bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A
Authors: Thapa Chandan , Roivas Pekka , Haataja Tatu , Permi Perttu , Pentikäinen Ulla
Published: March 2021

Protein phosphatase 2A (PP2A) activity is critical for maintaining normal physiological cellular functions. PP2A is inhibited by endogenous inhibitor proteins in several pathological conditions including cancer. A PP2A inhibitor protein, ARPP-19, has recently been connected to several human cancer types. Accordingly, the knowledge about ARPP-19—PP2A inhibition mechanism is crucial for the understanding the disease development and the therapeutic targeting of ARPP-19—PP2A. Here, we show the first structural characterization of ARPP-19, and its splice variant ARPP-16 using NMR spectroscopy, and SAXS. The results reveal that both ARPP proteins are intrinsically disordered but contain transient secondary structure elements. The interaction mechanism of ARPP-16/19 with PP2A was investigated using microscale thermophoresis and NMR spectroscopy. Our results suggest that ARPP—PP2A A-subunit interaction is mediated by linear motif and has modest affinity whereas, the interaction of ARPPs with B56-subunit is weak and transient. Like many IDPs, ARPPs are promiscuous binders that transiently interact with PP2A A- and B56 subunits using multiple interaction motifs. In summary, our results provide a good starting point for future studies and development of therapeutics that block ARPP-PP2A interactions.
Conversion of Reactive Astrocytes to Induced Neurons Enhances Neuronal Repair and Functional Recovery After Ischemic Stroke
Authors: Jiang Michael Qize , Yu Shan Ping , Wei Zheng Zachory , Zhong Weiwei , Cao Wenyuan , Gu Xiaohuan , Wu Anika , McCrary Myles Randolph , Berglund Ken , Wei Ling
Published: March 2021

The master neuronal transcription factor NeuroD1 can directly reprogram astrocytes into induced neurons (iNeurons) after stroke. Using viral vectors to drive ectopic ND1 expression in gliotic astrocytes after brain injury presents an autologous form of cell therapy for neurodegenerative disease. Cultured astrocytes transfected with ND1 exhibited reduced proliferation and adopted neuronal morphology within 2–3 weeks later, expressed neuronal/synaptic markers, and extended processes. Whole-cell recordings detected the firing of evoked action potentials in converted iNeurons. Focal ischemic stroke was induced in adult GFAP-Cre-Rosa-YFP mice that then received ND1 lentivirus injections into the peri-infarct region 7 days after stroke. Reprogrammed cells did not express stemness genes, while 2–6 weeks later converted cells were co-labeled with YFP (constitutively activated in astrocytes), mCherry (ND1 infection marker), and NeuN (mature neuronal marker). Approximately 66% of infected cells became NeuN-positive neurons. The majority (~80%) of converted cells expressed the vascular glutamate transporter (vGLUT) of glutamatergic neurons. ND1 treatment reduced astrogliosis, and some iNeurons located/survived inside of the savaged ischemic core. Western blotting detected higher levels of BDNF, FGF, and PSD-95 in ND1-treated mice. MultiElectrode Array (MEA) recordings in brain slices revealed that the ND1-induced reprogramming restored interrupted cortical circuits and synaptic plasticity. Furthermore, ND1 treatment significantly improved locomotor, sensorimotor, and psychological functions. Thus, conversion of endogenous astrocytes to neurons represents a plausible, on-site regenerative therapy for stroke.
PIRACY: An Optimized Pipeline for Functional Connectivity Analysis in the Rat Brain
Authors: Diao Yujian , Yin Ting , Gruetter Rolf , Jelescu Ileana O.
Published: March 2021

Resting state functional MRI (rs-fMRI) is a widespread and powerful tool for investigating functional connectivity (FC) and brain disorders. However, FC analysis can be seriously affected by random and structured noise from non-neural sources, such as physiology. Thus, it is essential to first reduce thermal noise and then correctly identify and remove non-neural artifacts from rs-fMRI signals through optimized data processing methods. However, existing tools that correct for these effects have been developed for human brain and are not readily transposable to rat data. Therefore, the aim of the present study was to establish a data processing pipeline that can robustly remove random and structured noise from rat rs-fMRI data. It includes a novel denoising approach based on the Marchenko-Pastur Principal Component Analysis (MP-PCA) method, FMRIB’s ICA-based Xnoiseifier (FIX) for automatic artifact classification and cleaning, and global signal regression (GSR). Our results show that: (I) MP-PCA denoising substantially improves the temporal signal-to-noise ratio, (II) the pre-trained FIX classifier achieves a high accuracy in artifact classification, and (III) both independent component analysis (ICA) cleaning and GSR are essential steps in correcting for possible artifacts and minimizing the within-group variability in control animals while maintaining typical connectivity patterns. Reduced within-group variability also facilitates the exploration of potential between-group FC changes, as illustrated here in a rat model of sporadic Alzheimer’s disease.
Functional and Structural Connectivity Between the Left Dorsolateral Prefrontal Cortex and Insula Could Predict the Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation
Authors: Fu Yixiao , Long Zhiliang , Luo Qinghua , Xu Zhen , Xiang Yisijia , Du Wanyi , Cao Yuanyuan , Cheng Xiaoli , Du Lian
Published: March 2021

Background

The efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is nonuniform across patients. This study aims to determine whether baseline neuroimaging characters can provide a pretreatment predictive effect for rTMS.

