bluuebunny/crossref_metadata_2025 huggingface dataset:
Hereditary Spastic Paraplegia and Future Therapeutic Directions: Beneficial Effects of Small Compounds Acting on Cellular Stress
Authors: Gumeni Sentiljana , Vantaggiato Chiara , Montopoli Monica , Orso Genny
Published: May 2021

Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative conditions that share a characteristic feature of degeneration of the longest axons within the corticospinal tract, which leads to progressive spasticity and weakness of the lower limbs. Mutations of over 70 genes produce defects in various biological pathways: axonal transport, lipid metabolism, endoplasmic reticulum (ER) shaping, mitochondrial function, and endosomal trafficking. HSPs suffer from an adequate therapeutic plan. Currently the treatments foreseen for patients affected by this pathology are physiotherapy, to maintain the outgoing tone, and muscle relaxant therapies for spasticity. Very few clinical studies have been conducted, and it’s urgent to implement preclinical animal studies devoted to pharmacological test and screening, to expand the rose of compounds potentially attractive for clinical trials. Small animal models, such asDrosophila melanogasterand zebrafish, have been generated, analyzed, and used as preclinical model for screening of compounds and their effects. In this work, we briefly described the role of HSP-linked proteins in the organization of ER endomembrane system and in the regulation of ER homeostasis and stress as a common pathological mechanism for these HSP forms. We then focused our attention on the pharmacodynamic and pharmacokinetic features of some recently identified molecules with antioxidant property, such as salubrinal, guanabenz, N-acetyl cysteine, methylene blue, rapamycin, and naringenin, and on their potential use in future clinical studies. Expanding the models and the pharmacological screening for HSP disease is necessary to give an opportunity to patients and clinicians to test new molecules.
MicroRNA-181a Is Involved in Methamphetamine Addiction Through the ERAD Pathway
Authors: Wang Yujing , Wei Tao , Zhao Wei , Ren Zixuan , Wang Yan , Zhou Yiding , Song Xun , Zhou Ruidong , Zhang Xiaochu , Jiao Dongliang
Published: May 2021

The regulation of microRNA (miRNA) is closely related to methamphetamine (METH) addiction. Past studies have reported that miR-181a is associated with METH addiction, but the mechanism pathways remain elusive. On the basis of our past studies, which reported the endoplasmic reticulum-associated protein degradation (ERAD) mediated ubiquitin protein degradation of GABAAα1, which was involved in METH addiction. The present study, using qRT-PCR and bioinformatics analysis, further revealed that miR-181a may be indirectly responsible for the METH addiction and downregulation of GABAAα1 through the regulation of ERAD.
Prognostic Impact of Muscle Quantity and Quality and Fat Distribution in Diffuse Large B-Cell Lymphoma Patients
Authors: Besutti Giulia , Massaro Fulvio , Bonelli Efrem , Braglia Luca , Casali Massimiliano , Versari Annibale , Ligabue Guido , Pattacini Pierpaolo , Cavuto Silvio , Merlo Domenico F. , Luminari Stefano , Merli Francesco , Vaccaro Salvatore , Pellegrini Massimo
Published: May 2021

Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination (p = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17–18.26; p < 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26–4.65; p = 0.008). After correction for sex, International Prognostic Index (IPI), BMI, and R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), low L3-SMD remained associated with poor OS (HR = 3.54; 95% CI = 1.10–11.40; p = 0.034) but not with PFS. Increased PT-IMAT was prognostic for poor OS and PFS after correction for sex, IPI, BMI, and R-CHOP therapy (HR = 1.35; CI = 1.03–1.7; p = 0.03, and HR = 1.30; CI = 1.04–1.64; p = 0.024, respectively). Reduced muscle quality (SMD) and increased intermuscular fat (IMAT), rather than low muscle quantity (SMI), are associated with poor prognosis in DLBCL, when measured at the L3 level, and particularly at the level of the proximal thigh. The proximal thigh represents a novel radiological landmark to study body composition.
Microbiota and Tuberculosis: A Potential Role of Probiotics, and Postbiotics
Authors: Liu Yue , Wang Jiaqi , Wu Changxin
Published: May 2021

Tuberculosis (TB), caused by Mycobacterium tuberculosis attacking the lungs and other organs, is one of the most common infectious disease worldwide. According to the WHO's 2020 report, a quarter of the world's population were infected with M. tuberculosis, and ~1.4 million people died of TB. Therefore, TB is a significant public health concern, which requires cost-effective strategies for prevention and treatment. The microbiota has been considered as a “forgotten organ” and a complex dynamic ecosystem, which plays a significant role in many physiological processes, and its dysbiosis is closely associated with infectious disease. Recently, a few studies have indicated associations between TB and microbiota. This review summarizes studies concerning the alterations of the gut and respiratory microbiota in TB, and their relationship with host susceptibility to M. tuberculosis infection, indicating that microbiota signatures in different stages in TB progression could be considered as biomarkers for TB diagnosis and control. In addition, the potential role of probiotics and postbiotics in TB treatment was discussed.
Overexpression of Endogenous Retroviruses and Malignancy Markers in Neuroblastoma Cell Lines by Medium-Induced Microenvironmental Changes
Authors: Wieland Lisa , Engel Kristina , Volkmer Ines , Krüger Anna , Posern Guido , Kornhuber Malte E. , Staege Martin S. , Emmer Alexander
Published: May 2021

