bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of CAR-Modified T Cell Therapy in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Prospective Clinical Trials
Authors: Xiang Xinrong , He Qiao , Ou Yang , Wang Wen , Wu Yu
Published: December 2020

Background: In recent years, chimeric antigen receptor-modified T (CAR-T) cell therapy for B-cell leukemia and lymphoma has shown high clinical efficacy. Similar CAR-T clinical trials have also been carried out in patients with refractory/relapsed multiple myeloma (RRMM). However, no systematic review has evaluated the efficacy and safety of CAR-T cell therapy in RRMM. The purpose of this study was to fill this literature gap.

Methods: Eligible studies were searched in PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, and WanFang from data inception to December 2019. For efficacy assessment, the overall response rate (ORR), minimal residual disease (MRD) negativity rate, strict complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) were calculated. The incidence of any grade cytokine release syndrome (CRS) and grade ≥3 adverse events (AEs) were calculated for safety analysis. The effect estimates were then pooled using an inverse variance method.

Results: Overall, 27 studies involving 497 patients were included in this meta-analysis. The pooled ORR and MRD negativity rate were 89% (95% Cl: 83–94%) and 81% (95% Cl: 67–91%), respectively. The pooled sCR, CR, VGPR, and PR were 14% (95% Cl: 5–27%), 13% (95% Cl: 4–26%), 23% (95% Cl: 14–33%), and 15% (95% Cl: 10–21%), respectively. Subgroup analyses of ORR by age, proportion of previous autologous stem cell transplantation (ASCT), and target selection of CAR-T cells revealed that age ≤ 55 years (≤55 years vs. > 55 years, p = 0.0081), prior ASCT ≤70% (≤70% vs. > 70%, p = 0.035), and bispecific CAR-T cells (dual B-cell maturation antigen (BCMA)/BCMA + CD19 vs specific BCMA, p = 0.0329) associated with higher ORR in patients. Subgroup analyses of remission depth by target selection suggested that more patients achieved a better response than VGPR with dual BCMA/BCMA + CD19 CAR-T cells compared to specific BCMA targeting (p = 0.0061). In terms of safety, the pooled incidence of any grade and grade ≥ 3 CRS was 76% (95% CL: 63–87%) and 11% (95% CL: 6–17%). The most common grade ≥ 3 AEs were hematologic toxic effects.

Conclusion: In heavily treated patients, CAR-T therapy associates with promising responses and tolerable AEs, as well as CRS in RRMM. However, additional information regarding the durability of CAR-T cell therapy, as well as further randomized controlled trials, is needed.
Effect of Glycosaminoglycan Replacement on Markers of Interstitial Cystitis In Vitro
Authors: Rooney Peadar , Ryan Christina , McDermott Barry J. , Dev Kapil , Pandit Abhay , Quinlan Leo R.
Published: December 2020

Aims:To examine the effect of three commercial intravesical formulations of glycosaminoglycan onin vitroinflammatory models of IC/BPS to better understand there effect on specific markers of disease.

Methods:Human urothelial cells (HTB-4) were cultured under four conditions in the presence or absence of commercial GAG formulations. Cells were cultured under a basal condition or pre-treated with protamine sulfate (100 ng/ml) (damages the endogenous glycosaminoglycan layer), hydrogen peroxide (1%) (a metabolic stressor) or TNFα (10 ng/ml) (creating an inflammatory environment). Each of these four culture conditions was then treated with one of three GAG formulations, CystistatⓇ, iAluRilⓇ and HyacystⓇ. Assays were then performed to examine the effect of the exogenous GAGs on cell viability, cell migration, sGAG production, cytokine and gene expression.

Results:All GAG formulations were well tolerated by the HTB-4 cells and supported cell growth and migration. iAluRilⓇ was most effective at stimulating endogenous sGAG production under all conditions, increasing sGAGs by up to 15-fold. All GAG formulations significantly reduced the production of the pro-inflammatory cytokine IL-8 under basal conditions, while no GAG treatment suppressed cytokine production under any other condition. Only CystistatⓇhad a significant effect on HA receptor expression, significantly increasing ICAM-1 expression at 3 h that returned to basal levels at 24 h. No GAG treatment significantly changed the expression of GAG synthesis enzymes (CSGALNACT1, CSGALNACT2) or markers of tissue remodeling (MMP2, TIMP1) and pain (COX-1/PTGS-1, NGF).

