bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Term Fasting and Ingestion of Caloric Drinks Affect Heartbeat-Evoked Potentials and Autonomic Nervous System Activity in Males
Authors: Flasbeck Vera , Bamberg Christoph , Brüne Martin
Published: June 2021

Central nervous systems receive and process information from the internal and external environment to maintain homeostasis. This includes interoceptive awareness of the organism’s nutritional state. Whenever food supply is required, feelings of hunger initiate the search for and the consumption of appropriate amounts of nutrients. How this is physiologically regulated in humans has been subjected to research into interoceptive awareness of body states during fasting and food consumption. However, there is no research on the distinct effects of carbohydrate or protein intake on interoception. Therefore, we aimed to investigate the impact of fasting and consumption of standardized carbohydrate and protein shakes on interoception in a repeated-measures cross-over design in a sample of 37 healthy, normal weight males. As a physiological correlate of interoception, we measured heartbeat-evoked potentials (HEPs), which are suggested to reflect the cortical representation of cardiac signals, during eight-minutes resting state EEG-recordings. After a 16-hour fasting period, the HEP amplitudes were lower over right central and parietal electrodes and increased after ingestion of the nutritional shake. Exploratory analyses indicated that the difference between fasting and satiety was more prominent at carbohydrate compared protein testing days. Correlation analyses with heart rate variability (HRV) suggested that high cardiac sympathetic activity is related to lower HEP amplitudes. Furthermore, cardiac sympathetic activity and stress indices decreased from before to after the intervention, whereas HRV increased. Together, this study shows for the first time that fasting and the intake of a nutritional shake affects cardiac measures of autonomic nervous system functioning and the neural correlates of cardiac interoception. These findings could be relevant for diets and psychosomatic disorders, including eating disorders.
Construction and Validation of a Novel Eight-Gene Risk Signature to Predict the Progression and Prognosis of Bladder Cancer
Authors: Wang Ruiliang , Zheng Zongtai , Mao Shiyu , Zhang Wentao , Liu Ji , Li Cheng , Liu Shenghua , Yao Xudong
Published: June 2021

The progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) increases the risk of death. It is therefore important to find new relevant molecular models that will allow for effective prediction of the progression and prognosis of bladder cancer (BC). Using RNA-Sequence data of 49 BC patients in Shanghai tenth people’s hospital (STPH) and weighted gene co-expression network analysis methods, a co-expression network of genes was developed and three key modules associated with malignant progression were selected. Based on the genes in three key modules, an eight-gene risk signature was established using univariate Cox regression and the Least absolute shrinkage and selection operator Cox model in The Cancer Genome Atlas Program (TCGA) and validated in validation sets. Subsequently, a nomogram based on the risk signature was constructed for prognostic prediction. The mRNA and protein expression levels of eight genes in cell lines and tissues were further investigated. The novel eight-gene risk signature was closely related to the malignant clinical features of BC and could predict the prognosis of patients in the training dataset (TCGA) and four validation sets (GSE32894, GSE13507, IMvigor210 trial, and STPH). The nomogram showed good prognostic prediction and calibration. The mRNA and protein expression levels of the eight genes were differentially expressed in cell lines and tissues. In our study, we established a novel eight-gene risk signature that could predict the progression and prognoses of BC patients.
The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy
Authors: Russell Bonnie L. , Sooklal Selisha A. , Malindisa Sibusiso T. , Daka Lembelani Jonathan , Ntwasa Monde
Published: June 2021

Through genetic and epigenetic alterations, cancer cells present the immune system with a diversity of antigens or neoantigens, which the organism must distinguish from self. The immune system responds to neoantigens by activating naïve T cells, which mount an anticancer cytotoxic response. T cell activation begins when the T cell receptor (TCR) interacts with the antigen, which is displayed by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs). Subsequently, accessory stimulatory or inhibitory molecules transduce a secondary signal in concert with the TCR/antigen mediated stimulus. These molecules serve to modulate the activation signal’s strength at the immune synapse. Therefore, the activation signal’s optimum amplitude is maintained by a balance between the costimulatory and inhibitory signals. This system comprises the so-called immune checkpoints such as the programmed cell death (PD-1) and Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and is crucial for the maintenance of self-tolerance. Cancers often evade the intrinsic anti-tumor activity present in normal physiology primarily by the downregulation of T cell activation. The blockade of the immune checkpoint inhibitors using specific monoclonal antibodies has emerged as a potentially powerful anticancer therapy strategy. Several drugs have been approved mainly for solid tumors. However, it has emerged that there are innate and acquired mechanisms by which resistance is developed against these therapies. Some of these are tumor-intrinsic mechanisms, while others are tumor-extrinsic whereby the microenvironment may have innate or acquired resistance to checkpoint inhibitors. This review article will examine mechanisms by which resistance is mounted against immune checkpoint inhibitors focussing on anti-CTL4-A and anti-PD-1/PD-Ll since drugs targeting these checkpoints are the most developed.
Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone
Authors: Ripari Luisina B. , Norton Emily S. , Bodoque-Villar Raquel , Jeanneret Stephanie , Lara-Velazquez Montserrat , Carrano Anna , Zarco Natanael , Vazquez-Ramos Carla A. , Quiñones-Hinojosa Alfredo , de la Rosa-Prieto Carlos , Guerrero-Cázares Hugo
Published: June 2021

Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs. We present a novel rodent model to analyze the bidirectional signaling between GBM tumors and cells contained within the SVZ. Patient-derived GBM cells expressing GFP and luciferase were engrafted at locations proximal, intermediate, and distal to the LVs in immunosuppressed mice. Mice were either sacrificed after 4 weeks for immunohistochemical analysis of the tumor and SVZ or maintained for survival analysis. Analysis of the GFP+ tumor bulk revealed that GBM tumors proximal to the LV show increased levels of proliferation and tumor growth than LV-distal counterparts and is accompanied by decreased median survival. Conversely, numbers of innate proliferative cells, neural stem cells (NSCs), migratory cells and progenitors contained within the SVZ are decreased as a result of GBM proximity to the LV. These results indicate that our rodent model is able to accurately recapitulate several of the clinical aspects of LV-associated GBM, including increased tumor growth and decreased median survival. Additionally, we have found the neurogenic and cell division process of the SVZ in these adult mice is negatively influenced according to the presence and proximity of the tumor mass. This model will be invaluable for further investigation into the bidirectional signaling between GBM and the neurogenic cell populations of the SVZ.
Sentinel Lymph Node Mapping in Endometrial Cancer: A Comprehensive Review
Authors: Zhai Lirong , Zhang Xiwen , Cui Manhua , Wang Jianliu
Published: June 2021

Endometrial cancer (EC) is known as a common gynecological malignancy. The incidence rate is on the increase annually. Lymph node status plays a crucial role in evaluating the prognosis and selecting adjuvant therapy. Currently, the patients with high-risk (not comply with any of the following: (1) well-differentiated or moderately differentiated, pathological grade G1 or G2; (2) myometrial invasion< 1/2; (3) tumor diameter < 2 cm are commonly recommended for a systematic lymphadenectomy (LAD). However, conventional LAD shows high complication incidence and uncertain survival benefits. Sentinel lymph node (SLN) refers to the first lymph node that is passed by the lymphatic metastasis of the primary malignant tumor through the regional lymphatic drainage pathway and can indicate the involvement of lymph nodes across the drainage area. Mounting evidence has demonstrated a high detection rate (DR), sensitivity, and negative predictive value (NPV) in patients with early-stage lower risk EC using sentinel lymph node mapping (SLNM) with pathologic ultra-staging. Meanwhile, SLNM did not compromise the patient’s progression-free survival (PFS) and overall survival (OS) with low operative complications. However, the application of SLNM in early-stage high-risk EC patients remains controversial. As revealed by the recent studies, SLNM may also be feasible, effective, and safe in high-risk patients. This review aims at making a systematic description of the progress made in the application of SLNM in the treatment of EC and the relevant controversies, including the application of SLNM in high-risk patients.
TCF11 Has a Potent Tumor-Repressing Effect Than Its Prototypic Nrf1α by Definition of Both Similar Yet Different Regulatory Profiles, With a Striking Disparity From Nrf2
Authors: Wang Meng , Ren Yonggang , Hu Shaofan , Liu Keli , Qiu Lu , Zhang Yiguo
Published: June 2021

Nrf1 and Nrf2, as two principal CNC-bZIP transcription factors, regulate similar but different targets involved in a variety of biological functions for maintaining cell homeostasis and organ integrity. Of note, the unique topobiological behavior of Nrf1 makes its functions more complicated than Nrf2, because it is allowed for alternatively transcribing and selectively splicing to yield multiple isoforms (e.g., TCF11, Nrf1α). In order to gain a better understanding of their similarities and differences in distinct regulatory profiles, all four distinct cell models for stably expressing TCF11, TCF11ΔN, Nrf1α or Nrf2 have been herein established by an Flp-In™ T-REx™-293 system and then identified by transcriptomic sequencing. Further analysis revealed that Nrf1α and TCF11 have similar yet different regulatory profiles, although both contribute basically to positive regulation of their co-targets, which are disparate from those regulated by Nrf2. Such disparity in those gene regulations by Nrf1 and Nrf2 was further corroborated by scrutinizing comprehensive functional annotation of their specific and/or common target genes. Conversely, the mutant TCF11ΔN, resulting from a deletion of the N-terminal amino acids 2–156 from TCF11, resembles Nrf2 with the largely consistent structure and function. Interestingly, our further experimental evidence demonstrates that TCF11 acts as a potent tumor-repressor relative to Nrf1α, albeit both isoforms possess a congruous capability to prevent malignant growth of tumor and upregulate those genes critical for improving the survival of patients with hepatocellular carcinoma.
Naturally Occurring Bioactives as Antivirals: Emphasis on Coronavirus Infection
Authors: Ayatollahi Seyed Abdulmajid , Sharifi-Rad Javad , Tsouh Fokou Patrick Valere , Mahady Gail B. , Ansar Rasul Suleria Hafiz , Krishna Kapuganti Shivani , Gadhave Kundlik , Giri Rajanish , Garg Neha , Sharma Rohit , Ribeiro Daniel , Rodrigues Célia F. , Reiner Željko , Taheri Yasaman , Cruz-Martins Natália
Published: June 2021

