bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrient Exposure Alters Microbial Composition, Structure, and Mercury Methylating Activity in Periphyton in a Contaminated Watershed
Authors: Carrell Alyssa A. , Schwartz Grace E. , Cregger Melissa A. , Gionfriddo Caitlin M. , Elias Dwayne A. , Wilpiszeski Regina L. , Klingeman Dawn M. , Wymore Ann M. , Muller Katherine A. , Brooks Scott C.
Published: March 2021

The conversion of mercury (Hg) to monomethylmercury (MMHg) is a critical area of concern in global Hg cycling. Periphyton biofilms may harbor significant amounts of MMHg but little is known about the Hg-methylating potential of the periphyton microbiome. Therefore, we used high-throughput amplicon sequencing of the 16S rRNA gene, ITS2 region, and Hg methylation gene pair (hgcAB) to characterize the archaea/bacteria, fungi, and Hg-methylating microorganisms in periphyton communities grown in a contaminated watershed in East Tennessee (United States). Furthermore, we examined how nutrient amendments (nitrate and/or phosphate) altered periphyton community structure and function. We found that bacterial/archaeal richness in experimental conditions decreased in summer and increased in autumn relative to control treatments, while fungal diversity generally increased in summer and decreased in autumn relative to control treatments. Interestingly, the Hg-methylating communities were dominated by Proteobacteria followed by Candidatus Atribacteria across both seasons. Surprisingly, Hg methylation potential correlated with numerous bacterial families that do not contain hgcAB, suggesting that the overall microbiome structure of periphyton communities influences rates of Hg transformation within these microbial mats. To further explore these complex community interactions, we performed a microbial network analysis and found that the nitrate-amended treatment resulted in the highest number of hub taxa that also corresponded with enhanced Hg methylation potential. This work provides insight into community interactions within the periphyton microbiome that may contribute to Hg cycling and will inform future research that will focus on establishing mixed microbial consortia to uncover mechanisms driving shifts in Hg cycling within periphyton habitats.
Insight Into Seeded Tau Fibril Growth From Molecular Dynamics Simulation of the Alzheimer’s Disease Protofibril Core
Authors: Leonard Cass , Phillips Christian , McCarty James
Published: March 2021

Aggregates of the microtubule associated tau protein are a major constituent of neurofibrillary lesions that define Alzheimer’s disease (AD) pathology. Increasing experimental evidence suggests that the spread of tau neurofibrillary tangles results from a prion-like seeding mechanism in which small oligomeric tau fibrils template the conversion of native, intrinsically disordered, tau proteins into their pathological form. By using atomistic molecular dynamics (MD) simulations, we investigate the stability and dissociation thermodynamics of high-resolution cryo-electron microscopy (cryo-EM) structures of both the AD paired-helical filament (PHF) and straight filament (SF). Non-equilibrium steered MD (SMD) center-of-mass pulling simulations are used to probe the stability of the protofibril structure and identify intermolecular contacts that must be broken before a single tau peptide can dissociate from the protofibril end. Using a combination of exploratory metadynamics and umbrella sampling, we investigate the complete dissociation pathway and compute a free energy profile for the dissociation of a single tau peptide from the fibril end. Different features of the free energy surface between the PHF and SF protofibril result from a different mechanism of tau unfolding. Comparison of wild-type tau PHF and post-translationally modified pSer356 tau shows that phosphorylation at this site changes the dissociation free energy surface of the terminal peptide. These results demonstrate how different protofibril morphologies template the folding of endogenous tau in distinct ways, and how post-translational modification can perturb the folding mechanism.
No Evidence That Cognitive and Physical Activities Are Related to Changes in EEG Markers of Cognition in Older Adults at Risk of Dementia
Authors: Laptinskaya Daria , Küster Olivia Caroline , Fissler Patrick , Thurm Franka , Von Arnim Christine A. F. , Kolassa Iris-Tatjana
Published: March 2021

An active lifestyle as well as cognitive and physical training (PT) may benefit cognition by increasing cognitive reserve, but the underlying neurobiological mechanisms of this reserve capacity are not well understood. To investigate these mechanisms of cognitive reserve, we focused on electrophysiological correlates of cognitive performance, namely on an event-related measure of auditory memory and on a measure of global coherence. Both measures have shown to be sensitive markers for cognition and might therefore be suitable to investigate potential training- and lifestyle-related changes. Here, we report on the results of an electrophysiological sub-study that correspond to previously published behavioral findings. Altogether, 65 older adults with subjective or objective cognitive impairment and aged 60–88 years were assigned to a 10-week cognitive (n = 19) or a 10-week PT (n = 21) or to a passive control group (n = 25). In addition, self-reported lifestyle was assessed at baseline. We did not find an effect of both training groups on electroencephalography (EEG) measures of auditory memory decay or global coherence (ps ≥ 0.29) and a more active lifestyle was not associated with improved global coherence (p = 0.38). Results suggest that a 10-week unimodal cognitive or PT and an active lifestyle in older adults at risk for dementia are not strongly related to improvements in electrophysiological correlates of cognition.
miR-96 Inhibits SV2C to Promote Depression-Like Behavior and Memory Disorders in Mice
Authors: Sun Lidong , Bai Donghao , Lin Maoguang , Eerdenidalai  , Zhang Li , Wang Fengzhen , Jin Shangwu
Published: March 2021

