bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity of Apgar Score as an Indicator of Neonatal SARS-CoV-2 Infection: A Scoping Review
Authors: Chao Melissa , Menon Carlo , Elgendi Mohamed
Published: January 2022

The coronavirus disease 2019 (COVID-19) pandemic has had profound impacts on healthcare systems worldwide, particularly regarding the care of pregnant women and their neonates. The use of the Apgar score—a discrete numerical index used to evaluate neonatal condition immediately following delivery that has been used ubiquitously as a clinical indicator of neonatal condition and widely reported in the literature for decades—has continued during the pandemic. Although health systems adopted protocols that addressed pregnant women and their neonates during the pandemic, limited research has assessed the validity of Apgar scores for determining neonatal conditions in the context of COVID-19. Therefore, this scoping review was conducted on the first 2 years of the pandemic and included mothers with reverse transcription-polymerase chain reaction confirmed COVID-19 and their resulting positive or negative neonates. In total, 1,966 articles were assessed for eligibility, yielding 246 articles describing 663 neonates. Neonates who tested negative had median Apgar scores of 9 and 9 at 1 and 5 mins, respectively, while test-positive neonates had median Apgar scores of 8 and 9 at the same time points. The proportions of test-negative neonates with Apgar scores below 7 were 29 (4%) and 11 (2%) at 1 and 5 mins, which was not statistically significant (p = 0.327, χ2 = 0.961). These proportions were even lower for positive neonates: 22 (3%) and 11 (2%) at 1 and 5 mins, respectively, which was not statistically significant (p = 1, χ2 = 0). The low proportion of Apgar scores below 7 suggests that low Apgar scores are likely to be associated with severe maternal COVID-19 symptoms during delivery rather than neonatal COVID-19. Therefore, this study indicated that Apgar scores are poor indicators of neonatal COVID-19 status.
The Effectiveness of Traditional Chinese Yijinjing Qigong Exercise for the Patients With Knee Osteoarthritis on the Pain, Dysfunction, and Mood Disorder: A Pilot Randomized Controlled Trial
Authors: Zhang Shuaipan , Guo Guangxin , Li Xing , Yao Fei , Wu Zhiwei , Zhu Qingguang , Fang Min
Published: January 2022

Background: Although traditional Chinese Yijinjing Qigong Exercise (YJJQE) is popularly used in China, to alleviate symptoms of people with knee osteoarthritis (KOA), no randomized controlled trials (RCTs) are available to evaluate the effects of YJJQE in patients with KOA. The purpose of this trial is to assess the clinical efficacy of YJJQE for patients with KOA.

Methods: A total of 50 participants clinically diagnosed with KOA are randomly (1:1) assigned to the YJJQE group (n = 25) and to the stretching training exercise (STE) group (n = 25), for a 40-min exercise session twice a week for 12 weeks. All outcome measures are collected at baseline and at 12-week ending intervention, which includes the primary outcomes of Western Ontario and McMaster Universities Osteoarthritis Index Scale (WOMAC), the secondary outcomes of visual analog scale (VAS), mental component summary (MCS), physical component summary (PCS), Beck depression inventory (BDI), perceived stress scale (PSS), Berg balance scale (BBS), and the Gait functional mobility data.

Results: The YJJQE group did not have any significant changes compared to the control group on the WOMAC score after the 12-week intervention (P > 0.05), though the YJJQE group demonstrated better performance in MCS, BDI, and PSS (P = 0.002, P = 0.001, and P = 0.026, respectively) than the control group. No serious adverse events occurred in either group, and only mild muscle soreness was reported during both exercise treatments.

Conclusion: Because no difference between both groups was shown, with regards to the primary outcome measurement (WOMAC), it can hardly explain that the YJJQE had an advantageous effect on patients experiencing the pain and dysfunction of knee osteoarthritis. However, compared to the control group, YJJQE appeared to be associated with improvements in psychological well-being including reduced stress, anxiety, depression, and mood disturbance to manage KOA. Further trials with larger sample sizes and follow-up studies will be required.

Clinical Trial Registration:https://www.chictr.org.cn/edit.aspx?pid=60357&htm=4, ChiCTR2000037256.
Optical Coherence Tomography Angiography Compared With Optical Coherence Tomography for Detection of Early Glaucoma With High Myopia
Authors: Chang Pei-Yao , Wang Jiun-Yi , Wang Jia-Kang , Huang Tzu-Lun , Hsu Yung-Ray
Published: January 2022

Purpose: To investigate the diagnostic abilities of the perfusion density (PD) and structural thickness parameters in the peripapillary and macular regions measured by optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) and to test if their diagnostic abilities of early glaucoma are different between highly myopic (HM) and non-highly myopic (NHM) patients.

Methods: A total of 75 glaucoma patients and 65 controls were included in the analyses. The glaucoma detection abilities of macular PD and peripapillary PD, along with macular ganglion cell-inner plexiform layer (mGCIPL) thickness and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were compared between the HM and NHM group. Diagnostic ability was assessed by area under the receiver operating characteristics (AUC) curves, adjusted by age, axial length, and signal strength.

