bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of the gastrointestinal microbiota to the protein metabolism of pond-cultured Japanese flounder (Paralichthys olivaceus)
Authors: Jiang Yan , Wang Jun , Lin Lin , Xu Yongjiang , Cui Aijun , Wang Kaijie , Liu Xuezhou , Wang Bin
Published: March 2023

Protein metabolism can provide energy for various biological activities of organisms. However, there have been few studies on the succession of gastrointestinal microbiota structure during the metabolism of protein by the host. In this study, physiological and biochemical, qRT-PCR, and 16S rDNA high throughput sequencing methods were used to detect the activity characteristics of proteases and the related gene expression levels in each gastrointestinal tissue, as well as the distribution characteristics and succession of the gastrointestinal microbiota structure of pond-cultured Japanese flounder (Paralichthys olivaceus). The results showed that the activity of pepsin, trypsin, and chymotrypsin in the pyloric caecum and gut, and the relative expression levels of the related genes, increased first and then decreased, but the aspartate aminotransferase (ASP) and alanine aminotransferase (ALA) activity showed the opposite tendency. These reflected that the nutrient composition of gastrointestinal tract contents was dynamic, which caused obvious changes to the alpha diversity and structure of gastrointestinal microbiota. Lactobacillus, Acinetobacter, Bacteroides, Escherichia-Shigella, Prevotella, the genera represented by the Lachnospiraceae_NK4A136_group and MND1, Sphingomonas, Alistipes, Alloprevotella, Enterobacter, Helicobacter, Myroides, Ruminiclostridium, and Romboutsia were the main gastrointestinal microbiota based on the dominance, commonality, and colonization. The relative abundance of Lactobacillus and Acinetobacter in the three gastrointestinal tissues increased first and then decreased. According to the number of shared and dominant genera, the consistency of succession of some genera, and the increase in the similarity of microbiota structure among the three tissues, we inferred that the microbiota was affected by the gastrointestinal tract nutrient composition. Gastrointestinal microbiota genes were mainly enriched in the metabolism pathway according to the KEGG pathway, and the ratio of Firmicutes to Bacteroidetes, the representative of energy accumulation, followed an at-first increasing and then decreasing trend in each tissue. This shows that the main gastrointestinal microbiota played a synergistic role in the energy accumulation of the host. This study will provide a reference for the development of high-efficiency compound feed formulae and improve feed efficiency by regulating the gastrointestinal tract microecology for pond-cultured Japanese flounder.
Improved fully convolutional neuron networks on small retinal vessel segmentation using local phase as attention
Authors: Kuang Xihe , Xu Xiayu , Fang Leyuan , Kozegar Ehsan , Chen Huachao , Sun Yue , Huang Fan , Tan Tao
Published: March 2023

Retinal images have been proven significant in diagnosing multiple diseases such as diabetes, glaucoma, and hypertension. Retinal vessel segmentation is crucial for the quantitative analysis of retinal images. However, current methods mainly concentrate on the segmentation performance of overall retinal vessel structures. The small vessels do not receive enough attention due to their small percentage in the full retinal images. Small retinal vessels are much more sensitive to the blood circulation system and have great significance in the early diagnosis and warning of various diseases. This paper combined two unsupervised methods, local phase congruency (LPC) and orientation scores (OS), with a deep learning network based on the U-Net as attention. And we proposed the U-Net using local phase congruency and orientation scores (UN-LPCOS), which showed a remarkable ability to identify and segment small retinal vessels. A new metric called sensitivity on a small ship (Sesv) was also proposed to evaluate the methods’ performance on the small vessel segmentation. Our strategy was validated on both the DRIVE dataset and the data from Maastricht Study and achieved outstanding segmentation performance on both the overall vessel structure and small vessels.
Unraveling the metabolic effects of benzophenone-3 on the endosymbiotic dinoflagellate Cladocopium goreaui
Authors: Zhang Kaidian , Shen Zhen , Yang Weilu , Guo Jianing , Yan Zhicong , Li Jiashun , Lin Jiamin , Cao Xiaocong , Tang Jia , Liu Zhaoqun , Zhou Zhi , Lin Senjie
Published: March 2023

As a well-known pseudo-persistent environmental pollutant, oxybenzone (BP-3) and its related organic ultraviolet (UV) filters have been verified to directly contribute to the increasing mortality rate of coral reefs. Previous studies have revealed the potential role of symbiotic Symbiodiniaceae in protecting corals from the toxic effects of UV filters. However, the detailed protection mechanism(s) have not been explained. Here, the impacts of BP-3 on the symbiotic Symbiodiniaceae Cladocopium goreaui were explored. C. goreaui cells exhibited distinct cell growth at different BP-3 doses, with increasing growth at the lower concentration (2 mg L–1) and rapid death at a higher concentration (20 mg L–1). Furthermore, C. goreaui cells showed a significant BP-3 uptake at the lower BP-3 concentration. BP-3 absorbing cells exhibited elevated photosynthetic efficiency, and decreased cellular carbon and nitrogen contents. Besides, the derivatives of BP-3 and aromatic amino acid metabolism highly responded to BP-3 absorption and biodegradation. Our physiological and metabolic results reveal that the symbiotic Symbiodiniaceae could resist the toxicity of a range of BP-3 through promoting cell division, photosynthesis, and reprogramming amino acid metabolism. This study provides novel insights into the influences of organic UV filters to coral reef ecosystems, which urgently needs increasing attention and management.
Altered cell function and increased replication of rhinoviruses and EV-D68 in airway epithelia of asthma patients
Authors: Essaidi-Laziosi Manel , Royston Léna , Boda Bernadett , Pérez-Rodriguez Francisco Javier , Piuz Isabelle , Hulo Nicolas , Kaiser Laurent , Clément Sophie , Huang Song , Constant Samuel , Tapparel Caroline
Published: March 2023

Introduction

Rhinovirus (RV) infections constitute one of the main triggers of asthma exacerbations and an important burden in pediatric yard. However, the mechanisms underlying this association remain poorly understood.

