bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life
Authors: Zhou Yan , Qiu Yali , Bao Wuping , Han Lei , Xue Yishu , Zhang Yingying , Tian Xue , Fu Qiang , Lv Chengjian , Yin Dongning , Zhang Min
Published: January 2023

Introduction

Asthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown.

Methods

We clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish “T2-high” asthma or OVA combined with ozone exposure (OVA + ozone) to induce “T2-low” asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed.

Results

Serum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV1%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (RL) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma.

Discussion

The potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.
Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines
Authors: Liu Shaojun , Tsun Joseph G. S. , Fung Genevieve P. G. , Lui Grace C. Y. , Chan Kathy Y. Y. , Chan Paul K. S. , Chan Renee W. Y.
Published: January 2023

Background

Immunity acquired from natural SARS-CoV-2 infection and vaccine wanes overtime. This longitudinal prospective study compared the effect of a booster vaccine (BNT162b2) in inducing the mucosal (nasal) and serological antibody between Covid-19 recovered patients and healthy unexposed subjects with two dose of mRNA vaccine (vaccine-only group).

Method

Eleven recovered patients and eleven gender-and-age matched unexposed subjects who had mRNA vaccines were recruited. The SARS-CoV-2 spike 1 (S1) protein specific IgA, IgG and the ACE2 binding inhibition to the ancestral SARS-CoV-2 and omicron (BA.1) variant receptor binding domain were measured in their nasal epithelial lining fluid and plasma.

Result

In the recovered group, the booster expanded the nasal IgA dominancy inherited from natural infection to IgA and IgG. They also had a higher S1-specific nasal and plasma IgA and IgG levels with a better inhibition against the omicron BA.1 variant and ancestral SARS-CoV-2 when compared with vaccine-only subjects. The nasal S1-specific IgA induced by natural infection lasted longer than those induced by vaccines while the plasma antibodies of both groups maintained at a high level for at least 21 weeks after booster.

Conclusion

The booster benefited all subjects to obtain neutralizing antibody (NAb) against omicron BA.1 variant in plasma while only the Covid-19 recovered subjects had an extra enrichment in nasal NAb against omicron BA.1 variant.
Evidence of resident coastal population(s) of false killer whales (Pseudorca crassidens) in northern Australian waters
Authors: Palmer Carol , Martien Karen K. , Raudino Holly , Robertson Kelly M. , Withers Alan , Withers Emma , Risk Robert , Cooper Dylan , D’Cruz Ellen , Jungine Edmund , Barrow Daniel , Cuff Nick , Lane Adrian , Keynes Daniel , Waples Kelly , Malpartida Allyson , Banks Sam
Published: January 2023

To help evaluate the distribution, residency, population size and structuring (and hence conservation status) of the poorly known false killer whalePseudorca crassidensin northern Australian waters, we undertook studies of sightings, movement patterns based on satellite telemetry, and genetics. Sighting data indicates that false killer whales are regular, year-round inhabitants of coastal areas of northern Australia. Satellite-tagged animals spent extended periods of time in shallow coastal waters, with no tagged animals leaving the continental shelf. The lack of spatial overlap in the areas visited by individuals tagged in the Arafura/Timor Seas compared to those tagged in the Gulf of Carpentaria suggests that there may be more than one population in northern Australia coastal waters. All 14 genetic samples collected across 1600 km of coastline possessed the same newly identified mitochondrial control region haplotype, designated haplotype 45. Notably, haplotype 45 is distinct from all previously published false killer whale haplotypes globally and is most similar to the two haplotypes that typify the endangered main Hawaiian Islands insular false killer whale population. Based on these results and evidence from recent movement records of those tagged, false killer whales in northern Australia are apparently demographically independent from the offshore population(s). Further assessment of the population conservation status is now required.
Symbiont-screener: A reference-free tool to separate host sequences from symbionts for error-prone long reads
Authors: Xu Mengyang , Guo Lidong , Qi Yanwei , Shi Chengcheng , Liu Xiaochuan , Chen Jianwei , Han Jinglin , Deng Li , Liu Xin , Fan Guangyi
Published: January 2023

Metagenomic sequencing facilitates large-scale constitutional analysis and functional characterization of complex microbial communities without cultivation. Recent advances in long-read sequencing techniques utilize long-range information to simplify repeat-aware metagenomic assembly puzzles and complex genome binning tasks. However, it remains methodologically challenging to remove host-derived DNA sequences from the microbial community at the read resolution due to high sequencing error rates and the absence of reference genomes. We here present Symbiont-Screener (https://github.com/BGI-Qingdao/Symbiont-Screener), a reference-free approach to identifying high-confidence host’s long reads from symbionts and contaminants and overcoming the low sequencing accuracy according to a trio-based screening model. The remaining host’s sequences are then automatically grouped by unsupervised clustering. When applied to both simulated and real long-read datasets, it maintains higher precision and recall rates of identifying the host’s raw reads compared to other tools and hence promises the high-quality reconstruction of the host genome and associated metagenomes. Furthermore, we leveraged both PacBio HiFi and nanopore long reads to separate the host’s sequences on a real host-microbe system, an algal-bacterial sample, and retrieved an obvious improvement of host assembly in terms of assembly contiguity, completeness, and purity. More importantly, the residual symbiotic microbiomes illustrate improved genomic profiling and assemblies after the screening, which elucidates a solid basis of data for downstream bioinformatic analyses, thus providing a novel perspective on symbiotic research.
Modified Valsalva maneuver after burr-hole drainage of chronic subdural hematomas: A single-center cohort study
Authors: Zeng Lang , Yu Jiasheng , Chen Rudong , Yang Hongkuan , Li Hua , Zeng Lingcheng , Wang Junhong , Xu Weidong , Hu Shengqi , Chen Kun
Published: January 2023