Neuroblastoma (NB) is the commonest solid tumor outside the central nervous system in infancy and childhood with a unique biological heterogeneity. In patients with advanced, metastasizing neuroblastoma, treatment failure and poor prognosis is often marked by resistance to chemo- or immunotherapy. Thus, identification of robust biomarkers seems essential for understanding tumor progression and developing effective therapy. Here, we have studied the expression of human endogenous retroviruses (HERV) as potential targets in NB cell lines during stem-cell medium-induced microenvironmental change. Quantitative PCR revealed that relative expression of the HERV-K family and HERV-W1 ENV were increased in all three NB cell lines after incubation in stem-cell medium. Virus transcriptome analyses revealed the transcriptional activation of three endogenous retrovirus elements: HERV-R ENV (ERV3-1), HERV-E1 and HERV-Fc2 ENV (ERVFC1-1). Known malignancy markers in NB, e.g. proto-oncogenic MYC or MYCN were expressed highly heterogeneously in the three investigated NB cell lines with up-regulation of MYC and MYCN upon medium-induced microenvironmental change. In addition, SiMa cells exclusively showed a phenotype switching from loosely-adherent monolayers to low proliferating grape-like cellular aggregates, which was accompanied by an enhanced CD133 expression. Interestingly, the overexpression of HERV was associated with a significant elevation of immune checkpoint molecule CD200 in both quantitative PCR and RNA-seq analysis suggesting tumor escape mechanism in NB cell lines after incubation in serum-free stem cell medium.
Cervical Cancer Stem-Like Cell Transcriptome Profiles Predict Response to Chemoradiotherapy
Authors: Zuccherato Luciana W. , Machado Christina M. T. , Magalhães Wagner C. S. , Martins Patrícia R. , Campos Larissa S. , Braga Letícia C. , Teixeira-Carvalho Andrea , Martins-Filho Olindo A. , Franco Telma M. R. F. , Paula Sálua O. C. , da Silva Israel Tojal , Drummond Rodrigo , Gollob Kenneth J. , Salles Paulo Guilherme O.
Published: May 2021

Cervical cancer (CC) represents a major global health issue, particularly impacting women from resource constrained regions worldwide. Treatment refractoriness to standard chemoradiotheraphy has identified cancer stem cells as critical coordinators behind the biological mechanisms of resistance, contributing to CC recurrence. In this work, we evaluated differential gene expression in cervical cancer stem-like cells (CCSC) as biomarkers related to intrinsic chemoradioresistance in CC. A total of 31 patients with locally advanced CC and referred to Mário Penna Institute (Belo Horizonte, Brazil) from August 2017 to May 2018 were recruited for the study. Fluorescence-activated cell sorting was used to enrich CD34+/CD45- CCSC from tumor biopsies. Transcriptome was performed using ultra-low input RNA sequencing and differentially expressed genes (DEGs) using Log2 fold differences and adjusted p-value < 0.05 were determined. The analysis returned 1050 DEGs when comparing the Non-Responder (NR) (n=10) and Responder (R) (n=21) groups to chemoradiotherapy. These included a wide-ranging pattern of underexpressed coding genes in the NR vs. R patients and a panel of lncRNAs and miRNAs with implications for CC tumorigenesis. A panel of biomarkers was selected using the rank-based AUC (Area Under the ROC Curve) and pAUC (partial AUC) measurements for diagnostic sensitivity and specificity. Genes overlapping between the 21 highest AUC and pAUC loci revealed seven genes with a strong capacity for identifying NR vs. R patients (ILF2, RBM22P2, ACO16722.1, AL360175.1 and AC092354.1), of which four also returned significant survival Hazard Ratios. This study identifies DEG signatures that provide potential biomarkers in CC prognosis and treatment outcome, as well as identifies potential alternative targets for cancer therapy.
Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study
Authors: Song Zhengbo , Lv Dongqing , Chen Shiqing , Huang Jianhui , Wang Liping , Xu Shuguang , Chen Huafei , Wang Guoqiang , Lin Quan
Published: May 2021

Background

Non-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited.

Patients and methods

We retrospectively included metastatic NSCLC patients harboring HER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed.

Results

We included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16–36%), the median PFS was 3.3 months (95% CI, 2.2–4.4), and the median OS was 13.9 months (95% CI, 11.4–16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2–5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3–14.8; P = 0.009) than patients with other mutations. For HER2-amplified patients, the ORR was 33% (95% CI, 14–61%), the median PFS was 3.3 months (95% CI, 2.6–4.0), and the median OS was 13.4 months (95% CI, 0–27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations.

