bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Checkpoint Gene Expression Profiling Identifies Programmed Cell Death Ligand-1 Centered Immunologic Subtypes of Oral and Squamous Cell Carcinoma With Favorable Survival
Authors: Yu Yang , Tang Huiwen , Franceschi Debora , Mujagond Prabhakar , Acharya Aneesha , Deng Yupei , Lethaus Bernd , Savkovic Vuk , Zimmerer Rüdiger , Ziebolz Dirk , Li Simin , Schmalz Gerhard
Published: January 2022

Objective

This study aimed to identify the programmed death ligand-1 (PDL1, also termed as CD274) and its positively correlated immune checkpoint genes (ICGs) and to determine the immune subtypes of CD274-centered ICG combinations in oral and squamous cell carcinoma (OSCC).

Materials and Methods

Firstly, the 95 ICGs obtained via literature reviews were identified in the Cancer Genome Atlas (TCGA) database in relation to OSCC, and such 88 ICG expression profiles were extracted. ICGs positively correlated with CD274 were utilized for subsequent analysis. The relationship between ICGs positively correlated with CD274 and immunotherapy biomarkers (tumor mutation burden (TMB), and adaptive immune resistance pathway genes) was investigated, and the relationships of these genes with OSCC clinical features were explored. The prognostic values of CD274 and its positively correlated ICGs and also their associated gene pairs were revealed using the survival analysis.

Results

Eight ICGs, including CTLA4, ICOS, TNFRSF4, CD27, B- and T-lymphocyte attenuator (BTLA), ADORA2A, CD40LG, and CD28, were found to be positively correlated with CD274. Among the eight ICGs, seven ICGs (CTLA4, ICOS, TNFRSF4, CD27, BTLA, CD40LG, and CD28) were significantly negatively correlated with TMB. The majority of the adaptive immune resistance pathway genes were positively correlated with ICGs positively correlated with CD274. The survival analysis utilizing the TCGA-OSCC data showed that, although CD274 was not significantly associated with overall survival (OS), the majority of ICGs positively correlated with CD274 (BTLA, CD27, CTLA4, CD40LG, CD28, ICOS, and TNFRSF4) were significantly correlated with OS, whereby their low-expression predicted a favorable prognosis. The survival analysis based on the gene pair subtypes showed that the combination subtypes of CD274_low/BTLA_low, CD274_low/CD27_low, CD274_low/CTLA4_low, CD8A_high/BTLA_low, CD8A_high/CD27_low, and CD8A_high/CTLA4_low predicted favorable OS.

Conclusion

The results in this study provide a theoretical basis for prognostic immune subtyping of OSCC and highlight the importance of developing future immunotherapeutic strategies for treating oral cancer.
Macular Microvasculature Is Associated With Total Cerebral Small Vessel Disease Burden in Recent Single Subcortical Infarction
Authors: Kwapong William Robert , Jiang Shuai , Yan Yuying , Wan Jincheng , Wu Bo
Published: January 2022

Purpose

To assess the retinal microvasculature, choriocapillaris, and choroidal thickness in recent single subcortical infarction (RSSI) patients compared with healthy controls. We also assessed the correlation between the macular microvascular changes and choroidal changes with their clinical implications in RSSI patients.

Methods

Forty-six RSSI patients and 39 healthy controls (HC) were enrolled in our study. Magnetic resonance imaging (MRI) was done for all RSSI patients, and a total cerebral small vessel disease (CSVD) score was assessed for all patients. Swept-source optical coherence tomography (SS-OCT) was used to image and assess the choroidal thickness and SS-OCT angiography (SS-OCTA) was used to image and assess the macular microvasculature and choriocapillaris in all participants. Clinical information was collected for all participants.

Results

RSSI patients showed significantly sparser inner retinal microvasculature (P = 0.003) when compared with healthy controls. RSSI patients showed significantly thinner choroidal thickness (P < 0.001) when compared with HC. No significant difference (P = 0.247) was seen when the choriocapillaris was compared between the two groups. CSVD burden (P = 0.014) and NIHSS score (P = 0.010) showed significant correlation with the inner retinal microvasculature of RSSI patients. The inner retinal microvasculature (P = 0.016) and choroidal thickness (P = 0.018) showed a significant correlation with the MoCA scores in RSSI patients.

Conclusions

Our report suggests that retinal and choroidal imaging may serve as useful indicators to expand our understanding of RSSI and its clinical validity.
Tinnitus: Characteristics, Need for Therapy, and Therapeutic Outcomes; Results of an International Patient Initiated Platform
Authors: Smit Adriana L. , Vesala Markku , Goedhart Hazel , Eijden Job van , Wempe Christiaan , Stegeman Inge
Published: January 2022

Introduction

So far, there is a gap of knowledge about factors influencing the impact of tinnitus, the need for treatment, as well as the experienced effect of regular and alternative tinnitus therapies. In this study, we analyzed the need for treatment and the outcomes of these treatments in an international patient initiated in tinnitus platform.

Materials and Methods

Two surveys were undertaken at an online tinnitus patient support community (www.tinnitustalk.com). The surveys were aimed at (1) using tinnitus treatment and outcomes and (2) the factors that influence tinnitus. Univariable logistic and linear regression were used to calculate the relation between the factors and the tinnitus impact as well as the relation with the used tinnitus treatments and the outcomes.

