bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Source Tracking of Fecal Indicating Bacteria in Coral Reef Waters, Recreational Waters, and Groundwater of Saipan by Real-Time Quantitative PCR
Authors: Sinigalliano Christopher , Kim Kiho , Gidley Maribeth , Yuknavage Kathy , Knee Karen , Palacios Dean , Bautista Charito , Bonacolta Anthony , Lee Hyo Won , Maurin Larry
Published: January 2021

The Commonwealth of the Northern Mariana Islands (CNMI) recently identified the need to improve its capacity for detecting and tracking land-based sources of pollution (LBSP) in coastal waters, particularly microbial contaminants like fecal indicator bacteria (FIB). Reported here is a baseline study of a suite of host-specific FIB microbial source tracking (MST) markers in the coastal shoreline and reef waters around the island of Saipan. Three sampling campaigns were conducted in September 2017, March 2018, and August 2018. Samples were collected from the nearshore surface waters of Saipan, the reef waters of Saipan Lagoon, and groundwater from beaches along the Saipan Lagoon shoreline. Measurements of submarine groundwater discharge (SGD) into nearshore waters and isotopic source tracking of nitrogen inputs were conducted concurrently with MST. Environmental DNA was extracted from the samples and analyzed by quantitative polymerase chain reaction (qPCR) for MST gene markers of fecal Bacteroidales specifically associated with humans, dogs, cows, and pigs, and for an MST gene marker of Catellicoccus associated with seabirds. MST assessments were combined with local knowledge, assessments of sanitary infrastructure, and routine watershed surveys. This study identified hotspots of human FIB along the western Saipan Lagoon shoreline in both surface waters and groundwater, plus another hotspot of human FIB at a popular tourist bathing area known as the Grotto. FIB hotspots on the Lagoon shoreline coincided with areas of high SGD and nitrogen isotopic data indicating sewage-derived N inputs. It appears that faulty sanitary infrastructure may be contributing to inputs to Saipan Lagoon, while bather shedding is likely a primary input for the Grotto area. Moderate levels of dog fecal contamination were common and widespread across the island. High levels of seabird fecal contamination were more random, both spatially and temporally, and mostly concentrated along the less developed northeast region of Saipan. No significant levels of cow or pig fecal marker were detected in coastal water samples. This study provides demonstration and establishment of analytical capacity to resource management in CNMI for MST technology to aid in trouble-shooting water quality issues involving land-based sources of microbial contaminants to CNMI coastal waters.
MacaquePose: A Novel “In the Wild” Macaque Monkey Pose Dataset for Markerless Motion Capture
Authors: Labuguen Rollyn , Matsumoto Jumpei , Negrete Salvador Blanco , Nishimaru Hiroshi , Nishijo Hisao , Takada Masahiko , Go Yasuhiro , Inoue Ken-ichi , Shibata Tomohiro
Published: January 2021

Video-based markerless motion capture permits quantification of an animal's pose and motion, with a high spatiotemporal resolution in a naturalistic context, and is a powerful tool for analyzing the relationship between the animal's behaviors and its brain functions. Macaque monkeys are excellent non-human primate models, especially for studying neuroscience. Due to the lack of a dataset allowing training of a deep neural network for the macaque's markerless motion capture in the naturalistic context, it has been challenging to apply this technology for macaques-based studies. In this study, we created MacaquePose, a novel open dataset with manually labeled body part positions (keypoints) for macaques in naturalistic scenes, consisting of >13,000 images. We also validated the application of the dataset by training and evaluating an artificial neural network with the dataset. The results indicated that the keypoint estimation performance of the trained network was close to that of a human-level. The dataset will be instrumental to train/test the neural networks for markerless motion capture of the macaques and developments of the algorithms for the networks, contributing establishment of an innovative platform for behavior analysis for non-human primates for neuroscience and medicine, as well as other fields using macaques as a model organism.
Retaining Adolescent and Young Adult Participants in Research During a Pandemic: Best Practices From Two Large-Scale Developmental Neuroimaging Studies (NCANDA and ABCD)
Authors: Nooner Kate B. , Chung Tammy , Feldstein Ewing Sarah W. , Brumback Ty , Arwood Zjanya , Tapert Susan F. , Brown Sandra A. , Cottler Linda
Published: January 2021

The novel coronavirus pandemic that emerged in late 2019 (COVID-19) has created challenges not previously experienced in human research. This paper discusses two large-scale NIH-funded multi-site longitudinal studies of adolescents and young adults – the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) and the Adolescent Brain Cognitive Development (ABCD) Study – and valuable approaches to learn about adaptive processes for conducting developmentally sensitive research with neuroimaging and neurocognitive testing across consortia during a global pandemic. We focus on challenges experienced during the pandemic and modifications that may guide other projects, such as implementing adapted protocols that protect the safety of participants and research staff, and addressing assessment challenges through the use of strategies such as remote and mobile assessments. Given the pandemic’s disproportionate impacts on participants typically underrepresented in research, we describe efforts to retain these individuals. The pandemic provides an opportunity to develop adaptive processes that can facilitate future studies’ ability to mobilize effectively and rapidly.
Online Tuning of PID Controller Using a Multilayer Fuzzy Neural Network Design for Quadcopter Attitude Tracking Control
Authors: Park Daewon , Le Tien-Loc , Quynh Nguyen Vu , Long Ngo Kim , Hong Sung Kyung
Published: January 2021

