bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three‐dimensional chromatin landscapes in somatotroph tumour
Authors: Guo Jing , Chen Yiyuan , Zhu Haibo , Tong Xinyu , Cao Lei , Zhang Yazhuo , Xie Weiyan , Li Chuzhong 
Published: May 2024

AbstractBackgroundThe three‐dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored.MethodsWe employed Hi‐C and RNA‐seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns.ResultsWe observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi‐C and RNA‐seq data demonstrated that changes inhigher‐order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt/β‐Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT‐PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro.ConclusionOur results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.
Therapeutic targeting of PLK1 in TERT promoter‐mutant hepatocellular carcinoma
Authors: Tang Qin , Hu Guanghui , Sang Ye , Chen Yulu , Wei Guangyan , Zhu Meiyan , Chen Mengke , Li Shiyong , Liu Rengyun , Peng Zhenwei 
Published: May 2024

AbstractBackgroundHotspot mutations in the promoter of telomerase reverse transcriptase (TERT) gene are the most common genetic variants in hepatocellular carcinoma (HCC) and associated with poor prognosis of the disease. However, no drug was currently approved for treating TERT promoter mutation positive HCC patients. Here, we aim to explore the potential therapeutic strategy for targeting TERT promoter mutation in HCC.MethodsThe Liver Cancer Model Repository database was used for screening potential drugs to selectively suppress the growth of TERT promoter mutant HCC cells. RNA‐seq, CRISPR‐Cas9 technology and siRNA transfection were performed for mechanistic studies. Cell counting kit‐8 (CCK8) assay and the xenograft tumour models were used for cell growth detection in vitro and in vivo, respectively. Cell apoptosis and cell cycle arrest were analysed by Annexin V‐FITC staining and/or propidium iodide staining.ResultsPLK1 inhibitors were remarkably more sensitive to HCC cells harbouring TERT promoter mutation than wild‐type cells in vitro and in vivo, which were diminished after TERT promoter mutation was edited to the wild‐type nucleotide. Comparing the HCC cells with wild‐type promoter of TERT, PLK1 inhibitors specifically downregulated Smad3 to regulate TERT for inducing apoptosis and G2/M arrest in TERT mutant HCC cells. Moreover, knockout of Smad3 counteracted the effects of PLK1 inhibitors in TERT mutant HCC cells. Finally, a cooperative effect of PLK1 and Smad3 inhibition was observed in TERT mutant cells.ConclusionsPLK1 inhibition selectively suppressed the growth of TERT mutant HCC cells through Smad3, thus contributed to discover a novel therapeutic strategy to treat HCC patients harbouring TERT promoter mutations.Key points
TERT promoter mutation confers sensitivity to PLK1 inhibitors in HCC.
The selective growth inhibition of TERT mutant HCC cells induced by PLK1 inhibitor was mediated by Smad3.
Combined inhibition of PLK1 and Smad3 showed a cooperative anti‐tumor effect in TERT mutant HCC cells.
CD62‐L down‐regulation after L18‐MDP stimulation as a complementary flow cytometry functional assay for the diagnosis of XIAP deficiency
Authors: Rizzo Agustín D. , Sanz Marianela , Roffe Georgina , Sajaroff Elisa O. , Prado Damian A. , Prieto Emma , Goris Verónica , Rossi Jorge G. , Bernasconi Andrea R. 
Published: May 2024

