bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence-Assisted Score Analysis for Predicting the Expression of the Immunotherapy Biomarker PD-L1 in Lung Cancer
Authors: Cheng Guoping , Zhang Fuchuang , Xing Yishi , Hu Xingyi , Zhang He , Chen Shiting , Li Mengdao , Peng Chaolong , Ding Guangtai , Zhang Dadong , Chen Peilin , Xia Qingxin , Wu Meijuan
Published: July 2022

Programmed cell death ligand 1 (PD-L1) is a critical biomarker for predicting the response to immunotherapy. However, traditional quantitative evaluation of PD-L1 expression using immunohistochemistry staining remains challenging for pathologists. Here we developed a deep learning (DL)-based artificial intelligence (AI) model to automatically analyze the immunohistochemical expression of PD-L1 in lung cancer patients. A total of 1,288 patients with lung cancer were included in the study. The diagnostic ability of three different AI models (M1, M2, and M3) was assessed in both PD-L1 (22C3) and PD-L1 (SP263) assays. M2 and M3 showed improved performance in the evaluation of PD-L1 expression in the PD-L1 (22C3) assay, especially at 1% cutoff. Highly accurate performance in the PD-L1 (SP263) was also achieved, with accuracy and specificity of 96.4 and 96.8% in both M2 and M3, respectively. Moreover, the diagnostic results of these three AI-assisted models were highly consistent with those from the pathologist. Similar performances of M1, M2, and M3 in the 22C3 dataset were also obtained in lung adenocarcinoma and lung squamous cell carcinoma in both sampling methods. In conclusion, these results suggest that AI-assisted diagnostic models in PD-L1 expression are a promising tool for improving the efficiency of clinical pathologists.
Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Authors: Miao Kang , Zhang Xiaotong , Wang Hanping , Si Xiaoyan , Ni Jun , Zhong Wei , Zhao Jing , Xu Yan , Chen Minjiang , Pan Ruili , Wang Mengzhao , Zhang Li
Published: July 2022

Background

Non–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.

Methods

To explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.

Results

The two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.

Conclusion

Peripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs.
Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis
Authors: Wang Qian , Sun Zhenzhen , Cao Shihan , Lin Xiuli , Wu Mengying , Li Yuanyuan , Yin Jie , Zhou Wei , Huang Songming , Zhang Aihua , Zhang Yue , Xia Weiwei , Jia Zhanjun
Published: July 2022

Cardiac dysfunction is manifested as decline of cardiac systolic function, and multiple cardiovascular diseases (CVDs) can develop cardiac insufficiency. Mitochondrial antiviral signaling (MAVS) is known as an innate immune regulator involved in viral infectious diseases and autoimmune diseases, whereas its role in the heart remains obscure. The alteration of MAVS was analyzed in animal models with non-hypertrophic and hypertrophic cardiac dysfunction. Then, MAVS-deficient mice were generated to examine the heart function, mitochondrial status and energy metabolism. In vitro, CRISPR/Cas9-based gene editing was used to delete MAVS in H9C2 cell lines and the phenotypes of mitochondria and energy metabolism were evaluated. Here we observed reduced MAVS expression in cardiac tissue from several non-hypertrophic cardiac dysfunction models, contrasting to the enhanced MAVS in hypertrophic heart. Furthermore, we examined the heart function in mice with partial or total MAVS deficiency and found spontaneously developed cardiac pump dysfunction and cardiac dilation as assessed by echocardiography parameters. Metabonomic results suggested MAVS deletion probably promoted cardiac dysfunction by disturbing energy metabolism, especially lipid metabolism. Disordered and mitochondrial homeostasis induced by mitochondrial oxidative stress and mitophagy impairment also advanced the progression of cardiac dysfunction of mice without MAVS. Knockout of MAVS using CRISPR/Cas9 in cardiomyocytes damaged mitochondrial structure and function, as well as increased mitochondrial ROS production. Therefore, reduced MAVS contributed to the pathogenesis of non-hypertrophic cardiac dysfunction, which reveals a link between a key regulator of immunity (MAVS) and heart function.
Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer
Authors: Jin Xin , Liu Zhaorui , Yang Dongxiao , Yin Kai , Chang Xusheng
Published: July 2022

As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.
Synthesis and Characterisation of Mg2+ and Al3+ Co-Doped CoCr2O4 Inorganic Pigments With High Near-Infrared Reflectance
Authors: Wei Xueling , Zou Xiangyu , Deng Zhifeng , Bao Weiwei , Ai Taotao , Zhang Qi
Published: July 2022

