bluuebunny/crossref_metadata_2025 huggingface dataset:
Building Effective Machine Learning Models for Ankle Joint Power Estimation During Walking Using FMG Sensors
Authors: Heeb Oliver , Barua Arnab , Menon Carlo , Jiang Xianta
Published: April 2022

Ankle joint power is usually determined by a complex process that involves heavy equipment and complex biomechanical models. Instead of using heavy equipment, we proposed effective machine learning (ML) and deep learning (DL) models to estimate the ankle joint power using force myography (FMG) sensors. In this study, FMG signals were collected from nine young, healthy participants. The task was to walk on a special treadmill for five different velocities with a respective duration of 1 min. FMG signals were collected from an FMG strap that consists of 8 force resisting sensor (FSR) sensors. The strap was positioned around the lower leg. The ground truth value for ankle joint power was determined with the help of a complex biomechanical model. At first, the predictors' value was preprocessed using a rolling mean filter. Following, three sets of features were formed where the first set includes raw FMG signals, and the other two sets contained time-domain and frequency-domain features extracted using the first set. Cat Boost Regressor (CBR), Long-Short Term Memory (LSTM), and Convolutional Neural Network (CNN) were trained and tested using these three features sets. The results presented in this study showed a correlation coefficient of R = 0.91 ± 0.07 for intrasubject testing and were found acceptable when compared to other similar studies. The CNN on raw features and the LSTM on time-domain features outperformed the other variations. Aside from that, a performance gap between the slowest and fastest walking distance was observed. The results from this study showed that it was possible to achieve an acceptable correlation coefficient in the prediction of ankle joint power using FMG sensors with an appropriate combination of feature set and ML model.
Processing of Odor Information During the Respiratory Cycle in Mice
Authors: Mori Kensaku , Sakano Hitoshi
Published: March 2022

In the mouse olfactory system, odor signals detected in the olfactory epithelium are converted to a topographic map of activated glomeruli in the olfactory bulb. The map information is then conveyed by projection neurons, mitral cells and tufted cells, to various areas in the olfactory cortex. An odor map is transmitted to the anterior olfactory nucleus by tufted cells for odor identification and recollection of associated memory for learned decisions. For instinct decisions, odor information is directly transmitted to the valence regions in the amygdala by specific subsets of mitral cells. Transmission of orthonasal odor signals through these two distinct pathways, innate and learned, are closely related with exhalation and inhalation, respectively. Furthermore, the retronasal/interoceptive and orthonasal/exteroceptive signals are differentially processed during the respiratory cycle, suggesting that these signals are processed in separate areas of the olfactory bulb and olfactory cortex. In this review article, the recent progress is summarized for our understanding of the olfactory circuitry and processing of odor signals during respiration.
Multi-Centroid Hyperdimensional Computing Approach for Epileptic Seizure Detection
Authors: Pale Una , Teijeiro Tomas , Atienza David
Published: March 2022

Long-term monitoring of patients with epilepsy presents a challenging problem from the engineering perspective of real-time detection and wearable devices design. It requires new solutions that allow continuous unobstructed monitoring and reliable detection and prediction of seizures. A high variability in the electroencephalogram (EEG) patterns exists among people, brain states, and time instances during seizures, but also during non-seizure periods. This makes epileptic seizure detection very challenging, especially if data is grouped under only seizure (ictal) and non-seizure (inter-ictal) labels. Hyperdimensional (HD) computing, a novel machine learning approach, comes in as a promising tool. However, it has certain limitations when the data shows a high intra-class variability. Therefore, in this work, we propose a novel semi-supervised learning approach based on a multi-centroid HD computing. The multi-centroid approach allows to have several prototype vectors representing seizure and non-seizure states, which leads to significantly improved performance when compared to a simple single-centroid HD model. Further, real-life data imbalance poses an additional challenge and the performance reported on balanced subsets of data is likely to be overestimated. Thus, we test our multi-centroid approach with three different dataset balancing scenarios, showing that performance improvement is higher for the less balanced dataset. More specifically, up to 14% improvement is achieved on an unbalanced test set with 10 times more non-seizure than seizure data. At the same time, the total number of sub-classes is not significantly increased compared to the balanced dataset. Thus, the proposed multi-centroid approach can be an important element in achieving a high performance of epilepsy detection with real-life data balance or during online learning, where seizures are infrequent.
Application of High-Tech Solution for Memory Assessment in Patients With Disorders of Consciousness
Authors: Kujawa Katarzyna , Żurek Alina , Gorączko Agata , Zurek Grzegorz
Published: March 2022

Testing cognitive function in patients after severe brain damage is a major clinical challenge. In the absence of both verbal and motor communication, tests commonly used to assess cognitive function are completely or partially undoable for disorders of consciousness patients. The study involved 12 patients with varying degrees of impaired consciousness due to brain damage, with no verbal and motor communication. Memory was assessed in study participants using oculography. Memory tasks were presented in four categories. The total percentage of correctly completed tasks obtained across the group was 39.58%. The most difficult tasks included category C.4 with tasks involving working memory. Regardless of the subjects' level of consciousness, there was no statistically significant difference in the percentage of correct responses obtained in subgroups distinguished by CRS-R score. Eye tracking technology can be successfully used in the assessment of cognitive function, particularly when eye movements are the only channel of communication in individuals after brain damage. We suggest that the cognitive functions of people after brain damage should be further analyzed using eye tracking.
Therapy-Induced Electrophysiological Changes in Primary Progressive Aphasia: A Preliminary Study
Authors: Stalpaert Jara , Standaert Sofie , D’Helft Lien , Miatton Marijke , Sieben Anne , Van Langenhove Tim , Duyck Wouter , van Mierlo Pieter , De Letter Miet
Published: March 2022

Aims

This preliminary study aimed to investigate therapy-induced electrophysiological changes in persons with primary progressive aphasia (PPA). The investigated event-related potential (ERP) components associated with language processing were the mismatch negativity, P300, N400, and P600.