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided.
Optimizing Autonomic Function Analysis via Heart Rate Variability Associated With Motor Activity of the Human Colon
Authors: Ali M. Khawar , Liu Lijun , Chen Ji-Hong , Huizinga Jan D.
Published: June 2021

The parameters of heart rate variability (HRV) can non-invasively assess some autonomic activities, and HRV is influenced by many bodily actions. Although parasympathetic activity is the primary driver of colonic propulsive activity, and sympathetic activity a major inhibitor of colonic motility, they are rarely measured and almost play no role in diagnosis of colon motor dysfunction or in standard treatments. Here we set out to optimize HRV analysis of autonomic nervous system changes related to human colon motility. The electrocardiogram and impedance were recorded in synchrony with colonic motor patterns by high-resolution manometry. Respiratory sinus arrhythmia (RSA), root mean square of successive differences of beat-to-beat intervals (RMSSD), the Baevsky Index or Sympathetic Index (SI), and the ratios of SI/RSA and SI/RMSSD were shown to indicate a marked increase in parasympathetic and withdrawal of sympathetic activity during the high-amplitude propagating pressure waves (HAPWs). Strong associations were seen with HAPWs evoked by a meal and rectal bisacodyl indicating a marked increase in parasympathetic and withdrawal of sympathetic activity during the gastrocolic reflex and the defecation reflex. When HAPWs occurred in quick succession, parasympathetic activation (RSA and RMSSD) occurred in a rhythmic fashion. Hence, during propulsive motor patterns, an overall shift in autonomic activity toward increased parasympathetic control was shown to be reflected in HRV. HRV assessment may therefore be valuable in the assessment of autonomic dysfunction related to colonic dysmotility.
Integrating External and Internal Load for Monitoring Fitness and Fatigue Status in Standard Microcycles in Elite Rink Hockey
Authors: Fernández Daniel , Moya David , Cadefau Joan A. , Carmona Gerard
Published: June 2021

The aims of this study were 3-fold: firstly, to present an integrative approach to external and internal load dynamics for monitoring fitness and fatigue status of specific in-court rink hockey training sessions in a standard microcycle; secondly, to assess the differences between training sessions and matches; the third and final aim was to assess the association between external and internal load metrics. The external load, using a local positioning system, and internal load, using the declared rate of perceived exertion, were measured during 23 in-season microcycles for nine top-level players. Training load data were analysed with regard to the number of days before or after a match [match day (MD) minus or plus]. In relation to the first aim, internal and external load metrics merged into a single integrated system using pooled data z-scores provided an invisible monitoring tool that places the players in the fitness-fatigue continuum throughout the different microcycle sessions. In this regard, MD-4 and MD-1 sessions tend to place, with a low dispersion, the players in a “low external and internal load” zone. On the contrary, in MD-3 and MD-2 sessions, as well as in MD, in which higher loads were recorded, most of the players were within a “high external and internal load” zone with a tendency towards dispersion towards the fitness or fatigue zones. Finally, and with regard to the second and third aims, an inverted “U-shape” load dynamic related to the specific goals of each training session was the main finding in terms of comparison between MD; a load peak between MD-3 and MD-2 sessions and a significant decrease in all the load variables in MD-1 sessions were found; and high-to-low correlations were found between external and internal load metrics. This study presents an integrative approach to the external and internal load of players for monitoring fitness and fatigue status during a standard microcycle in rink hockey that might provide team sport staff members with a deeper understanding of load distribution in the microcycle in relation to the match.
Variation for Photoperiod and Temperature Sensitivity in the Global Mini Core Collection of Sorghum
Authors: Upadhyaya Hari D. , Vetriventhan M. , Azevedo Vania C. R.
Published: June 2021

