bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-proliferative potential and oxidative reactivity of thermo-oxidative degradation products of stigmasterol and stigmasteryl esters for human intestinal cells
Authors: Kasprzak Maria , Rudzińska Magdalena , Juzwa Wojciech , Olejnik Anna 
Published: May 2023

AbstractStigmasterol in free and esterified form is incorporated in LDL cholesterol-lowering food products, intended for direct consumption and cooking, baking, and frying. Under thermal treatment, stigmasterol compounds may constitute a source of thermo-oxidative degradation products and oxyderivatives with potentially adverse health effects. This study aimed to analyze the anti-proliferative potential and genotoxicity of thermo-oxidatively treated stigmasterol (ST), stigmasteryl linoleate (ST-LA), and oleate (ST-OA). The effects on cell viability and proliferation, cell cycle progression, intracellular reactive oxygen species (ROS) generation, and DNA damage were analyzed in normal human intestinal cells. The mutagenic potential was assessed in a bacterial reverse mutation test using Salmonella enterica serovar Typhimurium strains involving metabolic activation. Stigmasteryl esters showed a significantly lower potential to affect intestinal cell viability and proliferation than non-esterified ST, regardless of heating. Thermo-oxidatively treated ST suppressed intestinal cell proliferation by arresting the cell cycle in the G2/M phase and DNA synthesis inhibition. The enhanced intracellular ROS generation and caspase 3/7 activity suggest targeting intestinal cells to the apoptosis pathway. Also, heated ST-LA intensified ROS production and elicited pro-apoptotic effects. Thermo-oxidative derivatives of ST and ST-LA may evoke harmful gastrointestinal effects due to their high oxidative reactivity towards intestinal cells.
N,N-dimethylacetamide targets neuroinflammation in Alzheimer’s disease in in-vitro and ex-vivo models
Authors: Wei Zeng-Hui , Koya Jagadish , Acharekar Nikita , Trejos Jesus , Dong Xing-Duo , Schanne Francis A. , Ashby Charles R. , Reznik Sandra E. 
Published: May 2023

AbstractAlzheimer’s disease (AD) is a chronic degenerative brain disorder with no clear pathogenesis or effective cure, accounting for 60–80% of cases of dementia. In recent years, the importance of neuroinflammation in the pathogenesis of AD and other neurodegenerative disorders has come into focus. Previously, we made the serendipitous discovery that the widely used drug excipient N,N-dimethylacetamide (DMA) attenuates endotoxin-induced inflammatory responses in vivo. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo models of AD. We show that DMA significantly suppresses the production of inflammatory mediators, such as reactive oxygen species (ROS), nitric oxide (NO) and various cytokines and chemokines, as well as amyloid-β (Aβ), in cultured microglia and organotypic hippocampal slices induced by lipopolysaccharide (LPS). We also demonstrate that DMA inhibits Aβ-induced inflammation. Finally, we show that the mechanism of DMA’s effect on neuroinflammation is inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway and we show how DMA dismantles the positive feedback loop between NF-κB and Aβ synthesis. Taken together, our findings suggest that DMA, a generally regarded as safe compound that crosses the blood brain barrier, should be further investigated as a potential therapy for Alzheimer’s disease and neuroinflammatory disorders.
Quality control system for mammographic breast positioning using deep learning
Authors: Watanabe Haruyuki , Hayashi Saeko , Kondo Yohan , Matsuyama Eri , Hayashi Norio , Ogura Toshihiro , Shimosegawa Masayuki 
Published: May 2023

AbstractThis study proposes a deep convolutional neural network (DCNN) classification for the quality control and validation of breast positioning criteria in mammography. A total of 1631 mediolateral oblique mammographic views were collected from an open database. We designed two main steps for mammographic verification: automated detection of the positioning part and classification of three scales that determine the positioning quality using DCNNs. After acquiring labeled mammograms with three scales visually evaluated based on guidelines, the first step was automatically detecting the region of interest of the subject part by image processing. The next step was classifying mammographic positioning accuracy into three scales using four representative DCNNs. The experimental results showed that the DCNN model achieved the best positioning classification accuracy of 0.7836 using VGG16 in the inframammary fold and a classification accuracy of 0.7278 using Xception in the nipple profile. Furthermore, using the softmax function, the breast positioning criteria could be evaluated quantitatively by presenting the predicted value, which is the probability of determining positioning accuracy. The proposed method can be quantitatively evaluated without the need for an individual qualitative evaluation and has the potential to improve the quality control and validation of breast positioning criteria in mammography.
Clinical and Radiological Outcomes of Dura-Splitting versus Duraplasty Techniques in Pediatric Chiari I Malformation: A Systematic Review and Meta-Analysis
Authors: Tavallaii Amin , Keykhosravi Ehsan , Ghorbanpour Ahmad , Shahriari Ali , Rezaee Hamid 
Published: May 2023