Results

Of the participants to the first survey (n = 5,017), 2,914 (58.1%) used one or more tinnitus therapies, whereas others most commonly self-administered sound therapy [n = 1,562 (31.1%)] and supplements/herbal medicines [n = 1,157 (23.1 %)]. Being female [odds ratio (OR) 0.83 (95% CI 0.74–0.93, p < 0.01)], tinnitus impact, and some degrees of hearing loss and hyperacusis were all statistically significantly associated with higher odds of having tinnitus treatment. Out of the second survey (n = 6,115), it was found that patient physical and psychological factors were statistically significantly related to tinnitus impact.

Conclusion

In this study, we demonstrated the usage and experience of (multiple) tinnitus therapy in patients. Several patient physical and psychological characteristics were found to be related to tinnitus impact and therapy usage. These outcomes might function as the next step to find a personalized treatment and to improve the tinnitus health care.
Blood-Based Markers of Neuronal Injury in Adult-Onset Myotonic Dystrophy Type 1
Authors: van der Plas Ellen , Long Jeffrey D. , Koscik Timothy R. , Magnotta Vincent , Monckton Darren G. , Cumming Sarah A. , Gottschalk Amy C. , Hefti Marco , Gutmann Laurie , Nopoulos Peggy C.
Published: January 2022

Introduction

The present study had four aims. First, neuronal injury markers, including neurofilament light (NF-L), total tau, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1), were compared between individuals with and without adult-onset myotonic dystrophy type 1 (DM1). Second, the impact of age and CTG repeat on brain injury markers was evaluated. Third, change in brain injury markers across the study period was quantified. Fourth, associations between brain injury markers and cerebral white matter (WM) fractional anisotropy (FA) were identified.

Methods

Yearly assessments, encompassing blood draws and diffusion tensor imaging on a 3T scanner, were conducted on three occasions. Neuronal injury markers were quantified using single molecule array (Simoa).

Results

The sample included 53 patients and 70 controls. NF-L was higher in DM1 patients than controls, with individuals in the premanifest phases of DM1 (PreDM1) exhibiting intermediate levels (χ(2)2=38.142, P < 0.001). Total tau was lower in DM1 patients than controls (Estimate = −0.62, 95% confidence interval [CI] −0.95: −0.28, P < 0.001), while GFAP was elevated in PreDM1 only (Estimate = 30.37, 95% CI 10.56:50.19, P = 0.003). Plasma concentrations of UCH-L1 did not differ between groups. The age by CTG interaction predicted NF-L: patients with higher estimated progenitor allelege length (ePAL) had higher NF-L at a younger age, relative to patients with lower CTG repeat; however, the latter exhibited faster age-related change (Estimate = −0.0021, 95% CI −0.0042: −0.0001, P = 0.045). None of the markers changed substantially over the study period. Finally, cerebral WM FA was significantly associated with NF-L (Estimate = −42.86, 95% CI −82.70: −3.02, P = 0.035).

Interpretation

While NF-L appears sensitive to disease onset and severity, its utility as a marker of progression remains to be determined. The tau assay may have low sensitivity to tau pathology associated with DM1.
Effects of Unilateral Stimulation in Parkinson's Disease: A Randomized Double-Blind Crossover Trial
Authors: Zeng Zhitong , Wang Linbin , Shi Weikun , Xu Lu , Lin Zhengyu , Xu Xinmeng , Huang Peng , Pan Yixin , Chen Zhonglue , Ling Yun , Ren Kang , Zhang Chencheng , Sun Bomin , Li Dianyou
Published: January 2022

Introduction

Previous studies have shown that subthalamic nucleus (STN) and unilateral globus pallidus interna (GPi) are similarly effective in the deep brain stimulation (DBS) treatment of motor symptoms. However, the counterintuitively more common clinical application of STN DBS makes us hypothesize that STN is superior to GPi in the treatment of motor symptoms.

Methods

In this prospective, double-blind, randomized crossover study, idiopathic PD patients treated with combined unilateral STN and contralateral GPi DBS (STN in one brain hemisphere and GPi in the other) for 2 to 3 years were enrolled. The MDS UPDRS-III total score and subscale scores for axial and bilateral limb symptoms were assessed preoperatively and at 2- to 3-year follow-up in four randomized, double-blinded conditions: (1) Med–STN+GPi–, (2) Med–STN–GPi+, (3) Med+STN+GPi–, and (4) Med+STN–GPi+.

Results

Eight patients had completed 30 trials of assessment. Compared with the preoperative Med– state, in the Med–STN+GPi– condition, the cardinal symptoms in both sides of the body were all improved. In the Med–STN–GPi+ condition, symptoms of the GPi-stim limb were improved, while only tremor was improved on the ipsilateral side, although all axial symptoms showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi– state, cardinal symptoms were improved on both sides, except that tremor was worsened on the STN-stim side. In the Med+STN–GPi+ state, the overall motor symptoms were aggravated compared with the preoperative Med+ state. Most axial symptoms worsened at acute unilateral STN or GPi DBS onset, compared to both preoperative Med– and Med+ states. No side effects associated with this study were seen.