This study presents an online tuning proportional-integral-derivative (PID) controller using a multilayer fuzzy neural network design for quadcopter attitude control. PID controllers are simple but effective control methods. However, finding the suitable gain of a model-based controller is relatively complicated and time-consuming because it depends on external disturbances and the dynamic modeling of plants. Therefore, the development of a method for online tuning of quadcopter PID parameters may save time and effort, and better control performance can be achieved. In our controller design, a multilayer structure was provided to improve the learning ability and flexibility of a fuzzy neural network. Adaptation laws to update network parameters online were derived using the gradient descent method. Also, a Lyapunov analysis was provided to guarantee system stability. Finally, simulations concerning quadcopter attitude control were performed using a Gazebo robotics simulator in addition to a robot operating system (ROS), and their results were demonstrated.
2D Virtual Reality-Based Exercise Improves Spatial Navigation in Institutionalized Non-robust Older Persons: A Preliminary Data Report of a Single-Blind, Randomized, and Controlled Study
Authors: Oliveira Luciana Mendes , Evangelista e Souza Eric Hudson , Alves Mariana Rocha , Carneiro Lara S. F. , Fagundes Daniel Ferreira , de Paula Alfredo Maurício Batista , Engedal Knut , Nascimento Osvaldo J. M. , Monteiro-Junior Renato Sobral
Published: January 2021

Background: Spatial navigation is a prodromal dementia marker. Exercise used alongside virtual reality improves many cognitive functions, but effects on spatial navigation are still unclear.

Objective: To investigate the effect of virtual reality-based physical exercise with 2D exergames on spatial navigation in institutionalized non-robust older persons.

Method: A total of 14 older persons (aged ≧ 60) were randomly allocated to the exergame (EG) and active control (ACG) groups. EG performed exercises with 2D exergames, while the ACG used the same movements as the EG, but without the use of virtual reality. Spatial navigation was assessed through the Floor Maze Test, where the immediate maze time (IMT) and delayed maze time (DMT) were recorded.

Results: Spatial navigation was enhanced in EG participants compared to ACG individuals. A significant (p = 0.01) IMT reduction between groups was observed, while DMT time without prior planning was significantly different at the significance threshold (p = 0.07).

Conclusions: Virtual reality-based exercise improves the spatial navigation of institutionalized non-robust older persons. This study should be replicated to confirm the findings reported herein.

Clinical Trial Registration: This study was registered in the Brazilian Registry of Clinical Trials (Protocol RBR-8dv3kg - https://ensaiosclinicos.gov.br/rg/RBR-8dv3kg).
The Effects of Bicycle Simulator Training on Anticipatory and Compensatory Postural Control in Older Adults: Study Protocol for a Single-Blind Randomized Controlled Trial
Authors: Batcir Shani , Lubovsky Omri , Bachner Yaacov G. , Melzer Itshak
Published: January 2021

Background: Falls are the leading cause of fatal and non-fatal injuries among older adults. Perturbation-Based-Balance Training (PBBT) is a promising approach to reduce fall rates by improving reactive balance responses. PBBT programs are designed for older adults who are able to stand and walk on a motorized treadmill independently. However, frail older adults, whose fall rates are higher, may not have this ability and they cannot participate. Thus, there is a critical need for innovative perturbation exercise programs to improve reactive balance and reduce the fall risks among older adults in a wider range of functioning. Trunk and arms are highly involved in reactive balance reactions. We aim to investigate whether an alternative PBBT program that provides perturbations during hands-free bicycling in a sitting position, geared to improve trunk and arm reactive responses, can be transferred to reduce fall risks and improve balance function among pre-frail older adults.

Methods: In a single-blinded randomized-controlled trial, 68 community-dwelling pre-frail older adults are randomly allocated into two intervention groups. The experimental group receives 24-PBBT sessions over 12-weeks that include self-induced internal and machine-induced external unannounced perturbations of balance during hands-free pedaling on a bicycle-simulator system, in combination with cognitive dual-tasks. The control group receives 24 pedaling sessions over 12-weeks by the same bicycle-simulator system under the same cognitive dual-tasks, but without balance perturbations. Participants' reactive and proactive balance functions and gait function are assessed before and after the 12-week intervention period (e.g., balance reactive responses and strategies, voluntary step execution test, postural stability in upright standing, Berg Balance Test, Six-meter walk test, as well as late life function and fear of falling questionnaires).

Discussion: This research addresses two key issues in relation to balance re-training: (1) generalization of balance skills acquired through exposure to postural perturbations in a sitting position investigating the ability of pre-frail older adults to improve reactive and proactive balance responses in standing and walking, and (2) the individualization of perturbation training to older adults' neuromotor capacities in order to optimize training responses and their applicability to real-life challenges.

