bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Ischemia as a Prelude to Alzheimer's Disease
Authors: Pluta Ryszard , Januszewski Sławomir , Czuczwar Stanisław J.
Published: February 2021

Transient ischemic brain injury causes massive neuronal death in the hippocampus of both humans and animals. This was accompanied by progressive atrophy of the hippocampus, brain cortex, and white matter lesions. Furthermore, it has been noted that neurodegenerative processes after an episode of ischemia-reperfusion in the brain can continue well-beyond the acute stage. Rarefaction of white matter was significantly increased in animals at 2 years following ischemia. Some rats that survived 2 years after ischemia developed severe brain atrophy with dementia. The profile of post-ischemic brain neurodegeneration shares a commonality with neurodegeneration in Alzheimer's disease. Furthermore, post-ischemic brain injury is associated with the deposition of folding proteins, such as amyloid and tau protein, in the intracellular and extracellular space. Recent studies on post-ischemic brain neurodegeneration have revealed the dysregulation of Alzheimer's disease-associated genes such as amyloid protein precursor, α-secretase, β-secretase, presenilin 1, presenilin 2, and tau protein. The latest data demonstrate that Alzheimer's disease-related proteins and their genes play a key role in the development of post-ischemic brain neurodegeneration with full-blown dementia in disease types such as Alzheimer's. Ongoing interest in the study of brain ischemia has provided evidence showing that ischemia may be involved in the development of the genotype and phenotype of Alzheimer's disease, suggesting that brain ischemia can be considered as a useful model for understanding the mechanisms responsible for the initiation of Alzheimer's disease.
The Impact of Neonatal Methamphetamine on Spatial Learning and Memory in Adult Female Rats
Authors: Petrikova-Hrebickova Ivana , Sevcikova Maria , Šlamberová Romana
Published: February 2021

The present study was aimed at evaluating cognitive changes following neonatal methamphetamine exposure in combination with repeated treatment in adulthood of female Wistar rats. Pregnant dams and their pups were used in this study. One half of the offspring were treated indirectly via the breast milk of injected mothers, and the other half of pups were treated directly by methamphetamine injection. In the group with indirect exposure, mothers received methamphetamine (5 mg/ml/kg) or saline (1 ml/kg) between postnatal days (PD) 1–11. In the group with direct exposure, none of the mothers were treated. Instead, progeny were either: (1) treated with injected methamphetamine (5 mg/ml/kg); or (2) served as controls and received sham injections (no saline, just a needle stick) on PD 1–11. Learning ability and memory consolidation were tested on PD 70–90 in the Morris Water Maze (MWM) using three tests: Place Navigation Test, Probe Test, and Memory Recall Test. Adult female progeny were injected daily, after completion of the last trial of MWM tests, with saline or methamphetamine (1 mg/ml/kg). The effects of indirect/direct neonatal methamphetamine exposure combined with acute adult methamphetamine treatment on cognitive functions in female rats were compared. Statistical analyses showed that neonatal drug exposure worsened spatial learning and the ability to remember the position of a hidden platform. The study also demonstrated that direct methamphetamine exposure has a more significant impact on learning and memory than indirect exposure. The acute dose of the drug did not produce any changes in cognitive ability. Analyses of search strategies (thigmotaxis, scanning) used by females during the Place Navigation Test and Memory Recall Test confirmed all these results. Results from the present study suggested extensive deficits in learning skills and memory of female rats that may be linked to the negative impact of neonatal methamphetamine exposure.
Endothelial Progenitor Cell-Derived Microvesicles Promote Angiogenesis in Rat Brain Microvascular Endothelial Cells In vitro
Authors: Zeng Wen , Lei Qiaoling , Ma Jiao , Gao Shuqiang , Ju Rong
Published: February 2021

Brain microvascular endothelial cells (BMECs) are a major component of the blood-brain barrier that maintains brain homeostasis. Preserving and restoring the normal biological functions of BMECs can reverse or reduce brain injury. Endothelial progenitor cells (EPCs) may promote brain vascular remodeling and restore normal endothelial function. As a novel vehicle for cell-cell communication, microvesicles (MVs) have varied biological functions. The present study investigated the biological effects of EPC-derived MVs (EPC-MVs) on BMECs in vitro. We isolated MVs from the supernatant of EPCs in a serum-depleted medium. BMECs were cultured alone or in the presence of EPC-MVs. BMEC viability and proliferation were evaluated with the Cell Counting Kit-8 and by flow cytometry, and the proangiogenic effect of EPC-MVs on BMECs was assessed with the transwell migration, wound healing, and tube formation assays. Our results showed that EPC-derived MVs labeled with DiI were internalized by cultured BMECs; this enhanced BMEC viability and promoted their proliferation. EPC-MVs also stimulated migration and tube formation in BMECs. These results demonstrate that EPC-derived MVs exert a proangiogenic effect on BMECs, which has potential applications in cell-free therapy for brain injury.
Microglia Fighting for Neurological and Mental Health: On the Central Nervous System Frontline of COVID-19 Pandemic
Authors: Gonçalves de Andrade Elisa , Šimončičová Eva , Carrier Micaël , Vecchiarelli Haley A. , Robert Marie-Ève , Tremblay Marie-Ève
Published: February 2021