Conclusions

Our results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.
Early Dissemination of Circulating Tumor Cells: Biological and Clinical Insights
Authors: Chemi Francesca , Mohan Sumitra , Guevara Tatiana , Clipson Alexandra , Rothwell Dominic G. , Dive Caroline
Published: May 2021

Circulating tumor cells (CTCs) play a causal role in the development of metastasis, the major cause of cancer-associated mortality worldwide. In the past decade, the development of powerful cellular and molecular technologies has led to a better understanding of the molecular characteristics and timing of dissemination of CTCs during cancer progression. For instance, genotypic and phenotypic characterization of CTCs, at the single cell level, has shown that CTCs are heterogenous, disseminate early and could represent only a minor subpopulation of the primary tumor responsible for disease relapse. While the impact of molecular profiling of CTCs has not yet been translated to the clinic, CTC enumeration has been widely used as a prognostic biomarker to monitor treatment response and to predict disease relapse. However, previous studies have revealed a major challenge: the low abundance of CTCs in the bloodstream of patients with cancer, especially in early stage disease where the identification and characterization of subsequently “lethal” cells has potentially the greatest clinical relevance. The CTC field is rapidly evolving with development of new technologies to improve the sensitivity of CTC detection, enumeration, isolation, and molecular profiling. Here we examine the technical and analytical validity of CTC technologies, we summarize current data on the biology of CTCs that disseminate early and review CTC-based clinical applications.
Difficult Airway Management in Neonates and Infants: Knowledge of Devices and a Device-Oriented Strategy
Authors: Sawa Teiji , Kainuma Atsushi , Akiyama Koichi , Kinoshita Mao , Shibasaki Masayuki
Published: May 2021

Difficult airway management (DAM) in neonates and infants requires anesthesiologists and critical care clinicians to respond rapidly with appropriate evaluation of specific situations. Therefore, organizing information regarding DAM devices and device-oriented guidance for neonate and infant DAM treatment will help practitioners select the safest and most effective strategy. Based on DAM device information and reported literature, there are three modern options for DAM in neonates and infants that can be selected according to the anatomical difficulty and device-oriented strategy: (1) video laryngoscope (VLS), (2) supraglottic airway device (SAD), and (3) flexible fiberoptic scope (FOS). Some VLSs are equipped with small blades for infants. Advanced SADs have small sizes for infants, and some effectively function as conduits for endotracheal intubation. The smallest FOS has an outer diameter of 2.2 mm and enables intubation with endotracheal tubes with an inner diameter of 3.0 mm. DAM in neonates and infants can be improved by effectively selecting the appropriate device combination and ensuring that available providers have the necessary skills.
Increased Incidence of Perforated Appendicitis in Children During COVID-19 Pandemic in a Bavarian Multi-Center Study
Authors: Schäfer Frank-Mattias , Meyer Johannes , Kellnar Stephan , Warmbrunn Jakob , Schuster Tobias , Simon Stefanie , Meyer Thomas , Platzer Julia , Hubertus Jochen , Seitz Sigurd T. , Knorr Christian , Stehr Maximilian
Published: May 2021

Introduction: Since early 2020 the COVID-19 pandemic and statutory preventive reorganization of treatment capacities with cancellation of elective surgery as well as curfew regulations led to vastly decreased utilization of primary health care.

Materials and Methods: To assess whether there are negative effects on pediatric acute care in Bavaria during the spring 2020 lockdown a state-wide retrospective multi-center study was performed to analyze the rate of perforated appendicitis during lockdown. Children who have been operated on during the corresponding period in 2018/19 served as control group.

Results: Overall, 514 patients (292 boys, 222 girls) were included (2020: 176 patients; 2019: 181 patients; 2018: 157 patients). Median age was 11.2 years. Four hundred thirty-nine patients (85.4%) underwent laparoscopic surgery, 69 (13.4%) open surgery and 1.2% underwent conversion from laparoscopic to open surgery. In 2020 a perforation rate of 27.8% (49/176 patients) was found, in 2018–2019 perforation rate was 20.7% (70/338 patients, p = 0.0359, Cochran-Mantel-Haenszel-Test). Subgroup analysis showed that in younger patients (≤ 11.2 years), in 2020 perforation rate was significantly higher with 37.6% (32/85 patients), while 22.2% (39/176) in 2018/2019 (p = 0.014, Fisher's exact test).In boys perforation rate was significantly higher in 2020 with 35.0% (35/100 patients) compared to 21.4% in 2018–2019 (p = 0.0165, Fisher's exact test).

Conclusion: During the period of curfew regulations in Bavaria the rate of perforated appendicitis in childhood increased significantly, especially in younger children and boys. Potentially this has to be attributed to delayed presentation to pediatric surgery care. Because of potential long-term sequelae of perforated appendicitis these adverse effects during curfew have to be taken into account for future political decision making to ensure reasonable patient care and avoid collateral damage in near-future or on-going pandemic situations.
Effects of a Common Eight Base Pairs Duplication at the Exon 7-Intron 7 Junction on Splicing, Expression, and Function of OCT1
Authors: Römer Sarah , Meyer Marleen J. , Klein Kathrin , Schneider Lennart V. , Matthaei Johannes , Tzvetkova Ana , Łapczuk-Romańska Joanna , Gaedcke Jochen , Droździk Marek , Brockmöller Jürgen , Nies Anne T. , Tzvetkov Mladen V.
Published: May 2021