A new class of near-infrared (NIR) reflectance pigments based on Co1−xMgxCr2−yAlyO4 (x = 0–1 and y = 0–2) was synthesised using the Pechini-type sol-gel process. The developed powders were characterised by thermogravimetry and differential scanning calorimetry, X-ray diffraction (XRD), ultraviolet–visible near-infrared diffuse reflectance spectroscopy, and colour Commission Internationale del'Eclairage (CIE) 1976 (L*a*b*) colour scales. The XRD patterns revealed characteristic peaks of the spinel structure with good crystallinity. Substituting Mg2+ for Co2+ ions in the tetrahedral positions and Al3+ for Cr3+ ions in the octahedral positions of CoCr2O4 reduces the cost and changes the colour of the pigment (green to yellow and then blue). Moreover, the synthesised pigments exhibited high NIR solar reflectance in the 780–2,500 nm wavelength range. The thermal and chemical stability of the pigments was also studied. Our findings demonstrate the potential for applying these pigments in cool colourants.
Management Practices Affecting Lesser Mealworm Larvae (Alphitobius diaperinus) Associated Microbial Community in a Broiler House and After Relocating With the Litter Into Pastureland
Authors: Crippen Tawni L. , Singh Baneshwar , Anderson Robin C. , Sheffield Cynthia L.
Published: July 2022

Lesser mealworms are often found infesting production houses used to raise broiler chickens. Previous studies have investigated pathogenic microorganisms associated with the larvae, but a more thorough study relating total microbiome changes due to management procedures and flock rotations was needed. Additionally, there is a question of what microbiota are transferred into the environment when the litter, in which larvae reside, is piled in pastureland for use as fertilizer and where interactions with the soil and other fauna can occur. This study chronicled, by the 16S rRNA sequencing, the bacterial community profile of larvae in a broiler grow-out house synchronizing to when birds were added to and removed from the house over 2.5 years. The profile was found to be relatively constant despite 11 flock rotations and management disruptions, specifically litter cleanout procedures and the addition of new birds or bedding. In contrast, once removed from the controlled broiler house environment and placed into open pastureland, the substantial microbial diversity brought with the larvae showed greater fluctuation in structure with environmental conditions, one of which was rainfall. Surprisingly, these larvae survived at least 19 weeks, so the potential for moving larval-associated microbes into the environment needs further assessment to minimize the risk of relocating foodborne pathogens and also to assess those bacteria-generating metabolites that have benefits to plant growth when using the litter as a fertilizer. The characterization of their microbiome is the first step to investigating the influences of their microbes on the manmade and environmental ecosystems.
Diagnostic Value and Clinical Application of mNGS for Post-Liver Transplantation Infection: A Cross-Sectional Study With Case Reports
Authors: Zhao Dong , Guo Liping , Lian Dongli , Gu Yuchen , Yan Xu , Hu Hongxing , Yuan Jing
Published: July 2022

Liver transplantation is widely acknowledged as the only effective treatment for end-stage liver disease, and infection is reportedly an important cause of postoperative death. Clinical use of metagenomic next-generation sequencing (mNGS) to diagnose postoperative infection and successfully guide drug therapy remains rare. This study included patients with infectious complications after liver transplantation from July 2019 to December 2020 and was divided into three groups: pneumonia, unknown fever, and others (including hepatic failure, kidney failure, cirrhosis after LT, and other postoperative complications that predispose to infection). The mNGS sequencing was used to detect microorganisms, and the results were compared with traditional culture. We found that mNGS yielded improved sensitivity over culture (85.19 vs. 22.22%; p<0.0001) but lower specificity (35.71 vs. 89.28%; p<0.0001). Among the 48 kinds of pathogens detected, the Torque teno virus 22 (15/122) was the most common, followed by Primate erythroparvovirus 1 (13/122). The top four bacteria included Klebsiella pneumoniae (n = 8), Enterococcus faecium (n = 5), Stenotrophomonas maltophilia (n = 4), and Escherichia coli (n = 4). Aspergillus fumigatus was the most common fungus. The bronchoalveolar lavage fluid (BALF) exhibited the highest proportion of positive findings among sample types, with viral, fungal, and bacterial mixed infection being the most common (n = 6, 19.35%). Besides, using mNGS for early diagnosis of infection after liver transplantation may effectively prolong patient survival. This is the first study to explore the application value of mNGS and its comparison with traditional culture in pneumonia and other infections in post-liver transplantation patients. The simultaneous application of these two methods suggested that the Torque teno virus 22, Klebsiella pneumoniae, and the Aspergillus fumigatus are the most common pathogens of viruses, bacteria, and fungi after LT, suggesting that these pathogens may be associated with postoperative pathogen infection and patient prognosis. The mNGS technique showed distinct advantages in detecting mixed, viral, and parasitic infections in this patient population. Further studies are warranted to systematically elucidate the dynamic evolution and molecular characteristics of infection after liver transplantation.
Identifying Markers of Emerging SARS-CoV-2 Variants in Patients With Secondary Immunodeficiency
Authors: Markarian Nathan M. , Galli Gaël , Patel Dhanesh , Hemmings Mark , Nagpal Priya , Berghuis Albert M. , Abrahamyan Levon , Vidal Silvia M.
Published: July 2022