Coronavirus disease 2019 (COVID-19) is marked by cardio-respiratory alterations, with increasing reports also indicating neurological and psychiatric symptoms in infected individuals. During COVID-19 pathology, the central nervous system (CNS) is possibly affected by direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion, exaggerated systemic inflammatory responses, or hypoxia. Psychosocial stress imposed by the pandemic further affects the CNS of COVID-19 patients, but also the non-infected population, potentially contributing to the emergence or exacerbation of various neurological or mental health disorders. Microglia are central players of the CNS homeostasis maintenance and inflammatory response that exert their crucial functions in coordination with other CNS cells. During homeostatic challenges to the brain parenchyma, microglia modify their density, morphology, and molecular signature, resulting in the adjustment of their functions. In this review, we discuss how microglia may be involved in the neuroprotective and neurotoxic responses against CNS insults deriving from COVID-19. We examine how these responses may explain, at least partially, the neurological and psychiatric manifestations reported in COVID-19 patients and the general population. Furthermore, we consider how microglia might contribute to increased CNS vulnerability in certain groups, such as aged individuals and people with pre-existing conditions.
Rehabilitation of Neuromuscular Diseases During COVID-19: Pitfalls and Opportunities
Authors: Liguori Sara , Moretti Antimo , Paoletta Marco , Gimigliano Francesca , Iolascon Giovanni
Published: February 2021

The outbreak of COVID-19 caused by SARS-CoV-2 has spread worldwide with a huge impact on the healthcare system. Compared to the previous coronaviruses-related pandemics, COVID-19 is more transmissible with potential systemic involvement and peculiar neurological manifestations, such as Guillan-Barrè syndrome up to critical illness myopathy, occurring in the intensive care setting. In this clinical scenario, people living with a neuromuscular disease (NMD) represent a vulnerable category with a high risk of a severe course of COVID-19. Moreover, in the NMD population, the management of respiratory and muscular impairments after SARS-CoV-2 infection might be troubling in terms of both pharmacological and rehabilitative approaches. To date, rehabilitation is still an unmet need in this population with several implications on NMD progression with and without SARS-CoV-2 infection. In particular, rehabilitation intervention for patients with NMD after COVID-19 are lacking. Therefore, in the current paper, we analyze the critical issues of COVID-19 on NMDs patients and propose a home-based rehabilitation program targeted for this population after mild to moderate SARS-CoV-2 infection.
Asymmetries in Accessing Vowel Representations Are Driven by Phonological and Acoustic Properties: Neural and Behavioral Evidence From Natural German Minimal Pairs
Authors: Riedinger Miriam , Nagels Arne , Werth Alexander , Scharinger Mathias
Published: February 2021

In vowel discrimination, commonly found discrimination patterns are directional asymmetries where discrimination is faster (or easier) if differing vowels are presented in a certain sequence compared to the reversed sequence. Different models of speech sound processing try to account for these asymmetries based on either phonetic or phonological properties. In this study, we tested and compared two of those often-discussed models, namely the Featurally Underspecified Lexicon (FUL) model (Lahiri and Reetz, 2002) and the Natural Referent Vowel (NRV) framework (Polka and Bohn, 2011). While most studies presented isolated vowels, we investigated a large stimulus set of German vowels in a more naturalistic setting within minimal pairs. We conducted an mismatch negativity (MMN) study in a passive and a reaction time study in an active oddball paradigm. In both data sets, we found directional asymmetries that can be explained by either phonological or phonetic theories. While behaviorally, the vowel discrimination was based on phonological properties, both tested models failed to explain the found neural patterns comprehensively. Therefore, we additionally examined the influence of a variety of articulatory, acoustical, and lexical factors (e.g., formant structure, intensity, duration, and frequency of occurrence) but also the influence of factors beyond the well-known (perceived loudness of vowels, degree of openness) in depth via multiple regression analyses. The analyses revealed that the perceptual factor of perceived loudness has a greater impact than considered in the literature and should be taken stronger into consideration when analyzing preattentive natural vowel processing.
MindLink-Eumpy: An Open-Source Python Toolbox for Multimodal Emotion Recognition
Authors: Li Ruixin , Liang Yan , Liu Xiaojian , Wang Bingbing , Huang Wenxin , Cai Zhaoxin , Ye Yaoguang , Qiu Lina , Pan Jiahui
Published: February 2021

