bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeding Limosilactobacillus fermentum K9-2 and Lacticaseibacillus casei K9-1, or Limosilactobacillus reuteri TMW1.656 Reduces Pathogen Load in Weanling Pigs
Authors: Wang Weilan , Zijlstra Ruurd T. , Gänzle Michael G.
Published: January 2021

Applying probiotics to improve gut health and growth performance of pigs is considered an effective approach to reduce use of antimicrobial growth promoters in swine production. Understanding the properties of these probiotics is a prerequisite for the selection of probiotic strains for pigs. Host-adapted probiotic strains were suggested to exert probiotic effects by different mechanisms when compared to free-living or nomadic probiotic strains. This study assessed the effect of probiotic intervention with Limosilactobacillus reuteri TMW1.656, a host-adapted species producing the antimicrobial compound reutericyclin, its isogenic and reutericyclin-negative L. reuteri TMW1.656ΔrtcN, and with Limosilactobacillus fermentum and Lacticaseibacillus casei, two species with a nomadic lifestyle. Probiotic strains were supplemented to the post weaning diet in piglets by fermented feed or as freeze-dried cultures. The composition of fecal microbiota was determined by high throughput sequencing of 16S rRNA gene sequence tags; Enterotoxigenic Escherichia coli and Clostridium perfringens were quantified by qPCR targeting specific virulence factors. Inclusion of host-adapted L. reuteri effectively reduced ETEC abundance in swine intestine. In contrast, nomadic L. fermentum and L. casei did not show inhibitory effects on ETEC but reduced the abundance of Clostridium spp. In addition, the increasing abundance of Bacteriodetes after weaning was correlated to a reduction of ETEC abundance. Remarkably, the early colonization of piglets with ETEC was impacted by maternal-neonatal transmission; the pattern of virulence factors changed significantly over time after weaning. Probiotic intervention or the production of reutericyclin showed limited effect on the overall composition of commensal gut microbiota. In conclusion, the present study provided evidence that the lifestyle of lactobacilli is a relevant criterion for selection of probiotic cultures while the production of antimicrobial compounds has only minor effects.
An Integrative Nomogram for Identifying Early-Stage Parkinson's Disease Using Non-motor Symptoms and White Matter-Based Radiomics Biomarkers From Whole-Brain MRI
Authors: Shu Zhenyu , Pang Peipei , Wu Xiao , Cui Sijia , Xu Yuyun , Zhang Minming
Published: January 2021

Purpose: To develop and validate an integrative nomogram based on white matter (WM) radiomics biomarkers and nonmotor symptoms for the identification of early-stage Parkinson's disease (PD).

Methods: The brain magnetic resonance imaging (MRI) and clinical characteristics of 336 subjects, including 168 patients with PD, were collected from the Parkinson's Progress Markers Initiative (PPMI) database. All subjects were randomly divided into training and test sets. According to the baseline MRI scans of patients in the training set, the WM was segmented to extract the radiomic features of each patient and develop radiomics biomarkers, which were then combined with nonmotor symptoms to build an integrative nomogram using machine learning. Finally, the diagnostic accuracy and reliability of the nomogram were evaluated using a receiver operating characteristic curve and test data, respectively. In addition, we investigated 58 patients with atypical PD who had imaging scans without evidence of dopaminergic deficit (SWEDD) to verify whether the nomogram was able to distinguish patients with typical PD from patients with SWEDD. A decision curve analysis was also performed to validate the clinical practicality of the nomogram.

Results: The area under the curve values of the integrative nomogram for the training, testing and verification sets were 0.937, 0.922, and 0.836, respectively; the specificity values were 83.8, 88.2, and 91.38%, respectively; and the sensitivity values were 84.6, 82.4, and 70.69%, respectively. A significant difference in the number of patients with PD was observed between the high-risk group and the low-risk group based on the nomogram (P < 0.05).

Conclusion: This integrative nomogram is a new potential method to identify patients with early-stage PD.
A Comparison of Isolation Stress and Unpredictable Chronic Mild Stress for the Establishment of Mouse Models of Depressive Disorder
Authors: Lee Jin-Seok , Kang Ji-Yun , Son Chang-Gue
Published: January 2021

This study aimed to help to understand the influence of stress on depression, which reflects the social environments of especially solitary life and the increasing prevalence of depressive disorders. To determine the distinguishable features of two-representative animal models of stress-induced depressive disorder, we compared isolation stress (IS) and unpredictable chronic mild stress (UCMS). After 4-week of stress, both models showed significant depressive- and anxiety-like behaviors in an open field test (OFT; p < 0.01 for IS, p < 0.01 for UCMS), forced swimming test (FST; p < 0.01 for IS, p < 0.01 for UCMS), and tail suspension test (TST; p < 0.01 for IS, p < 0.05 for UCMS) along with alterations in serum corticosterone levels, serotonin activity in the dorsal raphe nuclei (DRN) and microglial activity in the dentate gyrus of the hippocampus (p < 0.05 for both parameters). In a comparison of the two stress models, IS strongly induced depressive and anxiety features, as indicated by all parameters: behavior test scores (p < 0.05 for OFT, FST, and TST), serum corticosterone levels (p < 0.05), immunohistological alterations for serotonin activity (p < 0.05) and microglial activity (p = 0.072). Our results indicate the suitability of IS for the development of animal models of depressive disorders and may reveal the medical impact of social isolation environment in modern society.
Case Report: Postacute Rehabilitation of Guillain-Barré Syndrome and Cerebral Vasculitis-Like Pattern Accompanied by SARS-CoV-2 Infection
Authors: Colonna Stefano , Sciumé Luciana , Giarda Federico , Innocenti Alessandro , Beretta Giovanna , Dalla Costa Davide
Published: January 2021