Results: The diagnostic ability of macular PD and mGCIPL thickness had no significant difference in both HM and NHM groups. However, the diagnostic ability of peripapillary PD except in the temporal section was significantly lower in the HM group than in the NHM group (all p < 0.05). The diagnostic ability of the superior, nasal, and average pRNFL thickness was also significantly lower in the HM group than in the NHM group (all p < 0.05).

Conclusion: This study demonstrated that although peripapillary PD and macular PD were both significantly reduced in patients with highly myopia, the diagnostic ability of peripapillary PD in HM patients was significantly lower than that in NHM patients, while macular PD was not. Macular OCTA along with OCT imaging should be included in the imaging algorithm in early glaucoma diagnosis in highly myopic patients.
Association Between Sensory Loss and Falls Among Middle-Aged and Older Chinese Population: Cross-Sectional and Longitudinal Analyses
Authors: Zhou Yifan , Hu Yanping , Luo Jianfeng , Li Yinwen , Liu Haiyun , Sun Xiaodong , Zhou Minwen
Published: January 2022

Introduction: Previous studies have suggested that sensory loss is linked to falls. However, most of these studies were cross-sectional designed, focused on single sensory loss, and were conducted in developed countries with mixed results. The current study aims to investigate the longitudinal relationship between hearing loss (HL), vision loss (VL) and dual sensory loss (DSL) with falls among middle-aged and older Chinese population over 7 years.

Methods: The data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 7,623 Chinese older adults aged over 45 were included at baseline 2011 in this study. Self-reported falls and HL/VL/DSL were accepted. Other confounding variables included age, sex, BMI, educational level, marital status, various physical disorders and lifestyles. The impact of baseline sensory status on baseline prevalence of falls and incident falls over 7 years were assessed using logistic regression analyses. A logistic mixed model was used to assess the association between time-varying sensory loss with incident falls over 7 years after adjusted with multi-confounding factors.

Results: Single and dual sensory loss groups had significantly higher prevalence of falls compared to no sensory loss (NSL) group (DSL: 22.4%, HL: 17.4%, VL: 15.7%, NSL: 12.3%). Baseline HL (OR: 1.503, 95% CI: 1.240–1.820), VL (OR: 1.330, 95% CI: 1.075–1.646) and DSL (OR: 2.061, 95% CI: 1.768–2.404) were significantly associated with prevalence of falls. For longitudinal observation over 7 years, baseline HL/DSL and persistence of all types of sensory loss were associated with incidence of falls. Time-varying HL (OR: 1.203, 95% CI: 1.070–1.354) and DSL (OR: 1.479, 95% CI: 1.343–1.629) were associated with incident falls after adjusted with multi-confounders, while VL was not.

Conclusion: HL and DSL are significantly associated with both onset and increased incidence of falls over 7 year's observation in middle-aged and elderly Chinese population. Persistence or amelioration of sensory loss status could exert divergent influences on incidence of falls, which should be considered in the development of falls-prevention public health policies for aging population.
Management of Medico-Legal Risks in Digital Health Era: A Scoping Review
Authors: Oliva Antonio , Grassi Simone , Vetrugno Giuseppe , Rossi Riccardo , Della Morte Gabriele , Pinchi Vilma , Caputo Matteo
Published: January 2022

Artificial intelligence needs big data to develop reliable predictions. Therefore, storing and processing health data is essential for the new diagnostic and decisional technologies but, at the same time, represents a risk for privacy protection. This scoping review is aimed at underlying the medico-legal and ethical implications of the main artificial intelligence applications to healthcare, also focusing on the issues of the COVID-19 era. Starting from a summary of the United States (US) and European Union (EU) regulatory frameworks, the current medico-legal and ethical challenges are discussed in general terms before focusing on the specific issues regarding informed consent, medical malpractice/cognitive biases, automation and interconnectedness of medical devices, diagnostic algorithms and telemedicine. We aim at underlying that education of physicians on the management of this (new) kind of clinical risks can enhance compliance with regulations and avoid legal risks for the healthcare professionals and institutions.
Replication of Dengue Virus in K562-Megakaryocytes Induces Suppression in the Accumulation of Reactive Oxygen Species
Authors: Kaur Jaskaran , Rawat Yogita , Sood Vikas , Periwal Neha , Rathore Deepak Kumar , Kumar Shrikant , Kumar Niraj , Bhattacharyya Sankar
Published: January 2022

