizes the base model established within the Exposure Ontology (ExO). ECTO is developed using a combination of manual curation and Dead Simple OWL Design Patterns (DOSDP), and contains over 2700 environmental exposure terms, and incorporates chemical and environmental ontologies. ECTO is an Open Biological and Biomedical Ontology (OBO) Foundry ontology that is designed for interoperability, reuse, and axiomatization with other ontologies. ECTO terms have been utilized in axioms within the Mondo Disease Ontology to represent diseases caused or influenced by environmental factors, as well as for survey encoding for the Personalized Environment and Genes Study (PEGS).

Conclusions
We constructed ECTO to meet Open Biological and Biomedical Ontology (OBO) Foundry principles to increase translation opportunities between environmental health and other areas of biology. ECTO has a growing community of contributors consisting of toxicologists, public health epidemiologists, and health care providers to provide the necessary expertise for areas that have been identified previously as gaps.
Statistical actuarial estimation of the Capitation Payment Unit from copula functions and deep learning: historical comparability analysis for the Colombian health system, 2015–2021
Authors: Espinosa Oscar , Bejarano Valeria , Ramos Jeferson , Martínez Boris 
Published: February 2023

AbstractThe Capitation Payment Unit (CPU) financing mechanism constitutes more than 70% of health spending in Colombia, with a budget allocation of close to 60 trillion Colombian pesos for the year 2022 (approximately 15.7 billion US dollars). This article estimates actuarially, using modern techniques, the CPU for the contributory regime of the General System of Social Security in Health in Colombia, and compares it with what is estimated by the Ministry of Health and Social Protection. Using freely available information systems, by means of statistical copulas functions and artificial neural networks, pure risk premiums are calculated between 2015 and 2021. The study concludes that the weights by risk category are systematically different, showing historical pure premiums surpluses in the group of 0–1 years and deficits (for the regions normal and cities) in the groups over 54 years of age.
Biochemical characterization of extremozyme L-asparaginase from Pseudomonas sp. PCH199 for therapeutics
Authors: Darnal Sanyukta , Patial Vijeta , Kumar Virender , Kumar Subhash , Kumar Vijay , Padwad Yogendra S. , Singh Dharam 
Published: February 2023

AbstractL-asparaginase (L-ASNase) from microbial sources is a commercially vital enzyme to treat acute lymphoblastic leukemia. However, the side effects associated with the commercial formulations of L-ASNases intrigued to explore for efficient and desired pharmacological enzymatic features. Here, we report the biochemical and cytotoxic evaluation of periplasmic L-ASNase of Pseudomonas sp. PCH199 isolated from the soil of Betula utilis, the Himalayan birch. L-ASNase production from wild-type PCH199 was enhanced by 2.2-fold using the Response Surface Methodology (RSM). Increased production of periplasmic L-ASNase was obtained using an optimized osmotic shock method followed by its purification. The purified L-ASNase was a monomer of 37.0 kDa with optimum activity at pH 8.5 and 60 ℃. It also showed thermostability retaining 100.0% (200 min) and 90.0% (70 min) of the activity at 37 and 50 ℃, respectively. The Km and Vmax values of the purified enzyme were 0.164 ± 0.009 mM and 54.78 ± 0.4 U/mg, respectively. L-ASNase was cytotoxic to the K562 blood cancer cell line (IC50 value 0.309 U/mL) within 24 h resulting in apoptotic nuclear morphological changes as examined by DAPI staining. Therefore, the dynamic functionality in a wide range of pH and temperature and stability of PCH199 L-ASNase at 37 ℃ with cytotoxic potential proves to be pharmaceutically important for therapeutic application.
Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy
Authors: Xia Qin , Li Yang , Xu Wanting , Wu Chengwei , Zheng Hanfei , Liu Liqun , Dong Lei 
Published: February 2023

Abstract
Background
Macro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure.

Results
In this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpressed Smurf1 increased the activation of mTORC1 (mechanistic target of rapamycin complex 1), in turn leading to p62 Ser349 phosphorylation. Nrf2 activation increased the mRNA levels of Smurf1, p62, and NBR1, further promoting the droplet liquidity to enhance oxidative stress response. Importantly, we showed that Smurf1 maintained cellular homeostasis by promoting cargo degradation through the p62/LC3 autophagic pathway.

Conclusions
These findings revealed the complex interconnected role among Smurf1, p62/Nrf2/NBR1, and p62/LC3 axis in determining Nrf2 activation and subsequent clearance of condensates through LLPS mechanism.
On the distribution-tail behaviour of the product of normal random variables
Authors: Leipus Remigijus , Šiaulys Jonas , Dirma Mantas , Zovė Romualdas 
Published: February 2023

AbstractIn this paper we consider the product$\Pi _{n}=\prod_{k=1}^{n}\xi _{k}$Πn=∏k=1nξkofnindependent normally distributed zero mean random variables$\xi _{1},\dots ,\xi _{n}$ξ1,…,ξn. We derive an asymptotic formula for the survival probability${\mathbb{P}}(\Pi _{n}>x)$P(Πn>x), as$x\to \infty $x→∞, with the first remaining term.