bluuebunny/crossref_metadata_2025 huggingface dataset:
Halophilic Archaea Halorhabdus Rudnickae and Natrinema Salaciae Activate Human Dendritic Cells and Orient T Helper Cell Responses
Authors: Krawczyk Krzysztof T. , Locht Camille , Kowalewicz-Kulbat Magdalena
Published: June 2022

Halophilic archaea are procaryotic organisms distinct from bacteria, known to thrive in hypersaline environments, including salt lakes, salterns, brines and salty food. They have also been identified in the human microbiome. The biological significance of halophiles for human health has rarely been examined. The interactions between halophilic archaea and human dendritic cells (DCs) and T cells have not been identified so far. Here, we show for the first time that the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae activate human monocyte-derived DCs, induce DC maturation, cytokine production and autologous T cell activation. In vitro both strains induced DC up-regulation of the cell-surface receptors CD86, CD80 and CD83, and cytokine production, including IL-12p40, IL-10 and TNF-α, but not IL-23 and IL-12p70. Furthermore, autologous CD4+ T cells produced significantly higher amounts of IFN-γ and IL-13, but not IL-17A when co-cultured with halophile-stimulated DCs in comparison to T cells co-cultured with unstimulated DCs. IFN-γ was almost exclusively produced by naïve T cells, while IL-13 was produced by both naïve and memory CD4+ T cells. Our findings thus show that halophilic archaea are recognized by human DCs and are able to induce a balanced cytokine response. The immunomodulatory functions of halophilic archaea and their potential ability to re-establish the immune balance may perhaps participate in the beneficial effects of halotherapies.
Upper Gastrointestinal Tract IrAEs: A Case Report About Sintilimab-Induced Acute Erosive Hemorrhagic Gastritis
Authors: Ai Qi , Chen Wen , Li Yonggui , Li Guoqing
Published: June 2022

Introduction

Immune checkpoint inhibitors (ICIs) have now become the standard therapy for malignancies like non-small cell lung cancer and classical Hodgkin’s lymphoma. ICIs are associated with unique immune-related adverse events (irAEs) caused by dysregulated immune activation. Treatment of lower gastrointestinal (GI) tract irAEs, such as colitis, is more common. However, for upper gastrointestinal tract irAEs, there is a lack of consensus in terms of globally standardized disease classification and treatment guidelines. Here, we report a case of sintilimab-induced acute erosive hemorrhagic gastritis.

Case Presentation

A 54-year-old man with metastatic NSCLC (PT2N2M1 stage IV) underwent treatment with eight courses of sintilimab + bevacizumab, followed by maintenance therapy with sintilimab alone. However, he presented with epigastric pain and melena at the end of the first sintilimab treatment, and the symptoms occurred repeatedly after regular treatment with acute erosive hemorrhagic gastritis. Repeat esophagogastroduodenoscopy (EGD) showed severe hemorrhagic gastritis; symptomatic relief and improvement in EGD images were noted for as long as he was being treated with steroids, methylprednisolone sodium.

Conclusion

As far as we are aware, we here describe the first case of sintilimab-associated acute erosive hemorrhagic gastritis, an upper gastrointestinal toxicity event. Throughout the treatment progression, differential diagnosis, multidisciplinary discussion, and the use of immunosuppressants were instrumental in clarifying the diagnosis and were crucial to the prognosis of the patient and continued treatment with ICIs.
CCL5-Secreting Virtual Memory CD8+ T Cells Inversely Associate With Viral Reservoir Size in HIV‐1−Infected Individuals on Antiretroviral Therapy
Authors: Hu Wei , Li Yan-Jun , Zhen Cheng , Wang You-Yuan , Huang Hui-Huang , Zou Jun , Zheng Yan-Qing , Huang Gui-Chan , Meng Si-Run , Jin Jie-Hua , Li Jing , Zhou Ming-Ju , Fu Yu-Long , Zhang Peng , Li Xiao-Yu , Yang Tao , Wang Xiu-Wen , Yang Xiu-Han , Song Jin-Wen , Fan Xing , Jiao Yan-Mei , Xu Ruo-Nan , Zhang Ji-Yuan , Zhou Chun-Bao , Yuan Jin-Hong , Huang Lei , Qin Ya-Qin , Wu Feng-Yao , Shi Ming , Wang Fu-Sheng , Zhang Chao
Published: June 2022

Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (TCM) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (TEMRA). Moreover, a virtual memory CD8+ T cell (TVM) subset was enriched in CCL4-CCL5+ TEMRA cells and phenotypically distinctive from CCL4+ TCM subset, supported by single-cell RNA-Seq data. Specifically, TVM cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ TCM subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, TVM cells inhibited HIV-1 reactivation more effectively than non-TVM CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting TVM cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease.
Quantifying Reductions in Plasmodium falciparum Infectivity to Mosquitos: A Sample Size Calculator to Inform Clinical Trials on Transmission-Reducing Interventions
Authors: Ramjith Jordache , Alkema Manon , Bradley John , Dicko Alassane , Drakeley Chris , Stone Will , Bousema Teun
Published: June 2022