Methods

In the present study, we compared infections of in vitro reconstituted airway epithelia originating from asthmatic versus healthy donors with representative strains of RV-A major group and minor groups, RV-C, RV-B, and the respiratory enterovirus EV-D68.

Results

We found that viral replication was higher in tissues derived from asthmatic donors for all tested viruses. Viral receptor expression was comparable in non-infected tissues from both groups. After infection, ICAM1 and LDLR were upregulated, while CDHR3 was downregulated. Overall, these variations were related to viral replication levels. The presence of the CDHR3 asthma susceptibility allele (rs6967330) was not associated with increased RV-C replication. Regarding the tissue response, a significantly higher interferon (IFN) induction was demonstrated in infected tissues derived from asthmatic donors, which excludes a defect in IFN-response. Unbiased transcriptomic comparison of asthmatic versus control tissues revealed significant modifications, such as alterations of cilia structure and motility, in both infected and non-infected tissues. These observations were supported by a reduced mucociliary clearance and increased mucus secretion in non-infected tissues from asthmatic donors.

Discussion

Altogether, we demonstrated an increased permissiveness and susceptibility to RV and respiratory EV infections in HAE derived from asthmatic patients, which was associated with a global alteration in epithelial cell functions. These results unveil the mechanisms underlying the pathogenesis of asthma exacerbation and suggest interesting therapeutic targets.
Synergistic antibacterial effects of ultrasound combined nanoparticles encapsulated with cellulase and levofloxacin on Bacillus Calmette-Guérin biofilms
Authors: Zhang Zhifei , Zhang Yuqing , Yang Min , Hu Can , Liao Hongjian , Li Dairong , Du Yonghong
Published: March 2023

Tuberculosis is a chronic infectious disease, the treatment of which is challenging due to the formation of cellulose-containing biofilms by Mycobacterium tuberculosis (MTB). Herein, a composite nanoparticle loaded with cellulase (CL) and levofloxacin (LEV) (CL@LEV-NPs) was fabricated and then combined with ultrasound (US) irradiation to promote chemotherapy and sonodynamic antimicrobial effects on Bacillus Calmette-Guérin bacteria (BCG, a mode of MTB) biofilms. The CL@LEV-NPs containing polylactic acid-glycolic acid (PLGA) as the shell and CL and LEV as the core were encapsulated via double ultrasonic emulsification. The synthesized CL@LEV-NPs were uniformly round with an average diameter of 196.2 ± 2.89 nm, and the zeta potential of −14.96 ± 5.35 mV, displaying high biosafety and sonodynamic properties. Then, BCG biofilms were treated with ultrasound and CL@LEV-NPs separately or synergistically in vivo and in vitro. We found that ultrasound significantly promoted biofilms permeability and activated CL@LEV-NPs to generate large amounts of reactive oxygen species (ROS) in biofilms. The combined treatment of CL@LEV-NPs and US exhibited excellent anti-biofilm effects, as shown by significant reduction of biofilm biomass value and viability, destruction of biofilm architecture in vitro, elimination of biofilms from subcutaneous implant, and remission of local inflammation in vivo. Our study suggested that US combined with composite drug-loaded nanoparticles would be a novel non-invasive, safe, and effective treatment modality for the elimination of biofilm-associated infections caused by MTB.
Genetic characterization of four strains porcine circovirus-like viruses in pigs with diarrhea in Hunan Province of China
Authors: Ji Chihai , Zeng Meng , Wei Yingfang , Lv Xiaocheng , Sun Yuan , Ma Jingyun
Published: March 2023

In this study, we detected a circular replication-associated protein (Rep)-encoding single-stranded (CRESS) DNA virus [named Po-Circo-like (PCL) virus] in intestinal tissue and fecal samples of pigs. PCL virus contains a single-stranded DNA genome, and ORF1 encodes the Rep and not the typical capsid protein encoded in PCV. The Rep protein may be responsible for viral genome replication. In addition, PCL virus may be one of the pathogens causing diarrhea symptoms in pigs. We identified four strains of PCL virus in two different pig farms with severe diarrhea outbreaks in Hunan Province, China. The strains in this study share 85.7–99.7% nucleic acid identity and 84.7–100% amino acid identity with Rep of the reference strains. A multiple sequence alignment of these PCL viruses and Bo-Circo-like CH showed a identity of 93.2% for the Rep protein, and the nucleotide identity was 86.7–89.3%. Moreover, Bo-Circo-like CH and HN75, HN39-01, HN39-02 had similar stem-loop sequences. In conclusion, the present study is the first detailed report of the PCL virus in Hunan provinces, which is a potential new virus in pigs that might be involved in cross-species transmission. Further investigation is needed to determine the pathogenesis of this virus and its epidemiologic impact.
Altered neuroimaging patterns of cerebellum and cognition underlying the gait and balance dysfunction in cerebral small vessel disease
Authors: Mo Yuting , Mao Chenglu , Yang Dan , Ke Zhihong , Huang Lili , Yang Zhiyuan , Qin Ruomeng , Huang Yanan , Lv Weiping , Hu Zheqi , Xu Yun
Published: March 2023

Background

The mechanism of gait and balance dysfunction (GBD) in cerebral small vessel disease (CSVD) remains unclear. Evidence supports cognition engages in GBD of CSVD. The cerebellum is important in motor and cognition, while little is known about the influence of the cerebellum on GBD in CSVD.