Since the end of 2019, the world has been challenged by the coronavirus disease 2019 (COVID-19) pandemic. With COVID-19 cases rising globally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, resulting in the emergence of variants of interest (VOI) and of concern (VOC). Of the hundreds of millions infected, immunodeficient patients are one of the vulnerable cohorts that are most susceptible to this virus. These individuals include those with preexisting health conditions and/or those undergoing immunosuppressive treatment (secondary immunodeficiency). In these cases, several researchers have reported chronic infections in the presence of anti-COVID-19 treatments that may potentially lead to the evolution of the virus within the host. Such variations occurred in a variety of viral proteins, including key structural ones involved in pathogenesis such as spike proteins. Tracking and comparing such mutations with those arisen in the general population may provide information about functional sites within the SARS-CoV-2 genome. In this study, we reviewed the current literature regarding the specific features of SARS-CoV-2 evolution in immunocompromised patients and identified recurrent de novo amino acid changes in virus isolates of these patients that can potentially play an important role in SARS-CoV-2 pathogenesis and evolution.
Resurgence of Respiratory Syncytial Virus Infection During COVID-19 Pandemic Among Children in Shanghai, China
Authors: Jia Ran , Lu Lijuan , Su Liyun , Lin Ziyan , Gao Da , Lv Haiyan , Xu Menghua , Liu Pengcheng , Cao Lingfeng , Xu Jin
Published: July 2022

Respiratory syncytial virus (RSV) is the most common pathogen causing acute lower respiratory tract infection (LRTI) in children. RSV usually peaks in winter and declines by early spring in China. The outbreak of coronavirus disease 2019 (COVID-19) was reported to bring changes to the transmission pattern of respiratory pathogens including RSV. Here in this paper, we analyzed RSV-positive nasopharyngeal aspirates from inpatients in the Children’s Hospital of Fudan University from October 2019 to October 2021 and compared the clinical features of the RSV-positive patients before and during COVID-19. We found an atypical upsurge of RSV infection in the late summer of 2021 after a major suppression in 2020. RSV B was the main subtype spreading among children throughout the study. Phylogenetic analysis revealed that all RSV A strains belonged to ON1 genotype and all RSV B strains were BA9 genotype. Deduced amino acid analysis displayed different substitutions in the RSV strains observed before and during COVID-19. Demographic analysis suggested that males and infants aged under 5 months were the main populations infected with RSV by gender and age, respectively. Less severe clinical outcomes were observed in patients during COVID-19 than before the pandemic, especially in RSV B-positive patients. Our findings described the epidemiological changes in RSV infection brought by COVID-19, which further underscored the importance of continuous surveillance of RSV in the shadow of COVID-19 at both local and global scales.
Research on Rehabilitation Training Strategies Using Multimodal Virtual Scene Stimulation
Authors: Xie Ping , Wang Zihao , Li Zengyong , Wang Ying , Wang Nianwen , Liang Zhenhu , Wang Juan , Chen Xiaoling
Published: July 2022

It is difficult for stroke patients with flaccid paralysis to receive passive rehabilitation training. Therefore, virtual rehabilitation technology that integrates the motor imagery brain-computer interface and virtual reality technology has been applied to the field of stroke rehabilitation and has evolved into a physical rehabilitation training method. This virtual rehabilitation technology can enhance the initiative and adaptability of patient rehabilitation. To maximize the deep activation of the subjects motor nerves and accelerate the remodeling mechanism of motor nerve function, this study designed a brain-computer interface rehabilitation training strategy using different virtual scenes, including static scenes, dynamic scenes, and VR scenes. Including static scenes, dynamic scenes, and VR scenes. We compared and analyzed the degree of neural activation and the recognition rate of motor imagery in stroke patients after motor imagery training using stimulation of different virtual scenes, The results show that under the three scenarios, The order of degree of neural activation and the recognition rate of motor imagery from high to low is: VR scenes, dynamic scenes, static scenes. This paper provided the research basis for a virtual rehabilitation strategy that could integrate the motor imagery brain-computer interface and virtual reality technology.
Application of α-Syn Real-Time Quaking-Induced Conversion for Brain and Skin Specimens of the Chinese Patients With Parkinson’s Disease
Authors: Chen Dong-Dong , Jiao Ling , Huang Yue , Xiao Kang , Gao Li-Ping , Chen Cao , Shi Qi , Dong Xiao-Ping
Published: July 2022