Organic cation transporter 1 (OCT1, SLC22A1) is localized in the sinusoidal membrane of human hepatocytes and mediates hepatic uptake of weakly basic or cationic drugs and endogenous compounds. Common amino acid substitutions in OCT1 were associated with altered pharmacokinetics and efficacy of drugs like sumatriptan and fenoterol. Recently, the common splice variant rs35854239 has also been suggested to affect OCT1 function. rs35854239 represents an 8 bp duplication of the donor splice site at the exon 7-intron 7 junction. Here we quantified the extent to which this duplication affects OCT1 splicing and, as a consequence, the expression and the function of OCT1. We used pyrosequencing and deep RNA-sequencing to quantify the effect of rs35854239 on splicing after minigene expression of this variant in HepG2 and Huh7 cells and directly in human liver samples. Further, we analyzed the effects of rs35854239 on OCT1 mRNA expression in total, localization and activity of the resulting OCT1 protein, and on the pharmacokinetics of sumatriptan and fenoterol. The 8 bp duplication caused alternative splicing in 38% (deep RNA-sequencing) to 52% (pyrosequencing) of the minigene transcripts when analyzed in HepG2 and Huh7 cells. The alternatively spliced transcript encodes for a truncated protein that after transient transfection in HEK293 cells was not localized in the plasma membrane and was not able to transport the OCT1 model substrate ASP+. In human liver, however, the alternatively spliced OCT1 transcript was detectable only at very low levels (0.3% in heterozygous and 0.6% in homozygous carriers of the 8 bp duplication, deep RNA-sequencing). The 8 bp duplication was associated with a significant reduction of OCT1 expression in the human liver, but explained only 9% of the general variability in OCT1 expression and was not associated with significant changes in the pharmacokinetics of sumatriptan and fenoterol. Therefore, the rs35854239 variant only partially changes splicing, causing moderate changes in OCT1 expression and may be of only limited therapeutic relevance.
Clinical Application of Chinese Herbal Injection for Cancer Care: Evidence-Mapping of the Systematic Reviews, Meta-analyses, and Randomized Controlled Trials
Authors: Yang Ming , Zhu Si-jia , Shen Chen , Zhai Rui , Li Duo-duo , Fang Min , Xu Jing-nan , Gan Ye-na , Yang Lu , Ren Zhi-ying , Zheng Ruo-xiang , Robinson Nicola , Liu Jian-ping
Published: May 2021

Background and objective: Cancer is a life-threatening disease worldwide and current standard therapy cannot fulfill all clinical needs. Chinese herbal injections have been widely used for cancer in Chinese and Western hospitals in China. This study aimed to apply evidence mapping in order to provide an overview of the clinical application of Chinese herbal injections in cancer care based on randomized controlled trials, systematic reviews, and meta-analyses.

Methods and results: Seven databases were systematically searched for eligible randomized controlled trials, systematic reviews, and meta-analyses for ten Chinese herbal injections used in cancer treatment and covered in the Chinese national essential health insurance program. Excel 2016 and RStudio were used to integrate and process the data.

In total 366 randomized controlled trials and 48 systematic reviews and meta-analyses were included in the evidence mapping of herbal medicines including; Compound Kushen, Shenqi Fuzheng, Aidi, Kangai, Kanglaite, Xiaoaiping, Cinobufacin, Brucea javanica oil emulsion, Polyporus polysaccharide injection, and Astragalus polysaccharide for injection. Health insurance restricts the scope of clinical application for these herbal injections. The numbers of studies published increased, especially around 2013–2015. The most studied cancer types were lung cancer (118, 32.2%), colorectal cancer (39, 10.7%), and gastric cancer (39, 10.7%), and the most used injections were Compound Kushen (78, 21.3%), Shenqi Fuzheng (76, 20.8%), and Aidi (63, 17.2%). The most consistently reported benefits were observed for Compound Kushen, Shenqi Fuzheng, Aidi, and Kangai for tumor response, quality of life, myelosuppression, and enhancing immunity.

Conclusion: The current evidence mapping provides an overview of the outcomes and effects of Chinese herbal injections used in cancer care, and offers information on their clinical application which warrants further evidence-based research in order to inform clinical and policy decision-making.
Effects of Antiarrhythmic Drugs on hERG Gating in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1
Authors: Huang Mengying , Liao Zhenxing , Li Xin , Yang Zhen , Fan Xuehui , Li Yingrui , Zhao Zhihan , Lang Siegfried , Cyganek Lukas , Zhou Xiaobo , Akin Ibrahim , Borggrefe Martin , El-Battrawy Ibrahim
Published: May 2021

Aims: The short QT syndrome type 1 (SQT1) is linked to hERG channel mutations (e.g., N588K). Drug effects on hERG channel gating kinetics in SQT1-cells have not been investigated.

Methods: This study used hiPSC-CMs of a healthy donor and a SQT1-patient carrying the N588K mutation and patch clamp to examine the drug effects on hERG channel gating kinetics.

Results: Ajmaline, amiodarone, ivabradine, flecainide, quinidine, mexiletine and ranolazine inhibited the hERG channel current (IKr) less strongly in hiPSC-CMs from the SQTS1-patient (SQT1-hiPSC-CMs) comparing with cells from the healthy donor (donor-hiPSC-CMs). Quinidine and mexiletine reduced, but ajmaline, amiodarone, ivabradine and ranolazine increased the time to peak of IKr similarly in SQT1-hiPSC-CMs and donor-hiPSC-CMs. Although regarding the shift of activation and inactivation curves, tested drugs showed differential effects in donor- and SQT1-hiPSC-CMs, quinidine, ajmaline, ivabradine and mexiletine but not amiodarone, flecainide and ranolazine reduced the window current in SQT1-hiPSC-CMs. Quinidine, ajmaline, ivabradine and mexiletine differentially changed the time constant of recovery from inactivation, but all of them increased the time constant of deactivation in SQT1-hiPSC-CMs.