Methods

A linguistic ERP test battery and standardized language assessment were administered in four patients with PPA of which two received speech-language therapy (SLT) and two did not receive therapy. The battery was administered twice with approximately 6 months in between in each patient. The results of the follow-up assessments were compared to the results of the initial assessments.

Results

Although the results of the behavioral language assessment remained relatively stable between the initial and follow-up assessments, changes in the mean amplitudes, onset latencies, and duration of the ERP components were found in the four patients. In the two patients that did not receive SLT, an increased delay in 50% and a decreased mean amplitude in 25% of the measured ERP components were found. The electrophysiological changes found in the patients that received SLT were variable. Interestingly, the mismatch negativity and the N400 effect elicited by the categorical priming paradigm were less delayed and had an increased mean amplitude at the follow-up assessment in the patient with the non-fluent variant who received SLT. In this patient, the P600 component was absent at the initial assessment but present at the follow-up assessment.

Conclusion

Although no clear patterns in electrophysiological changes between patients who received SLT and patients who did not receive SLT were found by our preliminary study, it seems like the SLT induced improvements or compensation mechanisms in some specific language comprehension processes in the patient with the NFV. The results of this study are still preliminary because only four heterogeneous patients were included. Future studies should include larger patient groups of the three clinical variants because the therapy-induced electrophysiological changes might differ depending on the clinical variant and the underlying pathology.
Possible Mechanisms Underlying Neurological Post-COVID Symptoms and Neurofeedback as a Potential Therapy
Authors: Orendáčová Mária , Kvašňák Eugen
Published: March 2022

Theoretical considerations related to neurological post-COVID complications have become a serious issue in the COVID pandemic. We propose 3 theoretical hypotheses related to neurological post-COVID complications. First, pathophysiological processes responsible for long-term neurological complications caused by COVID-19 might have 2 phases: (1) Phase of acute Sars-CoV-2 infection linked with the pathogenesis responsible for the onset of COVID-19-related neurological complications and (2) the phase of post-acute Sars-CoV-2 infection linked with the pathogenesis responsible for long-lasting persistence of post-COVID neurological problems and/or exacerbation of another neurological pathologies. Second, post-COVID symptoms can be described and investigated from the perspective of dynamical system theory exploiting its fundamental concepts such as system parameters, attractors and criticality. Thirdly, neurofeedback may represent a promising therapy for neurological post-COVID complications. Based on the current knowledge related to neurofeedback and what is already known about neurological complications linked to acute COVID-19 and post-acute COVID-19 conditions, we propose that neurofeedback modalities, such as functional magnetic resonance-based neurofeedback, quantitative EEG-based neurofeedback, Othmer’s method of rewarding individual optimal EEG frequency and heart rate variability-based biofeedback, represent a potential therapy for improvement of post-COVID symptoms.
Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease
Authors: Vishweswaraiah Sangeetha , Akyol Sumeyya , Yilmaz Ali , Ugur Zafer , Gordevičius Juozas , Oh Kyung Joon , Brundin Patrik , Radhakrishna Uppala , Labrie Viviane , Graham Stewart F.
Published: March 2022

Parkinson’s disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer’s disease. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolomics and epigenetics (genome-wide DNA methylation; epimetabolomics) to profile the frontal lobe from people who died from PD and compared them with age-, and sex-matched controls. We identified 48 metabolites to be at significantly different concentrations (FDR q < 0.05), 4,313 differentially methylated sites [5’-C-phosphate-G-3’ (CpGs)] (FDR q < 0.05) and increased DNA methylation age in the primary motor cortex of people who died from PD. We identified Primary bile acid biosynthesis as the major biochemical pathway to be perturbed in the frontal lobe of PD sufferers, and the metabolite taurine (p-value = 5.91E-06) as being positively correlated with CpG cg14286187 (SLC25A27; CYP39A1) (FDR q = 0.002), highlighting previously unreported biochemical changes associated with PD pathogenesis. In this novel multi-omics study, we identify regulatory mechanisms which we believe warrant future translational investigation and central biomarkers of PD which require further validation in more accessible biomatrices.
User-Independent EMG Gesture Recognition Method Based on Adaptive Learning
Authors: Zheng Nan , Li Yurong , Zhang Wenxuan , Du Min
Published: March 2022

