bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust Antibody Responses to the BNT162b2 mRNA Vaccine Occur Within a Week After the First Dose in Previously Infected Individuals and After the Second Dose in Uninfected Individuals
Authors: Hirotsu Yosuke , Amemiya Kenji , Sugiura Hiroki , Shinohara Miyuki , Takatori Mika , Mochizuki Hitoshi , Omata Masao
Published: August 2021

Background

Vaccines against severe acute respiratory syndrome coronavirus 2 can trigger acquired immunity in infection-naïve individuals and offer a path toward ending the coronavirus disease pandemic that began in 2019. However, the kinetics of early antibody responses in vaccinated individuals remain poorly understood.

Method

We followed BNT162b2 mRNA-vaccinated health care workers (HCWs, N=108) including 103 infection-naïve and five previously infected individuals. A total of 763 blood samples were collected weekly or hourly basis before and after vaccination. Serological analysis of anti-spike and anti-nucleocapsid antibodies was performed.

Results

Seroconversion occurred in all infection-naïve HCWs 3 weeks after the first dose (just before the second vaccination) and a marked boosting effect was observed at 4 weeks (1 week after the second dose). Among previously infected HCWs with pre-existing antibodies against the spike protein, a remarkable boosting effect was observed during the first week after vaccination, and a further increase in antibody titres was observed after the second dose. In one previously infected patient, daily blood sampling was conducted. Antibody titres began to increase 96 hours (4 days) after the first dose.

Conclusion

The BNT162b2 mRNA vaccine remarkably enhanced antibody responses after the second dose in infection-naïve individuals and after the first dose in previously infected HCWs of all ages and genders. Antibody titres decreased slightly after the 5th week post-vaccination. The robust boosting effect of immunisation suggests that increased antibody titres following exposure to the virus may restrict viral replication, prolong the incubation period, or lessen the severity of disease.
Predictive Value of Metabolic Parameters Derived From 18F-FDG PET/CT for Microsatellite Instability in Patients With Colorectal Carcinoma
Authors: Liu Hao , Ye Zheng , Yang Ting , Xie Hongjun , Duan Ting , Li Mou , Wu Min , Song Bin
Published: August 2021

Background

Microsatellite instability (MSI) is one of the important factors that determine the effectiveness of immunotherapy in colorectal cancer (CRC) and serves as a prognostic biomarker for its clinical outcomes.

Purpose

To investigate whether the metabolic parameters derived from18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) can predict MSI status in patients with CRC.

Materials and Methods

A retrospective analysis was performed on CRC patients who underwent 18F-FDG PET/CT examination before surgery between January 2015 and April 2021. The metabolic 18F-FDG PET/CT parameters of the primary CRC lesion were calculated and recorded with different thresholds, including the maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean), as well as the metabolic tumor volume (MTV) and the total lesion glycolysis (TLG). The status of MSI was determined by immunohistochemical assessment. The difference of quantitative parameters between MSI and microsatellite stability (MSS) groups was assessed, and the receiver operating characteristic (ROC) analyses with area under ROC curves (AUC) was used to evaluate the predictive performance of metabolic parameters.

Results

A total of 44 patients (24 men and 20 women; mean ± standard deviation age: 71.1 ± 14.2 years) were included. There were 14 patients in the MSI group while there were 30 in the MSS group. MTV30%, MTV40%, MTV50%, and MTV60%, as well as TLG50% and TLG60% showed significant difference between two groups (all p-values <0.05), among which MTV50% demonstrated the highest performance in the prediction of MSI, with an AUC of 0.805 [95% confidence interval (CI): 0.657–0.909], a sensitivity of 92.9% (95% CI: 0.661–0.998), and a specificity of 66.7% (95% CI: 0.472–0.827). Patients’ age and MTV50% were significant predictive indicators of MSI in multivariate logistic regression.

Conclusion

The metabolic parameters derived from18F-FDG PET/CT were able to preoperatively predict the MSI status in CRC, with MTV50% demonstrating the highest predictive performance. PET/CT imaging could serve as a noninvasive tool in the guidance of immunotherapy and individualized treatment in CRC patients.
Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis
Authors: Jiao Baihai , An Changlong , Tran Melanie , Du Hao , Wang Penghua , Zhou Dong , Wang Yanlin
Published: August 2021