Emotion recognition plays an important role in intelligent human–computer interaction, but the related research still faces the problems of low accuracy and subject dependence. In this paper, an open-source software toolbox called MindLink-Eumpy is developed to recognize emotions by integrating electroencephalogram (EEG) and facial expression information. MindLink-Eumpy first applies a series of tools to automatically obtain physiological data from subjects and then analyzes the obtained facial expression data and EEG data, respectively, and finally fuses the two different signals at a decision level. In the detection of facial expressions, the algorithm used by MindLink-Eumpy is a multitask convolutional neural network (CNN) based on transfer learning technique. In the detection of EEG, MindLink-Eumpy provides two algorithms, including a subject-dependent model based on support vector machine (SVM) and a subject-independent model based on long short-term memory network (LSTM). In the decision-level fusion, weight enumerator and AdaBoost technique are applied to combine the predictions of SVM and CNN. We conducted two offline experiments on the Database for Emotion Analysis Using Physiological Signals (DEAP) dataset and the Multimodal Database for Affect Recognition and Implicit Tagging (MAHNOB-HCI) dataset, respectively, and conducted an online experiment on 15 healthy subjects. The results show that multimodal methods outperform single-modal methods in both offline and online experiments. In the subject-dependent condition, the multimodal method achieved an accuracy of 71.00% in the valence dimension and an accuracy of 72.14% in the arousal dimension. In the subject-independent condition, the LSTM-based method achieved an accuracy of 78.56% in the valence dimension and an accuracy of 77.22% in the arousal dimension. The feasibility and efficiency of MindLink-Eumpy for emotion recognition is thus demonstrated.
Lower-Limb Amputees Adjust Quiet Stance in Response to Manipulations of Plantar Sensation
Authors: Shell Courtney E. , Christie Breanne P. , Marasco Paul D. , Charkhkar Hamid , Triolo Ronald J.
Published: February 2021

Interfering with or temporarily eliminating foot-sole tactile sensations causes postural adjustments. Furthermore, individuals with impaired or missing foot-sole sensation, such as lower-limb amputees, exhibit greater postural instability than those with intact sensation. Our group has developed a method of providing tactile feedback sensations projected to the missing foot of lower-limb amputees via electrical peripheral nerve stimulation (PNS) using implanted nerve cuff electrodes. As a step toward effective implementation of the system in rehabilitation and everyday use, we compared postural adjustments made in response to tactile sensations on the missing foot elicited by our system, vibration on the intact foot-sole, and a control condition in which no additional sensory input was applied. Three transtibial amputees with at least a year of experience with tactile sensations provided by our PNS system participated in the study. Participants stood quietly with their eyes closed on their everyday prosthesis while electrically elicited, vibratory, or no additional sensory input was administered for 20 s. Early and steady-state postural adjustments were quantified by center of pressure location, path length, and average angle over the course of each trial. Electrically elicited tactile sensations and vibration both caused shifts in center of pressure location compared to the control condition. Initial (first 3 s) shifts in center of pressure location with electrically elicited or vibratory sensory inputs often differed from shifts measured over the full 20 s trial. Over the full trial, participants generally shifted toward the foot receiving additional sensory input, regardless of stimulation type. Similarities between responses to electrically elicited tactile sensations projected to the missing foot and responses to vibration in analogous regions on the intact foot suggest that the motor control system treats electrically elicited tactile inputs similarly to native tactile inputs. The ability of electrically elicited tactile inputs to cause postural adjustments suggests that these inputs are incorporated into sensorimotor control, despite arising from artificial nerve stimulation. These results are encouraging for application of neural stimulation in restoring missing sensory feedback after limb loss and suggest PNS could provide an alternate method to perturb foot-sole tactile information for investigating integration of tactile feedback with other sensory modalities.
Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases
Authors: Ravanfar Parsa , Loi Samantha M. , Syeda Warda T. , Van Rheenen Tamsyn E. , Bush Ashley I. , Desmond Patricia , Cropley Vanessa L. , Lane Darius J. R. , Opazo Carlos M. , Moffat Bradford A. , Velakoulis Dennis , Pantelis Christos
Published: February 2021

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.
The Effects of 0.01% Atropine on Adult Myopes’ Contrast Sensitivity
Authors: Cheng Ziyun , Mei Jianhui , Cao Suqi , Zhang Ran , Zhou Jiawei , Wang Yuwen
Published: February 2021

Purpose

Atropine at a low concentration is considered a safe and effective treatment to mitigate myopia progression. However, the potential unwanted side effects of administering atropine at a low dose on visual functions other than best corrected visual acuity has not been investigated. In this study, we investigate the short-term (12,16, and 20 h) and long-term (1, 2, and 4 weeks) effects of 0.01% atropine (i.e., 0.1 mg/ml) on contrast sensitivity (CS) in patients with myopia.

Methods

Thirty adults (23.33 ± 2.93 years old) with myopia between -1.00 and -6.00 diopters (D), astigmatism of -1.50 D or less, and anisometropia of 1.00 D or less, participated in this prospective, masked, placebo-controlled, randomized study. The participants were randomly assigned to receive 0.01% atropine or polyvinyl alcohol eye drops once nightly to both eyes for four weeks. CS was measured binocularly at baseline and 12, 16, 20 h, 1, 2, and 4 weeks after the first use of the eye drops.

Results

There was no statistically significant differences of CS found between atropine and placebo-controlled groups in both short-term and long-term. There was no statistically significant interaction effect found between the time and group.

