bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological shifts of salivary microbiota associated with metabolic-associated fatty liver disease
Authors: Wang Min , Yan Li-Ya , Qiao Cai-Yun , Zheng Chu-Chu , Niu Chen-Guang , Huang Zheng-Wei , Pan Yi-Huai
Published: February 2023

Introduction

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease related to metabolic syndrome. However, ecological shifts in the saliva microbiome in patients with MAFLD remain unknown. This study aimed to investigate the changes to the salivary microbial community in patients with MAFLD and explore the potential function of microbiota.

Methods

Salivary microbiomes from ten MAFLD patients and ten healthy participants were analyzed by 16S rRNA amplicon sequencing and bioinformatics analysis. Body composition, plasma enzymes, hormones, and blood lipid profiles were assessed with physical examinations and laboratory tests.

Results

The salivary microbiome of MAFLD patients was characterized by increased α-diversity and distinct β-diversity clustering compared with control subjects. Linear discriminant analysis effect size analysis showed a total of 44 taxa significantly differed between the two groups. Genera Neisseria, Filifactor, and Capnocytophaga were identified as differentially enriched genera for comparison of the two groups. Co-occurrence networks suggested that the salivary microbiota from MAFLD patients exhibited more intricate and robust interrelationships. The diagnostic model based on the salivary microbiome achieved a good diagnostic power with an area under the curve of 0.82(95% CI: 0.61–1). Redundancy analysis and spearman correlation analysis revealed that clinical variables related to insulin resistance and obesity were strongly associated with the microbial community. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to metabolism were more prevalent in the two groups.

Conclusions

Patients with MAFLD manifested ecological shifts in the salivary microbiome, and the saliva microbiome-based diagnostic model provides a promising approach for auxiliary MAFLD diagnosis.
Time domain adaptation of left ventricular diastolic intraventricular pressure in elite female ice hockey athletes
Authors: Yang Ping , Zhang Jianmei , Xue Jun , Bai Yunfei , Yang Hui , Zhang Ruiping , He Benxiang
Published: February 2023

Background

Ice hockey is a high-intensity dynamic sport for which competitive athletes train for longer than 20 hours each week for several years. The cumulative time of myocardial exposure to hemodynamic stress affects cardiac remodeling. However, the intracardiac pressure distribution of the elite ice hockey athletes' heart during adaptation to long-term training remains to be explored. This study aimed to compare the diastolic intraventricular pressure difference (IVPD) of the left ventricle (LV) between healthy volunteers and ice hockey athletes with different training times.

Methods

Fifty-three female ice hockey athletes (27 elite and 26 casual) and 24 healthy controls were included. The diastolic IVPD of the LV during diastole was measured by vector flow mapping. The peak amplitude of the IVPD during isovolumic relaxation (P0), diastolic rapid filling (P1), and atrial systole (P4); the difference in the peak amplitude between adjacent phases (DiffP01, DiffP14); the time interval between the peak amplitude of adjacent phases (P0P1, P1P4); and the maximum decrease rate in diastolic IVPD were calculated. Differences between groups, as well as correlations between hemodynamic parameters and training time, were analyzed.

Results

Structural parameters of the LV were significantly higher in elite athletes than in casual players and controls. No significant difference in the peak amplitude of the IVPD during the diastolic phase was found among the three groups. The analysis of covariance with heart rate as a covariate showed that P1P4 in the elite athlete and casual player groups was significantly longer than that in the healthy control group (p < 0.001 for all). An increased P1P4 was significantly associated with an increased training year (β = 4.90, p < 0.001).

Conclusions

The diastolic cardiac hemodynamics of the LV in elite female ice hockey athletes could be characterized by a prolonged diastolic IVPD, and P1P4 prolonged with an increase in the training years, reflecting a time–domain adaptation in diastolic hemodynamics after long-term training.
Microcirculatory tissue oxygenation correlates with kidney function after transcatheter aortic valve implantation–Results from a prospective observational study
Authors: Dietrich Maximilian , Antonovici Ana , Hölle Tobias , Nusshag Christian , Kapp Anne-Christine , Studier-Fischer Alexander , Arif Rawa , Nickel Felix , Weigand Markus Alexander , Frey Norbert , Lichtenstern Christoph , Leuschner Florian , Fischer Dania
Published: February 2023

Introduction

Kidney dysfunction is common in patients with aortic stenosis (AS) and correction of the aortic valve by transcatheter aortic valve implantation (TAVI) often affects kidney function. This may be due to microcirculatory changes.

Methods

We evaluated skin microcirculation with a hyperspectral imaging (HSI) system, and compared tissue oxygenation (StO2), near-infrared perfusion index (NIR), tissue hemoglobin index (THI) and tissue water index (TWI) in 40 patients undergoing TAVI versus 20 control patients. HSI parameters were measured before TAVI (t1), directly after TAVI (t2), and on postinterventional day 3 (t3). The primary outcome was the correlation of tissue oxygenation (StO2) to the creatinine level after TAVI.

