bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasonic Tomography Study of Metal Defect Detection in Lithium-Ion Battery
Authors: Yi Mengchao , Jiang Fachao , Lu Languang , Hou Sixuan , Ren Jianqiao , Han Xuebing , Huang Lili
Published: December 2021

Lithium-ion batteries are widely used in electric vehicles and energy storage systems. Sudden fire accident is one of the most serious issue, which is mainly caused by unpredicted internal short circuit. Metal particle defect is a key factor in internal short circuit it will not show an obvious abnormal change in battery external characteristic just like mechanical and thermal abuse. So, a non-destructive testing of battery internal metal defect is very necessary. This study is first time to scan and analyze different types of defects inside a battery by using ultrasonic technology, and it shows the detection capability boundary of this methodology. A non-contact ultrasonic scanning system with multi-channel was built to scan the battery sample with aluminum foil, copper foil and copper powder defects. The position and shape of those defects were clearly shown by using tomography methodology. It was found that the acoustic properties difference between metal defects and battery active materials has a strong influence on detection sensitivity. Compared with aluminum foil, copper foil and copper powder are easier to be detected and change the ultrasonic signal greatly, they will produce an obvious shadowing artifacts and speed displacement phenomena in tomography images. Ultrasonic tomography technology is an effective method for non-destructive testing of lithium-ion batteries.
Using Food Webs and Metabolic Theory to Monitor, Model, and Manage Atlantic Salmon—A Keystone Species Under Threat
Authors: Woodward Guy , Morris Olivia , Barquín José , Belgrano Andrea , Bull Colin , de Eyto Elvira , Friberg Nikolai , Guðbergsson Guðni , Layer-Dobra Katrin , Lauridsen Rasmus B. , Lewis Hannah M. , McGinnity Philip , Pawar Samraat , Rosindell James , O’Gorman Eoin J.
Published: December 2021

Populations of Atlantic salmon are crashing across most of its natural range: understanding the underlying causes and predicting these collapses in time to intervene effectively are urgent ecological and socioeconomic priorities. Current management techniques rely on phenomenological analyses of demographic population time-series and thus lack a mechanistic understanding of how and why populations may be declining. New multidisciplinary approaches are thus needed to capitalize on the long-term, large-scale population data that are currently scattered across various repositories in multiple countries, as well as marshaling additional data to understand the constraints on the life cycle and how salmon operate within the wider food web. Here, we explore how we might combine data and theory to develop the mechanistic models that we need to predict and manage responses to future change. Although we focus on Atlantic salmon—given the huge data resources that already exist for this species—the general principles developed here could be applied and extended to many other species and ecosystems.
STXBP6 and B3GNT6 Genes are Associated With Selective IgA Deficiency
Authors: Lim Che Kang , Bronson Paola G. , Varade Jezabel , Behrens Timothy W. , Hammarström Lennart
Published: December 2021

Immunoglobulin A Deficiency (IgAD) is a polygenic primary immune deficiency, with a strong genetic association to the human leukocyte antigen (HLA) region. Previous genome-wide association studies (GWAS) have identified five non-HLA risk loci (IFIH1, PVT1, ATG13-AMBRA1, AHI1 and CLEC16A). In this study, we investigated the genetic interactions between different HLA susceptibility haplotypes and non-MHC genes in IgAD. To do this, we stratified IgAD subjects and healthy controls based on HLA haplotypes (N = 10,993), and then performed GWAS to identify novel genetic regions contributing to IgAD susceptibility. After replicating previously published HLA risk haplotypes, we compared individuals carrying at least one HLA risk allele (HLA-B*08:01-DRB1*03:01-DQB1*02:01 or HLA-DRB1*07:01-DQB1*02:02 or HLA-DRB1*01-DQB1*05:01) with individuals lacking an HLA risk allele. Subsequently, we stratified subjects based on the susceptibility alleles/haplotypes and performed gene-based association analysis using 572,856 SNPs and 24,125 genes. A significant genome-wide association in STXBP6 (rs4097492; p = 7.63 × 10−9) was observed in the cohort carrying at least one MHC risk allele. We also identified a significant gene-based association for B3GNT6 (PGene = 2.1 × 10–6) in patients not carrying known HLA susceptibility alleles. Our findings indicate that the etiology of IgAD differs depending on the genetic background of HLA susceptibility haplotypes.
Identifying lncRNA- and Transcription Factor-Associated Regulatory Networks in the Cortex of Rats With Deep Hypothermic Circulatory Arrest
Authors: Liang Mengya , Zhang Yi , Gan Shuangjiao , Liu Yunqi , Li Huayang , Liu Quan , Liu Haoliang , Zhou Zhuoming , Wu Huawei , Chen Guangxian , Wu Zhongkai
Published: December 2021

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the mechanism underlying cerebral dysfunction after deep hypothermic circulatory arrest (DHCA), although the exact details have not been elucidated. To explore the expression profiles of lncRNAs and miRNAs in DHCA cerebral injury, we determined the lncRNA, miRNA and mRNA expression profiles in the cerebral cortex of DHCA and sham rats. First, a rat model of DHCA was established, and high-throughput sequencing was performed to analyze the differentially expressed RNAs (DERNAs). Then, the principal functions of the significantly deregulated genes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Expression networks (lncRNAs-miRNAs-mRNAs and transcription factors (TFs)-miRNAs-mRNAs) were also established. Finally, the expression of DERNAs was confirmed by quantitative real-time PCR (RT-qPCR). We identified 89 lncRNAs, 45 miRNAs and 59 mRNAs between the DHCA and sham groups and constructed a comprehensive competitive endogenous RNAs (ceRNAs) network. A TF-miRNA-mRNA regulatory network was also established. Finally, we predicted that Lcorl-miR-200a-3p-Ttr, BRD4-Ccl2 and Ep300-miR-200b-3p-Tmem72 may participate in the pathogenesis of DHCA cerebral injury.
Fibrocytes: A Critical Review and Practical Guide
Authors: Reinhardt James W. , Breuer Christopher K.
Published: December 2021