Methods

This study is a retrospective cohort study. All participants of this study were enrolled from the CSVD individuals in Nanjing Drum Tower Hospital from 2017 to 2021. The GBD of CSVD patients was defined as Tinetti Test score ≤ 23. Cerebral cortical thickness, cerebellar gray matter volume, the amplitude of low-frequency fluctuation, functional connectivity, and modular interaction were calculated to determine the cortical atrophy and activity patterns of CSVD patients with GBD. The effect of cognitive domains during GBD in CSVD patients was explored by correlation analyses.

Results

A total of 25 CSVD patients were recruited in CSVD patients with GBD group (Tinetti Test score ≤ 23, mean age ± standard deviation: 70.000 ± 6.976 years), and 34 CSVD patients were recruited in CSVD patients without GBD group (Tinetti Test score > 23, mean age ± standard deviation: 64.029 ± 9.453 years). CSVD patients with GBD displayed worse cognitive performance and cortical atrophy in the right cerebellum VIIIa and bilateral superior temporal gyrus than those without GBD. The right postcentral gyrus, left inferior temporal gyrus, right angular gyrus, right supramarginal gyrus and right middle frontal gyrus were functionally overactivated and showed decreased modular interaction with the right cerebellum. Tinetti Test scores were negatively related to the volume of the right cerebellum VIIIa in CSVD patients with GBD. Notably, memory, especially visuospatial memory, was greatly associated with GBD in CSVD.

Conclusion

The cortical atrophy and altered functional activity in sensorimotor area and ventral attention network in the cerebellum and cerebrum may underlying the GBD in CSVD. Memory might be critically cognitively responsible for GBD in CSVD.
Neurochemical and microstructural alterations in bipolar and depressive disorders: A multimodal magnetic resonance imaging study
Authors: Kong Lingmei , Li Hui , Lin Fengfeng , Zheng Wenbin , Zhang Haidu , Wu Renhua
Published: March 2023

Aims

Depression in bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatments and poor clinical outcomes in many bipolar patients. Herein, we report direct comparisons between medication-free patients with BD and those with UD in terms of the microstructure and neurometabolites in eight brain regions.

Methods

A total of 20 patients with BD, 30 with UD patients, and 20 matched healthy controls (HCs) underwent 3.0T magnetic resonance imaging with chemical exchange saturation transfer (CEST) for glutamate (Glu; GluCEST) imaging, multivoxel magnetic resonance spectroscopy, and diffusion kurtosis imaging.

Results

Compared with HCs, patients with UD showed significantly lower levels of multiple metabolites, GluCEST% values, and diffusional kurtosis [mean kurtosis (MK)] values in most brain regions. In contrast, patients with BD presented significantly higher levels of Glu in their bilateral ventral prefrontal white matter (VPFWM), higher choline (Cho)-containing compounds in their left VPFWM and anterior cingulate cortex (ACC), and higher GluCEST% values in their bilateral VPFWM and ACC; moreover, reduced MK in these patients was more prominent in the left VPFWM and left thalamus.

Conclusion

The findings demonstrated that both patients with UD and BD have abnormal microstructure and metabolic alterations, and the changes are not completely consistent in the prefrontal lobe region. Elevated Glu, Cho, and GluCEST% in the ACC and VPFWM of patients with UD and BD may help in differentiating between these two disorders. Our findings support the significance for the microstructural integrity and brain metabolic changes of the prefrontal lobe region in BD and UD.
The connection between heart rate variability (HRV), neurological health, and cognition: A literature review
Authors: Arakaki Xianghong , Arechavala Rebecca J. , Choy Elizabeth H. , Bautista Jayveeritz , Bliss Bishop , Molloy Cathleen , Wu Daw-An , Shimojo Shinsuke , Jiang Yang , Kleinman Michael T. , Kloner Robert A.
Published: March 2023

The heart and brain have bi-directional influences on each other, including autonomic regulation and hemodynamic connections. Heart rate variability (HRV) measures variation in beat-to-beat intervals. New findings about disorganized sinus rhythm (erratic rhythm, quantified as heart rate fragmentation, HRF) are discussed and suggest overestimation of autonomic activities in HRV changes, especially during aging or cardiovascular events. When excluding HRF, HRV is regulated via the central autonomic network (CAN). HRV acts as a proxy of autonomic activity and is associated with executive functions, decision-making, and emotional regulation in our health and wellbeing. Abnormal changes of HRV (e.g., decreased vagal functioning) are observed in various neurological conditions including mild cognitive impairments, dementia, mild traumatic brain injury, migraine, COVID-19, stroke, epilepsy, and psychological conditions (e.g., anxiety, stress, and schizophrenia). Efforts are needed to improve the dynamic and intriguing heart-brain interactions.
A bibliometric analysis of traditional Chinese non-pharmacological therapies in the treatment of knee osteoarthritis from 2012 to 2022
Authors: Zhang Shouyao , Wang Yuanwang , Zhou Meng , Jia Shan , Liu Ye , Zhang Xinghe , Tai Xiantao
Published: March 2023

Objective

The benefits of traditional Chinese non-pharmacological therapies in the treatment of Knee osteoarthritis (KOA) are receiving increasing attention. Therefore, this study aims to systematically analyze the global research on the treatment of KOA by Chinese traditional non-pharmacological therapies using bibliometric analysis and present the results with a knowledge map form.