Conclusions:The data presented in this study reveal that commercial intravesical formulation support cell viability and migration. In addition, the commercial GAG formulations have a mild anti-inflammatory effect in thein vitromodel of interstitial cystitis/bladder pain syndrome.
Bu-Shen-Huo-Xue Decoction Ameliorates Diabetic Nephropathy by Inhibiting Rac1/PAK1/p38MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Mice
Authors: Wang Weisong , Long Hongping , Huang Wei , Zhang Ting , Xie Lihua , Chen Cheng , Liu Jianhe , Xiong Dan , Hu Wei
Published: December 2020

Diabetic nephropathy (DN), a leading cause of end-stage renal disease, is associated with high morbidity and mortality rates worldwide and the development of new drugs to treat DN is urgently required. Bu-Shen-Huo-Xue (BSHX) decoction is a traditional Chinese herbal formula, made according to traditional Chinese medicine (TCM) theory, and has been used clinically to treat DN. In the present study, we established a high-fat diet/streptozotocin-induced diabetic mouse model and treated the mice with BSHX decoction to verify its therapeutic effects in vivo. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to analyze the chemical composition and active compounds of BSHX decoction. Markers of podocyte epithelial-mesenchymal transition and the Rac1/PAK1/p38MAPK signaling pathway were evaluated to investigate the mechanism underlying function of BSHX decoction. BSHX decoction effectively alleviated diabetic symptoms, according to analysis of the renal function indicators, serum creatinine, blood urea nitrogen, serum uric acid, and urinary albumin excretion rate, as well as renal histopathology and ultrastructural pathology of DN mice. We identified 67 compounds, including 20 likely active compounds, in BSHX decoction. The podocyte markers, nephrin and podocin, were down-regulated, while the mesenchymal markers, α-SMA and FSP-1, were up-regulated in DN mouse kidney; however, the changes in these markers were reversed on treatment with BSHX decoction. GTP-Rac1 was markedly overexpressed in DN mice and its levels were significantly decreased in response to BSHX decoction. Similarly, levels of p-PAK1 and p-p38MAPK which indicate Rac1 activation, were reduced on treatment with BSHX decoction. Together, our data demonstrated that BSHX decoction ameliorated renal function and podocyte epithelial-mesenchymal transition via inhibiting Rac1/PAK1/p38MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. Further, we generated a quality control standard and numerous potential active compounds from BSHX decoction for DN.
Antioxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Citrus lumia Juice
Authors: Smeriglio Antonella , Denaro Marcella , D’Angelo Valeria , Germanò Maria Paola , Trombetta Domenico
Published: December 2020

Citrus juices are a rich source of bioactive compounds with various and well-known health benefits. The aim of this study was to investigate the polyphenols and ascorbic acid content as well as to investigate the antioxidant, anti-inflammatory and anti-angiogenic properties of the juice of an ancient Mediterranean species, Citrus lumia Risso (CLJ). The antioxidant and anti-inflammatory activities were evaluated by several in vitro cell-free and cell-based assays, whereas two different in vivo models, the chick chorioallantoic membrane (CAM) and the zebrafish embryos, were used to characterize the anti-angiogenic properties. Twenty-eight polyphenols were identified by RP-LC-DAD-ESI-MS analysis (flavonoids 68.82% and phenolic acids 31.18%) with 1-caffeoyl-5-feruloylquinic acid and kaempferol 3′-rhamnoside, which represent the most abundant compounds (25.70 and 23.12%, respectively). HPLC-DAD analysis showed a high ascorbic acid content (352 mg/kg of CLJ), which contributes with polyphenols to the marked and dose-dependent antioxidant and anti-inflammatory properties observed. CLJ showed strong and dose-dependent anti-angiogenic activity as highlighted by the inhibition of blood vessel formation on CAMs and the decrease of endogenous alkaline phosphatase on zebrafish embryos. Moreover, within the concentration range tested, no dead or malformed embryos were recorded. Certainly, further studies are needed to investigate the molecular mechanisms underlying these promising biological effects, but considering the evidence of the present study, the use of CLJ as a ready-to drink safe prevention strategy for inflammatory-based diseases correlated to angiogenesis could be justified.
Napabucasin Reduces Cancer Stem Cell Characteristics in Hepatocellular Carcinoma
Authors: Li Ya , Han Qiuju , Zhao Huajun , Guo Quanjuan , Zhang Jian
Published: December 2020

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Cancer stem cells (CSCs) are a rare population with self-renewal and multipotent differentiation capacity, and reside among the more differentiated cancer cells. CSCs are associated with tumor recurrence, drug resistance and poor prognosis. The aim of this study was to determine the efficacy of napabucasin against HCC and elucidate the underlying molecular mechanisms. Napabucasin significantly decreased the viability of HCC cells in vitro by inducing apoptosis and cell cycle arrest. In addition, it suppressed CSC-related gene expression and spheroid formation in vitro, indicating depletion of CSCs. The anti-neoplastic effects of napabucasin was also evident in homograft tumor-bearing mouse models. Our findings provide the scientific basis of conducting clinical trials on napabucasin as a new therapeutic agent against HCC.
The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action
Authors: Dudysová Daniela , Janků Karolina , Šmotek Michal , Saifutdinova Elizaveta , Kopřivová Jana , Bušková Jitka , Mander Bryce Anthony , Brunovský Martin , Zach Peter , Korčák Jakub , Andrashko Veronika , Viktorinová Michaela , Tylš Filip , Bravermanová Anna , Froese Tom , Páleníček Tomáš , Horáček Jiří
Published: December 2020

Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin’s antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regarding the potential antidepressant properties, we hypothesized that psilocybin, similar to other classical antidepressants, would reduce rapid eye movement (REM) sleep and prolong REM sleep latency. Moreover, we also hypothesized that psilocybin would promote slow-wave activity (SWA) expression in the first sleep cycle, a marker of sleep-related neuroplasticity. Twenty healthy volunteers (10 women, age 28–53) underwent two drug administration sessions, psilocybin or placebo, in a randomized, double-blinded design. Changes in sleep macrostructure, SWA during the first sleep cycle, whole night EEG spectral power across frequencies in non-rapid eye movement (NREM) and REM sleep, and changes in subjective sleep measures were analyzed. The results revealed prolonged REM sleep latency after psilocybin administration and a trend toward a decrease in overall REM sleep duration. No changes in NREM sleep were observed. Psilocybin did not affect EEG power spectra in NREM or REM sleep when examined across the whole night. However, psilocybin suppressed SWA in the first sleep cycle. No evidence was found for sleep-related neuroplasticity, however, a different dosage, timing, effect on homeostatic regulation of sleep, or other mechanisms related to antidepressant effects may play a role. Overall, this study suggests that potential antidepressant properties of psilocybin might be related to changes in sleep.
Acute Lysergic Acid Diethylamide Does Not Influence Reward-Driven Decision Making of C57BL/6 Mice in the Iowa Gambling Task
Authors: Elsilä Lauri V. , Korhonen Nuppu , Hyytiä Petri , Korpi Esa R.
Published: December 2020

While interest in psychedelic drugs in the fields of psychiatry and neuroscience has re-emerged in recent last decades, the general understanding of the effects of these drugs remains deficient. In particular, there are gaps in knowledge on executive functions and goal-directed behaviors both in humans and in commonly used animal models. The effects of acute doses of psychedelic lysergic acid diethylamide (LSD) on reward-driven decision making were explored using the mouse version of the Iowa Gambling Task. A total of 15 mice were trained to perform in a touch-screen adaptation of the rodent version of the Iowa Gambling Task, after which single acute doses of LSD (0.025, 0.1, 0.2, 0.4 mg/kg), serotonin 2A receptor-selective agonist 25CN-NBOH (1.5 mg/kg), d-amphetamine (2.0 mg/kg), and saline were administered before the trial. 25CN-NBOH and the three lowest doses of LSD showed no statistically significant changes in option selection or in general functioning during the gambling task trials. The highest dose of LSD (0.4 mg/kg) significantly decreased premature responding and increased the omission rate, but had no effect on option selection in comparison with the saline control. Amphetamine significantly decreased the correct responses and premature responding while increasing the omission rate. In conclusion, mice can perform previously learned, reward-driven decision-making tasks while under the acute influence of LSD at a commonly used dose range.
Incidence of Suspected Serious Adverse Drug Reactions in Corona Virus Disease-19 Patients Detected by a Pharmacovigilance Program by Laboratory Signals in a Tertiary Hospital in Spain: Cautionary Data
Authors: Ramírez Elena , Urroz Mikel , Rodríguez Amelia , González-Muñoz Miguel , Martín-Vega Alberto , Villán Yuri , Seco Enrique , Monserrat Jaime , Frías Jesús , Carcas Antonio J. , Borobia Alberto M.
Published: December 2020

BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients vs. non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019.

METHODS: All ALSs that reflected potential SADRs including neutropenia, pancytopenia, thrombocytopenia, anemia, eosinophilia, leukocytes in cerebrospinal fluid, hepatitis, pancreatitis, acute kidney injury, rhabdomyolysis, and hyponatremia were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients.

RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients, 95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%).

CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events.
A Multi Waveform Adaptive Driving Scheme for Reducing Hysteresis Effect of Electrowetting Displays
Authors: Li Wei , Wang Li , Henzen Alex
Published: December 2020

Electrowetting display (EWD) is a new reflective display technology, which has the advantages of ultra-low power consumption, high contrast, fast response and full-color. However, due to a hysteresis effect, accurate gray scale display of EWDs cannot be achieved, which seriously restricted the display effect and performance of EWDs. In order to reduce the influence of hysteresis effect, a multi waveform adaptive driving scheme was proposed in this paper. Firstly, a multi waveform driving system was designed and implemented by a STM32 master chip and an AD5304 driver chip. The driving system could automatically select different driving waveforms according to the preset switching conditions. Then, different driving waveforms were designed and implemented according to different driving stages of EWDs. Finally, driving waveforms were mapped with each stage of the driving process one by one to realize the adaptive driving of multiple waveforms. The experimental results showed that, compared with the conventional square wave, the maximum hysteresis difference of hysteresis curve could be reduced by 39.19% with the multi waveform driving scheme.
Training Specificity of Inspiratory Muscle Training Methods: A Randomized Trial
Authors: Van Hollebeke Marine , Gosselink Rik , Langer Daniel
Published: December 2020

Introduction

Inspiratory muscle training (IMT) protocols are typically performed using pressure threshold loading with inspirations initiated from residual volume (RV). We aimed to compare effects of three different IMT protocols on maximal inspiratory pressures (PImax) and maximal inspiratory flow (V̇Imax) at three different lung volumes. We hypothesized that threshold loading performed from functional residual capacity (FRC) or tapered flow resistive loading (initiated from RV) would improve inspiratory muscle function over a larger range of lung volumes in comparison with the standard protocol.