Methods

Twenty-seven treatment-naive patients with major depressive disorder (MDD) were enrolled and scanned with resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging. Clinical symptoms were assessed pre- and post-rTMS. Functional and structural connectivity between the left dorsolateral prefrontal cortex (DLPFC) and bilateral insula were measured, and the connectivity strength in each modality was then correlated to the clinical efficacy of rTMS.

Results

When the coordinates of left DLPFC were located as a node in the central executive network, the clinical efficacy of rTMS was significantly correlated with the functional connectivity strength between left DLPFC and bilateral insula (left insula:r= 0.66; right insula:r= 0.65). The structural connectivity strength between the left DLPFC and left insular cortex also had a significantly positive correlation with symptom improvement (rs= 0.458).

Conclusion

This study provides implications that rTMS might act more effectively when the pretreatment functional and structural connectivity between the insula and left DLPFC is stronger.
Inflammatory Foreign Body Response Induced by Neuro-Implants in Rat Cortices Depleted of Resident Microglia by a CSF1R Inhibitor and Its Implications
Authors: Sharon Aviv , Jankowski Maciej M. , Shmoel Nava , Erez Hadas , Spira Micha E.
Published: March 2021

Inflammatory encapsulation of implanted cortical-neuro-probes [the foreign body response (FBR)] severely limits their use in basic brain research and in clinical applications. A better understanding of the inflammatory FBR is needed to effectively mitigate these critical limitations. Combining the use of the brain permeant colony stimulating factor 1 receptor inhibitor PLX5622 and a perforated polyimide-based multielectrode array platform (PPMP) that can be sectioned along with the surrounding tissue, we examined the contribution of microglia to the formation of inflammatory FBR. To that end, we imaged the inflammatory processes induced by PPMP implantations after eliminating 89–94% of the cortical microglia by PLX5622 treatment. The observations showed that: (I) inflammatory encapsulation of implanted PPMPs proceeds by astrocytes in microglia-free cortices. The activated astrocytes adhered to the PPMP’s surfaces. This suggests that the roles of microglia in the FBR might be redundant. (II) PPMP implantation into control or continuously PLX5622-treated rats triggered a localized surge of microglia mitosis. The daughter cells that formed a “cloud” of short-lived (T1/2 ≤ 14 days) microglia around and in contact with the implant surfaces were PLX5622 insensitive. (III) Neuron degeneration by PPMP implantation and the ensuing recovery in time, space, and density progressed in a similar manner in the cortices following 89–94% depletion of microglia. This implies that microglia do not serve a protective role with respect to the neurons. (IV) Although the overall cell composition and dimensions of the encapsulating scar in PLX5622-treated rats differed from the controls, the recorded field potential (FP) qualities and yield were undistinguishable. This is accounted for by assuming that the FP amplitudes in the control and PLX5622-treated rats were related to the seal resistance formed at the interface between the adhering microglia and/or astrocytes and the PPMP platform rather than across the scar tissue. These observations suggest that the prevention of both astrocytes and microglia adhesion to the electrodes is required to improve FP recording quality and yield.
Psychobiotic Supplementation of PS128TM Improves Stress, Anxiety, and Insomnia in Highly Stressed Information Technology Specialists: A Pilot Study
Authors: Wu Shu-I , Wu Chien-Chen , Tsai Pei-Joung , Cheng Li-Hao , Hsu Chih-Chieh , Shan Ian-Kai , Chan Po-Ying , Lin Ting-Wei , Ko Chih-Jung , Chen Wan-Lin , Tsai Ying-Chieh
Published: March 2021

Background: Information technology (IT) is an industry related to the production of computers, information processing, and telecommunications. Such industries heavily rely on the knowledge and solutions provided by IT specialists. Previous reports found that the subjective stress scores were higher in IT specialists who developed diabetes, hypertension, and depression. Specific probiotics, known as psychobiotics, may alleviate stress and mood symptoms. This study aimed to examine whether an 8-week intervention of a novel psychobiotic, Lactobacillus plantarum PS128TM (PS128TM), improved self-perceived stress and mood symptoms among high-stress IT specialists.

Methods: This open-label, single-arm, baseline-controlled study included IT specialists from a large IT company in Northern Taiwan. Participants with a Perceived Stress Scale (PSS) 10-item version score of 27 or higher were included. Participants were asked to take two capsules containing PS128TM powder, equivalent to 20 billion colony-forming units, daily. Self-report measures, such as the Job Stress Scale, Visual Analog Scale of Stress, the Insomnia Severity Index, the State and Trait Anxiety Index, the Questionnaire for Emotional Trait and State, the Patient Health Questionnaire, the Quality of Life Enjoyment and Satisfaction Questionnaire, and Gastrointestinal Severity Index were compared at baseline and at the end of the trial period. The primary outcome was a 20% reduction in the PSS score at endpoint. Objective measures included salivary levels of stress biomarkers, including cortisol, α-amylase, immunoglobulin A, lactoferrin, and lysozymes, as well as results of the Test of Attentional Performance.

Results: Of the 90 eligible IT specialists, 36 met the inclusion criteria. After the 8-week trial period, significant improvements in self-perceived stress, overall job stress, job burden, cortisol level, general or psychological health, anxiety, depression, sleep disturbances, quality of life, and both positive and negative emotions were found.

Conclusion: Our results suggest that PS128TM has the distinct advantage of providing stress relief and can improve mental health for people with a high-stress job. Future placebo-controlled studies are warranted to explore the effect and underlying mechanisms of action of PS128TM.