Conclusion: The window current-reducing and deactivation-slowing effects may be important for the antiarrhythmic effect of ajmaline, ivabradine, quinidine and mexiletine in SQT1-cells. This information may be helpful for selecting drugs for treating SQT1-patients with hERG channel mutation.
Attenuation of High Glucose-Induced Damage in RPE Cells through p38 MAPK Signaling Pathway Inhibition
Authors: Maugeri Grazia , Bucolo Claudio , Drago Filippo , Rossi Settimio , Di Rosa Michelino , Imbesi Rosa , D’Agata Velia , Giunta Salvatore
Published: May 2021

This study aimed to investigate the high glucose damage on human retinal pigment epithelial (RPE) cells, the role of p38 MAPK signaling pathway and how dimethyl fumarate can regulate that. We carried out in vitro studies on ARPE-19 cells exposed to physiological and high glucose (HG) conditions, to evaluate the effects of DMF on cell viability, apoptosis, and expression of inflammatory and angiogenic biomarkers such as COX-2, iNOS, IL-1β, and VEGF. Our data have demonstrated that DMF treatment attenuated HG-induced apoptosis, as confirmed by reduction of BAX/Bcl-2 ratio. Furthermore, in RPE cells exposed to HG we observed a significant increase of iNOS, COX-2, and IL-1β expression, that was reverted by DMF treatment. Moreover, DMF reduced the VEGF levels elicited by HG, inhibiting p38 MAPK signaling pathway. The present study demonstrated that DMF provides a remarkable protection against high glucose-induced damage in RPE cells through p38 MAPK inhibition and the subsequent down-regulation of VEGF levels, suggesting that DMF is a small molecule that represents a good candidate for diabetic retinopathy treatment and warrants further in vivo and clinical evaluation.
Feasibility of Hepatic Fat Quantification Using Proton Density Fat Fraction by Multi-Echo Chemical-Shift-Encoded MRI at 7T
Authors: Kořínek Radim , Pfleger Lorenz , Eckstein Korbinian , Beiglböck Hannes , Robinson Simon Daniel , Krebs Michael , Trattnig Siegfried , Starčuk Zenon , Krššák Martin
Published: May 2021

Fat fraction quantification and assessment of its distribution in the hepatic tissue become more important with the growing epidemic of obesity, and the increasing prevalence of diabetes mellitus type 2 and non-alcoholic fatty liver disease. At 3Tesla, the multi-echo, chemical-shift-encoded magnetic resonance imaging (CSE-MRI)-based acquisition allows the measurement of proton density fat-fraction (PDFF) even in clinical protocols. Further improvements in SNR can be achieved by the use of phased array coils and increased static magnetic field. The purpose of the study is to evaluate the feasibility of PDFF imaging using a multi-echo CSE-MRI technique at ultra-high magnetic field (7Tesla). Thirteen volunteers (M/F) with a broad range of age, body mass index, and hepatic PDFF were measured at 3 and 7T by multi-gradient-echo MRI and single-voxel spectroscopy MRS. All measurements were performed in breath-hold (exhalation); the MRI protocols were optimized for a short measurement time, thus minimizing motion-related problems. 7T data were processed off-line using Matlab® (MRI:multi-gradient-echo) and jMRUI (MRS), respectively. For quantitative validation of the PDFF results, a similar protocol was performed at 3T, including on-line data processing provided by the system manufacturer, and correlation analyses between 7 and 3T data were performed off-line. The multi-echo CSE-MRI measurements at 7T with a phased-array coil configuration and an optimal post-processing yielded liver volume coverage ranging from 30 to 90% for high- and low-BMI subjects, respectively. PDFFs ranged between 1 and 20%. We found significant correlations between 7T MRI and -MRS measurements (R2 ≅ 0.97; p < 0.005), and between MRI-PDFF at 7T and 3T fields (R2 ≅ 0.94; p < 0.005) in the evaluated volumes. Based on the measurements and analyses performed, the multi-echo CSE-MRI method using a 32-channel coil at 7T showed its aptitude for MRI-based quantitation of PDFF in the investigated volumes. The results are the first step toward qMRI of the whole liver at 7T with further improvements in hardware.
Fine Mapping and Candidate Gene Identification of a White Flower Gene BrWF3 in Chinese Cabbage (Brassica rapa L. ssp. pekinensis)
Authors: Yang Shuangjuan , Tian Xinxin , Wang Zhiyong , Wei Xiaochun , Zhao Yanyan , Su Henan , Zhao Xiaobin , Tian Baoming , Yuan Yuxiang , Zhang Xiao-Wei
Published: May 2021