Malaria transmission depends on the presence of mature Plasmodium transmission stages (gametocytes) that may render blood-feeding Anopheles mosquitos infectious. Transmission-blocking antimalarial drugs and vaccines can prevent transmission by reducing gametocyte densities or infectivity to mosquitos. Mosquito infection outcomes are thereby informative biological endpoints of clinical trials with transmission blocking interventions. Nevertheless, trials are often primarily designed to determine intervention safety; transmission blocking efficacy is difficult to incorporate in sample size considerations due to variation in infection outcomes and considerable inter-study variation. Here, we use clinical trial data from studies in malaria naive and naturally exposed study participants to present an online sample size calculator tool. This sample size calculator allows studies to be powered to detect reductions in the proportion of infected mosquitos or infection burden (oocyst density) in mosquitos. The utility of this online tool is illustrated using trial data with transmission blocking malaria drugs.
Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years
Authors: Tan Yong Chiang , Lahiri Chandrajit
Published: June 2022

In parallel to the uncontrolled use of antibiotics, the emergence of multidrug-resistant bacteria, like Acinetobacter baumannii, has posed a severe threat. A. baumannii predominates in the nosocomial setting due to its ability to persist in hospitals and survive antibiotic treatment, thereby eventually leading to an increasing prevalence and mortality due to its infection. With the increasing spectra of drug resistance and the incessant collapse of newly discovered antibiotics, new therapeutic countermeasures have been in high demand. Hence, recent research has shown favouritism towards the long-term solution of designing vaccines. Therefore, being a realistic alternative strategy to combat this pathogen, anti-A. Baumannii vaccines research has continued unearthing various antigens with variable results over the last decade. Again, other approaches, including pan-genomics, subtractive proteomics, and reverse vaccination strategies, have shown promise for identifying promiscuous core vaccine candidates that resulted in chimeric vaccine constructs. In addition, the integration of basic knowledge of the pathobiology of this drug-resistant bacteria has also facilitated the development of effective multiantigen vaccines. As opposed to the conventional trial-and-error approach, incorporating the in silico methods in recent studies, particularly network analysis, has manifested a great promise in unearthing novel vaccine candidates from the A. baumannii proteome. Some studies have used multiple A. baumannii data sources to build the co-functional networks and analyze them by k-shell decomposition. Additionally, Whole Genomic Protein Interactome (GPIN) analysis has utilized a rational approach for identifying essential proteins and presenting them as vaccines effective enough to combat the deadly pathogenic threats posed by A. baumannii. Others have identified multiple immune nodes using network-based centrality measurements for synergistic antigen combinations for different vaccination strategies. Protein-protein interactions have also been inferenced utilizing structural approaches, such as molecular docking and molecular dynamics simulation. Similar workflows and technologies were employed to unveil novel A. baumannii drug targets, with a similar trend in the increasing influx of in silico techniques. This review integrates the latest knowledge on the development of A. baumannii vaccines while highlighting the in silico methods as the future of such exploratory research. In parallel, we also briefly summarize recent advancements in A. baumannii drug target research.
Three Oxidative Stress-Related Genes That Associate Endometrial Immune Cells Are Considered as Potential Biomarkers for the Prediction of Unexplained Recurrent Implantation Failure
Authors: Lin Jia-zhe , Lin Nuan
Published: June 2022

Recurrent implantation failure (RIF) represents a new challenge in the field of assisted reproductive technology (ART). Considering the known effects of immune cell regulation on embryo implantation process, as well as our gene set variation analysis (GSVA) results that suggested the association between RIF and pathways of oxidative stress and immune responses, we hypothesized that oxidative stress- related genes (OSGs) associated with aberrant immunological factor may represent novel biomarkers for unexplained RIF. We therefore screened out the immune cell coexpressed OSGs by performing CIBERSORT, LM22 matrix and Pearson correlation, followed by constructing an OSG signature by least absolute shrinkage and selection operator (LASSO) regression. Three OSGs (AXL, SLC7A11 and UBQLN1) were then identified to establish a RIF risk signature, which showed high ability to discriminating RIF from fertile control. A nomogram was established, with a free online calculator for easier clinical application. Finally, Chilibot, protein-protein interaction analysis and BioGPS were sequentially applied for the investigation of functional relationships of these three genes with RIF and other OSGs, as well as their expression abundance across different human tissues. In conclusion, we identified an OSG signature that are relevant novel markers for the occurrence of unexplained RIF.
Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer
Authors: Zhang Pingxin , Gao Hang , Ye Chunwei , Yan Ruping , Yu Lu , Xia Chengxing , Yang Delin
Published: June 2022