Information on photoperiod and temperature sensitivity of sorghum germplasm is important to identify appropriate sources for developing cultivars with a broad adaptation. The sorghum mini core collection consisting of 242 accessions along with three control cultivars were evaluated for days to 50% flowering (DFL) and plant height in two long-day rainy and two short-day post-rainy seasons, and for grain yield and 100-seed weight in the two post-rainy seasons. Differences in DFL and cumulative growing degree days (CGDD) in the rainy and post-rainy seasons were used to classify the accessions for photoperiod and temperature sensitivity. Results revealed 18 mini core landraces as photoperiod and temperature insensitive (PTINS), 205 as photoperiod sensitive and temperature insensitive (PSTINS), and 19 as photoperiod and temperature-sensitive (PTS) sources. The 19 PTS sources and 80 PSTINS sources took less DFL in the long-day rainy seasons than in the short-day post-rainy season indicating their adaptation to the rainy season and a possible different mechanism than that trigger flowering in the short-day sorghums. In all three groups, several accessions with desirable combinations of agronomic traits were identified for use in the breeding programs to develop climate-resilient cultivars and for genomic studies to identify genes responsible for the photoperiod and temperature responses.
Insights Into Natural Genetic Resistance to Rice Yellow Mottle Virus and Implications on Breeding for Durable Resistance
Authors: Odongo Patrick J. , Onaga Geoffrey , Ricardo Oliver , Natsuaki Keiko T. , Alicai Titus , Geuten Koen
Published: June 2021

Rice is the main food crop for people in low- and lower-middle-income countries in Asia and sub-Saharan Africa (SSA). Since 1982, there has been a significant increase in the demand for rice in SSA, and its growing importance is reflected in the national strategic food security plans of several countries in the region. However, several abiotic and biotic factors undermine efforts to meet this demand. Rice yellow mottle virus (RYMV) caused by Solemoviridae is a major biotic factor affecting rice production and continues to be an important pathogen in SSA. To date, six pathogenic strains have been reported. RYMV infects rice plants through wounds and rice feeding vectors. Once inside the plant cells, viral genome-linked protein is required to bind to the rice translation initiation factor [eIF(iso)4G1] for a compatible interaction. The development of resistant cultivars that can interrupt this interaction is the most effective method to manage this disease. Three resistance genes are recognized to limit RYMV virulence in rice, some of which have nonsynonymous single mutations or short deletions in the core domain of eIF(iso)4G1 that impair viral host interaction. However, deployment of these resistance genes using conventional methods has proved slow and tedious. Molecular approaches are expected to be an alternative to facilitate gene introgression and/or pyramiding and rapid deployment of these resistance genes into elite cultivars. In this review, we summarize the knowledge on molecular genetics of RYMV-rice interaction, with emphasis on host plant resistance. In addition, we provide strategies for sustainable utilization of the novel resistant sources. This knowledge is expected to guide breeding programs in the development and deployment of RYMV resistant rice varieties.
Dynamics of Parental Opioid Use and Children's Health and Well-Being: An Integrative Systems Mapping Approach
Authors: Smith Jessica C. , Alderman Leigh , Attell Brandon K. , Avila Rodriguez Wendy , Covington Jana , Manteuffel Brigitte , DiGirolamo Ann M. , Snyder Susan M. , Minyard Karen
Published: June 2021

The seemingly intractable opioid epidemic compels researchers, the media, and families to better understand the causes and effects of this complex and evolving public health crisis. The effects of this crisis on people using opioids, maternal prenatal opioid exposure, and neonatal abstinence syndrome are well-documented, but less is known about the impact of caregivers' opioid use on children's health and well-being. One challenge to understanding the effects of parental opioid use disorder (OUD) on child and adolescent outcomes is the numerous interrelated pathways in which a child's health and well-being can be impacted. To better understand these dynamic relationships, we applied a systems mapping approach to visualize complex patterns and interactions between pathways and potential leverage points for interventions. Specifically, we developed a causal loop diagram system map to elucidate the complex and interconnected relationships between parental OUD, social determinants of health at the family and socio-environmental levels, family strengths, social supports, and possible adverse impacts on children's physical and mental health and risks for future substance misuse. The goals of this research are to (1) identify factors and dynamics that contribute to the relationship between parental OUD and children's health and well-being and (2) illustrate how systems mapping as a tool can aid in understanding the complex factors and dynamics of the system(s) that influence the well-being of children and their parents or primary caregivers.
Anxiety Is Associated With DPPIV Alterations in Children With Selective Mutism and Social Anxiety Disorder: A Pilot Study
Authors: Golub Yulia , Stonawski Valeska , Plank Anne C. , Eichler Anna , Kratz Oliver , Waltes Regina , von Hoersten Stephan , Roessner Veit , Freitag Christine M.
Published: June 2021

Background: Both selective mutism (SM) and social anxiety disorder (SAD) are severe pediatric anxiety disorders with the common trait of behavioral inhibition (BI). The underlying pathophysiology of these disorders remains poorly understood, however converging evidence suggests that alterations in several peripheral molecular pathways might be involved. In a pilot study, we investigated alterations in plasma molecular markers (dipeptidyl peptidase-4 [DPPIV], interleukin-6 [IL-6], tumor necrosis factor-β [TNF-β] and neuropeptide-Y [NPY]) in children with SM, SAD, and healthy controls, as well as the correlation of these markers to symptom severity.

