bluuebunny/crossref_metadata_2025 huggingface dataset:
Basal Ganglia Local Field Potentials as a Potential Biomarker for Sleep Disturbance in Parkinson's Disease
Authors: Baumgartner Alexander J. , Kushida Clete A. , Summers Michael O. , Kern Drew S. , Abosch Aviva , Thompson John A.
Published: October 2021

Sleep disturbances, specifically decreases in total sleep time and sleep efficiency as well as increased sleep onset latency and wakefulness after sleep onset, are highly prevalent in patients with Parkinson's disease (PD). Impairment of sleep significantly and adversely impacts several comorbidities in this patient population, including cognition, mood, and quality of life. Sleep disturbances and other non-motor symptoms of PD have come to the fore as the effectiveness of advanced therapies such as deep brain stimulation (DBS) optimally manage the motor symptoms. Although some studies have suggested that DBS provides benefit for sleep disturbances in PD, the mechanisms by which this might occur, as well as the optimal stimulation parameters for treating sleep dysfunction, remain unknown. In patients treated with DBS, electrophysiologic recording from the stimulating electrode, in the form of local field potentials (LFPs), has led to the identification of several findings associated with both motor and non-motor symptoms including sleep. For example, beta frequency (13–30 Hz) oscillations are associated with worsened bradykinesia while awake and decrease during non-rapid eye movement sleep. LFP investigation of sleep has largely focused on the subthalamic nucleus (STN), though corresponding oscillatory activity has been found in the globus pallidus internus (GPi) and thalamus as well. LFPs are increasingly being recognized as a potential biomarker for sleep states in PD, which may allow for closed-loop optimization of DBS parameters to treat sleep disturbances in this population. In this review, we discuss the relationship between LFP oscillations in STN and the sleep architecture of PD patients, current trends in utilizing DBS to treat sleep disturbance, and future directions for research. In particular, we highlight the capability of novel technologies to capture and record LFP data in vivo, while patients continue therapeutic stimulation for motor symptoms. These technological advances may soon allow for real-time adaptive stimulation to treat sleep disturbances.
A Novel Active Rehabilitation Model for Stroke Patients Using Electroencephalography Signals and Deep Learning Technology
Authors: Gao Ming , Mao Jie
Published: October 2021

The main clinical manifestations of stroke are motor, language, sensory, and mental disorders. After treatment, in addition to being conscious, other symptoms will still remain in varying degrees. This is the sequelae of stroke, including numbness, facial paralysis, central paralysis, and central paralysis. If the sequelae of stroke are not treated effectively, they can easily develop into permanent sequelae. Most of the affected people have sequelae, and most of them have symptoms of upper limb paralysis. Therefore, it is of great significance to study how to carry out effective rehabilitation training for stroke patients to reduce the disease and even restore their motor function. Based on this background, this research aims to use deep learning technology to design a stroke rehabilitation model based on electroencephalography (EEG) signals. First, the patient’s EEG signal will be preprocessed. Then, an improved deep neural network model (IDNN) is used to get the EEG classification results. The traditional DNN model construction process is simple and suitable for scenarios where there is no special requirement for the data format, but the generalization of a single DNN model is usually poor. Large margin support vector machine (LM_SVM) is an extension method of support vector machine (SVM), suitable for any occasion. By optimizing the edge distribution, better generalization performance can be obtained. Taking into account the advantages of DNN and LM_SVM and the high aliasing characteristics of stroke data, an improved DNN model is proposed. Finally, based on the EEG recognition result of the model, the rehabilitation equipment is controlled to assist the patient in rehabilitation treatment. The experimental results verify the superiority of the EEG classification model used, and further prove that this research has good practical value.
Heat Emitting Damage in Skin: A Thermal Pathway for Mechanical Algesia
Authors: Vincent-Dospital Tom , Toussaint Renaud , Måløy Knut Jørgen
Published: October 2021

Mechanical pain (or mechanical algesia) can both be a vital mechanism warning us for dangers or an undesired medical symptom important to mitigate. Thus, a comprehensive understanding of the different mechanisms responsible for this type of pain is paramount. In this work, we study the tearing of porcine skin in front of an infrared camera, and show that mechanical injuries in biological tissues can generate enough heat to stimulate the neural network. In particular, we report local temperature elevations of up to 24°C around fast cutaneous ruptures, which shall exceed the threshold of the neural nociceptors usually involved in thermal pain. Slower fractures exhibit lower temperature elevations, and we characterise such dependency to the damaging rate. Overall, we bring experimental evidence of a novel—thermal—pathway for direct mechanical algesia. In addition, the implications of this pathway are discussed for mechanical hyperalgesia, in which a role of the cutaneous thermal sensors has priorly been suspected. We also show that thermal dissipation shall actually account for a significant portion of the total skin's fracture energy, making temperature monitoring an efficient way to detect biological damages.
Complementary Feeding Habits in Children Under the Age of 2 Years Living in the City of Adama in the Oromia Region in Central Ethiopia: Traditional Ethiopian Food Study
Authors: Gudeta Adugna Negussie , Andrén Aronsson Carin , Balcha Taye Tolera , Agardh Daniel
Published: October 2021