Clinical Trial Registration:www.clinicaltrials.gov, NCT03636672 / BARZI0104; Registered: July 22, 2018; Enrolment of the first participant March: 1, 2019. See Supplementary File.
Training-Induced Neural Plasticity in Youth: A Systematic Review of Structural and Functional MRI Studies
Authors: Tymofiyeva Olga , Gaschler Robert
Published: January 2021

Experience-dependent neural plasticity is high in the developing brain, presenting a unique window of opportunity for training. To optimize existing training programs and develop new interventions, it is important to understand what processes take place in the developing brain during training. Here, we systematically review MRI-based evidence of training-induced neural plasticity in children and adolescents. A total of 71 articles were included in the review. Significant changes in brain activation, structure, microstructure, and structural and functional connectivity were reported with different types of trainings in the majority (87%) of the studies. Significant correlation of performance improvement with neural changes was reported in 51% of the studies. Yet, only 48% of the studies had a control condition. Overall, the review supports the hypothesized neural changes with training while at the same time charting empirical and methodological desiderata for future research.
Effect of Repeated Anodal HD-tDCS on Executive Functions: Evidence From a Pilot and Single-Blinded fNIRS Study
Authors: Lu Hongliang , Gong Yue , Huang Peng , Zhang Yajuan , Guo Zhihua , Zhu Xia , You Xuqun
Published: January 2021

Executive functions are of vital importance in the process of active cognition, which is thought to be associated with the dorsolateral prefrontal cortex (DLPFC). As a valid brain stimulation technology, high-definition transcranial direct current stimulation (HD-tDCS) has been used to optimize cognitive function in healthy adults. Substantial evidence indicates that short-term or single anodal tDCS sessions over the left DLPFC will enhance the performance of executive functions. However, the changes in performance and cortical activation of executive functions after modulation by repeated anodal HD-tDCS is as yet unexplored. This study aims to examine changes in three core components of executive functions (inhibitory control, working memory, and cognitive flexibility) produced by nine HD-tDCS sessions (1.5 mA, over left DLPFC, 20 min per session), and to use functional near-infrared spectroscopy (fNIRS) to bilaterally record DLPFC neural activity. A total of 43 participants were divided randomly into two study groups (anodal group vs. sham group) to complete nine interventions. Our results demonstrate that the enhancement of cognitive flexibility in the anodal group was significantly better than that in the sham group. Additionally, a Stroop effect-related decrease in oxygenated hemoglobin (HbO) concentration in the DLPFC was observed in the anodal group but not the sham group. In conclusion, our study found that repeated anodal HD-tDCS sessions can significantly promote cognitive flexibility, one of the core components of executive function, and that alterations in DLPFC activation can enhance our understanding of the neuroplastic modifications modulated by HD-tDCS.
Immersive Virtual Reality Reminiscence Reduces Anxiety in the Oldest-Old Without Causing Serious Side Effects: A Single-Center, Pilot, and Randomized Crossover Study
Authors: Niki Kazuyuki , Yahara Megumi , Inagaki Michiya , Takahashi Nana , Watanabe Akira , Okuda Takeshi , Ueda Mikiko , Iwai Daisuke , Sato Kosuke , Ito Toshinori
Published: January 2021

Background: Dementia is one the major problems of aging societies, and, novel and effective non-drug therapies are required as interventions in the oldest-old to prevent cognitive decline.

Objective: This study aims to examine the efficacy and safety of reminiscence using immersive virtual reality (iVR reminiscence) focusing on anxiety that often appears with cognitive decline. The secondary objective is to reveal the preference for VR image types for reminiscence: live-action (LA) or computer graphics (CG).

Methods: This was a pilot, open-label, and randomized crossover study which was conducted on January 2020 at a single nursing home. The subjects were randomly divided into two groups (A or B) in equal numbers, and they alternately viewed two types of VR images (LA and CG) themed on the mid- to late Showa era (A.D. 1955–1980) in Japan. In group A, the CG images were viewed first, and then the LA images were viewed (CG→ LA). In group B, the images were viewed in the opposite order (LA→ CG). Before VR viewing, subjects responded to Mini-Mental State Examination (MMSE) Japanese version and State-Trait Anxiety Inventory (STAI) Japanese version. After viewing the first and second VR, subjects responded to STAI and the numerical rating scale (NRS) for satisfaction and side effects (nausea, dizziness, headache, and tiredness).

Results: Ten subjects participated in this study. The values of analyses are presented in the mean (SD). The age was 87.1 years (4.2), and the MMSE was 28.5 (1.8). The total STAI score before VR viewing was 36.1 (7.2), but it significantly decreased to 26.8 (4.9) after the first VR viewing (P = 0.0010), and further decreased to 23.4 (2.8) after the second VR viewing (P < 0.001). The NRS score for satisfaction tended to be higher after viewing LA in group A (CG→ LA) (CG vs. LA; 7.0 (2.3) vs. 8.6 (1.5), P = 0.0993), while in group B (LA→ CG), the score after CG was slightly lower than that after LA. There were no serious side effects.

