bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective combination of biocompatible zinc oxide nanocrystals and high-energy shock waves for the treatment of colorectal cancer
Authors: Racca Luisa , Rosso Giada , Carofiglio Marco , Fagoonee Sharmila , Mesiano Giulia , Altruda Fiorella , Cauda Valentina 
Published: April 2023

Abstract
Background
Colorectal cancer (CRC) is the third most diagnosed tumor worldwide, with a very high mortality rate, second only to lung cancer. Current treatments, such as surgery, chemotherapy or radiotherapy, are not effective enough and show several limitations. Among the emerging strategies, nanomedicine offers very powerful tools in cancer treatment. Recently, the combination of nanoparticle antitumor effect with a triggering external stimulation was formulated to boost up the cytotoxic activity.

Results
In this work, we show the synergistic effect of oleic acid-capped zinc oxide nanocrystals (ZnO NCs) and mechanical high-energy shock waves (SW) in the treatment for CRC cells, in vitro. We tested two different types of ZnO NCs synthetized in our laboratory, the basal undoped ZnO NCs and the iron-doped ones (Fe:ZnO NCs). The presence of the oleic acid capping and the further amino-propyl functionalization guarantee a high colloidal stability to both NCs, while the iron doping confers to Fe:ZnO NCs interesting magnetic properties useful for imaging applications in a clinical perspective. Thus, the iron-doped ZnO NCs are very attractive as potentially theranostic nanoparticles, allowing both stimuli-responsive therapy and magnetic resonance imaging.
Importantly, two colon adenocarcinoma cell lines, the HT-29 and the Dukes’ type C Colo 320DM cells were tested, both showing a good bio-tolerance and internalization rates of NCs. With the aim of eradicating the CRC cells, the possible synergism between the undoped/iron-doped ZnO NCs and an external physical stimulus, i.e., high-energy SW, was then here investigated in vitro. We demonstrated that the combined treatment resulted in an augmentation of the antitumor activity, especially for Colo 320DM cells, when compared to controls. Moreover, a repeated and sequenced SW treatment (three times/day, 3SW) after ZnO NCs exposure resulted in a further increased mortality of CRC cells.

Conclusion
Our work proposes the combination of the cytotoxic activity of ZnO NCs with the SW external stimulation to obtain a booster of the antitumor activity, which warrants further investigation in vivo on CRC as well as on other tumors.

Graphical Abstract
Reintroducing genetic diversity in populations from cryopreserved material: the case of Abondance, a French local dairy cattle breed
Authors: Jacques Alicia , Leroy Grégoire , Rognon Xavier , Verrier Etienne , Tixier-Boichard Michèle , Restoux Gwendal 
Published: April 2023

Abstract
Background
Genetic diversity is a necessary condition for populations to evolve under natural adaptation, artificial selection, or both. However, genetic diversity is often threatened, in particular in domestic animal populations where artificial selection, genetic drift and inbreeding are strong. In this context, cryopreserved genetic resources are a promising option to reintroduce lost variants and to limit inbreeding. However, while the use of ancient genetic resources is more common in plant breeding, it is less documented in animals due to a longer generation interval, making it difficult to fill the gap in performance due to continuous selection. This study investigates one of the only concrete cases available in animals, for which cryopreserved semen from a bull born in 1977 in a lost lineage was introduced into the breeding scheme of a French local dairy cattle breed, the Abondance breed, more than 20 years later.

Results
We found that this re-introduced bull was genetically distinct with respect to the current population and thus allowed part of the genetic diversity lost over time to be restored. The expected negative gap in milk production due to continuous selection was absorbed in a few years by preferential mating with elite cows. Moreover, the re-use of this bull more than two decades later did not increase the level of inbreeding, and even tended to reduce it by avoiding mating with relatives. Finally, the reintroduction of a bull from a lost lineage in the breeding scheme allowed for improved performance for reproductive abilities, a trait that was less subject to selection in the past.