Conclusions

Improvement in motor symptoms was greater in all sub-scores favoring STN. The effects of STN+ were seen on both sides of the body, while GPi+ mainly acted on the contralateral side.
Action Intentions, Predictive Processing, and Mind Reading: Turning Goalkeepers Into Penalty Killers
Authors: Ridderinkhof K. Richard , Snoek Lukas , Savelsbergh Geert , Cousijn Janna , van Campen A. Dilene
Published: January 2022

The key to action control is one’s ability to adequately predict the consequences of one’s actions. Predictive processing theories assume that forward models enable rapid “preplay” to assess the match between predicted and intended action effects. Here we propose the novel hypothesis that “reading” another’s action intentions requires a rich forward model of that agent’s action. Such a forward model can be obtained and enriched through learning by either practice or simulation. Based on this notion, we ran a series of studies on soccer goalkeepers and novices, who predicted the intended direction of penalties being kicked at them in a computerized penalty-reading task. In line with hypotheses, extensive practice in penaltykickingimproved performance in penalty reading among goalkeepers who had extensive prior experience in penalty blocking but not in penalty kicking. A robust benefit in penalty reading did not result from practice in kinesthetic motorimageryof penalty kicking in novice participants. To test whether goalkeepers actually use such penalty-kicking imagery in penalty reading, we trained a machine-learning classifier on multivariate fMRI activity patterns to distinguish motor-imagery-related from attention-related strategies during a penalty-imagery training task. We then applied that classifier to fMRI data related to a separate penalty-reading task and showed that 2/3 of all correctly read penalty kicks were classified as engaging the motor-imagery circuit rather than merely the attention circuit. This study provides initial evidence that, in order to read our opponent’s action intention, it helps to observe their action kinematics, and use our own forward model to predict the sensory consequences of “our” penalty kick if we were to produce these action kinematics ourselves. In sum, it takes practice as a penalty kicker to become a penalty killer.
Aberrant Resting-State Functional Brain Connectivity of Insular Subregions in Obstructive Sleep Apnea
Authors: Kong Linghong , Li Haijun , Shu Yongqiang , Liu Xiang , Li Panmei , Li Kunyao , Xie Wei , Zeng Yaping , Peng Dechang
Published: January 2022

The insular cortex is a cortical regulatory area involved in dyspnea, cognition, emotion, and sensorimotor function. Previous studies reported that obstructive sleep apnea (OSA) shows insular tissue damage and abnormal functional connections for the whole insula. The insula can be divided into different subregions with distinct functional profiles, including the ventral anterior insula (vAI) participating in affective processing, dorsal anterior insula (dAI) involved in cognitive processing, and posterior insula (PI) involved in the processing of sensorimotor information. However, the functional connectivity (FC) of these insular subregions in OSA has yet to be established. Hence, the purpose of this study was to explore the resting-state FC of the insular subregions with other brain areas and its relationship with clinical symptoms of OSA. Resting-state functional magnetic resonance imaging data from 83 male OSA patients and 84 healthy controls were analyzed by whole-brain voxel-based FC using spherical seeds from six insular subregions, namely, the bilateral vAI, dAI, and PI, to identify abnormalities in the insular subregions network and related brain regions. Ultimately, the Pearson correlation analysis was carried out between the dysfunction results and the neuropsychological tests. Compared with the healthy control group, the OSA patients exhibited disturbed FC from the dAI to areas relevant to cognition, such as the bilateral cerebellum posterior lobe, superior frontal gyrus, right middle frontal gyrus and middle temporal gyrus; decreased FC from the vAI to areas linked with emotion, such as the bilateral fusiform gyrus, superior parietal lobule, precuneus and cerebellum posterior lobe; and abnormal FC from the PI to the brain regions involved in sensorimotor such as the bilateral precentral gyrus, right superior/middle temporal gyrus and left superior frontal gyrus. The linear regression result showed that the apnea-hypopnea index was positively correlated with the increased FC between the right PI and the right precuneus (after Bonferroni correlation, P < 0.001) In conclusion, the abnormal FC between insular subregions and other brain regions were related to cognitive, emotional and sensorimotor networks in OSA patients. These results may provide a new imaging perspective for further understanding of OSA-related cognitive and affective disorders.
Diagnostic Value of Non-Contrast CT in Cerebrospinal Fluid Leakage After Endoscopic Transnasal Surgery for Sellar and Suprasellar Tumors
Authors: Gao Wei , Wang Xiaoyu , Fang Yuanjian , Hong Yuan , Yan Wei , Zhang Sheng , Li Chenguang
Published: January 2022

We aimed to study the relationship between pneumocephalus on non-contrast CT (NCCT) and post-operative cerebrospinal fluid leakage (p-CFL) after endoscopic transsphenoidal sellar and suprasellar tumor surgeries. Data from patients who underwent endoscopic treatment for sellar or suprasellar tumors from January 2018 to March 2020 were consecutively collected and reviewed. The NCCT pneumocephalus (NP) was measured the first day after operation and the first day after the expansive sponge was extracted. p-CFL was determined according to post-operative clinical symptoms, high resolution CT and glucose test, and expert consensus. Of the 253 patients enrolled in this study, 32 (12.6%) had p-CFL. Compared with patients without p-CFL, patients with p-CFL had a higher occurrence of intra-operative CFL, a longer operation time, a higher rate of pneumocephalus on first-day NCCT after operation (i.e., first-day NP), and a higher rate of NP volume change between two NCCT measurements (referred to as the NP change) (all p < 0.05). In multivariate regression analysis, first-day NP was independently associated with p-CFL occurrence [odds ratio (OR)=6.395, 95% confidence interval (CI)=2.236-18.290, p=0.001). After adding the NP change into the regression model, first-day NP was no longer independently associated with p-CFL, and NP change (OR = 19.457, 95% CI = 6.095–62.107, p<0.001) was independently associated with p-CFL. The receiver operating characteristic curve comparison analysis showed that NP change had a significantly better predicting value than first-day NP (area under the curve: 0.988 vs. 0.642, Z=6.451, p=0.001). NP is an effective imaging marker for predicting p-CFL after endoscopic sellar and suprasellar tumors operation, and the NP change has a better predicting value.
Prognostic Value of Pretreatment Controlling Nutritional Status Score for Patients With Pancreatic Cancer: A Meta-Analysis
Authors: Ma Xiaofeng , Zou Weihua , Sun Yu
Published: January 2022