Introduction: The main clinical manifestation of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is respiratory issues. Neurological manifestations are being increasingly recognized, including febrile seizures, headache, dizziness, and myalgia, as well as encephalopathy, encephalitis, stroke, and acute peripheral nerve diseases. Cerebral vasculitis is rarely reported. We describe a case of SARS-CoV-2 interstitial pneumonia complicated by flaccid tetraplegia due to Guillain-Barré Syndrome (GBS) associated with a cerebral vasculitis-like pattern.

Case description: A 62-year-old man was hospitalized for cough, fever, and severe respiratory failure requiring tracheal intubation and invasive ventilation. The chest Computerized Tomography (CT) showed images related to interstitial pneumonia and the subsequent nasopharyngeal swab confirmed the presence of SARS-CoV-2 infection. During the hospitalization, there was a progressive deterioration of the senses associated with areflexic flaccid tetraplegia. The treatment with high doses of immunoglobulin G (IgG) led to the immediate improvement of the general conditions and a partial response in terms of recovery of the upper limb and of the distal lower limb movements. Subsequently the patient was admitted to our Rehabilitation Unit, where he received an intensive rehabilitation treatment consisting of physiotherapy and occupational therapy. Two months later the patient was discharged at home and able to walk independently even for long distances thanks to the use of Ankle-Foot Orthosis (AFO).

Conclusion: In this report, we present the case of a patient with peripheral and central neurological damage occurred later severe pneumonia induced by SARS-CoV-2. The Immunoglobulin G therapy allowed the patient to benefit considerably from early rehabilitation, reaching the walking, increasing the independence in daily living tasks, and enabling safe discharge from hospital to home. Related neurologic complications of SARS-CoV-2 infection suffer a lack of understanding and further investigations should be conducted.
Frontal Theta Oscillation as a Mechanism for Implicit Gender Stereotype Control: Electrophysiological Evidence From an Extrinsic Affective Simon Task
Authors: Jia Lei , Cheng Mengru , Sung Billy , Wang Cheng , Wang Jun , Li Feiming
Published: January 2021

Previous research has indicated that frontal midline theta (FMθ) reflects a domain-general cognitive control mechanism of the prefrontal cortex. Brain imaging studies have shown that the inhibition of implicit stereotypes was dependent on this domain-general cognitive control mechanism. Based on this knowledge, the present study investigated the neural oscillatory correlates of implicit gender stereotype control in an extrinsic affective Simon task (EAST) using electrophysiological methods. Participants in this task conducted verification to white gender names and colored gender traits, and their behavioral response and electroencephalogram (EEG) were recorded during their performances. As predicted, stereotype-inconsistent trials resulted in reduced response accuracies and slower response times than stereotype-consistent trials. For the event-related potential (ERP) results, the enhanced performance of stereotype-inconsistent trials was accompanied by an enhanced N400 amplitude but an attenuated late positive potential amplitude. In contrast, early attentional components such as P2 and N2 as well as their amplitudes were impacted by the experimental manipulations and individual differences in gender factors. In addition, based on time–frequency (TF) analysis, we found that the enhanced performance of stereotype-inconsistent trials was also accompanied by an event-related synchronization on the frontal theta oscillation. This frontal theta appeared at a late processing stage and persisted across a time window from N400 to late positive potential. Additionally, this enhanced frontal theta effect was not modulated by the experimental manipulations and individual differences in gender factors. Based on these findings, the feature of frontal theta oscillation in the implicit gender stereotype control process was discussed.
Characteristics of Epigenetic Clocks Across Blood and Brain Tissue in Older Women and Men
Authors: Grodstein Francine , Lemos Bernardo , Yu Lei , Iatrou Artemis , De Jager Philip L. , Bennett David A.
Published: January 2021

