bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Cholinergic Tone in the Basal Forebrain Reflects Reward-Seeking and Reinforcement During Olfactory Behavior
Authors: Hanson Elizabeth , Brandel-Ankrapp Katie L. , Arenkiel Benjamin R.
Published: February 2021

Sensory perception underlies how we internalize and interact with the external world. In order to adapt to changing circumstances and interpret signals in a variety of contexts, sensation needs to be reliable, but perception of sensory input needs to be flexible. An important mediator of this flexibility is top-down regulation from the cholinergic basal forebrain. Basal forebrain projection neurons serve as pacemakers and gatekeepers for downstream neural networks, modulating circuit activity across diverse neuronal populations. This top-down control is necessary for sensory cue detection, learning, and memory, and is disproportionately disrupted in neurodegenerative diseases associated with cognitive decline. Intriguingly, cholinergic signaling acts locally within the basal forebrain to sculpt the activity of basal forebrain output neurons. To determine how local cholinergic signaling impacts basal forebrain output pathways that participate in top-down regulation, we sought to define the dynamics of cholinergic signaling within the basal forebrain during motivated behavior and learning. Toward this, we utilized fiber photometry and the genetically encoded acetylcholine indicator GAChR2.0 to define temporal patterns of cholinergic signaling in the basal forebrain during olfactory-guided, motivated behaviors and learning. We show that cholinergic signaling reliably increased during reward seeking behaviors, but was strongly suppressed by reward delivery in a go/no-go olfactory-cued discrimination task. The observed transient reduction in cholinergic tone was mirrored by a suppression in basal forebrain GABAergic neuronal activity. Together, these findings suggest that cholinergic tone in the basal forebrain changes rapidly to reflect reward-seeking behavior and positive reinforcement and may impact downstream circuitry that modulates olfaction.
Disruption of Glutamate Transport and Homeostasis by Acute Metabolic Stress
Authors: Passlick Stefan , Rose Christine R. , Petzold Gabor C. , Henneberger Christian
Published: February 2021

High-affinity, Na+-dependent glutamate transporters are the primary means by which synaptically released glutamate is removed from the extracellular space. They restrict the spread of glutamate from the synaptic cleft into the perisynaptic space and reduce its spillover to neighboring synapses. Thereby, glutamate uptake increases the spatial precision of synaptic communication. Its dysfunction and the entailing rise of the extracellular glutamate concentration accompanied by an increased spread of glutamate result in a loss of precision and in enhanced excitation, which can eventually lead to neuronal death via excitotoxicity. Efficient glutamate uptake depends on a negative resting membrane potential as well as on the transmembrane gradients of the co-transported ions (Na+, K+, and H+) and thus on the proper functioning of the Na+/K+-ATPase. Consequently, numerous studies have documented the impact of an energy shortage, as occurring for instance during an ischemic stroke, on glutamate clearance and homeostasis. The observations range from rapid changes in the transport activity to altered expression of glutamate transporters. Notably, while astrocytes account for the majority of glutamate uptake under physiological conditions, they may also become a source of extracellular glutamate elevation during metabolic stress. However, the mechanisms of the latter phenomenon are still under debate. Here, we review the recent literature addressing changes of glutamate uptake and homeostasis triggered by acute metabolic stress, i.e., on a timescale of seconds to minutes.
Numerical Study on Electrode Design for Rodent Deep Brain Stimulation With Implantations Cranial to Targeted Nuclei
Authors: Butenko Konstantin , Köhling Rüdiger , van Rienen Ursula
Published: February 2021

The globus pallidus internus and the subthalamic nucleus are common targets for deep brain stimulation to alleviate symptoms of Parkinson's disease and dystonia. In the rodent models, however, their direct targeting is hindered by the relatively large dimensions of applied electrodes. To reduce the neurological damage, the electrodes are usually implanted cranial to the nuclei, thus exposing the non-targeted brain regions to large electric fields and, in turn, possible undesired stimulation effects. In this numerical study, we analyze the spread of the fields for the conventional electrodes and several modifications. As a result, we present a relatively simple electrode design that allows an efficient focalization of the stimulating field in the inferiorly located nuclei.
Primary Headache Disorder Among School Students in Kuwait
Authors: Shuaibi Sameera , AlAshqar Abdelrahman , Ahmed Samar Farouk , Alroughani Raed , AlThufairi Hawraa , Owayed Shaikhah , AlHamdan Fajer , Al-Hashel Jasem
Published: February 2021

Background: Primary headaches are remarkably prevalent worldwide and are increasingly reported among children. However, the exact trend in this age group, particularly in the Gulf region, remains largely unknown.

Aims and Objectives: To examine the prevalence of primary headache disorders among primary and middle school students in Kuwait.

Methods: We conducted a cross-sectional study that included Kuwaiti primary and middle school children and adolescents of both genders in randomly selected schools located in two governorates in Kuwait in the 2018/2019 academic year. Prevalence and attributable burden of headaches, definite and probable migraines, definite and probable tension-type headaches, chronic headaches (≥15 days/month), and probable medication-overuse headaches were assessed using the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire for children and adolescents.