Clinical Trial Registration:https://clinicaltrials.gov/ (identifier: NCT04452253-sub-project 2).
The Role of CD276 in Cancers
Authors: Liu Shengzhuo , Liang Jiayu , Liu Zhihong , Zhang Chi , Wang Yang , Watson Alice Helen , Zhou Chuan , Zhang Fan , Wu Kan , Zhang Fuxun , Lu Yiping , Wang Xianding
Published: March 2021

Objective

Aberrant expression of the immune checkpoint molecule, CD276, also known as B7-H3, is associated with tumorigenesis. In this review, we aim to comprehensively describe the role of CD276 in malignancies and its potential therapeutic effect.

Data Sources

Database including PubMed, EMbase, Cochrane Library, CNKI, and Clinical Trails.gov were searched for eligible studies and reviews. Study selection: Original studies and review articles on the topic of CD276 in tumors were retrieved.

Results

CD276 is an immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway. In this review, we evaluated the available evidence on the expression and regulation of CD276. We also assessed the role of CD276 within the immune micro-environment, effect on tumor progression, and the potential therapeutic effect of CD276 targeted therapy for malignancies.

Conclusion

CD276 plays an essential role in cell proliferation, invasion, and migration in malignancies. Results from most recent studies indicate CD276 could be a promising therapeutic target for malignant tumors.
Diagnosis and Treatment of Angiography Positive Medium to Large Vessel Childhood Primary Angiitis of Central Nervous System (p-cPACNS): An International Survey
Authors: Quan Angela S. , Brunner Jürgen , Rose Benjamin , Smitka Martin , Hahn Gabriele , Pain Clare E. , Häfner Renate , Speth Fabian , Gerstl Lucia , Hedrich Christian M.
Published: March 2021

Childhood Primary Angiitis of Central Nervous System (cPACNS) is rare, but can cause significant damage and result in disability or even death. Because of its rarity, the sometimes acute and variable presentation, limited awareness, and the absence of widely accepted diagnostic and therapeutic standards, cPACNS is a diagnostic and therapeutic challenge. Three subcategories of cPACNS exist, including angiography-positive non-progressive p-cPACNS, angiography-positive progressive p-cPACNS which both affects the medium to large vessels, and angiography-negative small vessel sv-cPACNS. Diagnosis and treatment of cPACNS relies on personal experience, expert opinion and case reports/case series. To collect information on diagnostic and therapeutic approaches to transient and progressive cPACNS, a survey was shared among international clinicians (German Society for Pediatric Rheumatology, the Pediatric Rheumatology European Society, the German speaking “Network Pediatric Stroke,” and members of the American College of Rheumatology/CARRA Pediatric Rheumatology list server). Results from this survey will be used to define statements toward a consensus process allowing harmonization of diagnostic and therapeutic approaches and the generation of evidence in a rare condition.
Monte Carlo Comparison of Proton and Helium-ion Minibeam Generation Techniques
Authors: Schneider Tim , De Marzi Ludovic , Patriarca Annalisa , Prezado Yolanda
Published: March 2021

Proton minibeam radiation therapy (pMBRT) is a novel therapeutic strategy that combines the normal tissue sparing of submillimetric, spatially fractionated beams with the improved dose deposition of protons. In contrast to conventional approaches which work with comparatively large beam diameters (5 mm to several centimetres) producing laterally homogeneous fields, pMBRT uses submillimetric minibeams to create a distinct spatial modulation of the dose featuring alternating regions of high dose (peaks) and low dose (valleys). This spatial fractionation can increase the tolerance of normal tissue and may allow a safe dose escalation in the tumour. Important quantities in this context are the valley dose as well as the peak-to-valley dose ratio (PVDR). Creating submillimetric proton beams for clinical applications is a challenging task that until now has been realized with mechanical collimators (metal blocks with thin slits or holes). However, this method is inherently inefficient, inflexible and creates undesirable secondary neutrons. We therefore recently proposed a method for obtaining clinical minibeams using only magnetic focusing. In this study, we performed Monte Carlo simulations in order to compare minibeams generated using the new method of magnetic focusing with two techniques involving mechanical collimators (collimator and broad beam irradiation, collimator and pencil beam scanning). The dose deposition in water was simulated and dosimetric aspects [beam broadening, depth-dose profiles, PVDR and Bragg-peak-to-entrance dose ratio (BEDR)] as well as irradiation efficiencies were evaluated. Apart from protons, we also considered helium ions which, due to their reduced lateral scattering and sharper Bragg peak, may present a promising alternative for minibeam radiation therapy. Magnetically focused minibeams exhibited a 20–60 times higher PVDR than mechanically collimated minibeams and yielded an increase in irradiation efficiency of up to two orders of magnitude. Compared to proton minibeams, helium ion minibeams were found to broaden at a slower rate and yield an even higher PVDR (at the same minibeam spacing) as well as a more favourable BEDR. Moreover, the simulations showed that methods developed for proton minibeams are suitable for the generation of helium ion minibeams.
Cardiovascular Risk Is Increased in Miner’s Chronic Intermittent Hypobaric Hypoxia Exposure From 0 to 2,500 m?
Authors: Pedreros-Lobos Andrés , Calderón-Jofré Rodrigo , Moraga Daniel , Moraga Fernando A.
Published: March 2021

