bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysfunction of the Auditory Brainstem as a Neurophysiology Subtype of Autism Spectrum Disorder
Authors: Chen Jierong , Wei Zhen , Liang Chun , Liu Binguang , Guo Jimin , Kong Xuejun , Huang Minshi , Peng Ziwen , Wan Guobin
Published: March 2021

Autism spectrum disorder (ASD) is very heterogeneous, particularly in language. Studies have suggested that language impairment is linked to auditory-brainstem dysfunction in ASD. However, not all ASD children have these deficits, which suggests potential subtypes of ASD. We classified ASD children into two subtypes according to their speech-evoked auditory brainstem response (speech-ABR) and explored the neural substrates for possible subtypes. Twenty-nine children with ASD and 25 typically developing (TD) peers were enrolled to undergo speech-ABR testing and structural magnetic resonance imaging (sMRI). There were significant differences between the ASD group and TD group in surface area, cortical volume and cortical thickness. According to speech-ABR results, ASD participants were divided into the ASD-typical (ASD-T) group and ASD-atypical (ASD-A) group. Compared with the ASD-T group, the ASD-A group had a lower score in language of the Gesell Developmental Diagnosis Scale (GDDS), increased left rostral middle frontal gyrus (lRMFG) area and decreased local gyrification index of the right superior temporal gyrus. GDDS-language and surface area of lRMFG were correlated to the wave-A amplitude in ASD. Surface area of lRMFG had an indirect effect on language performance via alteration of the wave-V amplitude. Thus, cortical deficits may impair language ability in children with ASD by causing subcortical dysfunction at preschool age. These evidences support dysfunction of the auditory brainstem as a potential subtype of ASD. Besides, this subtype-based method may be useful for various clinical applications.
Quantification of Cognitive Function in Alzheimer’s Disease Based on Deep Learning
Authors: He Yanxian , Wu Jun , Zhou Li , Chen Yi , Li Fang , Qian Hongjin
Published: March 2021

Alzheimer disease (AD) is mainly manifested as insidious onset, chronic progressive cognitive decline and non-cognitive neuropsychiatric symptoms, which seriously affects the quality of life of the elderly and causes a very large burden on society and families. This paper uses graph theory to analyze the constructed brain network, and extracts the node degree, node efficiency, and node betweenness centrality parameters of the two modal brain networks. The T test method is used to analyze the difference of graph theory parameters between normal people and AD patients, and brain regions with significant differences in graph theory parameters are selected as brain network features. By analyzing the calculation principles of the conventional convolutional layer and the depth separable convolution unit, the computational complexity of them is compared. The depth separable convolution unit decomposes the traditional convolution process into spatial convolution for feature extraction and point convolution for feature combination, which greatly reduces the number of multiplication and addition operations in the convolution process, while still being able to obtain comparisons. Aiming at the special convolution structure of the depth separable convolution unit, this paper proposes a channel pruning method based on the convolution structure and explains its pruning process. Multimodal neuroimaging can provide complete information for the quantification of Alzheimer’s disease. This paper proposes a cascaded three-dimensional neural network framework based on single-modal and multi-modal images, using MRI and PET images to distinguish AD and MCI from normal samples. Multiple three-dimensional CNN networks are used to extract recognizable information in local image blocks. The high-level two-dimensional CNN network fuses multi-modal features and selects the features of discriminative regions to perform quantitative predictions on samples. The algorithm proposed in this paper can automatically extract and fuse the features of multi-modality and multi-regions layer by layer, and the visual analysis results show that the abnormally changed regions affected by Alzheimer’s disease provide important information for clinical quantification.
Involvement of Astrocytes and microRNA Dysregulation in Neurodegenerative Diseases: From Pathogenesis to Therapeutic Potential
Authors: Bai Yang , Su Xing , Piao Lianhua , Jin Zheng , Jin Rihua
Published: March 2021

Astrocytes are the most widely distributed and abundant glial cells in the central nervous system (CNS). Neurodegenerative diseases (NDDs) are a class of diseases with a slow onset, progressive progression, and poor prognosis. Common clinical NDDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Although these diseases have different etiologies, they are all associated with neuronal loss and pathological dysfunction. Accumulating evidence indicates that neurotransmitters, neurotrophic factors, and toxic metabolites that are produced and released by activated astrocytes affect and regulate the function of neurons at the receptor, ion channel, antigen transfer, and gene transcription levels in the pathogenesis of NDDs. MicroRNAs (miRNAs) are a group of small non-coding RNAs that play a wide range of biological roles by regulating the transcription and post-transcriptional translation of target mRNAs to induce target gene expression and silencing. Recent studies have shown that miRNAs participate in the pathogenesis of NDDs by regulating astrocyte function through different mechanisms and may be potential targets for the treatment of NDDs. Here, we review studies of the role of astrocytes in the pathogenesis of NDDs and discuss possible mechanisms of miRNAs in the regulation of astrocyte function, suggesting that miRNAs may be targeted as a novel approach for the treatment of NDDs.
Case Report: Primary NK/T Cell Lymphoma Nasal Type of the Colon With Multiple Intestinal Perforations
Authors: Zhang Yan , Liu Weiping , Zhang Xinyue , Wu Bing
Published: March 2021

Background: Extranodal NK/T cell lymphoma is a rare non-Hodgkin lymphoma mainly involving the upper aerodigestive tract, even rarer is primary extranasal disease involving the intestine. We present a case of primary intestinal NK/T cell lymphoma with diagnostic challenge, which eventually developed into multiple intestinal perforations.