Fibrocytes are hematopoietic-derived cells that directly contribute to tissue fibrosis by producing collagen following injury, during disease, and with aging. The lack of a fibrocyte-specific marker has led to the use of multiple strategies for identifying these cellsin vivo. This review will detail how past studies were performed, report their findings, and discuss their strengths and limitations. The motivation is to identify opportunities for further investigation and promote the adoption of best practices during future study design.
Establishing the Molecular Diagnoses in a Cohort of 291 Patients With Predominantly Antibody Deficiency by Targeted Next-Generation Sequencing: Experience From a Monocentric Study
Authors: Rojas-Restrepo Jessica , Caballero-Oteyza Andrés , Huebscher Katrin , Haberstroh Hanna , Fliegauf Manfred , Keller Baerbel , Kobbe Robin , Warnatz Klaus , Ehl Stephan , Proietti Michele , Grimbacher Bodo
Published: December 2021

Predominantly antibody deficiencies (PAD) are a heterogeneous group of disorders characterized by dysfunctional antibody production, low immunoglobulin levels in serum and impaired vaccine responses. The clinical picture is variable, ranging from mild symptoms to severe complications, which may include autoimmunity, gastrointestinal disease, allergy, and malignancies. If left untreated, PAD patients are at risk of enduring disease progression, irreversible organ damage, and reduced life expectancy. A timely diagnosis has been shown to significantly improve disease prognosis. Here, we report on our experience using targeted gene panel sequencing by employing Agilent’s HaloPlex or SureSelect and Illumina’s MiSeq technologies in a cohort of 291 individuals who presented with low or absent immunoglobulin levels in combination with or without other clinical features. In total, we have detected over 57 novel or previously reported relevant mutations in ADA, ADA2, BTK, CTLA4, LRBA, NFKB1, NFKB2, PIK3CD, STAT3, and TNFRSF13B. Overall, a genetic diagnosis could be made in 24.7% of the investigated patients. The percentage of coverage for the targeted regions ranged from 90% to 98% in this study. Moreover, functional assays were performed on a defined group of the patients carrying candidate variants in CTLA4, LRBA, NFKB1 and BTK, which confirmed their deleterious effect on protein expression and/or function. This study reiterates that the immunological heterogeneity of predominantly antibody deficiencies may have a diverse genetic origin, although certain clinical features may hint towards a specific group of defects. Employing targeted sequencing panels proves to be a very time- and cost-efficient, yet reliable, method for the establishment of a genetic diagnosis in individuals with PAD. However, in case of negative panel results, or if functional testing reveals inconspicuous observations in patients with a clear indication for genetic testing, further work-up including whole exome or whole genome sequencing should be considered.
Tumor-Associated Macrophages: Critical Players in Drug Resistance of Breast Cancer
Authors: Xiao Maoyu , He Jun , Yin Liyang , Chen Xiguan , Zu Xuyu , Shen Yingying
Published: December 2021

Drug resistance is one of the most critical challenges in breast cancer (BC) treatment. The occurrence and development of drug resistance are closely related to the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs), the most important immune cells in TIME, are essential for drug resistance in BC treatment. In this article, we summarize the effects of TAMs on the resistance of various drugs in endocrine therapy, chemotherapy, targeted therapy, and immunotherapy, and their underlying mechanisms. Based on the current overview of the key role of TAMs in drug resistance, we discuss the potential possibility for targeting TAMs to reduce drug resistance in BC treatment, By inhibiting the recruitment of TAMs, depleting the number of TAMs, regulating the polarization of TAMs and enhancing the phagocytosis of TAMs. Evidences in our review support it is important to develop novel therapeutic strategies to target TAMs in BC to overcome the treatment of resistance.
L-DBF Elicits Cross Protection Against Different Serotypes of Shigella spp
Authors: Lu Ti , Das Sayan , Howlader Debaki R. , Zheng Qi , Ratnakaram Siva Sai Kumar , Whittier Sean K. , Picking William D. , Picking Wendy L.
Published: December 2021

Shigellosis is a severe diarrheal disease caused by members of the genus Shigella, with at least 80 million cases and 700,000 deaths annually around the world. The type III secretion system (T3SS) is the primary virulence factor used by the shigellae, and we have previously demonstrated that vaccination with the type T3SS proteins IpaB and IpaD, along with an IpaD/IpaB fusion protein (DBF), protects mice from Shigella infection in a lethal pulmonary model. To simplify the formulation and development of the DBF Shigella vaccine, we have genetically fused LTA1, the active subunit of heat-labile toxin from enterotoxigenic E. coli, with DBF to produce the self-adjuvanting antigen L-DBF. Here we immunized mice with L-DBF via the intranasal, intramuscular, and intradermal routes and challenged them with a lethal dose of S. flexneri 2a. While none of the mice vaccinated intramuscularly or intradermally were protected, mice vaccinated with L-DBF intranasally were protected from lethal challenges with S. flexneri 2a, S. flexneri 1b, S. flexneri 3a, S. flexneri 6, and S. sonnei. Intranasal L-DBF induced both B cell and T cell responses that correlated with protection against Shigella infection. Our results suggest that L-DBF is a candidate for developing an effective serotype-independent vaccine against Shigella spp.
Using RNA-Seq to Investigate Immune-Metabolism Features in Immunocompromised Patients With Sepsis
Authors: Cheng Po-Liang , Chen Hsin-Hua , Jiang Yu-Han , Hsiao Tzu-Hung , Wang Chen-Yu , Wu Chieh-Liang , Ko Tai-Ming , Chao Wen-Cheng
Published: December 2021