Background

Previous studies on the management of chronic subdural hematoma (cSDH) mainly focused on the risk of postoperative recurrence and measures to prevent it. In this study, we propose the use of a non-invasive postoperative treatment method, the modified Valsalva maneuver (MVM), as a means of reducing the recurrence of cSDH. This study aims to clarify the effects of MVM on functional outcomes and recurrence rates.

Methods

A prospective study was conducted at the Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2016 to December 2020. The study included 285 adult patients who underwent burr-hole drainage for the treatment of cSDH and received subdural drains. These patients were divided into two groups: the MVM group (n = 117) and the control group (n = 98). In the MVM group, patients received treatment with a customized MVM device for at least 10 times per hour, 12 h per day. The study's primary endpoint was the recurrence rate of SDH, while functional outcomes and morbidity 3 months after surgery were the secondary outcomes.

Results

In the current study, 9 out of 117 patients (7.7%) in the MVM group experienced a recurrence of SDH, while 19 out of 98 patients (19.4%, p < 0.05) in the HC group experienced a recurrence of SDH. Additionally, the infection rate of diseases such as pneumonia (1.7%) was significantly lower in the MVM group compared to the HC group (9.2%, p < 0.001, odds ratio (OR = 0.1). After 3 months of the surgery, 109 out of 117 patients (93.2%) in the MVM group achieved a favorable prognosis, compared to 80 out of 98 patients (81.6%) in the HC group (p = 0.008, with an OR of 2.9). Additionally, infection rate (with an OR of 0.2) and age (with an OR of 0.9) are independent predictors of a favorable prognosis at the follow-up stage.

Conclusions

The use of MVM in the postoperative management of cSDHs has been shown to be safe and effective, resulting in reduced rates of cSDH recurrence and infection following burr-hole drainage. These findings suggest that MVM treatment may lead to a more favorable prognosis at the follow-up stage.
Prognostic factors of traumatic optic neuropathy based on multimodal analysis—Especially the influence of postoperative dressing change and optic nerve blood supply on prognosis
Authors: Liu Xueru , Wang Jing , Zhang Wenyue , Li Lunhao , Zhang Leilei , Xiao Caiwen
Published: January 2023

Objective

To investigate the critical prognostic factors of patients with traumatic optic neuropathy (TON) treated with endoscopic transnasal optic canal decompression (ETOCD) and to perform multimodal analysis based on imaging examinations of optical coherence tomography angiography (OCTA) and CT scan. Subsequently, a new prediction model was established.

Methods

The clinical data of 76 patients with TON who underwent decompression surgery with the endoscope-navigation system in the Department of Ophthalmology, Shanghai Ninth People's Hospital from January 2018 to December 2021 were retrospectively analyzed. The clinical data included demographic characteristics, reasons for injury, interval between injury and surgery, multimode imaging information of CT scan and OCTA, including orbital fracture, optical canal fractures, vessel density of optic disc and macula, and the times of postoperative dressing change. Binary logistic regression was used to establish a model for best corrected visual acuity (BCVA) after treatment as a predictor of TON outcome.

Results

Postoperative BCVA improved in 60.5% (46/76) patients and did not improve in 39.5% (30/76) patients. The times of postoperative dressing change had a significant impact on the prognosis. Other factors affecting the prognosis were microvessel density of the central optic disc, the cause of injury, and the microvessel density above the macula. The area under the raw current curves of the predictive model was 0.7596.

Conclusions

The times of dressing changes after the operation, i.e., continuous treatment, is the key factor affecting prognosis. The microvessel density in the center of the optic disc and superior macula, quantitatively analyzed by OCTA, is the prognostic factor of TON and may be used as a prognostic marker of TON.
Manual acupuncture for neuromusculoskeletal disorders: The selection of stimulation parameters and corresponding effects
Authors: Wang Bing-Gan , Xu Liu-Liu , Yang Hua-Yuan , Xie Jian , Xu Gang , Tang Wen-Chao
Published: January 2023

