bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential miRNA expression of hypoxic MCF7 and PANC-1 cells
Authors: Al-Sisan Sandy M. , Zihlif Malek A. , Hammad Hana M. 
Published: July 2023

BackgroundHypoxia plays a critical role in the tumor microenvironment by affecting cellular proliferation, metabolism, apoptosis, DNA repair, and chemoresistance. Since hypoxia provokes a distinct shift of microRNA, it is important to illustrate the relative contribution of each hypoxamiR to cancer progression.AimsThe present study aims to shed light on the hypoxamiRs that are involved in pancreatic and breast cancer progression to highlight novel targets for the development of new therapies.MethodsFor 20 cycles, MCF7 breast cancer cells and PANC-1 pancreatic cancer cells were subjected to chronic cyclic hypoxia, which consisted of 72 hours of hypoxia followed by 24 hours of reoxygenation. After 10 and 20 cycles of hypoxia, miRNA expression alterations were profiled using RT-PCR array and further analyzed using a visual analytics platform. The MTT cell proliferation assay was used to determine hypoxic cells’ chemoresistance to doxorubicin.ResultsUnder chronic cyclic hypoxia, hypoxic PANC-1 cells have a comparable doubling time with their normoxic counterparts, whereas hypoxic MCF7 cells show a massive increase in doubling time when compared to their normoxic counterparts. Both hypoxic cell lines developed EMT-like phenotypes as well as doxorubicin resistance. According to the findings of miRNet, 6 and 10 miRNAs were shown to play an important role in enriching six hallmarks of pancreatic cancer in the 10th and 20th cycles of hypoxia, respectively, while 7 and 11 miRNAs were shown to play an important role in enriching the four hallmarks of breast cancer in the 10th and 20th cycles of hypoxia, respectively.ConclusionsmiR-221, miR-21, miR-155, and miR-34 were found to be involved in the potentiation of hypoxic PANC-1 hallmarks at both the 10th and 20th cycles, while miR-93, miR-20a, miR-15, and miR-17 were found to be involved in the potentiation of hypoxic MCF7 hallmarks at both the 10th and 20th cycles. This variation in miRNA expression was also connected to the emergence of an EMT-like phenotype, alterations in proliferation rates, and doxorubicin resistance. The chemosensitivity results revealed that chronic cyclic hypoxia is critical in the formation of chemoresistant phenotypes in pancreatic and breast cancer cells. miR-181a and let-7e expression disparities in PANC1, as well as miR-93, miR-34, and miR-27 expression disparities in MCF7, may be associated with the formation of chemoresistant MCF7 and PANC-1 cells following 20 cycles of chronic cyclic hypoxia. Indeed, further research is needed since the particular mechanisms that govern these processes are unknown.
Endometrial proteomic profile of patients with repeated implantation failure
Authors: Yang Jing , Wang Linlin , Ma Jingwen , Diao Lianghui , Chen Jiao , Cheng Yanxiang , Yang Jing , Li Longfei 
Published: July 2023

IntroductionSuccessful embryo implantation, is the initiating step of pregnancy, relies on not only the high quality of the embryo but also the synergistic development of a healthy endometrium. Characterization and identification of biomarkers for the receptive endometrium is an effective method for increasing the probability of successful embryo implantation.MethodsEndometrial tissues from 22 women with a history of recurrent implantation failure (RIF) and 19 fertile controls were collected using biopsy catheters on 7-9 days after the peak of luteinizing hormone. Differentially expressed proteins (DEPs) were identified in six patients with RIF and six fertile controls using isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis.ResultsTwo hundred and sixty-three DEPs, including proteins with multiple bioactivities, such as protein translation, mitochondrial function, oxidoreductase activity, fatty acid and amino acid metabolism, were identified from iTRAQ. Four potential biomarkers for receptive endometrium named tubulin polymerization-promoting protein family member 3 TPPP3, S100 Calcium Binding Protein A13 (S100A13), 17b-hydroxysteroid dehydrogenase 2 (HSD17B2), and alpha-2-glycoprotein 1, zinc binding (AZGP1) were further verified using ProteinSimple Wes and immunohistochemical staining in all included samples (n=22 for RIF and n=19 for controls). Of the four proteins, the protein levels of TPPP3 and HSD17B2 were significantly downregulated in the endometrium of patients with RIF.DiscussionPoor endometrial receptivity is considered the main reason for the decrease in pregnancy success rates in patients suffering from RIF. iTRAQ techniques based on isotope markers can identify and quantify low abundance proteomics, and may be suitable for identifying differentially expressed proteins in RIF. This study provides novel evidence that TPPP3 and HSD17B2 may be effective targets for the diagnosis and treatment of non-receptive endometrium and RIF.
High preoperative blood oxaloacetate and 2-aminoadipic acid levels are associated with postoperative delayed neurocognitive recovery
Authors: Mao Haoli , Huang Huimin , Zhou Ren , Zhu Jiao , Yan Jia , Jiang Hong , Zhang Lei 
Published: July 2023