Results: Of 1,485 questionnaires that were distributed, 1,089 students completed the questionnaire with a respondent rate of 73.4%. The study population consisted of 420 boys (38.56%) and 669 girls (61.43%) students with a mean age of 11.5 ± 2.11 years. The 1-year prevalence of primary headache disorders was 42.78%, with more middle schoolers reporting headaches than primary schoolers (50.37 vs. 30.48%; p < 0.02). The mean age of students with primary headaches was 11.98 ± 2.03 years in both genders. When stratified according to diagnostic criteria, migraine headaches were the most frequently reported (20.75%), followed by tension type headaches (18.8%), chronic headaches (2.75%), and probable medication-overuse headaches (0.46%). Primary headaches were significantly higher in girls compared to boys among middle schoolers (66.46 vs. 38.49%; p < 0.001); however, no significant difference between genders was noted among primary school students (33.12 vs. 22.33%; p < 0.118).

Conclusion: Primary headaches are remarkably common in Kuwaiti school students, with migraine headaches being the most frequently reported type. Age and female gender may play a role in the development of primary headaches. These findings necessitate the direction of health services and research efforts toward this age group and warrant the need for further epidemiological studies.
Neuromonitoring in Neonatal-Onset Epileptic Encephalopathies
Authors: Trollmann Regina
Published: February 2021

Considering the wide spectrum of etiologies of neonatal-onset epileptic encephalopathies (EE) and their unfavorable consequences for neurodevelopmental prognoses, neuromonitoring at-risk neonates is increasingly important. EEG is highly sensitive for early identification of electrographic seizures and abnormal background activity. Amplitude-integrated EEG (aEEG) is recommended as a useful bedside monitoring method but as a complementary tool because of methodical limitations. It is of special significance in monitoring neonates with acute symptomatic as well as structural, metabolic and genetic neonatal-onset EE, being at high risk of electrographic-only and prolonged seizures. EEG/aEEG monitoring is established as an adjunctive tool to confirm perinatal hypoxic-ischemic encephalopathy (HIE). In neonates with HIE undergoing therapeutic hypothermia, burst suppression pattern is associated with good outcomes in about 40% of the patients. The prognostic specificity of EEG/aEEG is lower compared to cMRI. As infants with HIE may develop seizures after cessation of hypothermia, recording for at least 24 h after the last seizure is recommended. Progress in the identification of genetic etiology of neonatal EE constantly increases. However, presently, no specific EEG changes indicative of a genetic variant have been characterized, except for individual variants associated with typical EEG patterns (e.g., KCNQ2, KCNT1). Long-term monitoring studies are necessary to define and classify electro-clinical patterns of neonatal-onset EE.
Clinical and MRI Differences Between Patients With Subacute Combined Degeneration of the Spinal Cord Related vs. Unrelated to Recreational Nitrous Oxide Use: A Retrospective Study
Authors: Gao Han , Li Weishuai , Ren Jing , Dong Xiaoyu , Ma Ying , Zheng Dongming
Published: February 2021

Objective: To explore the clinical and imaging characteristics of subacute combined degeneration of the spinal cord (SCD) related to recreational nitrous oxide (N2O) use.

Methods: Clinical and imaging data were retrospectively collected from patients with SCD related to recreational N2O use who were diagnosed and treated at Shengjing Hospital of China Medical University from January 2016 to June 2020. The clinical and imaging features of patients with recreational N2O-related SCD were compared with those of patients with N2O-unrelated SCD, who were diagnosed and treated during the same period of time.

Results: The study enrolled 50 patients (male/female: 22/28, age: 21.4 ± 4.7 years) with N2O-related SCD and 48 patients (male/female: 27/21, age: 62.0 ± 11.4 years) with SCD unrelated to N2O use. The most common signs/symptoms of the patients in both groups were limb numbness and weakness and unsteady gait, but the incidence of limb weakness, unsteady gait, disorders of urination and defecation, anorexia, reduced deep sensation in lower limbs, ataxia, and positive Babinski sign were lower in the N2O-related SCD group than those in the N2O-unrelated SCD group (P < 0.05). The functional disability rating score of patients in the N2O-related SCD group (median: 3, IQR: 2–5) was also significantly lower than the score in the N2O-unrelated SCD group (median: 5, IQR: 4–7) (P < 0.05). The serum vitamin B12 level was significantly lower in the N2O-unrelated SCD group (median: 96 pg/mL, IQR: 50–170 pg/mL) than the level in the N2O-related SCD group (median: 218 pg/mL, IQR:121–350 pg/mL) (P < 0.05), while both groups had similarly increased levels of homocysteine (P > 0.05). Compared with the N2O-unrelated SCD patients, more patients with N2O-related SCD had abnormal spinal magnetic resonance imaging (MRI) scans (80.0 vs. 64.2%). The patients with N2O-related SCD also had wider spinal lesions on sagittal MRI (5.3 ± 0.8 mm vs. 4.2 ± 1.0 mm), fewer spinal segments with lesions (median: 5, IQR: 4–6 segments vs. median: 6, IQR: 5–7.5 segments), and a higher incidence of the inverted V sign on axial MRI (72.0 vs. 31.2%) (all P < 0.05).