As a minimally invasive method of physical stimulation, manual acupuncture (MA) is used globally as a sort of therapy for neuromusculoskeletal disorders. In addition to selecting appropriate acupoints, acupuncturists should also determine the stimulation parameters of needling, such as the manipulation (lifting-thrusting or twirling), needling amplitude, velocity, and stimulation time. At present, most studies focus on acupoint combination and mechanism of MA, the relationship between stimulation parameters and their therapeutic effects, as well as the influence on mechanism of action are relatively scattered, and lack of systematic summary and analysis. This paper reviewed the three types of stimulation parameters of MA, their common options and values, corresponding effects and potential mechanisms of action. The purpose of such efforts is to provide a useful reference for the dose-effect relationship of MA and the quantification and standardization of its clinical treatment of neuromusculoskeletal disorders to further promote the application of acupuncture in the world.
Heterogeneous recurrent spiking neural network for spatio-temporal classification
Authors: Chakraborty Biswadeep , Mukhopadhyay Saibal
Published: January 2023

Spiking Neural Networks are often touted as brain-inspired learning models for the third wave of Artificial Intelligence. Although recent SNNs trained with supervised backpropagation show classification accuracy comparable to deep networks, the performance of unsupervised learning-based SNNs remains much lower. This paper presents a heterogeneous recurrent spiking neural network (HRSNN) with unsupervised learning for spatio-temporal classification of video activity recognition tasks on RGB (KTH, UCF11, UCF101) and event-based datasets (DVS128 Gesture). We observed an accuracy of 94.32% for the KTH dataset, 79.58% and 77.53% for the UCF11 and UCF101 datasets, respectively, and an accuracy of 96.54% on the event-based DVS Gesture dataset using the novel unsupervised HRSNN model. The key novelty of the HRSNN is that the recurrent layer in HRSNN consists of heterogeneous neurons with varying firing/relaxation dynamics, and they are trained via heterogeneous spike-time-dependent-plasticity (STDP) with varying learning dynamics for each synapse. We show that this novel combination of heterogeneity in architecture and learning method outperforms current homogeneous spiking neural networks. We further show that HRSNN can achieve similar performance to state-of-the-art backpropagation trained supervised SNN, but with less computation (fewer neurons and sparse connection) and less training data.
Network pharmacology integrated with experimental validation to explore the therapeutic role and potential mechanism of Epimedium for spinal cord injury
Authors: Fu Xuanhao , Ma Boyuan , Zhou Mengmeng , Cheng Yuelin , Liu Linyan , Kan Shunli , Liu Chengjiang , Zhao Xinyan , Feng Sa , Zhu Haoqiang , Hu Wei , Jiang Zehua , Zhu Rusen
Published: January 2023

Objective

Epimedium (EPI) is a common Chinese herb with neuroprotective effects against a variety of central nervous system disorders, especially spinal cord injury (SCI). In this study, we performed network pharmacology and molecular docking analyses to reveal the mechanism underlying EPI treatment of SCI, then validated its efficacy using animal models.

Methods

The active ingredients and targets of EPI were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and their targets annotated on the UniProt platform. SCI-related targets were searched from OMIM, TTD, and GeneCards databases. We employed the STRING platform to construct a protein–protein interaction (PPI) network then visualized the results using Cytoscape (3.8.2) software. We also subjected key EPI targets to ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, then docked the main active ingredients with the key targets. Finally, we established an SCI rat model to evaluate efficacy of EPI in treating SCI and validate the effects of different biofunctional modules predicted by network pharmacology.

Results

A total of 133 EPI targets were associated with SCI. GO terms and KEGG pathway enrichment results showed that EPI’s effect in treating SCI was significantly associated with inflammatory response, oxidative stress and the PI3K/AKT signaling pathway. Molecular docking results indicated that EPI’s active ingredients have a high affinity for the key targets. Results from animal experiments revealed that EPI not only markedly improved Basso, Beattie, and Bresnahan scores in SCI rats, but also significantly improved p-PI3K/PI3K and p-AKT/AKT ratio. Moreover, EPI treatment not only mediated a significant decrease in malondialdehyde (MDA) but also increased both superoxide dismutase (SOD), and glutathione (GSH). However, this phenomenon was successfully reversed by LY294002, a PI3K inhibitor.

Conclusion

EPI improves behavioral performance in SCI rats through anti-oxidative stress, which may be mediated by activation of the PI3K/AKT signaling pathway.
Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer
Authors: Li Huihui , Wang Li , Zhang Wei , Dong Youting , Cai Yefeng , Huang Xiaoli , Dong Xubin
Published: January 2023