A hallmark of chronic kidney disease is renal fibrosis, which can result in progressive loss of kidney function. Currently, there is no effective therapy for renal fibrosis. Therefore, there is an urgent need to identify potential drug targets for renal fibrosis. In this study, we examined the effect of a selective STAT6 inhibitor, AS1517499, on myeloid fibroblast activation, macrophage polarization, and development of renal fibrosis in two experimental murine models. To investigate the effect of STAT6 inhibition on myeloid fibroblast activation, macrophage polarization, and kidney fibrosis, wild-type mice were subjected to unilateral ureteral obstruction or folic acid administration and treated with AS1517499. Mice treated with vehicle were used as control. At the end of experiments, kidneys were harvested for analysis of myeloid fibroblast activation, macrophage polarization, and renal fibrosis and function. Unilateral ureteral obstruction or folic acid administration induced STAT6 activation in interstitial cells of the kidney, which was significantly abolished by AS1517499 treatment. Mice treated with AS1517499 accumulated fewer myeloid fibroblasts and myofibroblasts in the kidney with ureteral obstruction or folic acid nephropathy compared with vehicle-treated mice. Moreover, AS1517499 significantly suppressed M2 macrophage polarization in the injured kidney. Furthermore, AS1517499 markedly reduced the expression levels of extracellular matrix proteins, and development of kidney fibrosis and dysfunction. These findings suggest that AS1517499 inhibits STAT6 activation, suppresses myeloid fibroblast activation, reduces M2 macrophage polarization, attenuates extracellular matrix protein production, and preserves kidney function. Therefore, targeting STAT6 with AS1517499 is a novel therapeutic approach for chronic kidney disease.
SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression
Authors: Batalis Stephanie , Rogers LeAnn C. , Hemphill Wayne O. , Mauney Christopher H. , Ornelles David A. , Hollis Thomas
Published: August 2021

SAMHD1 activity is regulated by a network of mechanisms including phosphorylation, oxidation, oligomerization, and others. Significant questions remain about the effects of phosphorylation on SAMHD1 function and activity. We investigated the effects of a SAMHD1 T592E phosphorylation mimic on its cellular localization, catalytic activity, and cell cycle progression. We found that the SAMHD1 T592E is a catalytically active enzyme that is inhibited by protein oxidation. SAMHD1 T592E is retained in the nucleus at higher levels than the wild-type protein during growth factor-mediated signaling. This nuclear localization protects SAMHD1 from oxidation by cytoplasmic reactive oxygen species. The SAMHD1 T592E phosphomimetic further inhibits the cell cycle S/G2 transition. This has significant implications for SAMHD1 function in regulating innate immunity, antiviral response and DNA replication.
A Kiosk Station for the Assessment of Multiple Cognitive Domains and Cognitive Enrichment of Monkeys
Authors: Womelsdorf Thilo , Thomas Christopher , Neumann Adam , Watson Marcus R. , Banaie Boroujeni Kianoush , Hassani Seyed A. , Parker Jeremy , Hoffman Kari L.
Published: August 2021

Nonhuman primates (NHP’s) are self-motivated to perform cognitive tasks on touchscreens in their animal housing setting. To leverage this ability, fully integrated hardware and software solutions are needed that work within housing and husbandry routines while also spanning cognitive task constructs of the Research Domain Criteria (RDoC). Here, we detail such an integrated robust hardware and software solution for running cognitive tasks in cage-housed NHP’s with a cage-mounted Kiosk Station (KS-1). KS-1 consists of a frame for mounting flexibly on housing cages, a touchscreen animal interface with mounts for receptables, reward pumps, and cameras, and a compact computer cabinet with an interface for controlling behavior. Behavioral control is achieved with a Unity3D program that is virtual-reality capable, allowing semi-naturalistic visual tasks to assess multiple cognitive domains.KS-1 is fully integrated into the regular housing routines of monkeys. A single person can operate multiple KS-1’s. Monkeys engage with KS-1 at high motivation and cognitive performance levels at high intra-individual consistency. KS-1 is optimized for flexible mounting onto standard apartment cage systems and provides a new design variation complementing existing cage-mounted touchscreen systems. KS-1 has a robust animal interface with options for gaze/reach monitoring. It has an integrated user interface for controlling multiple cognitive tasks using a common naturalistic object space designed to enhance task engagement. All custom KS-1 components are open-sourced.In summary, KS-1 is a versatile new tool for cognitive profiling and cognitive enrichment of cage-housed monkeys. It reliably measures multiple cognitive domains which promises to advance our understanding of animal cognition, inter-individual differences, and underlying neurobiology in refined, ethologically meaningful behavioral foraging contexts.
Acupuncture as an Adjunctive Treatment for Post-stroke Epilepsy: Protocol for a Randomized Controlled Trial
Authors: Zhang Yang , Zhao Meidan , Zhang Baozhen , Zhang Kai , Zhou Zhen
Published: August 2021

Background: Acupuncture has been clinically used to treat epilepsy after stroke. However, most of the current clinical studies are observational studies, and there are few well-designed randomized controlled trials (RCTs). Hence, we designed a multicentre RCT to assess the advantages and efficacy of acupuncture for post-stroke epilepsy (PSE).

Methods/Design: This is a two-arm, parallel, participants-blinded and assessor-blinded and multicentre RCT. A total of 120 patients with PSE aged from 18 to 75 years will be randomly assigned to two groups (routine treatment plus acupuncture group and routine treatment plus sham acupuncture group) at a 1:1 ratio. The participants will perform acupuncture or sham acupuncture treatment three times a week and be ongoing 8-week treatment. The primary endpoint is the proportion of seizure-free patients. A safety profile will be established. We will record adverse events for the safety evaluation.

Discussion: The study will provide high-quality clinical evidence on the effectiveness and safety of acupuncture for treating patients with epilepsy after stroke.

Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR2100046114.
Cortical and Subcortical Anatomy of the Parietal Lobe From the Neurosurgical Perspective
Authors: Dziedzic Tomasz Andrzej , Bala Aleksandra , Marchel Andrzej
Published: August 2021

Introduction: The anatomical structures of the parietal lobe at the cortical and subcortical levels are related mainly to sensory, visuospatial, visual and language function. The aim of this study was to present an intraoperative perspective of these critical structures in terms of the surgical treatment of intra-axial lesions. The study also discusses the results of the technique and the results of direct brain stimulation under awake conditions.

Materials and Methods: Five adult brains were prepared according to the Klingler technique. Cortical assessments and all measurements were performed with the naked eye, while white matter dissection was performed with microscopic magnification.

Results: Intra-axial lesions within the parietal lobe can be approached through a lateral or superior trajectory. This decision is based on the location of the lesions in relation to the arcuate fascicle/superior longitudinal fascicle (AF/SLF) complex and ventricular system. Regardless of the approach, the functional borders of the resection are defined by the postcentral gyrus anteriorly and Wernicke's speech area inferiorly. On the subcortical level, active identification of the AF/SLF complex and of the optic radiation within the sagittal stratum should be performed. The intraparietal sulcus (IPS) is a reliable landmark for the AF/SLF complex in ~60% of cases.

Conclusion: Knowledge of the cortical and subcortical anatomical and functional borders of the resection is crucial in preoperative planning, prediction of the risk of postoperative deficits, and intraoperative decision making.
Prevention and Treatment of Hardware-Related Infections in Deep Brain Stimulation Surgeries: A Retrospective and Historical Controlled Study
Authors: Li Jiping , Zhang Wenjie , Mei Shanshan , Qiao Liang , Wang Yunpeng , Zhang Xiaohua , Li Jianyu , Hu Yongsheng , Jia Xiaofei , Zhang Yuqing
Published: August 2021

Background

Hardware-related infection in deep brain stimulation (DBS) is one of the most commonly reported complications frequently resulting in the removal of implantable pulse generator (IPG).

Objective

The aim of this study was to establish a useful strategy to better prevent and treat those infections and to improve the preservation rates of IPG.

Methods

We conducted a retrospective and historical controlled study of all adult patients (≥18 years old) who had undergone initial DBS implantation at a single center. All participants were enrolled in the control group (between June 2005 and June 2014) or intervention group (between July 2014 and May 2019) based on their surgery dates. We used the intraoperative irrigation with hydrogen dioxide solution in the intervention group. Based on the dates of diagnosis, patients with hardware-related infection after DBS were enrolled in group A (between June 2005 and June 2014) or group B (between July 2014 and May 2019). IPG-sparing algorithm (Isa) was applied for group B. The early-onset IPG infections of the control and intervention groups were evaluated. The IPG preservation rates in both groups A and B were statistically analyzed.

Results

Six cases of early IPG infection and subsequent IPG removal occurred in the control group, while none occurred after intraoperative usage of the hydrogen dioxide in the intervention group. IPG preservation rate of infected cases in group B was significantly higher than that in group A (70% vs.16%, p = 0.004).

Conclusion

The combined application of hydrogen dioxide solution and Isa seems to be an effective strategy to prevent IPG infection.
Category Congruence of Display-Only Products Influences Attention and Purchase Decisions
Authors: Karmarkar Uma R. , Carroll Ann L. , Burke Marina , Hijikata Shori
Published: August 2021

In e-commerce settings, shoppers can navigate to product-specific pages on which they are asked to make yes-or-no decisions about buying a particular item. Beyond that target, there are often other products displayed on the page, such as those suggested by the retailers’ recommendation systems, that can influence consumers’ buying behavior. We propose that display items that come from the same category as the target product (matched) may enhance target purchase by increasing the attractiveness of the presented opportunity. Contrasting this, mismatched display items may reduce purchase by raising awareness of opportunity costs. Eye-tracking was used to explore this framework by examining how different types of displays influenced visual attention. Although target purchase rates were higher for products with matched vs. mismatched displays, there was no difference in fixation time for the target images. However, participants attended to mismatched display items for more time than they did for matched ones consistent with the hypothesized processes. In addition, increases in display attractiveness increased target purchase, but only for matched items, in line with supporting the target category. Given the importance of relative attention and information in determining the impact of display items, we replicated the overall purchase effect across varying amounts of available display information in a second behavioral study. This demonstration of robustness supports the translational relevance of these findings for application in industry.
The Predictive Values of Advanced Non-Small Cell Lung Cancer Patients Harboring Uncommon EGFR Mutations—The Mutation Patterns, Use of Different Generations of EGFR-TKIs, and Concurrent Genetic Alterations
Authors: Tan Jiarong , Hu Chengping , Deng Pengbo , Wan Rongjun , Cao Liming , Li Min , Yang Huaping , Gu Qihua , An Jian , Jiang Juan
Published: August 2021

Introduction

Epidermal growth factor receptor (EGFR) 19del and L858R mutation are known as “common mutations” in non-small cell lung cancer (NSCLC) and predict sensitivities to EGFR tyrosine kinase inhibitors (TKIs), whereas 20ins and T790M mutations confer drug-resistance to EGFR-TKIs. The role of the remaining uncommon EGFR mutations remains elusive.