Methods

48 healthy volunteers (42% male, age: 48 ± 9 years, PImax: 110 ± 28%pred, [mean ± SD]) were randomly assigned to perform three daily IMT sessions of pressure threshold loading (either initiated from RV or from FRC) or tapered flow resistive loading (initiated from RV) for 4 weeks. Sessions consisted of 30 breaths against the highest tolerable load. Before and after the training period, PImax was measured at RV, FRC, and midway between FRC and total lung capacity (1/2 IC). V̇Imax was measured at the same lung volumes against a range of external threshold loads.

Results

While PImax increased significantly at RV and at FRC in the group performing the standard training protocol (pressure threshold loading from RV), it increased significantly at all lung volumes in the two other training groups (all p < 0.05). No significant changes in V̇Imax were observed in the group performing the standard protocol. Increases of V̇Imax were significantly larger at all lung volumes after tapered flow resistive loading, and at higher lung volumes (i.e., FRC and 1/2 IC) after pressure threshold loading from FRC in comparison with the standard protocol (all p < 0.05).

Conclusion

Only training with tapered flow resistive loading and pressure threshold loading from functional residual capacity resulted in consistent improvements in respiratory muscle function at higher lung volumes, whereas improvements after the standard protocol (pressure threshold loading from residual volume) were restricted to gains in PImax at lower lung volumes. Further research is warranted to investigate whether these results can be confirmed in larger samples of both healthy subjects and patients.
Manipulation of the Fascial System Applied During Acute Inflammation of the Connective Tissue of the Thoracolumbar Region Affects Transforming Growth Factor-β1 and Interleukin-4 Levels: Experimental Study in Mice
Authors: França Maria Elisa Duarte , Sinhorim Larissa , Martins Daniel Fernandes , Schleip Robert , Machado-Pereira Nicolas A. M. M. , de Souza Gabriel Melo , Horewicz Verônica Vargas , Santos Gilmar Moraes
Published: December 2020

Fascia can become rigid and assume a fibrotic pattern due to inflammatory processes. Manipulation of the fascial system (MFS), manual technique targeting connective tissues, is commonly used in clinical practice in pain management. We aimed to verify MFS effects on the connective tissue inflammatory changes in mice. SwissMus musculusmale mice (n= 44) were distributed into groups: carrageenan without treatment (Car,n= 11), carrageenan with MFS (Car + MFS,n= 12), saline without treatment (n= 10), and saline with MFS (saline + MFS,n= 11). Interleukin 4 (IL-4), IL-6, tumor necrosis factor (TNF), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein 1 (MCP-1) levels were verified by enzyme-linked immunosorbent assay. Neutrophil (Ly-6G), macrophage (F4/80), and nitric oxide synthase 2 (NOS-2) were identified using Western blot. The MFS protocol was applied from the first to the third day after inflammation of the connective tissue of the thoracolumbar region. There was a significant MFS effect on IL-4 (p= 0.02) and TGF-β1 (p= 0.04), without increasing MCP-1, TNF, and IL-6 levels (p> 0.05) on thoracolumbar region from Car + MFS, in comparison with saline. Ly-6G in Car + MFS presented lower levels when compared with saline (p= 0.003) or saline + MFS (0.003). NOS-2 levels were lower in Car + MFS than in saline + MFS (p= 0.0195) or saline (p= 0.003). MFS may have an anti-inflammatory effect, based on TGF-β1 and IL-4. IL-4 may have inhibited neutrophil migration. Lower levels of NOS-2 may be linked to the lack of macrophages, which are responsible for NOS-2 expression.
Higher Frequency of Hospital-Acquired Infections but Similar In-Hospital Mortality Among Admissions With Alcoholic Hepatitis at Academic vs. Non-academic Centers
Authors: Waleed Muhammad , Abdallah Mohamed A. , Kuo Yong-Fang , Arab Juan P. , Wong Robert , Singal Ashwani K.
Published: December 2020

Background

Alcoholic hepatitis (AH) is a unique syndrome characterized by high short-term mortality. The impact of the academic status of a hospital (urban and teaching) on outcomes in AH is unknown.

Methods

National Inpatient Sample dataset (2006–2014) on AH admissions stratified to academic center (AC) or non-academic center (NAC) and analyzed for in-hospital mortality (IHM), hospital resource use, length of stay in days (d), and total charges (TC) in United States dollars (USD). Admission year was stratified to 2006–2008 (TMI), 2009–2011 (TM2), and 2012–2014 (TM3).