Accumulating evidence continues to emphasize the role of microRNAs as significant contributors to depression-like behavior and memory disorders. The current study aimed to investigate the mechanism by which miR-96 influences depression-like behavior and memory deficit in mice. A depression-like behavior and memory disorder mouse model was initially established by means of intraperitoneal injection with lipopolysaccharide. Memory deficits in the mice were evaluated using the Novel Object Recognition Test and Morris water maze experiments, whereas the Sucrose Preference Experiment and forced swimming experiments were performed to identify depression-like behavior in mice. The levels of tumor necrosis factor-α, malondialdehyde, superoxide dismutase, glutathione, and the monoamine transmitters 5-hydroxytryptamine and dopamine were subsequently detected in the serum. Reverse transcription-quantitative polymerase chain reaction and Western blot analysis evaluated the expression of miR-96 and SV2C expression in the CA1 hippocampal region of the mice. Finally, the relationship of miR-96 and SV2C was verified by dual-luciferase reporter gene assay. Our data indicated that the expression of miR-96 was increased, whereas that of SV2C was decreased in the CA1 region of mice exhibiting depression-like behavior and memory impairment. When miR-96 was downregulated or SV2C was overexpressed via intra-cerebroventricular injection with a miR-96 antagonist (miR-96 antagomir) or overexpression of SV2C vector, the Novel Object Recognition Test and sucrose preference index were increased, whereas the escape latency, the number of water maze platform crossings, and the immobility time of the mice were decreased. The serum levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde in the mouse CA1 region of mice were reduced, whereas the levels of superoxide dismutase and glutathione were elevated after the downregulation of miR-96 or overexpression of SV2C. Collectively, our study demonstrates that miR-96 negatively regulates the expression of SV2C, which consequently leads to depression-like behavior and memory impairment in mice. Our findings highlight the potential of miR-96-targeted therapeutics.
Robot Communication: Network Traffic Classification Based on Deep Neural Network
Authors: Ge Mengmeng , Yu Xiangzhan , Liu Likun
Published: March 2021

With the rapid popularization of robots, the risks brought by robot communication have also attracted the attention of researchers. Because current traffic classification methods based on plaintext cannot classify encrypted traffic, other methods based on statistical analysis require manual extraction of features. This paper proposes (i) a traffic classification framework based on a capsule neural network. This method has a multilayer neural network that can automatically learn the characteristics of the data stream. It uses capsule vectors instead of a single scalar input to effectively classify encrypted network traffic. (ii) For different network structures, a classification network structure combining convolution neural network and long short-term memory network is proposed. This structure has the characteristics of learning network traffic time and space characteristics. Experimental results show that the network model can classify encrypted traffic and does not require manual feature extraction. And on the basis of the previous tool, the recognition accuracy rate has increased by 8%
Myelin Debris Stimulates NG2/CSPG4 Expression in Bone Marrow-Derived Macrophages in the Injured Spinal Cord
Authors: Liu Yang , Hammel Grace , Shi Minjun , Cheng Zhijian , Zivkovic Sandra , Wang Xiaoqi , Xu Pingyi , He Xijing , Guo Bing , Ren Yi , Zuo Li
Published: March 2021

Although the increased expression of members of the chondroitin sulfate proteoglycan family, such as neuron-glial antigen 2 (NG2), have been well documented after an injury to the spinal cord, a complete picture as to the cellular origins and function of this NG2 expression has yet to be made. Using a spinal cord injury (SCI) mouse model, we describe that some infiltrated bone marrow-derived macrophages (BMDMΦ) are early contributors to NG2/CSPG4 expression and secretion after SCI. We demonstrate for the first time that a lesion-related form of cellular debris generated from damaged myelin sheaths can increase NG2/CSPG4 expression in BMDMΦ, which then exhibit enhanced proliferation and decreased phagocytic capacity. These results suggest that BMDMΦ may play a much more nuanced role in secondary spinal cord injury than previously thought, including acting as early contributors to the NG2 component of the glial scar.
Effects of Menopause in Women With Multiple Sclerosis: An Evidence-Based Review
Authors: Bove Riley , Okai Annette , Houtchens Maria , Elias-Hamp Birte , Lugaresi Alessandra , Hellwig Kerstin , Kubala Havrdová Eva
Published: March 2021

Over two thirds of all individuals who develop multiple sclerosis (MS) will be women prior to the age of menopause. Further, an estimated 30% of the current MS population consists of peri- or postmenopausal women. The presence of MS does not appear to influence age of menopausal onset. In clinical practice, symptoms of MS and menopause can frequently overlap, including disturbances in cognition, mood, sleep, and bladder function, which can create challenges in ascertaining the likely cause of symptoms to be treated. A holistic and comprehensive approach to address these common physical and psychological changes is often suggested to patients during menopause. Although some studies have suggested that women with MS experience reduced relapse rates and increased disability progression post menopause, the data are not consistent enough for firm conclusions to be drawn. Mechanisms through which postmenopausal women with MS may experience disability progression include neuroinflammation and neurodegeneration from age-associated phenomena such as immunosenescence and inflammaging. Additional effects are likely to result from reduced levels of estrogen, which affects MS disease course. Following early retrospective studies of women with MS receiving steroid hormones, more recent interventional trials of exogenous hormone use, albeit as oral contraceptive, have provided some indications of potential benefit on MS outcomes. This review summarizes current research on the effects of menopause in women with MS, including the psychological impact and symptoms of menopause on disease worsening, and the treatment options. Finally, we highlight the need for more inclusion of MS patients from underrepresented racial and geographic groups in clinical trials, including among menopausal women.
Event-Related Potentials During Decision-Making in a Mixed-Strategy Game
Authors: Chang Fang-Yu , Wiratman Winnugroho , Ugawa Yoshikazu , Kobayashi Shunsuke
Published: March 2021