Breast cancer (BC) is one of the most common malignancies among women worldwide. It is necessary to search for improvement in diagnosis and treatment methods to improve the prognosis. Protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, has been studied in some tumors except BC. This study has explored that PKMYT1 functional role by bioinformatics methods combined with local clinical samples and experiments. Comprehensive analysis showed that PKMYT1 expression was higher in BC tissues, especially in advanced patients than that in normal breast tissues. The expression of PKMYT1 was an independent determinant for BC patients’ prognosis when combined with the clinical features. In addition, based on multi-omics analysis, we found that the PKMYT1 expression was closely relevant to several oncogenic or tumor suppressor gene variants. The analysis of single-cell sequencing indicated that PKMYT1 expression was upregulated in triple-negative breast cancer (TNBC), consistent with the results of bulk RNA-sequencing. High PKMYT1 expression was correlated with a poor prognosis. Functional enrichment analysis revealed that PKMYT1 expression was associated with cell cycle-related, DNA replication-related, and cancer-related pathways. Further research revealed that PKMYT1 expression was linked to immune cell infiltration in the tumor microenvironment. Additionally, loss-of-function experiments in vitro were performed to investigate the role of PKMYT1. TNBC cell lines’ proliferation, migration, and invasion were inhibited when PKMYT1 expression was knock-down. Besides, the down-regulation of PKMYT1 induced apoptosis in vitro. As a result, PKMYT1 might be a biomarker for prognosis and a therapeutic target for TNBC.
Baseline splenic volume as a biomarker for clinical outcome and circulating lymphocyte count in gastric cancer
Authors: Zeng Ziyang , Liu Zhen , Li Jie , Sun Juan , Ma Mingwei , Ye Xin , Yu Jianchun , Kang Weiming
Published: January 2023

Background

The spleen is the largest peripheral lymphoid organ in the body. Studies have implicated the spleen in the development of cancer. However, it is unknown whether splenic volume (SV) is associated with the clinical outcome of gastric cancer.

Methods

Data of gastric cancer patients treated with surgical resection were retrospectively analyzed. Patients were divided into three groups: underweight, normal-weight and overweight. Overall survival was compared in patients with high and low splenic volume. The correlation between splenic volume and peripheral immune cells were analyzed.

Results

Of 541 patients, 71.2% were male and the median age was 60. Underweight, normal-weight and overweight patients accounted for 5.4%, 62.3% and 32.3%, respectively. High splenic volume was associated with unfavorable prognosis across the three groups. In addition, the increase of splenic volume during neoadjuvant chemotherapy was not associated with prognosis. The baseline splenic volume was negatively correlated with lymphocytes (r=-0.21, p<0.001) and positively correlated with NLR (neutrophil-to-lymphocyte ratio) (r=0.24, p<0.001). In a group of patients (n=56), splenic volume was found to have negative correlation with CD4+T cells (r=-0.27, p=0.041) and NK cells (r=-0.30, p=0.025).

Conclusions

The presence of high splenic volume is a biomarker of unfavorable prognosis and reduced circulating lymphocytes in gastric cancer.
Transcriptome analysis reveals effects of leukemogenic SHP2 mutations in biosynthesis of amino acids signaling
Authors: Zhao Yuming , Chang Zhiguang , Hu Bingbing , Zhang Qi , Zhang Dengyang , He Chunxiao , Guo Yao , Peng Zhiyong , Chen Chun , Chen Yun
Published: January 2023

Gain-of-function mutations of SHP2, especially D61Y and E76K, lead to the development of neoplasms in hematopoietic cells. Previously, we found that SHP2-D61Y and -E76K confer HCD-57 cells cytokine-independent survival and proliferation via activation of MAPK pathway. Metabolic reprogramming is likely to be involved in leukemogenesis led by mutant SHP2. However, detailed pathways or key genes of altered metabolisms are unknown in leukemia cells expressing mutant SHP2. In this study, we performed transcriptome analysis to identify dysregulated metabolic pathways and key genes using HCD-57 transformed by mutant SHP2. A total of 2443 and 2273 significant differentially expressed genes (DEGs) were identified in HCD-57 expressing SHP2-D61Y and -E76K compared with parental cells as the control, respectively. Gene ontology (GO) and Reactome enrichment analysis showed that a large proportion of DEGs were involved in the metabolism process. Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis showed that DEGs were the mostly enriched in glutathione metabolism and biosynthesis of amino acids in metabolic pathways. Gene Set Enrichment Analysis (GSEA) revealed that the expression of mutant SHP2 led to a significant activation of biosynthesis of amino acids pathway in HCD-57 expressing mutant SHP2 compared with the control. Particularly, we found that ASNS, PHGDH, PSAT1, and SHMT2 involved in the biosynthesis of asparagine, serine, and glycine were remarkably up-regulated. Together, these transcriptome profiling data provided new insights into the metabolic mechanisms underlying mutant SHP2-driven leukemogenesis.
A new immune signature for survival prediction and immune checkpoint molecules in non-small cell lung cancer
Authors: Han Shuai , Jiang Dongjie , Zhang Feng , Li Kun , Jiao Kun , Hu Jingyun , Song Haihan , Ma Qin-Yun , Wang Jian
Published: January 2023

Background

Immune checkpoint blockade (ICB) therapy has brought remarkable clinical benefits to patients with advanced non-small cell lung carcinoma (NSCLC). However, the prognosis remains largely variable.

Methods

The profiles of immune-related genes for patients with NSCLC were extracted from TCGA database, ImmPort dataset, and IMGT/GENE-DB database. Coexpression modules were constructed using WGCNA and 4 modules were identified. The hub genes of the module with the highest correlations with tumor samples were identified. Then integrative bioinformatics analyses were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of NSCLC. Cox regression and Lasso regression analyses were conducted to screen prognostic signature and to develop a risk model.