Objective:Sepsis is life threatening and leads to complex inflammation in patients with immunocompromised conditions, such as cancer, and receiving immunosuppressants for autoimmune diseases and organ transplant recipients. Increasing evidence has shown that RNA-Sequencing (RNA-Seq) can be used to define subendotype in patients with sepsis; therefore, we aim to use RNA-Seq to identify transcriptomic features among immunocompromised patients with sepsis.

Methods:We enrolled patients who were admitted to medical intensive care units (ICUs) for sepsis at a tertiary referral centre in central Taiwan. Whole blood on day-1 and day-8 was obtained for RNA-Seq. We used Gene Set Enrichment Analysis (GSEA) to identify the enriched pathway of day-8/day-1 differentially expressed genes and MiXCR to determine the diversity of T cell repertoire.

Results:A total of 18 immunocompromised subjects with sepsis and 18 sequential organ failure assessment (SOFA) score-matched immunocompetent control subjects were enrolled. The ventilator-day, ICU-stay, and hospital-day were similar between the two groups, whereas the hospital mortality was higher in immunocompromised patients than those in immunocompetent patients (50.0 vs. 5.6%,p< 0.01). We found that the top day-8/day-1 upregulated genes in the immunocompetent group were mainly innate immunity and inflammation relevant genes, namely,PRSS33, HDC, ALOX15, FCER1A, andOLR1, whereas a blunted day-8/day-1 dynamic transcriptome was found among immunocompromised patients with septic. Functional pathway analyses of day-8/day-1 differentially expressed genes identified the upregulated functional biogenesis and T cell-associated pathways in immunocompetent patients recovered from sepsis, whereas merely downregulated metabolism-associated pathways were found in immunocompromised patients with septic. Moreover, we used MiXCR to identify a higher diversity of T cell receptor (TCR) in immunocompetent patients both on day-1 and on day-8 than those in immunocompromised patients.

Conclusions:Using RNA-Seq, we found compromised T cell function, altered metabolic signalling, and decreased T cell diversity among immunocompromised patients with septic, and more mechanistic studies are warranted to elucidate the underlying mechanism.
Sedation, Analgesia, and Muscle Relaxation During VV-ECMO Therapy in Patients With Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2): A Single-Center, Retrospective, Observational Study
Authors: Wu Fang , Li Mingna , Zhang Zhongwei , Shang Jiawei , Guo Yong , Li Yingchuan
Published: December 2021

Objective: The pharmacokinetics and pharmacodynamics of ECMO-supported sedative, analgesic, and muscle relaxants have changed, but there are insufficient data to determine the optimal dosing strategies for these agents. Sedation, analgesia and muscle relaxation therapy for patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) receiving ECMO support are more specific and have not been fully reported. This study observed and evaluated the use of sedative and analgesic drugs and muscle relaxants in SARS-CoV-2 patients treated with VV-ECMO.

Methods: This study was a single-center, retrospective and observational study. Our study includes 8 SARS-CoV-2 patients treated with VV-ECMO in an intensive care unit at Shanghai Public Health Center from February to June 2020. We collected the demographic data from these patients and the dose and course of sedation, analgesia, and muscle relaxants administered during ECMO treatment.

Results: The doses of sedative, analgesic and muscle relaxant drugs used in patients with VV-ECMO were significant. Over time, the doses of drugs that were used were increased, and the course of muscle relaxant treatment was extended.

Conclusion: Sedation, analgesia, and muscle relaxant use require individualized titration in patients with SARS-CoV-2 who have respiratory failure and who are receiving VV-ECMO.
Membrane Homeoviscous Adaptation in Sinorhizobium Submitted to a Stressful Thermal Cycle Contributes to the Maintenance of the Symbiotic Plant–Bacteria Interaction
Authors: Paulucci Natalia Soledad , Cesari Adriana Belén , Biasutti María Alicia , Dardanelli Marta Susana , Perillo María Angélica
Published: December 2021

Here, we estimate fast changes in the fluidity of Sinorhizobium meliloti membranes submitted to cyclic temperature changes (10°C–40°C–10°C) by monitoring the fluorescence polarization (P) of DPH and TMA-DPH of the whole cell (WC) as well as in its outer (OM) and inner (IM) membranes. Additionally, the long-term response to thermal changes is demonstrated through the dynamics of the phospholipid and fatty acid composition in each membrane. This allowed membrane homeoviscous adaptation by the return to optimal fluidity levels as measured by the PDPH/TMA-DPH in WC, OM, IM, and multilamellar vesicles of lipids extracted from OM and IM. Due to probe-partitioning preferences and membranes’ compositional characteristics, DPH and TMA-DPH exhibit different behaviors in IM and OM. The rapid effect of cyclic temperature changes on the P was the opposite in both membranes with the IM being the one that exhibited the thermal behavior expected for lipid bilayers. Interestingly, only after the incubation at 40°C, cells were unable to recover the membrane preheating P levels when cooled up to 10°C. Solely in this condition, the formation of threads and nodular structures in Medicago sativa infected with S. meliloti were delayed, indicating that the symbiotic interaction was partially altered but not halted.
Understanding Metabolic Flux Behaviour in Whole-Cell Model Output
Authors: Landon Sophie , Chalkley Oliver , Breese Gus , Grierson Claire , Marucci Lucia
Published: December 2021