Background

Previous studies have explored the prognostic value of the pretreatment Controlling Nutritional Status (CONUT) score of patients with pancreatic cancer. However, the results of those studies were inconsistent. We used meta-analysis to investigate the impact of the CONUT score on the prognosis for patients with pancreatic cancer.

Methods

We thoroughly searched the PubMed, Web of Science, Embase, and Cochrane Library databases for relevant articles from inception to November 19, 2021. Combined hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to estimate the prognostic value of the CONUT score with respect to survival duration. The pooled odds ratios (ORs) and 95% CIs were used to estimate the correlation between the CONUT score and clinical characteristics.

Results

The database search found seven studies with 2,294 patients for inclusion in this meta-analysis. A high CONUT score was significantly associated with poor overall survival (OS) (HR = 1.56, 95% CI = 1.13–2.16, p = 0.007), but not with recurrence-free survival (RFS) (HR = 1.47, 95% CI = 0.97–2.23, p = 0.072) of patients with pancreatic cancer. Moreover, there was a significant association between an elevated CONUT score and male patients (OR = 1.34, 95% CI = 1.03–1.75, p = 0.029). However, there was no significant association between the CONUT score and the clinical stage (OR = 1.11, 95% CI = 0.46–2.71, p = 0.576), lymph node metastasis (OR = 0.73, 95% CI = 0.39–1.36, p = 0.323), lymphatic vessel invasion (OR = 0.84, 95% CI = 0.55–1.28, p = 0.411), invasion of the portal vein system (OR = 1.04, 95% CI = 0.51–2.13, p = 0.915), and nerve plexus invasion (OR = 1.22, 95% CI = 0.83–1.80, p = 0.318) in patients with pancreatic cancer.

Conclusions

The results of our meta-analysis indicate that a high CONUT score predicts a poor OS in patients with pancreatic cancer. The CONUT score may be an effective prognostic factor in pancreatic cancer in clinical practice.
Genome-Wide Methylation Profiling of lncRNAs Reveals a Novel Progression-Related and Prognostic Marker for Colorectal Cancer
Authors: Lin Shujuan , Gu Simeng , Qian Sangni , Liu Yaxin , Sheng Jinghao , Li Qilong , Yang Jinhua , Ying Xiaojiang , Li Zhenjun , Tang Mengling , Wang Jianbing , Chen Kun , Jin Mingjuan
Published: January 2022

Sporadic colorectal cancer (CRC) develops principally through the adenoma-carcinoma sequence. Previous studies revealed that DNA methylation alterations play a significant role in colorectal neoplastic transformation. On the other hand, long noncoding RNAs (lncRNAs) have been identified to be associated with some critical tumorigenic processes of CRC. Accumulating evidence indicates more intricate regulatory relationships between DNA methylation and lncRNAs in CRC. Nevertheless, the methylation alterations of lncRNAs at different stages of colorectal carcinogenesis based on a genome-wide scale remain elusive. Therefore, in this study, we first used an Illumina MethylationEPIC BeadChip (850K array) to identify the methylation status of lncRNAs in 12 pairs of colorectal cancerous and adjacent normal tissues from cohort I, followed by cross-validation with The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Then, the abnormal hypermethylation of candidate genes in colorectal lesions was successfully confirmed by MassARRAY EpiTYPER in cohort II including 48 CRC patients, and cohort III including 286 CRC patients, 81 advanced adenoma (AA) patients and 81 nonadvanced adenoma (NAA) patients. DLX6-AS1 hypermethylation was detected at all stages of colorectal neoplasms and occurred as early as the NAA stage during colorectal neoplastic progression. The methylation levels were significantly higher in the comparisons of CRC vs. NAA (P < 0.001) and AA vs. NAA (P = 0.004). Moreover, the hypermethylation of DLX6-AS1 promoter was also found in cell-free DNA samples collected from CRC patients as compared to healthy controls (Padj = 0.003). Multivariate Cox proportional hazards regression analysis revealed DLX6-AS1 promoter hypermethylation was independently associated with poorer disease-specific survival (HR = 2.52, 95% CI: 1.35-4.69, P = 0.004) and overall survival (HR = 1.64, 95% CI: 1.02-2.64, P = 0.042) in CRC patients. Finally, a nomogram was constructed and verified by a calibration curve to predict the survival probability of individual CRC patients (C-index: 0.789). Our findings indicate DLX6-AS1 hypermethylation might be an early event during colorectal carcinogenesis and has the potential to be a novel biomarker for CRC progression and prognosis.
Enhancer RNA LINC00242-Induced Expression of PHF10 Drives a Better Prognosis in Pancreatic Adenocarcinoma
Authors: Tong Wen , Zhu Liuyang , Bai Yi , Yang Long , Liu Zirong , Zhang Yamin
Published: January 2022