Conclusions
The use of cryopreserved material is an efficient way to manage the genetic diversity of an animal population, by mitigating the effects of both inbreeding and strong selection. However, attention should be paid to mating of animals to limit the disadvantages associated with incorporating original genetic material, notably a discrepancy in the breeding values for selected traits or an increase in inbreeding. Therefore, careful characterization of the genetic resources available in cryobanks could help to ensure the sustainable management of populations, in particular local or small populations. These results could also be transferred to the conservation of wild threatened populations.
Identifying altered developmental pathways in human globoid cell leukodystrophy iPSCs-derived NSCs using transcriptome profiling
Authors: Lv Yafeng , Qin Yu , Wang Jing , Tian Guoshuai , Wang Wei , Cao Chunyu , Zhang Ye 
Published: April 2023

Abstract
Background
Globoid cell leukodystrophy (GLD) is a devastating neurodegenerative disease characterized by widespread demyelination caused by galactocerebrosidase defects. Changes in GLD pathogenesis occurring at the molecular level have been poorly studied in human-derived neural cells. Patient-derived induced pluripotent stem cells (iPSCs) are a novel disease model for studying disease mechanisms and allow the generation of patient-derived neuronal cells in a dish.

Results
In this study, we identified gene-expression changes in iPSCs and iPSC-derived neural stem cells (NSCs) from a patient with GLD (K-iPSCs/NSCs) and normal control (AF-iPSCs/NSCs), in order to investigate the potential mechanism underlying GLD pathogenesis. We identified 194 (K-iPSCs vs. AF-iPSCs) and 702 (K-NSCs vs. AF-NSCs) significantly dysregulated mRNAs when comparing the indicated groups. We also identified dozens of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway terms that were enriched for the differentially expressed genes. Among them, 25 differentially expressed genes identified by RNA-sequencing analysis were validated using real-time quantitative polymerase chain reaction analysis. Dozens of pathways involved in neuroactive ligand–receptor interactions, synaptic vesicle cycle signaling, serotonergic synapse signaling, phosphatidylinositol–protein kinase B signaling, and cyclic AMP signaling were identified as potential contributors to GLD pathogenesis.

Conclusions
Our results correspond to the fact that mutations in the galactosylceramidase gene may disrupt the identified signaling pathways during neural development, suggesting that alterations in signaling pathways contribute to GLD pathogenesis. At the same time, our results demonstrates that the model based on K-iPSCs is a novel tool that can be used to study the underlying molecular basis of GLD.
Genome-environment associations along elevation gradients in two snowbed species of the North-Eastern Calcareous Alps
Authors: Felkel Sabine , Tremetsberger Karin , Moser Dietmar , Dohm Juliane C. , Himmelbauer Heinz , Winkler Manuela 
Published: April 2023

Abstract
Background
Anthropogenic climate change leads to increasing temperatures and altered precipitation and snowmelt patterns, especially in alpine ecosystems. To understand species’ responses to climate change, assessment of genetic structure and diversity is crucial as the basis for the evaluation of migration patterns, genetic adaptation potential as well as the identification of adaptive alleles.

Results
We studied genetic structure, diversity and genome-environment associations of two snowbed species endemic to the Eastern Alps with a large elevational range, Achillea clusiana Tausch and Campanula pulla L. Genotyping-by-sequencing was employed to assemble loci de novo, call variants and perform population genetic analyses. Populations of either species were distinguishable by mountain, and to some extent by elevation. We found evidence for gene flow between elevations. Results of genome-environment associations suggested similar selective pressures acting on both species, emanating mainly from precipitation and exposition rather than temperature.

Conclusions
Given their genetic structure and amount of gene flow among populations the two study species are suitable to serve as a model for genetic monitoring of climate change adaptation along an elevation gradient. Consequences of climate change will predominantly manifest via changes in precipitation and, thus, duration of snow cover in the snowbeds and indirectly via shrub encroachment accompanied by increasing shading of snowbeds at lower range margins. Assembling genomes of the study species and studying larger sample sizes and time series will be necessary to functionally characterize and validate the herein identified genomic loci putatively involved in adaptive processes.
Median effective dose of esketamine for intranasal premedication in children with congenital heart disease
Authors: Huang Jiajia , Liu Daoqing , Bai Jie , Gu Hongbin 
Published: April 2023

Abstract
Background
Esketamine is commonly used as a premedication for its sedation effect. However, the proper dosage for intranasal use in children with congenital heart disease (CHD) has not been determined. This study aimed to estimate the median effective dose (ED50) of esketamine for intranasal premedication in children with CHD.