The decisions we make are sometimes influenced by interactions with other agents. Previous studies have suggested that the prefrontal cortex plays an important role in decision-making and that the dopamine system underlies processes of motivation, motor preparation, and reinforcement learning. However, the physiological mechanisms underlying how the prefrontal cortex and the dopaminergic system are involved in decision-making remain largely unclear. The present study aimed to determine how decision strategies influence event-related potentials (ERPs). We also tested the effect of levodopa, a dopamine precursor, on decision-making and ERPs in a randomized double-blind placebo-controlled investigation. The subjects performed a matching-pennies task against an opposing virtual computer player by choosing between right and left targets while their ERPs were recorded. According to the rules of the matching-pennies task, the subject won the trial when they chose the same side as the opponent, and lost otherwise. We set three different task rules: (1) with the alternation (ALT) rule, the computer opponent made alternating choices of right and left in sequential trials; (2) with the random (RAND) rule, the opponent randomly chose between right and left; and (3) with the GAME rule, the opponent analyzed the subject’s past choices to predict the subject’s next choice, and then chose the opposite side. A sustained medial ERP became more negative toward the time of the subject’s target choice. A biphasic potential appeared when the opponent’s choice was revealed after the subject’s response. The ERPs around the subject’s choice were greater in RAND and GAME than in ALT, and the negative peak was enhanced by levodopa. In addition to these medial ERPs, we observed lateral frontal ERPs tuned to the choice direction. The signals emerged around the choice period selectively in RAND and GAME when levodopa was administered. These results suggest that decision processes are modulated by the dopamine system when a complex and strategic decision is required, which may reflect decision updating with dopaminergic prediction error signals.
Efficacy of Anti-PD-1/PD-L1 Monotherapy or Combinational Therapy in Patients Aged 75 Years or Older: A Study-Level Meta-Analysis
Authors: Nie Run-Cong , Chen Guo-Ming , Wang Yun , Zhou Jie , Duan Jin-Ling , Zhou Zhi-Wei , Yuan Shu-Qiang
Published: March 2021

Recent trials have shown a promising anti-tumor activity for advanced cancer patients treated with PD-1/PD-L1 inhibitors; however, little is known on the use of PD-1/PD-L1 inhibitors in adults over 75 years of age. Here, we performed a study-level meta-analysis to compare the efficacy of anti-PD-1/PD-L1 agents between elderly (≥ 75 years) and non-elderly (< 75 years) patients. In the present study, we systematically reviewed phase 2/3 trials of PD-1/PD-L1 inhibitors of advanced solid tumors that reported treatment effect (hazard ratio [HR]) in patients based on age (≥ 75 years vs. < 75 years) and set anti-PD-1/PD-L1 monotherapy or combinational therapy as experimental arm. The HRs of OS and progression-free survival (PFS) are based on random-effect models. Overall, a total of eight qualifying trials comprising 5,393 subjects were included for meta-analysis, and 472 patients (8.8%) were aged 75 years or older. The overall estimated HR for OS was 0.70 (0.62–0.79) in patients < 75 years vs. 0.94 (0.67–1.30) in patients ≥ 75 years. Anti-PD-1/PD-L1 agents improved OS of melanoma patients in both elderly (HR 0.25 [0.10-0.60]) and non-elderly (HR 0.49 [0.33–0.71]) group. The OS difference in the efficacy of PD-1/PD-L1 inhibitors between elderly and non-elderly patients was significant (P = 0.043 for interaction). The overall estimated HR for PFS was 0.77 (0.60–1.00) in patients < 75 years vs. 0.97 (0.60–1.58) in patients ≥ 75 years. Therefore, with the exception of melanoma, elderly patients (≥ 75 years) could not benefit from the anti-PD-1/PD-L1 agents in survival, and toxicity profile of anti-PD-1/PD-L1 drugs should be explored in this population.
Knockdown of SNORA47 Inhibits the Tumorigenesis of NSCLC via Mediation of PI3K/Akt Signaling Pathway
Authors: Yu Huiqing , Tian Ling , Yang Liejun , Liu Shihong , Wang Sixiong , Gong Juan
Published: March 2021

Background

Non-small cell lung cancer (NSCLC) is a frequently diagnosed aggressive cancer all over the world. Small nucleolar RNAs (snoRNAs) are a group of non-coding mediatory RNAs. A previous report indicated that small nucleolar RNA 47 (SNORA47) is upregulated in NSCLC. However, the role of SNORA47 in NSCLC is unclear.

Material and Methods

Cell proliferation was measured by immunofluorescence staining. Cell apoptosis and cycle of NSCLC were tested by flow cytometry and the protein expressions were investigated by Western-blot. Meanwhile, cell migration and invasion were detected by transwell assay. Xenograft mice model was established to detect the effect of SNORA47 knockdown on tumor growth of NSLC in vivo.