Methods

We retrospectively screened a group of NSCLC patients with uncommon EGFR mutations other than 20ins and T790M. The mutation patterns, use of different generations of EGFR-TKIs, and concurrent genetic alterations were analyzed. Meanwhile, a cohort of patients with single 19del or L858R were included for comparison.

Results

A total of 180/1,300 (13.8%) patients were identified. There were 102 patients with advanced or recurrent NSCLC that received first-line therapy of gefitinib/erlotinib/icotinib and afatinib and were eligible for analysis. The therapeutic outcomes among patients with common mutations (EGFRcm, n = 97), uncommon mutation plus common mutations (EGFRum+EGFRcm, n = 52), complex uncommon mutations (complex EGFRum, n = 22), and single uncommon mutations (single EGFRum, n = 28) were significantly different (ORRs: 76.3%, 61.5%, 54.5%, and 50.0%, respectively, p = 0.023; and mPFS: 13.3, 14.7, 8.1, and 6.0 months, respectively, p = 0.004). Afatinib showed superior efficacy over gefitinib/erlotinib/icotinib in EGFRcm (ORR: 81.0% vs. 75.0%, p = 0.773; mPFS: 19.1 vs. 12.0m, p = 0.036), EGFRum+EGFRcm (ORR: 100% vs. 54.5%, p = 0.017; mPFS: NE vs. 13.6m, p = 0.032), and single EGFRum (ORR: 78.6% vs. 21.4%, p = 0.007; mPFS: 10.1 vs. 3.0m, p = 0.025) groups. Comprehensive genomic profiling by Next Generation Sequencing encompassing multiple cancer-related genes was performed on 51/102 patients; the mPFS of patients without co-mutation (n = 16) and with co-mutations of tumor-suppressor genes (n = 31) and driver oncogenes (n = 4) were 31.1, 9.2, and 12.4 months, respectively (p = 0.046). TP53 mutation was the most common co-alteration and showed significantly shorter mPFS than TP53 wild-type patients (7.0 vs. 31.1m, p < 0.001). Multivariate analysis revealed that concurrent 19del/L858R and tumor-suppressor gene alterations independently predicted better and worse prognosis in patients with uncommon mutations, respectively.

Conclusions

Uncommon EGFR mutations constitute a highly heterogeneous subgroup of NSCLC that confer different sensitivities to EGFR-TKIs with regard to the mutation patterns. Afatinib may be a better choice for most uncommon EGFR mutations. Concurrent 19del/L858R and tumor-suppressor gene alterations, especially TP53, can be established as prognostic biomarkers.
Identification and Validation of a Five-Gene Signature Associated With Overall Survival in Breast Cancer Patients
Authors: Wang Xiaolong , Li Chen , Chen Tong , Li Wenhao , Zhang Hanwen , Zhang Dong , Liu Ying , Han Dianwen , Li Yaming , Li Zheng , Luo Dan , Zhang Ning , Yang Qifeng
Published: August 2021

Background

Recent years, the global prevalence of breast cancer (BC) was still high and the underlying molecular mechanisms remained largely unknown. The investigation of prognosis-related biomarkers had become an urgent demand.

Results

In this study, gene expression profiles and clinical information of breast cancer patients were downloaded from the TCGA database. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1, and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the TCGA entire cohort and an independent external validation cohort. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression.

Conclusions

We established a predictive five-gene signature, which could be helpful for a personalized management in breast cancer patients.
A Prospective Study of Liver Regeneration After Radiotherapy Based on a New (Su’S) Target Area Delineation
Authors: Su Ting-Shi , Li Li-Qing , Liang Shi-Xiong , Xiang Bang-De , Li Jian-Xu , Ye Jia-Zhou , Li Le-Qun
Published: August 2021

Background

In this study, we designed a new (Su’S) target area delineation to protect the normal liver during liver regeneration and prospectively evaluate liver regeneration after radiotherapy, as well as to explore the clinical factors of liver regeneration and established a model and nomogram.

Methods

Thirty patients treated with preoperative downstaging radiotherapy were prospectively included in the training cohort, and 21 patients treated with postoperative adjuvant radiotherapy were included in the validation cohort. The cut-off points of each optimal predictor were obtained using receiver-operating characteristic analysis. A model and nomogram for liver regeneration after radiotherapy were developed and validated.

Results

After radiotherapy, 12 (40%) and 13 (61.9%) patients in the training and validation cohorts experienced liver regeneration, respectively. The risk stratification model based on the cutoffs of standard residual liver volume spared from at least 20 Gy (SVs20 = 303.4 mL/m2) and alanine aminotransferase (ALT=43 u/L) was able to effectively discriminate the probability of liver regeneration. The model and nomogram of liver regeneration based on SVs20 and ALT showed good prediction performance (AUC=0.759) in the training cohort and performed well (AUC=0.808) in the validation cohort.