Methods: We included 51 children and adolescents (aged 5–18 years; n = 29 girls): n = 20 children in the SM-, n = 16 in the SAD- and n = 15 in the control-group (CG). Peripheral blood samples were analyzed for DPPIV, IL-6, TNF-β, and NPY concentrations. Diverse psychometric measures were used for BI, anxiety, and mutism symptoms.

Results: Lower DPPIV-levels were correlated with more anxiety symptoms. However, we could not find a difference in any molecular marker between the patients with SAD and SM in comparison to the CG.

Conclusion: DPPIV is proposed as relevant marker for child and adolescent anxiety. Investigating the pathophysiology of SM and SAD focusing on state and trait variables as anxiety or BI might help better understanding the underlying mechanisms of these disorders. Further studies with especially larger cohorts are needed to validate the current pilot-findings.
fNIRS Evaluation of Frontal and Temporal Cortex Activation by Verbal Fluency Task and High-Level Cognition Task for Detecting Anxiety and Depression
Authors: Lang Xuenan , Wen Dan , Li Qiqi , Yin Qin , Wang Mingyu , Xu Yong
Published: June 2021

Anxiety and depression are widespread psychosis which are believed to affect cerebral metabolism, especially in frontal and temporal cortex. The comorbidity patients of anxiety and depression (A&D) have more serious clinical symptoms. Functional near-infrared spectroscopy (fNIRS) is a noninvasive modality used to monitor human brain oxygenation, and it could be considered as a potential tool to detect psychosis which may lead to abnormal cerebral oxygen status when the brain is activated. However, how sensitive the cerebral oxygenation response to the cortex activation and whether these responses are consistent at different stages of A&D or different regions still remains unclear. In this study, a conventional physiological paradigm for cortex activation, i.e., verbal fluency task (VFT), and a relatively new paradigm, i.e., high-level cognition task (HCT), were compared to detect A&D through a longitudinal measurement of cerebral oxygen status by fNIRS. The A&D patients at the acute, consolidation and maintenance stages as well as the healthy subjects participated in the VFT and HCT paradigms, respectively. For the VTF paradigm, the subject was instructed to answer questions of phrase constructions within 60 s. For the HCT paradigm, the subject was instructed to categorize items, logical reasoning, and comprehensive judgment and write down the answers within 60 s. For most of the subjects, the oxy-Hb is found to increase remarkably, accompanied with a relatively small reduction in deoxy-Hb when subject to both paradigms. The statistical analyses show a relatively large variability within any group, leading to the significant difference that was only found between A&D at the acute stage and healthy subjects in the temporal lobe region (p < 0.001). Nevertheless, HCT would activate more oxygen increment when compared with the VFT, with a large integral value in oxy-Hb. On average, the oxy-Hb integral value of the A&D patients differs substantially at different stages when subject to HCT paradigm. Moreover, the prefrontal lobe and temporal lobe responses were more consistent to the HCT paradigm rather than the VFT paradigm. Under the VFT paradigm, however, no remarkable difference in integral value was found among the three stages, either at the prefrontal lobe or at the temporal lobe. This study indicated that HCT, which is intensively involved in brain function, would activate more oxygenation changes in the cerebral cortex. Additionally, with good performance at distinguishing different stages according to the oxy-Hb criterion, the HCT has the potential to evaluate the therapeutic effects for A&D patients.
Brief Report: Preliminary Evidence of the N170 as a Biomarker of Response to Treatment in Autism Spectrum Disorder
Authors: Kala Shashwat , Rolison Max J. , Trevisan Dominic A. , Naples Adam J. , Pelphrey Kevin , Ventola Pamela , McPartland James C.
Published: June 2021

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by primary difficulties in social function. Individuals with ASD display slowed neural processing of faces, as indexed by the latency of the N170, a face-sensitive event-related potential. Currently, there are no objective biomarkers of ASD useful in clinical care or research. Efficacy of behavioral treatment is currently evaluated through subjective clinical impressions. To explore whether the N170 might have utility as an objective index of treatment response, we examined N170 before and after receipt of an empirically validated behavioral treatment in children with ASD.

Method: Electroencephalography (EEG) data were obtained on a preliminary cohort of preschool-aged children with ASD before and after a 16-week course of PRT and in a subset of participants in waitlist control (16-weeks before the start of PRT) and follow-up (16-weeks after the end of PRT). EEG was recorded while participants viewed computer-generated faces with neutral and fearful affect.

Results: Significant reductions in N170 latency to faces were observed following 16 weeks of PRT intervention. Change in N170 latency was not observed in the waitlist-control condition.