Flower color is an important trait in plants. However, genes responsible for the white flower trait in Chinese cabbage are rarely reported. In this study, we constructed an F2 population derived from the Y640-288 (white flower) and Y641-87 (yellow flower) lines for the fine mapping of the white flower gene BrWF3 in Chinese cabbage. Genetic analysis indicated that BrWF3 was controlled by a single recessive gene. Using BSA-seq and KASP assays, BrWF3 was fine-mapped to an interval of 105.6 kb. Functional annotation, expression profiling, and sequence variation analyses confirmed that the AtPES2 homolog, Bra032957, was the most likely candidate gene for BrWF3. Carotenoid profiles and transmission electron microscopy analysis suggested that BrWF3 might participate in the production of xanthophyll esters (particularly violaxanthin esters), which in turn disrupt chromoplast development and the formation of plastoglobules (PGs). A SNP deletion in the third exon of BrWF3 caused the loss of protein function, and interfered with the normal assembly of PGs, which was associated with reduced expression levels of genes involved in carotenoid metabolism. Furthermore, we developed and validated the functional marker TXBH83 for BrWF3. Our results provide insight into the molecular mechanism underlying flower color pigmentation and reveal valuable information for marker-assisted selection (MAS) breeding in Chinese cabbage.
Exogenous Methyl Jasmonate Improves Heat Tolerance of Perennial Ryegrass Through Alteration of Osmotic Adjustment, Antioxidant Defense, and Expression of Jasmonic Acid-Responsive Genes
Authors: Su Yanning , Huang Yizhi , Dong Xintan , Wang Ruijia , Tang Mingyu , Cai Jiabang , Chen Jiayi , Zhang Xinquan , Nie Gang
Published: May 2021

Perennial ryegrass (Lolium perenne L.) is an important cool-season grass species that is widely cultivated in temperate regions worldwide but usually sensitive to heat stress. Jasmonates (JAs) may have a positive effect on plant tolerance under heat stress. In this study, results showed that exogenous methyl jasmonic acid (MeJA) could significantly improve heat tolerance of perennial ryegrass through alteration of osmotic adjustment, antioxidant defense, and the expression of JA-responsive genes. MeJA-induced heat tolerance was involved in the maintenance of better relative water content (RWC), the decline of chlorophyll (Chl) loss for photosynthetic maintenance, as well as maintained lower electrolyte leakage (EL) and malondialdehyde (MDA) content under heat condition, so as to avoid further damage to plants. Besides, results also indicated that exogenous MeJA treatment could increase the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), thus enhancing the scavenging ability of reactive oxygen species, alleviating the oxidative damage caused by heat stress. Heat stress and exogenous MeJA upregulated transcript levels of related genes (LpLOX2, LpAOC, LpOPR3, and LpJMT) in JA biosynthetic pathway, which also could enhance the accumulation of JA and MeJA content. Furthermore, some NAC transcription factors and heat shock proteins may play a positive role in enhancing resistance of perennial ryegrass with heat stress.
Transgenic Kalanchoë blossfeldiana, Containing Individual rol Genes and Open Reading Frames Under 35S Promoter, Exhibit Compact Habit, Reduced Plant Growth, and Altered Ethylene Tolerance in Flowers
Authors: Favero Bruno Trevenzoli , Tan Yi , Lin Yan , Hansen Hanne Bøge , Shadmani Nasim , Xu Jiaming , He Junou , Müller Renate , Almeida Aldo , Lütken Henrik
Published: May 2021

Reduced growth habit is a desirable trait for ornamental potted plants and can successfully be obtained through Rhizobium rhizogenes transformation in a stable and heritable manner. Additionally, it can also be obtained by transformation with Agrobacterium tumefaciens harboring specific genes from R. rhizogenes. The bacterial T-DNA harbors four root oncogenic loci (rol) genes and 14 less known open reading frames (ORFs). The four rol genes, i.e., rolA, rolB, rolC, and rolD, are conceived as the common denominator for the compact phenotype and the other less characterized ORFs seem auxiliary but present a potential breeding target for less aberrant and/or more tailored phenotypes. In this study, Kalanchoë blossfeldiana ‘Molly’ was transformed with individual rol genes and selected ORFs in 35S overexpressing cassettes to comprehensively characterize growth traits, gene copy and expression, and ethylene tolerance of the flowers. An association of reduced growth habit, e.g. height and diameter, was observed for rolB2 and ORF14-2 when a transgene single copy and high gene expression were detected. Chlorophyll content was reduced in overexpressing lines compared to wild type (WT), except for one ΔORF13a (a truncated ORF13a, where SPXX DNA-binding motif is absent). The flower number severely decreased in the overexpressing lines compared to WT. The anthesis timing showed that WT opened the first flower at 68.9 ± 0.9 days and the overexpressing lines showed similar or up to 24 days delay in flowering. In general, a single or low relative gene copy insertion was correlated to higher gene expression, ca. 3 to 5-fold, in rolB and ΔORF13a lines, while in ORF14 such relation was not directly linked. The increased gene expression observed in rolB2 and ΔORF13a-2 contributed to reducing plant growth and a more compact habit. Tolerance of detached flowers to 0.5 μl L−1 ethylene was markedly higher for ORF14 with 66% less flower closure at day 3 compared to WT. The subcellular localization of rolC and ΔORF13a was investigated by transient expression in Nicotiana benthamiana and confocal images showed that rolC and ΔORF13a are soluble and localize in the cytoplasm being able to enter the nucleus.
Effect of Online Psychological Intervention on Burnout in Medical Residents From Different Majors: An Exploratory Study
Authors: Wang Jian , Song Bijia , Shao Yun , Zhu Junchao
Published: May 2021

Background: Work-related stress among healthcare professionals poses a serious economic and healthcare burden. This study aimed to investigate the prevalence of burnout as well as anxiety, depression, and stress in medical residents from different majors, and assess the effects of an online psychological intervention on the mental health status of medical residents with a high degree of burnout.