Epigenetic clocks are among the most promising biomarkers of aging. It is particularly important to establish biomarkers of brain aging to better understand neurodegenerative diseases. To advance application of epigenetic clocks—which were largely created with DNA methylation levels in blood samples—for use in brain, we need clearer evaluation of epigenetic clock behavior in brain, including direct comparisons of brain specimens with blood, a more accessible tissue for research. We leveraged data from the Religious Orders Study and Rush Memory and Aging Project to examine three established epigenetic clocks (Horvath, Hannum, PhenoAge clocks) and a newer clock, trained in cortical tissue. We calculated each clock in three different specimens: (1) antemortem CD4+ cells derived from blood (n = 41); (2) postmortem dorsolateral prefrontal cortex (DLPFC, n = 730); and (3) postmortem posterior cingulate cortex (PCC, n = 186), among older women and men, age 66–108 years at death. Across all clocks, epigenetic age calculated from blood and brain specimens was generally lower than chronologic age, although differences were smallest for the Cortical clock when calculated in the brain specimens. Nonetheless, we found that Pearson correlations of epigenetic to chronologic ages in brain specimens were generally reasonable for all clocks; correlations for the Horvath, Hannum, and PhenoAge clocks largely ranged from 0.5 to 0.7 (all p < 0.0001). The Cortical clock outperformed the other clocks, reaching a correlation of 0.83 in the DLFPC (p < 0.0001) for epigenetic vs. chronologic age. Nonetheless, epigenetic age was quite modestly correlated across blood and DLPFC in 41 participants with paired samples [Pearson r from 0.21 (p = 0.2) to 0.32 (p = 0.05)], indicating that broader research in neurodegeneration may benefit from clocks using CpG sites better conserved across blood and brain. Finally, in analyses stratified by sex, by pathologic diagnosis of Alzheimer disease, and by clinical diagnosis of Alzheimer dementia, correlations of epigenetic to chronologic age remained consistently high across all groups. Future research in brain aging will benefit from epigenetic clocks constructed in brain specimens, including exploration of any advantages of focusing on CpG sites conserved across brain and other tissue types.
The Sleep of Shift Workers in a Remote Mining Operation: Methodology for a Randomized Control Trial to Determine Evidence-Based Interventions
Authors: Maisey Gemma , Cattani Marcus , Devine Amanda , Lo Johnny , Dunican Ian C.
Published: January 2021

Shiftwork may adversely impact an individual’s sleep-wake patterns and result in sleep loss (<6 h. following night shift), due to the circadian misalignment and the design of rosters and shifts. Within a mining operation, this sleep loss may have significant consequences due to fatigue, including an increased risk of accidents and chronic health conditions. This study aims to (i) determine the efficacy of an intervention that comprises a sleep education program and biofeedback through a smartphone app on sleep quality, quantity, and alertness (ii) determine the prevalence of risk for a potential sleep disorder, and (iii) quantify and describe the sleep habits and behaviors of shift workers in a remote mining operation. This study consists of a randomized controlled trial whereby eighty-eight shift workers within a remote mining operation are randomized to a control group or one of three different treatment groups that are: (i) a sleep education program, (ii) biofeedback on sleep through a smartphone app, or (iii) a sleep education program and biofeedback on sleep through a smartphone app. This study utilizes wrist-activity monitors, biomathematical modeling, and a survey instrument to obtain data on sleep quantity, quality, and alertness. A variety of statistical methods will determine the prevalence of risk for a potential sleep disorder and associations with body mass index, alcohol, and caffeine consumption. A generalized linear mixed model will examine the dependent sleep variables assessed at baseline and post-intervention for the control group and intervention groups, as well as within and between groups to determine changes. The findings from this study will contribute to the current understanding of sleep and alertness behaviors, and sleep problems and disorders amongst shift workers. Importantly, the results may inform fatigue policy and practice on interventions to manage fatigue risk within the mining industry. This study protocol may have a broader application in other shiftwork industries, including oil and gas, aviation, rail, and healthcare.
Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer
Authors: Chen Beibei , Wang Sai-Qi , Huang Jinxi , Xu Weifeng , Lv Huifang , Nie Caiyun , Wang Jianzheng , Zhao Huichen , Liu Yingjun , Li Jitian , Lu Canrong , Zhang Jianying , Chen Xiao-Bing
Published: January 2021

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/β-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival in vitro and tumorigenesis in vivo of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G2/M phase and repression of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.
Vitamin D Status and Survival in Stage II-III Colorectal Cancer
Authors: Bao Yichao , Li Yaqi , Gong Yan , Huang Qianxia , Cai Sanjun , Peng Junjie
Published: January 2021

Vitamin D status has been shown to be positively correlated with the morbidity and prognosis of colorectal cancer (CRC) patients. However, the prognostic effect of vitamin D status on patients with stage II and III CRC, especially Asian patients, remains unclear. A total of 728 patients (523 in the primary cohort and 205 in the validation cohort) who were diagnosed with stage II-III CRC between January 2011 and December 2015 were enrolled. Their serum 25-hydroxyvitamin D3 [25(OH)D] levels were tested. Kaplan-Meier curves and Cox regression analyses were carried out. Subgroup analyses were conducted according to tumor location. In the primary cohort, the serum 25(OH)D level was positively correlated with the overall survival (OS) of all CRC patients (p= 0.016) and stage III patients (p= 0.009), while no correlation was found between 25(OH)D level and the prognosis of patients with stage II CRC. Moreover, 25(OH)D level was an independent prognostic factor for the OS of all patients with CRC [HR 0.541, 95% CI 0.334–0.875, p=0.012] and those with stage III CRC (HR 0.563, 95% CI 0.319–0.993, p=0.047). Subgroup analysis indicated that only in the left-sided subgroup, stage III CRC patients with high 25(OH)D levels had better OS than those with low 25(OH)D levels (HR 0.474, 95% CI 0.230–0.978, p=0.043). In the validation cohort, serum 25(OH)D levels were verified to have prognostic value for patients with stage III CRC (HR 0.220, 95% CI 0.080–0.602, p=0.003), and low 25(OH)D levels indicated worse OS for left-sided stage III CRC patients (HR 0.233, 95% CI 0.075–0.727, p=.012). In conclusion, vitamin D status is positively correlated with the survival of CRC patients, especially those with left-sided stage III CRC.
Regulation of Hedgehog Signaling by miRNAs and Nanoformulations: A Possible Therapeutic Solution for Colorectal Cancer
Authors: Javed Zeeshan , Javed Iqbal Muhammad , Rasheed Amna , Sadia Haleema , Raza Shahid , Irshad Asma , Koch Wojciech , Kukula-Koch Wirginia , Głowniak-Lipa Anna , Cho William C. , Sharifi-Rad Javad
Published: January 2021