Updated information on child feeding practices, nutritional status, and trends related to parental sociodemographic variables is required in developing countries. The objective of this study was to describe infant feeding practices and associated sociodemographic factors among Ethiopian children with an emphasis on complementary feeding (CF). Information on infant feeding and anthropometric measures was obtained from 1,054 mother-child pairs participating in a birth cohort study of children born between 2017 and 2020 prospectively followed in the city of Adama located in the Oromia region of central Ethiopia. Logistic regression models were used to identify sociodemographic and food groups associated with the initiation of CF. The introduction of complementary foods at 6 months of age was 84.7% (95% CI, 82.5, 86.8). Vegetables, cereals (teff, wheat, barley), and fruits were most often the earliest types of foods introduced. Wasting, stunting, underweight, and low body mass index (BMI) by age were found in 6.0, 16.9, 2.5, and 6.3%, respectively. Maternal age and occupation were the factors associated with timely initiation of CF [OR = 2.25, (95% CI, 1.14, 4.41)] and [OR = 0.68, (95% CI, 0.48, 0.97)], respectively. This study demonstrates that the majority of Ethiopian children in the Oromia region follow the recommendations of WHO on CF.
Present and Future Therapeutic Approaches to Barrier Dysfunction
Authors: Fortea Marina , Albert-Bayo Mercé , Abril-Gil Mar , Ganda Mall John-Peter , Serra-Ruiz Xavier , Henao-Paez Alejandro , Expósito Elba , González-Castro Ana María , Guagnozzi Danila , Lobo Beatriz , Alonso-Cotoner Carmen , Santos Javier
Published: October 2021

There is converging and increasing evidence, but also uncertainty, for the role of abnormal intestinal epithelial barrier function in the origin and development of a growing number of human gastrointestinal and extraintestinal inflammatory disorders, and their related complaints. Despite a vast literature addressing factors and mechanisms underlying changes in intestinal permeability in humans, and its connection to the appearance and severity of clinical symptoms, the ultimate link remains to be established in many cases. Accordingly, there are no directives or clinical guidelines related to the therapeutic management of intestinal permeability disorders that allow health professionals involved in the management of these patients to carry out a consensus treatment based on clinical evidence. Instead, there are multiple pseudoscientific approaches and commercial propaganda scattered on the internet that confuse those affected and health professionals and that often lack scientific rigor. Therefore, in this review we aim to shed light on the different therapeutic options, which include, among others, dietary management, nutraceuticals and medical devices, microbiota and drugs, and epigenetic and exosomes-manipulation, through an objective evaluation of the scientific publications in this field. Advances in the knowledge and management of intestinal permeability will sure enable better options of dealing with this group of common disorders to enhance quality of life of those affected.
Stereotactic Body Radiation Therapy for Oligometastatic Breast Cancer: A Retrospective Multicenter Study
Authors: Lemoine Pauline , Bruand Marie , Kammerer Emmanuel , Bogart Emilie , Comte Pauline , Royer Philippe , Thariat Juliette , Pasquier David
Published: October 2021

Introduction

Stereotactic radiotherapy may improve the prognosis of oligometastatic patients. In the literature, there is very little data available that is specific to breast cancer.

Materials and Methods

We conducted a multicenter retrospective study. The primary objective was to estimate progression-free survival after stereotactic body radiotherapy (SBRT) using Cyberknife of breast cancer oligometastases. The secondary objectives were to estimate overall survival, local control, and toxicity. The inclusion criteria were oligometastatic breast cancer with a maximum of five lesions distributed in one to three different organs, diagnosed on PET/CT and/or MRI, excluding brain metastases and oligoprogressions. This was combined with systemic medical treatment.

Findings

Forty-four patients were enrolled from 2007 to 2017, at three high-volume cancer centers. The patients mostly had one to two lesion(s) whose most widely represented site was bone (24 lesions or 44.4%), particularly in the spine, followed by liver (22 lesions or 40.7%), then pulmonary lesions (six lesions or 11.1%). The primary tumor expressed estrogen receptors in 33 patients (84.6%); the status was HER2+++ in 7 patients (17.9%). The median dose was 40 Gy (min-max: 15-54) prescribed at 80% isodose, the median number of sessions was three (min-max: 3-10). The median D50% was 42 Gy (min max 17-59). After a median follow-up of 3.4 years, progression-free survival (PFS) at one year, two years, and three years was 81% (95% CI: 66-90%), 58% (95% CI: 41-72%), and 45% (95% CI: 28-60%), respectively. The median PFS was 2.6 years (95% CI: 1.3 – 4.9). Overall survival at three years was 81% (95% CI: 63-90%). The local control rate at two and three years was 100%. Three patients (7.3%) experienced G2 acute toxicity, no grade ≥3 toxicity was reported.