Over the past 40 years, mining activities in Chile have relocated miners who normally live at sea level to work at high altitudes. This results in a form of chronic intermittent hypobaric hypoxia (CIHH) characterized by alternating periods of work at high altitude and rest periods at sea level. Previous studies performed in our laboratory showed that aerobic capacity is reduced at 3,800 m, even when oxygen content is maintained. Our study aimed to determine the corporal composition, food intake, maximum oxygen uptake, and concentration of high sensitivity C reactive protein (hsCRP) in an acclimatized miner population that work from 0 to 2,500 m with CIHH exposure over 4 years. All miners recruited for our study were operators of heavy trucks with CIHH for over 4 years (shiftwork 7*7 days), and our experimental population was composed of 54 miners at sea level, 61 at 1,600 m, and 38 at 2,500 m. All evaluations were performed on the 3rd or 4th day of diurnal shiftwork. To determine corporal composition, we measured weight and height (to calculate body mass index, BMI), skinfolds (to calculate body fatty, BF), and waist circumference (WC); maximal aerobic capacity was evaluated using a ramp-incremental cycling to exhaustion protocol and a venous blood sample before the exercise test to measure (hsCRP) via an ELISA test. We found higher values of BMI, BF, and WC, in the miners’ population but observed no significant difference between populations. We found a decrease in VO2 of 11.6% at 1,600 m and 25.9% at 2,500 m compared to miners at sea level. An increase in (hsCRP) at 1,600 and 2,500 m regards sea level. We observed a high prevalence of overweight and obese subjects, which was related to the ad libitum availability of food and low physical activity (sedentarism). We found that work capacity was maintained despite a decreased VO2 max at moderate altitude. However, overweight and obesity support an increased risk of cardiometabolic disease in miner’s which is unrelated to altitude. In contrast, an increased hsCRP level could be associated with increased inflammatory mechanisms at 1,600 and 2,500 m.
Workers' Decisions to Disclose a Mental Health Issue to Managers and the Consequences
Authors: Dewa Carolyn S. , van Weeghel Jaap , Joosen Margot C. W. , Gronholm Petra C. , Brouwers Evelien P. M.
Published: March 2021

Background: Stigma can be a barrier to accessing effective interventions and work accommodations for mental illnesses. Fear of stigma's concomitant prejudice and discrimination can inhibit workers from asking for help. Thus, it may be important to develop effective interventions addressing workplace stigma. To identify important targets for these interventions, this study addresses three questions: (1) what proportion of workers experiencing mental health issues disclosed their mental health issue to their managers, (2) what factors did they identify as contributing to their disclosure decisions, and (3) what were the consequences of their decisions?

Methods: The dataset is comprised of responses from respondents who were randomly drawn from a nationally representative sample of working Dutch adults who completed a web-based survey in February 2018. Respondents indicating they either had or have mental health issues were asked three sets of questions focusing on: (1) Did you disclose your mental health issue to you manager? (2) For what reasons did you disclose/not disclose the issue? (3) What were the consequences of your disclosure decision?

Results: About 73% of respondents with lived experience with mental health issues told their managers about their mental health issue. The structure of the survey questions identified four groups of workers who either: (1) disclosed and had a positive experience (64.2%), (2) disclosed and had a negative experience (9.0%), (3) did not disclose and had a positive experience (22.6%), or (4) did not disclose and had a negative experience (4.2%).

Conclusion: Our results reflect workers' diverse preferences for disclosing their mental health issues to their managers. Understanding both the factors that contributed to the decision to disclose and the consequences of disclosure decisions could help to better target workplace educational programs and interventions to address workplace stigma. Our findings suggest that addressing workplace stigma may not be as straightforward as requiring all employees to receive anti-stigma education. Rather, education should support workers to make the appropriate disclosure decision based on their workplace contexts. Future research is needed to understand the optimal ways for workers struggling with mental health issues to ask and receive help if they need it.
Personality Inventory for DSM-5 in China: Evaluation of DSM-5 and ICD-11 Trait Structure and Continuity With Personality Disorder Types
Authors: Fang Shulin , Ouyang Zirong , Zhang Panwen , He Jiayue , Fan Lejia , Luo Xingwei , Zhang Jianghua , Xiong Yan , Luo Fusheng , Wang Xiaosheng , Yao Shuqiao , Wang Xiang
Published: March 2021

The Personality Inventory for the DSM-5 (PID-5) is an established tool for assessing personality disorder (PD) traits that was developed based on section III of the DSM-5. It is composed of 220 items, organized into 25 facets, which are distributed among five domains. The psychometric properties of the Chinese version of the PID-5 remain to be demonstrated. Two samples were embodied in this study that included 3,550 undergraduates and 406 clinical patients. To probe the structure of the PID-5, parallel analyses were conducted to explore the unidimensionality of its 25 facets and a series of confirmatory factor analyses (CFAs) were carried out to confirm the 25 lower-order facets and their distribution among five higher-order domains. Then, the PID-5 was employed to measure the DSM-5 and ICD-11 trait models and to explore the relationship of DSM-IV categorical PDs with DSM-5 and ICD-11 personality traits. Correlation and regression analyses were conducted to probe how well DSM-IV categorical PDs correspond with maladaptive personality traits specified in the DSM-5 and five ICD-11 domains. The respective average internal reliability coefficients of the 25 facets obtained for undergraduate and clinical patient samples were 0.76 and 0.81, those obtained for the five DSM-5 domains were 0.89 and 0.91, and those obtained for the five ICD-11 domains were 0.87 and 0.89. Serial CFAs confirmed the rationality of the PID-5's lower-order 25-facet structure and higher-order five-domain structure in both samples. Correlation and regression analyses showed that DSM-5 specified traits explain the variance in PD presentation with a manifold stronger correlation (R2 = 0.24–0.44) than non-specified traits (R2 = 0.04–0.12). Overall, the PID-5 was shown to be a reliable, stable, and structurally valid assessment tool that captures pathological personality traits related to DSM-5 and ICD-11 PDs.
The Psychological Effect of COVID-19 on Home-Quarantined Nursing Students in China
Authors: Li Dandan , Zou Li , Zhang Zeyu , Zhang Pu , Zhang Jun , Fu Wenning , Mao Jing , Cao Shiyi
Published: March 2021