Case Presentation: A 35-year-old man presented with diarrhea and recurrent fever. Abdominal CT revealed multi-segmental intestinal wall thickening. Colonoscopy showed multiple irregular ulcers in colon. During the hospitalization, the patient developed intestinal perforation and an emergency surgery was performed. The resected specimen showed multiple perforations of the colon. The surgical samples underwent pathological analysis, and a diagnosis of extranodal NK/T cell lymphoma nasal type was confirmed. After recovering from surgery, the patient started receiving chemotherapy and PD-1 monoclonal antibody. Fortunately, he was discharged after significant improvement in his general condition. Eleven months follow-up was uneventful.

Conclusion: Early diagnosis of primary intestinal NK/T cell lymphoma is frequently difficult. Most patients were definitely diagnosed only after surgical resection following complications, resulting in a poor prognosis. Therefore, doctors should maintain high suspicion of this malignancy for early diagnosis at an early stage clinically.
Influence of Immune Microenvironment on Diagnosis and Prognosis of Head and Neck Squamous Cell Carcinoma
Authors: Liu Guohong , Yuan Chunjue , Ma Jiaojiao , Pan Yunbao , Xu Haibo
Published: March 2021

Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy accompanied by noted alterations in various immune cells and cytokines. Recognition of the immune system’s role in contributing to cancer development is an important advancement in our original understanding of carcinoma. We obtained HNSCC gene expression and clinical data from The Cancer Genome Atlas (TCGA) database. We assessed the relative proportion of 22 Infiltrating immune cell types in both HNSCC and adjacent non-cancer tissues using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, identifying the influence of the immune cells content in tumor staging and survival prediction. We further predicted the tumor purity, and the presence of infiltrating stromal/immune cells in HNSCC tissues using Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm, identifying its potential correlation with patient survival. Stromal and immune score-associated differentially expressed genes (DEGs) were subsequently verified and their roles in immune response were displayed by functional enrichment analysis and protein-protein interaction (PPI) network. Our research demonstrated the underlying association between the immune microenvironment and HNSCC, and the results were intended to serve as valuable terms for HNSCC diagnosis, prognosis, and targeted immune therapy.
Importance of Microvascular Invasion Risk and Tumor Size on Recurrence and Survival of Hepatocellular Carcinoma After Anatomical Resection and Non-anatomical Resection
Authors: Hu Haoyu , Qi Shuo , Zeng Silue , Zhang Peng , He Linyun , Wen Sai , Zeng Ning , Yang Jian , Zhang Weiqi , Zhu Wen , Xiang Nan , Fang Chihua
Published: March 2021

Purpose: To establish a valid prediction model to prognose the occurrence of microvascular invasion (MVI), and to compare the efficacy of anatomic resection (AR) or non-anatomic resection (NAR) for hepatocellular carcinoma (HCC).

Methods: Two hundred twenty-eight patients with HCC who underwent surgical treatment were enrolled. Their hematological indicators, MRI imaging features, and outcome data were acquired.

Result: In the multivariable analysis, alpha-fetoprotein >15 ng/mL, neutrophil to lymphocyte ratio >3.8, corona enhancement, and peritumoral hypointensity on hepatobiliary phase were associated with MVI. According on these factors, the AUROC of the predictive model in the primary and validation cohorts was 0.884 (95% CI: 0.829, 0.938) and 0.899 (95% CI: 0.821, 0.967), respectively. Patients with high risk of MVI or those with low risk of MVI but tumor size >5 cm in the AR group were associated with a lower rate of recurrence and death than patients in the NAR group; however, when patients are in the state of low-risk MVI with tumor size >5 cm, there is no difference in the rate of recurrence and death between AR and NAR.

Conclusion: Our predictive model for HCC with MVI is convenient and accurate. Patients with high-risk of MVI or low-risk of MVI but tumor size >5 cm executing AR is of great necessity.
Identification of a Novel Glycolysis-Related Gene Signature Correlates With the Prognosis and Therapeutic Responses in Patients With Clear Cell Renal Cell Carcinoma
Authors: Lv Zhengtong , Qi Lin , Hu Xiheng , Mo Miao , Jiang Huichuan , Li Yuan
Published: March 2021

Background

Accumulating evidences indicate significant alterations in the aerobic glycolysis in clear cell renal cell carcinoma (ccRCC). We aim to develop and validate a glycolysis-related genes signature for predicting the clinical outcomes of patients with ccRCC.

Methods

mRNA expression profiling of ccRCC was obtained from The Cancer Genome Atlas database. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. The protein expression levels of the core genes were obtained from the Human Protein Atlas database. We used four external independent data sets to verify the predictive power of the model for prognosis, tyrosine kinase inhibitor (TKI) therapy, and immunotherapy responses, respectively. Finally, we explored the potential mechanism of this signature through gene set enrichment analysis (GSEA).