Methods

Literature related to traditional Chinese non-pharmacological therapies used in the treatment of KOA from 2012 to 2022 was searched from the Web of Science core database and PubMed database. CiteSpace, SCImago Graphica and VOSviewer were used to extract nations, institutions, journals, authors, references, keywords, as well as the most widely used acupoints, therapies and evaluation indexes.

Results

A total of 375 literature have been included. 32 countries around the world have participated in the research. China, the United States, and Europe were at the center of the global cooperation network. The most prolific institutions and authors were from China represented by Cun-zhi Liu and Jian-feng Tu of Beijing University of Chinese Medicine, the institution with the highest cited frequency was University of York, and “Osteoarthritis Cartilage” was the most frequently cited journal. The most frequently cited literature was “OARSI guidelines for the non-surgical management of knee, hip, and poly articular osteoarthritis.” 22 kinds of Chinese non-pharmacological therapies were used to treat KOA, among which acupuncture was the most commonly used one, and ST36 (Zusanli) and WOMAC were the most commonly selected acupoint and evaluation index.

Conclusion

In the past decade, the value of Chinese non-pharmacological therapies in the treatment of KOA has received widespread attention. It was a common concern of global researchers to relieve the pain of KOA patients and restore the quality of life. Under the background that acupuncture accounts for a relatively high proportion, the next step may consider how to make the balanced development of a variety of Chinese non-pharmacological therapies. In addition, the problem of how to eliminate the placebo effect maybe the direction of future research.
Neuronal representation of bimanual arm motor imagery in the motor cortex of a tetraplegia human, a pilot study
Authors: Lai Dongrong , Wan Zijun , Lin Jiafan , Pan Li , Ren Feixiao , Zhu Junming , Zhang Jianmin , Wang Yueming , Hao Yaoyao , Xu Kedi
Published: March 2023

Introduction

How the human brain coordinates bimanual movements is not well-established.

Methods

Here, we recorded neural signals from a paralyzed individual’s left motor cortex during both unimanual and bimanual motor imagery tasks and quantified the representational interaction between arms by analyzing the tuning parameters of each neuron.

Results

We found a similar proportion of neurons preferring each arm during unimanual movements, however, when switching to bimanual movements, the proportion of contralateral preference increased to 71.8%, indicating contralateral lateralization. We also observed a decorrelation process for each arm’s representation across the unimanual and bimanual tasks. We further confined that these changes in bilateral relationships are mainly caused by the alteration of tuning parameters, such as the increased bilateral preferred direction (PD) shifts and the significant suppression in bilateral modulation depths (MDs), especially the ipsilateral side.

Discussion

These results contribute to the knowledge of bimanual coordination and thus the design of cutting-edge bimanual brain-computer interfaces.
Prognostic factors and treatment outcomes of spinal osteosarcoma: Surveillance, epidemiology, and end results database analysis
Authors: Wang Jing , Ni Xiang-zhi , Yang Ming-lei , Huang Xing , Hou Shu-ming , Peng Cheng , Cao Jia-shi , Liu Tie-Long
Published: March 2023

Objective

Spinal osteosarcoma is a rare osseous neoplasm. The aim of this study is to make a comprehensive analysis of the demographic features, clinicopathologic characteristics and factors affecting prognosis of spinal osteosarcoma using the Surveillance, Epidemiology and End Results (SEER) database.

Methods

SEER data were reviewed to identify patients diagnosed with spinal osteosarcoma between 1975 and 2016 and determine their overall survival (OS) and disease-specifc survival (DSS). Univariate and multivariate analyses were performed using the Cox-regression proportional hazards model and Kaplan-Meier method.

Results

A total of 668 patients (53.1% males) with spinal osteosarcoma were identified. The mean age at diagnosis was 45.2 years, including 67.5% patients younger than 60 years. The median OS of these patients was 15 months, and the 5-year OS was 16.8%. Multivariate analysis showed that age ≥60 year (HR=2.271, p = 0.008), high grade (HR=1.323, p = 0.008), regional stage (HR=1.658, p = 0.017), metastasis stage (HR=3.045, p < 0.001) and no-surgery treatment (HR=1.761, p < 0.001) were adversely associated with OS; gender (HR=0.657, p = 0.044), tumor grade (HR=1.616, p = 0.006), tumor stage (HR=3.329, p = 0.011; HR=7.983, p < 0.001) and radiotherapy (HR=0.606, p = 0.031) were independent prognostic factors affecting DSS.

Conclusion

Based on SEER data analysis, male, high tumor grade, regional stage, metastasis stage and radiotherapy are independent predictors of poor survival of patients with spinal osteosarcoma. The clinical treatment of spinal osteosarcoma still faces serious challenges. Future research should focus on the clinical impact and survival outcomes of the emerging targeted and immune therapies for the sake of improving the survival stalemate of spinal osteosarcoma.
A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer
Authors: Miller Katie Joanna , Henry Isla , Maylin Zoe , Smith Christopher , Arunachalam Einthavy , Pandha Hardev , Asim Mohammad
Published: March 2023