Conclusion: The recreational use of N2O has become an important cause of SCD in young patients. Compared with the N2O-unrelated SCD patients, the N2O-related SCD patients had less severe clinical presentations, less obvious decrease in serum VB12 levels, and more obvious MRI changes.
The Milk Metabolome of Non-secretor and Lewis Negative Mothers
Authors: Wang Aidong , Koleva Petya , du Toit Elloise , Geddes Donna T. , Munblit Daniel , Prescott Susan L. , Eggesbø Merete , Johnson Christine C. , Wegienka Ganesa , Shimojo Naoki , Campbell Dianne , Kozyrskyj Anita L. , Slupsky Carolyn M.
Published: February 2021

Introduction: The functional role of milk for the developing neonate is an area of great interest, and a significant amount of research has been done. However, a lot of work remains to fully understand the complexities of milk, and the variations imposed through genetics. It has previously been shown that both secretor (Se) and Lewis blood type (Le) status impacts the human milk oligosaccharide (HMO) content of human milk. While some studies have compared the non-HMO milk metabolome of Se+ and Se− women, none have reported on the non-HMO milk metabolome of Se− and Le– mothers.

Method and Results: To determine the differences in the non-HMO milk metabolome between Se–Le– mothers and other HMO phenotypes (Se+Le+, Se+Le–, and Se–Le+), 10 milk samples from 10 lactating mothers were analyzed using nuclear magnetic resonance (NMR) spectroscopy. Se or Le HMO phenotypes were assigned based on the presence and absence of 6 HMOs generated by the Se and Le genes. After classification, 58 milk metabolites were compared among the HMO phenotypes. Principal component analysis (PCA) identified clear separation between Se–Le– milk and the other milks. Fold change analysis demonstrated that the Se–Le– milk had major differences in free fatty acids, free amino acids, and metabolites related to energy metabolism.

Conclusion: The results of this brief research report suggest that the milk metabolome of mothers with the Se–Le– phenotype differs in its non-HMO metabolite composition from mothers with other HMO phenotypes.
Intra-Individual Comparison of 18F-PSMA-1007 and 18F-FDG PET/CT in the Evaluation of Patients With Prostate Cancer
Authors: Zhou Xing , Li YingChun , Jiang Xiao , Wang XiaoXiong , Chen ShiRong , Shen TaiPeng , You JinHui , Lu Hao , Liao Hong , Li Zeng , Cheng ZhuZhong
Published: February 2021

Purpose

18F labelled PSMA-1007 presents promising results in detecting prostate cancer (PC), while some pitfalls exists meanwhile. An intra-individual comparison of 18F-FDG and 18F-PSMA-1007 in patients with prostate cancer were aimed to be performed in the present study. Then, the pitfalls of 18F-PSMA-1007 PET/CT in imaging of patients with prostate cancer were analyzed.

Methods and Material

21 prostate cancer patients underwent 18F-PSMA-1007 PET/CT as well as 18F-FDG PET/CT before treatment. All positive lesions were noticed in both 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT, then differentiated PC metastasis from benign lesions. the SUVmax, SUVmean and TBR of lesions, up to 10 metastases and 10 benign lesions per patients were recorded (5 for bone, 5 for soft tissue metastasis ). The distribution of positive lesions were analyzed for two imaging. Detection rates, SUVmax, SUVmean and TBR in 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT were compared, respectively. The optimal cut-off values of SUVmax, SUVmean for metastases vs. benign lesions was found through areas under ROC in 18F-PSMA-1007.

Results

The detection rates of primary lesions in 18F-PSMA-1007 PET/CT was higher than that of 18F-FDG PET/CT(100% (21/21) vs. 67%(14/21)). For extra- prostatic lesions, 18F-PSMA-1007 PET/CT revealed 124 positive lesions, 49(49/124, 40%) attributed to a benign origin; 18F-FDG PET/CT revealed 68 positive lesions, 14(14/68, 21%) attributed to a benign origin. The SUVmax, SUVmean, TBR of primary tumor in 18F-PSMA-1007 PET/CT was higher than that in 18F-FDG PET/CT (15.20 vs. 4.20 for SUVmax; 8.70 vs. 2.80 for SUVmean; 24.92 vs. 4.82 for TBR, respectively); The SUVmax, SUVmean, TBR of metastases in 18F-PSMA-1007 PET/CT was higher than that in 18F-FDG PET/CT (10.72 vs. 4.42 for SUVmax; 6.67 vs. 2.59 for SUVmean; The TBR of metastases was 13.3 vs. 7.91). For 18F-FDG PET/CT, the SUVmax, SUVmean in metastases was higher than that in benign lesions (4.42 vs. 3.04 for SUVmax, 2.59 vs. 1.75 for SUVmean, respectively). Similarly, for 18F-PSMA-1007 PET/CT, the SUVmax, SUVmean in metastases was significantly higher than that in benign lesions(10.72 vs. 3.14 for SUVmax, 6.67 vs. 1.91 for SUVmean, respectively), ROC suggested that SUVmax=7.71, SUVmean=5.35 might be the optimal cut-off values for metastases vs. benign lesions.

Conclusion

The pilot study suggested that 18F-PSMA-1007 showed superiority over 18F-FDG because its high detecting rate of PC lesions and excellent tumor uptake. While non-tumor uptake in 18F-PSMA-1007 may lead to misdiagnosis, recognizing these pitfalls and careful analysis can improve the accuracy of diagnosis.
Comprehensive Analysis of Prognostic and Immune Infiltrates for E2F Transcription Factors in Human Pancreatic Adenocarcinoma
Authors: Liu Xu-Sheng , Gao Yan , Liu Chao , Chen Xue-Qin , Zhou Lu-Meng , Yang Jian-Wei , Kui Xue-Yan , Pei Zhi-Jun
Published: February 2021

Background

E2F transcription factors (E2Fs) are a group of genes encoding a family of transcription factors in higher eukaryotes. They are involved in a variety of cellular functions and are up-regulated in many tissues and organs. However, the expression level, genetic variation, molecular mechanism, and biological function of different E2Fs in PAAD and its relationship with the prognosis and immune infiltration in patients with PAAD have not been fully elucidated.