Conclusions

SVs20 and ALT were optimal predictors of liver regeneration. This model may be beneficial to the constraints of the normal liver outside the radiotherapy-targeted areas.
Integrated Bioinformatic Analysis of the Expression and Prognosis of Caveolae-Related Genes in Human Breast Cancer
Authors: Tian Yao , Liu Xiaofeng , Hu Jing , Zhang Huan , Wang Baichuan , Li Yingxi , Fu Li , Su Ran , Yu Yue
Published: August 2021

Caveolae-related genes, including CAVs that encodes caveolins and CAVINs that encodes caveolae-associated proteins cavins, have been identified for playing significant roles in a variety of biological processes including cholesterol transport and signal transduction, but evidences related to tumorigenesis and cancer progression are not abundant to correlate with clinical characteristics and prognosis of patients with cancer. In this study, we investigated the expression of these genes at transcriptional and translational levels in patients with breast cancer using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal databases, and immunohistochemistry of the patients in our hospital. Prognosis of patients with breast cancer based on the expressions of CAVs and CAVINs was summarized using Kaplan-Meier Plotter with their correlation to different subtyping. The relevant molecular pathways of these genes were further analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and Gene Set Enrichment Analysis (GSEA). Results elucidated that expression levels of CAV1, CAV2, CAVIN1, CAVIN2, and CAVIN3 were significantly lower in breast cancer tissues than in normal samples, while the expression level of CAVIN2 was correlated with advanced tumor stage. Furthermore, investigations on survival of patients with breast cancer indicated outstanding associations between prognosis and CAVIN2 levels, especially for the patients with estrogen receptor positive (ER+) breast cancer. In conclusion, our investigation indicated CAVIN2 is a potential therapeutic target for patients with ER+ breast cancer, which may relate to functions of cancer cell surface receptors and adhesion molecules.
Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer
Authors: Zhao Yang , Zhao Bin , Yan Wei-Hua , Xia Yan , Wang Zhi-Hui , Zheng Guo-Yang , Wang Wen-Da , Zhang Yu-Shi
Published: August 2021

Background

Bladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter 4 (MCT4), encoded by SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients.

Methods

The published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (TCGA) bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. The Kaplan–Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients.

Results

SLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (p = 0.016). High MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, p = 0.014). A nomogram was built based on the results of the multivariate Cox analysis.

Conclusion

Bladder cancer with high SLC16A3 mRNA expression has a poor OS. High MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy.
HDR Brachytherapy and SBRT as Bridging Therapy to Liver Transplantation in HCC Patients: A Single-Center Experience
Authors: Walter Franziska , Fuchs Frederik , Gerum Sabine , Rottler Maya C. , Erdelkamp Robert , Neumann Jens , Nierer Lukas , Guba Markus , De Toni Enrico N. , Seidensticker Max , Ricke Jens , Belka Claus , Corradini Stefanie
Published: August 2021

Background

In the treatment of patients with HCC awaiting liver transplantation (LT), local ablative treatments (LAT) are available either for downstaging or as bridging treatment. We present our clinical experience with both available radiation-based techniques, brachytherapy (BT), and stereotactic body radiotherapy (SBRT).

Methods

All patients diagnosed with HCC and who were treated with BT or SBRT at our institution between 2011 and 2018 were retrospectively reviewed. The current analysis included all patients who subsequently underwent LT.

Results

A total of 14 patients (male=9; female=5) were evaluated. Seven underwent BT for bridging before LT, and seven were treated with SBRT. BT was performed with a prescribed dose of 1 × 15 Gy, while SBRT was applied with 37 Gy (65%-iso) in three fractions in six patients, and one patient was treated with 54 Gy (100%-iso) in nine fractions. The treatment was generally well tolerated. One case of grade 3 bleeding was reported after BT, and one case of liver failure occurred following SBRT. All patients underwent LT after a median time interval of 152 days (range 47–311) after BT and 202 days (range 44–775) following SBRT. In eight cases, no viable tumor was found in the explanted liver, while four liver specimens showed vital tumor. The median follow-up after SBRT was 41 months and 17 months following BT. Overall, no hepatic HCC recurrence occurred following LT.

Conclusion

Both SBRT and BT are feasible and well tolerated as bridging to LT when applied with caution in patients with impaired liver function. Radiation-based treatments can close the gap for patients not suitable for other locally ablative treatment options.
Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats
Authors: Yu Xiaolu , Zhou Junnan , Zhao Fuli , Liu Xuan , Mao Yuhang , Diao Li , Wen Chuanjun , Liu Mei
Published: August 2021