Results

Functional analysis showed that immune-related hub genes were involved in the migration, activation, response, and cytokine-cytokine receptor interaction of immune cells. Most of the hub genes had a high frequency of gene amplifications. MASP1 and SEMA5A presented the highest mutation rate. The ratio of M2 macrophages and naïve B cells revealed a strong negative association while the ratio of CD8 T cells and activated CD4 memory T cells showed a strong positive association. Resting mast cells predicted superior overall survival. Interactions including protein–protein, lncRNA and transcription factor interactions were analyzed and 9 genes were selected by LASSO regression analysis to construct and verify a prognostic signature. Unsupervised hub genes clustering resulted in 2 distinct NSCLC subgroups. The TIDE score and the drug sensitivity of gemcitabine, cisplatin, docetaxel, erlotinib and paclitaxel were significantly different between the 2 immune-related hub gene subgroups.

Conclusions

These findings suggested that our immune-related genes can provide clinical guidance for the diagnosis and prognosis of different immunophenotypes and facilitate the management of immunotherapy in NSCLC.
Is percutaneous drainage better than endoscopic drainage in the management of patients with malignant obstructive jaundice? A meta-analysis of RCTs
Authors: Bian Cnogwen , Fang Yuan , Xia Jun , Shi Lan , Huang Hanfei , Xiong Qiru , Wu Ruolin , Zeng Zhong
Published: January 2023

To compare the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangial drainage (PTCD) in the treatment of malignant obstructive jaundice, a systematic review and meta-analysis of published studies was undertaken to assess the differences between the two procedures in terms of efficacy and safety. From November 2000 to November 2022, the Embase, PubMed, MEDLINE, and Cochrane databases were searched for randomized controlled trials (RCTs) on the treatment of malignant obstructive jaundice with ERCP or PTCD. Two investigators independently assessed the quality of the included studies and extracted the data. Six RCTs, including 407 patients, were included. The results of the meta-analysis showed that the overall technical success rate in the ERCP group was significantly lower than that in the PTCD group (Z=3.19, P=0.001, OR=0.31 (95% CI: 0.15-0.64)), but with a higher overall procedure-related complication incidence rate (Z=2.57, P=0.01, OR=0.55 (95% CI: 0.34-0.87)). The incidence of procedure-related pancreatitis in the ERCP group was higher than that in the PTCD group (Z=2.80, P=0.005, OR=5.29 (95% CI: 1.65-16.97)), and the differences were statistically significant. No significant difference was observed between the two groups when the clinical efficacy, postoperative cholangitis, and bleeding rate were compared.Both treatments for malignant obstructive jaundice were efficacious and safe. However, the PTCD group had a greater technique success rate and a lower incidence of postoperative pancreatitis.The present meta-analysis has been registered in PROSPERO
Targeted management of evolving and established chronic lung disease of prematurity assisted by cardiopulmonary ultrasound: A case report of four patients
Authors: Bruno Guglielmo , Chioma Roberto , Storti Enrico , De Luca Giovanni , Fantinato Margherita , Antonazzo Patrizio , Pierro Maria
Published: January 2023

Bronchopulmonary dysplasia (BPD) is one of the most common complications of premature birth. The current definition of BPD is based on the duration of oxygen therapy and/or respiratory support. Among the pitfalls of all the diagnostic definitions, the lack of a proper pathophysiologic classification makes it difficult to choose an appropriate drug strategy for BPD. In this case report, we describe the clinical course of four premature infants, admitted to the neonatal intensive care unit, for whom the use of lung and cardiac ultrasound was an integral part of the diagnostic and therapeutic process. We describe, for the first time to our knowledge, four different cardiopulmonary ultrasound patterns of evolving and established chronic lung disease of prematurity and the consequent therapeutic choices. This approach, if confirmed in prospective studies, may guide the personalized management of infants suffering from evolving and established BPD, optimizing the chances of success of the therapies and at the same time reducing the risk of exposure to inadequate and potentially harmful drugs.
Analysis of metabolites and metabolism-mediated biological activity assessment of ginsenosides on microfluidic co-culture system
Authors: Li Zhongyu , Li Jiwen , Sun Mei , Men Lei , Wang Enhua , Zhao Yiran , Li Keke , Gong Xiaojie
Published: January 2023