Results

We performed 116 HSI image recordings in patients undergoing TAVI for the treatment of severe aortic stenosis and 20 HSI image recordings in control patients. Patients with AS had a lower THI at the palm (p = 0.034) and a higher TWI at the fingertips (p = 0.003) in comparison to control patients. TAVI led to an increase of TWI, but had no uniform enduring effect on StO2 and THI. Tissue oxygenation StO2 at both measurement sites correlated negatively with creatinine levels after TAVI at t2 (palm: ρ = −0.415; p = 0.009; fingertip: ρ = −0.519; p < 0.001) and t3 (palm: ρ = −0.427; p = 0.008; fingertip: ρ = −0.398; p = 0.013). Patients with higher THI at t3 reported higher physical capacity and general health scores 120 days after TAVI.

Conclusion

HSI is a promising technique for periinterventional monitoring of tissue oxygenation and microcirculatory perfusion quality, which are related to kidney function, physical capacity, and clinical outcomes after TAVI.

Clinical trial registration

https://drks.de/search/de/trial, identifier DRKS00024765.
A teachers’ based approach to assessing the perception of critical thinking in Education university students based on their age and gender
Authors: Galindo-Domínguez Héctor , Bezanilla María-José , Campo Lucía , Fernández-Nogueira Donna , Poblete Manuel
Published: February 2023

In the 21st century, critical thinking (CT) is regularly presented as one of the most important competences to be developed by a majority of educational institutions. Teachers are expected to change and enrich their teaching and learning methodologies so that students could face future challenges. Nonetheless, few are the instruments that measure the perception of critical thinking based on teachers’ conception. The aim of this study is to design and validate an instrument for the assessment of CT in university students based on the conception of CT that university teachers have. For this study, a total of 312 Spanish university students have participated. Based on a good model fit from a Confirmatory Factor Analysis and good reliability indices, the results provide strength to the theoretical model to evaluate critical thinking in university students formed by six dimensions (Analyzing/Organizing; Reasoning/Argumenting; Questioning/Asking oneself; Evaluating; Positioning /Taking decisions, and Acting /Committing oneself) and 42 items. Similarly, age was not a predictor variable for the different dimensions; while gender was statistically in favor of women in some of the dimensions, and tendentially, the dimension of Positioning/Taking decisions, in favor of men. However, despite these differences, the model guaranteed its factorial invariance. These findings have important pedagogical implications for universities in particular, and educational institutions in general, when developing curricula and teaching plans that focus on the development of students’ critical thinking.
The underlying cause of the simple virilizing phenotype in patients with 21-hydroxylase deficiency harboring P31L variant
Authors: Zhao Zhiyuan , Gao Yinjie , Lu Lin , Tong Anli , Chen Shi , Zhang Wei , Zhang Xiaoxia , Sun Bang , Wu Xueyan , Mao Jiangfeng , Wang Xi , Nie Min
Published: February 2023

Objective

To analyze the relationship between genotype and phenotype in 21-Hydroxylase deficiency patients harboring P31L variant and the underlying mechanism.

Methods

A total of 29 Chinese patients with 21-OHD harboring P31L variant were recruited, and the detailed clinical features of the patients were extracted and analyzed retrospectively. The TA clone combined with sequencing of the region containing the promotor and exon1 of CYP21A2 was performed to determine whether the variants in promotor and P31L aligned in cis. We further compared the clinical characteristics of 21-OHD patients between the promoter variant group and no promoter variant group.

Results

Among the 29 patients diagnosed with 21-OHD harboring P31L variant, the incidence of classical simple virilizing form was 62.1%. Thirteen patients owned promoter variants (1 homozygote and 12 heterozygote) and all exhibited SV form. The promoter variants and the P31L variant were located in the same mutant allele as validated by TA cloning and sequencing. There were statistically significant differences in clinical phenotype and 17-OHP level between the patients with and without promoter region variations (P<0.05).

Conclusion

There exists high incidence (57.4%) of SV form among the 21-OHD patients harboring P31L variant, and the underlying mechanism is partially due to both the promoter variants and P31L aligning in cis on one allele. Further sequencing of promoter region will provide important hints for the explanation of phenotype in patients harboring P31L.
Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones
Authors: Liu Haizhao , Cao Min , Jin Yutong , Jia Beitian , Wang Liming , Dong Mengxue , Han Lu , Abankwah Joseph , Liu Jianwei , Zhou Tao , Chen Baogui , Wang Yiyang , Bian Yuhong
Published: February 2023

Introduction

Kidney stone disease (KS) is a complicated disease with an increasing global incidence. It was shown that Bushen Huashi decoction (BSHS) is a classic Chinese medicine formula that has therapeutic benefits for patients with KS. However, its pharmacological profile and mechanism of action are yet to be elucidated.

Methods

The present study used a network pharmacology approach to characterize the mechanism by which BSHS affects KS. Compounds were retrieved from corresponding databases, and active compounds were selected based on their oral bioavailability (≥30) and drug-likeness index (≥0.18). BSHS potential proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas KS potential genes were obtained from GeneCards and OMIM, TTD, and DisGeNET. Gene ontology and pathway enrichment analysis were used to determine potential pathways associated with genes. The ingredients of BSHS extract were identified by the ultra‐high‐performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS). The network pharmacology analyses predicted the potential underlying action mechanisms of BSHS on KS, which were further validated experimentally in the rat model of calcium oxalate kidney stones.