Methods

In this study, we investigated the mRNA expression level, genetic variation, prognostic value and gene–gene interaction network of E2Fs in PAAD using the Oncomine, GEPIA, Kaplan Meier plotter, cBioPortal, GeneMANIA, STRING and Metascape database. Then, the relationship between E2Fs expression and tumor immune invasion was studied by using the TIMER database. Finally, we confirmed the expression of E2Fs in PAAD by IHC.

Results

The transcription levels of E2F1/3/5/8 are obviously up-regulated in PAAD and the high expression of E2F2/3/6/8 was apparently associated with the tumor stage of patients with PAAD. The abnormal expression of E2F1/2/3/4/5/7/8 in PAAD patients is related to the clinical outcome of PAAD patients. We also found that PAAD tissues have higher expression levels of E2F1/3/5/8 compared with adjacent normal tissues. The function of E2Fs and its neighboring genes is mainly related to the transcription initiation of the RNA polymerase II promoter. The functions of E2Fs and its neighboring proteins are mainly related to cell cycle, virus carcinogenesis, FoxO signaling pathway, TGF-β signaling pathway, transcriptional disorders in cancer and Wnt signaling pathway. We also found that the expression of E2Fs was significantly correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+T cells, neutrophils, macrophages, and dendritic cells.

Conclusions

Our study may provide new insights into the choice of immunotherapy targets and prognostic biomarkers in PAAD patients.
Hemicolectomy Does Not Provide Survival Benefit for Right-Sided Mucinous Colon Adenocarcinoma
Authors: Huang Jia , Huang Qiulin , Tang Rong , Chen Guodong , Zhang Yiwei , He Rongfang , Zu Xuyu , Fu Kai , Peng Xiuda , Xiao Shuai
Published: February 2021

Background

The extent of bowel resection is widely debated in colon cancer surgery. Right hemicolectomy (RHC) and partial colectomy (PC) are the most common operation options for right-sided colon cancer (RCC). However, there are still no treatment guidelines or published studies to guide surgical options for mucinous adenocarcinoma (MAC) of RCC.

Methods

Patients with MAC and non-specific adenocarcinoma (AC) of RCC who underwent RHC and PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The general characteristics and survival were compared and analyzed.

Results

A total of 27,910 RCC patients were enrolled in this study, among them 3,413 were MAC. The results showed that race, carcinoembryonic antigen (CEA) level, perineural invasion (PNI), tumor size, tumor location, TNM stage, liver metastasis, chemotherapy were significantly different between MAC and AC groups. The MAC group had similar dissected lymph nodes, but more positive lymph nodes than the AC group. The overall survival (OS) of the MAC group was poorer than that of the AC group, but cancer-specific survival (CSS) was similar between the two groups. The RHC subgroup of the MAC group had more patients of age ≤60 years, larger tumor size, cecum/ascending colon location and dissected lymph nodes than the PC subgroup, but similar positive lymph nodes, perioperative mortality, OS and CSS as the PC subgroup. Moreover, the univariate and multivariable analyses for the survival of RCC patients with MAC showed that RHC might not be a superior predictor for OS and CSS compared with PC.

Conclusions

RHC could not dissect more positive lymph nodes or provide long-term survival benefits for RCC patients with MAC compared with PC. This study could provide some evidence for surgery treatment selection for MAC of RCC, which has important clinical value in individual management of colon cancer patients.
Survival Comparison of Neoadjuvant Chemotherapy Followed by Irreversible Electroporation Versus Conversional Resection for Locally Advanced Pancreatic Cancer
Authors: He Chaobin , Sun Shuxin , Huang Xin , Zhang Yu , Lin Xiaojun , Li Shengping
Published: February 2021

Locally advanced pancreatic cancer (LAPC) is a lethal disease and neoadjuvant chemotherapy and conversional resection is shown to provide the best survival for LAPC patients. Irreversible electroporation (IRE) is a new and effective method for the treatment of LAPC. This study aimed to compare the long-term survival of LAPC patients after neoadjuvant chemotherapy followed by conversional resection and IRE. A total of 140 LAPC patients were included from August 2015 to March 2020. The survival outcomes of patients after treatment with chemotherapy, chemotherapy combined with conversional resection or IRE were analyzed and compared. Patients in these three groups had similar clinical and pathological characteristics. Patients in the resection and IRE groups had similar median OS time (resection group vs. IRE group: 25.3 months vs. 26.0 months, P>0.050), which was significantly longer than that of the chemotherapy group (8.7 months, P<0.001). Additionally, patients in the resection and IRE groups had a median PFS of 10.6 and 12.0 months, respectively. Also, they were significantly higher than that of patients in the chemotherapy group. Chemotherapy combined with conversional resection and IRE was identified as significant prognostic factors for OS and PFS in LAPC patients. It was shown that compared with neoadjuvant chemotherapy followed by surgical resection, chemotherapy and IRE provided similar OS and PFS for LAPC patients with minimal invasion. This combination therapy may be a suitable treatment for LAPC patients.
An Integrative Pharmacology-Based Approach for Evaluating the Potential Effects of Purslane Seed in Diabetes Mellitus Treatment Using UHPLC-LTQ-Orbitrap and TCMIP V2.0
Authors: Hou Jinli , Zhou Xiang , Wang Ping , Zhao Chunhui , Qin Yuewen , Liu Feng , Yu Liping , Xu Haiyu
Published: February 2021