In a gesture recognition system based on surface electromyogram (sEMG) signals, the recognition model established by existing users cannot directly generalize to the across-user scenarios due to the individual variability of sEMG signals. In this article, we propose an adaptive learning method to handle the problem. The muscle synergy is chosen as the feature vector because it can well-characterize the neural origin of movement. The initial train set is composed of representative samples extracted from the synergy matrix of the existing user. When the new users use the system, the label is obtained by the adaptive K nearest neighbor algorithm (KNN). The recognition process does not require the pre-experiment for new users due to the introduction of adaptive learning strategy, namely, the qualified data and the label of new user data evaluated by a risk evaluator are used to update the train set and KNN weights, so as to adapt to the new users. We have tested the algorithm in DB1 and DB5 of Ninapro databases. The average recognition accuracy is 68.04, 73.35, and 83.05% for different types of gestures, respectively, achieving the effects of the user-dependent method. Our study can avoid the re-training steps and the recognition performance will improve with the increased frequency of uses, which will further facilitate the widespread implementation of sEMG control systems using pattern recognition techniques.
Could a Different View of Quiescence Help Us Understand How Neurogenesis Is Regulated?
Authors: Urbán Noelia
Published: March 2022

The majority of adult neural stem cells (aNSCs) are in a distinct metabolic state of reversible cell cycle exit also known as quiescence. The rate of aNSC activation determines the number of new neurons generated and directly influences the long-term maintenance of neurogenesis. Despite its relevance, it is still unclear how aNSC quiescence is regulated. Many factors contribute to this, like aNSC heterogeneity, the lack of reliable quiescence markers, the complexity of the neurogenic niches or the intricacy of the transcriptional and post-transcriptional mechanisms involved. In this perspective article I discuss possible solutions to these problems. But, first and foremost, I believe we require a model that goes beyond a simple transition toward activation. Instead, we must acknowledge the full complexity of aNSC states, which include not only activation but also differentiation and survival as behavioural outcomes. I propose a model where aNSCs dynamically transition through a cloud of highly interlinked cellular states driven by intrinsic and extrinsic cues. I also show how a new perspective enables us to integrate current results into a coherent framework leading to the formulation of new testable hypothesis. This model, like all others, is still far from perfect and will be reshaped by future findings. I believe that having a more complete view of aNSC transitions and embracing their complexity will bring us closer to understand how aNSC activity and neurogenesis are controlled throughout life.
From Reductionism Toward Integration: Understanding How Social Behavior Emerges From Integrated Circuits
Authors: Dickinson Sarah Y. , Kelly Diane A. , Padilla Stephanie L. , Bergan Joseph F.
Published: April 2022

Complex social behaviors are emergent properties of the brain’s interconnected and overlapping neural networks. Questions aimed at understanding how brain circuits produce specific and appropriate behaviors have changed over the past half century, shifting from studies of gross anatomical and behavioral associations, to manipulating and monitoring precisely targeted cell types. This technical progression has enabled increasingly deep insights into the regulation of perception and behavior with remarkable precision. The capacity of reductionist approaches to identify the function of isolated circuits is undeniable but many behaviors require rapid integration of diverse inputs. This review examines progress toward understanding integrative social circuits and focuses on specific nodes of the social behavior network including the medial amygdala, ventromedial hypothalamus (VMH) and medial preoptic area of the hypothalamus (MPOA) as examples of broad integration between multiple interwoven brain circuits. Our understanding of mechanisms for producing social behavior has deepened in conjunction with advances in technologies for visualizing and manipulating specific neurons and, here, we consider emerging strategies to address brain circuit function in the context of integrative anatomy.
Pediococcus acidilactici Promotes the Longevity of C. elegans by Regulating the Insulin/IGF-1 and JNK/MAPK Signaling, Fat Accumulation and Chloride Ion
Authors: Hu Rui , Zhang Yong , Qian Weiyi , Leng Yan , Long Yan , Liu Xinjie , Li Jinping , Wan Xiangyuan , Wei Xun
Published: April 2022

Probiotics are known to contribute to the anti-oxidation, immunoregulation, and aging delay. Here, we investigated the extension of lifespan by fermented pickles-origin Pediococcus acidilactici (PA) in Caenorhabditis elegans (C. elegans), and found that PA promoted a significantly extended longevity of wild-type C. elegans. The further results revealed that PA regulated the longevity via promoting the insulin/IGF-1 signaling, JNK/MAPK signaling but not TOR signaling in C. elegans, and that PA reduced the reactive oxygen species (ROS) levels and modulated expression of genes involved in fatty acids uptake and lipolysis, thus reducing the fat accumulation in C. elegans. Moreover, this study identified the nrfl-1 as the key regulator of the PA-mediated longevity, and the nrfl-1/daf-18 signaling might be activated. Further, we highlighted the roles of one chloride ion exchanger gene sulp-6 in the survival of C. elegans and other two chloride ion channel genes clh-1 and clh-4 in the prolonged lifespan by PA-feeding through the modulating expression of genes involved in inflammation. Therefore, these findings reveal the detailed and novel molecular mechanisms on the longevity of C. elegans promoted by PA.
Effect of Peanut Consumption on Cardiovascular Risk Factors: A Randomized Clinical Trial and Meta-Analysis
Authors: Parilli-Moser Isabella , Hurtado-Barroso Sara , Guasch-Ferré Marta , Lamuela-Raventós Rosa M.
Published: April 2022

