bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-SNAP (M105I) mutation promotes neuronal differentiation of neural stem/progenitor cells through overactivation of AMPK
Authors: Bustamante-Barrientos Felipe A. , Méndez-Ruette Maxs , Molina Luis , Koning Tania , Ehrenfeld Pamela , González Carlos B. , Wyneken Ursula , Henzi Roberto , Bátiz Luis Federico 
Published: April 2023

Background: The M105I point mutation in α-SNAP (Soluble N-ethylmaleimide-sensitive factor attachment protein-alpha) leads in mice to a complex phenotype known as hyh (hydrocephalus with hop gait), characterized by cortical malformation and hydrocephalus, among other neuropathological features. Studies performed by our laboratory and others support that the hyh phenotype is triggered by a primary alteration in embryonic neural stem/progenitor cells (NSPCs) that leads to a disruption of the ventricular and subventricular zones (VZ/SVZ) during the neurogenic period. Besides the canonical role of α-SNAP in SNARE-mediated intracellular membrane fusion dynamics, it also negatively modulates AMP-activated protein kinase (AMPK) activity. AMPK is a conserved metabolic sensor associated with the proliferation/differentiation balance in NSPCs.Methods: Brain samples from hyh mutant mice (hydrocephalus with hop gait) (B6C3Fe-a/a-Napahyh/J) were analyzed by light microscopy, immunofluorescence, and Western blot at different developmental stages. In addition, NSPCs derived from WT and hyh mutant mice were cultured as neurospheres for in vitro characterization and pharmacological assays. BrdU labeling was used to assess proliferative activity in situ and in vitro. Pharmacological modulation of AMPK was performed using Compound C (AMPK inhibitor) and AICAR (AMPK activator).Results: α-SNAP was preferentially expressed in the brain, showing variations in the levels of α-SNAP protein in different brain regions and developmental stages. NSPCs from hyh mice (hyh-NSPCs) displayed reduced levels of α-SNAP and increased levels of phosphorylated AMPKα (pAMPKαThr172), which were associated with a reduction in their proliferative activity and a preferential commitment with the neuronal lineage. Interestingly, pharmacological inhibition of AMPK in hyh-NSPCs increased proliferative activity and completely abolished the increased generation of neurons. Conversely, AICAR-mediated activation of AMPK in WT-NSPCs reduced proliferation and boosted neuronal differentiation.Discussion: Our findings support that α-SNAP regulates AMPK signaling in NSPCs, further modulating their neurogenic capacity. The naturally occurring M105I mutation of α-SNAP provokes an AMPK overactivation in NSPCs, thus connecting the α-SNAP/AMPK axis with the etiopathogenesis and neuropathology of the hyh phenotype.
Modelling the erythroblastic island niche of dyserythropoietic anaemia type IV patients using induced pluripotent stem cells
Authors: May Alisha , Ventura Telma , Fidanza Antonella , Volmer Helena , Taylor Helen , Romanò Nicola , D’Souza Sunita L. , Bieker James J. , Forrester Lesley M. 
Published: April 2023

Introduction: Congenital dyserythropoietic anaemia (CDA) type IV has been associated with an amino acid substitution, Glu325Lys (E325K), in the transcription factor KLF1. These patients present with a range of symptoms, including the persistence of nucleated red blood cells (RBCs) in the peripheral blood which reflects the known role for KLF1 within the erythroid cell lineage. The final stages of RBCs maturation and enucleation take place within the erythroblastic island (EBI) niche in close association with EBI macrophages. It is not known whether the detrimental effects of the E325K mutation in KLF1 are restricted to the erythroid lineage or whether deficiencies in macrophages associated with their niche also contribute to the disease pathology.Methods: To address this question, we generated an in vitro model of the human EBI niche using induced pluripotent stem cells (iPSCs) derived from one CDA type IV patient as well as two iPSC lines genetically modified to express an KLF1-E325K-ERT2 protein that could be activated with 4OH-tamoxifen. The one patient iPSC line was compared to control lines from two healthy donors and the KLF1-E325K-ERT2 iPSC line to one inducible KLF1-ERT2 line generated from the same parental iPSCS.Results: The CDA patient-derived iPSCs and iPSCs expressing the activated KLF1-E325K-ERT2 protein showed significant deficiencies in the production of erythroid cells with associated disruption of some known KLF1 target genes. Macrophages could be generated from all iPSC lines but when the E325K-ERT2 fusion protein was activated, we noted the generation of a slightly less mature macrophage population marked by CD93. A subtle trend in their reduced ability to support RBC enucleation was also associated with macrophages carrying the E325K-ERT2 transgene.Discussion: Taken together these data support the notion that the clinically significant effects of the KLF1-E325K mutation are primarily associated with deficiencies in the erythroid lineage but it is possible that deficiencies in the niche might have the potential to exacerbate the condition. The strategy we describe provides a powerful approach to assess the effects of other mutations in KLF1 as well as other factors associated with the EBI niche.
Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments
Authors: Chen Xiaoxia , Zhang Wanling , Lin Zhijun , Zheng Chunyan , Chen Shufang , Zhou Haihong , Liu Zhou 
Published: April 2023