Results

Knockdown of SNORA47 significantly inhibited the proliferation of NSCLC cells via inducing cell apoptosis. Moreover, migration and invasion of NSCLC cells were notably decreased by SNORA47 shRNA. SNORA47 knockdown significantly induced G1 arrest in NSCLC cells via regulation of p27 Kip1, CDK2, and cyclin D1. Meanwhile, SNORA47 shRNA inhibited EMT process and PI3K/Akt signaling in NSCLC cells. Finally, silencing of SNORA47 significantly inhibited the tumor growth of NSCLC in vivo.

Conclusion

Knockdown of SNORA47 significantly inhibited the tumorigenesis of NSCLC via inhibition of PI3K/Akt signaling and EMT process. Thereby, our finding might shed a new light on exploring the strategies for the treatment of NSCLC.
Complementing Prostate SBRT VMAT With a Two-Beam Non-Coplanar IMRT Class Solution to Enhance Rectum and Bladder Sparing With Minimum Increase in Treatment Time
Authors: Sharfo Abdul Wahab M. , Rossi Linda , Dirkx Maarten L. P. , Breedveld Sebastiaan , Aluwini Shafak , Heijmen Ben J. M.
Published: March 2021

Purpose

Enhance rectum and bladder sparing in prostate SBRT with minimum increase in treatment time by complementing dual-arc coplanar VMAT with a two-beam non-coplanar IMRT class solution (CS).

Methods

For twenty patients, an optimizer for automated multi-criterial planning with integrated beam angle optimization (BAO) was used to generate dual-arc VMAT plans, supplemented with five non-coplanar IMRT beams with individually optimized orientations (VMAT+5). In all plan generations, reduction of high rectum dose had the highest priority after obtaining adequate PTV coverage. A CS with two most preferred directions in VMAT+5 and largest rectum dose reductions compared to dual-arc VMAT was then selected to define VMAT+CS. VMAT+CS was compared with automatically generated i) dual-arc coplanar VMAT plans (VMAT), ii) VMAT+5 plans, and iii) IMRT plans with 30 patient-specific non-coplanar beam orientations (30-NCP). Plans were generated for a 4 x 9.5 Gy fractionation scheme. Differences in PTV doses, healthy tissue sparing, and computation and treatment delivery times were quantified.

Results

For equal PTV coverage, VMAT+CS, consisting of dual-arc VMAT supplemented with two fixed, non-coplanar IMRT beams with fixed Gantry/Couch angles of 65°/30° and 295°/-30°, significantly reduced OAR doses and the dose bath, compared to dual-arc VMAT. Mean relative differences in rectum Dmean, D1cc, V40GyEq and V60GyEq were 19.4 ± 10.6%, 4.2 ± 2.7%, 34.9 ± 20.3%, and 39.7 ± 23.2%, respectively (all p<0.001). There was no difference in bladder D1cc, while bladder Dmean reduced by 17.9 ± 11.0% (p<0.001). Also, the clinically evaluated urethra D5%, D10%, and D50% showed small, but statistically significant improvements. All patient VX with X = 2, 5, 10, 20, and 30 Gy were reduced with VMAT+CS, with a maximum relative reduction for V10Gy of 19.0 ± 7.3% (p<0.001). Total delivery times with VMAT+CS only increased by 1.9 ± 0.7 min compared to VMAT (9.1 ± 0.7 min). The dosimetric quality of VMAT+CS plans was equivalent to VMAT+5, while optimization times were reduced by a factor of 25 due to avoidance of individualized BAO. Compared to VMAT+CS, the 30-NCP plans were only favorable in terms of dose bath, at the cost of much enhanced optimization and delivery times.

Conclusions

The proposed two-beam non-coplanar class solution to complement coplanar dual-arc VMAT resulted in substantial plan quality improvements for OARs (especially rectum) and reduced irradiated patient volumes with minor increases in treatment delivery times.
Impact of the COVID-19 Pandemic on Patients and Staff in Radiation Oncology Departments in Belgium: A National Survey
Authors: Vaandering Aude , Ben Mustapha Selma , Lambrecht Maarten , Van Gestel Dirk , Veldmeman Liv
Published: March 2021

Purpose: COVID-19 reached Belgium in February and quickly became a major public health challenge. It is of importance to evaluate the actual impact of COVID-19 on patients and staff in Belgian radiotherapy departments (RTDs). This was evaluated through a weekly national survey sent to departments measuring key factors that were affected by the pandemic.

Materials and Methods: The Belgian SocieTy for Radiation Oncology (BeSTRO) together with the Belgian College for physicians in Radiation Oncology invited all 26 RTD to participate in a survey that started on March 2nd and was re- submitted weekly for 4 months to assess variations in time. The survey focused on: (1) the COVID-19 status of patients and staff; (2) the management of clinically suspected COVID patients and COVID positive patients; (3) the impact of COVID-19 on RTD activities; (4) its impact in radiotherapy indications and fractionation schemes.

Results: Seventy-three percent of 26 RTDs completed the first survey and 57% responded to all weekly surveys. In the RTD staff, 24 members were COVID-positive of whom 67% were RTTs. Over the study period, the number of patients treated dropped by a maximum of 18.8% when compared to March 2nd. In 32.3% of COVID-positive and 54% of COVID suspected patients, treatment was continued without any interruptions. Radiotherapy indications were adapted within the 1st weeks of the survey in 47.4% of RTD, especially for urological and breast tumors. Fractionation schemes were changed in 68.4% of RTD, mainly for urological, breast, gastro-intestinal, and lung tumors.