Although numerous studies have reported the protective effect of nut consumption on cardiovascular risk, evidence for the role of peanuts in maintaining cardiometabolic health is inconclusive. Presented here are the results from the ARISTOTLE study, a parallel randomized controlled trial evaluating the impact of regular peanut intake on anthropometric, biochemical, and clinical measurements. The 63 healthy subjects that completed the study consumed their habitual diet plus either: a) 25 g/day of skin roasted peanuts (SRP, n = 21), b) two tablespoons (32 g)/day of peanut butter (PB, n = 23) or c) two tablespoons (32 g)/day of a control butter based on peanut oil (CB, n = 19) for 6 months. In addition, a meta-analysis of clinical trials, including data from the ARISTOTLE study, was carried out to update the evidence for the effects of consuming peanuts, including high-oleic peanuts, and peanut butter on healthy subjects and those at high cardiometabolic risk. After a systematic search on PubMed, Web of Science, Cochrane Library and Scopus databases up to July 2021, 11 studies were found to meet the eligibility criteria. In the ARISTOTLE study, lower total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios were found in the SRP group compared to the CB group (p = 0.019 and p = 0.008). The meta-analysis of clinical trials revealed that peanut consumption is associated with a decrease in triglycerides (MD: −0.13; 95% CI, −0.20 to −0.07; p < 0.0001) and that healthy consumers had lower total cholesterol and LDL-cholesterol/HDL-cholesterol ratios compared to the control groups (MD: −0.40; 95% CI, −0.71 to −0.09; p = 0.01 and MD: −0.19; 95% CI, −0.36 to −0.01; p = 0.03, respectively). However, individuals at high cardiometabolic risk experienced an increase in body weight after the peanut interventions (MD: 0.97; 95% CI, 0.54 to 1.41; p < 0.0001), although not in body fat or body mass index. According to the dose-response analyses, body weight increased slightly with higher doses of peanuts. In conclusion, a regular consumption of peanuts seems to modulate lipid metabolism, reducing triglyceride blood levels.

Systematic Review Registration

https://osf.io/jx34y/, identifier: 10.17605/OSF.IO/MK35Y.
Prognostic Effect of Age in Resected Pancreatic Cancer Patients: A Propensity Score Matching Analysis
Authors: Xu Yaolin , Zhang Yueming , Han Siyang , Jin Dayong , Xu Xuefeng , Kuang Tiantao , Wu Wenchuan , Wang Dansong , Lou Wenhui
Published: March 2022

Background

While the elderly population account for an indispensable proportion in pancreatic ductal adenocarcinoma (PDAC), these patients are underrepresented in clinical trials. Whether surgery offered the same benefit for elderly patients as that for younger cohort and which factors affected long-term outcome of elderly population remained unclear.

Aims

This study aims to evaluate long-term prognosis of elderly PDAC patients (≥70 years old) after surgery and to investigate potential prognostic factors.

Methods

This retrospective study included PDAC patients receiving radical resection from January 2012 to July 2019 in Zhongshan Hospital Fudan University. Patients were divided into young (<70) and old groups (≥70). Propensity score matching (PSM) was conducted to eliminate the confounding factors. We investigated potential prognostic factors via Cox proportional hazards model and Kaplan–Meier estimator. Nomogram model and forest plot were constructed to illustrate the prognostic value of age.

Results

A total of 552 PDAC patients who received radical resection were included in this research. Elderly patients showed poorer nutritional status and were less likely to received adjuvant treatment. After matching, although age [hazard ratio (HR)=1.025, 95%CI 0.997–1.054; p=0.083] was not statistically significant in the multivariate cox regression analysis, further survival analysis showed that patients in the old group had poorer overall survival (OS) when compared with young group (p=0.039). Furthermore, reception of adjuvant chemotherapy (HR=0.411, 95%CI 0.201-0.837; p=0.014) was the only independent prognostic factor among elderly patients and could significantly improve OS. Subgroup analysis indicated that age had better prognostic value in PDAC patients with good preoperative nutritional status and relative low tumor burden. Finally, a prognostic prediction model contained age, reception of adjuvant chemotherapy, American Joint Committee on Cancer (AJCC) 8th T and N stage was constructed and presented in nomogram, whose Harrell’s concordance index was 0.7478 (95%CI, 0.6960–0.7996). The calibration curves at 1 and 3 years indicated an optimal conformity between actual and nomogram-predicted survival probability in the PDAC patient who received surgery.

Conclusion

The elderly PDAC patients were associated with worse OS survival after radical resection, and the noticeable negative effect of age was observed among PDAC patients with better preoperative nutritional status and less aggressive tumor biology. Adjuvant chemotherapy was essential to improve survival outcome of elderly PDAC patients following radical resection.
The Prognostic Value and Immune Infiltration of USP10 in Pan-Cancer: A Potential Therapeutic Target
Authors: Gao Dacheng , Zhang Zhiwen , Xu Rui , He Ziyang , Li Fangyi , Hu Yan , Chen Hui , Lu Jiawei , Cao Xingguo , Liu Yali , Xu Zengguang
Published: March 2022