Fibroblast-like synoviocytes (FLSs) are the prominent non-immune cells in synovium and play a pivotal role in rheumatoid arthritis (RA) pathogenesis. Searching for natural compounds that may suppress the pathological phenotypes of FLSs is important for the development of RA treatment. Tomatidine (Td), a steroidal alkaloid derived from the solanaceae family, has been reported to have anti-inflammatory, anti-tumor and immunomodulatory effects. However, its effect on RA remains unknown. Here, we examined the inhibitory effect of Td on TNFα-induced arthritic FLSs, and subsequently investigated its therapeutic effect on collagen-induced arthritis (CIA) rats. Our results revealed that Td significantly inhibited TNFα-induced proliferation and migration of arthritic FLSs. In addition, we found that Td treatment could efficaciously ameliorate synovial inflammation and joint destruction of rats with CIA. Both in vitro and in vivo studies showed that Td significantly suppressed the production of pro-inflammatory cytokines including IL-1β, IL-6 and TNFα, and downregulated the expression of MMP-9 and RANKL. Further molecular mechanism studies revealed that the inhibitory effect of Td on RA might attribute to the decreased activations of MAPKs (ERK and JNK) and NF-κB. These findings provide evidence that Td has the potential to be developed into a complementary or alternative agent for RA therapy.
The Influence of Actual Appraisals of Peers on the Self-Appraisals of Personality Traits for Chinese Late Adolescents: The Mediating Effect of Reflected Appraisals
Authors: Yue Caizhen , Long Yihong , Yang Zhiwen , Xiao Qianguo , Pan Weigang
Published: August 2021

Reflected appraisals refer to the perceptions of individuals of how they are perceived by others. Numerous studies in cultural psychology have revealed that individuals in the Eastern collectivist culture show an interdependent self-construal, which depends much on the social culture. Hence, the research on reflected appraisals in the Eastern culture can improve the understanding of how the social environment shapes the self-perception of an individual. In this study, we aimed to explore the relationships among self-appraisals, reflected appraisals, and actual appraisals of peers of the Big Five personality for Chinese late adolescents. Participants were divided into 16 groups, with two to four people of each group who were familiar with each other. Each participant was told to fill out the questionnaires of reflected appraisals, actual appraisals of peers, and self-appraisals. Through analyzing 164 sets of data, the results showed the following: (a) The scores of reflected appraisals are significantly lower than that of the actual appraisals of peers. (b) The relationships among the reflected appraisals, actual appraisals of peers, and self-appraisals are distinct on different personalities. For extroversion, there are significant medium- to high-degree relationships among the three types of appraisals; while for the agreeableness, conscientiousness, emotional stability, and openness, self-appraisals are highly correlated with reflected appraisals, and reflected appraisals show a low-degree correlation with the actual appraisals of peers. (c) Reflected appraisals play a mediating role between actual appraisals of peers and self-appraisals. Our study suggests that individuals in Chinese culture generally underestimate how their peers perceive them. Furthermore, actual appraisals of peers affect the self-concepts of individuals through reflected appraisals. This study revealed the unique personality feature of self-modesty under the background of Chinese culture and the importance of peers on the development of self-concepts for Chinese late adolescents. This study can shed new light on the understanding of the development of self-concepts for late adolescents under different cultural backgrounds.
Technology Integration in Higher Education During COVID-19: An Assessment of Online Teaching Competencies Through Technological Pedagogical Content Knowledge Model
Authors: Akram Huma , Yingxiu Yang , Al-Adwan Ahmad Samed , Alkhalifah Ali
Published: August 2021

The COVID-19 pandemic significantly shifted education from traditional to an online version, which was an emergent state for teachers and students. The substantive situation thus raises the importance of technology integration in education, and teachers are required to update their competencies, respectively. In this regard, the study assessed online teaching competencies of faculty members following, technological pedagogical content knowledge (TPACK) model. Closed-ended surveys were employed for quantitative analysis of randomly selected 256 faculty members from public universities in Karachi, Pakistan. Results indicated that teachers possessed adequate levels of knowledge across all the domains of TPACK. The highest competency was obtained by content knowledge (CK), while technological knowledge (TK) was reported at the lowest level. Furthermore, a significant difference was noted in terms of gender and teaching experience. Correspondingly, the study proposes that the TPACK model should be employed in the professional development programs to develop teachers’ TPACK for integrating information communication and technology in the pedagogical practices. The findings of the study present a constructive overview of teachers’ digital competencies and technology use in teaching and learning in the time of the COVID-19 and also play a significant role in the integration of technology in the post-pandemic time in higher education. The study also suggests relevant educational authorities and policymakers for assessing and enhancing the technological competencies of teachers for quality online education.
The Transplant Evaluation Rating Scale Predicts Clinical Outcomes 1 Year After Lung Transplantation: A Prospective Longitudinal Study
Authors: Nöhre Mariel , de Zwaan Martina , Bauer-Hohmann Maximilian , Ius Fabio , Valtin Christina , Gottlieb Jens
Published: August 2021

Objectives:It has been recommended that all candidates for lung transplantation undergo pre-transplant psychosocial evaluation for risk assessment. However, psychosocial issues are only important if they correlate with outcomes after transplantation.

Methods:In this prospective study patients who were referred for lung transplantation from 2016 to 2018 (n= 352) at Hannover Medical School were evaluated using the Transplant Evaluation Rating Scale (TERS). Clinical outcomes included listing, and post-transplant outcomes including mortality, medical aspects such as lung allograft dysfunction, hospitalizations, and renal function, behavioral aspects such as BMI and adherence, and mental issues such as levels of depression, anxiety, and quality of life. TERS scores were divided into tertiles and, in addition, the impact of the two subscale scores—“defiance” and “emotional sensitivity”—was investigated.