Conclusion

The PFS of oligometastatic breast cancer patients treated with SBRT appears long, with low toxicity. Local control is high. SBRT for oligometastases is rarely applied in breast cancer in light of the population in our study. Phase III studies are ongoing.
Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies
Authors: Zhu Sining , Jung Jaeyong , Victor Eton , Arceo Johann , Gokhale Samantha , Xie Ping
Published: October 2021

The BTK inhibitors ibrutinib and acalabrutinib are FDA-approved drugs for the treatment of B cell malignances. Both drugs have demonstrated clinical efficacy and safety profiles superior to chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia. Mounting preclinical and clinical evidence indicates that both ibrutinib and acalabrutinib are versatile and have direct effects on many immune cell subsets as well as other cell types beyond B cells. The versatility and immunomodulatory effects of both drugs have been exploited to expand their therapeutic potential in a wide variety of human diseases. Over 470 clinical trials are currently registered at ClinicalTrials.gov to test the efficacy of ibrutinib or acalabrutinib not only in almost every type of B cell malignancies, but also in hematological malignancies of myeloid cells and T cells, solid tumors, chronic graft versus host disease (cGHVD), autoimmune diseases, allergy and COVID-19 (http:www.clinicaltrials.gov). In this review, we present brief discussions of the clinical trials and relevant key preclinical evidence of ibrutinib and acalabrutinib as monotherapies or as part of combination therapies for the treatment of human diseases beyond B cell malignancies. Adding to the proven efficacy of ibrutinib for cGVHD, preliminary results of clinical trials have shown promising efficacy of ibrutinib or acalabrutinib for certain T cell malignancies, allergies and severe COVID-19. However, both BTK inhibitors have no or limited efficacy for refractory or recurrent solid tumors. These clinical data together with additional pending results from ongoing trials will provide valuable information to guide the design and improvement of future trials, including optimization of combination regimens and dosing sequences as well as better patient stratification and more efficient delivery strategies. Such information will further advance the precise implementation of BTK inhibitors into the clinical toolbox for the treatment of different human diseases.
Immune Evasion Mechanism and AXL
Authors: Son Hye-Youn , Jeong Hwan-Kyu
Published: October 2021

Extensive interest in cancer immunotherapy is reported according to the clinical importance of CTLA-4 and (PD-1/PD-L1) [programmed death (PD) and programmed death-ligand (PD-L1)] in immune checkpoint therapies. AXL is a receptor tyrosine kinase expressed in different types of cancer and in relation to resistance against various anticancer therapeutics due to poor clinical prognosis. AXL and its ligand, i.e., growth arrest-specific 6 (GAS6) proteins, are expressed on many cancer cells, and the GAS6/AXL pathway is reported to promote cancer cell proliferation, survival, migration, invasion, angiogenesis, and immune evasion. AXL is an attractive and novel therapeutic target for impairing tumor progression from immune cell contracts in the tumor microenvironment. The GAS6/AXL pathway is also of interest immunologically because it targets fewer antitumor immune responses. In effect, several targeted therapies are selective and nonselective for AXL, which are in preclinical and clinical development in multiple cancer types. Therefore, this review focuses on the role of the GAS6/AXL signaling pathway in triggering the immunosuppressive tumor microenvironment as immune evasion. This includes regulating its composition and activating T-cell exclusion with the immune-suppressive activity of regulatory T cells, which is related to one of the hallmarks of cancer survival. Finally, this article discusses the GAS6/AXL signaling pathway in the context of several immune responses such as NK cell activation, apoptosis, and tumor-specific immunity, especially PD-1/PDL-1 signaling.
Prognostic Value of Lymphocyte–C-Reactive Protein Ratio in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Population-Based Study
Authors: Zhang Houliang , Wang Yidi , Ni Jinliang , Shi Huajuan , Zhang Tao , Zhang Yifan , Guo Jing , Wang Keyi , Mao Weipu , Peng Bo
Published: October 2021

Purpose

This study aimed to assess the prognostic value of the lymphocyte–C-reactive protein ratio (LCR) in patients with bladder cancer (BCa) who underwent radical cystectomy (RC).

Materials and Methods

BCa patients between 2009 and 2018 were retrieved from our medical center. The predictive value of LCR on survival of BCa patients was evaluated through the Kaplan–Meier survival and receiver operating characteristic (ROC) curves. The multivariate Cox regression results were used for conducting the nomogram, which were further verified by ROC, decision curve analysis (DCA), and calibration curves. Propensity score matching (PSM) was performed to validate our findings.

Results

A total of 201 BCa patients who received RC were included in this study, with 62 (30.8%) patients in the low LCR group and 139 (69.2%) in the high LCR group. Multivariate analysis results revealed that the high LCR group was significantly related to better prognosis and functioned as a prognostic biomarker for overall survival (OS) [hazard ratio (HR) = 0.41, 95% CI, 0.26–0.66; p < 0.001] and disease-free survival (DFS) [HR = 0.40, 95% CI, 0.26–0.66; p < 0.001]. The nomogram processed better predictive capability and accuracy than TNM stage from ROC results (AUC = 0.754 vs. AUC = 0.715), with the confirmation of calibration curves and DCA. The result of PSM confirmed that LCR was significantly correlated with OS and DFS.