Conclusions: Between March and June 2020, the COVID-19 pandemic resulted in an important decrease in treatment activity in RTD in Belgium (18.8%). The COVID-19 infection status of patients influenced the continuity of the radiotherapy schedule. Changes in indications and fractionation schedules of radiotherapy were rapidly incorporated in the different RTD.
Kawasaki Disease Shock Syndrome in Japan and Comparison With Multisystem Inflammatory Syndrome in Children in European countries
Authors: Suzuki Junko , Abe Kota , Matsui Takuya , Honda Takafumi , Yasukawa Kumi , Takanashi Jun-ichi , Hamada Hiromichi
Published: March 2021

Multisystem inflammatory syndrome in children (MIS-C) is a severe Kawasaki-like illness that was first linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in European countries in the spring of 2020 and has been suggested to have overlap with Kawasaki disease shock syndrome (KDSS). There are few reports of MIS-C from Asia. This observational study aimed to identify the clinical features in children presenting with KDSS in Japan over a 5-year period and to summarize similarities and differences between KDSS and MIS-C. We retrospectively collected data on patient characteristics, clinical signs and symptoms, treatment, and prognosis including coronary artery abnormalities (CAAs), which were compared with data of patients with KDSS worldwide and patients with MIS-C from a review. KDSS was identified in 6 (1.1%) of 552 patients with Kawasaki disease (KD) treated at a single institution in Japan between 2015 and 2020 (1 in 2020). In patients with KDSS in Japan or worldwide vs. patients with MIS-C, KDSS was more likely to have a diagnosis of complete KD (100, 70 vs. 6.3%), a higher incidence of CAAs (50, 65 vs. 11%), and a greater requirement for vasoactive agonists (67, 67 vs. 43%) because of circulatory shock (100, 50 vs. 26%). Both KDSS and MIS-C had good prognosis (mortality 0, 6.7 vs. 1.7%). Although KDSS in Japan and MIS-C show some overlap in clinical symptoms, they are unlikely to be the same disease entity. KDSS is more likely to have a cardiovascular phenotype with CAAs and requires treatment with cardiovascular agents.
Mother-to-Infant Bonding in Women With a Bipolar Spectrum Disorder
Authors: Boekhorst Myrthe G. B. M. , Beerthuizen Annemerle , Hillegers Manon , Pop Victor J. M. , Bergink Veerle
Published: March 2021

Purpose: Offspring of mothers with a bipolar disorder are at high-risk for impaired developmental outcomes and psychopathology (e. g., mood, anxiety, sleep disorders) later in life. This increased risk of psychopathology is not only because of genetic vulnerability, but environmental factors may play an important role as well. The often long and debilitating mood episodes of mothers with bipolar disorder might hamper their qualities as a caregiver and may impact the child. We examined early mother-to-infant bonding 1 year postpartum in mothers with bipolar spectrum disorder as compared to mothers of the general population. The association between mother-to-infant bonding and the type of bipolar spectrum diagnosis (bipolar I, bipolar II, bipolar Not Otherwise Specified) as well as relapse within 12 months postpartum was also assessed.

Methods: In total, 75 pregnant women with a bipolar spectrum disorder participated in the current study. The participants were included in a longitudinal cohort study of women with bipolar spectrum disorder and were prospectively followed from pregnancy until 1 year postpartum. Mother-to-infant bonding was assessed using the Pre- and Postnatal Bonding Scale. A longitudinal population-based cohort of 1,419 pregnant women served as the control group. Multiple linear regression analyses were used to assess the association between bipolar spectrum disorder and mother-to-infant bonding scores, controlling for several confounders.

Results: Women with bipolar spectrum disorder perceived the bonding with their child as less positive compared to the control group. The type of bipolar spectrum disorder was not associated with poorer bonding scores. Relapse during the 1st year after delivery also did not affect bonding scores in women with bipolar spectrum disorder.

Conclusions: Our findings could imply that women with bipolar spectrum disorder are more vulnerable to impairments in bonding due to the nature of their psychopathology, regardless of the occurrence of postpartum relapse. Careful follow-up including monitoring of mother-to-infant bonding of pregnant women with a history of bipolar spectrum disorder should be a standard to this vulnerable group of women. In addition, regardless of severity and mood episode relapse, an intervention to improve bonding could be beneficial for all mothers with bipolar spectrum disorder and their newborns.
Gut Microbiota and Obesity in Adults and Children: The State of the Art
Authors: Petraroli Maddalena , Castellone Eleonora , Patianna Viviana , Esposito Susanna
Published: March 2021

In recent decades, obesity has become a serious public health problem affecting both children and adults. Considering the multifactorial origin of obesity, including modifiable factors, childhood was identified as the golden age for investing in obesity prevention by both promoting proper lifestyles and actively intervening in possible triggers. The gut microbiota is at the center of the most recent scientific studies and plays a key role in obesity development because it is intimately linked to energetic-humoral variations in the host: its alterations can promote a state of excessive energy storage, and it can be manipulated to maintain energy homoeostasis. This review aims to offer a panoramic understanding of the interplay between obesity and the gut microbiota, focusing on the contribution that the gut microbiota could have to the prevention of childhood obesity and its complications in adulthood. Currently, the use of some specific probiotic strains has been shown to be able to act on some secondary metabolic consequences of obesity (such as liver steatosis and insulin resistance) without any effect on weight loss. Although definitive conclusions cannot be drawn on the real impact of probiotics and prebiotics, there is no doubt that they represent an exciting new frontier in the treatment of obesity and associated metabolic dysfunctions. Targeted studies randomized on specific populations and homogeneous for ethnicity, sex, and age are urgently needed to reach definitive conclusions about the influence of microbiota on weight. In particular, we still need more studies in the pediatric population to better understand when the switch to an obese-like gut microbiota takes place and to better comprehend the right timing of each intervention, including the use of pre/probiotics, to improve it.
BNSTAVGABA-PVNCRF Circuit Regulates Visceral Hypersensitivity Induced by Maternal Separation in Vgat-Cre Mice
Authors: Huang Si-Ting , Song Zhi-Jing , Liu Yu , Luo Wen-Chen , Yin Qian , Zhang Yong-Mei
Published: March 2021