Conclusions: This exploratory study offers suggestive evidence that N170 latency may index response to behavioral treatment. Future, more rigorous, studies in larger samples are indicated to evaluate whether the N170 may be useful as a biomarker of treatment response.
Responding to the Call: Building a Training Program to Diversify the Academy in Alzheimer's Disease Research
Authors: Ingram Lucy Annang , Ford Marvella E. , Johnson Christiana L. , Ashford-Carroll Brianna , McCollum Quentin , Friedman Daniela B. , Levkoff Sue Ellen
Published: June 2021

Alzheimer's disease and related dementias (ADRD) are at the forefront of the United States (US) public health agenda due to their tremendous human and financial burden. Further, disproportionately high ADRD rates among racial/ethnic minorities require incorporating the unique perspectives of racially and ethnically diverse scientists, which will necessitate diversifying the scientific workforce that investigates disparities in aging. The purpose of this paper is to describe the training and mentorship initiatives of the National Institute on Aging (NIA)-funded Carolina Center on Alzheimer's Disease and Minority Research, emphasizing lessons learned from our engagement with underrepresented minority and minoritized (URM) Scientists. We highlight three aims of the Center's training and mentorship component: (1) Fund pilot projects for URM Scientists conducting research on sociocultural, behavioral, and environmental factors that influence ADRD-related health disparities; (2) Provide mentorship to build the research capacity of Center Scientists; and (3) Offer research education in Health Disparities and Minority Aging Research to Center Scientists and interested researchers at all partner institutions. Our experience may be a practical resource for others developing interdisciplinary training programs to increase the pipeline of URM Scientists conducting ADRD research.
Health-Related Quality of Life in Patients With Different Diseases Measured With the EQ-5D-5L: A Systematic Review
Authors: Zhou Ting , Guan Haijing , Wang Luying , Zhang Yao , Rui Mingjun , Ma Aixia
Published: June 2021

Background: The EQ-5D-5L is a generic preference-based questionnaire developed by the EuroQol Group to measure health-related quality of life (HRQoL) in 2005. Since its development, it has been increasingly applied in populations with various diseases and has been found to have good reliability and sensitivity. This study aimed to summarize the health utility elicited from EQ-5D-5L for patients with different diseases in cross-sectional studies worldwide.

Methods: Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched from January 1, 2012, to October 31, 2019. Cross-sectional studies reporting utility values measured with the EQ-5D-5L in patients with any specific disease were eligible. The language was limited to English. Reference lists of the retrieved studies were manually searched to identify more studies that met the inclusion criteria. Methodological quality was assessed with the Agency for Health Research and Quality (AHRQ) checklist. In addition, meta-analyses were performed for utility values of any specific disease reported in three or more studies.

Results: In total, 9,400 records were identified, and 98 studies met the inclusion criteria. In the included studies, 50 different diseases and 98,085 patients were analyzed. Thirty-five studies involving seven different diseases were included in meta-analyses. The health utility ranged from 0.31 to 0.99 for diabetes mellitus [meta-analysis random-effect model (REM): 0.83, (95% CI = 0.77–0.90); fixed-effect model (FEM): 0.93 (95% CI = 0.93–0.93)]; from 0.62 to 0.90 for neoplasms [REM: 0.75 (95% CI = 0.68–0.82); FEM: 0.80 (95% CI = 0.78–0.81)]; from 0.56 to 0.85 for cardiovascular disease [REM: 0.77 (95% CI = 0.75–0.79); FEM: 0.76 (95% CI = 0.75–0.76)]; from 0.31 to 0.78 for multiple sclerosis [REM: 0.56 (95% CI = 0.47–0.66); FEM: 0.67 (95% CI = 0.66–0.68)]; from 0.68 to 0.79 for chronic obstructive pulmonary disease [REM: 0.75 (95% CI = 0.71–0.80); FEM: 0.76 (95% CI = 0.75–0.77)] from 0.65 to 0.90 for HIV infection [REM: 0.84 (95% CI = 0.80–0.88); FEM: 0.81 (95% CI = 0.80–0.82)]; from 0.37 to 0.89 for chronic kidney disease [REM: 0.70 (95% CI = 0.48–0.92; FEM: 0.76 (95% CI = 0.74–0.78)].

Conclusions: EQ-5D-5L is one of the most widely used preference-based measures of HRQoL in patients with different diseases worldwide. The variation of utility values for the same disease was influenced by the characteristics of patients, the living environment, and the EQ-5D-5L value set.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020158694.
Mandatory Mask-Wearing and Hand Hygiene Associated With Decreased Infectious Diseases Among Patients Undergoing Regular Hemodialysis: A Historical-Control Study
Authors: Qin Jun-Jian , Xing Yan-Fang , Ren Jian-Hua , Chen Yong-Jian , Gan Ying-Fei , Jiang Yan-Qiu , Chen Jie , Li Xing
Published: June 2021

Background: Infections are the second leading cause of death among patients undergoing hemodialysis. However, preventive measures against infectious diseases are limited and have not been made mandatory for patients.

Objective: To investigate the incidence of infectious diseases before and during the coronavirus disease (COVID-19) pandemic.