Results

Our study found that BSHS reduced renal crystal deposition and improved renal function in ethylene glycol(EG)+ammonium chloride(AC)-induced rats, and also reversed oxidative stress levels and inhibited renal tubular epithelial cell apoptosis in rats. BSHS upregulated protein and mRNA expression of E2, ESR1, ESR2, BCL2, NRF2, and HO-1 in EG+AC-induced rat kidney while downregulating BAX protein and mRNA expression, consistent with the network pharmacology results.

Discussion

This study provides evidence that BSHS plays a critical role in anti-KS via regulation of E2/ESR1/2, NRF2/HO-1, and BCL2/BAX signaling pathways, indicating that BSHS is a candidate herbal drug for further investigation in treating KS.
STEK: A potential fast spectrum benchmark for fission product cross sections
Authors: van der Marck Steven , Koning Arjan
Published: February 2023

The reactivity worth of many fission product samples was measured in fast spectrum conditions in the STEK facility during the early 1970s. These results were then used to improve and validate nuclear data evaluations for fission products, but in the last 2 decades STEK has not been used: the nuclear data evaluations for fission products in the current versions of libraries like ENDF/B or JEFF have not been tested against STEK results. Here we argue that the STEK data are still valuable, because there is no other data set that can replace them, and the interest in fast spectrum conditions is picking up strongly of late. It should be considered to evaluate whether a benchmark can be defined for the International Reactor Physics Experiments Handbook.
Dynamic simulation of land use and land cover and its effect on carbon storage in the Nanjing metropolitan circle under different development scenarios
Authors: Tao Yu , Tian Lei , Wang Chun , Dai Wen
Published: February 2023

Land use and land cover (LULC) change is a pattern of alteration of the Earth’s land surface cover by human society and have a significant impact on the terrestrial carbon cycle. Optimizing the distribution of LULC is critical for the redistribution of land resources, the management of carbon storage in terrestrial ecosystems, and global climate change. We integrated the patch-generating land use simulation (PLUS) model and integrated valuation of ecosystem services and trade-offs (InVEST) model to simulate and assess future LULC and ecosystem carbon storage in the Nanjing metropolitan circle in 2030 under four scenarios: natural development (ND), economic development (ED), ecological protection (EP), and collaborative development (CD). The results showed that (1) LULC and carbon storage distribution were spatially heterogenous in the Nanjing metropolitan circle for the different scenarios, with elevation, nighttime lights, and population being the main driving factors of LULC changes; (2) the Nanjing metropolitan circle will experience a carbon increase of 0.50 Tg by 2030 under the EP scenario and losses of 1.74, 3.56, and 0.48 Tg under the ND, ED, and CD scenarios, respectively; and (3) the CD scenario is the most suitable for the development of the Nanjing metropolitan circle because it balances ED and EP. Overall, this study reveals the effects of different development scenarios on LULC and ecosystem carbon storage, and can provide a reference for policymakers and stakeholders to determine the development patterns of metropolitan areas under a dual carbon target orientation.
Effects of phosphorus application on soil phosphorus forms and phoD-harboring microbial communities in an alpine grassland on the Qinghai-Tibetan Plateau
Authors: Liu Dan , Song Xiaoyan , Liu Yang , Wang Changting
Published: February 2023

Phosphorus (P) application to terrestrial ecosystems affects not only aboveground plants but also soil P forms and phosphatase-associated microbes. The phoD gene is widespread in soil and plays an important role in P transformation. However, it is still unclear how phoD-harboring microbial communities respond to different P application rates, and the relationships between soil properties and phoD-harboring microbial community need to be better understood. In this study, the impacts of seven P application rates [0 (P0), 10 (P10), 20 (P20), 30 (P30), 40 (P40), 50 (P50), and 60 (P60) g⋅m–2⋅a–1] on the soil physicochemical properties, P forms, and phoD-harboring microbial communities were assessed. As the results, inorganic P (i.e., Resin-Pi, NaHCO3-Pi, NaOH-Pi, and HCl-Pi) and Bio-P increased firstly and then decreased with increasing P application rate, with the highest values in the P30 treatment. Soil phoD-harboring microbial community structures in low-P (P0∼P30) treatments were significantly different from that in high-P (P40∼P60) treatments. Soil phoD-harboring microbial Shannon and Simpson diversity increased firstly and then decreased with increasing P application rate, and there was a tipping point at the P application rate of 30 g⋅m–2⋅a–1. The Mantel test and structural equation modeling (SEM) revealed that Bio-P, TC (total carbon), Fe, NaOH-organic P (NaOH-Po), and soil pH were strongly related to the soil phoD-harboring microbial community structure. In conclusion, this study demonstrated that P application affected soil P forms and phoD-harboring microbes in an alpine grassland on the Qinghai-Tibetan Plateau, and there was a P application threshold for optimistic growth of phoD-harboring microbes in an alpine grassland on the Qinghai-Tibetan Plateau.
3PNMF-MKL: A non-negative matrix factorization-based multiple kernel learning method for multi-modal data integration and its application to gene signature detection
Authors: Mallik Saurav , Sarkar Anasua , Nath Sagnik , Maulik Ujjwal , Das Supantha , Pati Soumen Kumar , Ghosh Soumadip , Zhao Zhongming
Published: February 2023