Visceral hypersensitivity as a common clinical manifestation of irritable bowel syndrome (IBS) may contribute to the development of chronic visceral pain. Our prior studies authenticated that the activation of the corticotropin-releasing factor (CRF) neurons in paraventricular nucleus (PVN) contributed to visceral hypersensitivity in mice, but puzzles still remain with respect to the underlying hyperactivation of corticotropin-releasing factor neurons. Herein, we employed maternal separation (MS) to establish mouse model of visceral hypersensitivity. The neuronal circuits associated with nociceptive hypersensitivity involved paraventricular nucleus CRF neurons by means of techniques such as behavioral test, pharmacology, molecular biology, retrograde neuronal circuit tracers, electrophysiology, chemogenetics and optogenetics. MS could predispose the elevated firing frequency of CRF neurons in PVN in murine adulthood, which could be annulled via the injection of exogenous GABA (0.3mM, 0.2µl) into PVN. The PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), wherein the excitability of these GABAergic neurons was reduced. Casp3 virus was utilized to induce apoptosis of GABA neurons in BNST-AV region, resulting in the activation of CRF neurons in PVN and visceral hyperalgesia. In parallel, chemogenetic and optogenetic approaches to activate GABAergic BNSTAV-PVN circuit in MS mice abated the spontaneous firing frequency of PVN CRF neurons and prevented the development of visceral hypersensitivity. A priori, PVNCRF-projecting GABAergic neurons in BNST-AV region participated in the occurrence of visceral hypersensitivity induced by MS. Our research may provide a new insight into the neural circuit mechanism of chronic visceral pain.
Dual Targeting EGFR and STAT3 With Erlotinib and Alantolactone Co-Loaded PLGA Nanoparticles for Pancreatic Cancer Treatment
Authors: Bao Shihui , Zheng Hailun , Ye Jinyao , Huang Huirong , Zhou Bin , Yao Qing , Lin Guangyong , Zhang Hailin , Kou Longfa , Chen Ruijie
Published: March 2021

Pancreatic cancer (PC) is one of the most common malignancies and also a leading cause of cancer-related mortality worldwide. Many studies have shown that epidermal growth factor receptor (EGFR) is highly expressed in PC, which provides a potential target for PC treatment. However, EGFR inhibitors use alone was proven ineffective in clinical trials, due to the persistence of cellular feedback mechanisms which foster therapeutic resistance to single targeting of EGFR. Specifically, the signal transducer and activator of transcription 3 (STAT3) is over-activated when receiving an EGFR inhibitor and is believed to be highly involved in the failure and resistance of EGFR inhibitor treatment. Therein, we hypothesized that dual inhibition of EGFR and STAT3 strategy could address the STAT3 induced resistance during EGFR inhibitor treatment. To this end, we tried to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles to co-load Alantolactone (ALA, a novel STAT3 inhibitor) and Erlotinib (ERL, an EGFR inhibitor) for pancreatic cancer to test our guess. The loading ratio of ALA and ERL was firstly optimized in vitro to achieve a combined cancer-killing effect. Then, the ALA- and ERL-co-loaded nanoparticles (AE@NPs) were successfully prepared and characterized, and the related anticancer effects and cellular uptake of AE@NPs were studied. We also further detailly explored the underlying mechanisms. The results suggested that AE@NPs with uniform particle size and high drug load could induce significant pancreatic cancer cell apoptosis and display an ideal anticancer effect. Mechanism studies showed that AE@NPs inhibited the phosphorylation of both EGFR and STAT3, indicating the dual suppression of these two signaling pathways. Additionally, AE@NPs could also activate the ROS-p38 axis, which is not observed in the single drug treatments. Collectively, the AE@NPs prepared in this study possess great potential for pancreatic cancer treatment by dual suppressing of EGFR and STAT3 pathways and activating ROS-responsive p38 MAPK pathway.
Repurposing Anti-Malaria Phytomedicine Artemisinin as a COVID-19 Drug
Authors: Uckun Fatih M. , Saund Saran , Windlass Hitesh , Trieu Vuong
Published: March 2021