Enhancer RNA is a kind of non-coding RNA, which is transcribed from the enhancer region of gene and plays an important role in gene transcription regulation. However, the role of eRNA in pancreatic adenocarcinoma (PAAD) is still unclear. In this study, we identified the key eRNA and its target gene in PAAD. The transcriptome data and clinical information of pancreatic cancer were downloaded from the UCSC Xena platform. A total of 2,695 eRNAs and its target gene predicted by the PreSTIGE method were selected as candidate eRNA–target pairs. After survival analysis, we found that LINC00242 was the eRNA most related to patients’ survival, and correlation analysis further indicated that LINC00242 and its target gene PHF10 had a significant co-expression relationship. Downregulation of LINC00242 was significantly associated with unfavorable clinicopathological features. Based on pan-cancer analysis, we found that LINC00242 was associated with the survival of multiple cancers, and LINC00242 was co-expressed with its target genes in multiple cancer types. External experiments further demonstrated that PHF10 was the downstream target gene of LINC00242. After ssGSEA analysis, PAAD patients were classified as high, medium, and low immune cell infiltration clusters. Compared with the low and medium immune infiltration clusters, the expression level of PHF10 was significantly upregulated in the high immune infiltration clusters. After performing the CIBERSORT algorithm, we found that there was a significant difference in the abundance of immune infiltrating cells between the PHF10 high- and low-expression groups. Additionally, the web tool TIMER was used to detect the distribution and expression of PHF10 in pan-cancer.
Comparison of Conventional DWI, Intravoxel Incoherent Motion Imaging, and Diffusion Kurtosis Imaging in Differentiating Lung Lesions
Authors: Zheng Yu , Li Jie , Chen Kang , Zhang Xiaochun , Sun Huan , Li Shujiao , Zhang Xie , Deng Zhenping , Liang Na , Li Shihong
Published: January 2022

Purpose

To compare conventional diffusion weighted imaging (DWI), intravoxel incoherent motion imaging (IVIM) and diffusion kurtosis imaging (DKI) in differentiating malignant and benign lung lesions.

Method

Fifty-five consecutive patients with lung lesions underwent multiple b-value DWI. The apparent diffusion coefficient (ADC), IVIM and DKI parameters were calculated using postprocessing software and compared between the malignant and benign groups. Receiver operating characteristic (ROC) analysis was performed for all parameters.

Results

ADC and D were lower in malignant lesions than in benign lesions, while Kapp was higher (P < 0.05). The differences in D*, f, and Dapp between the two groups were not significant (P > 0.05). The areas under the curves (AUCs) of ADC, D, and Kapp were 0.816, 0.864, and 0.822. The combination of all the significant parameters yielded an AUC of 0.880. There were no significant differences in diagnostic efficacy among ADC, D, Kapp and the predictor factor (PRE).

Conclusions

In this study, traditional DWI (ADC), IVIM (D), and DKI (Kapp) all had good diagnostic performance in differentiating malignant lung lesions from benign lesions, but the combination of ADC, D, and Kapp value had better diagnostic efficacy than these parameters alone.
Identification and Validation Prognostic Impact of MiRNA-30a-5p in Lung Adenocarcinoma
Authors: Jiang Xiulin , Yuan Yixiao , Tang Lin , Wang Juan , Zhang Dahang , Cho William C. , Duan Lincan
Published: January 2022

MiRNA-30a-5p is a microRNA found to be decreased in various human cancers, including lung adenocarcinoma (LUAD). However, the molecular mechanisms of miRNA-30a-5p involve in the progression of LUAD remains unclear. In this study, we found that miRNA-30a-5p expression was significantly decreased in LUAD cells lines, LUAD tissues, and peripheral blood serum. Besides, LUAD patients with decreased miRNA-30a-5p expression exhibit worse clinical outcomes compared to the patients with higher miRNA-30a-5p expression, decreased expression of miRNA-30a-5p was associated with advanced clinical outcomes. Receiver operating characteristic (ROC) curve analysis of miRNA-30a-5p showed an area under the curve (AUC) value of 0.902, indicating its prognostic value in LUAD. Moreover, immune infiltration and gene set enrichment analysis (GSEA) enrichment analyze demonstrated that miRNA-30a-5p expression was associated with immune cell infiltrated in LUAD. Finally, we found that miRNA-30a-5p inhibits cell proliferation, migration, and self-renewal abilities of LUAD in vitro. In summary, this is the first report that miRNA-30a-5p correlated with progression and immune infiltration, which shed some lights on potential prognostic and therapeutic biomarker for LUAD.
High-Temperature Short-Time Preserves Human Milk's Bioactive Proteins and Their Function Better Than Pasteurization Techniques With Long Processing Times
Authors: Kontopodi Eva , Boeren Sjef , Stahl Bernd , van Goudoever Johannes B. , van Elburg Ruurd M. , Hettinga Kasper
Published: January 2022