Results:Of the patients who were transplanted (n= 271) and were still alive (n= 251), 240 had already reached their 1-year assessment at the end of 2020 and were evaluated 1 year after the operation. A subgroup of 143 received an extended mental assessment. BMI, adherence scores, levels of anxiety, depression, and quality of life 1 year post-transplantation differed significantly between TERS tertiles with higher TERS scores predicting less favorable outcomes. The TERS subscale “defiance” was predictive of BMI and adherence whereas the TERS subscale “emotional sensitivity” was predictive of symptoms of anxiety and depression, and quality of life 1 year after transplantation. Patients in the lowest TERS tertile were more likely to having been listed and—as a trend—to having survived the first year after transplantation

Conclusions:Our findings show that psychosocial factors as measured by TERS score are predictors of behavioral and mental outcomes 1 year after lung transplantation. The TERS allows us to focus on psychosocial risk factors that can be treated or minimized before or after transplantation.
Confirmation of a Causal Taar1 Allelic Variant in Addiction-Relevant Methamphetamine Behaviors
Authors: Phillips Tamara J. , Roy Tyler , Aldrich Sara J. , Baba Harue , Erk Jason , Mootz John R. K. , Reed Cheryl , Chesler Elissa J.
Published: August 2021

Sensitivity to rewarding and reinforcing drug effects has a critical role in initial use, but the role of initial aversive drug effects has received less attention. Methamphetamine effects on dopamine re-uptake and efflux are associated with its addiction potential. However, methamphetamine also serves as a substrate for the trace amine-associated receptor 1 (TAAR1). Growing evidence in animal models indicates that increasing TAAR1 function reduces drug self-administration and intake. We previously determined that a non-synonymous single nucleotide polymorphism (SNP) in Taar1 predicts a conformational change in the receptor that has functional consequences. A Taar1m1J mutant allele existing in DBA/2J mice expresses a non-functional receptor. In comparison to mice that possess one or more copies of the reference Taar1 allele (Taar1+/+ or Taar1+/m1J), mice with the Taar1m1J/m1J genotype readily consume methamphetamine, express low sensitivity to aversive effects of methamphetamine, and lack sensitivity to acute methamphetamine-induced hypothermia. We used three sets of knock-in and control mice in which one Taar1 allele was exchanged with the alternative allele to determine if other methamphetamine-related traits and an opioid trait are impacted by the same Taar1 SNP proven to affect MA consumption and hypothermia. First, we measured sensitivity to conditioned rewarding and aversive effects of methamphetamine to determine if an impact of the Taar1 SNP on these traits could be proven. Next, we used multiple genetic backgrounds to study the consistency of Taar1 allelic effects on methamphetamine intake and hypothermia. Finally, we studied morphine-induced hypothermia to confirm prior data suggesting that a gene in linkage disequilibrium with Taar1, rather than Taar1, accounts for prior observed differences in sensitivity. We found that a single SNP exchange reduced sensitivity to methamphetamine conditioned reward and increased sensitivity to conditioned aversion. Profound differences in methamphetamine intake and hypothermia consistently corresponded with genotype at the SNP location, with only slight variation in magnitude across genetic backgrounds. Morphine-induced hypothermia was not dependent on Taar1 genotype. Thus, Taar1 genotype and TAAR1 function impact multiple methamphetamine-related effects that likely predict the potential for methamphetamine use. These data support further investigation of their potential roles in risk for methamphetamine addiction and therapeutic development.
Early Fever Is Associated With Clinical Outcomes in Patients With Coronavirus Disease
Authors: Ding Feng-ming , Feng Yun , Han Lei , Zhou Yan , Ji Yong , Hao Hui-juan , Xue Yi-shu , Yin Dong-ning , Xu Zeng-chao , Luo Shan , Zhang Peng-yu , Zhang Min
Published: August 2021

Fever is one of the typical symptoms of coronavirus disease (COVID-19). We aimed to investigate the association between early fever (EF) and clinical outcomes in COVID-19 patients. A total of 1,014 COVID-19 patients at the Leishenshan Hospital were enrolled and classified into the EF and non-EF groups based on whether they had fever within 5 days of symptom onset. Risk factors for clinical outcomes in patients with different levels of disease severity were analyzed using multivariable analyses. Time from symptom onset to symptom alleviation, CT image improvement, and discharge were longer for patients with moderate and severe disease in the EF group than in the non-EF group. Multivariable analysis showed that sex, EF, eosinophil number, C-reactive protein, and IL-6 levels were positively correlated with the time from symptom onset to hospital discharge in moderate cases. The EF patients showed no significant differences in the development of acute respiratory distress syndrome, compared with the non-EF patients. The Kaplan–Meier curve showed no obvious differences in survival between the EF and non-EF patients. However, EF patients with increased temperature showed markedly lower survival than the non-EF patients with increased temperature. EF had no significant impact on the survival of critically ill patients, while an increase in temperature was identified as an independent risk factor. EF appears to be a predictor of longer recovery time in moderate/severe COVID-19 infections. However, its value in predicting mortality needs to be considered for critically ill patients with EF showing increasing temperature.
900 MHz Radiofrequency Field Induces Mitochondrial Unfolded Protein Response in Mouse Bone Marrow Stem Cells
Authors: Xie Wen , Xu Rui , Fan Caiyun , Yang Chunyu , Chen Haiyan , Cao Yi
Published: August 2021

Objective: To examine whether exposure of mouse bone marrow stromal cells (BMSC) to 900 MHz radiofrequency fields used in mobile communication devices can induce mitochondrial unfolded protein response (UPRmt).