Methods: We conducted an online survey that collected information on the demographics, mental health, and burnout conditions of medical residents from Shengjing Hospital. The mental health condition was assessed by the Depression, Anxiety, and Stress Scale (DASS)−21. Further, burnout was assessed by the Maslach Burnout Inventory (MBI). Medical residents with a total MBI score between 50 and 75 were selected to receive online psychological intervention for 3 months.

Results: Two-hundred and ten medical residents completed the questionnaire, of whom, 63 residents with an MBI score between 50 and 75 received the 3-month online psychological intervention. Anesthesia residents showed the highest level of depression, anxiety, and stress, and presented with a lower sense of personal accomplishment, higher emotional exhaustion, and higher depersonalization. Furthermore, pediatric residents had the second highest DASS and MBI scores following anesthesia residents. Following the online psychological intervention, negative emotional states and burnout levels were significantly lower among anesthesia and pediatric residents. There were no differences in the level of stress and sense of personal accomplishment pre- and post-online psychological intervention among the different majors.

Conclusion: Our findings revealed high levels of burnout, as well as depression, anxiety, and stress symptoms in medical residents, with marked differences among different majors. The online psychological intervention effectively improved emotional exhaustion, and depersonalization, and relieved the psychological problems such as anxiety and depression in medical residents.
The Role of Working Memory in the Processing of Scalar Implicatures of Patients With Schizophrenia Spectrum and Other Psychotic Disorders
Authors: Schaeken Walter , Van de Weyer Linde , De Hert Marc , Wampers Martien
Published: May 2021

A number of studies have demonstrated pragmatic language difficulties in people with Schizophrenia Spectrum and Other Psychotic Disorders. However, research about how people with schizophrenia spectrum and other psychotic disorders understand scalar implicatures (SIs) is surprisingly rare, since SIs have generated much of the most recent literature. Scalar implicatures are pragmatic inferences, based on linguistic expressions like some, must, or, which are part of a scale of informativeness (e.g., some/many/all). Logically, the less informative expressions imply the more informative ones, but pragmatically people usually infer that the presence of a less informative term implies that the more informative term was not applicable. In one of the few existing studies with people with schizophrenia spectrum and other psychotic disorders, Wampers et al. (2018) observed that in general, people with schizophrenia spectrum and other psychotic disorders were less likely to derive SIs than controls. The current study has three main aims. First, we want to replicate the original finding with the scalar terms some-all. Second, we want to investigate how these patients deal with different scalar terms, that is, we want to investigate if scalar diversity is also observed in this clinical group. Third, we investigate the role of working memory, often seen as another important mechanism to enable inferring SIs. Twenty-one individuals with a psychotic disorder and 21 matched controls answered 54 under-informative statements, in which seven different pairs of scalar terms were used. In addition, working memory capacity was measured. Patients with schizophrenia spectrum and other psychotic disorders did not make more logical interpretations when processing quantifiers, disconfirming Wampers et al. (2018). However, certain scalar scales elicited more pragmatic interpretations than others, which is in line with the scalar diversity hypothesis. Additionally, we observed only partial evidence for the role of working memory. Only for the scalar scale and-or, a significant effect of working memory was observed. The implications of these results for patients with schizophrenia spectrum and other psychotic disorders are discussed, but also the role of working memory for pragmatic inferences, as well as the place of SIs in experimental pragmatics.
Effects of Small-Sided Game Interventions on the Technical Execution and Tactical Behaviors of Young and Youth Team Sports Players: A Systematic Review and Meta-Analysis
Authors: Clemente Filipe Manuel , Ramirez-Campillo Rodrigo , Sarmento Hugo , Praça Gibson Moreira , Afonso José , Silva Ana Filipa , Rosemann Thomas , Knechtle Beat
Published: May 2021

Background: Small-sided games (SSGs) are an adjusted form of official games that are often used in training scenarios to introduce a specific tactical issue to team sports players. Besides the acute effects of SSGs on players' performance, it is expectable that the consistent use of these drill-based games induces adaptations in the technical execution and tactical behaviors of youth team sports players.

Objective: This systematic review with meta-analysis was conducted to assess the effects of SSG programs on the technical execution and tactical behaviors of young and youth team sports players.

Data Sources: The data sources utilized were PubMed, Scopus, SPORTDiscus, and Web of Science.

Study Eligibility Criteria: (i) Young and youth team sports players (i.e., < 18 years old) of any sex or skill level, without injury, illness, or other clinical conditions; (ii) SSGs-based programs not restricted to the duration and a minimum of one weekly training session; (iii) passive or active control groups; (iv) pre-post interventions values of technical execution and/or tactical behavior; (v) randomized and non-randomized controlled trials; and (vi) peer-reviewed original full-text studies written in English, Portuguese and/or Spanish.