Artemisinin is an anti-inflammatory phytomedicine with broad-spectrum antiviral activity. Artemisinin and its antimalarial properties were discovered by the Chinese scientist Tu Youyu, who became one of the laureates of the 2015 Nobel Prize in Physiology or Medicine for this breakthrough in tropical medicine. It is a commonly used anti-malaria drug. Artemisinin has recently been repurposed as a potential COVID-19 drug. Its documented anti-SARS-CoV-2 activity has been attributed to its ability to inhibit spike-protein mediated and TGF-β-dependent early steps in the infection process as well as its ability to disrupt the post-entry intracellular events of the SARS-CoV-2 infection cycle required for viral replication. In addition, Artemisinin has anti-inflammatory activity and reduces the systemic levels of inflammatory cytokines that contribute to cytokine storm and inflammatory organ injury in high-risk COVID-19 patients. We postulate that Artemisinin may prevent the worsening of the health condition of patients with mild-moderate COVID-19 when administered early in the course of their disease.
Pathophysiological Relevance of Renal Medullary Conditions on the Behaviour of Red Cells From Patients With Sickle Cell Anaemia
Authors: Lu David C.-Y. , Wadud Rasiqh , Hannemann Anke , Rees David C. , Brewin John N. , Gibson John Stanley
Published: March 2021

Red cells from patients with sickle cell anaemia (SCA) contain the abnormal haemoglobin HbS. Under hypoxic conditions, HbS polymerises and causes red cell sickling, a rise in intracellular Ca2+ and exposure of phosphatidylserine (PS). These changes make sickle cells sticky and liable to lodge in the microvasculature, and so reduce their lifespan. The aim of the present work was to investigate how the peculiar conditions found in the renal medulla – hypoxia, acidosis, lactate, hypertonicity and high levels of urea – affect red cell behaviour. Results show that the first four conditions all increased sickling and PS exposure. The presence of urea at levels found in a healthy medulla during antidiuresis, however, markedly reduced sickling and PS exposure and would therefore protect against red cell adherence. Loss of the ability to concentrate urine, which occurs in sickle cell nephropathy would obviate this protective effect and may therefore contribute to pathogenesis.
More Light? Opportunities and Pitfalls in Digitalized Psychotherapy Process Research
Authors: Domhardt Matthias , Cuijpers Pim , Ebert David Daniel , Baumeister Harald
Published: March 2021

While the evidence on the effectiveness of different psychotherapies is often strong, it is not settled whereby and how these therapies work. Knowledge on the causal factors and change mechanisms is of high clinical and public relevance, as it contributes to the empirically informed advancement of psychotherapeutic interventions. Here, digitalized research approaches might possess the potential to generate new insights into human behavior change, contributing to augmented interventions and mental healthcare practices with better treatment outcomes. In this perspective article, we describe recent findings of research into change mechanisms that were only feasible with digital tools and outline important future directions for this rather novel branch of research. Furthermore, we indicate several challenges and pitfalls that are to be solved, in order to advance digitalized psychotherapy process research, both methodologically and technologically.
“Like Pieces in a Puzzle”: Online Sacred Harp Singing During the COVID-19 Pandemic
Authors: Morgan-Ellis Esther M.
Published: March 2021

Sacred Harp singers the world over gather weekly to sing out ofThe Sacred Harp, a collection of shape-note songs first published in 1844. Their tradition is highly ritualized, and it plays an important role in the lives of many participants. Following the implementation of lockdown protocols to combat the COVID-19 pandemic, groups of Sacred Harp singers quickly and independently devised a variety of means by which to sing together online using Zoom (“zinging”), Jamulus (“jamzinging”), and Facebook Live (“stringing”). The rapidity and creativity with which Sacred Harp singers developed ways to sustain their activities attests to the strength and significance of this community of practice, and in this article I describe each modality and provide an account of how it came to be developed and widely used. As a participant-observer, I completed extensive fieldwork across these digital sites and conducted semi-structured interviews with 22 other singers. I found that online singing practices have reshaped the Sacred Harp community. Many singers who did not previously have the opportunity to participate now have access, while others have lost access due to technological barriers or lack of interest in online activities. At the same time, geographical barriers have disintegrated, and singing organizers must make an effort to maintain local identity. A stable community of singers has emerged in the digital realm, but it is by no means identical to the community that predated the pandemic. I also identify the ways in which online singing has proven meaningful to participants by providing continuity in their personal and communal practice. Specifically, online singing allows participants to access and celebrate their collective memories of the Sacred Harp community, carry out significant rituals, and continue to grow as singers. While no single modality replicates the complete Sacred Harp singing experience, together they function “like pieces in a puzzle” (as one singer put it), allowing individual participants to access many of the elements of Sacred Harp singing that are most meaningful to them.
Unraveling the Relationship Between Teacher-Assigned Grades, Student Personality, and Standardized Test Scores
Authors: Westphal Andrea , Vock Miriam , Kretschmann Julia
Published: March 2021

The Big Five personality traits play a major role in student achievement. As such, there is consistent evidence that students that are more conscientious receive better teacher-assigned grades in secondary school. However, research often does not support the claim that students that are more conscientious similarly achieve higher scores in domain-specific standardized achievement tests. Based on the Invest-and-Accrue Model, we argue that conscientiousness explains to some extent why certain students receive better grades despite similar academic accomplishments (i.e., achieving similar scores in domain-specific standardized achievement tests). Therefore, the present study examines to what extent the relationship between student personality and teacher-assigned grades consists of direct as opposed to indirect associations (via subject-specific standardized test scores). We used a representative sample of 14,710 ninth-grade students to estimate these direct and indirect pathways in mathematics and German. Structural equation models showed that test scores explained between 8 and 11% of the variance in teacher-assigned grades in mathematics and German. The Big Five personality traits in students additionally explained between 8 and 10% of the variance in grades. Finally, the personality-grade relationship consisted of direct (0.02 | β| ≤ 0.27) and indirect associations via test scores (0.01 | β| ≤ 0.07). Conscientiousness explained discrepancies between teacher-assigned grades and students’ scores in domain-specific standardized tests to a greater extent than any of the other Big Five personality traits. Our findings suggest that students that are more conscientious may invest more effort to accomplish classroom goals, but fall short of mastery.
A Process-Model for Minimizing Adverse Effects when Using Head Mounted Display-Based Virtual Reality for Individuals with Autism
Authors: Schmidt Matthew , Newbutt Nigel , Schmidt Carla , Glaser Noah
Published: March 2021