Portulaca oleracea L., known as the “vegetable for long life,” is an annual succulent herb that is widely distributed worldwide. Many clinical and experimental studies have demonstrated that purslane seed (MCXZ) can be used as an adjunctive and alternative therapy for the treatment of diabetes mellitus (DM). However, the underlying active constituents and pharmacological mechanisms through which MCXZ exerts effects in DM remain unclear. In the present study, we confirmed that MCXZ treatment resulted in hypoglycemic activity, lowering the fasting blood glucose and glycated hemoglobin levels in streptozotocin-induced diabetic mice. Then, ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was used to systematically analyze the chemical profile of MCXZ, resulting in the identification of 84 constituents, including 31 organic acids and nine flavonoids. Finally, the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine was employed to analyze the key active components of MCXZ and the molecular mechanisms through which these components acted in DM. Ten key active compounds were identified based on the topological importance of their corresponding putative targets within the known DM-associated therapeutic target network of known MCXZ putative targets. Functionally, these candidate targets play critical anti-hyperlipidemia, anti-hyperglycemia, immunity regulation, and inflammatory roles involving DM-related pathways, such as the vascular endothelial growth factor (VEGF) signaling pathway and Fc gamma R-mediated phagocytosis, which indicated that MCXZ exhibited anti-diabetic activity through multi-faced actions.
The Role of Bone Morphogenetic Protein 9 in Nonalcoholic Fatty Liver Disease in Mice
Authors: Sun Qin-Juan , Cai Ling-Yan , Jian Jie , Cui Ya-Lu , Huang Chen-Kai , Liu Shu-Qing , Lu Jin-Lai , Wang Wei , Zeng Xin , Zhong Lan
Published: February 2021

Background and Aims: It’s reported that bone morphogenetic protein 9 (BMP9) played an important role in lipid and glucose metabolism, but the role of BMP9 in nonalcoholic fatty liver disease (NAFLD) is unclear. Here, we evaluated the therapeutic efficacy of recombined BMP9 in NAFLD mice and investigated the potential mechanism.

Methods: The effects of recombinant BMP9 on NAFLD were assessed in HFD-induced NAFLD mice. C57BL/6 mice were administrated with high-fat diet (HFD) for 12 weeks. In the last 4 weeks, mice were treated with PBS or recombined BMP9 once daily. Insulin sensitivity was evaluated by glucose tolerance test (GTT) and insulin tolerance test (ITT) at the end of the 12th week. Then NAFLD related indicators were assessed by a variety of biological methods, including histology, western blotting, real-time PCR, RNA-seq and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses.

Results: BMP9 reduced obesity, improved glucose metabolism, alleviated hepatic steatosis and decreased liver macrophages infiltration in HFD mice. RNA-seq showed that Cers6, Cidea, Fabp4 involved in lipid and glucose metabolism and Fos, Ccl2, Tlr1 involved in inflammatory response downregulated significantly after BMP9 treatment in HFD mouse liver. ATAC-seq showed that chromatin accessibility on promoters of Cers6, Fabp4, Ccl2 and Fos decreased after BMP9 treatment in HFD mouse liver. KEGG pathway analysis of dysregulated genes in RNA-seq and integration of RNA-seq and ATAC-seq showed that TNF signaling pathway and Toll-like receptor signaling pathway decreased in BMP9 treated HFD mouse liver.

Conclusion: Our data revealed that BMP9 might alleviate NAFLD via improving glucose and lipid metabolism, decreasing inflammatory response and reshaping chromatin accessibility in HFD mouse liver. BMP9 downregulate genes related to lipid metabolism, glucose metabolism and inflammation expression, at least partially via decreasing promoter chromatin accessibility of Cers6, Fabp4, Fos and Tlr1. BMP9 may also reduce the expression of liver Ccl2, thereby changing the number or composition of liver macrophages, and ultimately reducing liver inflammation. The effect of BMP9 on NAFLD might be all-round, and not limit to lipid and glucose metabolism. Therefore, the underlying mechanism needs to be studied in detail further.
Safety of Dabigatran as an Anticoagulant: A Systematic Review and Meta-Analysis
Authors: Zhou Ya , Yao Zhihao , Zhu Linjie , Tang Yong , Chen Jie , Wu Jianming
Published: February 2021

Background: Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor which was developed as an alternative to vitamin K antagonists (VKAs). However, the safety of dabigatran remains controversial so far. In this study, we aimed to compare the risk of bleeding, fatal adverse events, and the all-cause mortality of dabigatran with those of the control group by a systematic review and meta-analysis of randomized controlled trials.

Methods: We systematically searched PubMed, Web of Science, Cochrane Library, Medline, Embase, Wanfang database, Clinical trial, China National Knowledge Infrastructure Chinese Scientific Journal database (VIP), and Chinese Biological Medicine database (CBM), for clinical trials on conventional treatments compared with dabigatran, published between January 2014 and July 2020. The reported outcomes, including the endpoints of primary safety, were systematically investigated.