Hedgehog (Hh) signaling aberrations trigger differentiation and proliferation in colorectal cancer (CRC). However, the current approaches which inhibit this vital cellular pathway provoke some side effects. Therefore, it is necessary to look for new therapeutic options. MicroRNAs are small molecules that modulate expression of the target genes and can be utilized as a potential therapeutic option for CRC. On the other hand, nanoformulations have been implemented in the treatment of plethora of diseases. Owing to their excessive bioavailability, limited cytotoxicity and high specificity, nanoparticles may be considered as an alternative drug delivery platform for the Hh signaling mediated CRC. This article reviews the Hh signaling and its involvement in CRC with focus on miRNAs, nanoformulations as potential diagnostic/prognostic and therapeutics for CRC.
Modeling the Leukemia Microenviroment In Vitro
Authors: Scielzo Cristina , Ghia Paolo
Published: January 2021

Over the last decade, the active role of the microenvironment in the pathogenesis, development and drug resistance of B cell malignancies has been clearly established. It is known that the tissue microenvironment promotes proliferation and drug resistance of leukemic cells suggesting that successful treatments of B cell malignancies must target the leukemic cells within these compartments. However, the cross-talk occurring between cancer cells and the tissue microenvironment still needs to be fully elucidated. In solid tumors, this lack of knowledge has led to the development of new and more complex in vitro models able to successfully mimic the in vivo settings, while only a few simplified models are available for haematological cancers, commonly relying only on the co-culture with stabilized stromal cells and/or the addition of limited cocktails of cytokines. Here, we will review the known cellular and molecular interactions occurring between monoclonal B lymphocytes and their tissue microenvironment and the current literature describing innovative in vitro models developed in particular to study chronic lymphocytic leukemia (CLL). We will also elaborate on the possibility to further improve such systems based on the current knowledge of the key molecules/signals present in the microenvironment. In particular, we think that future models should be developed as 3D culture systems with a higher level of cellular and molecular complexity, to replicate microenvironmental-induced signaling. We believe that innovative 3D-models may therefore improve the knowledge on pathogenic mechanisms leading to the dissemination and homing of leukemia cells and consequently the identification of therapeutic targets.
Optimal Timing to Surgery After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer
Authors: Wang Yinkui , Liu Zining , Shan Fei , Ying Xiangji , Zhang Yan , Li Shuangxi , Jia Yongning , Li Ziyu , Ji Jiafu
Published: January 2021

Background

The relationship between time to surgery (TTS) and survival benefit is not sufficiently demonstrated by previous studies in locally advanced gastric cancer (LAGC). This study aims to assess the impact of TTS after neoadjuvant chemotherapy (NACT) on long-term and short-term outcomes in LAGC patients.

Methods

Data were collected from patients with LAGC who underwent NACT between January 2007 and January 2018 at our institution. Outcomes assessed were long-term survival, pathologic complete response (pCR) rate, and postoperative complications.

Results

This cohort of 426 patients was divided into five groups by weeks of TTS. Under cox regression, compared to other groups, the 22–28 days and 29–35 days groups revealed a better OS (≤21 vs. 22–28 days: HR 1.54, 95% CI = 0.81–2.93, P = 0.185; 36–42 vs. 22–28 days: HR 2.20, 95% CI = 1.28−3.79, P = 0.004; 43–84 vs. 22–28 days: HR 1.83, 95% CI = 1.09–3.06, P = 0.022) and PFS (≤21 vs. 22–28 days: HR 1.54, 95% CI = 0.81–2.93, P = 0.256; 36–42 vs. 22–28 days: HR 2.20, 95% CI = 1.28−3.79, P = 0.111; 43–84 vs. 22–28 days: HR 1.83, 95% CI = 1.09–3.06, P = 0.047). Further analysis revealed a better prognosis in patients with TTS within 22–35 days (OS: HR 1.78 95% CI = 1.25−2.54, P = 0.001; PFS: HR 1.49, 95% CI = 1.07−2.08, P = 0.017). Postoperative stay was significantly higher in the ≤21 days group, while other parameters revealed no statistical significance (P > 0.05). Restricted cubic spline depicted the nonlinear relationship between TTS and OS/PFS.

Conclusion

Patients who received surgery within 3−5 weeks experienced the maximal survival benefit without an increase in postoperative complications or lowering the rate of pCR. Further investigations are warranted.
An Important Finding of White Matter Injury in Late Preterm Infant: Deep Medullary Vein Involvement
Authors: Chen Dan , Sun Jing , Li Qiuyu , Bai Wenjuan , Mao Jian
Published: January 2021

Objective: To investigate high risk factors and magnetic resonance imaging (MRI) features in late preterm infants with severe white matter injury (WMI) associated with abnormal deep medullary veins (DMVs).