Dengue virus can infect human megakaryocytes leading to decreased platelet biogenesis. In this article, we report a study of Dengue replication in human K562 cells undergoing PMA-induced differentiation into megakaryocytes. PMA-induced differentiation in these cells recapitulates steps of megakaryopoiesis including gene activation, expression of CD41/61 and CD61 platelet surface markers and accumulation of intracellular reactive oxygen species (ROS). Our results show differentiating megakaryocyte cells to support higher viral replication without any apparent increase in virus entry. Further, Dengue replication suppresses the accumulation of ROS in differentiating cells, probably by only augmenting the activity of the transcription factor NFE2L2 without influencing the expression of the coding gene. Interestingly pharmacological modulation of NFE2L2 activity showed a simultaneous but opposite effect on intracellular ROS and virus replication suggesting the former to have an inhibitory effect on the later. Also cells that differentiated while supporting intracellular virus replication showed reduced level of surface markers compared to uninfected differentiated cells.
Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity
Authors: Chen Fei , Fan Yumei , Liu Xiaopeng , Zhang Jianhua , Shang Yanan , Zhang Bo , Liu Bing , Hou Jiajie , Cao Pengxiu , Tan Ke
Published: January 2022

Heat shock factor 2 (HSF2), a transcription factor, plays significant roles in corticogenesis and spermatogenesis by regulating various target genes and signaling pathways. However, its expression, clinical significance and correlation with tumor-infiltrating immune cells across cancers have rarely been explored. In the present study, we comprehensively investigated the expression dysregulation and prognostic significance of HSF2, and the relationship with clinicopathological parameters and immune infiltration across cancers. The mRNA expression status of HSF2 was analyzed by TCGA, GTEx, and CCLE. Kaplan-Meier analysis and Cox regression were applied to explore the prognostic significance of HSF2 in different cancers. The relationship between HSF2 expression and DNA methylation, immune infiltration of different immune cells, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed using data directly from the TCGA database. HSF2 expression was dysregulated in the human pan-cancer dataset. High expression of HSF2 was associated with poor overall survival (OS) in BRCA, KIRP, LIHC, and MESO but correlated with favorable OS in LAML, KIRC, and PAAD. The results of Cox regression and nomogram analyses revealed that HSF2 was an independent factor for KIRP, ACC, and LIHC prognosis. GO, KEGG, and GSEA results indicated that HSF2 was involved in various oncogenesis- and immunity-related signaling pathways. HSF2 expression was associated with TMB in 9 cancer types and associated with MSI in 5 cancer types, while there was a correlation between HSF2 expression and DNA methylation in 27 types of cancer. Additionally, HSF2 expression was correlated with immune cell infiltration, immune checkpoint genes, and the tumor immune microenvironment in various cancers, indicating that HSF2 could be a potential therapeutic target for immunotherapy. Our findings revealed the important roles of HSF2 across different cancer types.
Application of Evans Index in Normal Pressure Hydrocephalus Patients: A Mini Review
Authors: Zhou Xi , Xia Jun
Published: January 2022

With an ever-growing aging population, the prevalence of normal pressure hydrocephalus (NPH) is increasing. Clinical symptoms of NPH include cognitive impairment, gait disturbance, and urinary incontinence. Surgery can improve symptoms, which leads to the disease's alternative name: treatable dementia. The Evans index (EI), defined as the ratio of the maximal width of the frontal horns to the maximum inner skull diameter, is the most commonly used index to indirectly assess the condition of the ventricles in NPH patients. EI measurement is simple, fast, and does not require any special software; in clinical practice, an EI >0.3 is the criterion for ventricular enlargement. However, EI's measurement methods, threshold setting, correlation with ventricle volume, and even its clinical value has been questioned. Based on the EI, the z-EI and anteroposterior diameter of the lateral ventricle index were derived and are discussed in this review.
Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells From Different Donors on Spinal Cord Injury in Mice
Authors: Zhu Xu , Wang Zhen , Sun Yi Eve , Liu Yuchen , Wu Zhourui , Ma Bei , Cheng Liming
Published: January 2022

Spinal cord injury (SCI) is caused by an external force, leading to severe dysfunction of the limbs below the injured segment. The inflammatory response plays a vital role in the prognosis of SCI. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation can promote repair of SCI by reducing the inflammatory response. We previously showed that hUCMSCs from 32 donors had different inhibitory abilities on BV2 cell proliferation. In this study, three experimental groups were established, and the mice were injected with different lines of hUCMSCs. Hind limb motor function, hematoxylin-eosin (H&E) staining, immunohistochemistry, Western blot (WB), qualitative real-time polymerase chain reaction (qRT-PCR), and RNA sequencing and correlation analysis were used to investigate the effects of hUCMSC transplantation on SCI mice and the underlying mechanisms. The results showed that the therapeutic effects of the three hUCMSC lines were positively correlated with their inhibitory abilities of BV2 cell proliferation ratesin vitro. The MSC_A line had a better therapeutic effect on improving the hind limb motor function and greater effect on reducing the expression of glial fibrillary acidic protein (Gfap) and ionized calcium binding adaptor molecule 1 (Iba1) and increasing the expression of neuronal nuclei (NeuN). Differentially expressed genes includingZbtb16,Per3, andHif3awere probably the key genes involved in the protective mechanism by MSC_A after nerve injury. qRT-PCR results further verified thatZbtb16, Per3, andHif3aexpressions reduced by SCI could be reversed by MSC_A application. These results suggest that the effect of hUCMSCs transplantation on acute SCI depends on their inhibitory abilities to inflammation reaction after nerve injury, which may help to shape future use of hUCMSCs combined with improving the effectiveness of clinical transformation.
Knowledge and Attitudes for the Management of Behavioral Variant of Frontotemporal Dementia
Authors: Castro-Suarez Sheila , Guevara-Silva Erik , Caparó-Zamalloa César , Osorio-Marcatinco Victor , Meza-Vega Maria , Miller Bruce , Cornejo-Olivas Mario
Published: January 2022