Prostate cancer (PCa) is one of the most prevalent cancers of the urinary system. In previous research, Kinesin family member 2C (KIF2C), as an oncogene, has been demonstrated to have a key role in the incidence and progression of different cancers. However, KIF2C has not been reported in PCa. We combined data from different databases, including The Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and the Genomics of Drug Sensitivity in Cancer database, to explore the potential oncogenic role of KIF2C in PCa through a series of bioinformatics approaches, including analysis of the association between KIF2C and prognosis, clinicopathological features, gene mutations, DNA methylation, immune cell infiltration, and drug resistance. The results showed that KIF2C was significantly up-regulated in PCa. High KIF2C expression was associated with age, pathological stage, lymph node metastases, prostate-specific antigen (PSA), and Gleason score and significantly predicted an unfavorable prognosis in PCa patients. Results from Gene Set Enrichment Analysis (GSEA) suggested that KIF2C was involved in the cell cycle and immune response. KIF2C DNA methylation was reduced in PCa and was inversely linked with KIF2C expression. KIF2C was shown to have a strong relationship with the tumor microenvironment (TME), infiltrating cells, and immune checkpoint genes. Furthermore, high KIF2C expression was significantly resistant to a variety of MAPK signaling pathway-related inhibitors. Our study reveals that KIF2C may be a possible predictive biomarker for assessing prognosis in PCa patients with immune infiltration.
Antimicrobial Resistance in the COVID-19 Landscape: Is There an Opportunity for Anti-Infective Antibodies and Antimicrobial Peptides?
Authors: Pérez de la Lastra José M. , Anand Uttpal , González-Acosta Sergio , López Manuel R. , Dey Abhijit , Bontempi Elza , Morales delaNuez Antonio
Published: June 2022

Although COVID-19 has captured most of the public health attention, antimicrobial resistance (AMR) has not disappeared. To prevent the escape of resistant microorganisms in animals or environmental reservoirs a “one health approach” is desirable. In this context of COVID-19, AMR has probably been affected by the inappropriate or over-use of antibiotics. The increased use of antimicrobials and biocides for disinfection may have enhanced the prevalence of AMR. Antibiotics have been used empirically in patients with COVID-19 to avoid or prevent bacterial coinfection or superinfections. On the other hand, the measures to prevent the transmission of COVID-19 could have reduced the risk of the emergence of multidrug-resistant microorganisms. Since we do not currently have a sterilizing vaccine against SARS-CoV-2, the virus may still multiply in the organism and new mutations may occur. As a consequence, there is a risk of the appearance of new variants. Nature-derived anti-infective agents, such as antibodies and antimicrobial peptides (AMPs), are very promising in the fight against infectious diseases, because they are less likely to develop resistance, even though further investigation is still required.
In vivo Confocal Microscopic Evaluation of Previously Neglected Oval Cells in Corneal Nerve Vortex: An Inflammatory Indicator of Dry Eye Disease
Authors: Jing Dalan , Jiang Xiaodan , Chou Yilin , Wei Shanshan , Hao Ran , Su Jie , Li Xuemin
Published: June 2022

This study aimed to investigate the association of between previously neglected oval cells located in the corneal vortex and dry eye disease (DED). This was an observational, prospective study involving 168 patients with different degrees of DED. In vivo confocal microscopy was used to observe the corneal subbasal nerves and Langerhans cells (LCs) in the corneal vortex and periphery. Bright and oval cells were also observed in the corneal vortex. An artificial intelligence technique was used to generate subbasal nerve fiber parameters. The patients were divided into the three groups based on the presence of inflammatory cells. Group 2 patients showed a significant increase in the corneal peripheral nerve maximum length and average corneal peripheral nerve density. Patients in group 3 had more LCs than other patients. A bright and oval cell was identified in the corneal vortex, which might be a type of immature LC related to the disease severity of DED.
Endothelial Activation and Microcirculatory Disorders in Sepsis
Authors: Raia Lisa , Zafrani Lara
Published: June 2022

The vascular endothelium is crucial for the maintenance of vascular homeostasis. Moreover, in sepsis, endothelial cells can acquire new properties and actively participate in the host's response. If endothelial activation is mostly necessary and efficient in eliminating a pathogen, an exaggerated and maladaptive reaction leads to severe microcirculatory damage. The microcirculatory disorders in sepsis are well known to be associated with poor outcome. Better recognition of microcirculatory alteration is therefore essential to identify patients with the worse outcomes and to guide therapeutic interventions. In this review, we will discuss the main features of endothelial activation and dysfunction in sepsis, its assessment at the bedside, and the main advances in microcirculatory resuscitation.
Antibiotic Treatment of Acinetobacter baumannii Superinfection in Patients With SARS-CoV-2 Infection Admitted to Intensive Care Unit: An Observational Retrospective Study
Authors: Casarotta Erika , Bottari Elisa , Vannicola Sara , Giorgetti Rachele , Domizi Roberta , Carsetti Andrea , Damiani Elisa , Scorcella Claudia , Gabbanelli Vincenzo , Pantanetti Simona , Marini Benedetto , Donati Abele , Adrario Erica
Published: June 2022

Introduction

In COVID-19 patients on mechanical ventilation, VAP from Acinetobacter baumannii remains a crucial risk factor for death. Antibiotic resistance represents an important problem in treating this infection. This study aims to describe the evolution of the superinfection from PDR Acinetobacter baumannii in patients with acute respiratory failure from SARS-CoV-2 infection admitted to ICU and compare the impact of two different antibiotic strategies on microbiological negativization.