Results: Seven RCTs (n = 10,743) were included in the present systematic review. Compared to the control groups, dabigatran was not associated with an increased risk of major bleeding (relative risk [RR] 0.86, 95% confidence interval [CI]: 0.61 to 1.21, p = 0.06), intracranial hemorrhage (RR 0.89, 95% CI: 0.58 to 1.36, p = 0.41), fatal adverse reactions (RR 0.87, 95% CI: 0.65 to 1.17, p = 0.66), all-cause mortality (RR 0.88, 95% CI: 0.70 to 1.11, p = 0.45, I2 = 0%), and significantly reduced risk of clinically relevant non-major bleeding (RR 0.96, 95% CI: 0.65 to 1.42, p = 0.0007). However, dabigatran is associated with an increased risk of gastrointestinal (GI) bleeding (RR 1.78, 95% CI: 1.02 to 3.13, p = 0.05).

Conclusion: Dabigatran has a favorable safety profile in terms of major bleeding, intracranial hemorrhage, and life-threatening events, among other safety outcomes. The present study suggested that dabigatran may be a suitable alternative to VKAs as an oral anticoagulant. However, more data are necessary to clarify the incidence of other adverse events and serious adverse reactions.
Phloem Sap Proteins Are Part of a Core Stress Responsive Proteome Involved in Drought Stress Adjustment
Authors: Castañeda Veronica , González Esther M. , Wienkoop Stefanie
Published: February 2021

During moderate drought stress, plants can adjust by changes in the protein profiles of the different organs. Plants transport and modulate extracellular stimuli local and systemically through commonly induced inter- and intracellular reactions. However, most proteins are frequently considered, cell and organelle specific. Hence, while signaling molecules and peptides can travel systemically throughout the whole plant, it is not clear, whether protein isoforms may exist ubiquitously across organs, and what function those may have during drought regulation. By applying shotgun proteomics, we extracted a core proteome of 92 identical protein isoforms, shared ubiquitously amongst several Medicago truncatula tissues, including roots, phloem sap, petioles, and leaves. We investigated their relative distribution across the different tissues and their response to moderate drought stress. In addition, we functionally compared this plant core stress responsive proteome with the organ-specific proteomes. Our study revealed plant ubiquitous protein isoforms, mainly related to redox homeostasis and signaling and involved in protein interaction networks across the whole plant. Furthermore, about 90% of these identified core protein isoforms were significantly involved in drought stress response, indicating a crucial role of the core stress responsive proteome (CSRP) in the plant organ cross-communication, important for a long-distance stress-responsive network. Besides, the data allowed for a comprehensive characterization of the phloem proteome, revealing new insights into its function. For instance, CSRP protein levels involved in stress and redox are relatively more abundant in the phloem compared to the other tissues already under control conditions. This suggests a major role of the phloem in stress protection and antioxidant activity enabling the plants metabolic maintenance and rapid response upon moderate stress. We anticipate our study to be a starting point for future investigations of the role of the core plant proteome. Under an evolutionary perspective, CSRP would enable communication of different cells with each other and the environment being crucial for coordinated stress response of multicellular organisms.
Comparing Depressive Symptoms, Emotional Exhaustion, and Sleep Disturbances in Self-Employed and Employed Workers: Application of Approximate Bayesian Measurement Invariance
Authors: Bergman Louise E. , Bernhard-Oettel Claudia , Bujacz Aleksandra , Leineweber Constanze , Toivanen Susanna
Published: February 2021

Studies investigating differences in mental health problems between self-employed and employed workers have provided contradictory results. Many of the studies utilized scales validated for employed workers, without collecting validity evidence for making comparisons with self-employed. The aim of this study was (1) to collect validity evidence for three different scales assessing depressive symptoms, emotional exhaustion, and sleep disturbances for employed workers, and combinators; and (2) to test if these groups differed. We first conducted approximate measurement invariance analysis and found that all scales were invariant at the scalar level. Self-employed workers had least mental health problems and employed workers had most, but differences were small. Though we found the scales invariant, we do not find them optimal for comparison of means. To be more precise in describing differences between groups, we recommend using clinical cut-offs or scales developed with the specific purpose of assessing mental health problems at work.
If Motivation Was a Key Factor in Aerobic Performance in Tropical Climate?
Authors: Coudevylle Guillaume R. , Sinnapah Stéphane , Collado Aurélie , Fenouillet Fabien , Hue Olivier , Parrat Matthieu , Robin Nicolas
Published: February 2021

This mini review examines the impact of tropical climate (TC) on motivational factors during aerobic performance and proposes the tracks of an integrative theoretical model to better understand the direct and indirect motivational mechanisms that can operate on athletic performances. TC is detrimental for aerobic performance and, although it clearly induces physiological constraints, these do not seem to be the only factors that explain the performance decline. Indeed, TC performance researchers have developed a theory of anticipation, which suggests that the brain commands a reduction in effort to protect the body from probable harm and heatstroke risk. The objective of this mini review is thus to examine the possibility that motivation may be a key factor in TC performance. The main psychological impacts of TC on aerobic performance are reviewed and an integrative theoretical model is presented that may help to better understand the mechanisms of motivation.
The Talent Training Mode of International Service Design Using a Human–Computer Interaction Intelligent Service Robot From the Perspective of Cognitive Psychology
Authors: Yang Yayun
Published: February 2021