Background: The diagnosis of the behavioral variant of frontotemporal dementia (bvFTD) can be especially challenging and is relatively underdiagnosed. There is scarce information on training and attitudes from care providers facing bvFTD in settings with limited resources. We aim to describe clinical knowledge and attitudes facing bvFTD from neurologists, psychiatrists, and residents in Peru.

Methods: Potential participants received invitations by email to complete an online questionnaire. In addition, we reviewed 21 curricula from undergraduate medical schools' programs offered by the main schools of medicine in Peru during 2020 and 2021.

Results: A total of 145 participants completed the survey. The responders were neurologists (51%), psychiatrists (25%), and residents in neurology or psychiatry (24%). Only 26% of the respondents acknowledged receiving at least one class on bvFTD in undergraduate medical training, but 66.6% received at least some training during postgraduate study. Participants identified isolated supportive symptoms for bvFTD; however, only 25% identified the possible criteria and 18% the probable bvFTD criteria. They identified MoCA in 44% and Frontal Assessment Battery (39%) as the most frequently used screening test to assess bvFTD patients. Memantine and Acetylcholinesterase inhibitors were incorrectly indicated by 40.8% of participants. Seventy six percentage of participants indicated that they did not provide education and support to the caregiver. The dementia topic was available on 95.2%, but FTD in only 19%.

Conclusion: Neuropsychiatry medical specialists in Peru receive limited training in FTD. Their clinical attitudes for treating bvFTD require appropriate training focused on diagnostic criteria, assessment tools, and pharmacological and non-pharmacological management.
Management of Epileptic Seizures in Disorders of Consciousness: An International Survey
Authors: Briand Marie-Michèle , Lejeune Nicolas , Zasler Nathan , Formisano Rita , Bodart Olivier , Estraneo Anna , Magee Wendy L. , Thibaut Aurore
Published: January 2022

Epileptic seizures/post-traumatic epilepsy (ES/PTE) are frequent in persons with brain injuries, particularly for patients with more severe injuries including ones that result in disorders of consciousness (DoC). Surprisingly, there are currently no best practice guidelines for assessment or management of ES in persons with DoC. This study aimed to identify clinician attitudes toward epilepsy prophylaxis, diagnosis and treatment in patients with DoC as well as current practice in regards to the use of amantadine in these individuals. A cross-sectional online survey was sent to members of the International Brain Injury Association (IBIA). Fifty physician responses were included in the final analysis. Withdrawal of antiepileptic drug/anti-seizure medications (AED/ASM) therapy was guided by the absence of evidence of clinical seizure whether or not the AED/ASM was given prophylactically or for actual seizure/epilepsy treatment. Standard EEG was the most frequent diagnostic method utilized. The majority of respondents ordered an EEG if there were concerns regarding lack of neurological progress. AED/ASM prescription was reported to be triggered by the first clinically evident seizure with levetiracetam being the AED/ASM of choice. Amantadine was frequently prescribed although less so in patients with epilepsy and/or EEG based epileptic abnormalities. A minority of respondents reported an association between amantadine and seizure. Longitudinal studies on epilepsy management, epilepsy impact on neurologic prognosis, as well as potential drug effects on seizure risk in persons with DoC appear warranted with the goal of pushing guideline development forward and improving clinical assessment and management of seizures in this unique, albeit challenging, population.
Accelerating DNN Training Through Selective Localized Learning
Authors: Krithivasan Sarada , Sen Sanchari , Venkataramani Swagath , Raghunathan Anand
Published: January 2022