In this current era, biomedical big data handling is a challenging task. Interestingly, the integration of multi-modal data, followed by significant feature mining (gene signature detection), becomes a daunting task. Remembering this, here, we proposed a novel framework, namely, three-factor penalized, non-negative matrix factorization-based multiple kernel learning with soft margin hinge loss (3PNMF-MKL) for multi-modal data integration, followed by gene signature detection. In brief, limma, employing the empirical Bayes statistics, was initially applied to each individual molecular profile, and the statistically significant features were extracted, which was followed by the three-factor penalized non-negative matrix factorization method used for data/matrix fusion using the reduced feature sets. Multiple kernel learning models with soft margin hinge loss had been deployed to estimate average accuracy scores and the area under the curve (AUC). Gene modules had been identified by the consecutive analysis of average linkage clustering and dynamic tree cut. The best module containing the highest correlation was considered the potential gene signature. We utilized an acute myeloid leukemia cancer dataset from The Cancer Genome Atlas (TCGA) repository containing five molecular profiles. Our algorithm generated a 50-gene signature that achieved a high classification AUC score (viz., 0.827). We explored the functions of signature genes using pathway and Gene Ontology (GO) databases. Our method outperformed the state-of-the-art methods in terms of computing AUC. Furthermore, we included some comparative studies with other related methods to enhance the acceptability of our method. Finally, it can be notified that our algorithm can be applied to any multi-modal dataset for data integration, followed by gene module discovery.
TNFR2 expression predicts the responses to immune checkpoint inhibitor treatments
Authors: Liao Ping , Jiang Mengmeng , Islam Md Sahidul , Wang Yiru , Chen Xin
Published: February 2023

Immune checkpoint inhibitors (ICIs) by targeting PD-1/PD-L1 or CTLA-4 have markedly improved the outcome of cancer patients. However, most solid tumor patients can’t benefit from such therapy. Identification of novel biomarkers to predict the responses of ICIs is crucial to enhance their therapeutic efficacy. TNFR2 is highly expressed by the maximally immunosuppressive subset of CD4+Foxp3+ regulatory T cells (Tregs), especially those present in tumor microenvironment (TME). Since Tregs represent a major cellular mechanism in tumor immune evasion, TNFR2 may be a useful biomarker to predict the responses to ICIs therapy. This notion is supported by our analysis of the computational tumor immune dysfunction and exclusion (TIDE) framework from published single-cell RNA-seq data of pan-cancer databases. The results show that, as expected, TNFR2 is highly expressed by tumor-infiltrating Tregs. Interestingly, TNFR2 is also expressed by the exhausted CD8 T cells in breast cancer (BRCA), hepatocellular carcinoma (HCC), lung squamous cell carcinoma (LUSC), and melanoma (MELA). Importantly, high expression of TNFR2 is associated with poor responses to the treatment with ICIs in BRCA, HCC, LUSC, and MELA. In conclusion, the expression of TNFR2 in TME may be a reliable biomarker for the precision of ICIs treatment of cancer patients, and this idea merits further research.
Priorities for ecological research on cetaceans in the Galápagos Islands
Authors: Palacios Daniel M. , Cantor Mauricio
Published: February 2023

Located in the eastern tropical Pacific, the Galápagos Islands are an oceanic insular ecosystem subject to strong environmental variability driven by local and regional processes. Past research has shown that such conditions can attract and sustain at least 23 cetacean species, out of which 14 are common, including nine Delphinids, one Ziphiid, one Physeterid, and three Balaenopterids. These species occupy both coastal and oceanic habitats, most are present year-round, and a few are migratory. However, research on cetaceans in Galápagos has been sporadic and chronically underfunded and is not currently considered a priority in the research agenda for Galápagos. Based on a review of existing information and an assessment of knowledge gaps, here we identify priorities for ecological research on cetaceans in Galápagos along five topical areas: 1) spatiotemporal occurrence, 2) population assessment, 3) health assessment, 4) social ecology, and 5) trophic ecology. Addressing these knowledge gaps will also help inform actions to preserve cetacean biodiversity and to manage human activities involving or affecting cetaceans in Galápagos. Given the logistical and funding challenges of conducting cetacean research in Galápagos, we recommend optimizing data sampling and accessibilityviaintegrated research protocols and open data repositories. We also recommend capitalizing on local citizen science activities, such as those conducted from cruise ships and whale-watching tours, which can serve as platforms of opportunity for obtaining basic data, thereby contributing to long-term data acquisition. Our proposed priorities should be assessed by Ecuadorian and Galápagos governmental institutions in broad and inclusive consultation with stakeholders and the scientific community prior to development and implementation of a research agenda. Collectively, these efforts will advance our understanding of the ecological role that marine megafauna, such as cetaceans, play in Galápagos and other oceanic islands, including maintaining large-scale connectivity and mitigating climate change.
Do intravitreal anti-vascular endothelial growth factor agents lead to renal adverse events? A pharmacovigilance real-world study
Authors: Jiang Lin , Peng Liying , Zhou Yangzhong , Chen Gang , Zhao Bin , Li Mingxi , Li Xuemei
Published: February 2023

Purpose

Intravitreal vascular endothelial growth factor (VEGF) blockade is essential in many macular edema diseases treatment. However, intravitreal VEGF treatment has been reported to lead to deteriorated proteinuria and renal function. This study aimed to explore the relationship between renal adverse events (AEs) and the intravitreal use of VEGF inhibitors.