Conclusion

Our finding demonstrates that LCR is a novel, convenient, and effective predictor that may provide vital assistance for clinical decision and individualized therapy in BCa patients after RC.
Review of Insulin Resistance in Dilated Cardiomyopathy and Implications for the Pediatric Patient Short Title: Insulin Resistance DCM and Pediatrics
Authors: Mak Daniel , Ryan Kaitlin A. , Han Joan C.
Published: October 2021

Energy metabolism in the heart is affected during states of dysfunction. Understanding how the heart utilizes substrates in cardiomyopathy may be key to the development of alternative treatment modalities. Myocardial insulin resistance has been proposed as a possible barrier to effective glucose metabolism in the heart. Extensive literature on the topic in adult individuals exists; however, review in the pediatric population is sparse. The pathophysiology of disease in children and adolescents is unique. The aim of this paper is to review the current knowledge on insulin resistance in dilated cardiomyopathy while also filling the gap when considering care in the pediatric population.
Reviewing Data Integrated for PBPK Model Development to Predict Metabolic Drug-Drug Interactions: Shifting Perspectives and Emerging Trends
Authors: Abouir Kenza , Samer Caroline F , Gloor Yvonne , Desmeules Jules A , Daali Youssef
Published: October 2021

Physiologically-based pharmacokinetics (PBPK) modeling is a robust tool that supports drug development and the pharmaceutical industry and regulatory authorities. Implementation of predictive systems in the clinics is more than ever a reality, resulting in a surge of interest for PBPK models by clinicians. We aimed to establish a repository of available PBPK models developed to date to predict drug-drug interactions (DDIs) in the different therapeutic areas by integrating intrinsic and extrinsic factors such as genetic polymorphisms of the cytochromes or environmental clues. This work includes peer-reviewed publications and models developed in the literature from October 2017 to January 2021. Information about the software, type of model, size, and population model was extracted for each article. In general, modeling was mainly done for DDI prediction via Simcyp® software and Full PBPK. Overall, the necessary physiological and physio-pathological parameters, such as weight, BMI, liver or kidney function, relative to the drug absorption, distribution, metabolism, and elimination and to the population studied for model construction was publicly available. Of the 46 articles, 32 sensibly predicted DDI potentials, but only 23% integrated the genetic aspect to the developed models. Marked differences in concentration time profiles and maximum plasma concentration could be explained by the significant precision of the input parameters such as Tissue: plasma partition coefficients, protein abundance, or Ki values. In conclusion, the models show a good correlation between the predicted and observed plasma concentration values. These correlations are all the more pronounced as the model is rich in data representative of the population and the molecule in question. PBPK for DDI prediction is a promising approach in clinical, and harmonization of clearance prediction may be helped by a consensus on selecting the best data to use for PBPK model development.
Precision Medicine in Graves’ Disease and Ophthalmopathy
Authors: Elia Giusy , Fallahi Poupak , Ragusa Francesca , Paparo Sabrina Rosaria , Mazzi Valeria , Benvenga Salvatore , Antonelli Alessandro , Ferrari Silvia Martina
Published: October 2021

Graves’ disease (GD) is a condition caused by an autoimmune process involving the thyroid gland, whose main outcome is hyperthyroidism. TSAb start the autoimmune process stimulating the overproduction of thyroid hormones. In addition, TSAb can stimulate TSH-R expressed in fibroblasts and orbital pre-adipocytes leading to the manifestation of Graves’ ophtalmopathy (GO). Also, autoantibodies directed against IGF-1R have an important role in immune-pathogenesis of GO. Fundamental is the role played by cytokines (IFN-γ, TNF-α, Il-6), and Th1 chemokines in the immune-pathogenesis of both disorders, particularly in the active phase. Novel discoveries in the field led to the investigation of promising therapies, such as immune-therapies towards specific antigens (for example against TSH-R), aiming in restoring the immune tolerance versus the immune dominant epitopes associated with autoimmunity in GD. Moreover, Etanercept (that blocks the TNF-mediated inflammatory responses), TCZ (that acts against the IL-6 receptor), and RTX (that acts against CD20) have proven to be useful and safe therapeutic options in refractory GO treatment. Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody), have been revealed effective in the treatment of patients with moderate-severe GO and it is now approved for GO therapy in United States. Molecules able to act as antagonists of CXCR3, or to block CXCL10, are also under study. More extensive researches are needed to deepen out these drugs as well as to identify new targeted and effective therapies, that will permit a more precise identification of GD, or GO, patients able to respond to specific targeted therapies.
Artificial Intelligence for Monte Carlo Simulation in Medical Physics
Authors: Sarrut David , Etxebeste Ane , Muñoz Enrique , Krah Nils , Létang Jean Michel
Published: October 2021