AbstractType I Chiari malformation is a developmental anomaly with various proposed surgical techniques for its management. The dura-splitting technique is a less invasive approach and involves the resection of the outer layer of the dura while sparing the internal layer. While this less-known approach may minimize the complication rates, there are concerns about its efficacy and outcome. Therefore, we have performed a systematic review and meta-analysis of available data on clinical and radiological outcomes of this technique in the pediatric population and compared them to the foramen magnum decompression and duraplasty technique.We have followed the Meta-analysis Of Observational Studies in Epidemiology guidelines in this review. Based on our predefined search strategy, we performed a systematic database search. Subsequently, the article screening process was done based on defined inclusion/exclusion criteria. Following the quality assessment of included studies, two authors performed data extraction. Finally, the extracted data were summarized and presented in form of tables. Forest plots were used to demonstrate the results of the meta-analysis.A review of 8 included studies consisting of 615 patients revealed the significant advantage of the dura-splitting technique in terms of shorter operation duration and hospital stay. The recurrence rate and clinical and radiological outcomes were almost similar between the two surgical techniques. Complication rates were significantly lower in the dura-splitting technique.Dura-splitting can be an effective and safe approach for the management of pediatric Chiari I malformation. However, these results are mostly extracted from observational studies and future randomized controlled trials are recommended.
Salivary Biomarker IL-8 Levels in Smokers and NonSmokers: A Comparative Study
Authors: Sahibzada Haafsa Arshad , Sohail Kanwal , Siddiqi Khalid Mahmood , Khurshid Zohaib , Mahmood Hina , Riaz Sana 
Published: May 2023

Abstract
Objective It is estimated that the mortality rate from tobacco-related diseases will reach 10 million worldwide by 2030. It is validated that every three out of four oral cancers are caused by the use of tobacco in various forms especially smoking. Early detection is the only way to reduce this burden. Molecular-level analysis has currently become a valuable tool in the diagnosis and prognosis of diseases. Around 1000 different salivary protein biomarkers are being investigated in saliva for this purpose. Some of these markers are being investigated to evaluate the proportionality of cigarette smoking. The objective of this study was to evaluate the levels of salivary biomarker interleukin-8 (IL-8) among smokers and nonsmokers as a control group.
Materials and Methods This is a comparative cross-sectional study conducted in Islamabad Dental Hospital, Bhara Kahu. A total of 60 patients were recruited and divided into two equal groups of smokers and nonsmokers. Unstimulated saliva samples were collected and analyzed using an enzyme-linked immunosorbent assay kit.
Statistical Analysis The results were then analyzed by SPSS v25 using an independent sample t-test to evaluate the statistical difference and significance.
Results A p-value (<0.001) was found to be significant for the IL-8 levels in smokers when compared with nonsmokers. The mean value for smokers was found to be 122.69 pg/mL and the mean for nonsmokers was evaluated to be 20.68 pg/mL.
Conclusion As the levels of IL-8 were high, it was concluded to be an effective biomarker for the evaluation of smoking-based initial inflammatory changes detectable from saliva.
ncRNALocate-EL: a multi-label ncRNA subcellular locality prediction model based on ensemble learning
Authors: Bai Tao , Liu Bin 
Published: May 2023

Abstract
Subcellular localizations of ncRNAs are associated with specific functions. Currently, an increasing number of biological researchers are focusing on computational approaches to identify subcellular localizations of ncRNAs. However, the performance of the existing computational methods is low and needs to be further studied. First, most prediction models are trained with outdated databases. Second, only a few predictors can identify multiple subcellular localizations simultaneously. In this work, we establish three human ncRNA subcellular datasets based on the latest RNALocate, including lncRNA, miRNA and snoRNA, and then we propose a novel multi-label classification model based on ensemble learning called ncRNALocate-EL to identify multi-label subcellular localizations of three ncRNAs. The results show that the ncRNALocate-EL outperforms previous methods. Our method achieved an average precision of 0.709,0.977 and 0.730 on three human ncRNA datasets. The web server of ncRNALocate-EL has been established, which can be accessed at https://bliulab.net/ncRNALocate-EL.
Hsa_circ_0084003 modulates glycolysis and epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma through targeting hsa-miR-143-3p/DNMT3A axis
Authors: Wang Kaiqiong , Chen Zhiju , Qiao Xin , Zheng Jinfang 
Published: May 2023

