bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Prognostic Signature Associated With the Homeobox Gene Family for Bladder Cancer
Authors: Dong Bingqi , Liang Jiaming , Li Ding , Song Wenping , Song Jinbo , Zhu Mingkai , Zhao Shiming , Ma Yongkang , Yang Tiejun
Published: July 2021

Background: Bladder cancer (BLCA) is a common malignant tumor of the genitourinary system, and there is a lack of specific, reliable, and non-invasive tumor biomarker tests for diagnosis and prognosis evaluation. Homeobox genes play a vital role in BLCA tumorigenesis and development, but few studies have focused on the prognostic value of homeobox genes in BLCA. In this study, we aim to develop a prognostic signature associated with the homeobox gene family for BLCA.

Methods: The RNA sequencing data, clinical data, and probe annotation files of BLCA patients were downloaded from the Gene Expression Omnibus database and the University of California, Santa Cruz (UCSC), Xena Browser. First, differentially expressed homeobox gene screening between tumor and normal samples was performed using the “limma” and robust rank aggregation (RRA) methods. The mutation data were obtained with the “TCGAmutation” package and visualized with the “maftools” package. Kaplan–Meier curves were plotted with the “survminer” package. Then, a signature was constructed by logistic regression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using “clusterProfiler.” Furthermore, the infiltration level of each immune cell type was estimated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, the performance of the signature was evaluated by receiver-operating characteristic (ROC) curve and calibration curve analyses.

Results: Six genes were selected to construct this prognostic model: TSHZ3, ZFHX4, ZEB2, MEIS1, ISL1, and HOXC4. We divided the BLCA cohort into high- and low-risk groups based on the median risk score calculated with the novel signature. The overall survival (OS) rate of the high-risk group was significantly lower than that of the low-risk group. The infiltration levels of almost all immune cells were significantly higher in the high-risk group than in the low-risk group. The average risk score for the group that responded to immunotherapy was significantly lower than that of the group that did not.

Conclusion: We constructed a risk prediction signature with six homeobox genes, which showed good accuracy and consistency in predicting the patient’s prognosis and response to immunotherapy. Therefore, this signature can be a potential biomarker and treatment target for BLCA patients.
Visual and Rapid Diagnosis of Neisseria gonorrhoeae Using Loop-Mediated Isothermal Amplification Combined With a Polymer Nanoparticle–Based Biosensor in Clinical Application
Authors: Chen Xu , Zhou Qingxue , Wu Xueli , Wang Shuoshi , Liu Rui , Dong Shilei , Yuan Wei
Published: July 2021

Neisseriagonorrhoeae is a host-adapted human pathogen that causes sexually transmitted gonorrhea and remains to be a serious global public health challenge, especially in low- and middle-income regions. It is vital to devise a reliable, simple, cost-saving, and easy-to-use assay for detecting the N. gonorrhoeae agent. In the current study, we firstly report a novel approach, loop-mediated isothermal amplification linked with a polymer nanoparticle–based biosensor (LAMP-PNB), that was used for identifying N. gonorrhoeae in clinical samples. The results showed that the LAMP primers based on the orf1 gene were valid for development of the N. gonorrhoeae-LAMP-PNB assay. The detection system with optimal conditions could be performed at a fixed temperature of 64°C for 40 min. The whole process, including genomic DNA preparation (approximately 10 min), LAMP reaction (40 min), and PNB reporting (approximately 2 min), could be accomplished within 60 min. The limit of detection (LoD) of the N. gonorrhoeae-LAMP-PNB assay was 50 copies per test. The specificity of the current assay was 100%, and no cross-reactions to non–N. gonorrhoeae isolates were observed. These results confirmed that the N. gonorrhoeae-LAMP-PNB technique is a reliable, specific, sensitive, rapid, low-cost, and easy-to-use method for detecting gonococci isolates. More importantly, this assay has great potential to develop a point-of-care (POC) testing method in clinical practice, especially in resource-constrained regions.
The Biogenesis, Biological Functions, and Applications of Macrophage-Derived Exosomes
Authors: Shan Xiaoxiao , Zhang Caiyun , Mai Chutian , Hu Xuerui , Cheng Nuo , Chen Weidong , Peng Daiyin , Wang Lei , Ji Zhaojie , Xie Ying
Published: July 2021

Macrophage-derived exosomes have been implicated on the modulation of inflammatory processes. Recent studies have shown that macrophage-derived exosomes contribute to the progression of many diseases such as cancer, atherosclerosis, diabetes and heart failure. This review describes the biogenesis of macrophage-derived exosomes and their biological functions in different diseases. In addition, the challenges facing the use of macrophage-derived exosomes as delivery tools for drugs, genes, and proteins in clinical applications are described. The application of macrophage-derived exosomes in the diagnosis and treatment of diseases is also discussed.
Alterations of Regional Homogeneity in the Mild and Moderate Stages of Parkinson’s Disease
Authors: Li Junli , Liao Haiyan , Wang Tianyu , Zi Yuheng , Zhang Lin , Wang Min , Mao Zhenni , Song ChenDie , Zhou Fan , Shen Qin , Cai Sainan , Tan Changlian
Published: July 2021

Objectives: This study aimed to investigate alterations in regional homogeneity (ReHo) in early Parkinson’s disease (PD) at different Hoehn and Yahr (HY) stages and to demonstrate the relationships between altered brain regions and clinical scale scores.