Results

Through the GSEA, glycolysis-related gene sets were significantly different between ccRCC tissues and normal tissues. Next, we identified and constructed a seven-mRNA signature (GALM, TGFA, RBCK1, CD44, HK3, KIF20A, and IDUA), which was significantly correlated with worse survival outcome and was an independent prognostic indicator for ccRCC patients. Furthermore, the expression levels of hub genes were validated based on the Human Protein Atlas databases. More importantly, the model can predict patients’ response to TKI therapy and immunotherapy. These findings were successfully validated in the external independent ccRCC cohorts. The mechanism exploration showed that the model may influence the prognosis by influencing tumor proliferation, base mismatch repair system and immune status of patients.

Conclusions

Our study has built up a robust glycolysis-based molecular signature that predicts the prognosis and TKI therapy and immunotherapy responses of patients with ccRCC with high accuracy, which might provide important guidance for clinical assessment. Also, clinical investigations in large ccRCC cohorts are greatly needed to validate our findings.
Progressive Study on the Non-thermal Effects of Magnetic Field Therapy in Oncology
Authors: Xu Aoshu , Wang Qian , Lv Xin , Lin Tingting
Published: March 2021

Cancer is one of the most common causes of death worldwide. Although the existing therapies have made great progress and significantly improved the prognosis of patients, it is undeniable that these treatment measures still cause some serious side effects. In this context, a new treatment method is needed to address these shortcomings. In recent years, the magnetic fields have been proposed as a novel treatment method with the advantages of less side effects, high efficiency, wide applications, and low costs without forming scars. Previous studies reported that static magnetic fields (SMFs) and low-frequency magnetic fields (LF-MFs, frequency below 300 Hz) exert anti-tumor function, independent of thermal effects. Magnetic fields (MFs) could inhibit cell growth and proliferation; induce cell cycle arrest, apoptosis, autophagy, and differentiation; regulate the immune system; and suppress angiogenesis and metastasis via various signaling pathways. In addition, they are effective in combination therapies: MFs not only promote the absorption of chemotherapy drugs by producing small holes on the surface of cell membrane but also enhance the inhibitory effects by regulating apoptosis and cell cycle related proteins. At present, MFs can be used as drug delivery systems to target magnetic nanoparticles (MNPs) to tumors. This review aims to summarize and analyze the current knowledge of the pre-clinical studies of anti-tumor effects and their underlying mechanisms and discuss the prospects of the application of MF therapy in cancer prevention and treatment.
Clinical Outcomes for Patients With Metastatic Breast Cancer Treated With Immunotherapy Agents in Phase I Clinical Trials
Authors: Schreiber Anna R. , Kagihara Jodi A. , Weiss Jennifer A. , Nicklawsky Andrew , Gao Dexiang , Borges Virginia F. , Kabos Peter , Diamond Jennifer R.
Published: March 2021

Background

Immuno-oncology (IO) agents have demonstrated efficacy across many tumor types and have led to change in standard of care. In breast cancer, atezolizumab and pembrolizumab were recently FDA-approved in combination with chemotherapy specifically for patients with PD-L1-positive metastatic triple-negative breast cancer (TNBC). However, the single agent PD-1/PD-L1 inhibitors demonstrate only modest single agent efficacy in breast cancer. The purpose of this study was to investigate the efficacy of novel IO agents in patients with metastatic breast cancer (MBC), beyond TNBC, treated in phase I clinical trials at the University of Colorado.

Methods

We performed a retrospective analysis using a database of patients with MBC who received treatment with IO agents in phase I/Ib clinical trials at the University of Colorado Hospital from January 1, 2012 to July 1, 2018. Patient demographics, treatments and clinical outcomes were obtained.

Results

We identified 43 patients treated with an IO agent either as a single agent or in combination. The average age was 53 years; 55.8% had hormone receptor-positive/HER2-negative breast cancer, 39.5% TNBC and 4.7% HER2-positive. Patients received an average of 2 prior lines of chemotherapy (range 0-7) in the metastatic setting. Most patients (72.1%) received IO alone and 27.9% received IO plus chemotherapy. Median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 12.1 months. Patients remaining on study ≥ 6 months (20.9%) were more likely to be treated with chemotherapy plus IO compared to patients with a PFS < 6 months (77.8% v. 14.7%). No differences in number of metastatic sites, prior lines of chemotherapy, breast cancer subtype, absolute lymphocyte count, or LDH were identified between patients with a PFS ≥ 6 months vs. < 6 months.

Conclusions

Our phase I experience demonstrates benefit from IO therapy that was not limited to patients with TNBC and confirms improved efficacy from IO agents in combination with chemotherapy. A subset of patients with MBC treated in phase I clinical trials with an IO agent derived prolonged clinical benefit. Predictors of response to immunotherapy in breast cancer remain uncharacterized and further research is needed to identify these factors.
Barriers and Facilitators for Implementing Paediatric Telemedicine: Rapid Review of User Perspectives
Authors: Tully Louise , Case Lucinda , Arthurs Niamh , Sorensen Jan , Marcin James P. , O'Malley Grace
Published: March 2021

Background: COVID-19 has brought to the fore an urgent need for secure information and communication technology (ICT) supported healthcare delivery, as the pertinence of infection control and social distancing continues. Telemedicine for paediatric care warrants special consideration around logistics, consent and assent, child welfare and communication that may differ to adult services. There is no systematic evidence synthesis available that outlines the implementation issues for incorporating telemedicine to paediatric services generally, or how users perceive these issues.