Conclusion

We demonstrated no significant deleterious effect of 0.01% atropine on adult myopes’ CS.
Endothelial Regulation by Exogenous Annexin A1 in Inflammatory Response and BBB Integrity Following Traumatic Brain Injury
Authors: Liu Han , He Junchi , Wu Yue , Du Yang , Jiang Yinghua , Chen Chengzhi , Yu Zhanyang , Zhong Jianjun , Wang Zhigang , Cheng Chongjie , Sun Xiaochuan , Huang Zhijian
Published: February 2021

Background and Target

Following brain trauma, blood–brain barrier (BBB) disruption and inflammatory response are critical pathological steps contributing to secondary injury, leading to high mortality and morbidity. Both pathologies are closely associated with endothelial remodeling. In the present study, we concentrated on annexin A1 (ANXA1) as a novel regulator of endothelial function after traumatic brain injury.

Methods

After establishing controlled cortical impact (CCI) model in male mice, human recombinant ANXA1 (rANXA1) was administered intravenously, followed by assessments of BBB integrity, brain edema, inflammatory response, and neurological deficits.

Result

Animals treated with rANXA1 (1 μg/kg) at 1 h after CCI exhibited optimal BBB protection including alleviated BBB disruption and brain edema, as well as endothelial junction proteins loss. The infiltrated neutrophils and inflammatory cytokines were suppressed by rANXA1, consistent with decreased adhesive and transmigrating molecules from isolated microvessels. Moreover, rANXA1 attenuated the neurological deficits induced by CCI. We further found that the Ras homolog gene family member A (RhoA) inhibition has similar effect as rANXA1 in ameliorating brain injuries after CCI, whereas rANXA1 suppressed CCI-induced RhoA activation.

Conclusion

Our findings suggest that the endothelial remodeling by exogenous rANXA1 corrects BBB disruption and inflammatory response through RhoA inhibition, hence improving functional outcomes in CCI mice.
Scaling Equilibrium Propagation to Deep ConvNets by Drastically Reducing Its Gradient Estimator Bias
Authors: Laborieux Axel , Ernoult Maxence , Scellier Benjamin , Bengio Yoshua , Grollier Julie , Querlioz Damien
Published: February 2021

Equilibrium Propagation is a biologically-inspired algorithm that trains convergent recurrent neural networks with a local learning rule. This approach constitutes a major lead to allow learning-capable neuromophic systems and comes with strong theoretical guarantees. Equilibrium propagation operates in two phases, during which the network is let to evolve freely and then “nudged” toward a target; the weights of the network are then updated based solely on the states of the neurons that they connect. The weight updates of Equilibrium Propagation have been shown mathematically to approach those provided by Backpropagation Through Time (BPTT), the mainstream approach to train recurrent neural networks, when nudging is performed with infinitely small strength. In practice, however, the standard implementation of Equilibrium Propagation does not scale to visual tasks harder than MNIST. In this work, we show that a bias in the gradient estimate of equilibrium propagation, inherent in the use of finite nudging, is responsible for this phenomenon and that canceling it allows training deep convolutional neural networks. We show that this bias can be greatly reduced by using symmetric nudging (a positive nudging and a negative one). We also generalize Equilibrium Propagation to the case of cross-entropy loss (by opposition to squared error). As a result of these advances, we are able to achieve a test error of 11.7% on CIFAR-10, which approaches the one achieved by BPTT and provides a major improvement with respect to the standard Equilibrium Propagation that gives 86% test error. We also apply these techniques to train an architecture with unidirectional forward and backward connections, yielding a 13.2% test error. These results highlight equilibrium propagation as a compelling biologically-plausible approach to compute error gradients in deep neuromorphic systems.
Decoding Spatial Versus Non-spatial Processing in Auditory Working Memory
Authors: Erhart Mira , Czoschke Stefan , Fischer Cora , Bledowski Christoph , Kaiser Jochen
Published: February 2021

Objective

Research on visual working memory has shown that individual stimulus features are processed in both specialized sensory regions and higher cortical areas. Much less evidence exists for auditory working memory. Here, a main distinction has been proposed between the processing of spatial and non-spatial sound features. Our aim was to examine feature-specific activation patterns in auditory working memory.

Methods

We collected fMRI data while 28 healthy adults performed an auditory delayed match-to-sample task. Stimuli were abstract sounds characterized by both spatial and non-spatial information, i.e., interaural time delay and central frequency, respectively. In separate recording blocks, subjects had to memorize either the spatial or non-spatial feature, which had to be compared with a probe sound presented after a short delay. We performed both univariate and multivariate comparisons between spatial and non-spatial task blocks.

Results

Processing of spatial sound features elicited a higher activity in a small cluster in the superior parietal lobe than did sound pattern processing, whereas there was no significant activation difference for the opposite contrast. The multivariate analysis was applied using a whole-brain searchlight approach to identify feature-selective processing. The task-relevant auditory feature could be decoded from multiple brain regions including the auditory cortex, posterior temporal cortex, middle occipital gyrus, and extended parietal and frontal regions.

Conclusion

In summary, the lack of large univariate activation differences between spatial and non-spatial processing could be attributable to the identical stimulation in both tasks. In contrast, the whole-brain multivariate analysis identified feature-specific activation patterns in widespread cortical regions. This suggests that areas beyond the auditory dorsal and ventral streams contribute to working memory processing of auditory stimulus features.
Breastfeeding Rate, Food Supplementation, Dietary Diversity Among Children Aged 6–59 Months, and Associated Factors in Papua New Guinea
Authors: Pham Bang Nguyen , Silas Vinson D. , Okely Anthony D. , Pomat William
Published: February 2021

Background: Along the socioeconomic changes in the past decades, Papua New Guinea (PNG) has undergone significant food transition. Little is known about the influence of household and maternal socioeconomic demographic factors on dietary intake and diversity among children under 5 years of age (CU5).