Materials and Methods: Preterm infants with severe WMI, who were hospitalized in Shengjing Hospital from 1st January 2009 to 31st December 2018, were enrolled in this retrospective study. High risk factors and MRI characteristics of infants with abnormal DMVs were analyzed and compared with those of infants without DMV abnormalities.

Results: A total of 2032 late preterm infants were examined by MRI; 71 cases (3.5%) had severe WMI and 15 of these (21.1%) had abnormal DMVs. The incidence of maternal diabetes was higher in infants with abnormal DMVs and neonatal convulsions were more likely (P < 0.05). The incidence of grade IV injury (P < 0.05), white matter periventricular cysts and thalamic injury (P < 0.01), cerebral venous sinus thrombus (P < 0.01) and germinal matrix/intraventricular hemorrhage (P < 0.05) were higher in infants with abnormal DMVs than in infants with normal DMVs.

Conclusions: Congestion/thrombosis of DMVs may be an important cause of severe WMI in late preterm infants, especially in periventricular leukomalacia-like WMI. WMI with abnormal DMVs is more likely to lead to thalamic injury.
Surgery-Related Quality of Life of Pediatric Patients With Crohn's Disease
Authors: Dipasquale Valeria , Antonelli Enrica , Cannavò Laura , Cavatoi Giorgio , Romeo Carmelo , Trimarchi Giuseppe , Navarra Giuseppe , Romano Claudio
Published: January 2021

Objective: Up to 30% of pediatric patients with Crohn's disease (CD) require surgery. The aim of the study was to evaluate long-term health-related quality of life (HRQoL) outcome in children with CD who have had ileocolonic resection.

Materials and methods: This was a retrospective cross-sectional study on all pediatric patients who had undergone surgery for CD between January 2015 and December 2017 in the Pediatric Surgery and Gastroenterology Units of the University Hospital of Messina. Surgical treatment was represented by laparoscopic ileocecal resection with latero-lateral anastomosis. Patients were asked to fill in a modified version of the IMPACT III questionnaire made up of 15 closed questions before and after surgery. The questionnaire was scored on a five-point scale with 5 reporting “not a problem” and 1 “a very severe problem.” The total score ranged from 15 (worst HRQoL) to 75 (best HRQoL). Frequency of relapses, reoperations, complications during follow-up, and postoperative bowel function were also studied.

Results: Data were obtained in 10 patients (9 males), who underwent surgery at a median age of 13.5 years (range 13–18), after a median post-diagnosis period of 2.5 years (range 0–8). Preoperative scores were low in all 4 domains of the questionnaire. Postoperatively, HRQoL measures improved significantly (p < 0.05) about symptoms, school attendance, social and emotional functioning. Overall, nearly all patients were completely satisfied with the surgical outcome.

Conclusions: HRQoL is low in CD children referred for possible operation, and surgery may positively affect the overall HRQoL. Collecting HRQoL data provides insight into the impact of treatment on children health status.
Synergetic Effect of rHDL and LXR Agonist on Reduction of Atherosclerosis in Mice
Authors: Morin Emily E. , Guo Yanhong , He Hongliang , Yuan Wenmin , Souery Whitney N. , Fawaz Maria V. , Chen Yuqing Eugene , Schwendeman Anna
Published: January 2021

High-density lipoproteins (HDLs) are unique in that they play an important role in the reverse cholesterol transport process. However, reconstituted HDL (rHDL) infusions have demonstrated limited beneficial effect in clinical practice. This is perhaps a consequence of the limited cholesterol efflux abilities of atheroma macrophages due to decreased expression of cholesterol transporters in advanced atheromas and following rHDL infusion treatment. Thus, we propose that a combination therapy of rHDL and a liver X receptor (LXR) agonist could maximize the therapeutic benefit of rHDL by upregulating ATP-binding cassette transporters A-1 (ABCA1) and ATP-binding cassette transporter G-1 (ABCG1), and enhancing cholesterol efflux to rHDL. In macrophages, rHDL downregulated the expression of ABCA1/G1 in a dose- and rHDL composition-dependent manner. Although LXR agonist, T0901317 (T1317), upregulated the expression of ABCA1 and ABCG1, the drug itself did not have any effect on cholesterol efflux (6.6 ± 0.5%) while the combination of rHDL and T1317 exhibited enhanced cholesterol efflux from [3H]-cholesterol loaded J774A.1 macrophages (23.3 ± 1.3%). Treatment with rHDL + T1317 significantly reduced the area of aortic plaque in ApoE−/− mice compared to PBS treated control animals (24.16 ± 1.42% vs. 31.59 ± 1.93%, p < 0.001), while neither rHDL nor T1317 treatment alone had a significant effect. Together, we show that rHDL paired with an LXR agonist can induce a synergetic effect in reducing atheroma burden. This synergy could lead to lower overall effective dose for both drugs, potentially overcoming the existing barriers in clinical development and renewing pharmaceutical interest in these two drug classes.
Volume Matters in Ultrasound-Guided Perineural Dextrose Injection for Carpal Tunnel Syndrome: A Randomized, Double-Blinded, Three-Arm Trial
Authors: Lin Meng-Ting , Liao Chun-Li , Hsiao Ming-Yen , Hsueh Hsueh-Wen , Chao Chi-Chao , Wu Chueh-Hung
Published: January 2021