Methods: BMSCs were exposed to continuous wave 900 MHz radiofrequency fields (RF) at 120 μW/cm2 power intensity for 4 h/d for 5 consecutive days. Cells in sham group (SH) were cultured in RF exposure system, but without RF radiation. The positive control cells were irradiated with 6 Gy X-ray at a dose rate of 1.103 Gy/min (XR). To inhibit the upstream molecular JNK2 of UPRmt, cells in siRNA + RF, and siRNA + XR group were also pretreated with 100 nM siRNA-JNK2 for 48 h before RF/XR exposure. Thirty minutes, 4 h, and 24 h post-RF/XR exposure, cells were collected, the level of ROS was measured with flow cytometry, the expression levels of UPRmt-related proteins were detected using western blot analysis.

Results: Compared with Sham group, the level of ROS in RF and XR group was significantly increased 30 min and 4 h post-RF/XR exposure (P < 0.05), however, the RF/XR-induced increase of ROS level reversed 24 h post-RF/XR exposure. Compared with Sham group, the expression levels of HSP10/HSP60/ClpP proteins in cells of RF and XR group increased significantly 30 min and 4 h post-RF/XR exposure (P < 0.05), however, the RF/XR-induced increase of HSP10/HSP60/ClpP protein levels reversed 24 h post-RF exposure. After interfering with siRNA-JNK2, the RF/XR exposures could not induce the increase of HSP10/HSP60/ClpP protein levels any more.

Conclusions: The exposure of 900 MHz RF at 120 μW/cm2 power flux density could increase ROS level and activate a transient UPRmt in BMSC cells. Mitochondrial homeostasis in term of protein folding ability is restored 24 h post-RF exposure. Exposure to RF in our experimental condition did not cause permanent and severe mitochondrial dysfunctions. However, the detailed underlying molecular mechanism of RF-induced UPRmt remains to be further studied.
Delivery of Healthcare Resources Using Autonomous Ground Vehicle Convoy Systems: An Overview
Authors: Cheung Calvin , Mohammadi Alireza , Rawashdeh Samir , Baek Stanley
Published: August 2021

Utilizing military convoys in humanitarian missions allows for increased overall performance of healthcare logistical operations. To properly gauge performance of autonomous ground convoy systems in military humanitarian operations, a proper framework for comparative performance metrics needs to be established. Past efforts in this domain have had heavy focus on narrow and specialized areas of convoy performance such as human factors, trust metrics, or string stability analysis. This article reviews available Army doctrine for manned convoy requirements toward healthcare missions and establishes a framework to compare performance of autonomous convoys, using metrics such as spacing error, separation distance, and string stability. After developing a framework of comparison for the convoy systems, this article compares the performance of two autonomous convoys with unique convoy control strategies to demonstrate the application and utility of the framework.
Prognostic Value of Highly Expressed Type VII Collagen (COL7A1) in Patients With Gastric Cancer
Authors: Oh Sung Eun , Oh Mi Yun , An Ji Yeong , Lee Jun Ho , Sohn Tae Sung , Bae Jae Moon , Choi Min-Gew , Kim Kyoung-Mee
Published: August 2021

Collagen is a major component in the tumor microenvironment. This study reveals a novel biomarker candidate, type VII collagen (COL7A1), in patients with gastric cancer. To identify genes differentially expressed in gastric cancer tissue, we analyzed cancerous (n = 20) and noncancerous tissues (n = 13) using a DNA microarray. To perform immunohistochemistry and validate the upregulation of COL7A1 expression, we collected 200 more gastric cancer tissues and 100 normal gastric tissues from 200 randomly selected patients who underwent gastrectomy for gastric cancer between January 2010 and December 2013. The correlations between COL7A1 expression and clinicopathological parameters and patients’ overall survival (OS) were analyzed. In the microarray, COL7A1 was upregulated in gastric cancer tissue compared with normal tissue. In the immunohistochemistry study, COL7A1 was more highly expressed in cancer tissue than in normal tissue (p = 0.001). Patients with intracellular COL7A1 expression had significantly poorer five-year OS than those with only extracellular expression (41.5 versus 69.7%, p = 0.001), and the site of expression was an independent prognostic factor of OS (hazard ratio 2.00, 95% CI 1.26–3.16, p = 0.003). Also, we found a significant association between the COL7A1 immunohistochemistry score and distant metastasis (high versus low, odds ratio 4.45, 95% CI 1.40–14.16, p = 0.011). The site and total immunohistochemistry score of COL7A1 expression in gastric cancer showed prognostic significance for OS and distant metastasis, respectively. COL7A1 could be a novel biomarker with diagnostic and therapeutic value.