The real-time quaking-induced conversion (RT-QuIC) assay has been developed and used as an in vitro diagnostic tool for Parkinson’s disease (PD). In this study, we established α-Syn RT-QuIC using recombinant human α-Syn as the substrate. All 5 brain homogenates of neuropathological PD cases and 13 skin homogenates of clinical PD cases showed positive results, whereas all the samples of negative controls remain negative. Meantime, randomly selected 6 skin samples of PD cases and 6 skin samples of sCJD cases showed negative in opposite prion RT-QuIC and α-Syn RT-QuIC. Our α-Syn RT-QuIC showed dose-dependent manner between the lag times and peak ThT fluorescent values. Additionally, the detecting limitation was about 10–7 dilution for brain tissues and 10–6 for skins. Those data indicate a reliable specificity and good sensitivity of the established α-Syn RT-QuIC in identifying and amplifying the misfolded α-Syn in brain and skin tissues of patients with PD.
Validation of At-Home Application of a Digital Cognitive Screener for Older Adults
Authors: Arioli Melissa , Rini James , Anguera-Singla Roger , Gazzaley Adam , Wais Peter E.
Published: July 2022

Standardized neuropsychological assessments of older adults are important for both clinical diagnosis and biobehavioral research. Over decades, in-person testing has been the basis for population normative values that rank cognitive performance by demographic status. Most recently, digital tools have enabled remote data collection for cognitive measures, which offers the significant promise to extend the basis for normative values to be more inclusive of a larger cross section of the older population. We developed a Remote Characterization Module (RCM), using a speech-to-text interface, as a novel digital tool to administer an at-home, 25-min cognitive screener that mimics eight standardized neuropsychological measures. Forty cognitively healthy participants were recruited from a longitudinal aging research cohort, and they performed the same measures of memory, attention, verbal fluency and set-shifting in both in-clinic paper-and-pencil (PAP) and at-home RCM versions. The results showed small differences, if any, for how participants performed on in-person and remote versions in five of eight tasks. Critically, robust correlations between their PAP and RCM scores across participants support the finding that remote, digital testing can provide a reliable assessment tool for rapid and remote screening of healthy older adults’ cognitive performance in several key domains. The implications for digital cognitive screeners are discussed.
Phototherapy for Cognitive Function in Patients With Dementia: A Systematic Review and Meta-Analysis
Authors: Zhu Genying , Tong Qifeng , Ye Xiangming , Li Juebao , Zhou Liang , Sun Peng , Liang Feng , Zhong Shuchang , Cheng Ruidong , Zhang Jie
Published: July 2022

Background

Dementia is a major health burden worldwide. As numerous pharmacological trials for dementia have failed, emerging phototherapy studies have evaluated the efficacy of alternative therapies for cognition.

Objective

The objective of this study was to evaluate the association between phototherapy and changes in cognitive deficits in patients with dementia.

Methods

PubMed, Embase, Web of Science, PsycINFO, CINAHL, and Cochrane Central Register of Controlled Trials were searched from inception to 27 March 2022. Inclusion criteria were controlled clinical trials of phototherapy interventions reporting pre-post changes in global cognitive function and subdomains in patients with dementia. Data were extracted by two independent reviewers and pooled in random-effects models. Subgroup and meta-regression analyses were conducted to investigate the sources of heterogeneity.

Results

Our analyses included 13 studies enrolling a total of 608 participants. Phototherapy showed significant associations with improvements of global cognitive function (standardized mean difference [SMD], 0.63; 95% confidence interval [CI], 0.33–0.94; P < 0.001) and subdomains, especially with respect to attention, executive function, and working memory. Near-infrared (NIR) light-emitting diodes (LEDs) photobiomodulation (SMD, 0.91; 95% CI, 0.46–1.36; P < 0.001) and lasers (SMD, 0.99; 95% CI, 0.56–1.43; P < 0.001) showed more significant associations with improved cognitive functions when compared with normal visible light. In addition, the effect sizes of short-term effects (SMD, 0.63; 95% CI, 0.33–0.94; P < 0.001) were larger than effects assessed in long-term follow-up (SMD, 0.49; 95% CI, -0.24–1.21; P = 0.189).

Conclusion

In this meta-analysis, phototherapy interventions were associated with cognitive improvement in patients with dementia. NIR LEDs and lasers had advantages over normal visible light. Domain-specific effects were indicated for attention, executive function, and working memory. Short-term improvement after phototherapy was supported, while evidence for long-term benefits was lacking. Stronger evidence for individualized parameters, such as optimal dosing, is needed in the future.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=267596], identifier [CRD42021267596].
A Presurgical Unfavorable Prediction Scale of Endovascular Treatment for Acute Ischemic Stroke
Authors: Li Jingwei , Zhu Wencheng , Zhou Junshan , Yun Wenwei , Li Xiaobo , Guan Qiaochu , Lv Weiping , Cheng Yue , Ni Huanyu , Xie Ziyi , Li Mengyun , Zhang Lu , Xu Yun , Zhang Qingxiu
Published: July 2022

Objective

To develop a prognostic prediction model of endovascular treatment (EVT) for acute ischemic stroke (AIS) induced by large-vessel occlusion (LVO), this study applied machine learning classification model light gradient boosting machine (LightGBM) to construct a unique prediction model.