Results: The database search initially yielded 803 titles. From those, six articles were eligible for the systematic review and meta-analysis. None of the included studies presented tactical behavior outcomes. The results showed a small effect of SSGs on technical execution (ES = 0.59; 95% CI = 0.29 to 0.89; p < 0.001; I2 = 0.0%; Egger's test p = 0.590) when compared to controls. Sub-group analysis of the training factor revealed similar (p = 0.433) moderate (ES = 0.68, four study groups) and small (ES = 0.44, three study groups) improvements in technical execution after >17 and <17 SSG training sessions, respectively.

Conclusions: This systematic review and meta-analysis revealed a significant beneficial effect of using SSG training programs for enhancing technical execution in young and youth players. The benefits were similar despite the various numbers of training sessions applied. Further studies should add tactical behaviors as one of the outcomes for controlling the effects of SSG training programs.
The COVID-19 Disappeared: From Traumatic to Ambiguous Loss and the Role of the Internet for the Bereaved in Italy
Authors: Testoni Ines , Azzola Claudia , Tribbia Noemi , Biancalani Gianmarco , Iacona Erika , Orkibi Hod , Azoulay Bracha
Published: May 2021

In Italy, in the very first phase of the COVID-19 pandemic there was a dramatic rise in mortality. However, families were forbidden because of lockdown regulations to be with their loved ones at their deathbeds or to hold funerals. This qualitative study examined bereavement experiences among family members, how they processed their grief, and how they used social networks in particular by uploading photographs during the working-through of bereavement. The sample was composed of 40 individuals aged 23–63 (80% women) from different Italian cities severely impacted by the virus, including a subgroup from the province of Bergamo, which was the city with the highest mortality rate during that time. All interviews were conducted by phone, Skype, or Zoom. Then, the transcriptions underwent a thematic analysis using Atlas.ti. The main themes that emerged were: abandonment anger and guilt, dehumanized disappeared, derealization and constant rumination, and social support and the importance of sharing photos on Facebook. Importantly, the use of social networks proved to be a valuable source of support and photographs were a powerful tool in facilitating the process of mourning by encouraging narration and sharing. Grief had a complex profile: on the one hand, it was traumatic and characterized by all the risk factors causing mourners to experience prolonged grief, but on the other, some features were similar to ambiguous loss (that occurs without closure and clear understanding) because of the impossibility to be with their relatives in their final moments. The possible relationships between ambiguous loss, the use of internet, and the risk of prolonged grief are discussed.
Time Distortions: A Systematic Review of Cases Characteristic of Alice in Wonderland Syndrome
Authors: Blom Jan Dirk , Nanuashvili Nutsa , Waters Flavie
Published: May 2021

Of the perceptual distortions characteristic of Alice in Wonderland syndrome, substantial alterations in the immediate experience of time are probably the least known and the most fascinating. We reviewed original case reports to examine the phenomenology and associated pathology of these time distortions in this syndrome. A systematic search in PubMed, Ovid Medline, and the historical literature yielded 59 publications that described 168 people experiencing time distortions, including 84 detailed individual case reports. We distinguished five different types of time distortion. The most common category comprises slow-motion and quick-motion phenomena. In 39% of all cases, time distortions were unimodal in nature, while in 61% there was additional involvement of the visual (49%), kinaesthetic (18%), and auditory modalities (14%). In all, 40% of all time distortions described were bimodal in nature and 19% trimodal, with 1% involving four modalities. Underlying neurological mechanisms are varied and may be triggered by intoxications, infectious diseases, metabolic disorders, CNS lesions, paroxysmal neurological disorders, and psychiatric disorders. Bizarre sensations of time alteration—such as time going backwards or moving in circles—were mostly associated with psychosis. Pathophysiologically, mainly occipital areas appear to be involved, although the temporal network is widely disseminated, with separate component timing mechanisms not always functioning synchronously, thus occasionally creating temporal mismatches within and across sensory modalities (desynchronization). Based on our findings, we propose a classification of time distortions and formulate implications for research and clinical practice.
Burnout Among Private Security Staff in Serbia: A Multicentic Cross-Sectional Study
Authors: Veljković Dejan R. , Rancic Natasa K. , Mirković Momčilo R. , Kulić Ljiljana M. , Stanković Veroslava V. , Stefanović Ljubomir S. , Stojanović Marko M. , Mirković Miloš V. , Ðurić Slađana M. , Ilić Danijela Z.
Published: May 2021

Background: Burnout is a special a state of physical or emotional exhaustion that also involves a sense of reduced accomplishment and loss of personal identity.

Objectives: To evaluate the predictors of burnout among work staff in the seven private agencies for support and defense of persons and their property.

Material and Method: We performed a multicentric cross-sectional study that involved representative sample of working staff from Agencies of Private Security in Central Serbia. Burnout was assessed using Maslach Burnout Inventory- (MBI)-Human Services Survey.

Results: A total number of participants were 353 (330 men and 23 women). Measured level of burnout as assessed by high emotional exhaustion, high depersonalization, and low personal accomplishment was 66.3, 82.4, and 13.4%, respectively. We identified that female gender, younger age, shorter work experience, working in shifts, working 12 h a day and more than 8–12 h a day as well as dissatisfaction with working conditions. Work in shifts, working 12 h a day and more than 8–12 h a day and dissatisfied with dissatisfaction with working conditions significantly increase the risk of total burnout.

Conclusion: Our results showed that significant predictors for the development of burnout syndrome were female gender, younger age, shorter work experience, working in shifts, as well as dissatisfaction with working conditions.