Ultrasound-guided perineural dextrose injection (PDI) has been reported effective for carpal tunnel syndrome (CTS). Higher volume of injectate may reduce adhesion of median nerve from other tissues, but volume-dependent effects of PDI in CTS remain unknown. We aimed to investigate whether PDI with different injectate volumes had different effects for CTS participants. In this randomized, double-blinded, three-arm trial, 63 wrists diagnosed with CTS were randomized into three groups that received ultrasound-guided PDI with either 1, 2 or 4 ml of 5% dextrose water. All participants finished this study. Primary outcome as visual analog scale (VAS) and secondary outcomes including Boston Carpal Tunnel Questionnaire (BCTQ), Disability of the Arm, Shoulder and Hand score (QuickDASH), electrophysiological studies and cross-sectional area (CSA) of the median nerve at carpal tunnel inlet were assessed before and after PDI at the 1st, 4th, 12th and 24th weeks. For within-group analysis, all three groups (21 participants, each) revealed significant improvement from baseline in VAS, BCTQ and QuickDASH at the 1st, 4th, 12th and 24th weeks. For between-group analysis, 4 ml-group yielded better VAS reduction at the 4th and 12th weeks as well as improvement of BCTQ and QuickDASH at the 1st, 4th, and 12th weeks, compared to other groups. No significant between-group differences were observed in electrophysiological studies or median nerve CSA at any follow-up time points. There were no severe complications in this trial, and transient minor adverse effects occurred equally in the three groups. In conclusion, ultrasound-guided PDI with 4 ml of 5% dextrose provided better efficacy than with 1 and 2 ml based on symptom relief and functional improvement for CTS at the 1st, 4th, and 12th week post-injection, with no reports of severe adverse effects. There was no significant difference between the three groups at the 24th-week post-injection follow-up.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03598322.
Characterization of Antennal Sensilla and Immunolocalization of Odorant-Binding Proteins on Spotted Alfalfa Aphid, Therioaphis trifolii (Monell)
Authors: Song Limei , Wang Xuemin , Liu Yanqi , Sun Yinpeng , Ban Liping
Published: January 2021

The spotted alfalfa aphid [Therioaphis trifolii (Monell), Homoptera, Drepanosiphidae] is a well-known destructive pest that can significantly reduce alfalfa yields. Herein, the morphology of antennal sensilla of T. trifolii has been examined by using scanning electron microscopy and the ultrastructure of sensilla stellate and placoidea was described by transmission electron microscopy. Stellate sensilla, placoid sensilla, and coeloconic sensilla were found on the 6th segment, and a single sensillum placoidea was located on the 5th segment. Placoid sensilla were also present on the 3rd antennal segment of alate and apterous aphids, and the number was similar between two morphs. Two types of trichoid sensilla and coeloconic sensilla were found on the antennae, respectively. The results of ultrastructure showed that stellate sensilla are innervated by three neurons, while placoid sensilla present three groups of neurons, equipped with 2–3 dendrites in each neuron group. Immunocytochemical localization of odorant-binding proteins (OBPs) was performed on ultrathin sections of sensilla stellate and placoidea, and we observed that the antiserum against OBP6 intensively labeled all placoid sensilla from both primary and secondary rhinaria. OBP7 and OBP8 could also be detected in placoid sensilla, but less strongly than OBP6. In addition, OBP6, OBP7, and OBP8 were densely labeled in stellate sensilla, suggesting OBP6, OBP7, and OBP8 may sense alarm pheromone germacrene A in T. trifolii.
Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-Associated Protein 9 Mediated Knockout Reveals Functions of the yellow-y Gene in Spodoptera litura
Authors: Liu Xiao-Long , Han Wei-Kang , Ze Long-Ji , Peng Ying-Chuan , Yang Yi-Lin , Zhang Jin , Yan Qi , Dong Shuang-Lin
Published: January 2021

Yellowgenes are thought to be involved in the melanin biosynthetic pathway and play a crucial role in pigmentation reactions in insects. However, little research has been done onyellowgenes in lepidopteran pests. To clarify the function of one of theyellowgenes (yellow-y) inSpodoptera litura, we cloned the full-length ofyellow-y, and investigated its spatial and temporal expression profiles by quantitative real-time PCR (qPCR). It revealed thatyellow-ywas highly expressed in larva of fourth, fifth, and sixth instars, as well as in epidermis (Ep), fat bodies (FB), Malpighian tubes (MT), and midguts (MG) of the larvae; whereas it was expressed in very low levels in different tissues of adults, and was almost undetected in pupa. This expression profile suggests an important role ofyellow-yin larvae, minor role in adults, and no role in pupae. To confirm this, we disruptedyellow-yusing the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, and obtained G0 insects with mutation inyellow-y. The mutation inyellow-yclearly rendered the larvae body, a color yellower than that of wide type insects, and in addition, the mutation resulted in abnormal segmentation and molting for older larvae. The mutation ofyellow-yalso made various adult tissues (antennae, proboscis, legs, and wings) yellowish. However, the mutation had no effect on pigmentation of the pupal cuticle. Taken together, our study clearly demonstrated the role ofyellow-ynot only in the body pigmentation of larvae and adults, and but also in segmentation and molting of larvae, providing new insights into the physiology of larval development, as well as a useful marker gene for genome editing based studies.
The Effect of Post-harvest Conditions in Narcissus sp. Cut Flowers Scent Profile
Authors: Terry Marta I. , Ruiz-Hernández Victoria , Águila Diego J. , Weiss Julia , Egea-Cortines Marcos
Published: January 2021