Conclusions: This study suggests that iVR reminiscence can reduce anxiety in the oldest-old without causing serious side effects. Furthermore, the impacts might be better with LA images.
Neuroanatomical Alterations in Patients With Tinnitus Before and After Sound Therapy: A Combined VBM and SCN Study
Authors: Wei Xuan , Lv Han , Chen Qian , Wang Zhaodi , Liu Chunli , Zhao Pengfei , Gong Shusheng , Yang Zhenghan , Wang Zhenchang
Published: January 2021

Many neuroanatomical alterations have been detected in patients with tinnitus in previous studies. However, little is known about the morphological and structural covariance network (SCN) changes before and after long-term sound therapy. This study aimed to explore alterations in brain anatomical and SCN changes in patients with idiopathic tinnitus using voxel-based morphometry (VBM) analysis 24 weeks before and after sound therapy. Thirty-three tinnitus patients underwent magnetic resonance imaging scans at baseline and after 24 weeks of sound therapy. Twenty-six age- and sex-matched healthy control (HC) individuals also underwent two scans over a 24-week interval; 3.0T MRI and high-resolution 3D structural images were acquired with a 3D-BRAVO pulse sequence. Structural image data preprocessing was performed using the VBM8 toolbox. The Tinnitus Handicap Inventory (THI) score was assessed for the severity of tinnitus before and after treatment. Two-way mixed model analysis of variance (ANOVA) and post hoc analyses were performed to determine differences between the two groups (patients and HCs) and between the two scans (at baseline and on the 24th week). Student-Newman-Keuls (SNK) tests were used in the post hoc analysis. Interaction effects between the two groups and the two scans demonstrated significantly different gray matter (GM) volume in the right parahippocampus gyrus, right caudate, left superior temporal gyrus, left cuneus gyrus, and right calcarine gyrus; we found significantly decreased GM volume in the above five brain regions among the tinnitus patients before sound therapy (baseline) compared to that in the HC group. The 24-week sound therapy group demonstrated significantly greater brain volume compared with the baseline group among these brain regions. We did not find significant differences in brain regions between the 24-week sound therapy and HC groups. The SCN results showed that the left superior temporal gyrus and left rolandic operculum were significantly different in nodal efficiency, nodal degree centrality, and nodal betweenness centrality after FDR correction. This study characterized the effect of sound therapy on brain GM volume, especially in the left superior temporal lobe. Notably, sound therapy had a normalizing effect on tinnitus patients.
Disrupted Subcortical-Cortical Connections in a Phonological but Not Semantic Task in Chinese Children With Dyslexia
Authors: Zhang Lihuan , Hu Jiali , Liu Xin , Nichols Emily S. , Lu Chunming , Liu Li
Published: January 2021

Reading disability has been considered as a disconnection syndrome. Recently, an increasing number of studies have emphasized the role of subcortical regions in reading. However, the majority of research on reading disability has focused on the connections amongst brain regions within the classic cortical reading network. Here, we used graph theoretical analysis to investigate whether subcortical regions serve as hubs (regions highly connected with other brain regions) during reading both in Chinese children with reading disability (N = 15, age ranging from 11.03 to 13.08 years) and in age-matched typically developing children (N = 16, age ranging from 11.17 to 12.75 years) using a visual rhyming judgment task and a visual meaning judgment task. We found that the bilateral thalami were the unique hubs for typically developing children across both tasks. Additionally, subcortical regions (right putamen, left pallidum) were also unique hubs for typically developing children but only in the rhyming task. Among these subcortical hub regions, the left pallidum showed reduced connectivity with inferior frontal regions in the rhyming judgment but not semantic task in reading disabled compared with typically developing children. These results suggest that subcortical-cortical disconnection, which may be particularly relevant to the phonological and phonology-related learning process, may be associated with Chinese reading disability.
Secondary Degeneration of White Matter After Focal Sensorimotor Cortical Ischemic Stroke in Rats
Authors: Li Zhaoqing , Gao Huan , Zeng Pingmei , Jia Yinhang , Kong Xueqian , Xu Kedi , Bai Ruiliang
Published: January 2021

Ischemic lesions could lead to secondary degeneration in remote regions of the brain. However, the spatial distribution of secondary degeneration along with its role in functional deficits is not well understood. In this study, we explored the spatial and connectivity properties of white matter (WM) secondary degeneration in a focal unilateral sensorimotor cortical ischemia rat model, using advanced microstructure imaging on a 14 T MRI system. Significant axonal degeneration was observed in the ipsilateral external capsule and even remote regions including the contralesional external capsule and corpus callosum. Further fiber tractography analysis revealed that only fibers having direct axonal connections with the primary lesion exhibited a significant degeneration. These results suggest that focal ischemic lesions may induce remote WM degeneration, but limited to fibers tied to the primary lesion. These “direct” fibers mainly represent perilesional, interhemispheric, and subcortical axonal connections. At last, we found that primary lesion volume might be the determining factor of motor function deficits.
Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus
Authors: Salisbury Aaron J. , Blackwood Christopher A. , Cadet Jean Lud
Published: January 2021

People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 h and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction analyses. Rats, given long-access (9 h per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 h per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6, and Grm8 subtypes of glutamate receptors after 31 days but not after 2 h of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.
The Prospective Association of Dietary Sugar Intake in Adolescence With Risk Markers of Type 2 Diabetes in Young Adulthood
Authors: Della Corte Karen A. , Penczynski Katharina , Kuhnle Gunter , Perrar Ines , Herder Christian , Roden Michael , Wudy Stefan A. , Remer Thomas , Alexy Ute , Buyken Anette E.
Published: January 2021

Purpose:To examine the prospective relevance of dietary sugar intake (based on dietary data as well as urinary excretion data) in adolescent years for insulin sensitivity and biomarkers of inflammation in young adulthood.