Training Deep Neural Networks (DNNs) places immense compute requirements on the underlying hardware platforms, expending large amounts of time and energy. We propose LoCal+SGD, a new algorithmic approach to accelerate DNN training by selectively combining localized or Hebbian learning within a Stochastic Gradient Descent (SGD) based training framework. Back-propagation is a computationally expensive process that requires 2 Generalized Matrix Multiply (GEMM) operations to compute the error and weight gradients for each layer. We alleviate this by selectively updating some layers' weights using localized learning rules that require only 1 GEMM operation per layer. Further, since localized weight updates are performed during the forward pass itself, the layer activations for such layers do not need to be stored until the backward pass, resulting in a reduced memory footprint. Localized updates can substantially boost training speed, but need to be used judiciously in order to preserve accuracy and convergence. We address this challenge through a Learning Mode Selection Algorithm, which gradually selects and moves layers to localized learning as training progresses. Specifically, for each epoch, the algorithm identifies a Localized→SGD transition layer that delineates the network into two regions. Layers before the transition layer use localized updates, while the transition layer and later layers use gradient-based updates. We propose both static and dynamic approaches to the design of the learning mode selection algorithm. The static algorithm utilizes a pre-defined scheduler function to identify the position of the transition layer, while the dynamic algorithm analyzes the dynamics of the weight updates made to the transition layer to determine how the boundary between SGD and localized updates is shifted in future epochs. We also propose a low-cost weak supervision mechanism that controls the learning rate of localized updates based on the overall training loss. We applied LoCal+SGD to 8 image recognition CNNs (including ResNet50 and MobileNetV2) across 3 datasets (Cifar10, Cifar100, and ImageNet). Our measurements on an Nvidia GTX 1080Ti GPU demonstrate upto 1.5× improvement in end-to-end training time with ~0.5% loss in Top-1 classification accuracy.
Discriminative Analysis of Schizophrenia Patients Using Topological Properties of Structural and Functional Brain Networks: A Multimodal Magnetic Resonance Imaging Study
Authors: Wang Jing , Ke Pengfei , Zang Jinyu , Wu Fengchun , Wu Kai
Published: January 2022

Interest in the application of machine learning (ML) techniques to multimodal magnetic resonance imaging (MRI) data for the diagnosis of schizophrenia (SZ) at the individual level is growing. However, a few studies have applied the features of structural and functional brain networks derived from multimodal MRI data to the discriminative analysis of SZ patients at different clinical stages. In this study, 205 normal controls (NCs), 61 first-episode drug-naive SZ (FESZ) patients, and 79 chronic SZ (CSZ) patients were recruited. We acquired their structural MRI, diffusion tensor imaging, and resting-state functional MRI data and constructed brain networks for each participant, including the gray matter network (GMN), white matter network (WMN), and functional brain network (FBN). We then calculated 3 nodal properties for each brain network, including degree centrality, nodal efficiency, and betweenness centrality. Two classifications (SZ vs. NC and FESZ vs. CSZ) were performed using five ML algorithms. We found that the SVM classifier with the input features of the combination of nodal properties of both the GMN and FBN achieved the best performance to discriminate SZ patients from NCs [accuracy, 81.2%; area under the receiver operating characteristic curve (AUC), 85.2%; p < 0.05]. Moreover, the SVM classifier with the input features of the combination of the nodal properties of both the GMN and WMN achieved the best performance to discriminate FESZ from CSZ patients (accuracy, 86.2%; AUC, 92.3%; p < 0.05). Furthermore, the brain areas in the subcortical/cerebellum network and the frontoparietal network showed significant importance in both classifications. Together, our findings provide new insights to understand the neuropathology of SZ and further highlight the potential advantages of multimodal network properties for identifying SZ patients at different clinical stages.
Use of Complementary and Alternative Medicine Among Patients With Epilepsy and Diabetes Mellitus, Focusing on the Outcome of Treatment
Authors: Girgis Michael Magdy Fahmy , Fekete Klára , Homoródi Nóra , Márton Sándor , Fekete István , Horváth László
Published: January 2022

Introduction: Millions all over the world live with epilepsy, and they may require long-term drug treatment. The use and interest in complementary and alternative medicine (CAM) have grown over the previous years. Coadministration of herbal products with medicines may result in adverse drug reactions (ADRs) and/or unfavorable interactions. The aims of this study were to determine the prevalence of CAM use among patients with epilepsy, to compare the results to those of the patients with diabetes mellitus (DM), to reveal factors that may drive the use of CAM, and to measure outcomes and adherence. It was also our intent to have state-of-the-art information on CAM use in our region among patients with the two diseases above.

Materials and Methods: We conducted a non-interventional study using a self-developed questionnaire. It was distributed among adult patients with either epilepsy or DM who also suffered from cardiovascular consequences. A database was compiled from the anonymous questionnaires filled in voluntarily by the patients. Basic statistics were used to analyze this database.

Results: A total of 227 questionnaires were filled in by 127 patients (55.9%) with epilepsy and 100 patients (44.1%) with DM. Mean age was 54.54 ± 17.33 years. Of the patients, 50.2% were male. Average body weight was 80.3 ± 17.3 kg. Of the patients, 22 (9.7%) used CAM because they believed in CAM. Two of them reported ADRs. Among the patients with epilepsy, the ratio was only 7.9% compared to 12% among those with DM. While the number of CAM users was higher among younger patients with epilepsy, it was the elderly patients with DM who tended to use CAM.