AbstractX‐linked inhibitor of apoptosis (XIAP) deficiency is an infrequent inborn error of immunity caused by mutations in XIAP gene. Most cases present with absence of XIAP protein which can be detected by flow cytometry (FC), representing a rapid diagnostic method. However, since some genetic defects may not preclude protein expression, it is important to include a complementary functional test in the laboratory workup of these patients. L‐selectin (CD62‐L) is a molecule that is cleaved from the surface membrane of leukocytes upon stimulation of different receptors such as toll like receptors (TLRs) and nucleotide‐binding oligomerization domain‐like receptors (NLRs), including NOD2. Considering that XIAP deficiency impairs NOD2 signaling, we decided to assess CD62‐L down‐regulation by FC post‐stimulation of neutrophils and monocytes with L18‐muramyl Di‐Peptide (L18‐MDP), a NOD2 specific agonist, in order to develop a novel assay for the functional evaluation of patients with suspicion of XIAP defects. Whole blood samples from 20 healthy controls (HC) and four patients with confirmed molecular diagnosis of XIAP deficiency were stimulated with 200 ng/mL of L18‐MDP for 2 h. Stimulation with 100 ng/mL of lipopolysaccharide (LPS) was carried out in parallel as a positive control of CD62‐L shedding. CD62‐L expression was evaluated by FC using an anti CD62‐L‐ antibody and down‐regulation was assessed by calculating the difference in CD62‐L expression before and after stimulation, both in terms of percentage of CD62‐L expressing cells (Δ%CD62‐L) and median fluorescence intensity (ΔMFI%). Neutrophils and monocytes from XIAP deficient patients displayed a significantly diminished response to L18‐MDP stimulation compared with HC (p < 0.0001), indicating a severely altered mechanism of CD62‐L down‐regulation following activation of NOD2‐XIAP axis. On the other hand, the response to LPS stimulation was comparable between patients and heathy controls, suggesting preserved CD62‐L shedding with a different stimulus. FC detection of CD62‐L down‐regulation in monocytes and neutrophils after whole blood stimulation with L18‐MDP results in an effective and rapid functional test for the identification of XIAP deficient patients.
Regime‐dependent commodity price dynamics: A predictive analysis
Authors: Crespo Cuaresma Jesus , Fortin Ines , Hlouskova Jaroslava , Obersteiner Michael 
Published: May 2024

AbstractWe develop an econometric modelling framework to forecast commodity prices taking into account potentially different dynamics and linkages existing at different states of the world and using different performance measures to validate the predictions. We assess the extent to which the quality of the forecasts can be improved by entertaining different regime‐dependent threshold models considering different threshold variables. We evaluate prediction quality using both loss minimization and profit maximization measures based on directional accuracy, directional value, the ability to predict turning points, and the returns implied by a simple trading strategy. Our analysis provides overwhelming evidence that allowing for regime‐dependent dynamics leads to improvements in predictive ability for the Goldman Sachs Commodity Index, as well as for its five sub‐indices (energy, industrial metals, precious metals, agriculture, and livestock). Our results suggest the existence of a trade‐off between predictive ability based on loss and profit measures, which implies that the particular aim of the prediction exercise carried out plays a very important role in terms of defining which set of models is the best to use.
Nanoemulsions of red quinoa and ginseng extracts with chitosan wall: Investigating the antioxidant properties and its effect on the shelf life of dairy cream
Authors: Aziminezhad Hadis , Esmaeilzadeh Kenari Reza , Raftani Amiri Zeynab 
Published: May 2024