Interest in the use of virtual reality technologies for individuals with autism spectrum disorders has been increasing for over two decades. Recently, research interest has been growing in the area of head mounted display-based virtual reality technologies, thanks to increased availability and affordability. Affordances and theorized benefits of headset-based virtual reality for individuals with autism spectrum disorders are quite promising. However, very little attention has been given in the literature to implementation safety and ethics. This is a particular concern in light of documented adverse effects associated with headset-based virtual reality. To approach this gap, this article details how the authors approached the issue of minimizing adverse effects with related and overlapping methods, but from two separate, independent research sites—one in the United States and one in the United Kingdom. A structured within- and across-case analysis of the two independent studies was conducted to identify central implementation processes and procedures. Analysis resulted in development of a model for minimizing potential adverse effects of headset-based virtual reality for this population. We assert that our model could provide clarity in terms of design and implementation of headset-based virtual reality for individuals with autism spectrum disorders, guide implementations of future researchers and practitioners, and contribute to minimizing and controlling for potential adverse effects.
Alleviation of Submergence Stress in Rice Seedlings by Plant Growth-Promoting Rhizobacteria With ACC Deaminase Activity
Authors: Bal Himadri Bhusan , Adhya Tapan Kumar
Published: March 2021

Submergence stress slows seed germination, imposes fatalities, and delays seedling establishment in rice. Seeds of submergence susceptible rice variety IR 42 were inoculated with four 1-aminocyclopropane-1-carboxylic acid (ACC) utilizing isolates viz., Bacillus sp. (AR-ACC1), Microbacterium sp. (AR-ACC2), Methylophaga sp. (AR-ACC3), and Paenibacillus sp. (ANR-ACC3) and subjected to submergence stress under controlled conditions for 7 days. Seeds treated with Microbacterium sp. AR-ACC2, Paenibacillus sp. ANR-ACC3, and Methylophaga sp. AR-ACC3 significantly enhanced the germination percentage (GP), seedling vigor index (SVI), and other growth parameters like root and shoot length and total chlorophyll contents, when compared with nonbacterized seeds submerged similarly. However, the values were statistically at par when control seeds were treated with l-α-(2-aminoethoxyvinyl) glycine hydrochloride (AVG), a known inhibitor of ethylene production. Results suggest that stress ethylene production was significantly reduced by around 85% in seedlings treated with Microbacterium sp. AR-ACC2 as compared with untreated control seeds under submergence. Paenibacillus sp. ANR-ACC3 and Methylophaga sp. AR-ACC3 were the next effective strains. Ethylene synthesis in seedlings was statistically at par with seeds treated with AVG suggesting ACC deaminase can effectively reduce ethylene levels in plants subjected to submergence. Bacillus sp. (AR-ACC1) was neither able to significantly promote seedling growth parameters nor inhibit ethylene production as compared with control seeds. Results suggest that flooded soil planted to rice harbor microorganisms with plant growth-promoting properties that can be used effectively to alleviate submergence stresses in susceptible rice varieties under field conditions.
Food Security in Venezuela: From Policies to Facts
Authors: Rodríguez García Janet J.
Published: March 2021

The 1948 Universal Declaration of Human Rights, approved by The General Assembly of the United Nations, recognized the right to food as a Basic Human Right. Consequently, at the national level, programs, norms, and laws were decreed to promote the population's health and nutrition. The 1999 Venezuelan Constitution explicitly included, for the first time, the term “Food Security” in Article 305. Subsequently, the government approved various laws and guidelines to regulate the right to food of the population. However, despite such laws, the well-being of the population has not improved. According to the 2020 State of Food Security and Nutrition in the World (2020), between 2017 and 2019, the undernourishment prevalence amounted to 31.4%. Also, reports from Caritas showed 14.4% of Global Acute Malnutrition in children under 5 years of age, and 20% of children were at risk of acute malnutrition for the period April–June 2020. Other factors have influenced the actual Venezuelan food insecurity condition. The current severe economic and social crisis has led to a Complex Humanitarian Emergency. This work aimed to consider if decreeing many laws related to food and nutrition is not enough to reduce this scourge, or if there is any guarantee that the Food and Nutrition Security (FNS) of the people would improve.
Application of the Threshold of Toxicological Concern (TTC) in Food Safety: Challenges and Opportunities
Authors: Serafimova Rositsa , Coja Tamara , Kass George E. N.
Published: March 2021

The safety assessment of chemicals added or found in food has traditionally made use of data from in vivo studies performed on experimental animals. The nature and amount of data required to carry out a risk assessment is generally stipulated either in the different food legislations or in sectoral guidance documents. However, there are still cases where no or only limited experimental data are available or not specified by law, for example for contaminants or for some minor metabolites from active substances in plant protection products. For such cases, the Threshold of Toxicological Concern (TTC) can be applied. This review explores the use of the TTC approach in food safety in the European Union, in relation to the different food sectors, legal requirements and future opportunities.