Coronavirus disease 2019 (COVID-19) has significantly caused socioeconomic impacts. However, little is known about the psychological effect of COVID-19 on home-quarantined nursing students. The present study aimed to identify the prevalence and major determinants of anxiety, depression and post-traumatic stress symptoms (PTSS) in Chinese nursing students during the COVID-19 pandemic quarantine period. An online survey was conducted on a sample of 6,348 home-quarantined nursing students. Mental health status was assessed by the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Patient Health Questionnaire 9-Item Scale (PHQ-9) and the Post Traumatic Stress Disorder Check List-Civilian version (PCL-C), respectively. Logistic regression analyses were performed to identify risk factors of anxiety, depression and PTSS. The overall prevalence of anxiety was 34.97%, and the rates of “mild,” “moderate,” and “severe” anxiety were 26.24, 7.04, and 1.69%, respectively. Depression was detected in 40.22% of the nursing students, and the prevalence of “mild,” “moderate,” “moderately severe,” and “severe” depression was 27.87, 7.18, 4.08, and 1.09%, respectively. The overall prevalence of PTSS was 14.97%, with the prevalence of “mild” and “moderate-to-severe” PTSS reported at 7.04 and 7.93%, respectively. Male gender and insufficient social support were common risk factors for anxiety, depression and PTSS. In conclusion, about one-third, two-fifths, and one-seventh of Chinese nursing students had anxiety, depression and PTSS during the period of home quarantine, respectively. Timely and appropriate psychological interventions for nursing students should be implemented to reduce the psychological harm caused by COVID-19 pandemic.
Associations Between Childhood Trauma and the Age of First-Time Drug Use in Methamphetamine-Dependent Patients
Authors: Huang Cui , Yuan Qiuyu , Zhang Ling , Wang Lei , Cui Shu , Zhang Kai , Zhou Xiaoqin
Published: March 2021

Childhood trauma is related to substance use disorder; however, few studies have examined the relationship between childhood trauma and the age at which the drug was first used. The aim of this study was to investigate the relationship between childhood trauma and the age of first-time drug use among methamphetamine-dependent patients. Moreover, we analyzed the characteristics of adverse family environment associated with severe childhood trauma and the risk factors for starting drugs in minors. A baseline interview was conducted with 110 participants who were in detoxification, including demographic information, past substance use, and age of first-time drug use. The participants' childhood trauma experience before 18 years of age was evaluated using the simplified version of the Childhood Trauma Questionnaire (CTQ-SF). The Chinese version of the Family Environment Scale (FES-CV) was used to assess the family environment of methamphetamine-dependent patients. Among 110 non-injecting methamphetamine-dependent patients, nearly half (n = 48, 43.6%) had moderate and severe childhood trauma. Correlation analysis showed that the age of first-time drug use negatively correlated with emotional abuse (r = −0.32, p < 0.01) and physical abuse (r = −0.27, p < 0.01). The age of first-time drug use negatively correlated with conflict (r = −0.20, p < 0.05) and independence (r = −0.22, p < 0.05) of family environment, but positively correlated with intellectual-cultural orientation (r = 0.28, p < 0.01). Additionally, childhood trauma factors significantly correlated with many indexes of family environment, especially cohesion (r = −0.45, p < 0.01), conflict (r = 0.49, p < 0.01), and independence (r = 0.33, p < 0.01). Additionally, the regression model showed that when emotional abuse increased by one point, the age of first-time drug use was 0.69 years earlier. These findings suggest that a detrimental family environment can aggravate childhood trauma, and the experience of childhood emotional or physical abuse may be an effective predictor of early drug use among methamphetamine-dependent patients.
Probiotics, Pre-biotics and Synbiotics in the Treatment of Pre-diabetes: A Systematic Review of Randomized Controlled Trials
Authors: Wang Xian , Yang Jiao , Qiu Xianliang , Wen Qing , Liu Min , Zhou Dongqi , Chen Qiu
Published: March 2021

Objectives: This study aimed to review the data from randomized controlled trials (RCTs) and identify evidence for microbiota's role and use of probiotics, pre-biotics, or synbiotics in pre-diabetes.

Methods: RCTs of pro-, pre-, synbiotics for the treatment of pre-diabetes population will be summarized. We searched for EMBASE, MEDLINE, Web of Science, Cochrane Central, Clinical Trials (ClinicalTrials.gov) from inception to February 2021.

Results: The gut microbiota influences host metabolic disorders via the modulation of metabolites, including short-chain fatty acids (SCFAs), the endotoxin lipopolysaccharides (LPS), bile acids (BA) and trimethylamine N-oxide (TMAO), as well as mediating the interaction between the gastrointestinal system and other organs. Due to the limited sources of studies, inconsistent outcomes between included studies. Probiotics can decrease glycated hemoglobin (HbA1c) and have the potential to improve post-load glucose levels. The supplementation of probiotics can suppress the rise of blood cholesterol, but the improvement cannot be verified. Pre-biotics are failed to show an evident improvement in glycemic control, but their use caused the changes in the composition of gut microbiota. A combination of probiotics and pre-biotics in the synbiotics supplementation is more effective than probiotics alone in glycemic control.