Methods

Single-center observational retrospective study, including patients admitted to our ICU from March 2020 to May 2021 for acute respiratory failure from SARS-CoV-2 infection who developed PDR Acinetobacter baumannii superinfection. Clinical data at ICU admission were collected, as well as the timing of isolation of Acinetobacter baumannii, its resistance profile, the site of infection, and the antibiotic therapy.

Results

Of the 32 patients enrolled, 10 patients (31.2%) were treated with the combination of high-dose ampicillin/sulbactam, high-dose tigecycline, intravenous and inhaled colistin (Protocol), the other 22 (68.8%) were treated with the combination of two antibiotics (Control). Of the 10 patients in the Protocol group, 8 patients (80%) received also fosfomycin. All patients (100%) in the Protocol group had microbiological negativization, while in the Control group microbiological negativization was observed in 8 (36.4%) patients, p < 0.01.

Conclusion

Our report shows microbiological negativization in all patients treated with the combination therapy of nebulized and intravenous colistin, high-dose tigecycline, and high-dose ampicillin/sulbactam. This combination of antibiotics seems to be a useful alternative when other treatments are not available or fail.
The Potential of Sequential Fermentations in Converting C1 Substrates to Higher-Value Products
Authors: Stark Christina , Münßinger Sini , Rosenau Frank , Eikmanns Bernhard J. , Schwentner Andreas
Published: June 2022

Today production of (bulk) chemicals and fuels almost exclusively relies on petroleum-based sources, which are connected to greenhouse gas release, fueling climate change. This increases the urgence to develop alternative bio-based technologies and processes. Gaseous and liquid C1 compounds are available at low cost and often occur as waste streams. Acetogenic bacteria can directly use C1 compounds like CO, CO2, formate or methanol anaerobically, converting them into acetate and ethanol for higher-value biotechnological products. However, these microorganisms possess strict energetic limitations, which in turn pose limitations to their potential for biotechnological applications. Moreover, efficient genetic tools for strain improvement are often missing. However, focusing on the metabolic abilities acetogens provide, they can prodigiously ease these technological disadvantages. Producing acetate and ethanol from C1 compounds can fuel via bio-based intermediates conversion into more energy-demanding, higher-value products, by deploying aerobic organisms that are able to grow with acetate/ethanol as carbon and energy source. Promising new approaches have become available combining these two fermentation steps in sequential approaches, either as separate fermentations or as integrated two-stage fermentation processes. This review aims at introducing, comparing, and evaluating the published approaches of sequential C1 fermentations, delivering a list of promising organisms for the individual fermentation steps and giving an overview of the existing broad spectrum of products based on acetate and ethanol. Understanding of these pioneering approaches allows collecting ideas for new products and may open avenues toward making full use of the technological potential of these concepts for establishment of a sustainable biotechnology.
Parameterizing Practice in a Longitudinal Measurement Burst Design to Dissociate Retest Effects From Developmental Change: Implications for Aging Neuroscience
Authors: Tamburri Nicholas , McDowell Cynthia , MacDonald Stuart W. S.
Published: June 2022

Background: In longitudinal designs, the extraneous influence of retest effects can confound and obscure estimates of developmental change. The current study provides a novel approach to independently parameterize short-term retest effects and long-term developmental change estimates by leveraging a measurement burst design and three-level multilevel modeling. We further employ these short- and long-term slopes as predictors of cognitive status at long-term follow-up assessments.

Methods: Participants included 304 older adults from Project MIND: a longitudinal measurement burst study assessing cognitive performance across both biweekly sessions and annual retests. Participants were classified as either Healthy controls (HC) or Cognitively Impaired, not Demented (CIND) at baseline, the final burst assessment (Year 4), and at an additional four-year follow-up (Year 8). Response time inconsistencies (RTI) were computed at each burst occasion for a simple choice response time (CRT) task and a one-back response time (BRT) task. Three-level multilevel models were employed to simultaneously examine change in RTI for both CRT and BRT across weeks within years, as well as across years, in order to dissociate within-individual retest effects (short-term) from developmental (long-term) change slopes. Individual slopes were then extracted and utilized in a series of multinomial logistic regression equations to contrast short- vs. long-term RTI change as predictors of cognitive status.

Results: Separately parameterizing short- and long-term change estimates yielded distinct patterns of variation. CRT RTI remained stable across short-term weekly assessments, while significantly increasing across years. In contrast, BRT RTI decreased significantly across short-term assessments but showed no change across long-term assessments. After dissociating change estimates, short-term BRT as well as long-term CRT and BRT estimates predicted cognitive status at long-term follow-ups; increases in RTI, suggesting either an inability to benefit from retest or process-based developmental decline, were associated with an increased likelihood of being classified as CIND.