Ubiquitin-specific peptidase 10 (USP10) can sustain cellular functions and regulate cellular processes. It plays an essential role in cancer inhibition or facilitation by reversing ubiquitin-proteasome degradation. Studies have identified USP10 to be involved in tumor progression in various cancers. However, the pan-cancer expression pattern of USP10, its prognostic value, and the association between tumor immune cell infiltration and USP10 expression remain to be discussed and thus comprised the aims of the present study. Based on clinical samples and bioinformatic analyses, high USP10 expression was observed in most cancer tissues except for ovarian cancer. High USP10 expression correlated with pathological stage and node metastasis and predicted poor patient prognosis. In addition, further analyses at the TIMER and GEPIA databases showed that USP10 is involved in the infiltration of multiple immune cells and regulated the infiltration levels of specific immune cell subpopulations, particularly in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). Importantly, USP10 might influence survival by modulating immune infiltration in patients with PAAD and LIHC. These results identified USP10 as a potential biomarker for pan-cancer prognosis, and in certain cancers, USP10 could identify clinical prognosis linked to tumor immune infiltration.
NRAGE Confers Radiation Resistance in 2D and 3D Cell Culture and Poor Outcome in Patients With Esophageal Squamous Cell Carcinoma
Authors: Zhou Huandi , Wang Guohui , Xiao Zhiqing , Yang Yu , Tian Zhesen , Gao Chen , Han Xuetao , Sun Wei , Hou Liubing , Liu Junling , Xue Xiaoying
Published: April 2022

Objective

The purpose of the study is to explore the mechanism of NRAGE enhancing radioresistance of esophageal squamous cell carcinoma (ESCC) in 2D and 3D levels.

Methods

Stably NRAGE-overexpressed ESCC cells and 3D-printing models for ESCC cells were established. Then, cellular malignancy indexes, such as cell morphology, proliferation, radioresistance, motility, apoptosis, cell cycle, and proteins of the Wnt/β-catenin pathway, were compared between radioresistant and its parental cells in 2D and 3D levels. Additionally, 44 paraffin ESCC specimens with radical radiotherapy were selected to examine NRAGE and β-catenin protein expression and analyze the clinical correlation.

Results

Experiments in 2D culture showed that morphology of the Eca109/NRAGE cells was more irregular, elongated spindle-shaped and disappeared polarity. It obtained faster growth ability, stronger resistance to irradiation, enhanced motility, reduced apoptosis ratio and cell cycle rearrangement. Moreover, Western blot results showed β-catenin, p-Gsk-3β and CyclinD1 expressions were induced, while p-β-catenin and Gsk-3β expressions decreased in Eca109/NRAGE cells. Experiments in the 3D-printing model showed Eca109/NRAGE cell-laden 3D scaffolds had the advantage on growth and spheroiding according to the brightfield observation, scanning electron microscopy and Ki-67 IHC staining, and higher expression at the β-catenin protein. Clinical analysis showed that NRAGE expression was higher in tumor tissues than in control tissues of ESCC patients from the Public DataBase. Compared with radiotherapy effective group, both NRAGE total and nuclear and β-catenin nuclear expressions were significantly upregulated from ESCC specimens in invalid group. Further analysis showed a positive and linear correlation between NRAGE nuclear and β-catenin nuclear expressions. Additionally, results from univariate and multivariate analyses revealed NRAGE nuclear expression could serve as a risk factor for ESCC patients receiving radical radiotherapy.

Conclusion

ESCC cells with NRAGE nuclear accumulation demonstrated greater radioresistance, which may be related to the activation of the Wnt/β-catenin signaling pathway. It indicated that NRAGE nuclear expression was a potential biomarker for monitoring radiotherapeutic response.
A Geriatric Assessment Intervention to Reduce Treatment Toxicity Among Older Adults With Advanced Lung Cancer: A Subgroup Analysis From a Cluster Randomized Controlled Trial
Authors: Presley Carolyn J. , Mohamed Mostafa R. , Culakova Eva , Flannery Marie , Vibhakar Pooja H. , Hoyd Rebecca , Amini Arya , VanderWalde Noam , Wong Melisa L. , Tsubata Yukari , Spakowicz Daniel J. , Mohile Supriya G.
Published: March 2022

Introduction

More older adults die from lung cancer worldwide than breast, prostate, and colorectal cancers combined. Current lung cancer treatments may prolong life, but can also cause considerable treatment-related toxicity.

Objective

This study is a secondary analysis of a cluster-randomized clinical trial which evaluated whether providing a geriatric assessment (GA) summary and GA-guided management recommendations can improve grade 3-5 toxicity among older adults with advanced lung cancer.

Methods

We analyzed participants aged ≥70 years(y) with stage III & IV (advanced) lung cancer and ≥1 GA domain impairment starting a new cancer treatment with high-risk of toxicity within the National Cancer Institute’s Community Oncology Research Program. Community practices were randomized to the intervention arm (oncologists received GA summary & recommendations) versus usual care (UC: no summary or recommendations given). The primary outcome was grade 3-5 toxicity through 3 months post-treatment initiation. Secondary outcomes included 6-month (mo) and 1-year overall survival (OS), treatment modifications, and unplanned hospitalizations. Outcomes were analyzed using generalized linear mixed and Cox proportional hazards models with practice site as a random effect. Trial Registration: NCT02054741.