Method

In the FDA’s Adverse Event Reporting System (FAERS) database, we searched for renal AEs of patients receiving various anti-VEGF drugs. We performed statistics on renal AEs in patients treated with Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab (from January 2004 to September 2022) using disproportionate and Bayesian analysis. We also investigated the time to onset, fatality, and hospitalization rates of renal AEs.

Results

We identified 80 reports. Renal AEs were most frequently associated with Ranibizumab (46.25%) and Aflibercept (42.50%). However, the association between intravitreal anti-VEGFs and renal AEs was insignificant since the reporting odds ratio of Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab were 0.23 (0.16, 0.32), 0.24 (0.11, 0.49), 0.37 (0.27, 0.51) and 0.15 (0.04, 0.61), respectively. The median time to renal AEs onsets was 37.5 (interquartile range 11.0–107.3) days. The hospitalization and fatality rates in patients who developed renal AEs were 40.24 and 9.76%, respectively.

Conclusion

There are no clear signals for the risk of renal AEs following various intravitreal anti-VEGF drugs based on FARES data.
Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics
Authors: Cardoso F. C. , Walker A. A. , King G. F. , Gomez M. V.
Published: February 2023

Introduction: Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. Phoneutria nigriventer, often referred to as the Brazilian wandering spider, banana spider or “armed” spider, is endemic to South America and amongst the most dangerous venomous spiders in the world. There are 4,000 envenomation accidents with P. nigriventer each year in Brazil, which can lead to symptoms including priapism, hypertension, blurred vision, sweating, and vomiting. In addition to its clinical relevance, P. nigriventer venom contains peptides that provide therapeutic effects in a range of disease models.

Methods: In this study, we explored the neuroactivity and molecular diversity of P. nigriventer venom using fractionation-guided high-throughput cellular assays coupled to proteomics and multi-pharmacology activity to broaden the knowledge about this venom and its therapeutic potential and provide a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We coupled proteomics with ion channel assays using a neuroblastoma cell line to identify venom compounds that modulate the activity of voltage-gated sodium and calcium channels, as well as the nicotinic acetylcholine receptor.

Results: Our data revealed that P. nigriventer venom is highly complex compared to other neurotoxin-rich venoms and contains potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides for which their activity and molecular target remains to be determined.

Discussion: Our findings provide a platform for studying the bioactivity of known and novel neuroactive components in the venom of P. nigriventer and other spiders and suggest that our discovery pipeline can be used to identify ion channel-targeting venom peptides with potential as pharmacological tools and to drug leads.
Psychological stress induces an increase in cholinergic enteric neuromuscular pathways mediated by glucocorticoid receptors
Authors: Blin Justine , Gautier Camille , Aubert Philippe , Durand Tony , Oullier Thibauld , Aymeric Laetitia , Naveilhan Philippe , Masson Damien , Neunlist Michel , Bach-Ngohou Kalyane
Published: February 2023

Introduction

Repeated acute stress (RASt) is known to be associated with gastrointestinal dysfunctions. However, the mechanisms underlying these effects have not yet been fully understood. While glucocorticoids are clearly identified as stress hormones, their involvement in RASt-induced gut dysfunctions remains unclear, as does the function of glucocorticoid receptors (GR). The aim of our study was to evaluate the involvement of GR on RASt-induced changes in gut motility, particularly through the enteric nervous system (ENS).

Methods

Using a murine water avoidance stress (WAS) model, we characterized the impact of RASt upon the ENS phenotype and colonic motility. We then evaluated the expression of glucocorticoid receptors in the ENS and their functional impact upon RASt-induced changes in ENS phenotype and motor response.

Results

We showed that GR were expressed in myenteric neurons in the distal colon under basal conditions, and that RASt enhanced their nuclear translocation. RASt increased the proportion of ChAT-immunoreactive neurons, the tissue concentration of acetylcholine and enhanced cholinergic neuromuscular transmission as compared to controls. Finally, we showed that a GR-specific antagonist (CORT108297) prevented the increase of acetylcholine colonic tissue level and in vivo colonic motility.

Discussion

Our study suggests that RASt-induced functional changes in motility are, at least partly, due to a GR-dependent enhanced cholinergic component in the ENS.
Association between bilirubin levels with incidence and prognosis of stroke: A meta-analysis
Authors: Zhao Kun , Wang Rui , Chen Rongrong , Liu Jialei , Ye Qing , Wang Kai , Li Juebao
Published: February 2023

Objective

Bilirubin has anti-inflammatory, antioxidant, and neuroprotective properties, but the association between bilirubin and stroke remains contentious. A meta-analysis of extensive observational studies on the relationship was conducted.

Methods

Studies published before August 2022 were searched in PubMed, EMBASE, and Cochrane Library. Cohort, cross-sectional and case-control studies that examined the association between circulating bilirubin and stroke were included. The primary outcome included the incidence of stroke and bilirubin quantitative expression level between stroke and control, and the secondary outcome was stroke severity. All pooled outcome measures were determined using random-effects models. The meta-analysis, subgroup analysis, and sensitivity analysis were performed using Stata 17.