BackgroundRecent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown.ObjectivesThis study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment.MethodsFive patients aged 54–80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period.ResultsThe MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study.ConclusionsIn this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.
Synergistic effect and antibiofilm activity of the antimicrobial peptide K11 with conventional antibiotics against multidrug-resistant and extensively drug-resistant Klebsiella pneumoniae
Authors: Chatupheeraphat Chawalit , Peamchai Jiratchaya , Luk-in Sirirat , Eiamphungporn Warawan 
Published: April 2023

IntroductionInfections caused by drug-resistant Klebsiella pneumoniae are now a serious problem for public health, associated with high morbidity and mortality due to limited treatment options. Therefore, new antibacterial agents or a combination of agents as the first line of treatment are urgently needed. K11 is a novel antimicrobial peptide (AMP) that has demonstrated in vitro antimicrobial activity against several types of bacteria. Additionally, K11 has previously shown no hemolytic activity. Herein, the antibacterial activity, the synergistic action of K11 in combination with different conventional antibiotics and the antibiofilm activity of K11 against multidrug-resistant (MDR) and extensively drug-resistant (XDR) K. pneumoniae were investigated. Meanwhile, the stability and ability to induce the bacterial resistance of K11 were also tested.MethodsFifteen clinical isolates of MDR/XDR K. pneumoniae were used in this study. The minimum inhibitory concentration (MIC) of K11 against these isolates was determined by the broth microdilution method. In vitro synergy between K11 and antibiotics was evaluated using the checkerboard methodology. The antibiofilm activity of K11 against K. pneumoniae strong biofilm producers were explored by the crystal violet staining. The stability in different environments and resistance induction of K11 were evaluated by MIC determination.ResultsThe MIC values of K11 against MDR/XDR K. pneumoniae isolates were 8-512 μg/mL. Intriguingly, the synergistic effects were clearly observed for K11 in combination with chloramphenicol, meropenem, rifampicin, or ceftazidime, whereas no synergy was observed when K11 was combined with colistin. Besides, K11 effectively prevented biofilm formation against K. pneumoniae strong biofilm producers in a concentration-dependent manner starting at 0.25×MIC and exerted an enhancing effect when administered in combination with meropenem, chloramphenicol, or rifampicin. Additionally, K11 demonstrated high thermal and wide pH stability along with good stability in serum and physiological salts. Significantly, K. pneumoniae showed no induction of resistance even after prolonged exposure to a sub-inhibitory concentration of K11.ConclusionThese findings indicate that K11 is a promising candidate with potent antibacterial and antibiofilm activities without inducing resistance and acts synergistically with conventional antibiotics against drug-resistant K. pneumoniae.
Impact of sex and role of coronary artery disease in out-of-hospital cardiac arrest presenting with refractory ventricular arrhythmias
Authors: Caputo Maria Luce , Baldi Enrico , Krüll Joel Daniel , Pongan Damiano , Cresta Ruggero , Benvenuti Claudio , Cianella Roberto , Primi Roberto , Currao Alessia , Bendotti Sara , Compagnoni Sara , Gentile Francesca Romana , Anselmi Luciano , Savastano Simone , Klersy Catherine , Auricchio Angelo 
Published: April 2023