Methods

A total of 973 patients were enrolled, primary outcome was assessed with modified Rankin scale (mRS) at 90 days, and favorable outcome was defined using mRS 0–2 scores. Besides, LightGBM algorithm and logistic regression (LR) were used to construct a prediction model. Then, a prediction scale was further established and verified by both internal data and other external data.

Results

A total of 20 presurgical variables were analyzed using LR and LightGBM. The results of LightGBM algorithm indicated that the accuracy and precision of the prediction model were 73.77 and 73.16%, respectively. The area under the curve (AUC) was 0.824. Furthermore, the top 5 variables suggesting unfavorable outcomes were namely admitting blood glucose levels, age, onset to EVT time, onset to hospital time, and National Institutes of Health Stroke Scale (NIHSS) scores (importance = 130.9, 102.6, 96.5, 89.5 and 84.4, respectively). According to AUC, we established the key cutoff points and constructed prediction scale based on their respective weightings. Then, the established prediction scale was verified in raw and external data and the sensitivity was 80.4 and 83.5%, respectively. Finally, scores >3 demonstrated better accuracy in predicting unfavorable outcomes.

Conclusion

Presurgical prediction scale is feasible and accurate in identifying unfavorable outcomes of AIS after EVT.
Miniature Autonomy as Means to Find New Approaches in Reliable Autonomous Driving AI Method Design
Authors: Tiedemann Tim , Schwalb Luk , Kasten Markus , Grotkasten Robin , Pareigis Stephan
Published: July 2022

Artificial Intelligence (AI) methods need to be evaluated thoroughly to ensure reliable behavior. In applications like autonomous driving, a complex environment with an uncountable number of different situations and conditions needs to be handled by a method whose behavior needs to be predictable. To accomplish this, simulations can be used as a first step. However, the physical world behaves differently, as the example of autonomous driving shows. There, erroneous behavior has been found in test drives that was not noticed in simulations. Errors were caused by conditions or situations that were not covered by the simulations (e.g., specific lighting conditions or other vehicle's behavior). However, the problem with real world testing of autonomous driving features is that critical conditions or situations occur very rarely—while the test effort is high. A solution can be the combination of physical world tests and simulations—and miniature vehicles as an intermediate step between both. With model cars (in a sufficiently complex model environment) advantages of both can be combined: (1) low test effort and a repeatable variation of conditions/situations as an advantage like in simulations and (2) (limited) physical world testing with unspecified and potentially unknown properties as an advantage like in real-world tests. Additionally, such physical tests can be carried out in less stable cases like already in the early stages of AI method testing and/or in approaches using online learning. Now, we propose to use a) miniature vehicles at a small scale of 1:87 and b) use sensors and computational power only on the vehicle itself. By this limitation, a further consequence is expected: Here, autonomy methods need to be optimized drastically or even redesigned from scratch. The resulting methods are supposed to be less complex—and, thus, again less error-prone. We call this approach “Miniature Autonomy” and apply it to the road, water, and aerial vehicles. In this article, we briefly describe a small test area we built (3 sqm.), a large test area used alternatively (1,545 sqm.), two last generation autonomous miniature vehicles (one road, one aerial vehicle), and an autonomous driving demo case demonstrating the application.
Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies
Authors: Goodspeed Kimberly , Bailey Rachel M. , Prasad Suyash , Sadhu Chanchal , Cardenas Jessica A. , Holmay Mary , Bilder Deborah A. , Minassian Berge A.
Published: July 2022

Genetic epilepsies are a spectrum of disorders characterized by spontaneous and recurrent seizures that can arise from an array of inherited or de novo genetic variants and disrupt normal brain development or neuronal connectivity and function. Genetically determined epilepsies, many of which are due to monogenic pathogenic variants, can result in early mortality and may present in isolation or be accompanied by neurodevelopmental disability. Despite the availability of more than 20 antiseizure medications, many patients with epilepsy fail to achieve seizure control with current therapies. Patients with refractory epilepsy—particularly of childhood onset—experience increased risk for severe disability and premature death. Further, available medications inadequately address the comorbid developmental disability. The advent of next-generation gene sequencing has uncovered genetic etiologies and revolutionized diagnostic practices for many epilepsies. Advances in the field of gene therapy also present the opportunity to address the underlying mechanism of monogenic epilepsies, many of which have only recently been described due to advances in precision medicine and biology. To bring precision medicine and genetic therapies closer to clinical applications, experimental animal models are needed that replicate human disease and reflect the complexities of these disorders. Additionally, identifying and characterizing clinical phenotypes, natural disease course, and meaningful outcome measures from epileptic and neurodevelopmental perspectives are necessary to evaluate therapies in clinical studies. Here, we discuss the range of genetically determined epilepsies, the existing challenges to effective clinical management, and the potential role gene therapy may play in transforming treatment options available for these conditions.
Systolic Blood Pressure Variability When Transitioning From Intravenous to Enteral Antihypertensive Agents in Patients With Hemorrhagic Strokes
Authors: Alshaya Abdulrahman I. , Alghamdi Meshari , Almohareb Sumaya N. , Alshaya Omar A. , Aldhaeefi Mohammed , Alharthi Abdullah F. , Almohaish Sulaiman
Published: July 2022