AbstractThe study aimed to investigate the antioxidant properties of ginseng and red quinoa extract nanoemulsion and its effect on the shelf life of dairy cream. Nanoemulsion includes dairy cream, Tween 80, chitosan, whey protein powder, chitosan/whey protein powder, red quinoa extract, ginseng extract, and a mixture of extracts (1:1). The highest total phenol content and total flavonoid content were related to ginseng extract (24,009.55 mg of gallic acid equivalent/kg, 883.16 mg quercetin/kg) with ethanol–water solvent (80:20). Most of the phenolic and flavonoid compounds of ginseng and red quinoa extracts were related to p‐coumaric acid (211.3 μg/g), catechin (29.6 μg/g), ellagic acid (73.88 μg/g), and rutin (34.12 μg/g), respectively. Considerable antioxidant power in the concentration of 800 ppm of red quinoa and ginseng extracts (ethanol–water solvent (50:50), (80:20)) in 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging (80%, 82%, 80%, and 78%), bleaching β‐carotene: linoleic acid (81%, 73%, 77%, and 86%), and ferric reducing antioxidant power assays (70%, 73%, 72%, and 76%) was observed. Nanoemulsions of red quinoa extract with chitosan wall had the smallest particle size (250.67 nm), the highest encapsulation efficiency (72.79%), and the polydispersity index (0.34). Nanoemulsions containing ginseng + quinoa (1:1) with chitosan/whey protein powder wall showed the highest viscosity (5.30 mPa/s) and the mostzeta potential (−32.6 mv). Also, nanoemulsions of red quinoa extract showed the lowest amount of peroxide value and the thiobarbituric acid value (12 milliequivalent O2/kg–0.48 μg/mL) in dairy cream oil. In general, the red quinoa extract with chitosan wall was superior to other samples due to the delay in oxidation and positive effect on the shelf life of dairy cream.
Ginsenoside Rg3 combined with near‐infrared photothermal reversal of multidrug resistance in breast cancer MCF‐7/ADR cells
Authors: Chang Ying , Fu Qiang , Lu Zhongqi , Jin Quanxin , Jin Tiefeng , Zhang Meihua 
Published: May 2024

AbstractAdriamycin (ADR) is a frequently employed chemotherapeutic agent for the management of breast cancer. Nevertheless, multidrug resistance (MDR) can impair its therapeutic efficacy in breast cancer. MDR is characterized by increased expression of the P‐glycoprotein (P‐gp) efflux pump, up‐regulation of anti‐apoptotic proteins, and downregulation of pro‐apoptotic proteins. Consequently, inhibition of ATP‐binding cassette (ABC) transporter proteins has been deemed the most efficacious approach to overcome MDR. In this study, we used MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide), Western blots, flow cytometry, immunofluorescence, and constructed xenograft tumors to investigate whether ginsenoside Rg3‐near‐infrared photothermal (Rg3‐NIR) combination reversed multidrug resistance in MCF‐7/ADR breast cancer. In vivo and in vitro experiments, the results showed that Rg3‐NIR co‐treatment was effective in inducing the apoptosis of MCF‐7/ADR breast cancer cells. This was achieved by reversing the expression of drug resistance‐associated proteins, while also inhibiting cell proliferation, migration, and epithelial–mesenchymal transition (EMT) processes via attenuation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway transduction. Ginsenoside Rg3 combined with near‐infrared photothermal therapy (NIR) effectively reverses multidrug resistance in breast cancer MCF‐7/ADR cells, providing a new therapeutic strategy for breast cancer drug resistance.
Skull base surgery for malignant tumors: The 2nd international collaborative study (1995–2015)
Authors: Shah Jatin P. , Levyn Helena , Valero Cristina , Adilbay Dauren , Eagan Alana , Zheng Junting , Gonen Mithat , Cohen Marc , Patel Snehal , Ganly Ian , Pai Prathamesh , Castelnuovo Paolo , Gao Fang Ju , Piazza Cesare , Nicolai Piero , Panizza Ben , Bowman James , Barnett Catherine , Kowalski Luiz P. , Toledo Ronaldo , Fliss Dan M. , DeAlmeida John , Witterick Ian , Herman Philippe , Fontanella Walter , Aniceto Gregorio Sanchez , Hosal Sefik , Ozer Serdar , Iyer Subramania , Harvey Richard , Leemans C. Rene , Hendrickx Jan‐Jaap , Figari Marcelo , Boccalatte Luis , Nibu Ken Ichi , Clarke Peter , Rennie Catherine , Ming Zhu Yi , Cernea Claudio , Goncalves Sergio , Schlosser Rodney , Dias Fernando , Sargi Zoukaa , Ahmed Shahzada , Golusinski Wojciech , Kim Se Heon , Su Shirley Y. , Raza Shaan M. , DeMonte Franco , Hanna Ehab 
Published: May 2024