In vivo, the complex process of drugs metabolism alters the change in drug composition and determines the final pharmacological properties of oral drugs. Ginsenosides are primary constituents of ginseng, whose pharmacological activities are greatly affected by liver metabolism. However, the predictive power of existing in vitro models is poor due to their inability to mimic the complexity of drug metabolism in vivo. The advance of organs-on-chip-based microfluidics system could provide a new in vitro drug screening platform by recapitulating the metabolic process and pharmacological activity of natural product. In this study, an improved microfluidic device was employed to establish an in vitro co-culture model by culturing multiple cell types in compartmentalized microchambers. Different cell lines were seeded on the device to examine the metabolites of ginsenosides from the hepatocytes in top layer and its resulting efficacy on the tumors in bottom layer. Metabolism dependent drug efficacy of Capecitabine in this system demonstrated the model is validated and controllable. High concentrations of CK, Rh2 (S), and Rg3 (S) ginsenosides showed significant inhibitory effects on two types of tumor cells. In addition, apoptosis detection showed that Rg3 (S) through liver metabolism promoted early apoptosis of tumor cells and displayed better anticancer activity than prodrug. The detected ginsenoside metabolites indicated that some protopanaxadiol saponins were converted into other anticancer aglycones in varying degrees due to orderly de-sugar and oxidation. Ginsenosides exhibited different efficacy on target cells by impacting their viabilities, indicating hepatic metabolism plays an important role in determining ginsenosides efficacy. In conclusion, this microfluidic co-culture system is simple, scalable, and possibly widely applicable in evaluating anticancer activity and metabolism of drug during the early developmental phases of natural product.
Characteristics of drug safety alerts issued by the Spanish Medicines Agency
Authors: Montané Eva , Santesmases Javier
Published: January 2023

Objectives: To describe the characteristics of safety alerts issued by the Spanish Medicines Agency (AEMPS) and the Spanish Pharmacovigilance System over a 7-year period and the regulatory actions they generated.

Methods: A retrospective analysis was carried out of drug safety alerts published on the AEMPS website from 1 January 2013 to 31 December 2019. Alerts that were not drug-related or were addressed to patients rather than healthcare professionals were excluded.

Results: During the study period, 126 safety alerts were issued, 12 of which were excluded because they were not related to drugs or were addressed to patients and 22 others were excluded as they were duplications of previous alerts. The remaining 92 alerts reported 147 adverse drug reactions (ADRs) involving 84 drugs. The most frequent source of information triggering a safety alert was spontaneous reporting (32.6%). Four alerts (4.3%) specifically addressed health issues related to children. ADRs were considered serious in 85.9% of the alerts. The most frequent ADRs were hepatitis (seven alerts) and congenital malformations (five alerts), and the most frequent drug classes were antineoplastic and immunomodulating agents (23%). Regarding the drugs involved, 22 (26.2%) were “under additional monitoring.” Regulatory actions induced changes in the Summary of Product Characteristics in 44.6% of alerts, and in eight cases (8.7%), the alert led to withdrawal from the market of medicines with an unfavorable benefit/risk ratio.

Conclusion: This study provides an overview of drug safety alerts issued by the Spanish Medicines Agency over a 7-year period and highlights the contribution of spontaneous reporting of ADRs and the need to assess safety throughout the lifecycle of medicines.
Prx1 cell subpopulations identified in various tissues with diverse quiescence and activation ability following fracture and BMP2 stimulation
Authors: Liu Yu , Ilinski Adrian , Gerstenfeld Louis C. , Bragdon Beth
Published: January 2023

The expression of Prx1 has been used as a marker to define the skeletal stem cells (SSCs) populations found within the bone marrow and periosteum that contribute to bone regeneration. However, Prx1 expressing SSCs (Prx1-SSCs) are not restricted to the bone compartments, but are also located within the muscle and able to contribute to ectopic bone formation. Little is known however, about the mechanism(s) regulating Prx1-SSCs that reside in muscle and how they participate in bone regeneration. This study compared both the intrinsic and extrinsic factors of the periosteum and muscle derived Prx1-SSCs and analyzed their regulatory mechanisms of activation, proliferation, and skeletal differentiation. There was considerable transcriptomic heterogeneity in the Prx1-SSCs found in muscle or the periosteum however in vitro cells from both tissues showed tri-lineage (adipose, cartilage and bone) differentiation. At homeostasis, periosteal-derived Prx1 cells were proliferative and low levels of BMP2 were able to promote their differentiation, while the muscle-derived Prx1 cells were quiescent and refractory to comparable levels of BMP2 that promoted periosteal cell differentiation. The transplantation of Prx1-SCC from muscle and periosteum into either the same site from which they were isolated, or their reciprocal sites showed that periosteal cell transplanted onto the surface of bone tissues differentiated into bone and cartilage cells but was incapable of similar differentiation when transplanted into muscle. Prx1-SSCs from the muscle showed no ability to differentiate at either site of transplantation. Both fracture and ten times the BMP2 dose was needed to promote muscle-derived cells to rapidly enter the cell cycle as well as undergo skeletal cell differentiation. This study elucidates the diversity of the Prx1-SSC population showing that cells within different tissue sites are intrinsically different. While muscle tissue must have factors that promote Prx1-SSC to remain quiescent, either bone injury or high levels of BMP2 can activate these cells to both proliferate and undergo skeletal cell differentiation. Finally, these studies raise the possibility that muscle SSCs are potential target for skeletal repair and bone diseases.
Collecting wild potato species (Solanum sect. Petota) in Peru to enhance genetic representation and fill gaps in ex situ collections
Authors: Sotomayor Diego A. , Ellis David , Salas Alberto , Gomez Rene , Sanchez Rosa A. , Carrillo Fredesvinda , Giron Carolina , Quispe Violeta , Manrique-Carpintero Norma C. , Anglin Noelle L. , Zorrilla Cinthya
Published: January 2023