IntroductionThere are limited data on sex-related differences in out-of hospital cardiac arrests (OHCAs) with refractory ventricular arrhythmias (VA) and, in particular, about their relationship with cardiovascular risk profile and severity of coronary artery disease (CAD).PurposeAim of this study was to characterize sex-related differences in clinical presentation, cardiovascular risk profile, CAD prevalence, and outcome in OHCA victims presenting with refractory VA.MethodsAll OHCAs with shockable rhythm that occurred between 2015 and 2019 in the province of Pavia (Italy) and in the Canton Ticino (Switzerland) were included.ResultsOut of 680 OHCAs with first shockable rhythm, 216 (33%) had a refractory VA. OHCA patients with refractory VA were younger and more often male. Males with refractory VA had more often a history of CAD (37% vs. 21%, p 0.03). In females, refractory VA were less frequent (M : F ratio 5 : 1) and no significant differences in cardiovascular risk factor prevalence or clinical presentation were observed. Male patients with refractory VA had a significantly lower survival at hospital admission and at 30 days as compared to males without refractory VA (45% vs. 64%, p &lt; 0.001 and 24% vs. 49%, p &lt; 0.001, respectively). Whereas in females, no significant survival difference was observed.ConclusionsIn OHCA patients presenting with refractory VA the prognosis was significantly poorer for male patients. The refractoriness of arrhythmic events in the male population was probably due to a more complex cardiovascular profile and in particular due to a pre-existing CAD. In females, OHCA with refractory VA were less frequent and no correlation with a specific cardiovascular risk profile was observed.
Surface impacts and associated mechanisms of a moisture intrusion into the Arctic observed in mid-April 2020 during MOSAiC
Authors: Kirbus Benjamin , Tiedeck Sofie , Camplani Andrea , Chylik Jan , Crewell Susanne , Dahlke Sandro , Ebell Kerstin , Gorodetskaya Irina , Griesche Hannes , Handorf Dörthe , Höschel Ines , Lauer Melanie , Neggers Roel , Rückert Janna , Shupe Matthew D. , Spreen Gunnar , Walbröl Andreas , Wendisch Manfred , Rinke Annette 
Published: April 2023

Distinct events of warm and moist air intrusions (WAIs) from mid-latitudes have pronounced impacts on the Arctic climate system. We present a detailed analysis of a record-breaking WAI observed during the MOSAiC expedition in mid-April 2020. By combining Eulerian with Lagrangian frameworks and using simulations across different scales, we investigate aspects of air mass transformations via cloud processes and quantify related surface impacts. The WAI is characterized by two distinct pathways, Siberian and Atlantic. A moist static energy transport across the Arctic Circle above the climatological 90th percentile is found. Observations at research vessel Polarstern show a transition from radiatively clear to cloudy state with significant precipitation and a positive surface energy balance (SEB), i.e., surface warming. WAI air parcels reach Polarstern first near the tropopause, and only 1–2 days later at lower altitudes. In the 5 days prior to the event, latent heat release during cloud formation triggers maximum diabatic heating rates in excess of 20 K d-1. For some poleward drifting air parcels, this facilitates strong ascent by up to 9 km. Based on model experiments, we explore the role of two key cloud-determining factors. First, we test the role moisture availability by reducing lateral moisture inflow during the WAI by 30%. This does not significantly affect the liquid water path, and therefore the SEB, in the central Arctic. The cause are counteracting mechanisms of cloud formation and precipitation along the trajectory. Second, we test the impact of increasing Cloud Condensation Nuclei concentrations from 10 to 1,000 cm-3 (pristine Arctic to highly polluted), which enhances cloud water content. Resulting stronger longwave cooling at cloud top makes entrainment more efficient and deepens the atmospheric boundary layer. Finally, we show the strongly positive effect of the WAI on the SEB. This is mainly driven by turbulent heat fluxes over the ocean, but radiation over sea ice. The WAI also contributes a large fraction to precipitation in the Arctic, reaching 30% of total precipitation in a 9-day period at the MOSAiC site. However, measured precipitation varies substantially between different platforms. Therefore, estimates of total precipitation are subject to considerable observational uncertainty.
Correlation between pancreatic cancer and metabolic syndrome: A systematic review and meta-analysis
Authors: Zhong Lei , Liu Jifeng , Liu Shuo , Tan Guang 
Published: April 2023