AbstractBackgroundThe current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide.Patients and methodsA total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes.ResultsThe median age was 56 years (IQR 44–67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow‐up of 7.1 years, the 5‐year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor.ConclusionThe progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.
A comparison of hippocampal and retrosplenial cortical spatial and contextual firing patterns
Authors: Subramanian Dev Laxman , Miller Adam M. P. , Smith David M. 
Published: May 2024

AbstractThe hippocampus (HPC) and retrosplenial cortex (RSC) are key components of the brain's memory and navigation systems. Lesions of either region produce profound deficits in spatial cognition and HPC neurons exhibit well‐known spatial firing patterns (place fields). Recent studies have also identified an array of navigation‐related firing patterns in the RSC. However, there has been little work comparing the response properties and information coding mechanisms of these two brain regions. In the present study, we examined the firing patterns of HPC and RSC neurons in two tasks which are commonly used to study spatial cognition in rodents, open field foraging with an environmental context manipulation and continuous T‐maze alternation. We found striking similarities in the kinds of spatial and contextual information encoded by these two brain regions. Neurons in both regions carried information about the rat's current spatial location, trajectories and goal locations, and both regions reliably differentiated the contexts. However, we also found several key differences. For example, information about head direction was a prominent component of RSC representations but was only weakly encoded in the HPC. The two regions also used different coding schemes, even when they encoded the same kind of information. As expected, the HPC employed a sparse coding scheme characterized by compact, high contrast place fields, and information about spatial location was the dominant component of HPC representations. RSC firing patterns were more consistent with a distributed coding scheme. Instead of compact place fields, RSC neurons exhibited broad, but reliable, spatial and directional tuning, and they typically carried information about multiple navigational variables. The observed similarities highlight the closely related functions of the HPC and RSC, whereas the differences in information types and coding schemes suggest that these two regions likely make somewhat different contributions to spatial cognition.
Analysis of the incidence and mortality trends of esophageal cancer in cancer registry areas of China and Japan
Authors: Guo Dongli , Jin Jing , Li Daojuan , He Yutong , Lin Yingsong 
Published: May 2024

AbstractThis study aims to analyze the prevalence trend of esophageal cancer in Japan and China to provide suggestions for the prevention and treatment of esophageal cancer. The results showed that the incidence rate for the years 2010–2018 significantly decreased with an APC of 5.66%, and the mortality rate from 2010 to 2015 had an APC of −5.87% in China. However, the incidence rate of Japanese women showed an upward trend, with an APC of 4.09% from 2010 to 2019. The mortality rate of esophageal cancer in Japan showed a downward trend, with an APC of −2.96% from 2010 to 2021. From 2010 to 2018, Chinese esophageal squamous cell carcinoma accounted for the highest proportion, accounting for 85.96%, with the largest distribution in the middle, accounting for 47.25%. Patients are mostly diagnosed at stage III, and the relative survival rate from 2012 to 2015 was 30.3%. Japan also has the highest proportion of squamous cell carcinoma, and the lesions are also mostly located in the middle segment. While Japanese esophageal cancer patients are mostly diagnosed at stage I, and the relative survival rate was 41.5% in Japan from 2009 to 2011. The results of this article indicate that the current prevalence of esophageal cancer in China and Japan is generally declining, and the quality of life of patients is gradually improving, but effective screening and prevention strategies are still needed to reduce the burden of this disease.
Professional activity and experience after a residency training program in ObGyn: A 10‐year analysis
Authors: Griggio Thauane Batalhoto , de Camargo Pedro Santos Ferreira , Costa Maria Laura , Luz Adriana Gomes 
Published: May 2024