Background/Objective

Systolic blood pressure variability (SBPV) in patients with intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is associated with an increased risk of acute kidney injury (AKI) and mortality. SBPV is a strong predictor of poor functional outcomes in patients with ICH. Intravenous (IV) antihypertensive agents are commonly used to achieve sustained target blood pressure goals; however, this is not a feasible long-term option. The transition from IV to enteral antihypertensives is not yet well established in patients with ICH and SAH. This study aimed to assess the effect of the number of antihypertensive agents and overlap time during the transition period from IV to enteral route on SBPV in patients with ICH and SAH.

Methods

This retrospective single-center study was conducted at a tertiary teaching hospital in Riyadh, Saudi Arabia. Data were extracted from electronic medical records after obtaining Institutional Review Board approval. Patients were included if they were >18 years old, admitted with spontaneous ICH or SAH, and received continuous infusion antihypertensives prior to transitioning to the enteral route. The major outcome was the effect of the number of antihypertensive agents and overlap time on SBPV during the transition process. Minor outcomes included the effect of the number of antihypertensive agents and overlap time on heart rate variability and the incidence of AKI on day 7.

Results

After the screening, we included 102 patients. Based on our regression model, the number of enteral antihypertensive agents upon transitioning from IV to enteral antihypertensive therapy had no effect on SBPV in the intensive care unit (ICU) among our patients (p-value = 0.274). However, the prolonged overlap was associated with reduced SBPV in the ICU (p-value = 0.012). No differences were observed between the groups in heart rate variation or AKI rate.

Conclusions

In patients with ICH and SAH, prolonged overlap of enteral antihypertensive agents to overlap with intravenous antihypertensive therapy may result in lower SBPV. This finding needs to be confirmed on a larger scale with more robust study designs for patients with ICH and SAH.
Prominent Fatigue but No Motor Fatigability in Non-Hospitalized Patients With Post-COVID-Syndrome
Authors: Weich Christian , Dettmers Christian , Saile Romina , Schleicher Luise , Vieten Manfred , Joebges Michael
Published: July 2022

Objectives

Fatigue is a frequent and often disabling symptom in patients with post-COVID syndrome. To better understand and evaluate the symptom of motor fatigue in the context of the post-COVID syndrome, we conducted treadmill walking tests to detect the phenomenon of motor fatigability or to evaluate whether evidence of organic lesions of the motor system could be found, similar to patients with multiple sclerosis.

Method

Twenty-nine non-hospitalized patients with post-COVID syndrome completed the Fatigue Scale for Motor and Cognitive Function (FSMC) questionnaire to determine the trait component of subjective fatigue before they were tested on a treadmill walking at a moderate speed for up to 60 min or until exhaustion. During the walking test oxygen uptake, ventilation and acceleration data of both feet were collected. To determine motor performance fatigability, the Fatigue Index Kliniken Schmieder (FKS) was calculated using the attractor method.

Results

The average walking duration was 42.7 ± 18.6 min with 15 subjects stopping the walking test prematurely. The FSMC score revealed a severe cognitive (37.6 ± 8.2) and motor (37.1 ± 7.8) fatigue averaged over all subjects but only two subjects showed an FKS above the normal range (>4), representing performance fatigability. There was no significant correlation between subjective fatigue (FSMC) and FKS as well as walking time. Absolute values of oxygen uptake and ventilation were in the normal range reported in literature (r = 0.9, p < 0.05), although eight subjects did not produce a steady-state behavior.

Conclusion

Almost all patients with post-COVID syndrome and subjectively severe motor fatigue, did not show motor fatigability nor severe metabolic anomalies. This is argued against organic, permanent damage to the motor system, as is often seen in MS. Many of the patients were - to our and their own surprise - motorically more exertable than expected.
Acute Unilateral Peripheral Vestibulopathy After COVID-19 Vaccination: Initial Experience in a Tertiary Neurotology Center
Authors: Schmid Marc Basil , Bächinger David , Pangalu Athina , Straumann Dominik , Dlugaiczyk Julia
Published: July 2022

Objective

The aim of the present study was to identify patients who developed acute unilateral peripheral vestibulopathy (AUPVP) after COVID-19 vaccination.

Methods

For this single-center, retrospective study, we screened the medical records of our tertiary interdisciplinary neurotology center for patients who had presented with AUPVP within 30 days after COVID-19 vaccination (study period: 1 June−31 December 2021). The initial diagnosis of AUPVP was based on a comprehensive bedside neurotological examination. Laboratory vestibular testing (video head impulse test, cervical and ocular vestibular evoked myogenic potentials, dynamic visual acuity, subjective visual vertical, video-oculography, caloric testing) was performed 1–5 months later.