Conclusion: In the current studies using probiotics, pre-biotics or synbiotics for the treatment of pre-diabetes, the benefits of modulating the abundance of gut microbiota were partially demonstrated. However, there is insufficient evidence to show significant benefits on glucose metabolism, lipid metabolism and body composition.
Theoretical Determination of Binding Energies of Small Molecules on Interstellar Ice Surfaces
Authors: Duflot Denis , Toubin Céline , Monnerville Maurice
Published: March 2021

The adsorption of a series of atoms and small molecules and radicals (H, C, N, O, NH, OH, H2O, CH3, and NH3) on hexagonal crystalline and amorphous ice clusters were obtained via classical molecular dynamics and electronic structure methods. The geometry and binding energies were calculated using a QMHigh:QMLow hybrid method on model clusters. Several combination of basis sets, density functionals and semi-empirical methods were compared and tested against previous works. More accurate binding energies were also refined via single point Coupled Cluster calculations. Most species, except carbon atom, physisorb on the surface, leading to rather small binding energies. The carbon atom forms a COH2 molecule and in some cases leads to the formation of a COH-H3O+ complex. Amorphous ices are characterized by slightly stronger binding energies than the crystalline phase. A major result of this work is to also access the dispersion of the binding energies since a variety of adsorption sites is explored. The interaction energies thus obtained may serve to feed or refine astrochemical models. The present methodology could be easily extended to other types of surfaces and larger adsorbates.
Duration of Static and Dynamic Periods of the Upper Arm During Daily Life of Manual Wheelchair Users and Matched Able-Bodied Participants: A Preliminary Report
Authors: Goodwin Brianna M. , Jahanian Omid , Cain Stephen M. , Van Straaten Meegan G. , Fortune Emma , Morrow Melissa M.
Published: March 2021

Background: Manual wheelchair (MWC) users with spinal cord injuries (SCI) are at a significantly higher risk of experiencing rotator cuff pathology than able-bodied individuals. A deeper understanding of where the arm is used dynamically within the humeral workspace during daily life may help explain why MWC users have higher shoulder pathology rates than able-bodied individuals. The purpose of this study was to report the daily percentage and consecutive durations MWC users and matched able-bodied individuals (controls) spent static and dynamic across the humeral elevation workspace.

Methods: MWC users with SCI and controls wore three inertial measurement units on their bilateral arms and torso for 1 or 2 days. The percentages of time and average consecutive duration individuals were static or dynamic while in five humeral elevation ranges (0–30°, 30–60°, 60–90°, 90–120°, and >120°) were calculated and compared between cohorts.

Results: Forty-four MWC users (10 females, age: 42.8 ± 12.0, time since injury: 12.3 ± 11.5) and 44 age- and sex-matched controls were enrolled. The MWC cohort spent significantly more time dynamic in 60–90° (p = 0.039) and 90–120° (p = 0.029) and had longer consecutive dynamic periods in 30–60° (p = 0.001), 60–90° (p = 0.027), and 90–120° (p = 0.043) on the dominant arm. The controls spent significantly more time dynamic in 0–30° of humeral elevation (p < 0.001) on both arms. Although the average consecutive static durations were comparable between cohorts across all humeral elevation ranges, the MWC cohort spent a significantly higher percentage of their day static in 30–60° of humeral elevation than controls (dominant: p = 0.001, non-dominant: p = 0.01). The MWC cohort had a moderate association of increased age with decreased time dynamic in 30–60° for both arms.

Discussion: Remote data capture of arm use during daily life can aid in understanding how arm function relates to shoulder pathology that follows SCI and subsequent MWC use. MWC users spent more time dynamic in higher elevations than controls, and with age, dynamic arm use decreased in the 30–60° humeral elevation range. These results may exemplify effects of performing activities from a seated position and of age on mobility.
Reassessing the Cost-Effectiveness of High-Provitamin A Bananas to Reduce Vitamin A Deficiency in Uganda
Authors: Kozicka Marta , Elsey Julia , Ekesa Beatrice , Ajambo Susan , Kikulwe Enoch , Gotor Elisabetta
Published: March 2021

There are two high-provitamin A (pVA) banana-based interventions potentially available in Uganda—biofortified genetically modified (GM) banana and fast-tracked banana landraces from outside Uganda that are naturally high in provitamin A (nHpVA). Based on the newest country statistics and using adoption scenarios obtained through focus group discussions and expert interviews, we assess obstacles and opportunities for adoption as well as cost-effectiveness of these interventions. In two alternative scenarios for the GM banana (M9 matooke), we assume 40% and 64% adoption rates, which would result in US$29,374,151 and US$63,259,415 in income saved, respectively. As an alternative, for the symmetrical scenarios, we calculate that if the nHpVA banana (Apantu plantain, native of Ghana) were to be adopted, US$46,100,148 and US$76,364,988 in income would be saved. Taking into account the full cost of R&D, we estimate that the M9 matooke could save one disability-adjusted life year (DALY) at a cost of US$67.37 at best and US$145.09 at worst. We estimate that the Apantu plantain could save one DALY at a cost of US$50.54 at best and US$83.72 at worst. Our DALY analysis estimates that all assessed HpVA banana interventions are extremely cost-effective in all scenarios, following both the World Bank's and the WHO criteria. Nevertheless, successful interventions would require extensive promotion campaigns and shifts in agricultural value chains.
Effectiveness of Fenbendazole and Metronidazole Against Giardia Infection in Dogs Monitored for 50-Days in Home-Conditions
Authors: Ciuca Lavinia , Pepe Paola , Bosco Antonio , Caccio Simone Mario , Maurelli Maria Paola , Sannella Anna Rosa , Vismarra Alice , Cringoli Giuseppe , Kramer Laura , Rinaldi Laura , Genchi Marco
Published: March 2021