Results

A total of 17 studies were included. Patients with stroke had a lower total bilirubin level (mean difference = −1.33 μmol/L, 95% CI: −2.12 to −0.53, P < 0.001). Compared with the lowest bilirubin level, total odds ratio (OR) of the highest bilirubin for the occurrence of stroke was 0.71 (95% CI: 0.61–0.82) and ischemic stroke was 0.72 (95% CI: 0.57–0.91), especially in cohort studies with accepted heterogeneity (I2 = 0). Serum total and direct bilirubin levels were significantly and positively associated with stroke severity. A stratified analysis based on gender showed that the total bilirubin level in males correlated with ischemic stroke or stroke, which was not noted in females.

Conclusion

While our findings suggest associations between bilirubin levels and stroke risk, existing evidence is insufficient to establish a definitive association. Better-designed prospective cohort studies should further clarify pertinent questions (PROSPERO registration number: CRD42022374893).
BMI growth trajectory from birth to 5 years and its sex-specific association with prepregnant BMI and gestational weight gain
Authors: Xie Jinting , Han Yan , Peng Lei , Zhang Jingjing , Gong Xiangjun , Du Yan , Ren Xiangmei , Zhou Li , Li Yuanhong , Zeng Ping , Shao Jihong
Published: February 2023

Objective

The purpose of the study was to identify the latent body mass index (BMI) z-score trajectories of children from birth to 5 years of age and evaluate their sex-specific association with prepregnant BMI and gestational weight gain (GWG).

Methods

This was a retrospective longitudinal cohort study performed in China. In total, three distinct BMI-z trajectories from birth to 5 years of age were determined for both genders using the latent class growth modeling. The logistic regression model was used to assess the associations of maternal prepregnant BMI and GWG with childhood BMI-z growth trajectories.

Results

Excessive GWG increased the risks of children falling into high-BMI-z trajectory relative to adequate GWG (OR = 2.04, 95% CI: 1.29, 3.20) in boys; girls born to mothers with prepregnancy underweight had a higher risk of low-BMI-z trajectory than girls born to mothers with prepregnancy adequate weight (OR = 1.85, 95% CI: 1.22, 2.79).

Conclusion

BMI-z growth trajectories of children from 0 to 5 years of age have population heterogeneity. Prepregnant BMI and GWG are associated with child BMI-z trajectories. It is necessary to monitor weight status before and during pregnancy to promote maternal and child health.
Undernutrition and associated factors among internally displaced lactating mothers in Sekota camps, northern Ethiopia: A cross-sectional study
Authors: Mengstie Misganaw Asmamaw , Worke Mulugeta Dile , Belay Yalemshet , Chekol Abebe Endeshaw , Asmamaw Dejenie Tadesse , Abdu Seid Mohammed , Azezew Muluken Teshome
Published: February 2023

Background

Undernutrition is the term used to describe when a person consumes insufficient amounts of nutrients and energy to meet their needs for maintaining health. Despite substantial progress, undernutrition remains a serious public health concern in many low and middle-income nations, including Ethiopia. Women and children are, in reality, the most nutritionally vulnerable individuals, particularly in times of crisis. In Ethiopia, 27 percent of lactating women are thin or malnourished, and 38% of children are stunted. Although the issue of undernutrition may worsen in times of emergency, like war, there are limited studies available in Ethiopia that show the nutritional status of lactating mothers in humanitarian settings.

Objectives

The main aim of this study was to determine the prevalence and investigate the factors associated with undernutrition among internally displaced lactating mothers in Sekota camps, in northern Ethiopia.

Methods

A cross-sectional study through a simple random sampling technique was conducted among 420 randomly selected lactating mothers in Sekota Internally Displaced Persons (IDP) camps. Data were collected using a structured questionnaire and anthropometric measurements. Logistic regression analysis was employed to identify independent factors associated with maternal undernutrition.

Results

Using a cut-off mid-upper arm circumference <23 cm, the prevalence of undernutrition among internally displaced lactating mothers was 54.8%. Large family size [adjusted odds ratio (AOR) = 4.35; 95% CI: 1.32, 10.22], short birth interval (AOR = 4.85; 95% CI: 1.24, 10.00), low maternal daily meal frequency (AOR = 2.54; 95% CI: 1.12, 5.75), and low dietary diversity score (AOR = 1.79; 95% CI: 1.03, 3.10) were all significantly associated with undernutrition.

Conclusion

The prevalence of undernutrition among internally displaced lactating mothers is relatively high. Governments and other concerned organizations involved in providing care and support to Sekota IDP camps should increase their efforts to improve the nutritional status of lactating mothers
Efficacy and safety of treatment regimens for patients with metastatic, locally advanced, or recurrent breast cancer carrying BRCA1/BRCA2 pathogenic variants: A network meta-analysis
Authors: Zhu Yingxuan , Li Yang , Liu Weida , Zhou Ruozhu , Tse Lap Ah , Wang Yang , Li Wei
Published: February 2023

Objective

Patients with breast cancer carrying BRCA1 and BRCA2 genetic alterations show poor prognoses. However, the efficacy of pharmacotherapies for patients with advanced breast cancer carrying BRCA1/2 pathogenic variants remains unclear. This study aimed to conduct a network meta-analysis to assess the efficacy and safety of various pharmacotherapies for patients with metastatic, locally advanced, or recurrent breast cancer carrying BRCA1/BRCA2 pathogenic variants.