Donor human milk is generally processed by holder pasteurization (HoP) at 62. 5°C for 30 min. This temperature-time combination is sufficient for eliminating pathogens in donor milk, but also negatively affects several bioactive milk components. Long heating up times may further affect the bioactive properties of pasteurized milk. High-Temperature-Short-Time (HTST), a treatment with shorter processing times (72°C for 15 sec), was investigated as a suitable alternative to HoP. In addition, pasteurization methods that follow the same temperature regime but with varying heating up times were compared. Human milk samples from four different donors were combined into one pool, which was then used to perform all analyses. The effects of these methods on the levels and functionality of immunoglobulin A, lactoferrin, lysozyme and bile salt-stimulated lipase, were evaluated with LC-MS/MS-based proteomics and activity assays, while the pasteurization efficacy was evaluated with an alkaline phosphatase test. HoP, a treatment with long processing times, times, caused the highest reduction in all proteins studied (reduced by 50–98%). Compounds such as lactoferrin and bile salt-stimulated lipase that are more sensitive to heat treatments were better retained with HTST, but their levels and functionality were still significantly lower than those of untreated donor milk (52 and 81% reduction of lactoferrin and bile salt-stimulated lipase activity, respectively). Our findings showed that a treatment with considerably shorter processing times, such as HTST, may reduce the thermal damage caused to the bioactive proteins compared to HoP, without affecting pasteurization efficacy. Since the vast majority of the donor human milk banks that are currently operating on a global level apply HoP to donor milk, our findings may provide relevant information for the optimization of donor milk processing.
Anti-Remodeling Cardiac Therapy in Patients With Duchenne Muscular Dystrophy, Meta-Analysis Study
Authors: Raccah Bruria Hirsh , Biton Bar , Amir Offer , Gotsman Israel , Nahman Dean , Matok Ilan
Published: January 2022

Background: Almost all Duchenne muscular dystrophy (DMD) patients that reach their 30s present cardiomyopathy. As a result, this population remains under-treated. There is no sufficient proof of the efficacy of anti-remodeling cardiac therapy for DMD cardiomyopathy (DMDCM). We aim to assess the efficacy of anti-remodeling cardiac therapy for DMDCM by using meta-analysis.

Methods: PubMed (MEDLINE), Embase, and Cochrane library were searched through January 2021. Randomized control trials, case-control studies, and observational studies that reported assessments of cardiovascular outcomes and death of participants using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid-receptor antagonists and Ivabradine, were included. The primary outcome was total mortality. Secondary outcomes included changes in left ventricular ejection fraction (LVEF), serum natriuretic peptide levels (BNP), and heart rate (HR). Data were extracted for eligibility by two independent reviewers. Random-effects meta-analysis was used to pool results.

Results: Twelve studies with 439 patients were included in our meta-analysis. Treated patients have lower HR, mean difference of −17 beats per minute (CI [−25]–[−9], p < 0.01). The LVEF was improved in treated patients, with a mean difference of LVEF of 3.77% (CI 0.44–7.12, p < 0.03). Although mortality rates did not reach statistical significance there was a trend for total mortality reduction (hazard ratio 0.36, CI (0.1–1.25), p = 0.107) and for BNP reduction (SSMD: 0.141, CI ([−0.19]–[0.47]), p = 0.3).

Conclusion: Pharmacologic treatment for DMDCM patients is associated with decreased HR and improved LVEF. Therefore, DMDCM patients may benefit from implementing guideline therapy for HF.
Neglected and Underutilised Crops: A Systematic Review of Their Potential as Food and Herbal Medicinal Crops in South Africa
Authors: Mudau Fhatuwani Nixwell , Chimonyo Vimbayi Grace Petrova , Modi Albert Thembinkosi , Mabhaudhi Tafadzwanashe
Published: January 2022

The African continent harbours many native species with nutraceutical and pharmaceutical potential. This study reviewed underutilised crops in South Africa to determine their potential as food and herbal medicinal crops. Over 5,000 species have been identified and earmarked for their medical attributes in formal and informal setups. Researchers, plant breeders and policymakers have mostly ignored the development potential of these crops. Consequently, their value chains are poorly developed. In South Africa, there is a wide range of neglected and underutilised crops, which were historically popular and used by communities; however, over the years, they have lost their status within farming systems and been relegated to the status of neglected and underutilised. Recently, driven by the need to transition to more sustainable and resilient food systems, there has been renewed interest in their potential as food and herbal medicinal crops to establish new value chains that include vulnerable groups. They are now gaining global attention, and their conservation and sustainable utilisation are now being prioritized. The review confirmed that several of these crops possess nutraceutical and pharmaceutical properties, highlighting their potential for development as food and herbal medicines. However, current production levels are too low to meet the requirements for industrial development; research and development should focus on all aspects of their value chain, from crop improvement to utilisation. A transdisciplinary approach involving a wide range of actors is needed to develop the identified neglected and underutilised crops’ potential as food and herbal medicinal crops and support the development of new and inclusive value chains.
Accumulated Epinephrine Dose is Associated With Acute Kidney Injury Following Resuscitation in Adult Cardiac Arrest Patients
Authors: Gao Qiang , Mok Hsiao-Pei , Qiu Hai-Long , Cen Jianzheng , Chen Jimei , Zhuang Jian
Published: January 2022