Monte Carlo simulation of particle tracking in matter is the reference simulation method in the field of medical physics. It is heavily used in various applications such as 1) patient dose distribution estimation in different therapy modalities (radiotherapy, protontherapy or ion therapy) or for radio-protection investigations of ionizing radiation-based imaging systems (CT, nuclear imaging), 2) development of numerous imaging detectors, in X-ray imaging (conventional CT, dual-energy, multi-spectral, phase contrast … ), nuclear imaging (PET, SPECT, Compton Camera) or even advanced specific imaging methods such as proton/ion imaging, or prompt-gamma emission distribution estimation in hadrontherapy monitoring. Monte Carlo simulation is a key tool both in academic research labs as well as industrial research and development services. Because of the very nature of the Monte Carlo method, involving iterative and stochastic estimation of numerous probability density functions, the computation time is high. Despite the continuous and significant progress on computer hardware and the (relative) easiness of using code parallelisms, the computation time is still an issue for highly demanding and complex simulations. Hence, since decades, Variance Reduction Techniques have been proposed to accelerate the processes in a specific configuration. In this article, we review the recent use of Artificial Intelligence methods for Monte Carlo simulation in medical physics and their main associated challenges. In the first section, the main principles of some neural networks architectures such as Convolutional Neural Networks or Generative Adversarial Network are briefly described together with a literature review of their applications in the domain of medical physics Monte Carlo simulations. In particular, we will focus on dose estimation with convolutional neural networks, dose denoising from low statistics Monte Carlo simulations, detector modelling and event selection with neural networks, generative networks for source and phase space modelling. The expected interests of those approaches are discussed. In the second section, we focus on the current challenges that still arise in this promising field.
An Expanded Survey of the Moth PBP/GOBP Clade in Bombyx mori: New Insight into Expression and Functional Roles
Authors: Guo Xia , Xuan Ning , Liu Guoxia , Xie Hongyan , Lou Qinian , Arnaud Philippe , Offmann Bernard , Picimbon Jean-François
Published: October 2021

We studied the expression profile and ontogeny (from the egg stage through the larval stages and pupal stages, to the elderly adult age) of four OBPs from the silkworm moth Bombyx mori. We first showed that male responsiveness to female sex pheromone in the silkworm moth B. mori does not depend on age variation; whereas the expression of BmorPBP1, BmorPBP2, BmorGOBP1, and BmorGOBP2 varies with age. The expression profile analysis revealed that the studied OBPs are expressed in non-olfactory tissues at different developmental stages. In addition, we tested the effect of insecticide exposure on the expression of the four OBPs studied. Exposure to a toxic macrolide insecticide endectocide molecule (abamectin) led to the modulated expression of all four genes in different tissues. The higher expression of OBPs was detected in metabolic tissues, such as the thorax, gut, and fat body. All these data strongly suggest some alternative functions for these proteins other than olfaction. Finally, we carried out ligand docking studies and reported that PBP1 and GOBP2 have the capacity of binding vitamin K1 and multiple different vitamins.
Non-invasive Characterization of Human AV-Nodal Conduction Delay and Refractory Period During Atrial Fibrillation
Authors: Karlsson Mattias , Sandberg Frida , Ulimoen Sara R. , Wallman Mikael
Published: October 2021

During atrial fibrillation (AF), the heart relies heavily on the atrio-ventricular (AV) node to regulate the heart rate. Thus, characterization of AV-nodal properties may provide valuable information for patient monitoring and prediction of rate control drug effects. In this work we present a network model consisting of the AV node, the bundle of His, and the Purkinje fibers, together with an associated workflow, for robust estimation of the model parameters from ECG. The model consists of two pathways, referred to as the slow and the fast pathway, interconnected at one end. Both pathways are composed of interacting nodes, with separate refractory periods and conduction delays determined by the stimulation history of each node. Together with this model, a fitness function based on the Poincaré plot accounting for dynamics in RR interval series and a problem specific genetic algorithm, are also presented. The robustness of the parameter estimates is evaluated using simulated data, based on clinical measurements from five AF patients. Results show that the proposed model and workflow could estimate the slow pathway parameters for the refractory period, RminSP and ΔRSP, with an error (mean ± std) of 10.3 ± 22 and −12.6 ± 26 ms, respectively, and the parameters for the conduction delay, Dmin,totSP and ΔDtotSP, with an error of 7 ± 35 and 4 ± 36 ms. Corresponding results for the fast pathway were 31.7 ± 65, −0.3 ± 77, 17 ± 29, and 43 ± 109 ms. These results suggest that both conduction delay and refractory period can be robustly estimated from non-invasive data with the proposed methodology. Furthermore, as an application example, the methodology was used to analyze ECG data from one patient at baseline and during treatment with Diltiazem, illustrating its potential to assess the effect of rate control drugs.
Unraveling Aβ-Mediated Multi-Pathway Calcium Dynamics in Astrocytes: Implications for Alzheimer’s Disease Treatment From Simulations
Authors: Liu Langzhou , Gao Huayi , Zaikin Alexey , Chen Shangbin
Published: October 2021