Conclusions: We showcase an innovative approach to dissociate retest effects from developmental change across and within individuals. Accurately parameterizing these distinct change estimates can both reduce systematic bias in longitudinal trend estimates as well as provide a clinically useful tool by utilizing retest effects to predict cognitive health and impairment.
Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases
Authors: Martín Giménez Virna Margarita , de las Heras Natalia , Lahera Vicente , Tresguerres Jesús A. F. , Reiter Russel J. , Manucha Walter
Published: June 2022

The concept of “aging” is defined as the set of gradual and progressive changes in an organism that leads to an increased risk of weakness, disease, and death. This process may occur at the cellular and organ level, as well as in the entire organism of any living being. During aging, there is a decrease in biological functions and in the ability to adapt to metabolic stress. General effects of aging include mitochondrial, cellular, and organic dysfunction, immune impairment or inflammaging, oxidative stress, cognitive and cardiovascular alterations, among others. Therefore, one of the main harmful consequences of aging is the development and progression of multiple diseases related to these processes, especially at the cardiovascular and central nervous system levels. Both cardiovascular and neurodegenerative pathologies are highly disabling and, in many cases, lethal. In this context, melatonin, an endogenous compound naturally synthesized not only by the pineal gland but also by many cell types, may have a key role in the modulation of multiple mechanisms associated with aging. Additionally, this indoleamine is also a therapeutic agent, which may be administered exogenously with a high degree of safety. For this reason, melatonin could become an attractive and low-cost alternative for slowing the processes of aging and its associated diseases, including cardiovascular and neurodegenerative disorders.
Electroencephalography Microstate Alterations in Otogenic Vertigo: A Potential Disease Marker
Authors: Li Yi-Ni , Lu Wen , Li Jie , Li Ming-Xian , Fang Jia , Xu Tao , Yuan Ti-Fei , Qian Di , Shi Hai-Bo , Yin Shan-Kai
Published: June 2022

Objectives

A huge population, especially the elderly, suffers from otogenic vertigo. However, the multi-modal vestibular network changes, secondary to periphery vestibular dysfunction, have not been fully elucidated. We aim to identify potential microstate electroencephalography (EEG) signatures for otogenic vertigo in this study.

Materials and Methods

Patients with recurrent otogenic vertigo and age-matched healthy adults were recruited. We performed 256-channel EEG recording of all participants at resting state. Neuropsychological questionnaires and vestibular function tests were taken as a measurement of patients’ symptoms and severity. We clustered microstates into four classes (A, B, C, and D) and identified their dynamic and syntax alterations of them. These features were further fed into a support vector machine (SVM) classifier to identify microstate signatures for vertigo.

Results

We compared 40 patients to 45 healthy adults, finding an increase in the duration of Microstate A, and both the occurrence and time coverage of Microstate D. The coverage and occurrence of Microstate C decreased significantly, and the probabilities of non-random transitions between Microstate A and D, as well as Microstate B and C, also changed. To distinguish the patients, the SVM classifier, which is built based on these features, got a balanced accuracy of 0.79 with a sensitivity of 0.78 and a specificity of 0.8.

Conclusion

There are several temporal dynamic alterations of EEG microstates in patients with otogenic vertigo, especially in Microstate D, reflecting the underlying process of visual-vestibular reorganization and attention redistribution. This neurophysiological signature of microstates could be used to identify patients with vertigo in the future.
Application of Deep Convolution Network Algorithm in Sports Video Hot Spot Detection
Authors: Zhang Yaling , Tang Huan , Zereg Fateh , Xu Dekai
Published: June 2022

Sports videos are blowing up over the internet with enriching material life and the higher pursuit of spiritual life of people. Thus, automatically identifying and detecting helpful information from videos have arisen as a relatively novel research direction. Accordingly, the present work proposes a Human Pose Estimation (HPE) model to automatically classify sports videos and detect hot spots in videos to solve the deficiency of traditional algorithms. Firstly, Deep Learning (DL) is introduced. Then, amounts of human motion features are extracted by the Region Proposal Network (RPN). Next, an HPE model is implemented based on Deep Convolutional Neural Network (DCNN). Finally, the HPE model is applied to motion recognition and video classification in sports videos. The research findings corroborate that an effective and accurate HPE model can be implemented using the DCNN to recognize and classify videos effectively. Meanwhile, Big Data Technology (BDT) is applied to count the playing amounts of various sports videos. It is convinced that the HPE model based on DCNN can effectively and accurately classify the sports videos and then provide a basis for the following statistics of various sports videos by BDT. Finally, a new outlook is proposed to apply new technology in the entertainment industry.
NLRP3-Dependent Pyroptosis: A Candidate Therapeutic Target for Depression
Authors: Wan Teng , Li Xiaoyu , Fu Mingyuan , Gao Xiaoyu , Li Peiling , Guo Weiming
Published: June 2022

Depression, a major public health problem, imposes a significant economic burden on society. Recent studies have gradually unveiled the important role of neuroinflammation in the pathogenesis of depression. Pyroptosis, a programmed cell death mediated by Gasdermins (GSDMs), is also considered to be an inflammatory cell death with links to inflammation. Pyroptosis has emerged as an important pathological mechanism in several neurological diseases and has been found to be involved in several neuroinflammatory-related diseases. A variety of chemical agents and natural products have been found to be capable of exerting therapeutic effects by modulating pyroptosis. Studies have shown that depression is closely associated with pyroptosis and the induced neuroinflammation of relevant brain regions, such as the hippocampus, amygdala, prefrontal cortex neurons, etc., in which the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome plays a crucial role. This article provides a timely review of recent findings on the activation and regulation of pyroptosis in relation to depression.
Multisite Dopamine Sensing With Femtomolar Resolution Using a CMOS Enabled Aptasensor Chip
Authors: Sessi Violetta , Ibarlucea Bergoi , Seichepine Florent , Klinghammer Stephanie , Ibrahim Imad , Heinzig André , Szabo Nadine , Mikolajick Thomas , Hierlemann Andreas , Frey Urs , Weber Walter M. , Baraban Larysa , Cuniberti Gianaurelio
Published: June 2022