Persistent androgen receptor (AR) signalling is the main driver of prostate cancer (PCa). Truncated isoforms of the AR called androgen receptor variants (AR-Vs) lacking the ligand binding domain often emerge during treatment resistance against AR pathway inhibitors such as Enzalutamide. This review discusses how AR-Vs drive a more aggressive form of PCa through the regulation of some of their target genes involved in oncogenic pathways, enabling disease progression. There is a pressing need for the development of a new generation of AR inhibitors which can repress the activity of both the full-length AR and AR-Vs, for which the knowledge of differentially expressed target genes will allow evaluation of inhibition efficacy. This review provides a detailed account of the most common variant, AR-V7, the AR-V7 regulated genes which have been experimentally validated, endeavours to understand their relevance in aggressive AR-V driven PCa and discusses the utility of the downstream protein products as potential drug targets for PCa treatment.
Identification of the mitophagy-related diagnostic biomarkers in hepatocellular carcinoma based on machine learning algorithm and construction of prognostic model
Authors: Tu Dao-yuan , Cao Jun , Zhou Jie , Su Bing-bing , Wang Shun-yi , Jiang Guo-qing , Jin Sheng-jie , Zhang Chi , Peng Rui , Bai Dou-sheng
Published: March 2023

Background and aims

As a result of increasing numbers of studies most recently, mitophagy plays a vital function in the genesis of cancer. However, research on the predictive potential and clinical importance of mitophagy-related genes (MRGs) in hepatocellular carcinoma (HCC) is currently lacking. This study aimed to uncover and analyze the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance.

Methods

In our research, by using Least absolute shrinkage and selection operator (LASSO) regression and support vector machine- (SVM-) recursive feature elimination (RFE) algorithm, six mitophagy genes (ATG12, CSNK2B, MTERF3, TOMM20, TOMM22, and TOMM40) were identified from twenty-nine mitophagy genes, next, the algorithm of non-negative matrix factorization (NMF) was used to separate the HCC patients into cluster A and B based on the six mitophagy genes. And there was evidence from multi-analysis that cluster A and B were associated with tumor immune microenvironment (TIME), clinicopathological features, and prognosis. After then, based on the DEGs (differentially expressed genes) between cluster A and cluster B, the prognostic model (riskScore) of mitophagy was constructed, including ten mitophagy-related genes (G6PD, KIF20A, SLC1A5, TPX2, ANXA10, TRNP1, ADH4, CYP2C9, CFHR3, and SPP1).

Results

This study uncovered and analyzed the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance. Based on the mitophagy-related diagnostic biomarkers, we constructed a prognostic model(riskScore). Furthermore, we discovered that the riskScore was associated with somatic mutation, TIME, chemotherapy efficacy, TACE and immunotherapy effectiveness in HCC patients.

Conclusion

Mitophagy may play an important role in the development of HCC, and further research on this issue is necessary. Furthermore, the riskScore performed well as a standalone prognostic marker in terms of accuracy and stability. It can provide some guidance for the diagnosis and treatment of HCC patients.
Case report: Tisagenlecleucel for treatment of relapsed B- acute lymphoblastic leukemia in a patient with CHEK2 mutation
Authors: Ipe Abraham , Angiolillo Anne , Jacobsohn David , Cheng Jinjun , Bornhorst Miriam , Turner Joyce , Vatsayan Anant
Published: March 2023

Background

Germline Checkpoint Kinase 2 gene (CHEK2) mutations can increase the risk of solid tumors. Recently, they have been identified as risk factors for hematologic malignancies. However, to the best of our knowledge, B-acute lymphoblastic leukemia (B-ALL) has never been described as a presenting manifestation of germline CHEK2 mutation. Chimeric antigen receptor-T (CAR-T) cell therapy directed against CD19 antigen (tisagenlecleucel) is a novel cellular therapy for treatment of relapsed/refractory (R/R) B-ALL. The use of tisagenlecleucel has not been described in patients with CHEK2 mutation.

Case Presentation

We describe a case of a pediatric patient with a heterozygous pathogenic germline CHEK2 mutation (c.1100delC; p.Thr367Metfs*15) successfully treated with tisagenlecleucel for relapsed B-ALL to avoid hematopoietic cell transplant (HCT). The twelve-year-old boy was diagnosed with National Cancer Institute (NCI) high-risk B-ALL (white blood cell count >50,000/mcL), with no extramedullary disease. Cytogenetic analysis revealed normal karyotype but fluorescent in situ hybridization (FISH) showed 93% positivity for CRLF2::P2RY8 rearrangement. He was treated as per Children's Oncology Group (COG) AALL1131 therapy and achieved a complete remission. Seven months after diagnosis, he was found to have papillary thyroid carcinoma with no evidence of metastatic disease. The patient underwent a total thyroidectomy with central lymph node biopsy and radioactive iodine therapy. The patient's biological mother and fraternal twin brother carry the same germline CHEK2 mutation with no history of malignancy. The biological father tested negative for the familial mutation. The patient's genetic panel also identified three variants of unclear significance: CDKN2A (c.37 °C > T; p.Arg124Cys), FLCN (c.62G > A; p.Cys21Tyr) and SDHAF2 (c.139A > G; p.Met47Val). Extended family history also revealed a diagnosis of anaplastic thyroid cancer in maternal uncle at the age of 44 years. Fifteen months after diagnosis the patient had a relapse of B-ALL (both medullary and extramedullary with blasts in CSF), which was successfully treated with tisagenlecleucel. The patient remains in remission 3 years after receiving tisagenlecleucel.