IntroductionThis study aimed to identify preoperative blood biomarkers related to development of delayed neurocognitive recovery (dNCR) following surgery.MethodsA total of 67 patients (≥65 years old) who underwent head and neck tumor resection under general anesthesia were assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Preoperative serum metabolomics were determined using widely targeted metabolomics technology.ResultsOf the 67 patients, 25 developed dNCR and were matched to 25 randomly selected patients from the remaining 42 without dNCR. Differential metabolites were selected using the criteria of variable importance in projection &gt; 1.0 in orthogonal partial least squares discrimination analysis, false discovery rate &lt;0.05, and fold-change &gt;1.2 or &lt;0.83 to minimize false positives. Preoperative serum levels of oxaloacetate (OR: 1.054, 95% CI: 1.027–1.095, P = 0.001) and 2-aminoadipic acid (2-AAA) (OR: 1.181, 95% CI: 1.087–1.334, P = 0.001) were associated with postoperative dNCR after adjusting for anesthesia duration, education, and age. Areas under the curve for oxaloacetate and 2-AAA were 0.86 (sensitivity: 0.84, specificity: 0.88) and 0.86 (sensitivity: 0.84, specificity: 0.84), respectively. High levels of preoperative oxaloacetate and 2-AAA also were associated with postoperative decreased MoCA (β: 0.022, 95% CI: 0.005–0.04, P = 0.013 for oxaloacetate; β: 0.077, 95%CI: 0.016–0.137, P = 0.014 for 2-AAA) and MMSE (β: 0.024, 95% CI: 0.009–0.039, P = 0.002 for oxaloacetate; β: 0.083, 95% CI: 0.032–0.135, P = 0.002 for 2-AAA) scores after adjusting for age, education level, and operation time.ConclusionHigh preoperative blood levels of oxaloacetate and 2-AAA were associated with increased risk of postoperative dNCR.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05105451, identifier NCT05105451.
Effects of neuromuscular electrical stimulation on glycemic control: a systematic review and meta-analysis
Authors: Sanchez Michael J. , Mossayebi Ali , Sigaroodi Solmaz , Apaflo Jehu N. , Galvan Michelle J. , Min Kisuk , Agullo Francisco J. , Wagler Amy , Bajpeyi Sudip 
Published: July 2023

BackgroundPhysical inactivity increases the risk for metabolic diseases such as obesity and type 2 diabetes. Neuromuscular electrical stimulation (NMES) is an effective method to induce muscle contraction, particularly for populations with physical impairments and/or metabolic diseases. However, its effectiveness to improve glycemic control is unclear. This review aimed to determine the effectiveness of NMES on glycemic control.MethodsElectronic search consisted of MEDLINE (PubMed), EMBASE, Cochrane Library, Google Scholar, and Web of Science to identify studies that investigated the effects of NMES on glycemic control for this systematic review. The meta-analysis consists of the studies designed as randomized controlled trials. Effect sizes were calculated as the standardized mean difference (SMD) and meta-analysis was conducted using a random-effects model.ResultsThirty-five studies met the inclusion criteria for systematic review and of those, nine qualified for the meta-analysis. Existing evidence suggested that NMES effectively improves glycemic control predominantly in middle-aged and elderly population with type 2 diabetes, obesity, and spinal cord injury. The meta-analysis is comprised of 180 participants and reported that NMES intervention lowered fasting blood glucose (SMD: 0.48; 95% CI: 0.17 to 0.78; p=0.002; I²=0%). Additional analysis using the primary measures reported by each study to indicate glycemic control (i.e., OGTT, HOMA-IR, and fasting glucose) also confirmed a significant effect of NMES on improving glycemic control (SMD: 0.41; 95% CI, 0.09 to 0.72; p=0.01; I²=11%). NMES protocol varied across studies and requires standardization.ConclusionNMES could be considered as a therapeutic strategy to improve glycemic control in populations with physical impairments and/or metabolic disorders.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020192491.
Risk as a process: a history informed hazard planning approach applied to the 2018 post-fire debris flows, Montecito, California
Authors: Serra-Llobet Anna , Radke John , Kondolf G. Mathias , Gurrola Larry , Rogers J. David , Lindbergh Sarah , Douvinet Johnny 
Published: July 2023