Many biomarkers including neurotransmitters are found in external body fluids, such as sweat or saliva, but at lower titration levels than they are present in blood. Efficient detection of such biomarkers thus requires, on the one hand, to use techniques offering high sensitivity, and, on the other hand, to use a miniaturized format to carry out diagnostics in a minimally invasive way. Here, we present the hybrid integration of bottom-up silicon-nanowire Schottky-junction FETs (SiNW SJ-FETs) with complementary-metal–oxide–semiconductor (CMOS) readout and amplification electronics to establish a robust biosensing platform with 32 × 32 aptasensor measurement sites at a 100 μm pitch. The applied hetero-junctions yield a selective biomolecular detection down to femtomolar concentrations. Selective and multi-site detection of dopamine is demonstrated at an outstanding sensitivity of ∼1 V/fM. The integrated platform offers great potential for detecting biomarkers at high dilution levels and could be applied, for example, to diagnosing neurodegenerative diseases or monitoring therapy progress based on patient samples, such as tear liquid, saliva, or eccrine sweat.
Using Advanced Diffusion-Weighted Imaging to Predict Cell Counts in Gray Matter: Potential and Pitfalls
Authors: Radhakrishnan Hamsanandini , Shabestari Sepideh Kiani , Blurton-Jones Mathew , Obenaus Andre , Stark Craig E. L.
Published: June 2022

Recent advances in diffusion imaging have given it the potential to non-invasively detect explicit neurobiological properties, beyond what was previously possible with conventional structural imaging. However, there is very little known about what cytoarchitectural properties these metrics, especially those derived from newer multi-shell models like Neurite Orientation Dispersion and Density Imaging (NODDI) correspond to. While these diffusion metrics do not promise any inherent cell type specificity, different brain cells have varying morphologies, which could influence the diffusion signal in distinct ways. This relationship is currently not well-characterized. Understanding the possible cytoarchitectural signatures of diffusion measures could allow them to estimate important neurobiological properties like cell counts, potentially resulting in a powerful clinical diagnostic tool. Here, using advanced diffusion imaging (NODDI) in the mouse brain, we demonstrate that different regions have unique relationships between cell counts and diffusion metrics. We take advantage of this exclusivity to introduce a framework to predict cell counts of different types of cells from the diffusion metrics alone, in a region-specific manner. We also outline the challenges of reliably developing such a model and discuss the precautions the field must take when trying to tie together medical imaging modalities and histology.
Geriatric Nutritional Risk Index is Associated with Hospital Death in Elderly Patients with Multiple Organ Dysfunction Syndrome: A Retrospective Study Based on the MIMIC-III Database
Authors: Mao Zhi , Wen Tao , Liu Xiaoli , Chen Jinsong , Hu Pan , Liu Chao , Liu Hui , Kang Hongjun , Zhang Zhengbo , Zhou Feihu
Published: June 2022

Purpose

Elderly patients with multiple organ dysfunction syndrome (MODS) have a higher mortality during hospitalization in the intensive care unit (ICU). Elderly patients often suffer from malnutrition. On the basis of the MIMIC-III database, this study analyzed the effect of the baseline nutritional status on the death of elderly patients with MODS during hospitalization.

Materials and Methods

Elderly patients with MODS were screened out from MIMIC-III 1.4 database. The geriatric nutritional risk index (GNRI) was calculated and used to group patients into: normal nutrition (GNRI > 98) and malnutrition (GNRI ≤ 98) groups. The malnutrition group was divided into mild (92–98), moderate (82–91), and severe (≤81) groups. The differences in the baseline data and the incidence of adverse events between groups were compared. The GAM model was used to determine whether a curve relationship was present between the hospital death of elderly patients with MODS and GNRI and analyze the threshold saturation effect. The multivariate logistic regression was used to calculate the odds ratio (OR) of in-hospital deaths in different GNRI groups. The interaction test was performed to find subgroups with differences.

Results

A total of 2456 elderly patients with MODS were enrolled. A total of 1,273 (51.8%) and 1183 (48.2%) patients were in the normal nutrition and malnutrition groups, respectively. The mortality rate of patients in the normal nutrition group during hospitalization was lower than that in the malnutrition group (206/1273 vs. 292/1183, X2 = 27.410, P < 0.001; OR = 0.59, 95% CI: 0.48–0.72). The GAM model fitting analysis showed a threshold saturation effect at GNRI = 92. Adjusted OR values with GNRI ≥ 92 began to change to 1, and GNRI and death had no association. At GNRI < 92, high GNRI related to low risk of death. Subgroup analysis of patients with GNRI < 92 showed that the risk of death in elderly male patients was lower than that of female patients.