Conclusion

As conventional chemotherapy and radiation can potentially increase the risk of DNA damage and development of secondary malignancies, CD19 CAR-T therapy (tisagenlecleucel) can be used as a substitute for intensive re-induction chemotherapy and HCT in patients with a germline CHEK2 mutation.
Neuroimaging of brain connectivity related to reading outcomes in children born preterm: A critical narrative review
Authors: Kelly Kaitlyn J. , Hutton John S. , Parikh Nehal A. , Barnes-Davis Maria E.
Published: March 2023

Premature children are at high risk for delays in language and reading, which can lead to poor school achievement. Neuroimaging studies have assessed structural and functional connectivity by diffusion MRI, functional MRI, and magnetoencephalography, in order to better define the “reading network” in children born preterm. Findings point to differences in structural and functional connectivity compared to children born at term. It is not entirely clear whether this discrepancy is due to delayed development or alternative mechanisms for reading, which may have developed to compensate for brain injury in the perinatal period. This narrative review critically appraises the existing literature evaluating the neural basis of reading in preterm children, summarizes the current findings, and suggests future directions in the field.
Thoracoscopic approach for massive thymic hyperplasia in an infant: Case report and literature review
Authors: Jiao Jinghua , Yu Jie , Chen Chenghao , Chen Tian , Zheng Tiehua , He Lejian , Zeng Qi
Published: March 2023

Introduction

Massive thymic hyperplasia (MTH) is a very rare entity, with fewer than 20 cases reported in the literature in infancy. Most patients have respiratory symptoms and the enlarged thymus gland occupies one side of the thoracic cavity. Posterolateral thoracotomy or median sternotomy is the main treatment for MTH in infants. We report a case of an infant with MTH in which the enlarged thymus occupied his bilateral thoracic cavity and he underwent video-assisted thoracoscopic surgery (VATS). In addition, we reviewed and summarized the relevant literature.

Case Report

A 4-month-old boy was admitted to the hospital with no apparent cause of dyspnea for 18 days, with cough and sputum. On examination, the patient was found to have cyanotic lips, diminished breath sounds in both lungs, and a positive three concave sign. There was no fever or ptosis. Preoperative imaging showed large soft tissue shadows in the bilateral thoracic cavity, with basic symmetry between the right and left sides. Tumor markers were within the normal range. Ultrasound-guided fine needle biopsy showed normal thymic structures with no evidence of malignancy. As his symptoms worsened, he eventually underwent unilateral thoracic approach video-assisted thoracoscopic exploratory surgery, during which a large mass occupying the bilateral thoracic cavity was removed in a separate block and part of the thymus in the left lobe was preserved. Pathological examination confirmed true thymic hyperplasia (TTH). No relevant complications occurred at the 2-month postoperative follow-up.

Conclusion

In infants, MTH occupying the bilateral thoracic cavity can produce severe respiratory and circulatory symptoms due to occupying effects. Although a definitive preoperative diagnosis is sometimes difficult, after combining computed tomography (CT) and fine needle biopsy to exclude evidence of other malignancies, the enlarged thymus occupying the bilateral thoracic cavity can be resected via VATS. Whether the enlarged thymus occupies the bilateral thoracic cavity and the size of the thymus are not absolute contraindications to thoracoscopic surgery. The method is safe, feasible, and minimally invasive to the patient.
Role of traditional Chinese medicine in ameliorating mitochondrial dysfunction via non-coding RNA signaling: Implication in the treatment of neurodegenerative diseases
Authors: Cai Zhongdi , Liu Mimin , Zeng Li , Zhao Kaiyue , Wang Chenyu , Sun Ting , Li Zhuorong , Liu Rui
Published: March 2023

Neurodegenerative diseases (NDs) are common chronic disorders associated with progressive nervous system damage, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, among others. Mitochondria are abundant in various nervous system cells and provide a bulk supply of the adenosine triphosphate necessary for brain function, considered the center of the free-radical theory of aging. One common feature of NDs is mitochondrial dysfunction, which is involved in many physiopathological processes, including apoptosis, inflammation, oxidative stress, and calcium homeostasis. Recently, genetic studies revealed extensive links between mitochondrion impairment and dysregulation of non-coding RNAs (ncRNAs) in the pathology of NDs. Traditional Chinese medicines (TCMs) have been used for thousands of years in treating NDs. Numerous modern pharmacological studies have demonstrated the therapeutic effects of prescription, herbal medicine, bioactive ingredients, and monomer compounds of TCMs, which are important for managing the symptoms of NDs. Some highly effective TCMs exert protective effects on various key pathological features regulated by mitochondria and play a pivotal role in recovering disrupted signaling pathways. These disrupted signaling pathways are induced by abnormally-expressed ncRNAs associated with mitochondrial dysfunction, including microRNAs, long ncRNAs, and circular RNAs. In this review, we first explored the underlying ncRNA mechanisms linking mitochondrial dysfunction and neurodegeneration, demonstrating the implication of ncRNA-induced mitochondrial dysfunction in the pathogenesis of NDs. The ncRNA-induced mitochondrial dysfunctions affect mitochondrial biogenesis, dynamics, autophagy, Ca2+ homeostasis, oxidative stress, and downstream apoptosis. The review also discussed the targeting of the disease-related mitochondrial proteins in NDs and the protective effects of TCM formulas with definite composition, standardized extracts from individual TCMs, and monomeric compounds isolated from TCM. Additionally, we explored the ncRNA regulation of mitochondrial dysfunction in NDs and the effects and potential mechanisms of representative TCMs in alleviating mitochondrial pathogenesis and conferring anti-inflammatory, antioxidant, and anti-apoptotic pathways against NDs. Therefore, this review presents an overview of the role of mitochondrion-related ncRNAs and the target genes for TCM-based therapeutic interventions in NDs, providing insight into understanding the “multi-level compound-target-pathway regulatory” treatment mechanism of TCMs.
Engineered multi-functional, pro-angiogenic collagen-based scaffolds loaded with endothelial cells promote large deep burn wound healing
Authors: Song Hengyue , Gao Kewa , Hao Dake , Li Andrew , Liu Ruiwu , Anggito Bryan , Yin Boyan , Jin Qianyu , Dartora Vanessa , Lam Kit S. , Smith Lucas R. , Panitch Alyssa , Zhou Jianda , Farmer Diana L. , Wang Aijun
Published: March 2023