Whole-cell modelling is a newly expanding field that has many applications in lab experiment design and predictive drug testing. Although whole-cell model output contains a wealth of information, it is complex and high dimensional and thus hard to interpret. Here, we present an analysis pipeline that combines machine learning, dimensionality reduction, and network analysis to interpret and visualise metabolic reaction fluxes from a set of single gene knockouts simulated in the Mycoplasma genitalium whole-cell model. We found that the reaction behaviours show trends that correlate with phenotypic classes of the simulation output, highlighting particular cellular subsystems that malfunction after gene knockouts. From a graphical representation of the metabolic network, we saw that there is a set of reactions that can be used as markers of a phenotypic class, showing their importance within the network. Our analysis pipeline can support the understanding of the complexity of in silico cells without detailed knowledge of the constituent parts, which can help to understand the effects of gene knockouts and, as whole-cell models become more widely built and used, aid genome design.
Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma
Authors: Wen Kai , Yan Yongcong , Shi Juanyi , Hu Lei , Wang Weidong , Liao Hao , Li Huoming , Zhu Yue , Mao Kai , Xiao Zhiyu
Published: December 2021

Background: Ferroptosis, as a unique programmed cell death modality, has been found to be closely related to the occurrence and development of hepatocellular carcinoma (HCC). Hypoxia signaling pathway has been found to be extensively involved in the transformation and growth of HCC and to inhibit anti-tumor therapy through various approaches. However, there is no high-throughput study to explore the potential link between ferroptosis and hypoxia, as well as their combined effect on the prognosis of HCC.

Methods: We included 370 patients in The Cancer Genome Atlas (TCGA) database and 231 patients in the International Cancer Genome Consortium (ICGC) database. Univariate COX regression and Least Absolute Shrinkage and Selection Operator approach were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (FHPS). Kaplan–Meier method and Receiver Operating Characteristic curves were analyzed to evaluate the predictive capability of FHPS. CIBERSOR and single-sample Gene Set Enrichment Analysis were used to explore the connection between FHPS and tumor immune microenvironment. Immunohistochemical staining was used to compare the protein expression of prognostic FRGs and HRGs between normal liver tissue and HCC tissue. In addition, the nomogram was established to facilitate the clinical application of FHPS.

Results: Ten FRGs and HRGs were used to establish the FHPS. We found consistent results in the TCGA training cohort, as well as in the independent ICGC validation cohort, that patients in the high-FHPS subgroup had advanced tumor staging, shorter survival time, and higher mortality. Moreover, patients in the high-FHPS subgroup showed ferroptosis suppressive, high hypoxia, and immunosuppression status. Finally, the nomogram showed a strong prognostic capability to predict overall survival (OS) for HCC patients.

Conclusion: We developed a novel prognostic signature combining ferroptosis and hypoxia to predict OS, ferroptosis, hypoxia, and immune status, which provides a new idea for individualized treatment of HCC patients.
Altered Spontaneous Brain Activity Related to Neurologic Dysfunction in Patients With Cerebral Small Vessel Disease
Authors: Feng Mengmeng , Wen Hongwei , Xin Haotian , Zhang Nan , Liang Changhu , Guo Lingfei
Published: December 2021

Cerebral small vessel disease (CSVD) encompasses several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain and refers to several pathological processes and etiologies. Neuroimaging is considered the gold standard for detecting CSVD, which can present diverse features on MRI. Cerebral microbleeds (CMBs) in CSVD have been demonstrated to play a synergistic role in both cerebrovascular and neurodegenerative pathology. Considering previous studies on brain structural abnormalities in CSVD, in the present study, we aimed to explore altered spontaneous brain activity among CSVD patients using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) methods based on resting-state functional MRI. In this study, we recruited 24 CSVD patients with CMBs (CSVD-c), 42 CSVD patients without CMBs (CSVD-n) and 36 healthy controls from outpatient clinics in Shandong Provincial Hospital affiliated to Shandong First Medical University between September 2018 and June 2019. All subjects underwent 3-T MRI, including blood oxygen level-dependent (BOLD) and susceptibility-weighted imaging (SWI). Anatomic structures were segmented, ALFF/fALFF values were calculated, and ReHo maps were generated. Further statistical analysis was applied to study the difference in ALFF/fALFF/ReHo among the three groups and the association between ALFF/fALFF/ReHo changes in different brain regions and clinical characteristics. Twenty-four CSVD-c patients (age: 67.54 ± 6.00 years, 10 females), 42 CSVD-n patients (age: 66.33 ± 5.25 years, 22 females) and 36 healthy subjects (age: 64.14 ± 8.57 years, 19 females) were evaluated. Compared with controls, the CSVD-c group showed significantly increased ALFF values in the right insula, putamen and left precuneus; decreased fALFF values in the right precentral gyrus and postcentral gyrus; and increased ReHo values in the left precuneus, fusiform gyrus, right supplementary motor area (SMA), and superior frontal gyrus. Notably, the mean ALFF values of the right insula and putamen were not only significantly related to all clinical parameters but also demonstrated the best performance in Receiver Operating Characteristic (ROC) curve analysis. These findings reveal CSVD-c patients have dysfunctions in the default mode network, sensorimotor network and frontoparietal network, which may implicate the underlying neurophysiological mechanisms of intrinsic brain activity. The correlation between altered spontaneous neuronal activity and clinical parameters provides early useful diagnostic biomarkers for CSVD.
Manipulations of Glutathione Metabolism Modulate IP3-Mediated Store-Operated Ca2+ Entry on Astroglioma Cell Line
Authors: Mokrane Nawfel , Snabi Yassin , Cens Thierry , Guiramand Janique , Charnet Pierre , Bertaud Anaïs , Menard Claudine , Rousset Matthieu , de Jesus Ferreira Marie-Céleste , Thibaud Jean-Baptiste , Cohen-Solal Catherine , Vignes Michel , Roussel Julien
Published: December 2021