Design: A historical comparative study of a prospective cohort.

Setting(s): February 1, 2015 to January 31, 2020 was defined as the period before the mitigative confrontation of the COVID-19 pandemic in China. The period from February 1 to June 29, 2020 was defined as the period of mitigative confrontation of the COVID-19 pandemic in China.

Participants: A cohort of patients undergoing hemodialysis whose infectious disease episodes were documented prospectively in the hemodialysis unit of the Third Affiliated Hospital of Guangzhou Medical University since February 1, 2015.

Methods: Mandatory mask-wearing and reinforced hand-hygiene education were implemented to prevent COVID-19 from January 23, 2020 in China. The incidence of infectious episodes, including catheter-related infection, digestive tract infection, upper respiratory tract infection (UTRI), pneumonia, and infection at other sites, were documented and compared in the periods before and during the pandemic.

Results: The historical control group consisted of 157 patients, with 79 patients in the COVID-19 prevention group. The mask-wearing rate of patients increased from 1.5 to 100%. Hand sanitizer consumption increased significantly during the COVID-19 pandemic. The compliance rates of hand hygiene increased from 66, 75.5, to 55% in physicians, nurses, and other employees before the pandemic to 90.5, 92.5, and 76.5%, respectively. The incidences of UTRI and pneumonia decreased during the pandemic (p < 0.001). Notably, catheter-related and digestive tract infections also decreased during the pandemic (p = 0.003 and 0.034, respectively). A matched-pair study was conducted to further analyze the 79 individual changes in the incidences of infectious disease before and during the pandemic. As a result, the incidences of UTRI, pneumonia, catheter-related infections, digestive tract infections, and infections at other sites all decreased during the pandemic.

Conclusions: The present study indicated an association between mandatory mask-wearing and reinforced hand hygiene education and decreased respiratory, catheter-related, and digestive tract infection episodes in the hemodialysis unit.
Deep Learning–Based COVID-19 Pneumonia Classification Using Chest CT Images: Model Generalizability
Authors: Nguyen Dan , Kay Fernando , Tan Jun , Yan Yulong , Ng Yee Seng , Iyengar Puneeth , Peshock Ron , Jiang Steve
Published: June 2021

Since the outbreak of the COVID-19 pandemic, worldwide research efforts have focused on using artificial intelligence (AI) technologies on various medical data of COVID-19–positive patients in order to identify or classify various aspects of the disease, with promising reported results. However, concerns have been raised over their generalizability, given the heterogeneous factors in training datasets. This study aims to examine the severity of this problem by evaluating deep learning (DL) classification models trained to identify COVID-19–positive patients on 3D computed tomography (CT) datasets from different countries. We collected one dataset at UT Southwestern (UTSW) and three external datasets from different countries: CC-CCII Dataset (China), COVID-CTset (Iran), and MosMedData (Russia). We divided the data into two classes: COVID-19–positive and COVID-19–negative patients. We trained nine identical DL-based classification models by using combinations of datasets with a 72% train, 8% validation, and 20% test data split. The models trained on a single dataset achieved accuracy/area under the receiver operating characteristic curve (AUC) values of 0.87/0.826 (UTSW), 0.97/0.988 (CC-CCCI), and 0.86/0.873 (COVID-CTset) when evaluated on their own dataset. The models trained on multiple datasets and evaluated on a test set from one of the datasets used for training performed better. However, the performance dropped close to an AUC of 0.5 (random guess) for all models when evaluated on a different dataset outside of its training datasets. Including MosMedData, which only contained positive labels, into the training datasets did not necessarily help the performance of other datasets. Multiple factors likely contributed to these results, such as patient demographics and differences in image acquisition or reconstruction, causing a data shift among different study cohorts.
Using Tactile Sensing to Improve the Sample Efficiency and Performance of Deep Deterministic Policy Gradients for Simulated In-Hand Manipulation Tasks
Authors: Melnik Andrew , Lach Luca , Plappert Matthias , Korthals Timo , Haschke Robert , Ritter Helge
Published: June 2021

Deep Reinforcement Learning techniques demonstrate advances in the domain of robotics. One of the limiting factors is a large number of interaction samples usually required for training in simulated and real-world environments. In this work, we demonstrate for a set of simulated dexterous in-hand object manipulation tasks that tactile information can substantially increase sample efficiency for training (by up to more than threefold). We also observe an improvement in performance (up to 46%) after adding tactile information. To examine the role of tactile-sensor parameters in these improvements, we included experiments with varied sensor-measurement accuracy (ground truth continuous values, noisy continuous values, Boolean values), and varied spatial resolution of the tactile sensors (927 sensors, 92 sensors, and 16 pooled sensor areas in the hand). To facilitate further studies and comparisons, we make these touch-sensor extensions available as a part of the OpenAI Gym Shadow-Dexterous-Hand robotics environments.
Role-Play as Responsible Robotics: The Virtual Witness Testimony Role-Play Interview for Investigating Hazardous Human-Robot Interactions
Authors: Webb Helena , Dumitru Morgan , van Maris Anouk , Winkle Katie , Jirotka Marina , Winfield Alan
Published: June 2021