Abstract
Pancreatic ductal adenocarcinoma, one of the deadliest tumors of the digestive tract, is a difficult and invasive malignancy. Current treatment for pancreatic ductal adenocarcinoma mainly depends on surgery combined with radiotherapy and chemotherapy, which, however, often resulting in questionable curative effect. Therefore, new targeted therapies are needed in future treatment. We first interfered with hsa_circ_0084003 expression in pancreatic ductal adenocarcinoma cells, and further studied how hsa_circ_0084003 functioned in regulating pancreatic ductal adenocarcinoma cell aerobic glycolysis and epithelial-mesenchymal transition, and also evaluated the regulatingeffect of hsa_circ_0084003 on hsa-miR-143-3p and its target DNA methyltransferase 3A. Hsa_circ_0084003 knockdown could notably inhibit the aerobic glycolysis and epithelial-mesenchymal transition of pancreatic ductal adenocarcinoma cells. Mechanistically, hsa_circ_0084003 could regulate its downstream target DNA methyltransferase 3A by binding to hsa-miR-143-3p, and overexpression of hsa_circ_0084003 could reverse the anticarcinogenic effect of hsa-miR-143-3p on aerobic glycolysis and epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells. Hsa_circ_0084003, as a carcinogenic circular RNA, regulated its downstream target DNA methyltransferase 3A to promote pancreatic ductal adenocarcinoma cell aerobic glycolysis and epithelial-mesenchymal transition through sponging hsa-miR-143-3p. Therefore, hsa_circ_0084003 could be studied as a possible therapeutic target regarding pancreatic ductal adenocarcinoma.
Evaluation of Nursing Coursework for Biased Content
Authors: Jennings Sarah J. , Mikos Kathleen A. , Caruso Brown Amy E. , Osborne Kathryn , Livesay Sarah L. 
Published: May 2023

Abstract
Bias-free content in nursing education prepares students to provide equitable care. The process of assessing content promotes the dismantling of systemic bias in health care, advancing social justice, diversity, equity, and inclusion. Unfortunately, there are no published studies to guide the evaluation of nursing curricula for the presence of bias. This innovative project aimed to identify bias in a course and develop a structure to guide the wider evaluation of the curriculum to identify and remove biased content. A modified version of the Upstate Bias Checklist was applied to a 15-week, three-semester hour, prelicensure, graduate-level nursing course.
Development of a Physician Assistant Orientation Program in a Pediatric Emergency Department
Authors: Jenkins Susannah , Zaveri Pavan , Zhao Xian 
Published: May 2023

Introduction
The role of physician assistants (PAs) in the care of emergency department (ED) patients has been expanding in recent years. However, little is known about how PAs are prepared to practice in pediatric emergency medicine (PEM), and there is no published literature on how to train PAs in independently managing low-acuity visits in the pediatric emergency department (PED).

Methods
We created a preorientation, orientation, and postorientation program for PAs who are onboarding in the PED at a large, free-standing pediatric acute care hospital. We implemented an evaluation system that assessed readiness for independent practice based on number and type of patients seen as well as supervising physicians' feedback.

Results
On average, PAs took care of 877 patients over the course of their first year of employment at the hospital before achieving readiness for independent practice. Most PAs were deemed ready to see low-acuity patients without direct supervision by PEM attendings during their third or fourth quarter of employment.