Methods
Thirty-four children with CHD who needed premedication in March 2021 were enrolled. Intranasal esketamine was initiated at a dose of 1 mg/kg. Based on the outcome of sedation in the previous patient, the dose for the subsequent patient was either increased or reduced by 0.1 mg/kg, which was adjusted between each child. Successful sedation was defined as a Ramsay Sedation Scale score ≥ 3 and Parental Separation Anxiety Scale score ≤ 2. The required ED50 of esketamine was calculated using the modified sequential method. Non-invasive blood pressure, heart rate, saturation of peripheral oxygen, sedation onset time, and adverse reactions were recorded at 5 min intervals after drug administration.

Results
The 34 children enrolled had a mean age of 22.5 ± 16.4 (4–54) months and a mean weight of 11.2 ± 3.6 (5.5–20.5) kg; American Society of Anesthesiologists classification I–III. The ED50 of intranasal S(+)-ketamine (esketamine) required for preoperative sedation in pediatric patients with CHD was 0.7 (95% confidence interval: 0.54–0.86) mg/kg, and the mean sedation onset time was 16.39 ± 7.24 min. No serious adverse events, such as respiratory distress, nausea, and vomiting were observed.

Conclusions
The ED50 of intranasal esketamine was 0.7 mg/kg, which was safe and effective for preoperative sedation in pediatric patients with CHD.

Trial registration
: The trial was registered in the Chinese Clinical Trial Registry Network (ChiCTR2100044551) on 24/03/2021.
Predicting cholangiocarcinoma in primary sclerosing cholangitis: using artificial intelligence, clinical and laboratory data
Authors: Hu Chang , Iyer Ravishankar K. , Juran Brian D. , McCauley Bryan M. , Atkinson Elizabeth J. , Eaton John E. , Ali Ahmad H. , Lazaridis Konstantinos N. 
Published: April 2023

AbstractBackgroundPrimary sclerosing cholangitis (PSC) patients have a risk of developing cholangiocarcinoma (CCA). Establishing predictive models for CCA in PSC is important.MethodsIn a large cohort of 1,459 PSC patients seen at Mayo Clinic (1993–2020), we quantified the impact of clinical/laboratory variables on CCA development using univariate and multivariate Cox models and predicted CCA using statistical and artificial intelligence (AI) approaches. We explored plasma bile acid (BA) levels’ predictive power of CCA (subset of 300 patients, BA cohort).ResultsEight significant risk factors (false discovery rate: 20%) were identified with univariate analysis; prolonged inflammatory bowel disease (IBD) was the most important one. IBD duration, PSC duration, and total bilirubin remained significant (p < 0.05) with multivariate analysis. Clinical/laboratory variables predicted CCA with cross-validated C-indexes of 0.68–0.71 at different time points of disease, significantly better compared to commonly used PSC risk scores. Lower chenodeoxycholic acid, higher conjugated fraction of lithocholic acid and hyodeoxycholic acid, and higher ratio of cholic acid to chenodeoxycholic acid were predictive of CCA. BAs predicted CCA with a cross-validated C-index of 0.66 (std: 0.11, BA cohort), similar to clinical/laboratory variables (C-index = 0.64, std: 0.11, BA cohort). Combining BAs with clinical/laboratory variables leads to the best average C-index of 0.67 (std: 0.13, BA cohort).ConclusionsIn a large PSC cohort, we identified clinical and laboratory risk factors for CCA development and demonstrated the first AI based predictive models that performed significantly better than commonly used PSC risk scores. More predictive data modalities are needed for clinical adoption of these models.
Association between infant birthweight and pelvic floor muscle strength: a population-based cohort study
Authors: Zhu Junyan , Si Junwen , Zhao Lu , Liu Wei 
Published: April 2023

Abstract
Background
To assess the relationship between infant birthweight and pelvic floor muscle (PFM) strength in China.