The lack of vascularization associated with deep burns delays the construction of wound beds, increases the risks of infection, and leads to the formation of hypertrophic scars or disfigurement. To address this challenge, we have fabricated a multi-functional pro-angiogenic molecule by grafting integrin αvβ3 ligand LXW7 and collagen-binding peptide (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY (LDS), and further employed this to functionalize collagen-based Integra scaffolds. Using a large deep burn wound model in C57/BLK6 mice (8–10 weeks old, 26–32g, n = 39), we demonstrated that LDS-modified collagen-based Integra scaffolds loaded with endothelial cells (ECs) accelerate wound healing rate, re-epithelialization, vascularization, and collagen deposition. Specifically, a 2 cm × 3 cm full-thickness skin burn wound was created 48 h after the burn, and then wounds were treated with four groups of different dressing scaffolds, including Integra + ECs, Integra + LDS, and Integra + LDS + ECs with Integra-only as the control. Digital photos were taken for wound healing measurement on post-treatment days 1, 7, 14, 21, 28, and 35. Post-treatment photos revealed that treatment with the Intgera + LDS + ECs scaffold exhibited a higher wound healing rate in the proliferation phase. Histology results showed significantly increased re-epithelialization, increased collagen deposition, increased thin and mixed collagen fiber content, increased angiogenesis, and shorter wound length within the Integra + LDS + ECs group at Day 35. On Day 14, the Integra + LDS + ECs group showed the same trend. The relative proportions of collagen changed from Day 14 to Day 35 in the Integra + LDS + ECs and Integra + ECs groups demonstrated decreased thick collagen fiber deposition and greater thin and mixed collagen fiber deposition. LDS-modified Integra scaffolds represent a promising novel treatment to accelerate deep burn wound healing, thereby potentially reducing the morbidity associated with open burn wounds. These scaffolds can also potentially reduce the need for autografting and morbidity in patients with already limited areas of harvestable skin.
Drought tolerance of Aspergillus violaceofuscus and Bacillus licheniformis and their influence on tomato growth and potassium uptake in mica amended tropical soils under water-limiting conditions
Authors: Muthuraja Raji , Muthukumar Thangavelu , Natthapol Chittamart
Published: March 2023

Drought is a significant abiotic stress that alters plant physiology and ultimately affects crop productivity. Among essential plant nutrients, potassium (K) is known to mitigate the deleterious effect of drought on plant growth. If so, K addition or inoculation of potassium solubilizing microorganisms (KSMs) that are tolerant to drought should promote plant growth during water stress. Therefore, in this study, K solubilizing Aspergillus violaceofuscus and Bacillus licheniformis, isolated from saxicolous environments, were tested for their capacity to tolerate drought using different molecular weights (~4000, 6000, and 8000 Da), and concentrations (0, 250, 500, 750, 1000, and 1250 mg/L) of polyethylene glycol (PEG) under in vitro conditions. The results showed that high concentrations (750 and 1000 mg/L) of PEG with different molecular weight considerably improved bacterial cell numbers/fungal biomass and catalase (CAT) and proline activities. Moreover, the ability of KSMs alone or in combination to impart drought tolerance and promote plant growth in the presence and absence of mica (9.3% K2O) supplementation was tested in Alfisol and Vertisol soil types under greenhouse conditions. The results revealed that the tomato plants inoculated with KSMs individually or dually with/without mica improved the physiological and morphological traits of the tomato plants under drought. Generally, tomato plants co-inoculated with KSMs and supplemented with mica were taller (2.62 and 3.38-fold) and had more leaf area (2.03 and 1.98-fold), total root length (3.26 and 8.86-fold), shoot biomass (3.87 and 3.93-fold), root biomass (9.00 and 7.24-fold), shoot K content (3.08 and 3.62-fold), root K content (3.39 and 2.03-fold), relative water content (1.51 and 1.27-fold), CAT activity (2.11 and 2.14-fold), proline content (3.41 and 3.28-fold), and total chlorophyll content (1.81 and 1.90-fold), in unsterilized Alfisol and Vertisol soil types, respectively, than uninoculated ones. Dual inoculation of the KSMs along with mica amendment, also improved the endorrhizal symbiosis of tomato plants more than their individual inoculation or application in both soil types. These findings imply that the A. violaceofuscus and B. licheniformis isolates are promising as novel bioinoculants for improving crop growth in water-stressed and rainfed areas of the tropics in the future.
The estimation and partitioning of evapotranspiration in a coniferous plantation in subtropical China
Authors: Xu Mingjie , Ma Qianhui , Li Shengtong , Yang Fengting , Zhang Tao , Xu Fei , Yang Bin , Zhang Hui , Zhang Shu , Wang Qianyu , Tang Yuanyuan , Wang Huimin
Published: March 2023