AbstractObjectiveTo describe the profile and professional trajectory of the obstetrics and gynecology (ObGyn) graduates over the past decade, at a referral university hospital.MethodsA cross‐sectional study was conducted, utilizing a survey that targeted graduates of the ObGyn residency program from the last decade, asking about demographics, medical undergraduate, residency details, post‐residency trajectory, satisfaction levels, and social media usage. A descriptive analysis was performed. Comparative analyses, including gender‐based differences, were assessed using chi‐squared or Fisher exact tests (P < 0.05).ResultsAmong 126 graduates, 84 agreed to participate (66.67%), predominantly comprising females with an average age of 33 years. Most identified themselves as white. The majority had pursued their undergraduate studies at the same institution (78.6%) and subsequently acquired specialized titles in ObGyn from the national society. Most of them were employed in both public and private sectors (71.08%). Male graduates held the majority of medical shifts in obstetrics. A significant gender‐based salary discrepancy was noted, favoring males. More than half of the professionals utilized social media for work‐related purposes. Many expressed the necessity for supplementary education beyond public health, particularly career management.ConclusionThe findings highlight a predominance of female and white individuals among the graduates. Overall, graduates expressed contentment with their education and professional engagements. A gender‐based income disparity was identified, favoring male graduates. Studies like this can provide insights for improving medical residency education.
Evaluating pre‐and post‐oral health literacy of undergraduate nursing students on an oral‐systemic health learning intervention
Authors: Koo Fung Kuen , Chen Rebecca , Fethney Judith , Balante Jay , Wong Grace 
Published: May 2024

AbstractIntroductionOral health is significantly linked with systemic health. Nurses play a crucial role in patient education. Improving oral health literacy in nursing students can pave the way for the seamless integration of oral health into nursing practice.ObjectiveThis study aimed to evaluate an interprofessional co‐designed oral‐systemic health learning intervention using a pre‐and‐post study design that measured oral health literacy levels among Year 2 undergraduate nursing students.MethodsEvaluation was measured using the validated Comprehensive Measure of Oral Health Knowledge questionnaire before and after the semester‐long education intervention. Data were analyzed using independent and paired t‐tests and an analysis of variance one‐way analysis of variance.ResultsA total of 78 out of 164 students (82% female, 42% aged 21–24, and 52% speaking English as a first language) participated in the pre‐ and post‐study surveys. Statistically significant improvement was noted in pre‐and‐post total oral health literacy scores (Pre 14.92 [3.85] vs.. Post 15.85 [3.74], p = 0.031). Students showed the highest proficiency in the domain of oral disease prevention, while oral cancer knowledge was the least mastered domain. Those without English as their first language and those with secondary education as the highest qualification showed the greatest improvement in oral health literacy scores post‐intervention.ConclusionsThis study highlights the efficacy of an interprofessional co‐designed oral‐systemic educational intervention in increasing oral health literacy among undergraduate nursing students. This intervention marks a preliminary step towards integrating oral health into future nursing practice. Further research is warranted to explore the enduring impact of these interventions on their future clinical endeavors.
On the fate of protonated chloroformates in the gas phase: a competition between forming HCl and chloroformic acid
Authors: Diedhiou Malick , Mayer Paul M. 
Published: May 2024

AbstractChloroformates are prevalent in the atmosphere due to their utilization as fuel additives and industrial solvents. These species may undergo interactions with atmospheric water resulting in protonated chloroformates. This study delves into the gas‐phase dissociation of these protonated species. Tandem mass spectrometry was employed to scrutinize the unimolecular dissociation of protonated methyl (1), ethyl (2), neopentyl (3), and phenyl chloroformate (4). Notably, 1 and 4 exhibited HCl loss, yielding CH3OCO+ and C6H5OCO+, respectively, with 1 additionally generating neutral methanol and ClCO+. 4 additionally loses CO and CO2. In contrast, 2 and 3 each only exhibit a single fragmentation channel, with 2 losing C2H4 to generate protonated chloroformic acid and 3 generating protonated 2‐methylbutene by losing neutral chloroformic acid. Density functional theory at the B3LYP/6‐311+G(d,p) level of theory was employed to explore minimum energy reaction pathways for each ion, and CBS‐QB3 single‐point energy calculations were added to provide reliable energetics. The Rice–Ramsperger–Kassel–Marcus (RRKM) calculations of the rate constants for selected competing processes were carried out to link theory and experiment. One common unimolecular process observed was the 1,3‐H shift of the proton from the carbonyl oxygen to the ester oxygen before dissociation.