Results

Of 62,136 AH admissions, the proportion at AC increased from 46% in TM1 to 57% in TM3, Armitage trend, p < 0.001. On logistic regression, TM3, younger age, black race, Medicaid and private insurance, and development of acute on chronic liver failure (ACLF) were associated with admission to an AC. Of 53,264 admissions propensity score matched for demographics, pay status, and disease severity, admissions to AC vs. NAC (26,622 each) were more likely to have liver disease complications (esophageal varices, ascites, and hepatic encephalopathy) and hospital-acquired infections (HAI), especially Clostridioides difficile and ventilator-associated pneumonia. Admissions to AC were more likely transfers from outside hospital (1.6% vs. 1.3%) and seen by palliative care (4.8% vs. 3.3%), p < 0.001. Use of endoscopy, dialysis, and mechanical ventilation were similar. With similar IHM comparing AC vs. NAC (7.7% vs. 7.8%, p = 0.93), average LOS and number of procedures were higher at AC (7.7 vs. 7.1 d and 2.3 vs. 1.9, respectively, p < 0.001) without difference on total charges ($52,821 vs. $52,067 USD, p = 0.28). On multivariable logistic regression model after controlling for demographics, ACLF grade, and calendar year, IHM was similar irrespective of academic status of the hospital, HR (95% CI): 1.01 (0.93–1.08, p = 0.70). IHM decreased over time, with ACLF as strongest predictor. A total of 63 and 22% were discharged to home and skilled nursing facility, respectively, without differences on academic status of the hospital.

Conclusion

Admissions with AH to AC compared to NAC have higher frequency of liver disease complications and HAI, with longer duration of hospitalization. Prospective studies are needed to reduce HAI among hospitalized patients with AH.
Evidence for Training-Induced Changes in miRNA Levels in the Skeletal Muscle of Patients With Type 2 Diabetes Mellitus
Authors: Simaitis Sarah , Schulte-Körne Benedikt , Schiffer Thorsten , Bloch Wilhelm , Predel Hans-Georg , Brixius Klara , Brinkmann Christian
Published: December 2020

Physical training can improve glycemic control in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are not entirely clear. An interesting piece of the puzzle could be the regulation of micro-RNAs (miRNAs). They are important modulators of protein expression. Some miRNAs were found to be both linked to poor glycemic control/insulin resistance (with evidence from in vivo and/or in vitro studies) and dysregulated in the skeletal muscle of T2DM patients. This pilot study examines whether a 3-month endurance training program [three times a week, 70–80% peak heart rate (HRpeak)] can down-regulate their levels in T2DM men (n = 7). One skeletal muscle biopsy sample was obtained from each patient at T1 (6 weeks pre-intervention), one at T2 (1 week pre-intervention) and one at T3 (3–4 days post-intervention). miRNA-27a-3p, −29a-3p, −29b-3p, −29c-3p, −106b-5p, −135a-5p, −143-3p, −144-3p, −194-5p, and − 206 levels were determined by RT-qPCR. Friedman ANOVA and post-hoc tests showed that miRNA-29b-3p, −29c-3p and -135a-5p levels were significantly reduced post-training (T3 vs. T2 and/or T1). Glycated hemoglobin (HbA1c) and HOMA insulin resistance index did not change significantly. However, HbA1c was reduced in 6 of 7 patients post-training. Furthermore, Spearman’s rank correlation analyses with all values from all time points showed significant negative associations between miRNA-29c-3p, −106b-5p, −144-3p and −194-5p levels and cardiorespiratory fitness (VO2peak). The study results imply that regular exercise and improving one’s physical fitness is helpful for the regulation of skeletal muscle miRNAs in T2DM patients. Whether or not changes in the miRNA profile can affect the clinical situation of T2DM patients warrants further research.
Endogenous Auxin Content Contributes to Larger Size of Apple Fruit
Authors: Bu Haidong , Yu Wenquan , Yuan Hui , Yue Pengtao , Wei Yun , Wang Aide
Published: December 2020

Fruit size is an important economic trait that is controlled by multiple genes. However, the regulatory mechanism for fruit size remains poorly understood. A bud sport variety of “Longfeng” (LF) apple (Malus domestica) was identified and named “Grand Longfeng” (GLF). The fruit size of GLF is larger than that of LF, and both varieties are diploid. We found that the cell size in GLF fruit was larger than that of LF. Then, we compared the fruit transcriptomes of the two varieties using RNA-Seq technology. A total of 1166 differentially expressed genes (DEGs) were detected between GLF and LF fruits. The KEGG analysis revealed that the phytohormone pathway was the most enriched, in which most of the DEGs were related to auxin signaling. Moreover, the endogenous auxin levels of GLF fruit were higher than those of LF. The expressions of auxin synthetic genes, including MdTAR1 and MdYUCCA6, were higher in GLF fruit than LF. Collectively, our findings suggest that auxin plays an important role in fruit size development.
Updates on BES1/BZR1 Regulatory Networks Coordinating Plant Growth and Stress Responses
Authors: Kono Alfredo , Yin Yanhai
Published: December 2020

Brassinosteroids (BRs) play pivotal roles in the regulation of many dimensions of a plant’s life. Hence, through extensive efforts from many research groups, BR signaling has emerged as one of the best-characterized plant signaling pathways. The key molecular players of BR signaling from the cell surface to the nucleus important for the regulation of plant growth and development are well-established. Recent data show that BRs also modulate plant responses to environmental stresses such as drought and pathogen infection. In this mini review, we present the recent progress in BR signaling specifically in the post-translational SUMO modification of BR’s master regulators, BES1/BZR1. We also discuss recent findings on the crosstalk between BR, UV light, and jasmonic acid signaling pathways to balance growth during light stress and pathogen infections. Finally, we describe the current update on the molecular link between BR signaling and intracellular auxin transport that essential for plant development.
Trust Toward Robots and Artificial Intelligence: An Experimental Approach to Human–Technology Interactions Online
Authors: Oksanen Atte , Savela Nina , Latikka Rita , Koivula Aki
Published: December 2020