The regulation of the redox status involves the activation of intracellular pathways as Nrf2 which provides hormetic adaptations against oxidative stress in response to environmental stimuli. In the brain, Nrf2 activation upregulates the formation of glutathione (GSH) which is the primary antioxidant system mainly produced by astrocytes. Astrocytes have also been shown to be themselves the target of oxidative stress. However, how changes in the redox status itself could impact the intracellular Ca2+ homeostasis in astrocytes is not known, although this could be of great help to understand the neuronal damage caused by oxidative stress. Indeed, intracellular Ca2+ changes in astrocytes are crucial for their regulatory actions on neuronal networks. We have manipulated GSH concentration in astroglioma cells with selective inhibitors and activators of the enzymes involved in the GSH cycle and analyzed how this could modify Ca2+ homeostasis. IP3-mediated store-operated calcium entry (SOCE), obtained after store depletion elicited by Gq-linked purinergic P2Y receptors activation, are either sensitized or desensitized, following GSH depletion or increase, respectively. The desensitization may involve decreased expression of the proteins STIM2, Orai1, and Orai3 which support SOCE mechanism. The sensitization process revealed by exposing cells to oxidative stress likely involves the increase in the activity of Calcium Release-Activated Channels (CRAC) and/or in their membrane expression. In addition, we observe that GSH depletion drastically impacts P2Y receptor-mediated changes in membrane currents, as evidenced by large increases in Ca2+-dependent K+ currents. We conclude that changes in the redox status of astrocytes could dramatically modify Ca2+ responses to Gq-linked GPCR activation in both directions, by impacting store-dependent Ca2+-channels, and thus modify cellular excitability under purinergic stimulation.
The Correlation Among the Immunoglobulin G Synthesis Rate, IgG Index and Albumin Quotient in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Retrospective Case–Control Study
Authors: Tu Yu , Gong Xuan , Zhang Yuanyuan , Peng Jiewei , Zhuo Wenyan , Yu Xueying
Published: December 2021

Background: The immunoglobulin G synthesis rate (IgG SR) and immunoglobulin G (IgG) index are indicators of abnormal intrathecal humoural immune responses, and the albumin quotient (QALB) is an indicator used to evaluate the completeness of the blood-cerebrospinal fluid barrier (BCB). No systematic reports regarding differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are available. We assessed differences in the IgG SR, IgG index and QALB between GBS and CIDP patients in a Chinese cohort.

Methods: A total of 234 patients were retrospectively enrolled in this study, and 167 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 67 non-GBS and non-CIDP patients requiring cerebrospinal fluid (CSF) examination were enrolled as the control group. The IgG SR, IgG index and QALB were calculated using formulas. The relevant clinical data were subjected to statistical analysis.

Results: Among the GBS and CIDP study groups and the control group, the QALB had the highest positive rate (80.00%) in the CIDP group (P < 0.01). The QALB stratification analysis showed that the ranges of 10 < QALB ≤ 30 were dominant in the GBS and CIDP groups, and the positive rate of CIDP was higher than that of GBS. Furthermore, a QALB ≤ 7 was dominant in the control group, and a QALB > 30 was dominant in the CIDP group. In receiver operating characteristic (ROC) curve analysis with the CIDP group as the trial group and the GBS group as the control group, the differences in the QALB were statistically significant (P < 0.01). To achieve a high specificity of 98~99%, the diagnostic cut-off value for the QALB was above 57.37 (sensitivity: 9.33%) or below 0.60 (sensitivity: 4.35%). Multivariate logistic regression analysis showed that the CIDP patients had a QALB higher than 57.37, and compared with that in the GBS patients, the difference in the QALB was statistically significant (P < 0.01).

Conclusion: QALB elevation was associated with CIDP, while QALB values above 57.37 or below 0.60 had high specificity in differentiating between GBS and CIDP. In CIDP, the BCB is generally moderately to severely damaged; in GBS, the BCB is generally moderately damaged.
Mechanical Thrombectomy With and Without Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis Using Nested Knowledge
Authors: Adusumilli Gautam , Pederson John M. , Hardy Nicole , Kallmes Kevin M. , Hutchison Kristen , Kobeissi Hassan , Heiferman Daniel M. , Heit Jeremy J.
Published: December 2021

Background: Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of intravenous tissue plasminogen activator (IV-tPA) eligibility prior to the procedure. This study aims to understand better if tPA leads to higher rates of reperfusion and improves functional outcomes in AIS patients after MT and to simultaneously evaluate the functionality and efficiency of a novel semi-automated systematic review platform.