Methods
We performed a retrospective, single-center cohort study of 1575 women delivering vaginally between January 2017 and May 2020. All participants completed pelvic floor examinations within 5–10 weeks after delivery and were evaluated for PFM strength, which was estimated by vaginal pressure. Data were collected from electronic records. We evaluated the association between infant birthweight and vaginal pressure through multivariable-adjusted linear regression analysis. We also performed subgroup analyses stratified by potential confounders.

Results
Vaginal pressure decreased as the quartile of birthweight increased (P for trend < 0.001). Beta coefficients were -5.04 (95%CI -7.98 to -2.1), -5.53 (95%CI -8.5 to -2.57), -6.07 (95%CI -9.08 to -3.07) for birthweight quartile 2–4, respectively (P for trend < 0.001), independent of age, postpartum hemorrhage, and the number of vaginal deliveries. In addition, the results of subgroup analyses showed the same patterns across strata.

Conclusions
This study demonstrates that infant birthweight was associated with decreased vaginal pressure in women after vaginal delivery and could be considered a risk factor for decreased PFM strength in the population with vaginal delivery. This association may provide an extra basis for appropriate fetal weight control during pregnancy, and for earlier pelvic floor rehabilitation of postpartum women delivering babies with larger birthweight.
Improved uptake and survival with systemic treatments for metastatic non-small cell lung cancer: younger versus older adults
Authors: Leung Bonnie , Shokoohi Aria , Al-Hashami Zamzam , Moore Sara , Pender Alexandra , Wong Selina K. , Wang Ying , Wu Jonn , Ho Cheryl 
Published: April 2023

Abstract
Background
Over the past decade, there has been increasing availability of novel therapeutics with improved tolerability and efficacy for advanced non-small cell lung cancer (NSCLC). The study goals were: to compare the uptake of systemic therapy (ST) before and after the availability of targeted tyrosine kinase inhibitors (TKI) and immunotherapy and to examine the changes in overall survival (OS) over time between younger and older adults with advanced NSCLC.

Methods
All patients with advanced NSCLC referred to British Columbia (BC) Cancer in 2009, 2011, 2015 and 2017 were included. One-year time points were based on molecular testing implementation and funded drug availability: baseline (2009), epidermal growth factor receptor TKI (2011), anaplastic lymphoma kinase TKI (2015) and Programed Death-1 (PD-1) inhibitors (2017). Age groups were <70years and ≥70years. Baseline demographics, simplified comorbidity scores (SCS), disease characteristics, and ST details were collected retrospectively. Variables were compared using X2, Fisher’s exact tests and logistic-regression analysis. OS was calculated using the Kaplan-Meier method and compared using the log-rank test.

Results
3325 patients were identified. Baseline characteristics were compared between ages < 70 years and ≥ 70 years for each time cohort with significant differences noted in baseline Eastern Cooperative Oncology Group (ECOG) performance status and SCS. The rate of ST delivery trended upwards over time with age <70 years: 2009 44%, 2011 53%, 2015 50% and 2017 52% and age ≥70 years: 22%, 25%, 28% and 29% respectively. Predictors for decreased use of ST for age <70 years: ECOG ≥2, SCS ≥9, year 2011, and smoking history; and age ≥70 years: ECOG ≥2, years 2011 and 2015, and smoking history. The median OS of patients who received ST improved from 2009 to 2017: age <70 years 9.1 m vs. 15.5 m and age ≥70 years 11.4 m vs. 15.0 m.

Conclusions
There was an increased uptake of ST for both age groups with the introduction of novel therapeutics. Although a smaller proportion of older adults received ST, those who received treatment had comparable OS to their young counterpart. The benefit of ST in both age groups was seen across the different types of treatments. With careful assessment and selection of appropriate candidates, older adults with advanced NSCLC appear to benefit from ST.
The association between schizophrenia and white blood cells count: a bidirectional two-sample Mendelian randomization study
Authors: Gao Zibo , Li Biao , Guo Xinru , Bai Wei , Kou Changgui 
Published: April 2023

Abstract
Background
Positive associations between the risk of schizophrenia and the level of white blood cells (WBC) count have been suggested by observational studies. However, the causality of this association is still unclear.