Results

Twenty-six patients were diagnosed with AUPVP within the study period. Of those, n = 8 (31%) had developed acute vestibular symptoms within 30 days after COVID-19 vaccination (mean interval: 11.9 days, SD: 4.8, range: 6–20) and were thus included in the study. The mean age of the patients (two females, six males) was 46 years (SD: 11.7). Seven patients had received the Moderna mRNA vaccine and one the Pfizer/BioNTech mRNA vaccine. All patients displayed a horizontal(-torsional) spontaneous nystagmus toward the unaffected ear and a pathological clinical head impulse test toward the affected ear on initial clinical examination. Receptor-specific laboratory vestibular testing performed 1–5 months later revealed recovery of vestibular function in two patients, and heterogeneous lesion patterns of vestibular endorgans in the remaining six patients.

Discussion and Conclusions

The present study should raise clinicians' awareness for AUPVP after COVID-19 vaccination. The relatively high fraction of such cases among our AUPVP patients may be due to a certain selection bias at a tertiary neurotology center. Patients presenting with acute vestibular symptoms should be questioned about their vaccination status and the date of the last vaccination dose. Furthermore, cases of AUPVP occurring shortly after a COVID-19 vaccination should be reported to the health authorities to help determining a possible causal relationship.
A Scientometric Visualization Analysis for Molecular Mechanisms of Substance Abuse and Its Neurotoxicity From 1997 to 2021
Authors: Zhang Aijia , Liu Zilong , Liang Man
Published: July 2022

Substance abuse has become a global problem due to drug-induced addiction and neurotoxicity, which causes a huge physical, social, and financial burden. Various kinds of drugs can hijack the users’/abusers’ behavior and associated neurocircuitry. To summarize recent scientific advances on drug abuse, we reviewed relevant publications to analyze research progress and such trends through bibliometric ways. Based on retrieval strategies, a total of 681 scientific records published from 1997 to 2021 were screened and included in the Web of Science (WoS) database. Further scientometric analysis revealed that annual publication output increased across this period, with the United States of America (USA) contributing a significant number of reasons. Research has focused on neurotransmitter, oxidative stress, mitochondrial system injury, and other neurotoxic mechanisms. Neuroimmune, neurotoxic targets, and new psychoactive substances have been hot topics in recent years, which deserve continued research in the future. Specific research on molecular mechanisms has progressed across this period, with an emphasis on the root cause of toxicity and molecular targets for therapy. Moreover, collaborations of international multi-disciplinary research teams have been efficient and need to be encouraged for addiction research and the development of appropriate therapeutic processes.
The Circadian Molecular Machinery in CNS Cells: A Fine Tuner of Neuronal and Glial Activity With Space/Time Resolution
Authors: Fagiani Francesca , Baronchelli Eva , Pittaluga Anna , Pedrini Edoardo , Scacchi Chiara , Govoni Stefano , Lanni Cristina
Published: July 2022

The circadian molecular machinery is a fine timekeeper with the capacity to harmonize physiological and behavioral processes with the external environment. This tight-knit regulation is coordinated by multiple cellular clocks across the body. In this review, we focus our attention on the molecular mechanisms regulated by the clock in different brain areas and within different cells of the central nervous system. Further, we discuss evidence regarding the role of circadian rhythms in the regulation of neuronal activity and neurotransmitter systems. Not only neurons, but also astrocytes and microglia actively participate in the maintenance of timekeeping within the brain, and the diffusion of circadian information among these cells is fine-tuned by neurotransmitters (e.g., dopamine, serotonin, and γ-aminobutyric acid), thus impacting on the core clock machinery. The bidirectional interplay between neurotransmitters and the circadian clockwork is fundamental in maintaining accuracy and precision in daily timekeeping throughout different brain areas. Deepening the knowledge of these correlations allows us to define the basis of drug interventions to restore circadian rhythms, as well as to predict the onset of drug treatment/side effects that might promote daily desynchronization. Furthermore, it may lead to a deeper understanding of the potential impacts of modulations in rhythmic activities on the pace of aging and provide an insight in to the pathogenesis of psychiatric diseases and neurodegenerative disorders.
Effects of Single Nucleotide Polymorphisms and Mediterranean Diet in Overweight or Obese Postmenopausal Women With Breast Cancer Receiving Adjuvant Hormone Therapy: A Pilot Randomized Controlled Trial
Authors: Cho A-Ra , Hong Kyung-Won , Kwon Yu-Jin , Choi Ja-Eun , Lee Hye-Sun , Kim Hyung-Mi , Bae Soong June , Ahn Sung Gwe , Jeong Joon , Lee Ji-Won
Published: July 2022

Background and Aims

Weight management is recommended in overweight or obese breast cancer patients, as they have an increased risk of cancer recurrence and poor prognosis. Furthermore, identifying the relationships between genetic factors and nutrition could help suggest possible individualized nutritional solutions in weight management. The objective of this pilot randomized controlled trial was to investigate the influence of two obesity-associated single nucleotide polymorphisms and the Mediterranean diet intervention on weight loss and modification of nutrient intake and metabolic parameters in overweight or obese, postmenopausal, breast cancer patients receiving adjuvant hormone therapy.