Methods: The Nested Knowledge AutoLit semi-automated systematic review platform was utilized to identify randomized control trials published between 2010 and 2021 reporting the use of mechanical thrombectomy and IV-tPA (MT+tPA) vs. MT alone for AIS treatment. The primary outcome was the rate of successful recanalization, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS) 0–2, 90-day mortality, distal embolization to new territory, and symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure.

Results: We subjectively found Nested Knowledge to be highly streamlined and effective at sourcing the correct literature. Four studies with 1,633 patients, 816 in the MT+tPA arm and 817 in the MT arm, were included in the meta-analysis. In each study, patient populations consisted of only tPA-eligible patients and all imaging and clinical outcomes were adjudicated by an independent and blinded core laboratory. Compared to MT alone, patients treated with MT+tPA had higher odds of eTICI ≥2b (OR = 1.34 [95% CI: 1.10; 1.63]). However, there were no statistically significant differences in the rates of 90-day mRS 0-2 (OR = 0.98 [95% CI: 0.77; 1.24]), 90-day mortality (OR = 0.94 [95% CI: 0.67; 1.32]), distal emboli (OR = 0.94 [95% CI: 0.25; 3.60]), or sICH (OR = 1.17 [95% CI: 0.80; 1.72]).

Conclusions: Administering tPA prior to MT may improve the rates of recanalization compared to MT alone in tPA-eligible patients being treated for AIS, but a corresponding improvement in functional and safety outcomes was not present in this review. Further studies looking at the role of tPA before mechanical thrombectomy in different cohorts of patients could better clarify the role of tPA in the treatment protocol for AIS.
Estimated Sweetness in US Diet Among Children and Adults Declined From 2001 to 2018: A Serial Cross-Sectional Surveillance Study Using NHANES 2001–2018
Authors: Kamil Alison , Wilson Alissa R. , Rehm Colin D.
Published: December 2021

An agreed-upon measure of total dietary sweetness is lacking hindering assessments of population-level patterns and trends in dietary sweetness. This cross-sectional study used 24-h dietary recall data for 74,461 participants aged ≥ 2 y from nine cycles (2001–2018) of the National Health and Nutrition Examination Survey (NHANES) to evaluate trends in the sweetness of the diet in the United States (US). LCS-containing items were matched to a sugar-sweetened counterpart (e.g., diet cola–regular cola or sucralose sugar). The matched pair was used to estimate the sugar equivalents from LCS-sweetened foods or beverages to estimate dietary level sweetness, which was described as grams of approximate sugar equivalent (ASE) per day. Trends in ASE were estimated overall and by subgroup, and trends were further disaggregated by food or beverage category. Overall, LCS sources contributed about 10.5% of ASE. Total ASE declined from 152 g/d to 117 g/d from 2001–2002 to 2017–2018 (p-trend < 0.001), with comparable declines in children and adults. Declines in total ASE were predominantly driven by beverages (−36.7% from 2001–2002 to 2017–2018) and tabletop sweeteners (−23.8%), but not food (−1.5%). Observed trends were robust to sensitivity analyses incorporating random, systematic, and sensory trial informed estimates of sweetness and also an analysis excluding possible under-reporters of dietary energy. This practical approach and underlying data may help researchers to apply the technique to other dietary studies to further these questions.
High ATF4 Expression Is Associated With Poor Prognosis, Amino Acid Metabolism, and Autophagy in Gastric Cancer
Authors: Wang Mingliang , Lu Yida , Wang Huizhen , Wu Youliang , Xu Xin , Li Yongxiang
Published: December 2021

Background

The role of activating transcription factor 4 (ATF4) underlying gastric cancer (GC) remains unclear. The purpose of this study was to investigate the expression levels and biological functions of ATF4 in GC.

Methods

Expression of ATF4 was detected by quantitative PCR (qPCR), Western blotting, and immunohistochemistry. Cox regression was used for survival analysis and the construction of the nomogram. Immunofluorescence was used to identify the intracellular localization of ATF4. Knockdown and overexpression of ATF4 in GC cells followed by wound healing and Transwell assays, EdU and Calcein-AM/propidium iodide (PI) staining, and cell cycle detection were performed to examine its function in vitro. Transmission electron microscopy was performed to assess the autophagy levels upon ATF4 silencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) were used to determine gene enrichment. SPSS 22.0 software, GraphPad Prism 7.0, and R version 3.6.1 were used for statistical analysis.

Results

ATF4 expression was upregulated in GC cells and tissues compared with corresponding normal tissues. Survival analysis suggested that a high ATF4 expression was strongly associated with worse overall survival (OS) of GC patients (p < 0.001). The nomogram and the receiver operating characteristic (ROC) curves demonstrated that ATF4 was a highly sensitive and specific prognostic marker of GC [C-index = 0.797, area under the ROC curve (AUC) of 3-year OS = 0.855, and AUC of 5-year OS = 0.863]. In addition, ATF4 knockdown inhibited the cell proliferation, migration, invasion, and cell cycle progression of GC cells in vitro, while overexpression of ATF4 exerted the opposite effects. Bioinformatics analysis showed that ATF4 could promote GC progression possibly by regulating asparagine (Asn) metabolism and autophagy pathways. Further experiments indicated that ATF4 expression was significantly positively correlated with ASNS expression. The inhibition of cell clone formation in Asn-deprived conditions was more significant in the shATF4 group. Finally, we found that ATF4 promoted autophagy through regulating the mTORC1 pathway in GC cells.