Methods
We used a group of bidirectional two-sample Mendelian randomization (MR) analyses to estimate the causal relationship between schizophrenia and WBC count traits (i.e., WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count). The threshold of FDR-adjusted P < 0.05 was considered as showing potential evidence of a causal effect. Instrument variables were included based on the genome-wide significance threshold (P < 5 × 10− 8) and linkage disequilibrium (LD) clumping (r2 < 0.01). In total, 81, 95, 85, 87, 76, and 83 schizophrenia-related single nucleotide polymorphisms (SNPs) were used as genetic instruments from Psychiatric Genomics Consortium for six WBC count traits, respectively. And in reverse MR analysis, 458, 206, 408, 468, 473, and 390 variants extracted from six WBC count traits were utilized as genetic instruments, which were obtained from a recent large-scale Genome-Wide Association Study (GWAS).

Results
Genetically predicted schizophrenia was positively associated with the level of WBC count [odds ratio (OR) 1.017, 95% confidence interval (CI) 1.008–1.026; P = 7.53 × 10− 4], basophil count (OR 1.014, 95%CI 1.005–1.022; P = 0.002), eosinophil count (OR 1.021, 95%CI 1.011–1.031; P = 2.77 × 10− 4), monocyte count (OR 1.018, 95%CI 1.009–1.027; P = 4.60 × 10− 4), lymphocyte count (OR 1.021, 95%CI 1.012–1.030; P = 4.51 × 10− 5), and neutrophil count (OR 1.013, 95%CI 1.005–1.022; P = 0.004). WBC count traits are not associated with the risk of schizophrenia in our reverse MR results.

Conclusion
Schizophrenia is associated with elevated levels of WBC count (i.e., higher WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count).
Alterations in inflammasome-related immunometabolites in individuals with severe psychiatric disorders
Authors: Hylén Ulrika , Särndahl Eva , Bejerot Susanne , Humble Mats B , Hyötyläinen Tuulia , Salihovic Samira , Eklund Daniel 
Published: April 2023

AbstractIntroductionPsychiatric disorders are common and significantly impact the quality of life. Inflammatory processes are proposed to contribute to the emergence of psychiatric disorders. In addition to inflammation, disturbances in metabolic pathways have been observed in individuals with different psychiatric disorders. A suggested key player in the interaction between inflammation and metabolism is the Nod-like receptor 3 (NLRP3) inflammasome, and NLRP3 is known to react to a number of specific metabolites. However, little is known about the interplay between these immunometabolites and the NLRP3 inflammasome in mental health disorders.AimTo assess the interplay between immunometabolites and inflammasome function in a transdiagnostic cohort of individuals with severe mental disorders.MethodsMass spectrometry-based analysis of selected immunometabolites, previously known to affect inflammasome function, were performed in plasma from low-functioning individuals with severe mental disorders (n = 39) and sex and aged-matched healthy controls (n = 39) using a transdiagnostic approach. Mann Whitney U test was used to test differences in immunometabolites between psychiatric patients and controls. To assess the relationship between inflammasome parameters, disease severity, and the immunometabolites, Spearman’s rank-order correlation test was used. Conditional logistic regression was used to control for potential confounding variables. Principal component analysis was performed to explore immunometabolic patterns.ResultsAmong the selected immunometabolites (n = 9), serine, glutamine, and lactic acid were significantly higher in the patient group compared to the controls. After adjusting for confounders, the differences remained significant for all three immunometabolites. No significant correlations were found between immunometabolites and disease severity.ConclusionPrevious research on metabolic changes in mental disorders has not been conclusive. This study shows that severely ill patients have common metabolic perturbations. The changes in serine, glutamine, and lactic acid could constitute a direct contribution to the low-grade inflammation observed in severe psychiatric disorders.