Narcissus flowers are used as cut flowers and to obtain high quality essential oils for the perfume industry. As a winter crop in the Mediterranean area, it flowers at temperatures ranging between 10 and 15°C during the day and 3–10°C during the night. Here we tested the impact of different light and temperature conditions on scent quality during post-harvest. These two types of thermoperiod and photoperiod. We also used constant darkness and constant temperatures. We found that under conditions of 12:12 Light Dark and 15-5°C, Narcissus emitted monoterpenes and phenylpropanoids. Increasing the temperature to 20°-10°C in a 12:12 LD cycle caused the loss of cinnamyl acetate and emission of indole. Under constant dark, there was a loss of scent complexity. Constant temperatures of 20°C caused a decrease of scent complexity that was more dramatic at 5°C, when the total number of compounds emitted decreased from thirteen to six. Distance analysis confirmed that 20°C constant temperature causes the most divergent scent profile. We found a set of four volatiles, benzyl acetate, eucalyptol, linalool, and ocimene that display a robust production under differing environmental conditions, while others were consistently dependent on light or thermoperiod. Scent emission changed significantly during the day and between different light and temperature treatments. Under a light:dark cycle and 15-5°C the maximum was detected during the light phase but this peak shifted toward night under 20-10°C. Moreover, under constant darkness the peak occurred at midnight and under constant temperature, at the end of night. Using Machine Learning we found that indole was the volatile with a highest ranking of discrimination followed by D-limonene. Our results indicate that light and temperature regimes play a critical role in scent quality. The richest scent profile is obtained by keeping flowers at 15°-5°C thermoperiod and a 12:12 Light Dark photoperiod.
Deciphering the Genetic Diversity of Landraces With High-Throughput SNP Genotyping of DNA Bulks: Methodology and Application to the Maize 50k Array
Authors: Arca Mariangela , Mary-Huard Tristan , Gouesnard Brigitte , Bérard Aurélie , Bauland Cyril , Combes Valérie , Madur Delphine , Charcosset Alain , Nicolas Stéphane D.
Published: January 2021

Genebanks harbor original landraces carrying many original favorable alleles for mitigating biotic and abiotic stresses. Their genetic diversity remains, however, poorly characterized due to their large within genetic diversity. We developed a high-throughput, cheap and labor saving DNA bulk approach based on single-nucleotide polymorphism (SNP) Illumina Infinium HD array to genotype landraces. Samples were gathered for each landrace by mixing equal weights from young leaves, from which DNA was extracted. We then estimated allelic frequencies in each DNA bulk based on fluorescent intensity ratio (FIR) between two alleles at each SNP using a two step-approach. We first tested either whether the DNA bulk was monomorphic or polymorphic according to the two FIR distributions of individuals homozygous for allele A or B, respectively. If the DNA bulk was polymorphic, we estimated its allelic frequency by using a predictive equation calibrated on FIR from DNA bulks with known allelic frequencies. Our approach: (i) gives accurate allelic frequency estimations that are highly reproducible across laboratories, (ii) protects against false detection of allele fixation within landraces. We estimated allelic frequencies of 23,412 SNPs in 156 landraces representing American and European maize diversity. Modified Roger’s genetic Distance between 156 landraces estimated from 23,412 SNPs and 17 simple sequence repeats using the same DNA bulks were highly correlated, suggesting that the ascertainment bias is low. Our approach is affordable, easy to implement and does not require specific bioinformatics support and laboratory equipment, and therefore should be highly relevant for large-scale characterization of genebanks for a wide range of species.
The PTI to ETI Continuum in Phytophthora-Plant Interactions
Authors: Naveed Zunaira Afzal , Wei Xiangying , Chen Jianjun , Mubeen Hira , Ali Gul Shad
Published: January 2021

Phytophthora species are notorious pathogens of several economically important crop plants. Several general elicitors, commonly referred to as Pathogen-Associated Molecular Patterns (PAMPs), from Phytophthora spp. have been identified that are recognized by the plant receptors to trigger induced defense responses in a process termed PAMP-triggered Immunity (PTI). Adapted Phytophthora pathogens have evolved multiple strategies to evade PTI. They can either modify or suppress their elicitors to avoid recognition by host and modulate host defense responses by deploying hundreds of effectors, which suppress host defense and physiological processes by modulating components involved in calcium and MAPK signaling, alternative splicing, RNA interference, vesicle trafficking, cell-to-cell trafficking, proteolysis and phytohormone signaling pathways. In incompatible interactions, resistant host plants perceive effector-induced modulations through resistance proteins and activate downstream components of defense responses in a quicker and more robust manner called effector-triggered-immunity (ETI). When pathogens overcome PTI—usually through effectors in the absence of R proteins—effectors-triggered susceptibility (ETS) ensues. Qualitatively, many of the downstream defense responses overlap between PTI and ETI. In general, these multiple phases of Phytophthora-plant interactions follow the PTI-ETS-ETI paradigm, initially proposed in the zigzag model of plant immunity. However, based on several examples, in Phytophthora-plant interactions, boundaries between these phases are not distinct but are rather blended pointing to a PTI-ETI continuum.
Diversity of Expression Types of Ht Genes Conferring Resistance in Maize to Exserohilum turcicum
Authors: Navarro Barbara Ludwig , Hanekamp Hendrik , Koopmann Birger , von Tiedemann Andreas
Published: January 2021