Results & Conclusion

Among 180 participants with advanced lung cancer, the mean age was 76.3y (SD 5.1), 39.4% were female and 82.2% had stage IV disease. The proportion of patients who experienced grade 3-5 toxicity was significantly lower in the intervention arm vs UC (53.1% vs 71.6%, P=0.01). More participants in the intervention arm received lower intensity treatment at cycle 1 (56.3% vs 35.3%; P<0.01). Even with a cycle 1 dose reduction, OS at 6mo and 1 year was not significantly different (adjusted hazard ratio [HR] intervention vs. UC: 6mo HR=0.90, 95% CI: 0.52-1.57, P=0.72; 1 year HR=0.89, 95% CI: 0.58-1.36, P=0.57). Frequent toxicity checks, providing education and counseling materials, and initiating direct communication with the patient’s primary care physician were among the most common GA-guided management recommendations. Providing a GA summary and management recommendations can significantly improve tolerability of cancer treatment among older adults with advanced lung cancer.
Generation of Tumor-Specific Cytotoxic T Cells From Blood via In Vitro Expansion Using Autologous Dendritic Cells Pulsed With Neoantigen-Coupled Microbeads
Authors: Kiessling Adela , Ramanathan Keerthana , Nilsson Ola B. , Notari Luigi , Renken Stefanie , Kiessling Rolf , Grönlund Hans , Wickström Stina L.
Published: March 2022

For the past decade, adoptive cell therapy including tumor-infiltrating lymphocytes, genetically modified cytotoxic lymphocytes expressing a chimeric antigen receptor, or a novel T-cell receptor has revolutionized the treatment of many cancers. Progress within exome sequencing and neoantigen prediction technologies provides opportunities for further development of personalized immunotherapies. In this study, we present a novel strategy to deliver in silico predicted neoantigens to autologous dendritic cells (DCs) using paramagnetic beads (EpiTCer beads). DCs pulsed with EpiTCer beads are superior in enriching for healthy donor and patient blood-derived tumor-specific CD8+ T cells compared to DC loaded with whole-tumor lysate or 9mer neoantigen peptides. A dose-dependent effect was observed, with higher EpiTCer bead per DC being favorable. We concluded that CD8+ T cells enriched by DC loaded with EpiTCer beads are tumor specific with limited tumor cross-reactivity and low recognition of autologous non-activated monocytes or CD8+ T cells. Furthermore, tumor specificity and recognition were improved and preserved after additional expansion using our Good Manufacturing Process (GMP)-compatible rapid expansion protocol. Phenotypic analysis of patient-derived EpiTCer DC expanded CD8+ T cells revealed efficient maturation, with high frequencies of central memory and effector memory T cells, similar to those observed in autologous expanded tumor-infiltrating lymphocytes. These results indicate that DC pulsed with EpiTCer beads enrich for a T-cell population with high capacity of tumor recognition and elimination, which are features needed for a T-cell product to be used for personalized adoptive cell therapy.
Expression of Helper and Regulatory T Cells in Atopic Dermatitis: A Meta-Analysis
Authors: Zhang Dao-jun , Hao Fei , Qian Tian , Cheng Hai-xing
Published: April 2022

Background

Atopic dermatitis (AD) is a common inflammatory skin disease, with the incidence peaks in infancy. A meta-analysis was performed to assess the levels of T helper type 22 (Th22) cells, T helper type 17 (Th17) cells, interleukin (IL)-17, and Tregs in peripheral blood of patients with AD.

Methods

A comprehensive literature search was performed in PubMed, Embase, China National Knowledge Internet, and Wan-fang Data from the day of inception of this study to July 2021. Two authors independently extracted the data, which were pooled and calculated using Stata software version 15.

Results

A total of eight studies met the inclusion criteria. Compared with control group, patients with AD had an increased proportion of Th22 cells [weighted mean difference (WMD) = 2.07, 95% CI (1.33, 2.81), p < 0.001], Th17 cells [WMD = 1.04, 95% CI [0.66, 1.43], p < 0.001], IL-17 [WMD = 17.56, 95% CI (11.1, 24.03), p < 0.001], and a decreased proportion of Tregs [WMD = −2.49, 95% CI (−2.93, −2.05), p < 0.001] in peripheral blood. The subgroup analysis showed that patients with higher disease severity had higher levels of Th22 [mild: WMD = 1.33, 95% CI (1.24, 1.41), p < 0.001; moderate: WMD = 1.41, 95% CI (1.36, 1.54), p < 0.001; severe: WMD = 3.46, 95% CI (3.34, 2.81), p < 0.001] and lower levels of Tregs [mild: WMD = −1.43, 95% CI (−1.75, −1.11), p < 0.001; moderate: WMD = −2.16, 95% CI (−2.46, −1.86), p < 0.001; severe: WMD = −2.96, 95% CI (−3.25, −2.67), p < 0.001] in peripheral blood compared to healthy controls.

Conclusion

The random effect model of the meta-analysis showed patients with AD had an increased proportion of Th22 cells, Th17 cells, and IL-17, whereas a decreased proportion of Tregs was found in peripheral blood. The results demonstrated that Th22 cells, Th17 cells, IL-17, and Tregs may be involved in the pathogenic mechanisms of AD.
The Relationship Between Lipoprotein-Associated Phospholipase-A2 and Coronary Artery Aneurysm in Children With Kawasaki Disease
Authors: Cheng Zhenli , Weng Haobo , Zhang Jing , Yi Qijian
Published: March 2022

Background

Coronary artery lesions including aneurysm, as the most severe complications of Kawasaki disease (KD), remain of great concern. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is implicated in the regulation of inflammatory response and lipid metabolism. Since excessive inflammatory response and aberrant lipid metabolism have involved in the development of KD, we in this study sought to investigate the relationship between coronary artery aneurysm (CAA) and Lp-PLA2 and other blood parameters in children with KD.