Methods: We conducted a rapid mixed-methods evidence synthesis to identify barriers, facilitators, and documented stakeholder experiences of implementing paediatric telemedicine, to inform the pandemic response. A systematic search was undertaken by a research librarian in MEDLINE for relevant studies. All identified records were blind double-screened by two reviewers. Implementation-related data were extracted, and studies quality appraised using the Mixed-Methods Appraisal Tool. Qualitative findings were analysed thematically and then mapped to the Consolidated Framework for Implementation Research. Quantitative findings about barriers and facilitators for implementation were narratively synthesised.

Results: We identified 27 eligible studies (19 quantitative; 5 mixed-methods, 3 qualitative). Important challenges highlighted from the perspective of the healthcare providers included issues with ICT proficiency, lack of confidence in the quality/reliability of the technology, connectivity issues, concerns around legal issues, increased administrative burden and/or fear of inability to conduct thorough examinations with reliance on subjective descriptions. Facilitators included clear dissemination of the aims of ICT services, involvement of staff throughout planning and implementation, sufficient training, and cultivation of telemedicine champions. Families often expressed preference for in-person visits but those who had tried tele-consultations, lived far from clinics, or perceived increased convenience with technology considered telemedicine more favourably. Concerns from parents included the responsibility of describing their child's condition in the absence of an in-person examination.

Discussion: Healthcare providers and families who have experienced tele-consultations generally report high satisfaction and usability for such services. The use of ICT to facilitate paediatric healthcare consultations is feasible for certain clinical encounters and can work well with appropriate planning and quality facilities in place.
Multipronged Attack of Stem Cell Therapy in Treating the Neurological and Neuropsychiatric Symptoms of Epilepsy
Authors: Sadanandan Nadia , Saft Madeline , Gonzales-Portillo Bella , Borlongan Cesar V.
Published: March 2021

Epilepsy stands as a life-threatening disease that is characterized by unprovoked seizures. However, an important characteristic of epilepsy that needs to be examined is the neuropsychiatric aspect. Epileptic patients endure aggression, depression, and other psychiatric illnesses. Therapies for epilepsy can be divided into two categories: antiepileptic medications and surgical resection. Antiepileptic drugs are used to attenuate heightened neuronal firing and to lessen seizure frequency. Alternatively, surgery can also be conducted to physically cut out the area of the brain that is assumed to be the root cause for the anomalous firing that triggers seizures. While both treatments serve as viable approaches that aim to regulate seizures and ameliorate the neurological detriments spurred by epilepsy, they do not serve to directly counteract epilepsy’s neuropsychiatric traits. To address this concern, a potential new treatment involves the use of stem cells. Stem cell therapy has been employed in experimental models of neurological maladies, such as Parkinson’s disease, and neuropsychiatric illnesses like depression. Cell-based treatments for epilepsy utilizing stem cells such as neural stem cells (NSCs), mesenchymal stem cells (MSCs), and interneuron grafts have been explored in preclinical and clinical settings, highlighting both the acute and chronic stages of epilepsy. However, it is difficult to create an animal model to capitalize on all the components of epilepsy due to the challenges in delineating the neuropsychiatric aspect. Therefore, further preclinical investigation into the safety and efficacy of stem cell therapy in addressing both the neurological and the neuropsychiatric components of epilepsy is warranted in order to optimize cell dosage, delivery, and timing of cell transplantation.
Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel
Authors: Huang Jian , Zhang Ruilin , Wang Shangwen , Zhang Dongxian , Leung Chi-Kwan , Yang Genmeng , Li Yuanyuan , Liu Liu , Xu Yue , Lin Shucheng , Wang Chan , Zeng Xiaofeng , Li Juan
Published: March 2021