The development of responsible robotics requires paying attention to responsibility within the research process in addition to responsibility as the outcome of research. This paper describes the preparation and application of a novel method to explore hazardous human-robot interactions. The Virtual Witness Testimony role-play interview is an approach that enables participants to engage with scenarios in which a human being comes to physical harm whilst a robot is present and may have had a malfunction. Participants decide what actions they would take in the scenario and are encouraged to provide their observations and speculations on what happened. Data collection takes place online, a format that provides convenience as well as a safe space for participants to role play a hazardous encounter with minimal risk of suffering discomfort or distress. We provide a detailed account of how our initial set of Virtual Witness Testimony role-play interviews were conducted and describe the ways in which it proved to be an efficient approach that generated useful findings, and upheld our project commitments to Responsible Research and Innovation. We argue that the Virtual Witness Testimony role-play interview is a flexible and fruitful method that can be adapted to benefit research in human robot interaction and advance responsibility in robotics.
Virtual Reality-Induced Sensorimotor Conflict Evokes Limb-Specific Sensory Disturbances in Complex Regional Pain Syndrome
Authors: Brun Clémentine , Pinard Anne Marie , McCabe Candida S. , Mercier Catherine
Published: June 2021

The origin of sensory disturbances in complex regional pain syndrome (CRPS) remains unclear. It has been hypothesized that such disturbances are due to attentional effects and/or sensorimotor integration deficits. If sensory disturbances are explained by sensorimotor integration deficits, they would be expected to be specific in terms of the category of sensation evoked and in terms of localization. Objective 1: To test whether sensory disturbances evoked by a unilateral sensorimotor conflict are specific to the painful limb and differ according to the category of sensory disturbances in individuals with a unilateral CRPS compared to healthy controls (HC). Objective 2: To assess the association between clinical characteristics and conflict-induced sensory disturbances. Objective 3: To assess conflict-induced motor disturbances. Ten adults with upper limb (UL) CRPS and 23 HC were recruited. Sensorimotor conflict was elicited with a KINARM exoskeleton interfaced with a 2D virtual environment allowing the projection of a virtual UL that was moving in either a congruent or incongruent manner relative to the actual UL movement. Participants rated sensory disturbances from 0 (no change) to 3 (high change) on a 8-item questionnaire. Items were classified into two Categories (Category 1: pain, discomfort, the feeling of losing a limb, change in weight and temperature; Category 2: feelings of peculiarity, the impression of gaining a limb and losing control). Motor disturbances were quantified as mediolateral drift and changes in amplitude of UL movement. Clinical characteristics included the intensity and duration of pain, proprioception, and body perception. CRPS participants report higher Category 1 than Category 2 disturbances for the Affected limb (while the reverse was observed for HC and for the Unaffected limb). In addition, no difference was observed between the Unaffected limb in CRPS and the Dominant limb in HC for Category 2 disturbances, while higher conflict sensitivity was observed for Category 1 disturbances. Conflict sensitivity was only related to higher pain for Category 1 disturbances in the Affected limb. Finally, no effect on motor disturbances was observed. While they do not completely rule out the attentional hypothesis, these results support the hypothesis of sensorimotor integration deficits.
Sustainable Development Goal Drivers in Food Systems
Authors: Kretschmer Sebastian , Kahl Johannes
Published: June 2021

Interacting driving forces in food systems, resulting in cumulative driver effects and synergies, induce non-linear processes in multiple directions. This paper critically reviews the discourse on driving forces in food systems and argues that mindset is the primary predictor for food system outcomes. In the epoch of sustainable development goals (SDGs) and the Anthropocene, mindset matters more than ever. Transformative narratives are beginning to transcend the dominant social paradigm, which is still driving the food system's overall trajectory. The psychosocial portrayal of the systemic mindset found in organic food systems presented in this paper “flips the script” and hypothesizes that worldview and paradigm have the most causal linkages with unsustainable driver synergies and reversely the biggest leverage on the mitigation thereof. Borrowing from ecological economics discourses, the paper sharpens the driver definition by applying the DPSIR analytical tool as a modified diagnostic framework and modeling approach for food systems. This research sheds new light on the nature of drivers of change, which are often portrayed as almighty and inevitable trends shaping food systems. Instead, it is proposed that drivers emerge from the actors' mindset, affecting food system behavior in a non-linear way. Mindset drives reinforcing feedback loops, resulting in vicious and virtuous cycles. These driver motives manifest in subsystems and continue to drive their interaction across food system elements. Mindset acts as an encapsulated input of food systems, all the while responding to feedback and releasing new drivers. A transformation framework along leverage points of the food system is presented that features the concept of SDG drivers.