Objective: This study aimed to examine breastfeeding rate, food supplementation, dietary intake, and diversity among children aged 6–59 months and to identify associations with household and maternal socioeconomic demographic factors in PNG.

Method: Data from 2,943 children were extracted from the Comprehensive Health and Epidemiological Surveillance System database, operated by the PNG Institute of Medical Research and used to estimate breastfeeding rate, food supplementation, and dietary intake of CU5 in a typical week. Dietary diversity score (DDS) was used as a proxy indicator to measure nutrient adequacy. Associations of DDS with household and maternal socioeconomic and demographic factors were examined using multivariate logistic regression analysis.

Result: The breastfeeding rate among children aged 6–8 months was 85% (70% in urban and 90% in rural sectors), and 50% of children of this age group were fed with supplementary foods. Twenty percent of children aged 6–23 months were currently breastfed and received solid, semisolid, and soft foods three times or more per day. Forty-eight percent of children aged 6–59 months had a total DDS below the average level (23 scores). Place of residence, mother's education, and household wealth were associated with dietary diversity among studied children. Children in urban areas are 10% more likely to have a lower level of total DDS than those in rural areas (OR: 1.11 [0.79–1.56]; p-value: 0.5). Children whose mothers had a primary education level were 1.6-fold more likely to have a lower level of total DDS than children whose mothers had vocational training or college education (OR: 1.63 [0.68–3.92]; p-value: 0.28). Children from the poorest households were 1.2-fold more likely to have a lower DDS than those from the richest households (OR: 1.22 [0.79–1.87]; p-value: 0.37).

Discussion: A range of factors has been identified, contributing to the eating behaviors among CU5 in PNG, in which mother's education and household wealth are among the most important determinants of childhood dietary diversity as they have a direct effect on accessibility to and affordability of a variety of foods at the household level.

Conclusion: Evidence-based integrated and comprehensive approaches are needed to improve women education and household wealth, contributing to the improvement of food diversity among young children in PNG.
Capsule Size Alters the Timing of Metabolic Alkalosis Following Sodium Bicarbonate Supplementation
Authors: Middlebrook India , Peacock Joe , Tinnion Daniel J. , Leach Nicholas K. , Hilton Nathan P. , Saunders Bryan , Sparks S. Andy , Mc Naughton Lars R.
Published: February 2021

Introduction: Sodium bicarbonate (NaHCO3) is a well-established nutritional ergogenic aid that is typically ingested as a beverage or consumed in gelatine capsules. While capsules may delay the release of NaHCO3 and reduce gastrointestinal (GI) side effects compared with a beverage, it is currently unclear whether the capsule size may influence acid–base responses and GI symptoms following supplementation.

Aim: This study aims to determine the effects of NaHCO3 supplementation, administered in capsules of different sizes, on acid–base responses, GI symptoms, and palatability.

Methods: Ten healthy male subjects (mean ± SD: age 20 ± 2 years; height 1.80 ± 0.09 m; weight 78.0 ± 11.9 kg) underwent three testing sessions whereby 0.3 g NaHCO3/kg of body mass was consumed in either small (size 3), medium (size 0), or large (size 000) capsules. Capillary blood samples were procured pre-ingestion and every 10 min post-ingestion for 180 min. Blood samples were analyzed using a radiometer (Radiometer ABL800, Denmark) to determine blood bicarbonate concentration ([HCO3-]) and potential hydrogen (pH). GI symptoms were measured using a questionnaire at the same timepoints, whereas palatability was recorded pre-consumption.

Results: Capsule size had a significant effect on lag time (the time [HCO3-] changed, Tlag) and the timing of peak blood [HCO3-] (Tmax). Bicarbonate Tlag was significantly higher in the large-sized (28 ± 4 min) compared with the small-sized (13 ± 2 min) capsules (P = 0.009). Similarly, Tmax was significantly lower in the small capsule (94 ± 24 min) compared with both the medium-sized (141 ± 27 min; P < 0.001) and the large-sized (121 ± 29 min; P < 0.001) capsules. The GI symptom scores were similar for small-sized (3 ± 3 AU), medium-sized (5 ± 3 AU), and large-sized (3 ± 3 AU) capsules, with no significant difference between symptom scores (F = 1.3, P = 0.310). Similarly, capsule size had no effect on palatability (F = 0.8, P = 0.409), with similar scores between different capsule sizes.