Synergistic impairment of the blood-brain barrier (BBB) induced by methamphetamine (METH) and HIV-Tat protein increases the risk of HIV-associated neurocognitive disorders (HAND) in HIV-positive METH abusers. Studies have shown that oxidative stress plays a vital role in METH- and HIV-Tat-induced damage to the BBB but have not clarified the mechanism. This study uses the human brain microvascular endothelial cell line hCMEC/D3 and tree shrews to investigate whether the transient receptor potential melastatin 2 (TRPM2) channel, a cellular effector of the oxidative stress, might regulate synergistic damage to the BBB caused by METH and HIV-Tat. We showed that METH and HIV-Tat damaged the BBB in vitro, producing abnormal cell morphology, increased apoptosis, reduced protein expression of the tight junctions (TJ) including Junctional adhesion molecule A (JAMA) and Occludin, and a junctional associated protein Zonula occludens 1 (ZO1), and increased the flux of sodium fluorescein (NaF) across the hCMEC/D3 cells monolayer. METH and HIV-Tat co-induced the oxidative stress response, reducing catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activity, as well as increased reactive oxygen species (ROS) and malonaldehyde (MDA) level. Pretreatment with n-acetylcysteine amide (NACA) alleviated the oxidative stress response and BBB damage characterized by improving cell morphology, viability, apoptosis levels, TJ protein expression levels, and NaF flux. METH and HIV-Tat co-induced the activation and high protein expression of the TRPM2 channel, however, early intervention using 8-Bromoadenosine-5′-O-diphosphoribose (8-Br-ADPR), an inhibitor of TPRM2 channel, or TRPM2 gene knockdown attenuated the BBB damage. Oxidative stress inhibition reduced the activation and high protein expression of the TRPM2 channel in the in vitro model, which in turn reduced the oxidative stress response. Further, 8-Br-ADPR attenuated the effects of METH and HIV-Tat on the BBB in tree shrews—namely, down-regulated TJ protein expression and increased BBB permeability to Evans blue (EB) and NaF. In summary, the TRPM2 channel can regulate METH- and HIV-Tat-induced oxidative stress and BBB injury, giving the channel potential for developing drug interventions to reduce BBB injury and neuropsychiatric symptoms in HIV-infected METH abusers.
A Phase I, Randomized, Single-Dose Study to Evaluate the Biosimilarity of HOT-3010 to Adalimumab Among Healthy Chinese Male Subjects
Authors: Zhang Hong , Chen Hong , Li Xiaojiao , Wu Min , Zhu Xiaoxue , Li Cuiyun , Liu Jingrui , Wei Haijing , Hu Yue , Wang Jingjing , Yang Yongmin , Zhu Xiangyang , Ding Yanhua
Published: March 2021

Objective: This study explored the bioequivalence of a proposed biosimilar HOT-3010 vs. its reference product (adalimumab) among healthy Chinese male subjects. The study also investigated the tolerance, immunogenicity, and pharmacokinetics (PK).

Methods: A randomized, double-blind, two-arm, parallel study was performed to examine the bioequivalence of HOT-3010 (40 mg) with that of adalimumab (Humira®, AbbVie) as a reference drug. The study subjects were followed up for 71 days.

Results: PK properties exhibited by HOT-3010 (N = 66) and adalimumab (N = 68) groups were similar. The 90% confidence intervals of the ratios for Cmax, AUC0-t, and AUC0∞ were observed to be in the range 80–125% on comparing the two groups. For anti-drug antibodies (ADA), the number of subjects found to be positive in the HOT-3010 group and adalimumab group were 29 (43.94%) and 32 (47.06%), whereas 27 (40.91%) and 27 (39.71%) subjects were found to be positive for NAb, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were recorded in 32 subjects each in both the groups, respectively.

Conclusion: The PK characteristics and immunogenicity exhibited by HOT-3010 were similar to that of the reference product, adalimumab. The safety profiles were similar in both the treatment groups with mild-moderate adverse effects.
Transcriptome Analysis Reveals Downregulation of Urocortin Expression in the Hypothalamo-Neurohypophysial System of Spontaneously Hypertensive Rats
Authors: Martin Andrew , Mecawi Andre S. , Antunes Vagner R. , Yao Song T. , Antunes-Rodrigues Jose , Paton Julian F. R. , Paterson Alex , Greenwood Michael , Šarenac Olivera , Savić Bojana , Japundžić-Žigon Nina , Murphy David , Hindmarch Charles C. T.
Published: March 2021

The chronically increased blood pressure characteristic of essential hypertension represents an insidious and cumulative risk for cardiovascular disease. Essential hypertension is a multifactorial condition, with no known specific aetiology but a strong genetic component. The Spontaneously Hypertensive rat (SHR) shares many characteristics of human essential hypertension, and as such is a commonly used experimental model. The mammalian hypothalamo-neurohypophyseal system (HNS) plays a pivotal role in the regulation of blood pressure, volume and osmolality. In order to better understand the possible role of the HNS in hypertension, we have used microarray analysis to reveal differential regulation of genes in the HNS of the SHR compared to a control normotensive strain, the Wistar Kyoto rat (WKY). These results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). One of the genes identified and validated as being downregulated in SHR compared to WKY was that encoding the neuropeptide urocortin (Ucn). Immunohistochemical analyses revealed Ucn to be highly expressed within magnocellular neurons of the PVN and SON, with pronounced localisation in dendritic projections containing oxytocin and vasopressin. When Ucn was overexpressed in the PVN of the SHR by in vivo lentiviral mediated gene transfer, blood pressure was unaffected but there were significant, transient reductions in the VLF spectra of systolic blood pressure consistent with an action on autonomic balance. We suggest that Ucn may act, possibly via dendritic release, to subtly regulate neurohumoral aspects of arterial pressure control.
Supplementation of Lipoic Acid, Zinc and Clopidogrel Reduces Mortality Rate and Incidence of Ventricular Arrhythmia in Experimental Myocardial Infarction
Authors: Abdel-Hady Enas , Mohamed Fatma , Ahmed Mona , Abdel-Salam Mohamed , Ayobe Mahmoud
Published: March 2021