Discussion
The successful implementation of a 12-month curriculum and individualized feedback allowed our PED to prepare PAs for independent management of the low-acuity PED patient.
Association of Merkel Cell Polyomavirus Status With p53, RB1, and PD-L1 Expression and Patient Prognosis in Merkel Cell Carcinomas: Clinical, Morphologic, and Immunohistochemical Evaluation of 17 Cases
Authors: Öğüt Betül , Bayram Elif Kolay , İnan Mehmet Arda , Kestel Selin , Erdem Özlem 
Published: May 2023

Background:
Merkel cell carcinoma (MCC) is a rare, aggressive, primary neuroendocrine carcinoma of the skin whose main risk factors are immunosuppression, UV radiation exposure, and Merkel cell polyomavirus. Programmed death-1/programmed death ligand-1 (PD-L1)-based immunotherapy is currently the first choice for treating patients with metastatic MCC.

Methods:
MCC biopsies (17) were evaluated for their nucleus and cytoplasm characteristics and growth patterns, as well as for intratumor lymphocytes, mitotic number, and lymphovascular invasion. Paraffin-embedded tissue samples of the biopsies were stained with MCPyV large T-antigen (LTag), RB1, p53, and PD-L1.

Results:
We observed MCPyV LTag expression in 9 out of the 17 tumors, and all 9 cases were positive for RB1 (P<0.000). p53 staining was not significantly correlated with MCPyV LTag. We observed no relationship between p53 expression and any other parameters, and PD-L1 expression was low in the MCC samples. We evaluated PD-L1 using both the combined positive score and tumor proportion score (TPS), and found that TPS was correlated with MCPyV LTag expression (P=0.016). Tumors with tumor-infiltrating lymphocytes showed a better prognosis than those without these lymphocytes (P=0.006).

Discussion:
Our data demonstrated that RB1 was effective for immunohistochemically investigating the MCPyV status of tumors. TPS was superior to the combined positive score in evaluating PD-L1 in MCC. Tumor-infiltrating lymphocytes were the only parameters that were associated with survival. Further studies with larger series are required to confirm these results.
Caring for Critically Ill Children With the ICU Liberation Bundle (ABCDEF): Results of the Pediatric Collaborative*
Authors: Lin John C. , Srivastava Avantika , Malone Sara , Jennison Susan , Simino Megan , Traube Chani , LaRose Kimberly , Kawai Yu , Neu Lori , Kudchadkar Sapna , Wieczorek Beth , Hajnik Krista , Kordik Christina M. , Kumar Vishakha K. , Aghamohammadi Sara , Arteaga Grace M. , Smith Heidi A. B. , Spentzas Thomas , Orman Andrea , Landman Becky McGee , Valdivia Hector , Browne Heather , Fang Timothy , Zimmerman Jerry J. ,   for the Society of Critical Care Medicine’s Pediatric ICU Liberation Campaign Collaborative
Published: May 2023

OBJECTIVES:
Assess clinical outcomes following PICU Liberation ABCDEF Bundle utilization.

DESIGN:
Prospective, multicenter, cohort study.

SETTING:
Eight academic PICUs.

PATIENTS:
Children greater than 2 months with expected PICU stay greater than 2 days and need for mechanical ventilation (MV).

INTERVENTIONS:
ABCDEF Bundle implementation.

MEASUREMENT AND MAIN RESULTS:
Over an 11-month period (3-mo baseline, 8-mo implementation), Bundle utilization was measured for 622 patients totaling 5,017 PICU days. Risk of mortality was quantified for 532 patients (4,275 PICU days) for correlation between Bundle utilization and MV duration, PICU length of stay (LOS), delirium incidence, and mortality. Utilization was analyzed as subject-specific (entire PICU stay) and day-specific (single PICU day). Median overall subject-specific utilization increased from 50% during the 3-month baseline to 63.9% during the last four implementation months (p < 0.001). Subject-specific utilization for elements A and C did not change; utilization improved for B (0–12.5%; p = 0.007), D (22.2–61.1%; p < 0.001), E (17.7–50%; p = 0.003), and F (50–79.2%; p = 0.001). We observed no association between Bundle utilization and MV duration, PICU LOS, or delirium incidence. In contrast, on adjusted analysis, every 10% increase in subject-specific utilization correlated with mortality odds ratio (OR) reduction of 34%, p < 0.001; every 10% increase in day-specific utilization correlated with a mortality OR reduction of 1.4% (p = 0.006).