Methods: We recruited 75 PD patients, including 43 with mild PD (PD-mild; HY stage: 1.0–1.5) and 32 with moderate PD (PD-moderate; HY stage: 2.0–2.5). We also recruited 37 age- and sex-matched healthy subjects as healthy controls (HC). All subjects underwent neuropsychological assessments and a 3.0 Tesla magnetic resonance scanning. Regional homogeneity of blood oxygen level-dependent (BOLD) signals was used to characterize regional cerebral function. Correlative relationships between mean ReHo values and clinical data were then explored.

Results: Compared to the HC group, the PD-mild group exhibited increased ReHo values in the right cerebellum, while the PD-moderate group exhibited increased ReHo values in the bilateral cerebellum, and decreased ReHo values in the right superior temporal gyrus, the right Rolandic operculum, the right postcentral gyrus, and the right precentral gyrus. Reho value of right Pre/Postcentral was negatively correlated with HY stage. Compared to the PD-moderate group, the PD-mild group showed reduced ReHo values in the right superior orbital gyrus and the right rectus, in which the ReHo value was negatively correlated with cognition.

Conclusion: The right superior orbital gyrus and right rectus may serve as a differential indicator for mild and moderate PD. Subjects with moderate PD had a greater scope for ReHo alterations in the cortex and compensation in the cerebellum than those with mild PD. PD at HY stages of 2.0–2.5 may already be classified as Braak stages 5 and 6 in terms of pathology. Our study revealed the different patterns of brain function in a resting state in PD at different HY stages and may help to elucidate the neural function and early diagnosis of patients with PD.
Nanoparticles and Gut Microbiota in Colorectal Cancer
Authors: Perumal Komathi , Ahmad Suhana , Mohd-Zahid Manali Haniti , Wan Hanaffi Wan Nurhidayah , Z.A. Iskander , Six Jean-Luc , Ferji Khalid , Jaafar Juhana , Boer Jennifer C. , Plebanski Magdalena , Uskoković Vuk , Mohamud Rohimah
Published: July 2021

Recent years have witnessed an unprecedented growth in the research area of nanomedicine. There is an increasing optimism that nanotechnology applied to medicine will bring significant advances in the diagnosis and treatment of various diseases, including colorectal cancer (CRC), a type of neoplasm affecting cells in the colon or the rectum. Recent findings suggest that the role of microbiota is crucial in the development of CRC and its progression. Dysbiosis is a condition that disturbs the normal microbial environment in the gut and is often observed in CRC patients. In order to detect and treat precancerous lesions, new tools such as nanotechnology-based theranostics, provide a promising option for targeted marker detection or therapy for CRC. Because the presence of gut microbiota influences the route of biomarker detection and the route of the interaction of nanoparticle/drug complexes with target cells, the development of nanoparticles with appropriate sizes, morphologies, chemical compositions and concentrations might overcome this fundamental barrier. Metallic particles are good candidates for nanoparticle-induced intestinal dysbiosis, but this aspect has been poorly explored to date. Herein, we focus on reviewing and discussing nanotechnologies with potential applications in CRC through the involvement of gut microbiota and highlight the clinical areas that would benefit from these new medical technologies.
A Review of Working Memory Training in the Management of Attention Deficit Hyperactivity Disorder
Authors: Al-Saad Maha Saleh Habsan , Al-Jabri Basma , Almarzouki Abeer F.
Published: July 2021

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Working memory deficits underlie many of the behavioural symptoms of ADHD. Alongside psychostimulant medications, strategies to improve working memory may play an important adjuvant role in the management of ADHD. In this study, we review the role of working memory deficits in ADHD, the evidence surrounding working memory training strategies in the management of the condition, and the factors affecting the success of these strategies in alleviating ADHD symptoms. More specifically, we review several non-pharmacological interventions that target working memory deficits in ADHD, with special emphasis on cognitive working memory training. We conclude that the development of evidence-based interventions such as computerised cognitive training (CCT) could provide an alternative or adjunct to the use of psychostimulants, especially in cases where side effects are a major issue.
The Long-Term Effects of Neonatal Inflammatory Pain on Cognitive Function and Stress Hormones Depend on the Heterogeneity of the Adolescent Period of Development in Male and Female Rats
Authors: Butkevich Irina P. , Mikhailenko Viktor A. , Vershinina Elena A. , Barr Gordon A.
Published: July 2021