Methods

A literature search was conducted using Embase, PubMed, and Cochrane Library (CENTRAL), from inception to 11th May 2022. The references of included articles were screened to identify relevant literature. This network meta-analysis included patients with metastatic locally advanced or recurrent breast cancer who received pharmacotherapy and carried deleterious variants of BRCA1/2. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed for conducting and reporting this systematic meta-analysis. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was employed to evaluate evidential certainty. Frequentist random-effect model was applied. Results of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and rates of any-grade adverse events were presented.

Results

Nine randomized controlled trials were obtained comprising six treatment regimens, including 1912 patients with pathogenic variants of BRCA1 and BRCA2. The orchestration of PARP inhibitors with platinum-based chemotherapy was found to be the most effective with a pooled odds ratio (OR) of 3.52 (95% CI 2.14, 5.78) for ORR; 1.53 (1.34,1.76), 3.05 (1.79, 5.19), and 5.80 (1.42, 23.77) for 3-, 12-, and 24-month PFS, respectively, and 1.04 (1.00, 1.07), 1.76 (1.25, 2.49) and 2.31 (1.41, 3.77) for 3-, 12-, and 36-month OS, respectively compared to those receiving non-platinum-based chemotherapy. However, it posed an elevated risk of some adverse events. Platinum-based chemotherapy alone or PARP inhibitors markedly improved ORR, PFS, and OS compared to non-platinum-based chemotherapy. Interestingly, platinum-based chemotherapy surpassed PARP inhibitors in terms of efficacy. Evidence on programmed death-ligand 1(PD-L1) inhibitors and sacituzumab govitecan (SG) suggested low quality and insignificant results.

Conclusions

Among all treatment regimens, PARP inhibitors with platinum exhibited the best efficacy, although with a trade-off of elevated risk of some types of adverse events. Future research on direct comparisons between different treatment regimens specifically targeting patients with breast cancer carrying BRCA1/2 pathogenic variants with a pre-specified adequate sample size is warranted.
Segmental chromosomal aberrations as the poor prognostic factor in children over 18 months with stage 3 neuroblastoma without MYCN amplification
Authors: Wieczorek Aleksandra , Szewczyk Katarzyna , Klekawka Tomasz , Stefanowicz Joanna , Ussowicz Marek , Drabik Grazyna , Pawinska-Wasikowska Katarzyna , Balwierz Walentyna
Published: February 2023

Introduction

Patients with stage 3 neuroblastoma (NBL) according to International Neuroblastoma Staging System (INSS) without MYCN amplification represent a heterogenous group with respect to disease presentation and prognosis.

Methods

Retrospective analysis of 40 stage 3 patients with NBL without MYCN amplification was performed. The prognostic value of age at diagnosis (under 18 vs over 18 months), International Neuroblastoma Pathology Classification (INPC) diagnostic category and presence of segmental or numerical chromosomes aberrations were evaluated, as well as biochemical markers. Array comparative genomic hybridization (aCGH) for analyzing copy number variations and Sanger sequencing for ALK point mutations were done.

Results

In 12 patients (two patients under 18 months), segmental chromosomal aberrations (SCA) were found and numerical chromosomal aberrations (NCA) were found in 16 patients (14 patients under 18 months). In children over 18 months SCA were more common (p=0.0001). Unfavorable pathology was significantly correlated with SCA genomic profile (p=0.04) and age over 18 months (p=0.008). No therapy failures occurred in children with NCA profile over or under 18 months or in children under 18 months, irrespective of pathology and CGH results. Three treatment failures occurred in the SCA group, in one patient CGH profile was not available. For the whole group at 3, 5 and 10-year OS and DFS were 0.95 (95% CI 0.81-0.99), 0.91 (95% CI 0.77-0.97) and 0.91 (95% CI 0.77-0.97), and 0.95 (95% CI 0.90-0.99), 0.92 (95% CI 0.85-0.98) and 0.86 (95% CI 0.78-0.97), respectively. DFS was significantly lower in the SCA group than in the NCA group (3-years, 5-years, and 10-years DFS 0.92 (95% CI 0.53-0.95), 0.80 (95% CI 0.40-0.95) and 0.60 (95% CI 0.16-0.87) vs 1.0, 1.0 and 1.0, respectively, p=0.005).

Conclusions

The risk of treatment failure was higher in patients with SCA profile, but only in patients over 18 months. All relapses occurred in children having obtained the complete remission, with no previous radiotherapy. In patients over 18 months, SCA profile should be taken into consideration for therapy stratification as it increases the risk of relapse and this group may require more intensive treatment.
Case Report: Add-on treatment with odevixibat in a new subtype of progressive familial intrahepatic cholestasis broadens the therapeutic horizon of genetic cholestasis
Authors: Pepe Angela , Colucci Angelo , Carucci Martina , Nazzaro Lucia , Bucci Cristina , Ranucci Giusy , Di Giorgio Angelo , Vajro Pietro , Mandato Claudia
Published: February 2023