Northern corn leaf blight (NCLB) is an important leaf disease in maize (Zea mays) worldwide and is spreading into new areas with expanding maize cultivation, like Germany. Exserohilum turcicum, causal agent of NCLB, infects and colonizes leaf tissue and induces elongated necrotic lesions. Disease control is based on fungicide application and resistant cultivars displaying monogenic resistance. Symptom expression and resistance mechanisms differ in plants carrying different resistance genes. Therefore, histological studies and DNA quantification were performed to compare the pathogenesis of E. turcicum races in maize lines exhibiting compatible or incompatible interactions. Maize plants from the differential line B37 with and without resistance genes Ht1, Ht2, Ht3, and Htn1 were inoculated with either incompatible or compatible races (race 0, race 1 and race 23N) of E. turcicum. Leaf segments from healthy and inoculated plants were collected at five different stages of infection and disease development from penetration (0–1 days post inoculation - dpi), until full symptom expression (14–18 dpi). Symptoms of resistance responses conveyed by the different Ht genes considerably differed between Ht1 (necrotic lesions with chlorosis), Ht2 (chlorosis and small lesions), Ht3 (chlorotic spots) and Htn1 (no lesions or wilt-type lesions). In incompatible interactions, fungal DNA was only detected in very low amounts. At 10 dpi, DNA content was elevated in all compatible interactions. Histological studies with Chlorazol Black E staining indicated that E. turcicum formed appressoria and penetrated the leaf surface directly in both types of interaction. In contrast to incompatible interactions, however, the pathogen was able to penetrate into xylem vessels at 6 dpi in compatible interactions and strongly colonized the mesophyll at 12 dpi, which is considered the crucial process differentiating susceptible from resistant interactions. Following the distinct symptom expressions, resistance mechanisms conferred by Ht1, Ht2, Ht3, and Htn1 genes apparently are different. Lower disease levels and a delayed progress of infection in compatible interactions with resistant lines imply that maize R genes to E. turcicum are associated with or confer additional quantitative resistance.
Predictive Validity of Interviewer Post-interview Notes on Candidates’ Job Outcomes: Evidence Using Text Data From a Leading Chinese IT Company
Authors: Liu Shanshi , Chang Yuanzheng , Jiang Jianwu , Ma Haigang , Zhou Huaikang
Published: January 2021

Despite the popularity of the employment interview in the employee selection literature and organizational talent selection process, few have examined the comments interviewers give after each interview. This study investigated the predictability of the match between interviewer post-interview notes and radar charts from job analysis on the candidate’s later career performance using text mining techniques and data from one of the largest internet-based technology companies in China. A large sample of 7,650 interview candidates who passed the interviews and joined the company was obtained to show that the number of job-related capabilities interviewers mentioned in their notes was positively related to candidate’s job performance, the number of promotions, and negatively related to turnover. Moreover, the dimensions of the radar chart from job analysis covered in the interview moderated the predictability of interview post-interview notes. Our results indicated that a smaller number of radar chart dimensions by which interviewers assessed the candidates in the interview positively moderated candidates’ promotion for product development jobs, and negatively moderated turnover for technical jobs. The implications of these results for structured interview research in both theory and practice are discussed.
The Effects of Synchrony on Group Moral Hypocrisy
Authors: Chvaja Radim , Kundt Radek , Lang Martin
Published: January 2021

Humans have evolved various social behaviors such as interpersonal motor synchrony (i.e., matching movements in time), play and sport or religious ritual that bolster group cohesion and facilitate cooperation. While important for small communities, the face-to-face nature of such technologies makes them infeasible in large-scale societies where risky cooperation between anonymous individuals must be enforced through moral judgment and, ultimately, altruistic punishment. However, the unbiased applicability of group norms is often jeopardized by moral hypocrisy, i.e., the application of moral norms in favor of closer subgroup members such as key socioeconomic partners and kin. We investigated whether social behaviors that facilitate close ties between people also promote moral hypocrisy that may hamper large-scale group functioning. We recruited 129 student subjects that either interacted with a confederate in the high synchrony or low synchrony conditions or performed movements alone. Subsequently, participants judged a moral transgression committed by the confederate toward another anonymous student. The results showed that highly synchronized participants judged the confederate’s transgression less harshly than the participants in the other two conditions and that this effect was mediated by the perception of group unity with the confederate. We argue that for synchrony to amplify group identity in large-scale societies, it needs to be properly integrated with morally compelling group symbols that accentuate the group’s overarching identity (such as in religious worship or military parade). Without such contextualization, synchrony may create bonded subgroups that amplify local preferences rather than impartial and wide application of moral norms.