Conclusion

GNRI is related to the severity of illness in elderly patients with MODS. At GNRI < 92, moderate to severe malnutrition increases the risk of death in elderly patients with MODS during hospitalization.
Differences in the Impact of Heart Rate Variability on the Surgical Approach in Patients With Early Cervical Cancer: Laparoscopic versus Open Surgery
Authors: Liu Jian , Wang Jingfeng , Deng Zhaoya , Liu Shiqi , Li Guangqiao , Sun Yilin , Gao Longfei , Li Chenghui , Shi Bo
Published: June 2022

Background

Evidence suggests that the risk of recurrence and death in patients with early cervical cancer (ECC) undergoing minimally invasive surgery is significantly higher than that in patients undergoing open surgery. However, the mechanisms underlying such a difference remain unclear. Heart rate variability (HRV) represents autonomic nerve activity, which is related to tumorgenesis and can be used as a prognostic indicator for various cancers. The main purpose of this study was to explore the difference in the effects of laparoscopic and open surgery on HRV in ECC patients.

Methods

A total of 68 ECC (FIGO IA1 with lymphovascular space invasion -IIA2) patients undergoing radical hysterectomy for the first time (84% open group vs. 16% laparoscopic group) were included. A single-lead micro-ECG recorder was used to collect 5 min electrocardiograms 1 day before the operation and 3 days after the operation, and then HRV time domain and frequency domain indices were analyzed, including mean heart rate (MeanHR), maximum heart rate (MaxHR), minimum heart rate (MinHR), the standard deviation of all normal-to-normal intervals (SDNN), the root mean square of successive interval differences (RMSSD), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), total power (TP), and the ratio of LF to HF (LF/HF).

Results

Heart rate (i.e., MeanHR, MaxHR, and MinHR) were significantly higher, and HRV (i.e., SDNN, RMSSD, LF, HF, and TP) were significantly lower after the operation than before the operation in both the laparoscopic and open groups (P < 0.05). The postoperative reduction in RMSSD and HF was significantly higher in the laparoscopic group than in the open group (P < 0.05).

Conclusions

These data suggest that radical hysterectomy can lead to increased heart rate and decreased HRV in patients with ECC, which can negatively affect cardiac autonomic regulation. Compared with open surgery, laparoscopic surgery has a greater negative impact on the HRV of ECC patients.
Olaparib Induces RPL5/RPL11-Dependent p53 Activation via Nucleolar Stress
Authors: Han Tao , Tong Jing , Wang Mengxin , Gan Yu , Gao Bo , Chen Jiaxiang , Liu Youxun , Hao Qian , Zhou Xiang
Published: June 2022

The poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) Olaparib is a widely used targeted therapy for a variety of solid tumors with homologous recombination deficiency (HRD) caused by mutation of BRCA1/2 or other DNA repair genes. The anti-tumor activity of Olaparib has been largely attributed to its ability to inhibit PARP enzymes and block DNA single-strand break (SSB) repair, which eventually leads to the most detrimental DNA damage, double-strand breaks (DSB), in HRD cells. Although PARPi was found to induce p53-dependent cell death, the underlying molecular mechanism remains incompletely understood. Here, we report that Olaparib treatment leads to p53 stabilization and activation of its downstream target genes in a dose- and time-dependent manner. Mechanistically, Olaparib triggers nucleolar stress by inhibiting biosynthesis of the precursor of ribosomal RNAs (pre-rRNA), resulting in enhanced interaction between ribosomal proteins (RPs), RPL5 and RPL11, and MDM2. Consistently, knockdown of RPL5 and RPL11 prevents Olaparib-induced p53 activation. More importantly, Olaparib efficiently suppresses breast and colorectal cancer cell survival and proliferation through activation of p53. Altogether, our study demonstrates that Olaparib activates the nucleolar stress-RPs-p53 pathway, suggesting rRNA biogenesis as a novel target for PARPi.
Prediction of Transcription Factor Binding Sites Using a Combined Deep Learning Approach
Authors: Cao Linan , Liu Pei , Chen Jialong , Deng Lei
Published: June 2022

In the process of regulating gene expression and evolution, such as DNA replication and mRNA transcription, the binding of transcription factors (TFs) to TF binding sites (TFBS) plays a vital role. Precisely modeling the specificity of genes and searching for TFBS are helpful to explore the mechanism of cell expression. In recent years, computational and deep learning methods searching for TFBS have become an active field of research. However, existing methods generally cannot meet high performance and interpretability simultaneously. Here, we develop an accurate and interpretable attention-based hybrid approach, DeepARC, that combines a convolutional neural network (CNN) and recurrent neural network (RNN) to predict TFBS. DeepARC employs a positional embedding method to extract the hidden embedding from DNA sequences, including the positional information from OneHot encoding and the distributed embedding from DNA2Vec. DeepARC feeds the positional embedding of the DNA sequence into a CNN-BiLSTM-Attention-based framework to complete the task of finding the motif. Taking advantage of the attention mechanism, DeepARC can gain greater access to valuable information about the motif and bring interpretability to the work of searching for motifs through the attention weight graph. Moreover, DeepARC achieves promising performances with an average area under the receiver operating characteristic curve (AUC) score of 0.908 on five cell lines (A549, GM12878, Hep-G2, H1-hESC, and Hela) in the benchmark dataset. We also compare the positional embedding with OneHot and DNA2Vec and gain a competitive advantage.
Recurrent Solitary Fibrous Tumor (Intracranial Hemangiopericytoma) Treated With a Novel Combined-Modality Radiosurgery Technique: A Case Report and Review of the Literature
Authors: Allen Alexander J. , Labella Dominic Angelo , Richardson K. Martin , Sheehan Jason P. , Kersh Charles R.
Published: June 2022