Despite the significant advances in management of coronary heart diseases, myocardial infarction (MI) is still associated with a high mortality rate. The present study was planned to investigate the possible protective effects of the anti-oxidants lipoic acid and zinc sulfate as well as the anti-platelet clopidogrel on cardiac dysfunction in experimental isoproterenol (ISO)-induced MI, aiming at achieving useful means for protection and therapy against MI. Wistar rats of both sexes were allocated into five groups: control, untreated MI and MI pre-treated with lipoic acid, zinc, or clopidogrel. All rats were subjected to ECG recording and measurement of plasma levels of troponin I, creatine kinase-MB (CK-MB) unit, triglycerides and total cholesterol. The hearts were isolated and studied on Langendorff preparation for assessment of intrinsic cardiac activities. The results revealed that the percent mortality was markedly reduced upon pre-treatment and the total arrhythmia was also decreased except for the zinc pre-treated rats. The ST-segment elevation was significantly reduced and the plasma levels of CK-MB were only decreased in lipoic acid and clopidogrel pre-treated rats with variable hypolipidemic effect. Hearts of clopidogrel pre-treated rats showed augmented inotropic activity both basal and in response to β-adrenergic stimulation. While zinc pre-treated hearts revealed improved rate of contraction and increased myocardial flow rate. Overall, these results indicate that lipoic acid, zinc and clopidogrel were variably effective in modifying the ISO-induced MI insults and offered partial protection against experimental myocardial damage.
Nutrition and Exercise in a Case of Carnitine Palmitoyl-Transferase II Deficiency
Authors: Parimbelli Mauro , Pezzotti Elena , Negro Massimo , Calanni Luca , Allemano Silvia , Bernardi Marco , Berardinelli Angela , D’Antona Giuseppe
Published: March 2021

In the mild subtype of inherited carnitine palmitoyltransferase II (CPTII) deficiency, muscular mitochondrial fatty acid β-oxidation is impaired. In this condition, interventions involve daily dietary restriction of fats and increase of carbohydrates, whereas physical exercise is commonly contraindicated due to the risk of muscle pain and rhabdomyolysis. We present the case of a 14-year-old female with CPTII deficiency who underwent a 1-h session of unsupervised exercise training for 6 months, 3 days per week, including interval and resistance exercises, after diet assessment and correction. Before and after intervention, the resting metabolic rate (RMR) and respiratory quotient (RQ) were measured by indirect calorimetry, and a cardiopulmonary exercise test (CPET, 10 W/30 s to exhaustion) was performed. Interval training consisted of a 1 min run and a 5 min walk (for 15 min progressively increased to 30 min). During these efforts, the heart rate was maintained over 70% HR max corresponding to respiratory exchange ratio (RER) of 0.98. Resistance training included upper/lower split workouts (3 sets of 8 repetitions each, with 2 min rest between sets). Blood CK was checked before and 36 h after two training sessions chosen randomly without significant difference. After training, RMR increased (+8.1%) and RQ lowered into the physiological range (from 1.0 to 0.85). CPET highlighted an increase of peak power output (+16.7%), aerobic performance (VO2 peak, 8.3%) and anaerobic threshold (+5.7%), oxygen pulse (+4.5%) and a much longer isocapnic buffering duration (+335%). No muscle pain or rhabdomyolysis was reported. Results from our study highlight that training based on short-duration high-intensity exercise improves overall metabolism and aerobic fitness, thus being feasible, at least in a case of CPTII deficiency.
A Metabolic Reprogramming of Glycolysis and Glutamine Metabolism Is a Requisite for Renal Fibrogenesis—Why and How?
Authors: Hewitson Timothy D. , Smith Edward R.
Published: March 2021

Chronic Kidney Disease (CKD) is characterized by organ remodeling and fibrosis due to failed wound repair after on-going or severe injury. Key to this process is the continued activation and presence of matrix-producing renal fibroblasts. In cancer, metabolic alterations help cells to acquire and maintain a malignant phenotype. More recent evidence suggests that something similar occurs in the fibroblast during activation. To support these functions, pro-fibrotic signals released in response to injury induce metabolic reprograming to meet the high bioenergetic and biosynthetic demands of the (myo)fibroblastic phenotype. Fibrogenic signals such as TGF-β1 trigger a rewiring of cellular metabolism with a shift toward glycolysis, uncoupling from mitochondrial oxidative phosphorylation, and enhanced glutamine metabolism. These adaptations may also have more widespread implications with redirection of acetyl-CoA directly linking changes in cellular metabolism and regulatory protein acetylation. Evidence also suggests that injury primes cells to these metabolic responses. In this review we discuss the key metabolic events that have led to a reappraisal of the regulation of fibroblast differentiation and function in CKD.
The UDP-Glycosyltransferase Family in Drosophila melanogaster: Nomenclature Update, Gene Expression and Phylogenetic Analysis
Authors: Ahn Seung-Joon , Marygold Steven J.
Published: March 2021