Crop wild relatives (CWRs) are important sources of novel genes, due to their high variability of response to biotic and abiotic stresses, which can be invaluable for crop genetic improvement programs. Recent studies have shown that CWRs are threatened by several factors, including changes in land-use and climate change. A large proportion of CWRs are underrepresented in genebanks, making it necessary to take action to ensure their long-term ex situ conservation. With this aim, 18 targeted collecting trips were conducted during 2017/2018 in the center of origin of potato (Solanum tuberosum L.), targeting 17 diverse ecological regions of Peru. This was the first comprehensive wild potato collection in Peru in at least 20 years and encompassed most of the unique habitats of potato CWRs in the country. A total of 322 wild potato accessions were collected as seed, tubers, and whole plants for ex situ storage and conservation. They belonged to 36 wild potato species including one accession of S. ayacuchense that was not conserved previously in any genebank. Most accessions required regeneration in the greenhouse prior to long-term conservation as seed. The collected accessions help reduce genetic gaps in ex situ conserved germplasm and will allow further research questions on potato genetic improvement and conservation strategies to be addressed. These potato CWRs are available by request for research, training, and breeding purposes under the terms of the International Treaty for Plant Genetic Resources for Food and Agriculture (ITPGRFA) from the Instituto Nacional de Innovacion Agraria (INIA) and the International Potato Center (CIP) in Lima-Peru.
Arbuscular mycorrhizal fungi affect the expression of PxNHX gene family, improve photosynthesis and promote Populus simonii×P. nigra growth under saline-alkali stress
Authors: Dong Fengxin , Wang Yihan , Tao Jing , Xu Tingying , Tang Ming
Published: January 2023

Introduction

Saline-alkali stress seriously endangers the normal growth of Populus simonii×P. nigra. Arbuscular mycorrhizal (AM) fungi can enhance the saline-alkali tolerance of plants by establishing a symbiotic relationship with them.

Methods

In this study, a pot experiment was conducted to simulate a saline-alkali environment where Populus simonii×P. nigra were inoculated with Funneliformis mosseae to explore their effects on the saline-alkali tolerance of Populus simonii×P. nigra.

Results and Discussion

Our results show that a total of 8 NHX gene family members are identified in Populus simonii×P. nigra. F. mosseae regulate the distribution of Na+ by inducing the expression of PxNHXs. The pH value of poplar rhizosphere soil is reduced, result in the promote absorption of Na+ by poplar, that ultimately improved the soil environment. Under saline-alkali stress, F. mosseae improve the chlorophyll fluorescence and photosynthetic parameters of poplar, promote the absorption of water, K+ and Ca2+, thus increase the plant height and fresh weight of aboveground parts, and promote the growth of poplar. Our results provide a theoretical basis for further exploring the application of AM fungi to improve the saline-alkali tolerance of plants.
Prevalence and correlates of dyslipidemia in first-episode and drug-naïve major depressive disorder patients with comorbid abnormal glucose metabolism: Sex differences
Authors: Zhu Quanfeng , Zheng Yali , Lang XiaoE , Fu Zhengchuang , Zhang Peng , Jiang Guojun , Zhang Xiangyang
Published: January 2023

Background

Lipid metabolism is associated with glucose metabolism, but whether there are variations between sexes in risk factors and prevalence of abnormal lipid metabolism in major depressive disorder (MDD) patients with glucose metabolism abnormalities remains ambiguous. In the present study, the frequency and risk factors of dyslipidemia in first-episode and drug-naïve (FEDN) MDD patients with dysglycemia were examined according to sex.

Methods

One thousand seven hundred and eighteen FEDN MDD patients were recruited and their demographic data, clinical data, various biochemical indicators and scale assessment scores including 17-item Hamilton Rating Scale for Depression (HAMD-17), 14-item Hamilton Anxiety Rating Scale (HAMA-14), and positive subscale of the Positive and Negative Syndrome Scale (PANSS) were collected.

Results

The prevalence of abnormal lipid metabolism in both male and female MDD patients with abnormal glucose metabolism was higher than that in patients without abnormal glucose metabolism. Among male MDD patients with abnormal glucose metabolism, TC was positively correlated with HAMD score, TSH and TgAb levels, but negatively correlated with PANSS positive subscale scores. LDL-C was positively correlated with TSH and BMI, but negatively correlated with PANSS positive subscale scores. HDL-C was negatively correlated with TSH levels. Among females, TC was positively correlated with HAMD score, TSH, and BMI, but negatively correlated with PANSS positive subscale score. LDL-C was positively correlated with HADM score and negatively correlated with FT3 level. HDL-C was negatively correlated with TSH and BMI levels.