Historical information about floods is not commonly used in the US to inform land use planning decisions. Rather, the current approach to managing floods is based on static maps derived from computer simulations of the area inundated by floods of specified return intervals. These maps provide some information about flood hazard, but they do not reflect the underlying processes involved in creating a flood disaster, which typically include increased exposure due to building on flood-prone land, nor do they account for the greater hazard resulting from wildfire. We developed and applied an approach to analyze how exposure has evolved in flood hazard zones in Montecito, California, an area devastated by post-fire debris flows in January 2018. By combining historical flood records of the past 200 years, human development records of the past 100 years, and geomorphological understanding of debris flow generation processes, this approach allows us to look at risk as a dynamic process influenced by physical and human factors, instead of a static map. Results show that floods after fires, in particular debris flows and debris laden floods, are very common in Montecito (15 events in the last 200 years), and that despite policies discouraging developments in hazard areas, developments in hazard zones have increased substantially since Montecito joined the National Flood Insurance Program in 1979. We also highlight the limitation of using conventional Flood Insurance Rate Maps (FIRMs) to manage land use in alluvial fan areas such as Montecito. The knowledge produced in this project can help Montecito residents better understand how they came to be vulnerable to floods and identify action they are taking now that might increase or reduce their vulnerability to the next big flood. This science-history-centric approach to understand hazard and exposure evolution using geographic information systems (GIS) and historical records, is generalizable to other communities seeking to better understand the nature of the hazard they are exposed to and some of the root causes of their vulnerabilities, in other words, both the natural and social processes producing disasters.
A large-scale study on the nocturnal behavior of African ungulates in zoos and its influencing factors
Authors: Gübert Jennifer , Hahn-Klimroth Max , Dierkes Paul W. 
Published: July 2023

IntroductionThe nocturnal behavior of many ungulate species has currently not been sufficiently studied. However, the behavioral patterns of large herbivores vary greatly between day and night, and knowledge about species’ behavior is not only scientifically interesting, but also required for successful animal management and husbandry.Material and methodsIn the current study, the nocturnal behavior of 196 individuals of 19 ungulate species in 20 European zoos is studied, providing the first description of the nocturnal behavior of some of the species. The importance of a wide range of possible factors influencing nocturnal behavior is discussed. Specifically, the behavioral states of standing and lying were analyzed, evaluating the proportion and number of phases in each behavior. The underlying data consist of 101,629 h of video material from 9,239 nights. A deep learning-based software package named Behavioral Observations by Videos and Images Using Deep-Learning Software (BOVIDS) was used to analyze the recordings. The analysis of the influencing factors was based on random forest regression and Shapley additive explanation (SHAP) analysis.ResultsThe results indicate that age, body size, and feeding type are the most important factors influencing nocturnal behavior across all species. There are strong differences between the zebra species and the observed Cetartiodactyla as well as white rhinos. The main difference is that zebras spend significantly less time in a lying position than Cetartiodactyla.DiscussionOverall, the results fit well into the sparse existing literature and the data can be considered a valid reference for further research and might help to assess animal's welfare in zoos.
Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis
Authors: Cheng Qi , Mou Lijun , Su Wenjing , Chen Xin , Zhang Ting , Xie Yifan , Xue Jing , Lee Pui Y. , Wu Huaxiang , Du Yan 
Published: July 2023