Robotization and artificial intelligence (AI) are expected to change societies profoundly. Trust is an important factor of human–technology interactions, as robots and AI increasingly contribute to tasks previously handled by humans. Currently, there is a need for studies investigating trust toward AI and robots, especially in first-encounter meetings. This article reports findings from a study investigating trust toward robots and AI in an online trust game experiment. The trust game manipulated the hypothetical opponents that were described as either AI or robots. These were compared with control group opponents using only a human name or a nickname. Participants (N = 1077) lived in the United States. Describing opponents with robots or AI did not impact participants’ trust toward them. The robot called jdrx894 was the most trusted opponent. Opponents named “jdrx894” were trusted more than opponents called “Michael.” Further analysis showed that having a degree in technology or engineering, exposure to robots online and robot use self-efficacy predicted higher trust toward robots and AI. Out of Big Five personality characteristics, openness to experience predicted higher trust, and conscientiousness predicted lower trust. Results suggest trust on robots and AI is contextual and it is also dependent on individual differences and knowledge on technology.
Improving Cognitive Workload in Radiation Therapists: A Pilot EEG Neurofeedback Study
Authors: Campbell Alana M. , Mattoni Matthew , Yefimov Mae Nicopolis , Adapa Karthik , Mazur Lukasz M.
Published: December 2020

Radiation therapy therapists (RTTs) face challenging daily tasks that leave them prone to high attrition and burnout and subsequent deficits in performance. Here, we employed an accelerated alpha-theta neurofeedback (NF) protocol that is implementable in a busy medical workplace to test if 12 RTTs could learn the protocol and exhibit behavior and brain performance-related benefits. Following the 3-week protocol, participants showed a decrease in subjective cognitive workload and a decrease in response time during a performance task, as well as a decrease in desynchrony of the alpha electroencephalogram (EEG) band. Additionally, novel microstate analysis for neurofeedback showed a significant decrease in global field power (GFP) following neurofeedback. These results suggest that the RTTs successfully learned the protocol and improved in perceived cognitive workload following 3 weeks of neurofeedback. In sum, this study presents promising behavioral improvements as well as brain performance-related evidence of neurophysiological changes following neurofeedback, supporting the feasibility of implementing neurofeedback in a busy workplace and encouraging the further study of neurofeedback as a tool to mitigate burnout.
Risk and Resilience Factors During the COVID-19 Pandemic: A Snapshot of the Experiences of Canadian Workers Early on in the Crisis
Authors: Coulombe Simon , Pacheco Tyler , Cox Emily , Khalil Christine , Doucerain Marina M. , Auger Emilie , Meunier Sophie
Published: December 2020

Research highlights several risk and resilience factors at multiple ecological levels that influence individuals’ mental health and wellbeing in their everyday lives and, more specifically, in disaster or outbreak situations. However, there is limited research on the role of these factors in the early days of the COVID-19 crisis. The present study examined if and how potential risk factors (i.e., reduction in income, job insecurity, feelings of vulnerability to contracting the virus, lack of confidence in avoiding COVID-19, compliance with preventative policies) and resilience factors (i.e., trait resilience, family functioning, social support, social participation, and trust in healthcare institutions) are associated with mental health and well-being outcomes, and whether these resilience factors buffer (i.e., moderate) the associations between risk factors and said outcomes. One to two weeks after the government recommended preventative measures, 1,122 Canadian workers completed an online questionnaire, including multiple wellbeing outcome scales in addition to measures of potential risk and resilience factors. Structural equation models were tested, highlighting that overall, the considered risk factors were associated with poorer wellbeing outcomes, except social distancing which was associated with lower levels of stress. Each of the potential resilience factors was found to have a main effect on one or more of the wellbeing outcomes. Moderation analysis indicated that in general these resilience factors did not, however, buffer the risk factors. The findings confirm that the COVID-19 crisis encompasses several stressors related to the virus as well as to its impact on one’s social, occupational, and financial situation, which put people at risk for lower wellbeing as early as one to two weeks after the crisis began. While several resilience factors emerged as positively related to wellbeing, such factors may not be enough, or sufficiently activated at that time, to buffer the effects of the numerous life changes required by COVID-19. From an ecological perspective, while mental health professionals and public health decision-makers should offer/design services directly focused on mental health and wellbeing, it is important they go beyond celebrating individuals’ inner potential for resilience, and also support individuals in activating their environmental resources during a pandemic.
Chinese College Students Have Higher Anxiety in New Semester of Online Learning During COVID-19: A Machine Learning Approach
Authors: Wang Chongying , Zhao Hong , Zhang Haoran
Published: December 2020