Conclusion

There are sex differences in the correlated factors of lipid markers in MDD patients with impaired glucose.
Lower adherence to a prudent dietary pattern is associated with earlier age at menarche in adolescents from the Growth and Obesity Chilean Cohort Study
Authors: Martínez-Arroyo Angela , Cantor Erika , Fisberg Regina Mara , Corvalán Camila
Published: January 2023

Introduction

Early menarche is associated with obesity, and metabolic and mental health risks, among other diseases. Thus, it is relevant to identify modifiable risk factors of early menarche. Some nutrients and foods have been linked to pubertal timing, but how menarche relates to overall dietary patterns is unclear.

Methods

The aim of this study was to analyze the association between dietary patterns and age at menarche in a prospective cohort of Chilean girls from low and middle-income families. We conducted a survival analysis of 215 girls (median = 12.7 years, IQR = 12.2–13.2) from the Growth and Obesity Cohort Study (GOCS) who had been followed prospectively since 4 years of age (2006). Age at menarche and anthropometric measurements were recorded every 6 months since 7 years of age while diet (24-hour dietary recall) was collected for 11 years. Dietary patterns were obtained from exploratory factor analysis. Accelerated Failure Time models adjusted for potential confounding variables were used to study the association between dietary patterns and age at menarche.

Results

Girls' median age at menarche was 12.7 years. Three dietary patterns were identified: “Breakfast/Light Dinner,” “Prudent” and “Snacking” which explained 19.5% of the diet variation. Girls in the lowest tertile of the “Prudent” pattern had menarche 3 months earlier than girls in the highest tertile (β: 0.022; 95% CI: 0.003; 0.041). “Breakfast/Light Dinner” and “Snacking” patterns were not associated with age at menarche.

Conclusion

Our results suggest that healthier dietary patterns during puberty might be associated with menarche timing. Nevertheless, further studies are required to confirm this result and to clarify the association between diet and puberty.
Associations of COVID-19 vaccination during pregnancy with adverse neonatal and maternal outcomes: A systematic review and meta-analysis
Authors: Ding Cailin , Liu Yakun , Pang Wenbo , Zhang Dan , Wang Kai , Chen Yajun
Published: January 2023

Objectives

The low COVID-19 vaccine uptake rate among pregnant women is mainly due to safety concerns about COVID-19 vaccines due to limited safety evidence. Our goal was to evaluate the safety of COVID-19 vaccination during pregnancy with up-to-date evidence.

Methods

A comprehensive search of MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov was performed on April 5th, 2022, and updated on May 25th, 2022. Studies evaluating the association of COVID-19 vaccination during pregnancy with adverse maternal and neonatal outcomes were included. Two reviewers independently performed the risk of bias assessment and data extraction. Inverse variance random effect meta-analyses were performed to pool outcome data.

Results

Forty-three observational studies were included. COVID-19 vaccination [96,384 (73.9%) BNT162b2, 30,889 (23.7%) mRNA-1273, and 3,172 (2.4%) other types] during pregnancy [23,721 (18.3%) in the first trimester, 52,778 (40.5%) in the second trimester, and 53,886 (41.2%) in the third trimester].was associated with reduced risks of stillbirth or neonatal death (OR, 0.74; 95% CI, 0.60–0.92). Sensitivity analysis restricted to studies in participants without COVID-19 showed that the pooled effect was not robust. COVID-19 vaccination during pregnancy was not associated with congenital anomalies (OR, 0.83; 95% CI, 0.63–1.08), preterm birth (OR, 0.98; 95% CI, 0.90–1.06), NICU admission or hospitalization (OR, 0.94; 95% CI, 0.84–1.04), an Apgar score at 5 min <7 (OR, 0.93; 95% CI, 0.86–1.01), low birth weight (OR, 1.00; 95% CI, 0.88–1.14), miscarriage (OR, 0.99; 95% CI, 0.88–1.11), cesarean delivery (OR, 1.07; 95% CI, 0.96–1.19), or postpartum hemorrhage (OR, 0.91; 95% CI, 0.81–1.01).

Conclusions

COVID-19 vaccination during pregnancy was not associated with any of the adverse neonatal or maternal outcomes studied. Interpretation of study findings is limited by the types and timing of vaccination. The vaccinations in our study received during pregnancy were primarily mRNA vaccines administered in the second and third trimester. Future RCTs and meta-analysis are warranted to evaluate the efficacy and long-term effects of the COVID-19 vaccines.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322525, identifier: PROSPERO, CRD42022322525.
Six-week grit training course reduces school bullying: A quasi-experimental study
Authors: Wang Lei , Chen Qianqian , Peng Zhenzhen , Ye Caixia , Zhou Xinyi
Published: January 2023

Objective

To investigate the effectiveness of intervention programs in reducing school bullying, a 6-week series of grit training courses was designed and developed.

Methods

Using a quasi-experimental design, 163 middle school students were selected as the experimental group and 201 middle school students as the control group to test the implementation effect of the grit training course.

Results

The intervention program significantly reduced the traditional bullying behavior of the bullies and the traditional victimization of victims.

Conclusion

The 6-week grit course has produced positive results in reducing school bullying. In the future, school-based courses with the theme of grit can be designed to achieve the purpose of preventing school bullying by improving the positive qualities of individuals.