A field trial performed in-home conditions was conducted on 24 dogs naturally infected withGiardia, in order to compare the efficacy of fenbendazole and metronidazole. Animals were allocated in groups randomly in order to obtain two groups of 12 dogs each with similar parasitic loads ofGiardiacysts: dogs in Group A were treated with fenbendazole (Panacur®, Intervet Italia Srl) administered at the dose of 50 mg/kg orally once a day for 5 consecutive days, dogs in Group B were treated with metronidazole (Flagyl®, Zambon Italia Srl) administered orally at the dose of 50 mg/kg, once a day for 5 consecutive days. All the dogs that were sheddingGiardiacysts after the first treatment (Day 0) were retreated (either at Day 7 or at Day 14 or at Day 21) until a negative result was obtained with the same treatment. Additionally, all the dogs were re-examined at Day 50. All the dogs were tested for the presence ofGiardiacysts using a fecal flotation method (FLOTAC). The percent efficacy of the treatments (A and B) was calculated at each sampling point (Days 7, 14, 21, and 50) as reduction in meanGiardiacysts. After the first therapy, on day 7, 4/12 (33.3%) dogs tested positive forGiardiacysts in the Group A and 5/12 (41.7%) in the Group B. Efficacies at (Days 7, 14, 21, and 50) of the treatments againstGiardiainfection were 80.9, 94, 100, and 97% in the Group A and 70.8, 99, 100, and 97.1% in the Group B. Statistically significant differences were not observed between the efficacy of Fenbendazole and Metronidazole against infection byG. duodenalis(P= 0.686). Molecular analysis revealed full homology (i.e., 100% with JN416550) with the canine specific assemblage D in six positive dogs. Different hypotheses might explain the re-appearance of theGiardiacysts in some dogs after treatment, e.g., re-infection from the home environment, the correct medication given by the owners, the diet, as well as treatment failure, but also biological issues related to the intermittent excretion ofGiardiacysts.
Age and Staphylococcus aureus Inoculation Route Differentially Alter Metabolic Potential and Immune Cell Populations in Laying Hens
Authors: Fries-Craft Krysten , Meyer Meaghan M. , Sato Yuko , El-Gazzar Mohamed , Bobeck Elizabeth A.
Published: March 2021

In 2018 and 2019, Staphylococcus aureus was isolated from multiple post-molt commercial laying hens with unusually high mortality. A challenge study was conducted to elucidate the role of S. aureus in this disease outbreak and the work herein represents the assessment of immunological responses in laying hens experimentally infected with S. aureus isolates from these cases. A total of 200 laying hens at 22 or 96 weeks of age (100/ age group) were assigned to 1 of 4 experimental inoculation groups (negative control, oral gavage, subcutaneous injection, or intravenous injection) after a 72 h acclimation period. Blood samples were taken prior to inoculation (baseline), 6 h post-inoculation (pi), 24 hpi, 3 dpi, and 7 dpi. Additional spleen samples to further assess systemic immunity were taken at baseline, 3 and 8 dpi. Metabolic phenotypes of peripheral blood mononuclear cells (PBMC) were isolated and assessed by Seahorse metabolic assay. Immune cell profiles in the spleen and PBMC were assessed by multicolor flow cytometry. At baseline, 96-week-old laying hens had 26.7% fewer PBMC-derived T cells compared to 22-week-old birds. Older hens had 28.9% increased helper T cell (TH) populations and 60.5% reduced γδ T cells (P = 0.03 and < 0.0001) which may contribute to variable clinical responses between age groups; however, no age-related differences in metabolic potential were observed. Metabolic outcomes showed that birds remained stressed from transport and re-housing past a 72 h acclimation period and through 24 h- 3 days post-inoculation. Inoculation with S. aureus generally reduced oxidative and glycolytic potentials compared to the control, with the greatest reductions observed in birds inoculated by intravenous injection (P < 0.05). Overall CD3+ T cell populations showed significant reductions in the intravenous group compared to other inoculation routes from 24 hpi to 7 dpi (23.6–39.0%; P ≤ 0.0001). These results suggest that age-related baseline differences in T cell populations and changes to T cell subpopulations and other immune cells due to inoculation route may have an additive effect on S. aureus- induced reductions in metabolic potential; however, further research linking metabolic potential and immune cell profiles is needed.
Spiroplasma Isolated From Third-Generation Laboratory Colony Ixodes persulcatus Ticks
Authors: Beliavskaia Alexandra , Hönig Vaclav , Erhart Jan , Vyhlidalova Tereza , Palus Martin , Cerny Jiri , Kozlova Irina , Ruzek Daniel , Palomar Ana M. , Bell-Sakyi Lesley
Published: March 2021