Conclusion: Attention should be paid to reliance on CAM during the follow-up. Our finding that health-conscious patients tend to use CAM more often (than the general population) may indicate it is necessary to discuss CAM usage sincerely. CAMs modulating cytochrome P450 (CYP) enzymes were the most common, leading to interactions with medication used and resulting in ADRs. This shows the importance of educating patients and treating team including clinical pharmacists in this field.
Bidirectional Modulation of Neuronal Cells Electrical and Mechanical Properties Through Pristine and Functionalized Graphene Substrates
Authors: Zummo Francesca , Esposito Pietro , Hou Huilei , Wetzl Cecilia , Rius Gemma , Tkatchenko Raphaela , Guimera Anton , Godignon Philippe , Prato Maurizio , Prats-Alfonso Elisabet , Criado Alejandro , Scaini Denis
Published: January 2022

In recent years, the quest for surface modifications to promote neuronal cell interfacing and modulation has risen. This course is justified by the requirements of emerging technological and medical approaches attempting to effectively interact with central nervous system cells, as in the case of brain-machine interfaces or neuroprosthetic. In that regard, the remarkable cytocompatibility and ease of chemical functionalization characterizing surface-immobilized graphene-based nanomaterials (GBNs) make them increasingly appealing for these purposes. Here, we compared the (morpho)mechanical and functional adaptation of rat primary hippocampal neurons when interfaced with surfaces covered with pristine single-layer graphene (pSLG) and phenylacetic acid-functionalized single-layer graphene (fSLG). Our results confirmed the intrinsic ability of glass-supported single-layer graphene to boost neuronal activity highlighting, conversely, the downturn inducible by the surface insertion of phenylacetic acid moieties. fSLG-interfaced neurons showed a significant reduction in spontaneous postsynaptic currents (PSCs), coupled to reduced cell stiffness and altered focal adhesion organization compared to control samples. Overall, we have here demonstrated that graphene substrates, both pristine and functionalized, could be alternatively used to intrinsically promote or depress neuronal activity in primary hippocampal cultures.
Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice
Authors: Liu Lanxiang , Wang Haiyang , Chen Xueyi , Zhang Yangdong , Li Wenxia , Rao Xuechen , Liu Yiyun , Zhao Libo , Pu Juncai , Gui Siwen , Yang Deyu , Fang Liang , Xie Peng
Published: January 2022

Major depressive disorder is caused by gene–environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the underlying mechanisms remain elusive. Herein, the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls were detected, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level, and in further to explore the microbial-regulated pathological mechanisms of depression. As a result, 200 mRNAs, 358 lncRNAs, and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differential mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting these differential mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, a microbial-regulated lncRNA–miRNA–mRNA network based on RNA–RNA interactions was constructed. Subsequently, according to the competitive endogenous RNAs (ceRNA) hypothesis and the biological functions of these intersected genes, two neurodevelopmental ceRNA sub-networks implicating in depression were identified, one including two lncRNAs (4930417H01Rik and AI480526), one miRNA (mmu-miR-883b-3p) and two mRNAs (Adcy1 and Nr4a2), and the other including six lncRNAs (5930412G12Rik, 6430628N08Rik, A530013C23Rik, A930007I19Rik, Gm15489, and Gm16251), one miRNA (mmu-miR-377-3p) and three mRNAs (Six4, Stx16, and Ube3a), and these molecules could be recognized as potential genetic and epigenetic biomarkers in microbial-associated depression. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants.
Spindle-Shaped Neurons in the Human Posteromedial (Precuneus) Cortex
Authors: Fuentealba-Villarroel Francisco Javier , Renner Josué , Hilbig Arlete , Bruton Oliver J. , Rasia-Filho Alberto A.
Published: January 2022

The human posteromedial cortex (PMC), which includes the precuneus (PC), represents a multimodal brain area implicated in emotion, conscious awareness, spatial cognition, and social behavior. Here, we describe the presence of Nissl-stained elongated spindle-shaped neurons (suggestive of von Economo neurons, VENs) in the cortical layer V of the anterior and central PC of adult humans. The adapted “single-section” Golgi method forpostmortemtissue was used to study these neurons close to pyramidal ones in layer V until merging with layer VI polymorphic cells. From three-dimensional (3D) reconstructed images, we describe the cell body, two main longitudinally oriented ascending and descending dendrites as well as the occurrence of spines from proximal to distal segments. The primary dendritic shafts give rise to thin collateral branches with a radial orientation, and pleomorphic spines were observed with a sparse to moderate density along the dendritic length. Other spindle-shaped cells were observed with straight dendritic shafts and rare branches or with an axon emerging from the soma. We discuss the morphology of these cells and those considered VENs in cortical areas forming integrated brain networks for higher-order activities. The presence of spindle-shaped neurons and the current discussion on the morphology of putative VENs address the need for an in-depth neurochemical and transcriptomic characterization of the PC cytoarchitecture. These findings would include these spindle-shaped cells in the synaptic and information processing by the default mode network and for general intelligence in healthy individuals and in neuropsychiatric disorders involving the PC in the context of the PMC functioning.
Nutritional Characterization of a Traditional Cultivar of Tomato Grown Under Organic Conditions—cv. “Malacara”
Authors: Raigón María D. , García-Martínez María D. , Chiriac Octavian P.
Published: January 2022