Methods:Overall 254 participants of the DONALD study who had at least two 3-day weighed dietary records for calculating intakes of fructose, glucose, sucrose, total, free, added sugars, total sugars from sugar-sweetened beverages (SSB), juice, and sweets/sugar or at least two complete 24 h urine samples (n= 221) for calculating sugar excretion (urinary fructose and urinary fructose + sucrose) in adolescence (females: 9–15 years, males: 10–16 years) and a fasting blood sample in adulthood (18–36 years), were included in multivariable linear regression analyses assessing their prospective associations with adult homeostasis model assessment insulin sensitivity (HOMA2-%S) and a pro-inflammatory score (based on CRP, IL-6, IL-18, leptin, chemerin, adiponectin).

Results:On the dietary intake level, no prospective associations were observed between adolescent fructose, sucrose, glucose, added, free, total sugar, or total sugar from SSB, juice or sweets/sugar intake and adult HOMA2-%S (p> 0.01). On the urinary level, however, higher excreted fructose levels were associated with improved adult HOMA2-%S (p= 0.008) among females only. No associations were observed between dietary or urinary sugars and the adult pro-inflammatory score (p> 0.01).

Conclusion:The present study did not provide support that dietary sugar consumed in adolescence is associated with adult insulin sensitivity. The one potential exception was the moderate dietary consumption of fructose, which showed a beneficial association with adult fasting insulin and insulin sensitivity.
Elevated Red Blood Cell Distribution Width as a Poor Prognostic Factor in Patients With Hematopoietic Stem Cell Transplantation
Authors: Jia Xiaojiong , Cheng Si , Zhang Long , Zheng Yuan , Zou Hua , Huang Shifeng , Wang Hongxu , Lu Juan , Tang Dijiao
Published: January 2021

Red cell distribution width (RDW), a measure of erythrocyte size variability, has been recently reported as an effective prognostic factor in critical illness. Hematopoietic stem cell transplantation (HSCT) has become the first choice of most patients with hematological malignancies. The aim of this study was to assess the changes of RDW in patients with HSCT and analyze the relationship between RDW and HSCT. In this study, we retrospectively enrolled 114 hematopoietic stem cell transplant patients during the period from 2015 to 2019. Logistic regression and Kaplan–Meier survival analysis were used for retrospective analysis. Multivariate analysis suggested that patients with elevated RDW (>14.5%) at three months post-transplantation have a poor clinical outcome compared with those with normal RDW ≤14.5% [odds ratio (OR) 5.12; P = 0.002]. Kaplan–Meier method analysis demonstrated that patients with elevated RDW levels (>14.5%) after hematopoietic stem cell transplantation experienced shorter progression-free survival compared to those with normal RDW levels (P = 0.008). Our study demonstrated that RDW could be an easily available and potential predictive biomarker for risk stratification in patients with HSCT. Further prospective studies are determined to confirm the prognostic value of RDW in HSCT patients.
Rationale for Involved Field Stereotactic Body Radiation Therapy-Enhanced Intermittent Androgen Deprivation Therapy in Hormone-Sensitive Nodal Oligo-Recurrent Prostate Cancer Following Prostate Stereotactic Body Radiation Therapy
Authors: Carrasquilla Michael , Creswell Michael L. , Pepin Abigail N. , Wang Edina , Forsthoefel Matthew , McGunigal Mary , Bullock Elizabeth , Lei Siyuan , Collins Brian T. , Lischalk Jonathan W. , Esposito Giuseppe , Aghdam Nima , Kumar Deepak , Suy Simeng , Leger Paul , Hankins Ryan A. , Dawson Nancy A. , Collins Sean P.
Published: January 2021

Lymph node recurrent prostate cancer is a common clinical scenario that is likely to increase significantly with the widespread adoption of novel positron emission tomography (PET) agents. Despite increasing evidence that localized therapy is disease modifying, most men with lymph node recurrent prostate cancer receive only systemic therapy with androgen deprivation therapy (ADT). For men who receive localized therapy the intent is often to delay receipt of systemic therapy. Little evidence exists on the optimal combination of local and systemic therapy in this patient population. In this hypothesis generating review, we will outline the rationale and propose a framework for combining involved field SBRT with risk adapted intermittent ADT for hormone sensitive nodal recurrent prostate cancer. In patients with a limited number of nodal metastases, involved field stereotactic body radiation therapy (SBRT) may have a role in eliminating castrate-resistant clones and possibly prolonging the response to intermittent ADT. We hypothesize that in a small percentage of patients, such a treatment approach may lead to long term remission or cure.
4-Hydroxyphenylpyruvate Dioxygenase-Like Protein Promotes Pancreatic Cancer Cell Progression and Is Associated With Glutamine-Mediated Redox Balance
Authors: Ye Xianglai , Wei Xiujuan , Liao Jing , Chen Peipei , Li Xueyun , Chen Yulong , Yang Yue , Zhao Qiongya , Sun Hongwei , Pan Liming , Chen Guorong , He Xujun , Lyu Jianxin , Fang Hezhi
Published: January 2021