The goal of this study was to investigate the association between total epinephrine dosage during resuscitation and acute kidney injury after return of spontaneous circulation in patients with cardiac arrest. We performed a secondary analysis of previously published data on the resuscitation of cardiac arrest patients. Bivariate, multivariate logistic regression, and subgroup analyses were conducted to investigate the association between total epinephrine dosage during resuscitation and acute kidney injury after return of spontaneous circulation. A total of 312 eligible patients were included. The mean age of the patients was 60.8 ± 15.2 years. More than half of the patients were male (73.4%) and had an out-of-hospital cardiac arrest (61.9%). During resuscitation, 125, 81, and 106 patients received ≤2, 3 - 4, and ≥5 mg epinephrine, respectively. After return of spontaneous circulation, there were 165 patients (52.9%) and 147 patients (47.1%) with and without acute kidney injury, respectively. Both bivariate and multivariate analysis showed a statistically significant association between total epinephrine dosage and acute kidney injury. The subgroup analysis showed that the strength of the association between epinephrine dosage and acute kidney injury varied by location of cardiac arrest. Further multivariate regression analysis found that the association between epinephrine dosage and acute kidney injury was only observed in patients with in-hospital cardiac arrest after adjusting for multiple confounding factors. Compared with in-hospital cardiac arrest patients who received ≤2 mg of epinephrine, patients with 3–4 mg of epinephrine or ≥5 mg of epinephrine had adjusted odds ratios of 4.2 (95% confidence interval 1.0–18.4) and 11.3 (95% confidence interval 2.0–63.0), respectively, to develop acute kidney injury. Therefore, we concluded that a higher epinephrine dosage during resuscitation was associated with an increased incidence of acute kidney injury after return of spontaneous circulation in adult patients with in-hospital cardiac arrest.
How Ethical Leadership Prompts Employees’ Voice Behavior? The Roles of Employees’ Affective Commitment and Moral Disengagement
Authors: Cheng Jin , Sun Xin , Lu Jinting , He Yuqing
Published: January 2022

Previous literature has demonstrated that ethical leadership could predict employees’ voice behavior. However, it’s not clear how to heighten these positive effects of ethical leadership on employees’ voice behavior. Building on the AET and moral disengagement studies, we developed an integrated model. A three-wave field study (N = 232) investigated the relationship between ethical leadership and voice behavior by focusing on the mediating role of employees’ affective commitment and the moderating role of employees’ moral disengagement. Our matched data analysis results indicated that: (1) employees’ affective commitment partly mediated the relationship between ethical leadership and employees’ voice behavior. In addition, employees’ moral disengagement moderated (2) the effect of ethical leadership on employees’ affective commitment and (3) the effect of employees’ affective commitment on voice behavior, similarly, (4) the indirect effect of ethical leadership on employees’ voice behavior via employees’ affective commitment. Theoretical and practical implications of these results are discussed.
The Boundary Conditions of High-Performance Work Systems–Organizational Citizenship Behavior Relationship: A Multiple-Perspective Exploration in the Chinese Context
Authors: Zhang Bo , Liu Lihua , Cooke Fang Lee , Zhou Peng , Sun Xiangdong , Zhang Songbo , Sun Bo , Bai Yang
Published: January 2022

This research synthesizes social exchange, organizational culture, and social identity theories to explore the boundary conditions of the relationship between high-performance work systems and employee organizational citizenship behavior. In particular, it draws on the China-specific management context. In this country, in spite of the wide use of a long-term-oriented and loose-control-focused Western-styled strategic human resource management (HRM) model, a short-term-focused and tight-control-oriented error aversion culture is still popular. The study uses multi-source individual-level survey data in a large state-owned enterprise to test the hypotheses. It is found that employee-experienced, Western-styled high-performance work systems positively impact a China-specific employee’s organizational citizenship behavior (OCB), and the—joint—moderation effects of employee-perceived error aversion culture and organizational identification are significant. The research findings deepen the understanding of the HRM-OCB relationship by demonstrating that culture and identity can jointly adjust the effects of HRM on OCB. The findings also challenge an established argument in the HRM-OCB literature that compatibility between employees’ personalities and organizational values – organizational identification – can enhance OCB.
How Smart Technology Affects the Well-Being and Supportive Learning Performance of Logistics Employees?
Authors: Jiang Fei , Wang Li , Li Jian-Xin , Liu Jie
Published: January 2022

The rapid improvement of technologies such as artificial intelligence in recent years has resulted in the development of smart technologies (ST) that can influence learning performance in different fields. The purpose of study is to explore the link between smart technology and learning performance. Using the S-O-R model as a framework, the researchers argue that smart technology (Stimuli) will increase corporate trust, self-efficacy, and well-being (Organism), resulting in improved learning performance (Response). The current model regards corporate trust and self-efficacy as relationship factors and investigates their direct influence on employee well-being and learning performance and the mediating role played by these variables. Additionally, the function of employee well-being in moderating the relationship between corporate trust, self-efficacy, and employee learning performance is also explored. The respondents (n = 516) in the present study are made up of employees from 10 logistics companies located in China. The data analysis is conducted using the AMOS software. The results show that that smart technologies can affect learning performance through corporate trust, self-efficacy, and employee well-being. The implementation of smart technology initiatives by corporations may provide positive workplace outcomes for employees (increased well-being), corporations (more engagement in workplace learning performance), and the relationship between employees and the companies that employ them (corporate trust and self-efficacy).
Personality Traits Induce Different Brain Patterns When Processing Social and Valence Information
Authors: Hevia-Orozco Jorge Carlos , Reyes-Aguilar Azalea , Hernández-Pérez Raúl , González-Santos Leopoldo , Pasaye Erick H. , Barrios Fernando A.
Published: January 2022