The COVID-19 pandemic has caused tremendous loss starting from early this year. This article aims to investigate the change of anxiety severity and prevalence among non-graduating undergraduate students in the new semester of online learning during COVID-19 in China and also to evaluate a machine learning model based on the XGBoost model. A total of 1172 non-graduating undergraduate students aged between 18 and 22 from 34 provincial-level administrative units and 260 cities in China were enrolled onto this study and asked to fill in a sociodemographic questionnaire and the Self-Rating Anxiety Scale (SAS) twice, respectively, during February 15 to 17, 2020, before the new semester started, and March 15 to 17, 2020, 1 month after the new semester based on online learning had started. SPSS 22.0 was used to conduct t-test and single factor analysis. XGBoost models were implemented to predict the anxiety level of students 1 month after the start of the new semester. There were 184 (15.7%, Mean = 58.45, SD = 7.81) and 221 (18.86%, Mean = 57.68, SD = 7.58) students who met the cut-off of 50 and were screened as positive for anxiety, respectively, in the two investigations. The mean SAS scores in the second test was significantly higher than those in the first test (P < 0.05). Significant differences were also found among all males, females, and students majoring in arts and sciences between the two studies (P < 0.05). The results also showed students from Hubei province, where most cases of COVID-19 were confirmed, had a higher percentage of participants meeting the cut-off of being anxious. This article applied machine learning to establish XGBoost models to successfully predict the anxiety level and changes of anxiety levels 4 weeks later based on the SAS scores of the students in the first test. It was concluded that, during COVID-19, Chinese non-graduating undergraduate students showed higher anxiety in the new semester based on online learning than before the new semester started. More students from Hubei province had a different level of anxiety than other provinces. Families, universities, and society as a whole should pay attention to the psychological health of non-graduating undergraduate students and take measures accordingly. It also confirmed that the XGBoost model had better prediction accuracy compared to the traditional multiple stepwise regression model on the anxiety status of university students.
Novelty Seeking and Mental Health in Chinese University Students Before, During, and After the COVID-19 Pandemic Lockdown: A Longitudinal Study
Authors: Li Wendy Wen , Yu Huizhen , Miller Dan J. , Yang Fang , Rouen Christopher
Published: December 2020

COVID-19 has created significant concern surrounding the impact of pandemic lockdown on mental health. While the pandemic lockdown can be distressing, times of crisis can also provide people with the opportunity to think divergently and explore different activities. Novelty seeking, where individuals explore novel and unfamiliarly stimuli and environments, may enhance the creativity of individuals to solve problems in a way that allows them to adjust their emotional responses to stressful situations. This study employs a longitudinal design to investigate changes in novelty seeking and mental health outcomes (namely, stress, anxiety, and depression) before, during, and after COVID-19 pandemic lockdown, among a group of students (final N = 173; Mage = 19.81; SDage = 0.98; 135 females and 38 males) from a university in southeast China. Participants were surveyed at three points: November, 2019 (prior to the COVID-19 pandemic); between February and March, 2020 (during the peak of the pandemic and intense lockdown in China); and between May and June, 2020 (after lockdown had been lifted in China). Cross-sectionally, correlation analysis indicated that greater novelty seeking was associated with lower levels of stress, anxiety, and depression at all three time points. Univariate latent curve modeling (LCM) indicated a growth trajectory in which novelty seeking increased over time and then remained high during the post-lockdown period. Stress, anxiety, and depression all showed V-shaped growth trajectories in which these variables decreased during lockdown, before increasing in the post-lockdown period. Multivariate LCM indicated the growth trajectory for novelty seeking was associated with the growth trajectories for stress, anxiety, and depression. This suggests that the observed decreases in stress, anxiety, and depression during the lockdown period may be attributable to the sample’s observed increase in novelty seeking. These findings are valuable in that they challenge the notion that lockdown measures are inherently detrimental to mental health. The findings indicate the important role of novelty seeking in responding to crises. It may be possible for future public health measures to incorporate the promotion of novelty seeking to help individuals’ respond to stressful situations and maintain good mental health in the face of crises.
A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population
Authors: Yuan Aihua , Wang Zengge , Xu Wen , Ding Qiang , Zhao Ying , Han Jingjing , Sun Jinhua
Published: December 2020

Rare inherited variations in multiplex families with Gilles de la Tourette syndrome (GTS) are suggested to play an important role in the genetic etiology of GTS. In order to explore the rare inherited variations with the risk of GTS, whole-exome sequencing (WES) was performed in a family with three affected patients with GTS. Among the five novel rare variations identified by WES, CLCN2 G161S was presented in three patients, but not in four unaffected individuals, and thus co-segregated with GTS. A validation study was also performed in a cohort of Chinses Han population to further examine the identified rare variants. CLCN2 G161S was genotyped in 207 sporadic patients with tic disorder including 111 patients with GTS and 489 healthy controls. Compared with that in controls [allele frequency (AF) = 0], CLCN2 G161S had higher variant AF in patients with tic (AF = 0.00483) and in patients with GTS (0.00900), respectively. However, this variant was absent from the current 1000 Genome databases, and the variant AF is very low in the current public databases including ExAC (AF = 0.00001) and gnomAD (AF = 0.00003). Our results suggest that CLCN2 G161S might play a major role in the genetic etiology of GTS, at least in a Chinese Han population.
Tele-Psychiatry Assessment of Post-traumatic Stress Symptoms in 100 Patients With Bipolar Disorder During the COVID-19 Pandemic Social-Distancing Measures in Italy
Authors: Carmassi Claudia , Bertelloni Carlo Antonio , Dell'Oste Valerio , Barberi Filippo Maria , Maglio Alessandra , Buccianelli Beatrice , Cordone Annalisa , Dell'Osso Liliana
Published: December 2020