CONCLUSIONS:
ABCDEF Bundle is applicable to children. Although enhanced Bundle utilization correlated with decreased mortality, increased utilization did not correlate with duration of MV, PICU LOS, or delirium incidence. Additional research in the domains of comparative effectiveness, implementation science, and human factors engineering is required to understand this clinical inconsistency and optimize PICU Liberation concept integration into clinical practice.
Transplantation of the Uterus in the Male Rat
Authors: Yang Liu , Wang Tong , Chen Lin , Li Xia , Song Yajuan , Yu Zhou , Song Baoqiang 
Published: May 2023

Background.
Uterus transplantation (UTx) is one of the potential methods to cure absolute uterine factor infertility of transgender. However, this mostly comes with many technological challenges.

Methods.
Left inguinal UTx was performed in 13 castrated male rats. End-to-end anastomosis of donor common iliac vessels to recipient femoral vessels was used for transsexual UTx. Sampling was performed on day 30 after transplantation. Grafts were used to analyze the histological changes. TUNEL assay was applied to stain the apoptotic cells. Immunological rejection was judged by flow cytometry.

Results.
Six uteri, 4 ovaries, and 4 upper vaginas were found at day 30 posttransplantation. Similar histological changes to proestrus, estrus, and diestrus of female rats were examined in the transplanted uteri. The histological changes of transplanted vaginas showed similarity to proestrus, estrus, and metestrus of the female rats. Follicles of different stages and corpus luteum with distinct morphological appearances were also observed. The TUNEL assay revealed a higher apoptosis of granulosa cells in transplanted ovaries compared with normal ovaries.

Conclusions.
A rat model of transsexual unilateral inguinal uterine transplantation in castrated rats was established, which will provide a reference for bilateral transsexual UTx in animals and genetically 46 XY individuals who wish to become real women through transsexual UTx.
Behavioral effects of zonisamide on L-DOPA-induced dyskinesia in Parkinson’s disease model mice
Authors: Sano Hiromi , Nambu Atsushi 
Published: May 2023

AbstractZonisamide (ZNS; 1,2-benzisoxazole-3-methanesulfonamide) was initially developed and is commonly used as an anticonvulsant drug. However, it has also shown beneficial effects on Parkinson’s disease (PD), a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the midbrain. Recent clinical studies have suggested that ZNS can also have beneficial effects on L-DOPA-induced dyskinesia (LID), which is a major side effects of long-term L-DOPA treatments for PD. In the present study, we examined the behavioral effects of ZNS on LID in PD model mice. Acute ZNS treatment did not have any observable behavioral effects on LID. Contrastingly, chronic ZNS treatment with L-DOPA delayed the peak of LID and reduced the severity of LID before the peak, but increased the duration of LID in a dose-dependent manner of ZNS, compared to PD model mice treated with L-DOPA alone. Thus, ZNS appears to have both beneficial and adverse effects on LID.
Dispersal, habitat filtering, and eco-evolutionary dynamics as drivers of local and global wetland viral biogeography
Authors: ter Horst Anneliek M. , Fudyma Jane D. , Sones Jacqueline L. , Emerson Joanne B. 
Published: May 2023

AbstractWetlands store 20-30% of the world’s soil carbon, and identifying the microbial controls on these carbon reserves is essential to predicting feedbacks to climate change. Although viral infections likely play important roles in wetland ecosystem dynamics, we lack a basic understanding of wetland viral ecology. Here 63 viral size-fraction metagenomes (viromes) and paired total metagenomes were generated from three time points in 2021 at seven fresh- and saltwater wetlands in the California Bodega Marine Reserve. We recovered 12,826 viral population genomic sequences (vOTUs), 4.4% of which were also detected at the same field site two years prior, indicating a small degree of population stability or recurrence. Viral communities differed most significantly across the seven wetland sites and were also structured by habitat (plant community composition and salinity). Read mapping to a new version of our reference database, PIGEONv2.0 (now with 515,763 vOTUs), revealed 196 vOTUs present over large geographic distances, often reflecting shared habitat characteristics. Wetland vOTU microdiversity was significantly lower locally than globally and lower within than between time points, indicating greater divergence with increasing spatiotemporal distance. Viruses tended to have broad predicted host ranges via CRISPR spacer linkages to metagenome-assembled genomes (whether this reflects true biology remains to be seen), and increased SNP frequencies in CRISPR-targeted major tail protein genes suggest viral eco-evolutionary dynamics, potentially in response to both immune targeting and to changes in host cell receptors involved in viral attachment. Together, these results highlight the importance of dispersal, environmental selection, and eco-evolutionary dynamics as drivers of local and global wetland viral biogeography.