Solitary Fibrous Tumor (SFT) is a rare and aggressive mesenchymal malignancy of the dura with a predilection for recurrence after treatment. We report a case of a SFT initially treated with subtotal surgical resection followed by a combination of Gamma Knife (GK) and linear accelerator-based radiosurgery. Forty-four days post-resection, the tumor had demonstrated radiographic evidence of recurrent disease within the post-operative bed. GK radiosurgery treatment was delivered in a “four-matrix” fashion targeting the entire surgical cavity as well as three nodular areas within this wide field. This treatment was delivered in one fraction with a stereotactic head frame for immobilization. A consolidation radiosurgery treatment course was then delivered over three additional fractions to the resection bed using a linear accelerator and mesh mask for immobilization. The total biologically effective dose (BED) was calculated as 32.50 Gy to the surgical bed and approximately 76.50 Gy to each nodular area. Almost three years post-operatively, the patient is alive and without radiographic or clinical evidence of disease recurrence. To our knowledge, no prior experiences have documented treatment of SFT using a mixed-modality, multi-fraction radiosurgery technique like the method detailed in this report. Our experience describes a combined modality, multi-fraction radiosurgery approach to treating recurrent SFT that maximizes radiation dose to the targets while minimizing complication risk. We believe this novel radiosurgery method should be considered in cases of grade II SFT post-resection.
Childhood Maltreatment, Low Serum Cortisol Levels, and Non-Suicidal Self-Injury in Young Adults With Major Depressive Disorders
Authors: Peng Bo , Li Jinmeng , Liu Haitao , Fang Han , Zhao Weitan , Chen Guanjie , Xiu Meihong , Zhang Yingli
Published: June 2022

Background

Non-suicidal self-injury (NSSI) is a serious public health problem widely present among young adults and adolescents. While finding risk factors associated with NSSI among young patients with major depressive disorder (MDD) is challenging, the current study aims to measure childhood adversity and serum cortisol levels and elucidate their relationship in MDD patients with NSSI.

Methods

In this cross-sectional study, 126 young patients with MDD (aged 16 to 35 years) were recruited. The depressive symptoms were assessed by the Beck Depression Inventory (BDI-II), and the childhood adversity was evaluated by the Chinese version of the Childhood Trauma Questionnaire (CTQ) scale. Serum cortisol levels were determined by the kits in patients.

Results

Relative to MDD patients without NSSI, MDD patients with NSSI had a higher CTQ total score and its four subscores. Moreover, the cortisol levels in patients with MDD/NSSI were significantly decreased than in MDD patients without NSSI. For patients with MDD/NSSI, there is a negative association between cortisol levels and emotional neglect, but not for MDD patients without NSSI. Further regression analysis showed that low cortisol levels, BDI-II, and emotional neglect were risk factors for NSSI in young patients with MDD.

Conclusion

Our findings suggest that young MDD patients with NSSI experience more childhood adversity and have lower cortisol levels. Also, lower cortisol levels were associated with childhood adversity but not with depressive symptoms. Further, lower cortisol levels, depressive symptoms, and emotional neglect were risk factors for NSSI in young patients with MDD.
The Perspectives of Biomarkers in Predicting the Survival of the Renal Graft
Authors: Aldea Paul Luchian , Rachisan Andreea Liana , Stanciu Bogdan Ioan , Picos Andrei , Picos Alina Monica , Delean Dan Ioan , Stroescu Ramona , Starcea Magdalena Iuliana , Borzan Cristina Maria , Elec Florin Ioan
Published: June 2022

Kidney transplantation (KT) is currently the elective approach for patients with end-stage renal disease. Although it is a safe choice for these patients, the early complications can lead to graft dysfunction. One of the most redoubtable complications is delayed graft function (DGF), having no specific treatment. The effects of DGF on the graft survival are large enough to justify the formulation of specific biological protocols. Therefore, discovering biomarkers of acute impairment in renal transplanted patients is required. Creatinine is a poor marker to establish the kidney injury. Estimated glomerular filtration rate together with creatinine is ready to approximately measure the kidney function. Different serum and urine proteins are being studied as possible predictive biomarkers for delayed graft function. This review will concentrate on recent and existing research which provide insight concerning the contribution of some molecules for the estimation and evaluation of graft function after kidney transplantation. Further studies examining various aspects of DGF after KT are urgently needed to address a hitherto less-known clinical question.