The accumulation of amyloid β peptide (Aβ) in the brain is hypothesized to be the major factor driving Alzheimer’s disease (AD) pathogenesis. Mounting evidence suggests that astrocytes are the primary target of Aβ neurotoxicity. Aβ is known to interfere with multiple calcium fluxes, thus disrupting the calcium homeostasis regulation of astrocytes, which are likely to produce calcium oscillations. Ca2+ dyshomeostasis has been observed to precede the appearance of clinical symptoms of AD; however, it is experimentally very difficult to investigate the interactions of many mechanisms. Given that Ca2+ disruption is ubiquitously involved in AD progression, it is likely that focusing on Ca2+ dysregulation may serve as a potential therapeutic approach to preventing or treating AD, while current hypotheses concerning AD have so far failed to yield curable therapies. For this purpose, we derive and investigate a concise mathematical model for Aβ-mediated multi-pathway astrocytic intracellular Ca2+ dynamics. This model accounts for how Aβ affects various fluxes contributions through voltage-gated calcium channels, Aβ-formed channels and ryanodine receptors. Bifurcation analysis of Aβ level, which reflected the corresponding progression of the disease, revealed that Aβ significantly induced the increasing [Ca2+]i and frequency of calcium oscillations. The influence of inositol 1,4,5-trisphosphate production (IP3) is also investigated in the presence of Aβ as well as the impact of changes in resting membrane potential. In turn, the Ca2+ flux can be considerably changed by exerting specific interventions, such as ion channel blockers or receptor antagonists. By doing so, a “combination therapy” targeting multiple pathways simultaneously has finally been demonstrated to be more effective. This study helps to better understand the effect of Aβ, and our findings provide new insight into the treatment of AD.
Mutagenic Effect of Proton Beams Characterized by Phenotypic Analysis and Whole Genome Sequencing in Arabidopsis
Authors: Lee Sang Woo , Kwon Yu-Jeong , Baek Inwoo , Choi Hong-Il , Ahn Joon-Woo , Kim Jin-Baek , Kang Si-Yong , Kim Sang Hoon , Jo Yeong Deuk
Published: October 2021

Protons may have contributed to the evolution of plants as a major component of cosmic-rays and also have been used for mutagenesis in plants. Although the mutagenic effect of protons has been well-characterized in animals, no comprehensive phenotypic and genomic analyses has been reported in plants. Here, we investigated the phenotypes and whole genome sequences of Arabidopsis M2 lines derived by irradiation with proton beams and gamma-rays, to determine unique characteristics of proton beams in mutagenesis. We found that mutation frequency was dependent on the irradiation doses of both proton beams and gamma-rays. On the basis of the relationship between survival and mutation rates, we hypothesized that there may be a mutation rate threshold for survived individuals after irradiation. There were no significant differences between the total mutation rates in groups derived using proton beam or gamma-ray irradiation at doses that had similar impacts on survival rate. However, proton beam irradiation resulted in a broader mutant phenotype spectrum than gamma-ray irradiation, and proton beams generated more DNA structural variations (SVs) than gamma-rays. The most frequent SV was inversion. Most of the inversion junctions contained sequences with microhomology and were associated with the deletion of only a few nucleotides, which implies that preferential use of microhomology in non-homologous end joining was likely to be responsible for the SVs. These results show that protons, as particles with low linear energy transfer (LET), have unique characteristics in mutagenesis that partially overlap with those of low-LET gamma-rays and high-LET heavy ions in different respects.
Functional and Structural Investigation of Chalcone Synthases Based on Integrated Metabolomics and Transcriptome Analysis on Flavonoids and Anthocyanins Biosynthesis of the Fern Cyclosorus parasiticus
Authors: Niu Meng , Fu Jie , Ni Rong , Xiong Rui-Lin , Zhu Ting-Ting , Lou Hong-Xiang , Zhang Peng , Li Jianxu , Cheng Ai-Xia
Published: October 2021

The biosynthesis of flavonoids and anthocyanidins has been exclusively investigated in angiosperms but largely unknown in ferns. This study integrated metabolomics and transcriptome to analyze the fronds from different development stages (S1 without spores and S2 with brown spores) of Cyclosorus parasiticus. About 221 flavonoid and anthocyanin metabolites were identified between S1 and S2. Transcriptome analysis revealed several genes encoding the key enzymes involved in the biosynthesis of flavonoids, and anthocyanins were upregulated in S2, which were validated by qRT-PCR. Functional characterization of two chalcone synthases (CpCHS1 and CpCHS2) indicated that CpCHS1 can catalyze the formation of pinocembrin, naringenin, and eriodictyol, respectively; however, CpCHS2 was inactive. The crystallization investigation of CpCHS1 indicated that it has a highly similar conformation and shares a similar general catalytic mechanism to other plants CHSs. And by site-directed mutagenesis, we found seven residues, especially Leu199 and Thr203 that are critical to the catalytic activity for CpCHS1.
Foreign Language Effect on Dishonesty
Authors: Yang Xiaolan , Li Li , Li Rui
Published: October 2021

The purpose of this paper is to investigate whether the use of foreign languages affects individuals’ dishonesty. We recruited native Chinese speakers who can speak English as a foreign language at universities in China, and they were randomly assigned to a native language (NL) or foreign language (FL) condition. Participants in each condition were required to finish the same tasks, in which they would benefit more from lying; the tasks were administered in either Chinese or English. We conducted one die-roll game in Study 1 and one cheap-talk sender-receiver game in Study 2. In both Study 1 and Study 2, we found that the proportion of lying was significantly lower in the FL condition than in the NL condition. Our results imply that the FL effect on dishonesty may be due to the cognitive load of communicating in a FL.
Self-Reported Health in Patients on or at Risk of Sick Leave Due to Depression and Anxiety: Validity of the EQ-5D
Authors: Sandin Kenneth , Shields Gemma E. , Gjengedal Ragne G. H. , Osnes Kåre , Bjørndal Marianne Tranberg , Hjemdal Odin
Published: October 2021

Objectives: The EQ-5D is a generic, self-report measure of health that is increasingly used in clinical settings, including mental health. The EQ-5D captures health using five dimensions: Mobility, Self-care, Usual activities, Pain/discomfort, and Anxiety/Depression. The validity of the EQ-5D is previously unexplored in patients on or at risk of sick leave due to depression and anxiety. The study’s aim was to examine its validity in this group of patients.