Methods

The participants included 71 KD patients, 63 healthy controls (HCs) and 51 febrile controls (FCs). KD patients were divided into KD-CAA (KD with CAA) group and KD-NCAA (KD without CAA) group. Serum Lp-PLA2 levels were measured using enzyme-linked immunosorbent assays. Other routine clinical parameters were also detected.

Results

Serum Lp-PLA2 levels in KD group [4.83 μg/mL (3.95–6.77)] were significantly higher than those in HC [1.29 μg/mL (0.95–2.05)] and FC [1.74 μg/mL (1.18–2.74)] groups. KD-CAA group [5.56 μg/mL (4.55–22.01)] presented substantially higher serum Lp-PLA2 levels as compared with KD-NCAA group [4.64 μg/mL (2.60–5.55)]. In KD group, serum Lp-PLA2 level was positively related with erythrocyte sedimentation rate, the levels of leukocytes, platelets, albumin, creatine kinase-MB, and D-dimer, and the Z-scores of left main CA, right CA, left anterior descending CA, and left circumflex CA; and negatively related with mean corpuscular hemoglobin concentration and mean platelet volume. Moreover, receiver operating characteristic curves showed that Lp-PLA2 exhibited superior and moderate diagnostic performance for distinguishing KD patients from HC and FC ones, respectively, and possessed the potential ability to predict the occurrence of CAAs in KD.

Conclusion

Lp-PLA2 may be related to KD and the formation of CAAs, and thus may serve as a potential diagnostic biomarker for KD.
Case Report: COVID-19-Associated ROHHAD-Like Syndrome
Authors: Artamonova Irina N. , Petrova Natalia A. , Lyubimova Natalia A. , Kolbina Natalia Yu , Bryzzhin Alexander V. , Borodin Alexander V. , Levko Tatyana A. , Mamaeva Ekaterina A. , Pervunina Tatiana M. , Vasichkina Elena S. , Nikitina Irina L. , Zlotina Anna M. , Efimtsev Alexander Yu. , Kostik Mikhail M.
Published: March 2022

It is known that the SARS-CoV-2 virus may cause neurologic damage. Rapid-onset obesity, hypoventilation, hypothalamus dysfunction, and autonomic dysregulation (ROHHAD) syndrome is a disease of unknown etiology with a progressive course and unclear outcomes. The etiology of ROHHAD syndrome includes genetic, epigenetic, paraneoplastic, and immune-mediated theories, but to our knowledge, viral-associated cases of the disease have not been described yet. Here we present the case of a 4-year-old girl who developed a ROHHAD syndrome-like phenotype after a COVID-19 infection and the results of 5 months of therapy. She had COVID-19 pneumonia, followed by electrolyte disturbances (hypernatremia and hyperchloremia), hypocorticism and hypothyroidism, central hypoventilation—requiring prolonged assisted lung ventilation—bulimia, and progressive obesity with hypertriglyceridemia, dyslipidemia, hyperuricemia, and hyperinsulinemia. The repeated MRI of the brain and hypothalamic–pituitary region with contrast enhancement showed mild post-hypoxic changes. Prader–Willi/Angelman syndrome as well as PHOX2B-associated variants was ruled out. Treatment with non-steroidal anti-inflammatory drugs and monthly courses of intravenous immunoglobulin led to a dramatic improvement. Herein the first description of ROHHAD-like syndrome is timely associated with a previous COVID-19 infection with possible primarily viral or immune-mediated hypothalamic involvement.
Practical Considerations for Use of Direct Oral Anticoagulants in Children
Authors: Whitworth Hilary , Raffini Leslie
Published: April 2022

Direct oral anticoagulants (DOACs) provide an attractive alternative for the management and prevention of thrombosis in pediatric patients. With multiple ongoing and published pediatric trials and recent regulatory approval of dabigatran and rivaroxaban, the landscape of pediatric anticoagulation is rapidly changing. However, as pediatricians gain experience with these drugs, it is important to be mindful of pediatric-specific considerations that may limit the use of DOACs in certain children and adolescents. While there is increasing adult data and experience, there is a paucity of real-world evidence to guide the use of these drugs in children who would not have met clinical trial inclusion criteria. In this mini review, we summarize pediatric specific data, areas for future research, and practical considerations for the use of DOACs in children and adolescents.
Efficacy and Safety of Intranasal Dexmedetomidine vs. Oral Chloral Hydrate for Sedation in Children Undergoing Computed Tomography/Magnetic Resonance Imaging: A Meta-Analysis
Authors: Lyu Xiaoqian , Tao Yujuan , Dang Xiujing
Published: March 2022

Objective

This meta-analysis aims to evaluate the sedative efficacy and safety of intranasal administration of dexmedetomidine (DEX) compared with oral chloral hydrate for Computed tomography (CT) or Magnetic Resonance Imaging (MRI) examination in Children.

Methods

Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and China WanFang Databases were searched to collect randomized controlled trials (RCTs) investigating intranasal DEX (test group) vs. oral chloral hydrate (control group) in pediatric CT/MRI examinations up to December 30, 2021. The data were analyzed using Stata 15.0 software.