Conclusion

These findings suggested that ATF4 can significantly promote GC development and serve as an independent prognostic factor for GC.
SIPL1, Regulated by MAZ, Promotes Tumor Progression and Predicts Poor Survival in Human Triple-Negative Breast Cancer
Authors: He Juanjuan , Wang Jing , Li Teng , Chen Kunlun , Li Songchao , Zhang Shaojin
Published: December 2021

Background

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer owing to a lack of effective targeted therapy and acquired chemoresistance. Here, we explored the function and mechanism of shank-interacting protein-like 1 (SIPL1) in TNBC progression.

Methods

SIPL1 expression was examined in human TNBC tissues and cell lines by quantitative reverse transcription PCR, western blot, and immunohistochemistry. SIPL1 overexpression and silenced cell lines were established in BT-549 and MDA-MB-231 cells. The biological functions of SIPL1 in TNBC were studied in vitro using the CCK-8 assay, CellTiter-Glo Luminescent Cell Viability assay, caspase-3/8/9 assay, wound healing assay, and transwell assay and in vivo using a nude mouse model. The potential mechanisms underlying the effects of SIPL1 on TNBC progression were explored using bioinformatics analysis, luciferase reporter assays, and chromatin immunoprecipitation followed by qPCR.

Results

SIPL1 expression was higher in human TNBC tissues and cell lines than in adjacent normal tissues and a breast epithelial cell line (MCF10A). High expression of SIPL1 was positively correlated with poor overall and disease-free survival in patients with TNBC. SIPL1 overexpression elevated and SIPL1 silencing repressed the malignant phenotypes of TNBC cells in vitro. SIPL1 overexpression promoted xenograft tumor growth in vivo. Myc-associated zinc-finger protein (MAZ) transcriptionally activated SIPL1. Finally, we found that SIPL1 promoted TNBC malignant phenotypes via activation of the AKT/NF-κB signaling pathways.

Conclusions

These results indicate that the MAZ/SIPL1/AKT/NF-κB axis plays a crucial role in promoting the malignant phenotypes of TNBC cells.
Maintenance Therapy Can Improve the Oncologic Prognosis and Obstetrical Outcome of Patients With Atypical Endometrial Hyperplasia and Endometrial Cancer After Fertility-Preserving Treatment: A Multicenter Retrospective Study
Authors: He Yijiao , Wang Jianliu , Wang Yiqin , Zhou Rong , Lu Qun , Liu Guoli , Tang Huiru , Guo Hongyan , He Mian , Wu Guizhu
Published: December 2021

Objective

To evaluate the effect of maintenance therapy for patients with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) after successful fertility-preserving management on prognosis and pregnancy outcome.

Methods

We performed a retrospectively analysis of 109 young women with atypical endometrial hyperplasia and early endometrioid endometrial cancer who had received complete response after fertility-preserving treatment at 5centers between May 2005 and March 2021. Maintenance therapy regimes included low-dose oral progesterone, levonorgestrel intrauterine device(LNG-IUD) and combination oral contraceptive (COC). The patients were divided into two groups, maintenance therapy group and non-maintenance therapy group. Clinical characteristics, treatment regimens, prognosis, and pregnancy outcome were compared between the two groups.

Results

The overall disease recurrence rate of the maintenance therapy group was significantly lower than that of the non-maintenance therapy group (P < 0.001). The recurrence rate of atypical endometrial hyperplasia and endometrial cancer in the maintenance therapy group were significantly lower than those in the non-maintenance group (P < 0.001). Maintenance therapy can reduce pregnancy rates and live birth rates. Maintenance therapy can protect the endometrium in patients treated with assisted reproductive technology (ART), greatly reducing the recurrence rate after ART (P<0.001).

Conclusion

Maintenance therapy plays a very important protective role in fertility-preserving treatment for patients with atypical endometrial hyperplasia and endometrial cancer, which could significantly reduce the risk of recurrence. It is recommended that patients could receive maintenance therapy as long as possible during the period from achieving complete response to pregnancy preparation if possible. It may provide recurrence-free survival long enough for childless young women to prepare for pregnancy in the future. It can also protect the endometrium of those who are preparing to use assisted reproductive technology, possibly by reducing the risk of recurrence by excessive stimulation with assisted reproductive drugs.
18KHT01, a Potent Anti-Obesity Polyherbal Formulation
Authors: Pandeya Prakash Raj , Lamichhane Ramakanta , Lamichhane Gopal , Lee Kyung-Hee , Lee Hyeong Kyu , Rhee Su-jin , Jung Hyun-Ju
Published: December 2021