ObjectivePancreatic cancer is a globally frequent cause of death, which can be caused by many factors. This meta-analysis was performed to assess the correlation between pancreatic cancer and metabolic syndrome (MetS).MethodsPublications were identified by searching PubMed, EMBASE, and the Cochrane Library for studies published until November 2022. Case-control and cohort studies published in English that provided information on the odds ratio (OR), relative risk (RR), or hazard ratio (HR) of metabolic syndrome and pancreatic cancer were included in the meta-analysis. Two researchers separately retrieved the core data from the included Random effects meta-analysis was conducted to summarize the findings. Results were presented as relative risk (RR) and 95% confidence interval (CI).ResultsMetS showed a strong association with an increased risk of developing pancreatic cancer (RR1.34, 95% CI1.23–1.46, P&lt;0.001), and gender differences were also observed (men: RR 1.26, 95% CI 1.03–1.54, P=0.022; women: RR 1.64, 95% CI 1.41–1.90, P&lt; 0.001). Moreover, an increased risk of developing pancreatic cancer was strongly linked to hypertension, poor high-density lipoprotein cholesterol, and hyperglycemia (hypertension: RR 1.10 CI 1.01–1.19, P=0.027; low high-density lipoprotein cholesterol: RR 1.24 CI 1.11–1.38, P&lt;0.001; hyperglycemia: RR 1.55, CI 1.42–1.70, P&lt; 0.001). However, pancreatic cancer was independent of obesity and hypertriglyceridemia (obesity: RR 1.13 CI 0.96–1.32, P=0.151, hypertriglyceridemia: RR 0.96, CI 0.87–1.07, P=0.486).ConclusionsAlthough further prospective studies are required for confirmation, this meta-analysis indicated a strong relationship between MetS and pancreatic cancer. Regardless of gender, a greater risk of pancreatic cancer existed in people with MetS. Patients with MetS were more likely to develop pancreatic cancer, regardless of gender. Hypertension, hyperglycemia, and low HDL-c levels may largely account for this association. Further, the prevalence of pancreatic cancer was independent of obesity and hypertriglyceridemia.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022368980.
Research on COD measurement method based on UV-Vis absorption spectra of transmissive and reflective detection systems
Authors: Xu Xin , Wang Jihui , Li Jianan , Fan Axin , Zhang Yuhan , Xu Chang , Qin Haolin , Mu Feng , Xu Tingfa 
Published: April 2023

The world’s rapid industrialisation and population expansion have led to water pollution, causing significant disruption to the activities of humans, animals, and plants. Organic contamination content in water is commonly evaluated by measuring the chemical oxygen demand (COD). However, traditional COD detection methods often require additional reagents, resulting in secondary contamination and extended detection time. In this study, we propose and implement a reflective detection system that measures the UV-Vis absorption spectra of COD in water without contact measurement. We compared the modeling results of the transmissive and reflective detection systems using three regression analysis algorithms. We also assessed the modeling results using various spectral preprocessing and different feature selection bands. The results of the standard samples confirmed the viability of the reflective detection system for detecting COD, with the impressive coefficient of determination (R2) of 0.98892, the root mean square error (RMSE) of 2.86776, and the detection time of only 47.6 s. For the transmissive detection system, the R2 was 0.99976, the RMSE was 0.41979, and the detection time was 162.4 s. Overall, this study proposes two referenceable detection methods for measuring COD concentrations, which can be adapted to suit various job demands.
A novel prognostic related lncRNA signature associated with amino acid metabolism in glioma
Authors: Lei Qiang , Yuan Bo , Liu Kun , Peng Li , Xia Zhiwei 
Published: April 2023

BackgroundGlioma is one of the deadliest malignant brain tumors in adults, which is highly invasive and has a poor prognosis, and long non-coding RNAs (lncRNAs) have key roles in the progression of glioma. Amino acid metabolism reprogramming is an emerging hallmark in cancer. However, the diverse amino acid metabolism programs and prognostic value remain unclear during glioma progression. Thus, we aim to find potential amino-related prognostic glioma hub genes, elaborate and verify their functions, and explore further their impact on glioma.MethodsGlioblastoma (GBM) and low-grade glioma (LGG) patients’ data were downloaded from TCGA and CCGA datasets. LncRNAs associated with amino acid metabolism were discriminated against via correlation analysis. LASSO analysis and Cox regression analysis were conducted to identify lncRNAs related to prognosis. GSVA and GSEA were performed to predict the potential biological functions of lncRNA. Somatic mutation data and CNV data were further built to demonstrate genomic alterations and the correlation between risk scores. Human glioma cell lines U251 and U87-MG were used for further validation in vitro experiments.ResultsThere were eight amino-related lncRNAs in total with a high prognostic value that were identified via Cox regression and LASSO regression analyses. The high risk-score group presented a significantly poorer prognosis compared with the low risk-score group, with more clinicopathological features and characteristic genomic aberrations. Our results provided new insights into biological functions in the above signature lncRNAs, which participate in the amino acid metabolism of glioma. LINC01561 is one of the eight identified lncRNAs, which was adopted for further verification. In in vitro experiments, siRNA-mediated LINC01561 silencing suppresses glioma cells’ viability, migration, and proliferation.ConclusionNovel amino-related lncRNAs associated with the survival of glioma patients were identified, and a lncRNA signature can predict glioma prognosis and therapy response, which possibly has vital roles in glioma. Meanwhile, it emphasized the importance of amino acid metabolism in glioma, particularly in providing deeper research at the molecular level.