Methods: Baseline data were collected from self-report questionnaires in an observational study (N=890) at a Norwegian outpatient-clinic. Participants were adults on or at risk of sick leave due to depression and anxiety who were referred for treatment by general practitioners. The crosswalk methodology was applied to estimate the EQ-5D value. Validity was assessed by comparing responses on the EQ-5D with the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI), and Subjective Health Complaints (SHC). An ordinal regression model was used to assess known-groups validity. Convergent validity was assessed using Pearson’s correlation coefficient, and a multivariate regression model that included sociodemographic characteristics.

Results: The mean EQ-5D value was 0.631, indicating reduced health status compared to “full health” anchored at 1.0, and patients reported moderate levels of depression and anxiety. Ordinal regression indicated that the EQ-5D could discriminate between different levels of symptom severity for depression and anxiety. The EQ-5D value showed significant correlation with the clinical measures; r=−0.52 for the BDI-II, r=−0.49 for the BAI, and r=−0.44 for SHC. The multivariate regression showed that the clinical variables significantly predicted the EQ-5D value, explaining 40.1% of the variance. Depression and anxiety scores were the largest determinants of EQ-5D value, respectively, whilst sick leave, subjective health complaints, and gender made moderate contributions.

Conclusion: The EQ-5D showed indication of validity in patients on or at risk of sick leave due to depression and anxiety in the present study. The EQ-5D value was sensitive to both symptom severity and functional impairment in the form of sick leave. The findings support the EQ-5D as a feasible and relevant measure of health status in these patients.
Efficacy of Group Music Therapy Based on Emotion-Regulation Skills on Male Inpatients With Alcohol Dependence: A Randomized, Controlled Pilot Trial
Authors: Huang Yi , Chen Xu
Published: October 2021

Objective: This study aimed to determine the benefits and feasibility of using group music therapy based on emotion-regulation skills to treat male inpatients with alcohol dependence (AD).

Methods: We recruited male inpatients with alcohol dependence and randomly assigned those eligible for enrollment to either the study group or the control group. The study group received group music therapy along with treatment-as-usual (TAU), while the control group received only treatment-as-usual. Primary outcomes, including anxiety levels, sleep quality, and alcohol craving, were assessed at baseline and after 2 weeks of treatment. Secondary outcomes included feasibility measures such as dropout rates. We evaluated the acceptability of group music therapy based on semi-structured interviews and feedback from patients and therapists.

Results: The average attendance rate of the study group patients who underwent group music therapy was 70.77%, and the drop-out rate was 7.69%. Based on intention-to-treat analysis, we found no differences in baseline assessments (p > 0.05). Assessment after 2 weeks of treatment showed that study group patients were less anxious, slept better, and had reduced alcohol cravings than control group patients. However, these differences were not statistically significant. Participants reported that group music therapy made them feel more relaxed and improved their mood.

Conclusion: Group music therapy based on emotion-regulation skills is feasible with potential for efficacy and can be used to treat men with alcohol dependence in a closed inpatient environment. Further long-term research is required to gain a better understanding of the efficacy of using group music therapy to treat alcohol dependence.
The Impact of Cross-Cultural Adaptation on Entrepreneurial Psychological Factors and Innovation Ability for New Entrepreneurs
Authors: Zhou Qianfu
Published: October 2021

In the context of economic slowdown and unemployment upsurge in China, many college graduates set their goals on entrepreneurship. To help more new entrepreneurs improve their innovation ability and entrepreneurial success rate, the synergy theory of entrepreneurial psychology and entrepreneurial ability in the entrepreneurial period was put forward from the perspective of cross-cultural adaptation. On the basis of positive psychology, the entrepreneur’s psychological quality and innovation ability were combined to help explore the entrepreneur’s inner psychology and innovation ability. The study first analyzed the current development status and characteristics of new entrepreneurs through the literature review method, and explored the relationship between cross-cultural adaptation and new ventures. Second, it examined the relationship among achievement incentives, knowledge level, and the role of communication and entrepreneurs’ entrepreneurial intentions from the perspective of positive psychology. Finally, based on the influence relationship and personal experience, research hypotheses and models, the study verified the hypotheses by designing questionnaire surveys, and used the controlled variable method to conduct single-factor test analysis on influencing factors and perform a t-test on the data. The results show that the Cronbach’s α coefficient in the QS is 0.894, which has good reliability. According to the regression analysis results, achievement motivation (AM) can significantly affect entrepreneurial intention (EI) (β = 487, p < 0.05), knowledge level (KL) and EI (β = 316, p < 0.05), and the regression coefficient is greater than 0, but there is no significant effect of communicate effectiveness (CE) on EI (p = 0.109 > 0.05). In the control variables influence analysis, the level of education of new entrepreneurs was negatively correlated with AM. When the college students’ educational level improved, their EI decreased. It shows that AM can promote new entrepreneurs to pursue higher goals, and different level of education has a greater impact on entrepreneurs’ AM, which has a more significant impact on entrepreneurial intention. The results further prove that entrepreneurs’ psychological factors have a particular impact on the development of enterprises.
The Positive Loop at Work: A Longitudinal Long-Term Study of Transformational Leadership, Group Passion, and Employee Results
Authors: Mindeguia Rosa , Aritzeta Aitor , Garmendia Alaine , Aranberri Ainara
Published: October 2021