Obesity is a life-threatening metabolic disorder necessitating urgent development of safe and effective therapy. Currently, limited such therapeutic measures are available for obesity. The present study was designed to develop a novel, safe and effective herbal therapy for the management of obesity. A polyherbal formulation (18KHT01) was developed by homogeneously mixing a specific proportion of crude Quercus acutissima (acorn jelly powder), Camellia sinensis (dry leaf buds), and Geranium thunbergii (dry aerial part) along with Citrus limon (fruit juice). Synergistic antioxidant, antiadipogenic, and anti-obesity activities were evaluated by in vitro as well as in vivo studies. In vitro experiments revealed strong synergistic antioxidant and anti-adipogenic activities of 18KHT01. Molecular assessment of 18KHT01 showed significant down-regulation of vital adipogenic factors such as PPARγ, C/EBPα, aP2, SREBP-1c, FAS, and LPL. Based on the results of the preliminary toxicity study, 75 and 150 mg/kg, twice daily doses of 18KHT01 were administered to evaluate anti-obesity activity in diet-induced obese (DIO) C57BL/6J mice model. The major obesity-related parameters such as body weight, weight gain, food efficiency ratio, as well as serum lipid profile were significantly reduced by 18KHT01 with potential synergism. Also, the high-fat diet-induced insulin resistance was suggestively alleviated by the formulation, and thus ameliorated fasting blood glucose. Histological evaluation of liver and white adipose tissue revealed that the significant reduction of fat depositions and thus reduction of these tissue weights. Synergy evaluation experiments exhibited that the 18KHT01 offered strong synergism by improving efficacy and reducing the toxicity of its ingredients. Overall results evidenced the 18KHT01 as a safe and potent anti-obesity herbal therapy.
Novel Computerized Method for Automated Determination of Ventilatory Threshold and Respiratory Compensation Point
Authors: Kim Kyoung Jae , Rivas Eric , Prejean Brian , Frisco Dillon , Young Millennia , Downs Meghan
Published: December 2021

Introduction: The ventilatory threshold (named as VT1) and the respiratory compensation point (named as VT2) describe prominent changes of metabolic demand and exercise intensity domains during an incremental exercise test.

Methods: A novel computerized method based on the optimization method was developed for automatically determining VT1 and VT2 from expired air during a progressive maximal exercise test. A total of 109 peak cycle tests were performed by members of the US astronaut corps (74 males and 35 females). We compared the automatically determined VT1 and VT2 values against the visual subjective and independent analyses of three trained evaluators. We also characterized VT1 and VT2 and the respective absolute and relative work rates and distinguished differences between sexes.

Results: The automated compared to the visual subjective values were analyzed for differences with t test, for agreement with Bland–Altman plots, and for equivalence with a two one-sided test approach. The results showed that the automated and visual subjective methods were statistically equivalent, and the proposed approach reliably determined VT1 and VT2 values. Females had lower absolute O2 uptake, work rate, and ventilation, and relative O2 uptake at VT1 and VT2 compared to men (p ≤ 0.04). VT1 and VT2 occurred at a greater relative percentage of their peak VO2 for females (67 and 88%) compared to males (55 and 74%; main effect for sex: p < 0.001). Overall, VT1 occurred at 58% of peak VO2, and VT2 occurred at 79% of peak VO2 (p < 0.0001).

Conclusion: Improvements in determining of VT1 and VT2 by automated analysis are time efficient, valid, and comparable to subjective visual analysis and may provide valuable information in research and clinical practice as well as identifying exercise intensity domains of crewmembers in space.
Research Progress on the Mechanism Between Polycystic Ovary Syndrome and Abnormal Endometrium
Authors: Xue Zhu , Li Juanli , Feng Jiaxing , Han Han , Zhao Jing , Zhang Jiao , Han Yanhua , Wu Xiaoke , Zhang Yuehui
Published: December 2021

As a highly dynamic tissue, the endometrium is periodically shed in response to the secretion of estrogen and progesterone. After menarche, the endometrium of healthy women proliferates and differentiates under the action of steroid hormones (e.g., 17β-estradiol and progesterone) that are secreted by the ovaries to provide appropriate conditions for embryo implantation. Polycystic ovary syndrome (PCOS), a prevalent endocrine and metabolic disorder in reproductive-aged women, is usually associated with multiple cysts within the ovaries and excess levels of androgen and is characterized by hirsutism, acne, menstrual irregularity, infertility, and increased risk of insulin resistance. Multiple factors, such as anovulation, endocrine-metabolic abnormalities, and inflammation, can disrupt the endometrium in PCOS patients and can lead to endometrial hyperplasia, pregnancy complications, or even cancer. Despite many recent studies, the relationship between PCOS and abnormal endometrial function is still not fully understood. In this review, we investigate the correlation of PCOS patient endometrium with anovulation, hyperandrogenemia, insulin resistance, progesterone resistance, and inflammatory cytokines, aiming to provide a theoretical basis for the treatment of disorders caused by endometrial dysfunction in PCOS patients.
Tonoplast-Localized Theanine Transporter CsCAT2 May Mediate Theanine Storage in the Root of Tea Plants (Camellia sinensis L.)
Authors: Feng Lin , Yu Yongchao , Lin Shijia , Yang Tianyuan , Chen Qi , Liu Linlin , Sun Jun , Zheng Pengcheng , Zhang Zhaoliang , Wan Xiaochun
Published: December 2021

Theanine is the component endowing tea infusion with “umami” taste and antidepression benefits. Theanine is primarily synthesized and stored in root in winter and is transported via vascular tissues to the new shoot in spring. However, the mechanism underlying theanine storage in the root of tea plants remains largely unknown. Cationic amino acid transporter 2 (CsCAT2) in tea plants is homologous to glutamine permease 1 (GNP1), the specific glutamine transporter in yeast. In this study, we identified CsCAT2 as an H+-dependent theanine transporter with medium affinity for theanine. The result of subcellular localization showed that CsCAT2 was a tonoplast-localized transporter. Importantly, CsCAT2 highly expressed in the root in winter during theanine storage and reduced its expression in the root during theanine transport from root-to-shoot in spring. In addition, CsCAT2 expression in the roots of 5 varieties at four time points during December and April was significant negatively correlated with the capacity of theanine root-to-shoot movement. Taken together, these results suggested that CsCAT2 may mediate theanine storage in the vacuole of root cells and may negatively modulate theanine transport from root to shoot.