BackgroundDysregulation of cell death and defective clearance of dying cells are closely related to the pathogenesis of lupus nephritis (LN). However, the contribution of a recently discovered form of programmed cell death (PCD) called ferroptosis to LN has not been explored in detail. The purpose of this study was to investigate the role of ferroptosis and its associated metabolic pathways in the pathogenesis of LN.MethodsThe composite gene expression scores were calculated by averaging the z-scored transformed log2 expressed genes within each form of PCD and pathway. Immunohistochemistry and immunofluorescence assays were used to verify the bioinformatics results.ResultsWe determined that ferroptosis is prominently and specifically elevated in the glomerular compartment of LN patients compared to other forms of PCD and kidney disease. This finding was then verified by immunohistochemical staining of 4-HNE (a key indicator for ferroptosis) expression in our own cohort (P &lt; 0.0001). Intercorrelation networks were observed between 4-HNE and blood urea nitrogen, SLE disease activity index, serum creatinine, and complement 4, and negatively correlated with glomerular filtration rate in our own LN cohort (P &lt; 0.05). Furthermore, enhanced iron metabolism and reduced fatty acid synthesis may be the most important factors for ferroptosis within the glomerulus. Through analysis of a single cell sequencing dataset and verification of immunohistochemical and immunofluorescence staining, aberrantly activated lipid peroxidation in CD163+ macrophages and CD10+ PC+ (pyruvate carboxylase) epithelial cells indicated that they may be undergoing ferroptosis in the glomerular compartment.ConclusionsTwo dysregulated genes, CD163 and PC, were identified and verified that were significantly associated with lipid peroxidation. Targeting ferroptosis in CD163+ macrophages and CD10+ PC+ epithelial cells may provide novel therapeutic approaches in LN.
Gelsevirine is a novel STING-specific inhibitor and mitigates STING-related inflammation in sepsis
Authors: Chen Yuhong , Bian Huihui , Lv Juan , Song Wanxue , Xing Chunlei , Hui Chunlei , Zhang Dinglei , Zhang Chenxi , Zhao Liang , Li Yingke , Su Li 
Published: July 2023

BackgroundStimulation of IFN genes (STING) is central to the production of interferon and proinflammatory cytokines in response to microbial DNA or self-DNA in the cytosol. The detrimental role of the activation of STING during sepsis has been well documented.MethodsHere, we found that gelsevirine (GS) potently inhibit interferon and inflammatory cytokine induction in macrophages exposed to STING agonists (2'3'-cGAMP, IFN stimulatory DNA (ISD), and poly(dA:dT)). I n silico docking analysis and surface plasmon resonance binding study showed that GS bonds with high affinity to the cyclic dinucleotide (CDN)-binding pocket of STING. Biotin pull-down assay also confirmed that GS competitively bonded to STING protein. Furthermore, GS inhibited 2’3’-cGAMP-induced STING dimerization and subsequent activation. In addition, GS induced K48-linked STING ubiquitination and degradation, which was likely through upregulating and recruiting TRIM21. In mice exposed to cecal ligation and puncture (CLP)-induced sepsis, post-operative administration of GS significantly extended the survival period and mitigated acute organ damage.ResultsOverall, GS inhibited STING signaling by competitively binding to the CDN-binding pocket to lock STING in an inactive open conformation, while also promoting K48-linked STING ubiquitination and degradation.ConclusionsOur findings identify a novel STING-specific inhibitor that could be applied in the treatment of sepsis.
Transarterial chemoembolization combined with molecularly targeted agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma: a retrospective cohort study
Authors: Jiang Nan , Zhong Binyan , Huang Jintao , Li Wanci , Zhang Shuai , Zhu Xiaoli , Ni Caifang , Shen Jian 
Published: July 2023