Positive psychology and positive organizational behavior studies recognize that leadership is extremely important for generating positive well-being. Despite the frequently reported significant positive correlations, the causal long-term relationship between leadership, positive high intense affect, and employee results remains unclear. The main objective of this study was to analyze the long-term (longitudinal) relation of transformational leadership and positive high-intensity emotions with employee group satisfaction, commitment, and proactive behavior. We built a longitudinal structural equation model to test a mediation model with two time points; 2,480 workers from 166 work units completed questionnaires at both time points. Our results reveal that positive high-intensity emotions mediate the relation between transformational leadership and proactive behavior of workers, the bidirectional relations between the variables were also analyzed. The present study is, to our knowledge, the first analyzing the long-term effect of TFL and collective high-intensity emotions on worker’s results longitudinally. Our findings reflect the great complexity of affect and affect-related results in organizations and highlight the need for more longitudinal research to clarify emotional processes at work.
Entrepreneurship Education, Psychological Cognition, and Entrepreneurship Activities: An Analysis Based on a Fuzzy-Set Qualitative Comparative Analysis
Authors: Jiang Yujia , Li Guobiao , Cai Xu , Yang Zihan , Huang Yangjie , Zhang Ling , Huang Leilei
Published: October 2021

At present, research in the field of college students' entrepreneurship has proliferated, but these studies tend to analyze the net benefits of various factors on entrepreneurial activities, which are affected by the configuration effects of multiple factors; hence, it remains unclear whether entrepreneurial education can make graduates more efficient to started their own companies. To fill this gap in the literature, drawing on general systems theory and using fuzzy-set qualitative comparative analysis (fsQCA), we take 1,87,914 undergraduate and junior college students from 1,231 colleges and universities in China as a sample to explore the relationships among the five conditions in the entrepreneurship education environment and cognitive level (i.e., the quality of staff, subject curriculum, entrepreneurial competition, intentions, and opportunity identifications) and entrepreneurial activities. The fsQCA results show that none of these factors are sufficient for entrepreneurial activity. In contrast, three combinations of the five conditions (i.e., co-creation type, competition-oriented environment, and entrepreneurship education that fits under the guidance of entrepreneurial intention) can produce high entrepreneurial activity, as well as substitution and complementarity among the various elements within the configuration. These results show that the combined effect of the five conditions is more conducive to the entrepreneurial activities of college students. Finally, after a discussion of the study's findings, theoretical, and practical contributions are analyzed with regard to the field of entrepreneurship in Chinese colleges, and alternative options indicate that college students are more likely to become entrepreneurs in the future.
Teleworking While Sick: A Three-Wave Study of Psychosocial Safety Climate, Psychological Demands, and Presenteeism
Authors: Biron Caroline , Karanika-Murray Maria , Ivers Hans , Salvoni Sandra , Fernet Claude
Published: October 2021

Introduction: The COVID-19 pandemic has led to a significant increase in the proportion of employees for whom teleworking became mandatory. Presenteeism, or the behavior of working while ill, has hardly been studied in the context of telework. The pandemic forced millions of workers to abruptly transition to working from home for a prolonged period of time, leaving employers often unaware of their health status or work capacity of the workers. This change also eroded the work experience itself, the workplace, and their protective impact on both individual health and work outcomes. This study focused on the longitudinal relationships among psychosocial safety climate (PSC), a lead indicator of workplace conditions, psychological demands, an indicator of quality of work, and presenteeism among a representative sample of teleworkers. PSC was expected to have an indirect impact on presenteeism with psychological demands as a mediator of this impact.

Method: We collected the data from a representative sample of teleworkers in the first months (T1: April, T2: June, and T3: December 2020) of the pandemic using a three-wave online survey (n = 275). We tested a model of PSC as a determinant of presenteeism in teleworkers with psychological demands as a mediator. A cross-lagged panel model was estimated to test cross-sectional and longitudinal relationships.

Findings: As expected, psychological demands increased over time. Contrary to expectations, the prevalence of presenteeism remained unchanged while PSC increased over time. The data fully supported the mediating effect of psychological demands such that a higher evaluation of PSC at T1 led to lower psychological demands at T2, which led to reduced presenteeism at T3. We also found a reciprocal relationship, with higher psychological demands at T2 leading to decreased evaluation of PSC at T3. These results show that the perception of teleworkers on their organization as giving a high priority to their psychological health is an important determinant of their work experience, ultimately influencing their decision to work while ill. The context of the pandemic has highlighted the importance of a positive workplace climate and working conditions for reducing the behaviors that can be harmful to health and productivity. Implications for theory and practice, beyond the pandemic, are discussed.