UDP-glycosyltransferases (UGTs) are important conjugation enzymes found in all kingdoms of life, catalyzing a sugar conjugation with small lipophilic compounds and playing a crucial role in detoxification and homeostasis. The UGT gene family is defined by a signature motif in the C-terminal domain where the uridine diphosphate (UDP)-sugar donor binds. UGTs have been identified in a number of insect genomes over the last decade and much progress has been achieved in characterizing their expression patterns and molecular functions. Here, we present an update of the complete repertoire of UGT genes in Drosophila melanogaster and provide a brief overview of the latest research in this model insect. A total of 35 UGT genes are found in the D. melanogaster genome, localized to chromosomes 2 and 3 with a high degree of gene duplications on the chromosome arm 3R. All D. melanogaster UGT genes have now been named in FlyBase according to the unified UGT nomenclature guidelines. A phylogenetic analysis of UGT genes shows lineage-specific gene duplications. Analysis of anatomical and induced gene expression patterns demonstrate that some UGT genes are differentially expressed in various tissues or after environmental treatments. Extended searches of UGT orthologs from 18 additional Drosophila species reveal a diversity of UGT gene numbers and composition. The roles of Drosophila UGTs identified to date are briefly reviewed, and include xenobiotic metabolism, nicotine resistance, olfaction, cold tolerance, sclerotization, pigmentation, and immunity. Together, the updated genomic information and research overview provided herein will aid further research in this developing field.
The Light-Induced WD40-Repeat Transcription Factor DcTTG1 Regulates Anthocyanin Biosynthesis in Dendrobium candidum
Authors: Jia Ning , Wang Jingjing , Wang Yajuan , Ye Wei , Liu Jiameng , Jiang Jinlan , Sun Jing , Yan Peipei , Wang Peiyu , Wang Fengzhong , Fan Bei
Published: March 2021

Dendrobium candidum is used as a traditional Chinese medicine and as a raw material in functional foods. D. candidum stems are green or red, and red stems are richer in anthocyanins. Light is an important environmental factor that induces anthocyanin accumulation in D. candidum. However, the underlying molecular mechanisms have not been fully unraveled. In this study, we exposed D. candidum seedlings to two different light intensities and found that strong light increased the anthocyanin content and the expression of genes involved in anthocyanin biosynthesis. Through transcriptome profiling and expression analysis, we identified a WD40-repeat transcription factor, DcTTG1, whose expression is induced by light. Yeast one-hybrid assays showed that DcTTG1 binds to the promoters of DcCHS2, DcCHI, DcF3H, and DcF3′H, and a transient GUS activity assay indicated that DcTTG1 can induce their expression. In addition, DcTTG1 complemented the anthocyanin deficiency phenotype of the Arabidopsis thaliana ttg1-13 mutant. Collectively, our results suggest that light promotes anthocyanin accumulation in D. candidum seedlings via the upregulation of DcTTG1, which induces anthocyanin synthesis-related gene expression.
Volatiles Influencing Sensory Attributes and Bayesian Modeling of the Soluble Solids–Sweetness Relationship in Strawberry
Authors: Fan Zhen , Plotto Anne , Bai Jinhe , Whitaker Vance M.
Published: March 2021

Descriptive analysis via trained sensory panels has great power to facilitate flavor improvement in fresh fruits and vegetables. When paired with an understanding of fruit volatile organic compounds, descriptive analysis can help uncover the chemical drivers of sensory attributes. In the present study, 213 strawberry samples representing 56 cultivars and advanced selections were sampled over seven seasons and subjected to both sensory descriptive and chemical analyses. Principal component analysis and K-cluster analyses of sensory data highlighted three groups of strawberry samples, with one classified as superior with high sweetness and strawberry flavor and low sourness and green flavor. Partial least square models revealed 20 sweetness-enhancing volatile organic compounds and two sweetness-reducing volatiles, many of which overlap with previous consumer sensory studies. Volatiles modulating green, sour, astringent, overripe, woody, and strawberry flavors were also identified. The relationship between soluble solids content (SSC) and sweetness was modeled with Bayesian regression, generating probabilities for sweetness levels from varying levels of soluble solids. A hierarchical Bayesian model with month effects indicated that SSC is most correlated to sweetness toward the end of the fruiting season, making this the best period to make phenotypic selections for soluble solids. Comparing effects from genotypes, harvest months, and their interactions on sensory attributes revealed that sweetness, sourness, and firmness were largely controlled by genetics. These findings help formulate a paradigm for improvement of eating quality in which sensory analyses drive the targeting of chemicals important to consumer-desired attributes, which further drive the development of genetic tools for improvement of flavor.
Galactolipid and Phospholipid Profile and Proteome Alterations in Soybean Leaves at the Onset of Salt Stress
Authors: Liu Ailin , Xiao Zhixia , Wang Zhili , Lam Hon-Ming , Chye Mee-Len
Published: March 2021

Salinity is a major environmental factor that constrains soybean yield and grain quality. Given our past observations using the salt-sensitive soybean (Glycine max [L.] Merr.) accession C08 on its early responses to salinity and salt-induced transcriptomic modifications, the aim of this study was to assess the lipid profile changes in this cultivar before and after short-term salt stress, and to explore the adaptive mechanisms underpinning lipid homeostasis. To this end, lipid profiling and proteomic analyses were performed on the leaves of soybean seedlings subjected to salt treatment for 0, 0.5, 1, and 2 h. Our results revealed that short-term salt stress caused dynamic lipid alterations resulting in recycling for both galactolipids and phospholipids. A comprehensive understanding of membrane lipid adaption following salt treatment was achieved by combining time-dependent lipidomic and proteomic data. Proteins involved in phosphoinositide synthesis and turnover were upregulated at the onset of salt treatment. Salinity-induced lipid recycling was shown to enhance jasmonic acid and phosphatidylinositol biosyntheses. Our study demonstrated that salt stress resulted in a remodeling of membrane lipid composition and an alteration in membrane lipids associated with lipid signaling and metabolism in C08 leaves.
Investigation of a Progressive Relaxation Training Intervention on Precompetition Anxiety and Sports Performance Among Collegiate Student Athletes
Authors: Liang Dongmei , Chen Shuqing , Zhang Wenting , Xu Kai , Li Yuting , Li Donghao , Cheng Huiying , Xiao Junwei , Wan Liyi , Liu Chengyi
Published: March 2021