Odevixibat, an ileal bile acid transporter (IBAT) inhibitor, is effective for the treatment of pruritus in children diagnosed with progressive familial intrahepatic cholestasis (PFIC) type 1 and 2. There are no studies showing the efficacy of Odevixibat in children with different subtypes of PFIC. We describe the case of a 6-year-old girl with chronic cholestatic jaundice. In the last 12 months laboratory data showed high serum levels of bilirubin (total bilirubin x 2.5 ULN; direct bilirubin x 1.7 ULN) and bile acids (sBA x 70 ULN), elevated transaminases (x 3–4 ULN), and preserved synthetic liver function. Genetic testing showed homozygous mutation in ZFYVE19 gene, which is not included among the classic causative genes of PFIC and determined a new non-syndromic phenotype recently classified as PFIC9 (OMIM # 619849). Due to the persistent intensity of itching [score of 5 (very severe) at the Caregiver Global Impression of Severity (CaGIS)] and sleep disturbances not responsive to rifampicin and ursodeoxycholic acid (UDCA), Odevixibat treatment was started. After treatment with odevixibat we observed: (i) reduction in sBA from 458 to 71 μmol/L (absolute change from baseline: −387 μmol/L), (ii) reduction in CaGIS from 5 to 1, and (iii) resolution of sleep disturbances. The BMI z-score progressively increased from −0.98 to +0.56 after 3 months of treatment. No adverse drug events were recorded. Treatment with IBAT inhibitor was effective and safe in our patient suggesting that Odevixibat may be potentially considered for the treatment of cholestatic pruritus also in children with rare subtypes of PFIC. Further studies on a larger scale could lead to the increasing of patients eligible for this treatment.
The TRPM4 channel inhibitor 9-phenanthrol alleviates cerebral edema after traumatic brain injury in rats
Authors: Ma Ping , Huang Ning , Tang Jun , Zhou Zunjie , Xu Jing , Chen Yi , Zhang Maoxin , Huang Qin , Cheng Yuan
Published: February 2023

Cerebral edema (CE) exerts an important effect on brain injury after traumatic brain injury (TBI). Upregulation of transient receptor potential melastatin 4 (TRPM4) in vascular endothelial cells (ECs) results in damage to capillaries and the blood-brain barrier (BBB), which is critical for the development of CE. Many studies have shown that 9-phenanthrol (9-PH) effectively inhibits TRPM4. The current study aimed to investigate the effect of 9-PH on reducing CE after TBI. In this experiment, we observed that 9-PH markedly reduced brain water content, BBB disruption, proliferation of microglia and astrocytes, neutrophil infiltration, neuronal apoptosis and neurobehavioral deficits. At the molecular level, 9-PH significantly inhibited the protein expression of TRPM4 and MMP-9, alleviated the expression of apoptosis-related molecules and inflammatory cytokines, such as Bax, TNF-α and IL-6, near injured tissue, and diminished serum SUR1 and TRPM4 levels. Mechanistically, treatment with 9-PH inhibited activation of the PI3K/AKT/NF-kB signaling pathway, which was reported to be involved in the expression of MMP-9. Taken together, the results of this study indicate that 9-PH effectively reduces CE and alleviates secondary brain injury partly through the following possible mechanisms: ①9-PH inhibits TRPM4-mediated Na + influx and reduces cytotoxic CE; ②9-PH hinders the expression and activity of MMP-9 by inhibiting the TRPM4 channel and decreases disruption of the BBB, thereby preventing vasogenic cerebral edema. ③9-PH reduces further inflammatory and apoptotic damage to tissues.
Can the use of magnetized water affect the seedling development and the metabolite profiles of two different species: Lentil and durum wheat?
Authors: Sestili Sara , Platani Cristiano , Palma Daniela , Dattoli Maria Assunta , Beleggia Romina
Published: February 2023

Seedlings of durum wheat and lentil were utilized to investigate the efficiency of magnetic water on growth and metabolic epicotyl profile. Tap water was passed through a magnetic device with a flow rate of max. 12900 - 13200 Gauss (G). Seeds and plantlets were grown on sand-free paper soaked by magnetized water, with unmagnetized tap water used in a control group. The growth parameters were collected at three time points (48, 96, and 144 hours after treatment), the same times at which metabolomic analysis was conducted on seeds, roots, and epicotyls. Although the effects varied with the species, tissues, and time point considered, compared with tap water (TW), the use of magnetized water treatment (MWT) led to higher root elongation in both genotypes. On the contrary, epicotyl length was not affected by treatment both in durum wheat and lentil. The results indicate that the use of magnetized water in agriculture can be considered a sustainable technology to promote plant development and quality with reduced and more efficient water usage, leading to cost-saving and environmental protection.
Reciprocal exchange orientation to organization, challenge stressor and construal level: Three-way interaction effects on voice behavior
Authors: Chen Long , Unsworth Kerrie L. , Zhang Li
Published: February 2023

This study extends our understanding of voice behavior by considering a more complete set of reciprocity antecedents. We add employees-organization reciprocal exchange orientation (EO REO) into the antecedent of voice behavior and clarify the boundary condition by examining the joint moderating role of challenge stressors and construal level. The presence of challenge stressors represents a positive work environment, thus employees with a strong EO REO are likely to reciprocate with voice. However, such stressors also lead employees to focus on how to deal with the current challenges, which only aligns with employees who have a low construal level mindset and prefer to think about the details of the job at hand. Hence, we hypothesized that the positive relationship between EO REO and voice behavior in the face of challenge stressors was more likely to exist for employees whose construal level is low rather than high. We collected data from 237 employee-supervisor matched dyads in study 1 and 225 employee-supervisor matched dyads in study 2. These two studies offered support for the three-way interaction hypothesis. Our studies further voice by extending the antecedent and delineating the boundary condition of challenge stressors and construal level.