The acute phase of the COrona VIrus Disease-19 (COVID-19) emergency determined relevant stressful burdens in psychiatric patients, particularly those with chronic mental disorders such as bipolar disorder (BD), not only for the threat of being infected but also for the strict lock-down and social-distancing measures adopted, the economic uncertainty, and the limited possibilities to access psychiatric services. In this regard, telepsychiatry services represented a new important instrument that clinicians could adopt to monitor and support their patients. The aim of the present study was to investigate acute post-traumatic stress symptoms (PTSS) reported by patients with BD followed in the framework of a telepsychiatry service, set up in the acute phase of the COVID-19 outbreak at the psychiatric clinic of the University of Pisa (Italy). A sample of 100 patients were consecutively enrolled and assessed by the IES-r, GAD-7, HAM-D, and YMRS. Patients reported a mean (±SD) IES-r total score of 18.15 ± 13.67. Further, 17% of the sample reported PTSS (IES-r > 32), 17% depressive symptoms (HAM-D > 17), and 26% anxiety symptoms (GAD-7 > 10). Work and financial difficulties related to the COVID-19 pandemic and anxiety symptoms appeared to be positively associated with the development of acute PTSS. Acute manic symptoms appeared to be protective. The data of the present study suggest the relevance of monitoring patients with BD exposed to the burden related to the COVID-19 outbreak for prompt assessment and treatment of PTSS.
How Resilience Promotes Mental Health of Patients With DSM-5 Substance Use Disorder? The Mediation Roles of Positive Affect, Self-Esteem, and Perceived Social Support
Authors: Yang Chunyu , Zhou You , Xia Mengfan
Published: December 2020

Objectives: The existing studies found that resilience is a salient trait that can significantly affect people's psychological well-being with substance use disorders (SUDs). However, few studies examined how the mechanisms are connected between resilience and mental health among patients with Diagnostic and Statistical Manual of Mental Disorders—fifth edition SUD. This study investigated the mediation effects of positive affect, perceived social support, and self-esteem on the effect of resilience on perceived stress and life satisfaction in SUD patients.

Design: A total of 415 patients diagnosed with Diagnostic and Statistical Manual of Mental Disorders—fifth edition SUD from the south of China joined the research.

Outcome Measures: The study applied Connor–Davidson Resilience Scale, Positive and Negative Affect Scale, Multidimensional Scale of Perceived Social Support, Rosenberg Self-Esteem Scale, and Satisfaction with Life Scale to measure patients' resilience, positive affect, self-esteem, perceived social support, perceived stress, and life satisfaction.

Results: Structural equation model analysis revealed that positive affect and self-esteem partially mediate the relationship between resilience and perceived stress. In contrast, positive affect and perceived social support partially mediate the relationship between resilience and life satisfaction.

Conclusion: The findings provide insights for evidence-based substance abuse intervention that positive affect, self-esteem, and perceived social support can conditional the effects of resilience on promoting the mental health of SUD patients.
Prevalence, Associated Factors, and Consequences of Burnout Among Egyptian Physicians During COVID-19 Pandemic
Authors: Abdelhafiz Ahmed Samir , Ali Asmaa , Ziady Hany H. , Maaly Ayman Mohamed , Alorabi Mohamed , Sultan Eman A.
Published: December 2020

Objectives: COVID-19 has been recognized as a pandemic by the World Health Organization, and physicians are at the frontline to confront the disease. Burnout syndrome (BOS) is a syndrome resulting from chronic workplace stress that has not been successfully managed. The objective of this study is to evaluate the frequency and associated risk factors of BOS among a sample of Egyptian physicians during the COVID-19 pandemic.

Methods: Using Maslach Burnout Inventory Human Services Survey, a cross-sectional electronic survey was conducted to assess BOS among the target group.

Results: Two hundred and twenty physicians participated in the study. The frequency of BOS among the research group was 36.36%. The possibility of development of BOS increased two times with the need to buy personal protective equipment (PPE) from participants' own money, with harassment by patients' families, and was less likely to develop in doctors with older age. While male gender was a predictor of depersonalization (DP), female gender showed a significant association with higher emotional exhaustion (EE). Infection or death from COVID-19 among colleagues or relatives showed significant association with elevated EE and lowered personal achievement (PA), respectively.

Conclusion: COVID-19 pandemic added new factors to the development of BOS in our research group. Several measures should be taken to support physicians at this stage. These measures include psychological support, organizing work hours, adjusting salaries, and providing personal protective equipment and training on safety measures.