Results

Seven RCTs with 1,846 children were identified. The meta-analysis results showed that the success rate of sedation (RR = 1.14, 95% CI: 1.03–1.26, P = 0.011), sedation onset time [weighted mean difference (WMD) = –0.87, 95% CI: –1.42 to –0.31, P = 0.002], sedation duration (WMD = –9.05, 95% CI:-14.69 to –3.42, P = 0.002), time to awakening (WMD = –9.75, 95% CI:-17.57 to –1.94, P = 0.014), and incidence of nausea and vomiting [relative risk (RR) = 0.09, 95% CI:0.04–0.23, P < 0.001) of the test group were significantly better than those of the control group. However, no significant differences were identified in incidence of hypotension (RR = 1.18, 95% CI: 0.51–2.74) and bradycardia (RR = 1.17, 95% CI: 0.13–22.11) between the two groups.

Conclusion

Intranasal administration of DEX is superior to oral chloral hydrate for sedation during pediatric CT/MRI examinations and has a better safety profile.
The Use of Artificial Intelligence in Complementary and Alternative Medicine: A Systematic Scoping Review
Authors: Chu Hongmin , Moon Seunghwan , Park Jeongsu , Bak Seongjun , Ko Youme , Youn Bo-Young
Published: April 2022

Background: The development of artificial intelligence (AI) in the medical field has been growing rapidly. As AI models have been introduced in complementary and alternative medicine (CAM), a systematized review must be performed to understand its current status.

Objective: To categorize and seek the current usage of AI in CAM.

Method: A systematic scoping review was conducted based on the method proposed by the Joanna Briggs Institute. The three databases, PubMed, Embase, and Cochrane Library, were used to find studies regarding AI and CAM. Only English studies from 2000 were included. Studies without mentioning either AI techniques or CAM modalities were excluded along with the non-peer-reviewed studies. A broad-range search strategy was applied to locate all relevant studies.

Results: A total of 32 studies were identified, and three main categories were revealed: 1) acupuncture treatment, 2) tongue and lip diagnoses, and 3) herbal medicine. Other CAM modalities were music therapy, meditation, pulse diagnosis, and TCM syndromes. The majority of the studies utilized AI models to predict certain patterns and find reliable computerized models to assist physicians.

Conclusion: Although the results from this review have shown the potential use of AI models in CAM, future research ought to focus on verifying and validating the models by performing a large-scale clinical trial to better promote AI in CAM in the era of digital health.
Radix Astragalus Polysaccharide Accelerates Angiogenesis by Activating AKT/eNOS to Promote Nerve Regeneration and Functional Recovery
Authors: Zhang Geyi , Huang Jinsheng , Hao Shuang , Zhang Jingchao , Zhou Nan
Published: April 2022

Peripheral nerve injury (PNI) results in loss of neural control and severe disabilities in patients. Promoting functional nerve recovery by accelerating angiogenesis is a promising neuroprotective treatment strategy. Here, we identified a bioactive Radix Astragalus polysaccharide (RAP) extracted from traditional Chinese medicine (TCM) as a potent enhancer of axonal regeneration and remyelination. Notably, RAP promoted functional recovery and delayed gastrocnemius muscle atrophy in a rat model of sciatic nerve crush injury. Further, RAP treatment may induce angiogenesis in vivo. Moreover, our in vitro results showed that RAP promotes endothelial cell (EC) migration and tube formation. Altogether, our results show that RAP can enhance functional recovery by accelerating angiogenesis, which was probably related to the activation of AKT/eNOS signaling pathway, thereby providing a polysaccharide-based therapeutic strategy for PNI.
Hormone Therapy: A Potential Risk Factor Affecting Survival and Functional Restoration of Transplanted Lymph Nodes
Authors: Dong Dong , Wang Heng , Chen Liang , Wang Wei , Liu Tianyi
Published: March 2022

Background: Transplantation of lymph nodes (LNs) is an increasingly popular option for treating lymphedema. Increasing evidence indicates an intrinsic correlation between estrogen signaling and the lymphatic system. We explored the effects of 17β estradiol and antiestrogen treatment (tamoxifen) on the survival and functional restoration of transplanted popliteal lymph nodes (PLNs).

Methods: A total of forty-eight ovariectomized mice were divided into three groups of 16: OVX + E2 (treated with 17β-estradiol), OVX + TMX (treated with tamoxifen), and OVX (control; treated with olive oil as a solvent). After 2 weeks, PLNs were transplanted. Then, reconnections of lymphatic vessels were observed, and the morphology and survival of transplanted PLNs were evaluated 4 weeks after transplantation. T cells, B cells, lymphatic vessels, and high endothelial venules (HEVs) were subjected to immunofluorescence staining or immunohistochemical staining and quantified.

Results: The percentage of lymphatic reconnections was 93.75% in the OVX + E2 group, 68.75% in the OVX + TMX group, and 75% in the OVX group. Surviving PLNs were observed in 16 of 16 in the OVX + E2 group, seven of 16 in the OVX + TMX group, and 13 of 16 in the OVX group. The mean size of PLNs in the largest cross section of the OVX + TMX group was significantly lower than that in the other groups. The distributions of B cells and T cells in surviving PLNs were similar to those in normal LNs. The ratio of dilated HEVs/total HEVs and density of lymphatic vessels in the OVX + E2 group were the highest among the three groups, whereas the lowest ratio and density were observed in the OVX + TMX group.

Conclusion: Tamoxifen treatment might lead to cellular loss of transplanted LNs and interfere with the structural reconstruction and functional restoration, thereby inhibiting the survival of transplanted PLNs. Estrogen treatment facilitated the maintenance and regeneration of functional HEVs as well as lymphangiogenesis.