Conclusion: Small capsule sizes led to quicker Tlag and Tmax of blood [HCO3-] concentration compared to medium and large capsules, suggesting that individuals could supplement NaHCO3 in smaller capsules if they aim to increase extracellular buffering capacity more quickly.
Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
Authors: Zhu Jinyu , Tang Bufu , Lv Xiuling , Meng Miaomiao , Weng Qiaoyou , Zhang Nannan , Li Jie , Fan Kai , Zheng Liyun , Fang Shiji , Xu Min , Ji Jiansong
Published: February 2021

In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and prognosis of hepatocellular carcinoma. RNA sequencing data and corresponding clinical information were obtained from multiple databases. After matching with the apoptotic genes from the Deathbase database, 14 differentially expressed human apoptosis genes were obtained. Using univariate and multivariate Cox regression analyses, two apoptosis genes (BAK1 and CSE1L) were determined to be closely associated with overall survival (OS) in HCC patients. And subsequently experiments also validated that knockdown of BAK1 and CSE1L significantly inhibited cell proliferation and promoted apoptosis in the HCC. Then the two genes were used to construct a prognostic signature and diagnostic models. The high-risk group showed lower OS time compared to low-risk group in the TCGA cohort (P < 0.001, HR = 2.11), GSE14520 cohort (P = 0.003, HR = 1.85), and ICGC cohort (P < 0.001, HR = 4). And the advanced HCC patients showed higher risk score and worse prognosis compared to early-stage HCC patients. Moreover, the prognostic signature was validated to be an independent prognostic factor. The diagnostic models accurately predicted HCC from normal tissues and dysplastic nodules in the training and validation cohort. These results indicated that the two apoptosis-related signature effectively predicted diagnosis and prognosis of HCC and may serve as a potential biomarker and therapeutic target for HCC.
Identification and Validation of a Novel Six-Gene Prognostic Signature of Stem Cell Characteristic in Colon Cancer
Authors: Liang Yichao , Su Qi , Wu Xin
Published: February 2021

Cancer stem cells play crucial roles in the development of colon cancer (COAD). This study tried to explore new markers for predicting the prognosis of colon cancer based on stem cell-related genes. In our study, 424 COAD samples from TCGA were divided into three subtypes based on 412 stem cell-related genes; there were significant differences in prognosis, clinical characteristics, and immune scores between these subtypes. 694 genes were screened between subgroups. Subsequently a six-gene signature (DYDC2, MS4A15, MAGEA1, WNT7A, APOD, and SERPINE1) was established. This model had strong robustness and stable predictive performance in cohorts of different platforms. Taken together, the six-gene signature constructed in this study could be used as a novel prognostic marker for COAD patients.
Multiple Myeloma Cells Alter Adipogenesis, Increase Senescence-Related and Inflammatory Gene Transcript Expression, and Alter Metabolism in Preadipocytes
Authors: Fairfield Heather , Costa Samantha , Falank Carolyne , Farrell Mariah , Murphy Connor S. , D’Amico Anastasia , Driscoll Heather , Reagan Michaela R.
Published: February 2021

Within the bone marrow microenvironment, mesenchymal stromal cells (MSCs) are an essential precursor to bone marrow adipocytes and osteoblasts. The balance between this progenitor pool and mature cells (adipocytes and osteoblasts) is often skewed by disease and aging. In multiple myeloma (MM), a cancer of the plasma cell that predominantly grows within the bone marrow, as well as other cancers, MSCs, preadipocytes, and adipocytes have been shown to directly support tumor cell survival and proliferation. Increasing evidence supports the idea that MM-associated MSCs are distinct from healthy MSCs, and their gene expression profiles may be predictive of myeloma patient outcomes. Here we directly investigate how MM cells affect the differentiation capacity and gene expression profiles of preadipocytes and bone marrow MSCs. Our studies reveal that MM.1S cells cause a marked decrease in lipid accumulation in differentiating 3T3-L1 cells. Also, MM.1S cells or MM.1S-conditioned media altered gene expression profiles of both 3T3-L1 and mouse bone marrow MSCs. 3T3-L1 cells exposed to MM.1S cells before adipogenic differentiation displayed gene expression changes leading to significantly altered pathways involved in steroid biosynthesis, the cell cycle, and metabolism (oxidative phosphorylation and glycolysis) after adipogenesis. MM.1S cells induced a marked increase in 3T3-L1 expression of MM-supportive genes including Il-6 and Cxcl12 (SDF1), which was confirmed in mouse MSCs by qRT-PCR, suggesting a forward-feedback mechanism. In vitro experiments revealed that indirect MM exposure prior to differentiation drives a senescent-like phenotype in differentiating MSCs, and this trend was confirmed in MM-associated MSCs compared to MSCs from normal donors. In direct co-culture, human mesenchymal stem cells (hMSCs) exposed to MM.1S, RPMI-8226, and OPM-2 prior to and during differentiation, exhibited different levels of lipid accumulation as well as secreted cytokines. Combined, our results suggest that MM cells can inhibit adipogenic differentiation while stimulating expression of the senescence associated secretory phenotype (SASP) and other pro-myeloma molecules. This study provides insight into a novel way in which MM cells manipulate their microenvironment by altering the expression of supportive cytokines and skewing the cellular diversity of the marrow.
Multiregional-Based Magnetic Resonance Imaging Radiomics Combined With Clinical Data Improves Efficacy in Predicting Lymph Node Metastasis of Rectal Cancer
Authors: Liu Xiangchun , Yang Qi , Zhang Chunyu , Sun Jianqing , He Kan , Xie Yunming , Zhang Yiying , Fu Yu , Zhang Huimao
Published: February 2021

Objective

To develop and validate a multiregional-based magnetic resonance imaging (MRI) radiomics model and combine it with clinical data for individual preoperative prediction of lymph node (LN) metastasis in rectal cancer patients.