The loss of genetic diversity due to the replacement of local tomato (Solanum lycopersicumL.) varieties by improved cultivars has been mitigated in many cases by the good work of organic farmers in maintaining local agricultural biodiversity. In parallel to these initiatives, in recent years, consumers have developed an increasing awareness of both food-related health, environmental issues, and food demand to recover the flavors of the past. In the case of tomatoes, these attributes (nutritional, organoleptic, social, and environmental) are closely related to organic production using local varieties. “Malacara” tomato is an example of a local variety. Coming from Sierra de Cádiz, it is a varietal type called “Cuelga” (“for hanging,” because the tomato trusses are hung from beams in the farmhouses). Cultivated and harvested in the open air during the summer months, these tomatoes are commercialized and consumed in the winter. Historically, this variety has enabled the fresh consumption of tomatoes during the winter, without the need to force cultivation. It is highly appreciated in the local cuisine and is the basis for sauces figuring in typical dishes. Its characteristic traits are small, pallid fruits, and long shelf life. The main objective of this work has been to typify two Malacara tomato cultivars (red and yellow color) grown under organic farming conditions, through the characterization of morphological, nutritional, and volatile parameters. The main differences are due to morphological parameters (fruit weight and color of the exocarp and endocarp). Other characteristics such as the content of ash, fiber, moisture, the concentration of iron, magnesium, and calcium, and content of lycopene are different between both cultivars. This study provides information on the nutritional and aromatic composition of two Malacara tomato cultivars, differentiated by their color and grown under organic farming conditions. The results add value to the native horticultural heritage and can aid in the selection of tomato varieties suitable for a sustainable production system and to produce tomatoes with high nutritional value and rich in aroma.
Trends in Obesity and Metabolic Status in Northern and Southern China Between 2012 and 2020
Authors: Li Ying , Yang Lin , Yin Lu , Liu Qingqi , Wang Yaqin , Yang Pingting , Wang Jiangang , Chen Zhiheng , Li Xiaohui , Yang Qinyu , He Yongmei , Huang Xin
Published: January 2022

Background: The trends of obesity-associated metabolic status in Chinese are lacking, especially those from different regions.

Objectives: To examine the trends of obesity and metabolic status among Chinese population in 2012–2020.

Methods: In a series cross-sectional study, data on 256,782 participants surveyed between 2014 and 2020 in Beijing, northern China, and 697,170 participants surveyed between 2012 and 2020 in Hunan, southern China were analyzed. Anthropometrics, blood pressure measurements, and blood tests were performed according to standard protocols. Trends in obesity and metabolic status were evaluated using the Joinpoint software.

Results: Based on age- and sex-standardized values, the mean BMI values in northern and southern participants were 23.94 (95% CI: 23.93, 23.95) and 23.68 (95% CI: 23.67, 23.69) kg/m2, respectively. Between 2014 and 2020, the overall obesity prevalence among northern participants increased from 12.70% (95% CI: 12.17, 13.23%) to 14.33% (95% CI: 13.97, 14.70%) (P = 0.009), mainly derived by the 20–39 and 40–59 age groups. Moreover, the prevalence of metabolically healthy obese significantly increased from 2.07% (95% CI: 1.84, 2.30%) to 4.33% (95% CI: 4.13, 4.53%) in Northerners. Between 2012 and 2020, no significant trend in obesity was found among overall southern participants, but the prevalence of metabolically unhealthy obese significantly increased from 5.36% (95% CI: 5.18, 5.54%) to 7.35% (95% CI: 7.11, 7.58%), mainly derived by the 20–39 and 40–59 age groups.

Conclusions: The trends in obesity and metabolic status were different between southern and northern Chinese. A national weight control plan is needed in China, focusing on young and middle-aged population.
Prognostic Significance and Gene Co-Expression Network of PLAU and PLAUR in Gliomas
Authors: Li Junhong , Fan Huanhuan , Zhou Xingwang , Xiang Yufan , Liu Yanhui
Published: January 2022

The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.
Efficacy and Safety of Albumin-Bound Paclitaxel Compared to Docetaxel as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer
Authors: Lv Zhi-Dong , Song Hong-Ming , Niu Zhao-He , Nie Gang , Zheng Shuai , Xu Ying-Ying , Gong Wei , Wang Hai-Bo
Published: January 2022

Background

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as neoadjuvant chemotherapy (NAC) for breast cancer remains controversial. We conducted a retrospective study to compare the efficacy and safety of nab-paclitaxel with those of docetaxel as neoadjuvant regimens for HER2-negative breast cancer.

Methods

In this retrospective analysis, a total of 159 HER2-negative breast cancer patients who had undergone operation after NAC were consecutively analyzed from May 2016 to April 2018. Patients were classified into the nab-paclitaxel group (n = 79, nab-paclitaxel 260 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) and the docetaxel group (n = 80, docetaxel 75 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) according to the drug they received for neoadjuvant treatment. The efficacy and adverse events were evaluated in the two groups.