Accurate estimations of forest evapotranspiration (ET) and its components, transpiration (T) and evaporation (E), are important for deep understanding and predicting the responses of forest water cycles to climate change. In this study, the improved Shuttleworth-Wallace model (SWH) was applied to estimate ET, T, and E during 2003–2014 in a subtropical planation, and the modeled results were verified using in situ measurements by the eddy covariance technique, sap flow, and micro-lysimeter method. The study aimed to clarify whether it is feasible and reliable to use the SWH model to estimate and partition ET in forests. In addition, depending on the long-term data, the specific performances in modeling ET under different climatic backgrounds were investigated, and the underlying mechanisms were explored. The results verified that the SWH performed relatively well in the subtropical forest, and the modeled ET, T and E could track the seasonal variations, although overestimations were found in the peak seasons. However, the model was relatively weaker in estimating the interannual variabilities. It performed well in modeling ET in normal years but showed larger model residuals in years with obvious climatic anomalies. In the severe summer-drought (2003) and cold-spring (2005) years, the model greatly overestimated ET. It also overestimated ET in summer since 2010, which may be ascribed to the less dependency of ET on VPD induced by the more humid microclimate in forest accompanied with forest development. For the ET partitioning results, the modeled and measured E and T values were all in reasonable ranges. The possible reasons for underestimations (overestimations) of E and T by measurements (SWH model) were discussed. In this study, the data obtained using different methods and from different scales matched each other and could be cross validated, and the discussion on discrepancies would be beneficial for understanding the advantages and flaws of different methods and could be the basis for optimizing the measurement and model methods. In sum, this study verified that it is feasible to use the SWH model in forests and provided a basis for further improving and optimizing the modeled results under different climate backgrounds.
Identification of SNP loci and candidate genes genetically controlling norisoprenoids in grape berry based on genome-wide association study
Authors: Sun Qi , He Lei , Sun Lei , Xu Hai-Ying , Fu Ya-Qun , Sun Zheng-Yang , Zhu Bao-Qing , Duan Chang-Qing , Pan Qiu-Hong
Published: March 2023

Obtaining new grapevine varieties with unique aromas has been a long-standing goal of breeders. Norisoprenoids are of particular interest to wine producers and researchers, as these compounds are responsible for the important varietal aromas in wine, characterized by a complex floral and fruity smell, and are likely present in all grape varieties. However, the single-nucleotide polymorphism (SNP) loci and candidate genes genetically controlling the norisoprenoid content in grape berry remain unknown. To this end, in this study, we investigated 13 norisoprenoid traits across two years in an F1 population consisting of 149 individuals from a hybrid of Vitis vinifera L. cv. Muscat Alexandria and V. vinifera L. cv. Christmas Rose. Based on 568,953 SNP markers, genome-wide association analysis revealed that 27 candidate SNP loci belonging to 18 genes were significantly associated with the concentrations of norisoprenoid components in grape berry. Among them, 13 SNPs were confirmed in a grapevine germplasm population comprising 97 varieties, including two non-synonymous mutations SNPs within the VvDXS1 and VvGGPPS genes, respectively in the isoprenoid metabolic pathway. Genotype analysis showed that the grapevine individuals with the heterozygous genotype C/T at chr5:2987350 of VvGGPPS accumulated higher average levels of 6-methyl-5-hepten-2-one and β-cyclocitral than those with the homozygous genotype C/C. Furthermore, VvGGPPS was highly expressed in individuals with high norisoprenoids concentrations. Transient overexpression of VvGGPPS in the leaves of Vitis quinquangularis and tobacco resulted in an increase in norisoprenoid concentrations. These findings indicate the importance of VvGGPPS in the genetic control of norisoprenoids in grape berries, serving as a potential molecular breeding target for aroma.
The other side of COVID-19: A cross-sectional study on mental health in a sample of Italian nurses during the second wave
Authors: Renzi Erika , Imeshtari Valentin , Masud Dima , Baccolini Valentina , Migliara Giuseppe , Gasperini Giulia , De Vito Corrado , Marzuillo Carolina , Villari Paolo , Massimi Azzurra
Published: March 2023

Introduction

The COVID-19 pandemic has led to a drastic increase in the workload of healthcare professionals, particularly nurses, with serious consequences for their psychological well-being. Our study aimed to identify demographic and work-related factors, as well as clinical predictors of post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD), in nurses employed during the COVID-19 pandemic.

Methods

We carried out a cross-sectional study between December 2020 and April 2021 on nurses employed during the COVID-19 second wave (October - December 2020). We evaluated PTSD and GAD using two validated questionnaires: i) the Impact of Event Scale – Revised (IES-R); and ii) General Anxiety Disorder –7 (GAD-7).

Results

Overall, 400 nurses, whose mean age was 34.3 years (SD ± 11.7), were included in the study. Most were female (78.5%), unmarried (58.5%) and employed in the central (61.5%) regions of Italy. A total of 56.8% of all participants had clinical predictors of PTSD, recording a median IES-R score (IQR) of 37.0 (22.0, 51.0) (range 1-84; cut-off >33 for PTSD). Furthermore, 50% of respondents reported moderate-to-severe symptoms consistent with GAD, recording a median GAD-7 score (IQR) of 9.5 (6.0,14.0) (range 0-21; cut-off >10 for GAD). Multivariable analysis showed that moderate-to-severe GAD (aOR = 4.54, 95% CI: 2.93 - 7.05), being employed in the critical care area (aOR = 1.74, 95% CI: 1.01 - 3.00) and being female (aOR= 1.88, 95% CI: 1.09 - 3.22) were significantly associated with the presence of clinical predictors of PTSD.

Discussion

The levels of PTSD symptoms and anxiety among nurses were high during the pandemic. PTSD and GAD represent a public health problem that should be addressed in the post-pandemic period. Healthcare organizations need to activate specific support and rehabilitation networks and programs for healthcare professionals employed during the COVID-19 pandemic.