Methods

186 rectal adenocarcinoma patients from our retrospective study cohort were randomly selected as the training (n = 123) and testing cohorts (n = 63). Spearman’s rank correlation coefficient and the least absolute shrinkage and selection operator were used for feature selection and dimensionality reduction. Five support vector machine (SVM) classification models were built using selected clinical and semantic variables, single-regional radiomics features, multiregional radiomics features, and combinations, for predicting LN metastasis in rectal cancer. The performance of the five SVM models was evaluated via the area under the receiver operator characteristic curve (AUC), accuracy, sensitivity, and specificity in the testing cohort. Differences in the AUCs among the five models were compared using DeLong’s test.

Results

The clinical, single-regional radiomics and multiregional radiomics models showed moderate predictive performance and diagnostic accuracy in predicting LN metastasis with an AUC of 0.725, 0.702, and 0.736, respectively. A model with improved performance was created by combining clinical data with single-regional radiomics features (AUC = 0.827, (95% CI, 0.711–0.911), P = 0.016). Incorporating clinical data with multiregional radiomics features also improved the performance (AUC = 0.832 (95% CI, 0.717–0.915), P = 0.015).

Conclusion

Multiregional-based MRI radiomics combined with clinical data can improve efficacy in predicting LN metastasis and could be a useful tool to guide surgical decision-making in patients with rectal cancer.
Treatment-Related Toxicities During Anti-GD2 Immunotherapy in High-Risk Neuroblastoma Patients
Authors: Blom Thomas , Lurvink Roosmarijn , Aleven Leonie , Mensink Maarten , Wolfs Tom , Dierselhuis Miranda , van Eijkelenburg Natasha , Kraal Kathelijne , van Noesel Max , van Grotel Martine , Tytgat Godelieve
Published: February 2021

The introduction of immunotherapy using an anti-GD2 antibody (dinutuximab, ch14.18) has significantly improved survival rates for high-risk neuroblastoma patients. However, this improvement in survival is accompanied by a substantial immunotherapy-related toxicity burden. The primary objective of this study was to describe treatment-related toxicities during immunotherapy with dinutuximab, IL-2, GM-CSF, and isotretinoin. A retrospective, single center analysis of immunotherapy-related toxicities was performed in twenty-six consecutive high-risk neuroblastoma patients who received immunotherapy as maintenance therapy in the Princess Máxima Center (Utrecht, Netherlands). Toxicities were recorded and graded according to the CTCAE. Particular attention was drawn to pain and fever management and toxicities leading to dose modifications of dinutuximab and IL-2. Twenty-three patients (88%) completed all six courses of immunotherapy. Disease progression, isotretinoin-associated liver toxicity, and catheter-related infection in combination with peripheral neuropathy were reasons for immunotherapy discontinuation. The most common grade ≥3 toxicities for courses 1–5, respectively, were pain, catheter-related infections, and fever. In total, 310 grade ≥3 toxicities were recorded in 124 courses. Thirty-three grade 4 toxicities in 19/26 patients and no grade 5 toxicities (death) were seen. Fifty-nine percent of grade ≥3 toxicities were recorded in the two courses with IL-2. Catheter-related bloodstream infections were identified in 81% of patients. Four of these episodes led to intensive care admission followed by full recovery (grade 4).
The Latest Overview of circRNA in the Progression, Diagnosis, Prognosis, Treatment, and Drug Resistance of Hepatocellular Carcinoma
Authors: Xiong Dandan , He Rongquan , Dang Yiwu , Wu Huayu , Feng Zhenbo , Chen Gang
Published: February 2021

Hepatocellular carcinoma (HCC) is one of the main causes of tumor-related deaths worldwide. Due to the lack of obvious early symptoms and the lack of sensitive screening indicators in the early stage of HCC, the vast majority of patients are diagnosed with advanced or metastatic HCC, resulting in dissatisfactory treatment result. Therefore, it is urgent to determine effective and sensitive diagnostic and prognostic indicators and to determine new therapeutic targets. Circular RNA (circRNA) is a type of non-coding RNA that has been neglected for a long time. In recent years, it has been proved to play an important role in the development of many human diseases. Increasing evidence shows that change in circRNA expression has an extensive effect on the biological behavior of HCC. In this study, we comprehensively tracked the latest progress of circRNA in the pathogenesis of HCC, and reviewed its role as a biomarker for diagnosis and prognosis prediction in patients with HCC. In addition, we also summarized the potential of circRNA as therapeutic target in HCC and its relationship with HCC drug resistance, providing clues for the clinical development of circRNA-based therapeutic strategies.
Hypofractionated Radiotherapy in African Cancer Centers
Authors: Swanson William , Kamwa Francesca , Samba Richard , Ige Taofeeq , Lasebikan Nwamaka , Mallum Abba , Ngoma Twalib , Sajo Erno , Elzawawy Ahmed , Incrocci Luca , Ngwa Wilfred
Published: February 2021