To effectively improve the efficiency of international service design talent training and make it more in line with society's needs, we analyze the current status of international service design talent training and its professional training focus. Based on the above problems, from the perspective of cognitive psychology, artificial intelligence and human–computer interaction (HCI) technology are used to construct the international service design talent training mode of the HCI intelligent service robot. This mode can be used to solve the existing teaching problems by using novel means to ensure the quality of teaching. Finally, through the actual analysis of teaching cases, the effectiveness of the proposed talent training mode is verified. The HCI system is based on knowledge of cognitive psychology. According to the characteristics and functions of an educational robot, the robot is combined with traditional teaching activities, and the robot-assisted talent training mode is designed. Robot-assisted talent training is a feasible training method that can improve the efficiency of talent training. Students have confidence in their learning skills before the course, and the confidence is further strengthened after the end of the course. After the course, the students have a stronger sense of cooperation. This study can provide theoretical ideas for the research of international service talent training mode.
Experimental Nuclear Astrophysics With the Light Elements Li, Be and B: A Review
Authors: Rapisarda G.G. , Lamia L. , Caciolli A. , Li Chengbo , Degl’Innocenti S. , Depalo R. , Palmerini S. , Pizzone R.G. , Romano S. , Spitaleri C. , Tognelli E. , Wen Qungang
Published: February 2021

Light elements offer a unique opportunity for studying several astrophysical scenarios from Big Bang Nucleosynthesis to stellar physics. Understanding the stellar abundances of light elements is key to obtaining information on internal stellar structures and mixing phenomena in different evolutionary phases, such as the pre-main-sequence, main-sequence or red-giant branch. In such a case, light elements, i.e., lithium, beryllium and boron, are usually burnt at temperatures of the order of 2–5 × 106 K. Consequently, the astrophysical S(E)-factor and the reaction rate of the nuclear reactions responsible for the burning of such elements must be measured and evaluated at ultra-low energies (between 0 and 10 keV). The Trojan Horse Method (THM) is an experimental technique that allows us to perform this kind of measurements avoiding uncertainties due to the extrapolation and electron screening effects on direct data. A long Trojan Horse Method research program has been devoted to the measurement of light element burning cross sections at astrophysical energies. In addition, dedicated direct measurements have been performed using both in-beam spectroscopy and the activation technique. In this review we will report the details of these experimental measurements and the results in terms of S(E)-factor, reaction rate and electron screening potential. A comparison between astrophysical reaction rates evaluated here and the literature will also be given.
The Initial Months of COVID-19: Dog Owners' Veterinary-Related Concerns
Authors: Kogan Lori R. , Erdman Phyllis , Bussolari Cori , Currin-McCulloch Jennifer , Packman Wendy
Published: February 2021

Veterinarians, like many other professions, were significantly impacted by the onset of COVID-19 in the spring of 2020. Standard practices were disrupted, and veterinary hospitals had to quickly modify standard protocols to safely serve their clients and patients. The purpose of this study was to better understand dog owners' fears and concerns pertaining to veterinary care and obtainment of pet care products and food during the lock down phase of a pandemic to be better prepared to address these concerns now and in the future. To this end, an online, anonymous, cross-sectional survey was designed and distributed to adult dog owners via social media. The results, from a total of 4,105 participants (the majority from the United States and Canada), indicated substantial areas of concern. The number one concern of dog owners during this time was the availability of emergency veterinary care. Owners under 30 years of age, compared to older owners, were significantly more concerned about both availability and cost of veterinary care (emergency and non-emergency). The ability to care for one's dog if they were to become ill was a concern for many owners, yet only 60% had identified a caretaker for their dog if one was needed. These results suggest that the majority of dog owners remained true steadfast guardians of their dogs, continuing to make them a priority, even during pandemic times. Suggestions to help mitigate dog owners' concerns and improve communication between owners and veterinarian teams are offered.
Does Loneliness Have a Cost? A Population-Wide Study of the Association Between Loneliness and Healthcare Expenditure
Authors: Meisters Rachelle , Westra Daan , Putrik Polina , Bosma Hans , Ruwaard Dirk , Jansen Maria
Published: February 2021

Objectives: Loneliness has been associated with unhealthy behavior, poorer health, and increased morbidity. However, the costs of loneliness are poorly understood.

Methods: Multiple sources were combined into a dataset containing a nationally representative sample (n = 341,376) of Dutch adults (18+). The association between loneliness and total, general practitioner (GP), specialized, pharmaceutical, and mental healthcare expenditure was tested using Poisson and Zero-inflated negative binomial models, controlling for numerous potential confounders (i.e., demographic, socioeconomic, lifestyle-related factors, self-perceived health, and psychological distress), for four age groups.

Results: Controlling for demographic, socioeconomic, and lifestyle-related factors, loneliness was indirectly (via poorer health) associated with higher expenditure in all categories. In fully adjusted models, it showed a direct association with higher expenditure for GP and mental healthcare (0.5 and 11.1%, respectively). The association with mental healthcare expenditure was stronger in younger than in older adults (for ages 19–40, the contribution of loneliness represented 61.8% of the overall association).