Results

The pathological complete response (pCR)(ypT0/isN0) rate was significantly higher in the nab-paclitaxel group than in the docetaxel group (36.71% vs 20.00%; P = 0.031). The multivariate analysis revealed that therapeutic drugs, lymph node status, and tumor subtype were the most significant factor influencing treatment outcome. At a median follow-up of 47 months, disease-free survival (DFS) was not significantly different in those assigned to nab-paclitaxel compared with docetaxel (82.28% vs 76.25%; P = 0.331). The incidence of peripheral sensory neuropathy in the nab-paclitaxel group was higher than that in the docetaxel group (60.76% vs 36.25%; P = 0.008), while the incidence of arthralgia was observed more frequently in the docetaxel group (57.50% vs 39.97%; P = 0.047).

Conclusions

Compared with docetaxel, nab-paclitaxel achieved a higher pCR rate, especially those patients with triple-negative breast cancer or lymph node negative breast cancer. However, there was no significant difference in DFS between the two groups. This study provides a valuable reference for the management of patients with HER2-negative breast cancer.
Extensive Dissection at No. 12 Station During D2 Lymphadenectomy Improves Survival for Advanced Lower-Third Gastric Cancer: A Retrospective Study From a Single Center in Southern China
Authors: Dai Weigang , Zhai Er-Tao , Chen Jianhui , Chen Zhihui , Zhao Risheng , Chen Chuangqi , Yuan Yujie , Wu Hui , Cai Shirong , He Yulong
Published: January 2022

Background

D2 lymphadenectomy including No. 12a dissection has been accepted as a standard surgical management of advanced lower-third gastric cancer (GC). The necessity of extensive No. 12 nodes (No. 12a, 12b, and 12p) dissection remains controversial. This study aims to explore its impact on long-term survival for resectable GC.

Methods

From 2009 to 2016, 353 advanced lower-third GC patients undergoing at least D2 lymphadenectomy during a radical surgery were included, with 179 patients receiving No. 12a, 12b, and 12p dissection as study group. A total of 174 patients with No. 12a dissection were employed as control group. Surgical and long-term outcomes including 90-day complications incidence, therapeutic value index (TVI), 3-year progression-free survival (PFS), and 5-year overall survival (OS) were compared between both groups.

Results

No. 12 lymph node metastasis was observed in 20 (5.7%) patients, with 10 cases in each group (5.6% vs. 5.7%, p = 0.948). The metastatic rates at No. 12a, 12b, and 12p were 5.7%, 2.2%, and 1.7%, respectively. The incidence of 90-day complications was identical between both groups. Extensive No. 12 dissection was associated with increased TVI at No. 12 station (3.9 vs. 0.6), prolonged 3-year PFS rate (67.0% vs. 55.9%, p = 0.045) and 5-year OS rate (66.2% vs. 54.0%, p = 0.027). The further Cox-regression analysis showed that the 12abp dissection was an independent prognostic factor of improved survival (p = 0.026).

Conclusion

Adding No. 12b and 12p lymph nodes to D2 lymphadenectomy might be effective in surgical treatment of advanced lower-third GC and improve oncological outcomes compared with No. 12a-based D2 lymphadenectomy.
Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study
Authors: Masson Ingrid , Bellanger Martine , Perrocheau Geneviève , Mahé Marc-André , Azria David , Pommier Pascal , Mesgouez-Nebout Nathalie , Giraud Philippe , Peiffert Didier , Chauvet Bruno , Dudouet Philippe , Salem Naji , Noël Georges , Khalifa Jonathan , Latorzeff Igor , Guérin-Charbonnel Catherine , Supiot Stéphane
Published: January 2022

Background

Intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.

Material and Methods

We used data from the “RCMI pelvis” prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.

Results

The mean total cost for HT, €2019 3,069 (95% CI, 2,885–3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443–2,651) (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.

Conclusion

Use of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.
Dynamic Activity of Histone H3-Specific Chaperone Complexes in Oncogenesis
Authors: Wen Ting , Chen Qiao Yi
Published: January 2022

Canonical histone H3.1 and variant H3.3 deposit at different sites of the chromatin via distinct histone chaperones. Histone H3.1 relies on chaperone CAF-1 to mediate replication-dependent nucleosome assembly during S-phase, while H3.3 variant is regulated and incorporated into the chromatin in a replication-independent manner through HIRA and DAXX/ATRX. Current literature suggests that dysregulated expression of histone chaperones may be implicated in tumor progression. Notably, ectopic expression of CAF-1 can promote a switch between canonical H3.1 and H3 variants in the chromatin, impair the chromatic state, lead to chromosome instability, and impact gene transcription, potentially contributing to carcinogenesis. This review focuses on the chaperone proteins of H3.1 and H3.3, including structure, regulation, as well as their oncogenic and tumor suppressive functions in tumorigenesis.