In the advent of the coronavirus disease (COVID-19) pandemic, professional societies including the American Society for Radiation Oncology and the National Comprehensive Cancer Network recommended adopting evidence-based hypofractionated radiotherapy (HFRT). HFRT benefits include reduction in the number of clinical visits for each patient, minimizing potential exposure, and reducing stress on the limited workforce, especially in resource-limited settings as in Low-and-Middle-Income Countries (LMICs). Recent studies for LMICs in Africa have also shown that adopting HFRT can lead to significant cost reductions and increased access to radiotherapy. We assessed the readiness of 18 clinics in African LMICs to adopting HFRT. An IRB-approved survey was conducted at 18 RT clinics across 8 African countries. The survey requested information regarding the clinic’s existing equipment and human infrastructure and current practices. Amongst the surveyed clinics, all reported to already practicing HFRT, but only 44% of participating clinics reported adopting HFRT as a common practice. Additionally, most participating clinical staff reported to have received formal training appropriate for their role. However, the survey data on treatment planning and other experience with contouring highlighted need for additional training for radiation oncologists. Although the surveyed clinics in African LMICs are familiar with HFRT, there is need for additional investment in infrastructure and training as well as better education of oncology leaders on the benefits of increased adoption of evidence-based HFRT during and beyond the COVID-19 era.
Mifepristone Repurposing in Treatment of High-Grade Gliomas
Authors: Llaguno-Munive Monserrat , Vazquez-Lopez Maria Ines , Jurado Rafael , Garcia-Lopez Patricia
Published: February 2021

Glioma is the most common and aggressive primary tumor of the central nervous system. The standard treatment for malignant gliomas is surgery followed by chemoradiotherapy. Unfortunately, this treatment has not produced an adequate patient response, resulting in a median survival time of 12–15 months and a 5-year overall survival of <5%. Although new strategies have been sought to enhance patient response, no significant increase in the global survival of glioma patients has been achieved. The option of developing new drugs implies a long and costly process, making drug repurposing a more practical alternative for improving glioma treatment. In the last few years, researchers seeking more effective cancer therapy have pursued the possibility of using anti-hormonal agents, such as mifepristone. The latter drug, an antagonist for progesterone and glucocorticoid receptors, has several attractive features: anti-tumor activity, low cytotoxicity to healthy cells, and modulation of the chemosensitivity of several cancer cell lines in vitro. Hence, the addition of mifepristone to temozolomide-based glioblastoma chemotherapy may lead to a better patient response. The mechanisms by which mifepristone enhances glioma treatment are not yet known. The current review aims to discuss the potential role of mifepristone as an adjuvant drug for the treatment of high-grade gliomas.
Chemotherapy Plus Radiotherapy Versus Chemotherapy Alone for Patients With Peripheral T-Cell Lymphoma, Not Otherwise Specified
Authors: Chen Zegeng , Huang He , Li Xiaoqian , Fang Xiaojie , Wang Zhao , Hong Huangming , Zhang Zhihui , Cai Qingqing , Li Zhiming , Chen Meiting , Yao Yuyi , Pan Fei , Chen Limin , Lin Tongyu
Published: February 2021

Purpose

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a clinically and biologically heterogeneous disease with poor prognosis. As the role of radiation therapy (RT) is still unclear, we carried out this study to evaluate the potential efficacy of RT in PTCL-NOS.

Methods

Patients diagnosed with PTCL-NOS between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching was used to balance the characteristics between patients who received radiotherapy and those who did not receive radiotherapy. In addition, we validated the findings in an external validation cohort retrospectively recruited from two high-capacity cancer center in China between 2006 and 2016. Kaplan-Meier curves and Cox regression models were used for survival analysis.

Results

Of the 2,768 patients with chemotherapy records in the SEER cohort, 27.6% of 844 patients with early-stage disease and 6.8% of 1,924 patients with advanced-stage disease received RT. The application of RT was significantly associated with an improvement in overall survival (5-year OS rate 58.5 versus 35.1%, P <0.001) and disease-specific survival (5-year DSS rate 66.3 versus 44.0%, P <0.001) in the early-stage subgroup, while no apparent survival benefit of adding RT was identified in patients with advanced-stage disease (5-year OS rate 28.7 versus 24.4%, P = 0.089; 5-year DSS rate 32.9 versus 31.3%, P = 0.223). After adjustment, a matched cohort of 1,044 patients (348 in the RT combined with CT group and 696 in the CT alone group) was created. And RT was still significantly associated with a survival benefit in the early-stage subset, but not in the advanced-stage disease group. In the validation cohort with more comprehensive data, RT also significantly improved the survival of early-stage PTCL-NOS patients.

Conclusion

Adding RT was associated with significant improvement in survival in early-stage PTCL-NOS, but the survival benefit of RT was not obvious in advanced-stage disease. The incorporation of RT for treatment in early-stage PTCL-NOS should be highly considered. Further prospective studies with more comprehensive data are needed to evaluate the effectiveness and toxicity of RT in PTCL-NOS.