Tumor cells develop a series of metabolic reprogramming mechanisms to meet the metabolic needs for tumor progression. As metabolic hubs in cells, mitochondria play a significant role in this process, including energy production, biosynthesis, and redox hemostasis. In this study, we show that 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL), a previously uncharacterized protein, is positively associated with the development of pancreatic ductal adenocarcinoma (PDAC) and disease prognosis. We found that overexpression of HPDL in PDAC cells promotes tumorigenesis in vitro, whereas knockdown of HPDL inhibits cell proliferation and colony formation. Mechanistically, we found that HPDL is a mitochondrial intermembrane space localized protein that positively regulates mitochondrial bioenergetic processes and adenosine triphosphate (ATP) generation in a glutamine dependent manner. Our results further reveal that HPDL protects cells from oxidative stress by reprogramming the metabolic profile of PDAC cells toward glutamine metabolism. In short, we conclude that HPDL promotes PDAC likely through its effects on glutamine metabolism and redox balance.
Covid-19 in Children and Young Adolescents in Al Ain, United Arab Emirates- a Retrospective Cross-Sectional Study
Authors: Elghoudi Ahmed , Aldhanhani Huda , Ghatasheh Ghassan , Sharif Elsadeq , Narchi Hassib
Published: January 2021

Aim: In this retrospective single-center study, we report our experience with a cohort of children admitted to our hospital in Al Ain City, United Arab Emirates, with confirmed COVID-19. We also compare our findings to similar reports in the literature.

Patients and Methods: Between 1st March and 31st May 2020, we reviewed the electronic patient medical records of all children with confirmed COVID-19 (ICD-10 code U07.1) managed in Al Ain hospital, designated as the only COVID-19 center in the city.

Results: There were 288 children admitted with a confirmed diagnosis of Covid-19 during the study period (mean age 7.3 years, median 6.5, range 1 month to 16.9 years). The age-specific point prevalence was the highest under the age of 5 years (mean 2.0 per 1,000, 95% ci 1.7, 2.4) and decreased progressively to 0.6 per 1,000 (95% ci 0.4, 0.9) over the age of 14 years. Hospital admission was required for 193 (67%) children while 95 (33%) were discharged from the emergency department. Most children (n = 214, 74%) had been exposed to a family member with suspected or confirmed COVID-19 and asthma which was the most frequent comorbidity (n = 37, 13%). The most common symptoms were cough (n = 130, 45%), fever (n = 14, 4.8%), upper respiratory tract infection (n = 93, 32.3%), and lower respiratory tract infection in 28 (9.7%). None of the children presented with acute respiratory distress syndrome, neurological symptoms, sepsis, or septic shock. Neutropenia (absolute neutrophil count or ANC< 1.5 × 109/L) was observed in 10.4% and thrombocytopenia (<150 platelets × 109/L) in 72% of children. Nineteen patients (9%) had abnormal imaging studies (chest X-ray and chest computed tomography). Abnormalities were bilateral in six (43%), right-sided in seven (50%) with only one child (7%) with left-sided involvement. None of the children required invasive respiratory support, but four (1.4%) required noninvasive respiratory support. The median length of hospital stay was 3.3 days [1.9, 5.9]. There were no deaths in the hospital even in those with comorbidities.

Conclusions: Our results confirm previous reports of mild illness of COVID-19 in our child population, even in those with comorbidities. The age-standardized prevalence was higher in children (<5 years) compared to young adolescents.
Sleep Disturbances in Children With Autism Spectrum Disorder at a Malaysian Tertiary Hospital
Authors: Koo Ho Wai , Ismail Juriza , Yang Wai Wai , Syed Zakaria Syed Zulkifli
Published: January 2021

Introduction: Children with autism spectrum disorder (ASD) have a variety of co-morbid medical problems, including sleep disturbances. Prevalence of sleep disorders has been reported to be higher in this group as compared to the general population. Identifying sleep problems in children with ASD may help increase awareness and improve the overall quality of care for them. The aim of this study was to determine the prevalence of sleep problems and associated factors in a group of Malaysian children aged 6–16 years, with ASD.

Method: This is a cross-sectional study at the Child Development Centre of UKM Medical Centre (UKM MC) on ASD children aged 6–16 years. Demographic data was obtained and the Sleep Disturbances Scale for Children (SDSC) questionnaire was completed by the main caregiver. Logistic regression analysis was used to determine factors related to higher total SDSC scores.

Results: A total of 128 patients were recruited (111 boys) with a median age of 8 years 3 months (IQR: 2 years 10 months). Forty-seven (36.7%) of them obtained total SDSC scores in the pathological range with 19 (14.8%) scoring high for overall disturbances and 28 (21.9%) for at least one subtype of sleep disorders: 25 (19.5%) DIMS, 18 (14.1%) SBD, 10 (7.8%) DOES, 5 (3.9%) DOA, 6 (4.7%) SWTD, and 3 (2.3%) SHY. More than half of the children (57.8%) were reported to have sufficient sleep duration of 8–11 h, but longer sleep latency of at least 15 min (82.8%). Half of the ASD children also had co-morbidities in which one-third (34.4%) had attention-deficit hyperactivity disorder (ADHD). Using logistic regression analysis, four factors were significantly associated with higher total SDSC scores; female gender (p = 0.016), older age group (11–16 years old) (p = 0.039), shorter sleep length (p = 0.043), and longer sleep latency (p < 0.001).

Conclusion: The prevalence of sleep disturbances is high among Malaysian children with ASD, especially DIMS. Female gender, older age group, shorter sleep length, and longer sleep latency were found to be associated with the sleep disturbances. Evaluation of sleep problems should form part of the comprehensive care of children with ASD.
Using Artificial Intelligence to Obtain More Evidence? Prediction of Length of Hospitalization in Pediatric Burn Patients
Authors: Elrod Julia , Mohr Christoph , Wolff Ruben , Boettcher Michael , Reinshagen Konrad , Bartels Pia ,   German Burn Registry, Koenigs Ingo
Published: January 2021

Background: It is not only important for counseling purposes and for healthcare management. This study investigates the prediction accuracy of an artificial intelligence (AI)-based approach and a linear model. The heuristic expecting 1 day of stay per percentage of total body surface area (TBSA) serves as the performance benchmark.