Conclusion: Loneliness contributes to health expenditure both directly and indirectly, particularly in younger age groups. This implies a strong financial imperative to address this issue.
Influence of Physicochemical Characteristics of Bean Crop Soil in Trichoderma spp. Development
Authors: Mayo-Prieto Sara , Porteous-Álvarez Alejandra J. , Mezquita-García Sergio , Rodríguez-González Álvaro , Carro-Huerga Guzmán , del Ser-Herrero Sara , Gutiérrez Santiago , Casquero Pedro A.
Published: February 2021

Spain has ranked 6th on the harvested bean area and 8th in bean production in the European Union (EU). The soils of this area have mixed silt loam and sandy loam texture, with moderate clay content, neutral or acidic pH, rich in organic matter and low carbonate levels, providing beans with high water absorption capacity and better organoleptic qualities after cooking. Similar to other crops, it is attacked by some phytopathogens. Hitherto, chemical methods have been used to control these organisms. However, with the Reform of the Community Agrarian Policy in the EU, the number of authorized plant protection products has been reduced to prevail food security, as well as to be sustainable in the long term, giving priority to the non-chemical methods that use biological agents, such as Trichoderma. This study aimed to investigate the relative importance of various crop soil parameters in the adaptation of Trichoderma spp. autoclaved soils (AS) and natural soils (NS) from the Protected Geographical Indication (PGI) “Alubia La Bañeza—León” that were inoculated with Trichoderma velutinum T029 and T. harzianum T059 and incubated in a culture chamber at 25 °C for 15 days. Their development was determined by quantitative PCR. Twelve soil samples were selected and analyzed from the productive zones of Astorga, La Bañeza, La Cabrera, Esla-Campos and Páramo. Their physicochemical characteristics were different by zone, as the texture of soils ranged between sandy loam and silt loam and the pH between strongly acid and slightly alkaline, as well as the organic matter (OM) concentration between low and remarkably high. Total C and N concentrations and their ratio were between medium and high in most of the soils and the rest of the micronutrients had an acceptable concentration except for Paramo’s soil. Both Trichoderma species developed better in AS than in NS, T. velutinum T029 grew better with high levels of OM, total C, ratio C:N, P, K, Fe, and Zn than T. harzianum T059 in clay soils, with the highest values of cation exchange capacity (CEC), pH, Ca, Mg and Mn. These effects were validated by Canonical Correlation Analysis (CCA), texture, particularly clay concentration, OM, electrical conductivity (EC), and pH (physical parameters) and B and Cu (soil elements) are the main factors explaining the influence in the Trichoderma development. OM, EC, C:N ratio and Cu are the main soil characteristics that influence in T. velutinum T029 development and pH in the development of T. harzianum T059.
Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment
Authors: Li Jiayin , Sheng Yueying , Ma Ruijing , Xu Mengsha , Liu Fuli , Qin Rong , Zhu Mingxi , Zhu Xianchao , He Ping
Published: February 2021

Carbapenem-resistant Klebsiella pneumoniae (CRKP), one of the major nosocomial pathogens, is increasingly becoming a serious threat to global public health. There is an urgent need to develop effective therapeutic and preventive approaches to combat the pathogen. Here, we identified and characterized a novel capsule depolymerase (K64-ORF41) derived from Klebsiella phage SH-KP152410, which showed specific activities for K. pneumoniae K64-serotype. We showed that this depolymerase could be used in the identification of K64 serotypes based on the capsular typing, and the results agreed well with those from the conventional serotyping method using antisera. From this study, we also identified K64 mutant strains, which showed typing discrepancy between wzi-sequencing based genotyping and depolymerase-based or antiserum-based typing methods. Further investigation indicated that the mutant strain has an insertion sequence (IS) in wcaJ, which led to the alteration of the capsular serotype structure. We further demonstrated that K64-ORF41 depolymerase could sensitize the bacteria to serum or neutrophil killing by degrading the capsular polysaccharide. In summary, the identified K64 depolymerase proves to be an accurate and reliable tool for capsular typing, which will facilitate the preventive intervention such as vaccine development. In addition, the polymerase may represent a potential and promising therapeutic biologics against CRKP-K64 infections.
Impact of Mycotoxins on Animals’ Oxidative Status
Authors: Mavrommatis Alexandros , Giamouri Elisavet , Tavrizelou Savvina , Zacharioudaki Maria , Danezis George , Simitzis Panagiotis E. , Zoidis Evangelos , Tsiplakou Eleni , Pappas Athanasios C. , Georgiou Constantinos A. , Feggeros Kostas
Published: February 2021

Mycotoxins appear to be the “Achilles’ heel” of the agriculture sector inducing enormous economic losses and representing a severe risk to the health of humans and animals. Although novel determination protocols have been developed and legislation has been implemented within Europe, the side effects of mycotoxins on the homeostatic mechanisms of the animals have not been extensively considered. Feed mycotoxin contamination and the effects on the antioxidant status of livestock (poultry, swine, and ruminants) are presented. The findings support the idea that the antioxidant systems in both monogastrics and ruminants are challenged under the detrimental effect of mycotoxins by increasing the toxic lipid peroxidation by-product malondialdehyde (MDA) and inhibiting the activity of antioxidant defense mechanisms. The degree of oxidative stress is related to the duration of contamination, co-contamination, the synergetic effects, toxin levels, animal age, species, and productive stage. Since the damaging effects of MDA and other by-products derived by lipid peroxidation as well as reactive oxygen species have been extensively studied on human health, a more integrated monitoring mechanism (which will take into account the oxidative stability) is urgently required to be implemented in animal products.