This study aims to investigate whether simple and convenient progressive relaxation training (PRT) is effective in enhancing collegiate student athletes’ mental health and sports performance. An experimental group of 14 (6 female) and a control group of 10 (5 female) collegiate student athletes were recruited from among track and field athletes who were preparing for provincial competition. The experimental group was exposed to a PRT intervention in 30-min sessions conducted twice per week for a duration of one month. At baseline, the Competitive State Anxiety Inventory-2 (CSAI-2), State-Trait Anxiety Inventory (STAI), and Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC) were completed, while only the CSAI-2 was reassessed at one, two, and three weeks after initiation of the intervention. Additionally, within half a day after completing all one’s individual competition events, the CSAI-2 was again assessed in the two groups recalling their memory of their precompetition state anxiety. Then, the differences in the three dimensions of the CSAI-2 between the two groups at the five time points introduced above were compared. This study also explored whether PRT affected sports performance, defined by the athletes reaching their best records or not, by logistic regressive analysis. This study found significant between-group differences in the self-confidence dimension score at the second and third time points. Through logistic regression analysis, a positive effect of PRT was found for the enhancement of sports performance. In sum, PRT showed positive effects on precompetition state self-confidence and enhanced sports performance among collegiate student athletes.
Financial Self-Efficacy and General Life Satisfaction: The Sequential Mediating Role of High Standards Tendency and Investment Satisfaction
Authors: Hu Jianping , Quan Lei , Wu Yanwei , Zhu Jia , Deng Mingliang , Tang Song , Zhang Wei
Published: March 2021

Important strides have been made toward understanding the relationship between self-efficacy and life satisfaction. However, existing studies have largely focused on work and academic domains, leaving self-efficacy in the finance domain less frequently investigated. The present study applied the self-efficacy construct to the finance domain, namely “financial self-efficacy” (FSE), and tested the sequential mediating roles of high standards tendency and investment satisfaction in the relationship between FSE and general life satisfaction. A total of 323 employees from finance-related businesses completed anonymous questionnaires regarding FSE, high standards tendency, investment satisfaction, and general life satisfaction. Results indicated that FSE influenced general life satisfaction through investment satisfaction, and sequentially through high standards tendency and investment satisfaction. These results provide contributions to the current literature on life satisfaction, and positive psychology literature by shedding light on the roles of high standards tendency and investment satisfaction in the relation between FSE and general life satisfaction.
The Dual Effect of Transformational Leadership on Individual- and Team-Level Performance: The Mediational Roles of Motivational Processes
Authors: Lu Hairong , Li Feng
Published: March 2021

Using matched four-stage data from 477 team members and their 132 team leaders in Chinese companies, we examined a cross-level model in which group- and individual-focused transformational leadership (TFL) and their influence on team and member performance from the perspective of multilevel model of motivation in teams. The results indicated that group-focused TFL exerts positive effects through sequential mediation of team efficacy and team process whereas individual-focused TFL has a positive effect on team members' performance through sequential mediation of followers' self-efficacy and individual regulation process. In addition, we also find significant cross-level mediation effects demonstrating that group-focused TFL was positively related to self-efficacy through the mediator of team efficacy, team efficacy was positively related to the individual regulation process through the mediator of the team process, team process was positively related to individual performance through the mediator of the individual regulation process. Theoretical and applied implications are discussed.
Pre-natal Attachment and Parent-To-Infant Attachment: A Systematic Review
Authors: Trombetta Tommaso , Giordano Maura , Santoniccolo Fabrizio , Vismara Laura , Della Vedova Anna Maria , Rollè Luca
Published: March 2021

During the perinatal period, the establishment of the attachment relationship with the fetus and subsequently with the real child is crucial for the parents' and the child's well-being. Coherently with the assumption that the attachment relationship starts to develop during pregnancy, this systematic review aims to analyze and systematize studies focused on the association between pre-natal attachment and parent-to-infant attachment, in order to clarify the emerging results and provide useful information for clinical purposes. Nineteen studies were included. Sixteen researches identified a positive relationship between pre-natal attachment and parent-to-infant attachment, and three articles highlighted a negative association between antenatal attachment and post-partum bonding disorders. These results were found both in women and men, in normative and at-risk pregnancies, adopting different assessment approaches (i.e., self-report measures, observations, and projective measures). However, only small or moderate associations were found. Future studies are needed to further confirm these findings across different populations (e.g., male samples, non-normative samples or samples in disadvantaged conditions) and with different methodological approaches (e.g., observational measures). Moreover, studies would be needed in order to clarify mechanisms through which pre-natal attachment influences parent-to-infant attachment, as well as protective and risk factors which intervene between these two variables.