PurposeTo retrospectively evaluate and compare treatment effectiveness and safety between transarterial chemoembolization (TACE) combined with molecularly targeted agents plus immune checkpoint inhibitors (TACE+T+I) and TACE combined with molecularly targeted agents (TACE+T) for unresectable hepatocellular carcinoma (uHCC).MethodsWe retrospectively analyzed the data of patients with unresectable HCC from January 2018 to June 2022. The patients were screened based on the inclusion criteria and were divided into the triple combination group (TACE+T+I) and the double combination group (TACE+T). The primary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events (AEs). The secondary outcomes were objective response rate (ORR) and disease control rate (DCR). Risk factors associated with PFS and OS were determined by Cox regression analysis.ResultsA total of 87 patients were enrolled in this study, including 42 patients in the TACE+T+I group and 45 patients in the TACE+T group. Over a median follow-up of 29.00 and 26.70 months, patients who received TACE+T+I therapy achieved a significantly longer median OS (24.00 vs. 21.40 months, p = 0.007) and median PFS (9.70 vs. 7.00 months, p = 0.017); no grade 4 AEs or treatment-related death occurred in the two groups. Grade 3 AEs attributed to systemic agents in the two groups showed no significant difference (19.0% vs. 15.6%, p = 0.667). Patients in the TACE+T+I group demonstrated better tumor response when compared with patients in the TACE+T group, with an ORR of 52.4% vs. 17.8% (p = 0.001). No significant difference was observed in DCR between the two groups (83.3% vs. 77.8%, p = 0.514). Cox regression analysis showed that only the treatment method was an independent factor of OS, and both age and treatment method were independent factors related to PFS.ConclusionCompared with TACE plus molecularly targeted agents (TACE+T), the triple therapy (TACE+T+I) could improve survival and tumor response in unresectable HCC with manageable toxicities.
Transitioning from pediatric to adult healthcare with an inborn error of immunity: a qualitative study of the lived experience of youths and their families
Authors: Ouimet François , Fortin Justine , Bogossian Aline , Padley Nicole , Chapdelaine Hugo , Racine Eric 
Published: July 2023

IntroductionTransition from pediatric to adult healthcare is a multifaceted and consequential process with important health implications for youth. Although research on transition has grown significantly, research on transition for patients living with an inborn error of immunity (IEI) is scarce. We undertook a qualitative study to better understand the perspectives of youths and parents in an outpatient immunology clinic.MethdosSemi-structured interviews were conducted with 9 youths, 6 parents and 5 clinicians, all recruited from the same clinic. All youths recently transferred to adult care with or without an established diagnosis of IEI. Interviews were transcribed verbatim and thematic analysis was conducted. Two sets of themes were generated. The first set captured the positive and negative aspects experienced during transition, as well as recommendations to facilitate the process. The second set focused on key topics discussed in the interviews that were merged into overarching themes.ResultsPerspectives of participants were clustered into 6 overarching themes: (1) lack of knowledge about IEIs; (2) scattered transitions; (3) changing healthcare teams; (4) approaching an unknown environment; (5) transitioning to adulthood; (6) assuming responsibility for the management of the condition. Overall, the challenges encountered with respect to these themes had profound clinical and humanistic implications for patients such as generating significant distress.DiscussionWe discuss the unique challenges of the youths in our study in comparison to common problems reported by youths with chronic illness in the broader transition literature (for example: the change of healthcare team, the lack of information about the transition process and navigating the adult care system, growth towards self-management and the co-occurring developmental transition to adulthood). There is an urgency to attend to the specific problems created by the rarity of IEIs and related lack of knowledge about them as well as the need for multidisciplinary cross-clinic care during transition and beyond.
Impact of clomazone on bacterial communities in two soils
Authors: He Hairong , Huang Jiarui , Zhao Zhenzhu , Feng Weisheng , Zheng Xiaoke , Du Pengqiang 
Published: July 2023

IntroductionBacterial communities are important for soil functions, but the effect of clomazone on network complexity, composition, and stability is not well studied.MethodIn this study, two agricultural soils were used to test the impact of clomazone on bacterial communities, and the two soils were treated with three concentrations of clomazone (0, 0.8, 8, and 80 mg kg1) in an incubator.Results and discussionBacterial network nodes, links, and average degrees were all decreased by 9–384, 648–829, and 0.703–2.429, respectively. Based on keystone nodes, the topological roles of the nodes were also influenced by clomazone. Bacterial network composition was also impacted based on the analysis of similarity (ANOSIM) and network dissimilarity. Compared with control and clomazone treatments in both soils, the ANOSIM between control and all clomazone treatments was higher than 0.6, network dissimilarities were 0.97–0.98, shared nodes were 131–260, and shared links were 12–100. The bacterial network stability was decreased by clomazone, with decreased robustness by 0.01–0.016 and increased vulnerability by 0.00023–0.00147 in both soils. There were fewer bacterial network modules preserved after clomazone treatment, and the bacterial network community functions were also impacted in both soils. Based on these results, soil bacterial species connections, modularization, and network stability were significantly impacted by clomazone.