Methods: The study is based on pediatric burn patient's data sets from an international burn registry (N = 8,542). Mean absolute error and standard error are calculated for each prediction model (rule of thumb, linear regression, and random forest). Factors contributing to a prolonged stay and the relationship between TBSA and the residual error are analyzed.

Results: The random forest-based approach and the linear model are statistically superior to the rule of thumb (p < 0.001, resp. p = 0.009). The residual error rises as TBSA increases for all methods. Factors associated with a prolonged LOS are particularly TBSA, depth of burn, and inhalation trauma.

Conclusion: Applying AI-based algorithms to data from large international registries constitutes a promising tool for the purpose of prediction in medicine in the future; however, certain prerequisites concerning the underlying data sets and certain shortcomings must be considered.
Prevalence and Clinical Characteristics of SARS-CoV-2 Confirmed and Negative Kawasaki Disease Patients During the Pandemic in Spain
Authors: Fernández-Cooke Elisa , Grasa Carlos D. , Domínguez-Rodríguez Sara , Barrios Tascón Ana , Sánchez-Manubens Judith , Anton Jordi , Mercader Beatriz , Villalobos Enrique , Camacho Marisol , Navarro Gómez María Luisa , Oltra Benavent Manuel , Giralt Gemma , Bustillo Matilde , Bello Naranjo Ana María , Rocandio Beatriz , Rodríguez-González Moisés , Núñez Cuadros Esmeralda , Aracil Santos Javier , Moreno David , Calvo Cristina ,   The KAWA-RACE Study Group
Published: January 2021

Introduction: COVID-19 has a less severe course in children. In April 2020, some children presented with signs of multisystem inflammation with clinical signs overlapping with Kawasaki disease (KD), most of them requiring admission to the pediatric intensive care unit (PICU). This study aimed to describe the prevalence and clinical characteristics of KD SARS-CoV-2 confirmed and negative patients during the pandemic in Spain.

Material and Methods: Medical data of KD patients from January 1, 2018 until May 30, 2020 was collected from the KAWA-RACE study group. We compared the KD cases diagnosed during the COVID-19 period (March 1–May 30, 2020) that were either SARS-CoV-2 confirmed (CoV+) or negative (CoV–) to those from the same period during 2018 and 2019 (PreCoV).

Results: One hundred and twenty-four cases were collected. There was a significant increase in cases and PICU admissions in 2020 (P-trend = 0.001 and 0.0004, respectively). CoV+ patients were significantly older (7.5 vs. 2.5 yr) and mainly non-Caucasian (64 vs. 29%), had incomplete KD presentation (73 vs. 32%), lower leucocyte (9.5 vs. 15.5 × 109) and platelet count (174 vs. 423 × 109/L), higher inflammatory markers (C-Reactive Protein 18.5vs. 10.9 mg/dl) and terminal segment of the natriuretic atrial peptide (4,766 vs. 505 pg/ml), less aneurysm development (3.8 vs. 11.1%), and more myocardial dysfunction (30.8 vs. 1.6%) than PreCoV patients. Respiratory symptoms were not increased during the COVID-19 period.

Conclusion: The KD CoV+ patients mostly meet pediatric inflammatory multisystem syndrome temporally associated with COVID-19/multisystem inflammatory syndrome in children criteria. Whether this is a novel entity or the same disease on different ends of the spectrum is yet to be clarified.
Oleoylethanolamide Protects Against Acute Liver Injury by Regulating Nrf-2/HO-1 and NLRP3 Pathways in Mice
Authors: Hu Jiaji , Zhu Zhoujie , Ying Hanglu , Yao Jie , Ma Huabin , Li Long , Zhao Yufen
Published: January 2021

Acute liver injury is a rapidly deteriorating clinical condition with markedly high morbidity and mortality. Oleoylethanolamide (OEA) is an endogenous lipid messenger with multiple bioactivities, and has therapeutic effects on various liver diseases. However, effects of OEA on acute liver injury remains unknown. In this study, effects and mechanisms of OEA in lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced acute liver injury in mice were investigated. We found that OEA treatment significantly attenuated LPS/D-Gal-induced hepatocytes damage, reduced liver index (liver weight/body weight), decreased plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels. Moreover, mechanism study suggested that OEA pretreatment significantly reduced hepatic MDA levels, increased Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-PX) activities via up-regulate Nrf-2 and HO-1 expression to exert anti-oxidation activity. Additionally, OEA markedly reduced the expression levels of Bax, Bcl-2 and cleaved caspase-3 to suppress hepatocyte apoptosis. Meanwhile, OEA remarkedly reduced the number of activated intrahepatic macrophages, and alleviated the mRNA expression of pro-inflammatory factors, including TNF-α, IL-6, MCP1 and RANTES. Furthermore, OEA obviously reduced the expression of IL-1β in liver and plasma through inhibit protein levels of NLRP3 and caspase-1, which indicated that OEA could suppress NLRP3 inflammasome pathway. We further determined the protein expression of PPAR-α in liver and found that OEA significantly increase hepatic PPAR-α expression. In addition, HO-1 inhibitor ZnPP blocked the therapeutic effects of OEA on LPS/D-Gal-induced liver damage and oxidative stress, suggesting crucial role of Nrf-2/HO-1 pathway in the protective effects of OEA in acute liver injury. Together, these findings demonstrated that OEA protect against the LPS/D-Gal-induced acute liver injury in mice through the inhibition of apoptosis, oxidative stress and inflammation, and its mechanisms might be associated with the Nrf-2/HO-1 and NLRP3 inflammasome signaling pathways.
Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE
Authors: Zhao Yifan , Sun Peng , Ma Yue , Chang Xiaoqiang , Chen Xingyu , Ji Xin , Bai Yue , Zhang Dong , Yang Lan
Published: January 2021