Spiroplasma are vertically-transmitted endosymbionts of ticks and other arthropods. Field-collected Ixodes persulcatus have been reported to harbour Spiroplasma, but nothing is known about their persistence during laboratory colonisation of this tick species. We successfully isolated Spiroplasma from internal organs of 6/10 unfed adult ticks, belonging to the third generation of an I. persulcatus laboratory colony, into tick cell culture. We screened a further 51 adult male and female ticks from the same colony for presence of Spiroplasma by genus-specific PCR amplification of fragments of the 16S rRNA and rpoB genes; 100% of these ticks were infected and the 16S rRNA sequence showed 99.8% similarity to that of a previously-published Spiroplasma isolated from field-collected I. persulcatus. Our study shows that Spiroplasma endosymbionts persist at high prevalence in colonised I. persulcatus through at least three generations, and confirms the usefulness of tick cell lines for isolation and cultivation of this bacterium.
Automated PD-L1 Scoring for Non-Small Cell Lung Carcinoma Using Open-Source Software
Authors: Naso Julia R. , Povshedna Tetiana , Wang Gang , Banyi Norbert , MacAulay Calum , Ionescu Diana N. , Zhou Chen
Published: March 2021

PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to immunotherapy, but scoring of PD-L1 immunohistochemistry shows considerable interobserver variability. Automated methods may allow more consistent and expedient PD-L1 scoring. We aimed to assess the technical concordance of PD-L1 scores produced using free open source QuPath software with the manual scores of three pathologists. A classifier for PD-L1 scoring was trained using 30 NSCLC image patches. A separate test set of 207 image patches from 69 NSCLC resection cases was used for comparison of automated and manual scores. Automated and average manual scores showed excellent correlation (concordance correlation coeffecient = 0.925), though automated scoring resulted in significantly more 1–49% scores than manual scoring (p = 0.012). At both 1% and 50% thresholds, automated scores showed a level of concordance with our ‘gold standard’ (the average of three pathologists’ manual scores) similar to that of individual pathologists. Automated scoring showed high sensitivity (95%) but lower specificity (84%) at a 1% threshold, and excellent specificity (100%) but lower sensitivity (71%) at a 50% threshold. We conclude that our automated PD-L1 scoring system for NSCLC has an accuracy similar to that of individual pathologists. The detailed protocol we provide for free open source scoring software and our discussion of the limitations of this technology may facilitate more effective integration of automated scoring into clinical workflows.
Morphological and Molecular Characterization of Quinoa Genotypes
Authors: EL-Harty Ehab H. , Ghazy Abdelhalim , Alateeq Talal K. , Al-Faifi Sulieman A. , Khan Muhammad Altaf. , Afzal Muhammed , Alghamdi Salem S. , Migdadi Hussein M.
Published: March 2021

Quinoa cultivation has expanded from South America to many countries because of its wide adaptability and nutritional value. We evaluated 32 introduced quinoa genotypes using 17 qualitative and 11 quantitative traits under Saudi Arabia conditions during the 2018–2019 season. The quinoa genotypes showed considerable variation during the vegetative and maturity stages. Plant height values varied between 60 and 18 cm, and maturity ranged from 98 to 177 days. Leaf shapes were rhomboidal or triangular, with dentate or serrate margins. Green was the standard color for leaves and panicles at the flowering stage. The leaf granule colors were white, purple, and white-red. At 150 units of the Euclidean distance, the genotypes aggregated into four major groups based on their morphological traits. Twenty-one sequence-related amplified polymorphism (SRAP) primer pair combinations generated 75 amplified fragments (alleles), with a mean of 3.57 alleles per primer pair combination. Unweighted Pair-Group Method with Arithmetic means (UPGMA) clustering analysis showed that the quinoa genotypes were grouped based on origin or according to genetic background. Genotypes from South America presented higher mean values for the average number of alleles, Shannon index (0.411), gene diversity (0.271), and polymorphic percentage (83.95). Analysis of molecular variance (AMOVA) showed that most of the genetic variation was because of differences within populations (86%). The wide variability of the genotypes studied herein is of great importance for quinoa breeders.
Biochar for Circular Horticulture: Feedstock Related Effects in Soilless Cultivation
Authors: Amery Fien , Debode Jane , Ommeslag Sarah , Visser Rian , De Tender Caroline , Vandecasteele Bart
Published: March 2021

Biochar has previously been used in growing media blends as fertilizer or for improving plant growth, disease suppression, and as a sustainable replacement of peat. To achieve optimal circular horticulture, we propose here to reuse the biochar from spent growing media. However, it is unclear to what extent the biochar feedstock determines the mode of action of the biochar and if use of spent growing media biochar may encounter nutrient or salt problems. Differences in chemical characteristics, nutrient release, and interaction in a leaching experiment and effects on plant growth, nutrient uptake, and disease suppression in a strawberry greenhouse trial were studied for 11 biochars either processed from spent growing media or from lignocellulosic biomass. A well-studied biochar produced from oak wood was set as reference. Biochars produced from spent growing media were characterized by higher electrical conductivity, extractable and total nutrient concentrations compared with biochars produced from lignocellulosic biomass. Especially in the first phase of the leaching experiment, all biochars showed nutrient and salt release, with most prominent effects for spent growing media biochars and the reference biochar. The latter biochars were an important source of phosphorus and in particular of potassium. Only for the reference biochar, strawberry plants showed increased uptake of phosphorus, potassium and calcium, and increased chlorophyll concentration. No Bortrytis cinerea disease suppression and no increase in plant growth was observed for the tested biochars. It is concluded that spent growing media can be recycled as biochar in growing media without adverse effects compared to biochars produced from lignocellulosic biomass.