Methods

Seventy-eight breast cancer patients were randomly assigned to the Mediterranean diet (MeDiet) group or control group, and seventy-one were finally analyzed. Body composition, nutrient intake, and metabolic parameters were assessed at baseline and after the 8-week intervention. Fat mass and obesity-associated (FTO) rs7185735 and melanocortin-4 receptor (MC4R) rs476828 variants were genotyped.

Results

We found that both variants did not influence weight loss or improvement of metabolic parameters within the Mediterranean diet intervention. Intake of saturated fatty acid (SFA) and trans fat was significantly increased in C carriers compared with the TT genotype of MC4R rs476828 only in the control group (p = 0.002 for SFA; p = 0.016 for trans fat), whereas no significant difference was observed between genotypes in the MeDiet group. There were statistically significant interactions between MC4R rs476828 and dietary intervention for changes in SFA intake (p = 0.009) and trans fat intake (p = 0.049).

Conclusion

Our data suggest that considering the effects of genotype may be more necessary when the Mediterranean diet is not followed and that this diet may have a protective role against the effects of certain genotypes. Further studies are required to determine the potential mechanism of the observed gene-diet interaction.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT04045392].
Effects of Multispecies Synbiotic Supplementation on Anthropometric Measurements, Glucose and Lipid Parameters in Children With Exogenous Obesity: A Randomized, Double Blind, Placebo-Controlled Clinical Trial (Probesity-2 Trial)
Authors: Kilic Yildirim Gonca , Dinleyici Meltem , Vandenplas Yvan , Dinleyici Ener Cagri
Published: July 2022

Studies on the effects of synbiotics on obesity in children are limited. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic during 12 weeks on anthropometric measurements, glucose metabolism and lipid parameters in 61 children with exogenous obesity. All children were treated with a standard diet and increased physical activity and received once daily a synbiotic supplement (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium and fructo-oligosaccharides) or daily placebo for 12 weeks. At baseline, no statistically significant differences existed in anthropometric measurements, glucose and lipid parameters between both groups. We observed changes for anthropometric measures (% reduction comparing to baseline) in both synbiotic and placebo groups. After 12 weeks; changes (% reduction comparing to baseline) in weight (p < 0.01), BMI (p < 0.05), waist circumference (p < 0.05) and waist circumference to height ratio (p < 0.05) were significantly higher in the children receiving the synbiotic supplement. There is no difference in glucose metabolism, lipid parameters, presence of non-alcoholic fatty liver disease between both groups after 12 weeks. The daily intake of a multispecies synbiotic in addition to diet and increased physical activity did improve anthropometric measurements: body weight, BMI, waist circumference and waist/height ratio. The supplementation of this synbiotic is an efficient weight-loss strategy above diet and exercise in pediatric obesity (Trial identifier: NCT05162209).
Box–Behnken Design: Wet Process Optimization for Saponins Removal From Chenopodium quinoa Seeds and the Study of Its Effect on Nutritional Properties
Authors: El Hazzam Khadija , Mhada Manal , Metougui Mohamed Louay , El Kacimi Kamal , Sobeh Mansour , Taourirte Moha , Yasri Abdelaziz
Published: July 2022

The pseudocereal grain, Quinoa (Chenopodium quinoaWilld.), has a great nutritional value due to its high contents of proteins, fiber, minerals, and vitamins. However, saponins naturally present outside the grains represent an obstacle to their consumption as human food. Before consumption, the grains are subjected to various treatments, which alter their nutritional value. In an attempt to eliminate the maximum of saponins using the wet process, while minimizing the washing conditions and preserving the nutritional quality, we explored the effects of several parameters, including volume of water, treatment time, soaking time, number of washing, and water temperature, followed by an optimization process using Box–Behnken Design, and finally, the impact of this process on the physicochemical and techno-functional properties of six quinoa genotypes seeds was evaluated. As a result, the variation of the treatment time, volume, and temperature of the water positively affected the saponins leaching. According to the quadratic model, the maximum percentages of eliminated saponins (96.53%−96.77%) were found at a temperature of 50°C, treatment times from 60 to 69 min, and water volumes from 6.99 to 7.50 mL per gram of seeds. The optimized method did not affect the proteins and microelements content (Zn, Mn, B, Mo), while a slight decrease of macro-elements (K, P, Ca, S, Mg) was noted in the level of some genotypes. On the other hand, a significant improvement of the techno-functional properties such as water and oil holding capacity was noted, with a sharp drop-in emulsifying activity in all genotypes without affecting the standard values of pH (6.4–6.8) and moisture content (10%−11%) of the seeds. Hence, the optimized method showed to be a more potential method for saponins removal than the currently used dry method.