Dihydroartemisinin (DHA) and its’ derivatives have been employed as the most powerful first-line drugs for malarial treatment for several decades. The metabolism of DHA has not been studied clearly. Previous reports were focused on the pharmacokinetics procedure of DHA in healthy rats. The metabolites of DHA in red blood cells (RBC), especially in the RBC from Plasmodium-infected models, have rarely been studied. The Plasmodium species parasitize inside RBC, and these cells should be the final place where DHA performs its activity. In this study, the profile of DHA metabolites in biosample (blood, plasma, and RBC) of the infected and healthy mice was investigated with UPLC-Q-TOF-MS and UNIFI platform to gain insight into DHA metabolism. Results show that a total of 25 metabolites were successfully identified in infected (30 in healthy) blood, 27 in infected (27 in healthy) plasma, and 15 in infected (22 in healthy) RBC. Results show that hydroxylation, OH-dehydration, and glucuronidation reactions were important in the metabolic pathway in vivo. Significantly, DHA metabolites inside RBC were identified for the first time. 8-Hydroxy (8-OH) DHA, 4α-OH deoxy ART, and 6β-OH deoxy ART were identified in vivo for the first time.
An Shen Ding Zhi Ling Alleviates Symptoms of Attention Deficit Hyperactivity Disorder via Anti-Inflammatory Effects in Spontaneous Hypertensive Rats
Authors: Song Yuchen , Yuan Haixia , Chen Tianyi , Lu Manqi , Lei Shuang , Han Xinmin
Published: January 2021

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset chronic neurobehavioral disorder, with multiple genetic and environmental risk factors. Chronic inflammation may be critical for the progression of ADHD. An Shen Ding Zhi Ling (ASDZL) decoction, a traditional Chinese medicine prescription, is clinically used in ADHD treatment. In this study, we investigated the effects and underlying anti-inflammatory mechanisms of ASDZL in young spontaneously hypertensive rats (SHRs), a widely used model of ADHD. SHRs were divided into the SHR model group (vehicle), atomoxetine group (4.56 mg/kg/day) and ASDZL group (21.25 g/kg/day), and orally administered for four weeks. Wistar Kyoto rats were used as controls (vehicle). We found that ASDZL significantly controlled hyperactivity and impulsivity, and improved spatial memory of SHRs in the open field test and Morris water maze test. ASDZL reduced the pro-inflammatory factors interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 and increased anti-inflammatory factor IL-10 in SHRs, and decreased the activation of microglia, astrocytes and mast cells in the prefrontal cortex (PFC) and hippocampus. Furthermore, the results indicated that ASDZL inhibited the neuroinflammatory response by protecting the integrity of the blood-brain barrier and suppressing the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways of SHRs. In conclusion, these findings revealed that ASDZL attenuated ADHD symptoms in SHRs by reducing neuroinflammation.
Koumine Suppresses IL-1β Secretion and Attenuates Inflammation Associated With Blocking ROS/NF-κB/NLRP3 Axis in Macrophages
Authors: Luo Yufei , Xiong Bojun , Liu Haiping , Chen Zehong , Huang Huihui , Yu Changxi , Yang Jian
Published: January 2021

Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both in vitro using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and in vivo using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation. Furthermore, KM treatment efficiently attenuated the infiltration of neutrophils and suppressed IL-1β production in mice with MSU-induced peritonitis. These results indicated that KM inhibited NLRP3 inflammasome activation, and consistent with this finding, KM effectively inhibited caspase-1 activation, mature IL-1β secretion, NLRP3 formation and pro-IL-1β expression in LPS-primed macrophages treated with ATP, nigericin or MSU. The mechanistic study showed that, KM exerted a potent inhibitory effect on the NLRP3 priming step, which decreased the phosphorylation of IκBα and p65, the nuclear localization of p65, and the secretion of TNF-α and IL-6. Moreover, the assembly of NLRP3 was also interrupted by KM. KM blocked apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and its oligomerization and hampered the NLRP3-ASC interaction. This suppression was attributed to the ability of KM to inhibit the production of reactive oxygen species (ROS). In support of this finding, the inhibitory effect of KM on ROS production was completely counteracted by H2O2, an ROS promoter. Our results provide the first indication that KM exerts an inhibitory effect on NLRP3 inflammasome activation associated with blocking the ROS/NF-κB/NLRP3 signal axis. KM might have potential clinical application in the treatment of NLRP3 inflammasome-related diseases.