This paper shows the brain correlates of Cloninger’s personality model during the presentation of social scenarios under positive or negative valence situations. Social scenarios were constructed when participants played the Dictator game with two confederates that had two opposites roles as the cooperator (Coop) and non-cooperator (NoCoop). Later the same day during a fMRI scanning session, participants read negative (Neg) and positive (Pos) situations that happened to confederates in the past. Participants were asked to think “how do you think those people felt during that situation?” A dissimilarity matrix between stimuli were obtained from fMRI results. Results shown that Harm Avoidance trait people make use of right middle frontal gyrus and left superior frontal gyrus to discriminate between Coop and NoCoop. Cooperation as a trait makes use of the right superior temporal gyrus and the right precuneus to discriminate between Coop and NoCoop in positive social scenarios. Finally, Self-directedness trait people make use of the right inferior parietal lobe to discriminate between Coop and NoCoop in negative social scenarios and the right precuneus to discriminate between Coop and Strangers. An intuitive link between discrimination findings and behavioral patterns of those personality traits is proposed.
How Does Social Support Affect the Retention Willingness of Cross-Border E-Commerce Sellers?
Authors: Shen Huiyun , Yu Jie , Zhang Hua , Gou Jin , Zhang Xiangqian
Published: January 2022

E-commerce research usually focuses more on how to protect consumers’ rights and increase their purchase intention from the perspective of consumers. However, we still lack understanding of e-commerce sellers, especially cross-border e-commerce sellers. Based on the stimulus-body-response theory, this paper built a moderated mediation model to test the relationships among social support, perceived benefits, perceived usefulness and sellers’ willingness to retain. The results show that social support has a positive impact on perceived benefits and sellers’ willingness to retain; perceived benefits play a partial intermediary role between social support and sellers’ willingness to retain; and perceived usefulness moderates these mediating effects. The research results further expand the perspective of e-commerce research and reveal the mechanism and boundary conditions of the influence of social support on the retention willingness of cross-border e-commerce sellers.
What Drives Employees' Innovative Behaviors in Emerging-Market Multinationals? An Integrated Approach
Authors: Jin Shanyue , Li Yannan , Xiao Shufeng
Published: January 2022

The coronavirus disease 2019 (COVID-19) pandemic has severely damaged the global industrial supply chain and accelerated the digital transformation of the global economy. In such rapidly changing environments, multinational corporations (MNCs) should encourage employees to be more innovative in various fields than ever before. With the onset of the COVID-19 pandemic, employees have become psychologically anxious, their working conditions have deteriorated, and they are in danger of losing their jobs. In this study, we aim to address the question of whether servant leadership facilitates the innovative behavior of employees working in emerging-market MNCs when servant leadership is adopted within the firms. In addition, we explore the mediating roles of work–life balance and psychological stability perceived by employees, and the moderating role of organizational climate in the relationship between servant leadership and MNC employees' innovative behavior. In doing so, we collected data from a sample of 307 Chinese employees who are employed by five different Chinese MNCs from the Internet, information technology, electronics, and e-commerce industries. Based on a sample of survey data collected from employees of Chinese MNCs, we empirically test these ideas by specifically examining how servant leadership may shape the innovation behavior of employees in these MNCs. The results suggest that servant leadership positively influences employees' innovative behavior, and that the contribution of servant leadership to employees' innovative behavior is mediated by work–life balance and psychological stability as well as moderated by the degree of organizational climate. Moreover, the different organizational climates of these MNC employees are also expected to significantly shape the relationship between servant leadership and employees' innovative behavior. This study enriches our understanding of the importance of servant leadership in driving the innovative behaviors of employees in emerging-market MNCs and provides new insights into the mechanisms through which emerging-market MNCs can motivate their employees to be more innovative in their jobs. Thus, this study contributes to the research on human resource management by offering important implications vis-à-vis how MNCs manage their employees more effectively in addressing and responding to the dramatically changing global landscape in the post COVID-19 era.
Keeping the Faith: Religion, Positive Coping, and Mental Health of Caregivers During COVID-19
Authors: Sen Heera Elize , Colucci Laura , Browne Dillon T.
Published: January 2022

The COVID-19 pandemic has resulted in major stressors such as unemployment, financial insecurity, sickness, separation from family members, and isolation for much of the world population. These stressors have been linked to mental health difficulties for parents and caregivers. Religion and spirituality (R/S), on the other hand, is often viewed as promotive of mental health. However, the mechanisms by which R/S might promote mental health for parents during the pandemic remain unclear. Thus, this longitudinal study explores how R/S is associated with better caregiver mental health during the COVID-19 pandemic through higher levels of positive coping skills. A sample of N = 549 caregivers (parents and other adults in childrearing roles) across Canada, the United States, the United Kingdom, and Australia were recruited through the Prolific® research panel [67.8% female; age M = 41.33 years (SD = 6.33), 72.3% White/European]. Participants were assessed on measures of psychological distress, coping, R/S, and COVID-19 disruption at three time points between May and November 2020. Cross-lagged panel analysis revealed that caregiver coping mediated the relationship between caregiver R/S and caregiver mental health. Findings highlight a mechanism through which R/S naturally conveys a mental health benefit during periods of social disruption, which may provide an important target for public health promotion and clinical intervention.