Exposure to stress at an early age programs the HPA axis which can lead to cognitive deficits in adults. However, it is not known whether these deficits emerge in adulthood or are expressed earlier in life. The aims of the study were to investigate (1) the immediate effects of early injury-induced stress in one-day-old (P1) and repeated stress on at P1 and P2 rat pups on plasma corticosterone levels; and (2) examine the subsequent long-term effects of this early stress on spatial learning and memory, and stress reactivity in early P26-34 and late P45-53 adolescent male and female rats. Intra-plantar injection of formalin induced prolonged and elevated levels of corticosterone in pups and impaired spatial learning and short- and long-term memory in late adolescent males and long-term memory in early adolescent females. There were sex differences in late adolescence in both learning and short-term memory. Performance on the long-term memory task was better than that on the short-term memory task for all early adolescent male and female control and stressed animals. Short-term memory was better in the late age control rats of both sexes and for formalin treated females as compared with the early age rats. These results are consistent with an impaired function of structures involved in memory (the hippocampus, amygdala, prefrontal cortex) after newborn pain. However, activation of the HPA axis by neonatal pain did not directly correlate with spatial learning and memory outcomes and the consequences of neonatal pain remain are likely multi-determined.
Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause
Authors: Koebele Stephanie V. , Hiroi Ryoko , Plumley Zachary M. T. , Melikian Ryan , Prakapenka Alesia V. , Patel Shruti , Carson Catherine , Kirby Destiney , Mennenga Sarah E. , Mayer Loretta P. , Dyer Cheryl A. , Bimonte-Nelson Heather A.
Published: July 2021

A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, including estrogen-only, progestogen-only, or combined estrogen plus progestogen options. There is little known about how these formulations, or their unique pharmacodynamics, impact neurobiological processes. Seemingly disparate pre-clinical and clinical findings regarding the cognitive effects of hormone therapies, such as the negative effects associated with conjugated equine estrogens and medroxyprogesterone acetate vs. naturally circulating 17β-estradiol (E2) and progesterone, signal a critical need to further investigate the neuro-cognitive impact of hormone therapy formulations. Here, utilizing a rat model of transitional menopause, we administered either E2, progesterone, levonorgestrel, or combinations of E2 with progesterone or with levonorgestrel daily to follicle-depleted, middle-aged rats. A battery of assessments, including spatial memory, anxiety-like behaviors, and depressive-like behaviors, as well as endocrine status and ovarian follicle complement, were evaluated. Results indicate divergent outcomes for memory, anxiety, and depression, as well as unique physiological profiles, that were dependent upon the hormone regimen administered. Overall, the combination hormone treatments had the most consistently favorable profile for the domains evaluated in rats that had undergone experimentally induced transitional menopause and remained ovary-intact. The collective results underscore the importance of investigating variations in hormone therapy formulation as well as the menopause background upon which these formulations are delivered.
The Need to Work Arm in Arm: Calling for Collaboration in Delivering Neuroprosthetic Limb Replacements
Authors: Karczewski Alison M. , Dingle Aaron M. , Poore Samuel O.
Published: July 2021

Over the last few decades there has been a push to enhance the use of advanced prosthetics within the fields of biomedical engineering, neuroscience, and surgery. Through the development of peripheral neural interfaces and invasive electrodes, an individual's own nervous system can be used to control a prosthesis. With novel improvements in neural recording and signal decoding, this intimate communication has paved the way for bidirectional and intuitive control of prostheses. While various collaborations between engineers and surgeons have led to considerable success with motor control and pain management, it has been significantly more challenging to restore sensation. Many of the existing peripheral neural interfaces have demonstrated success in one of these modalities; however, none are currently able to fully restore limb function. Though this is in part due to the complexity of the human somatosensory system and stability of bioelectronics, the fragmentary and as-yet uncoordinated nature of the neuroprosthetic industry further complicates this advancement. In this review, we provide a comprehensive overview of the current field of neuroprosthetics and explore potential strategies to address its unique challenges. These include exploration of electrodes, surgical techniques, control methods, and prosthetic technology. Additionally, we propose a new approach to optimizing prosthetic limb function and facilitating clinical application by capitalizing on available resources. It is incumbent upon academia and industry to encourage collaboration and utilization of different peripheral neural interfaces in combination with each other to create versatile limbs that not only improve function but quality of life. Despite the rapidly evolving technology, if the field continues to work in divided “silos,” we will delay achieving the critical, valuable outcome: creating a prosthetic limb that is right for the patient and positively affects their life.
Impaired Performance on a Cognitively-Based Instrumental Activities of Daily Living Task, the 10-Item Weekly Calendar Planning Activity, in Individuals With Stroke Undergoing Acute Inpatient Rehabilitation
Authors: Jaywant Abhishek , Arora Catherine , Lussier Alexis , Toglia Joan
Published: July 2021

Performance-based, functionally relevant, and standardized measures of cognitive-instrumental activities of daily living (C-IADL) can complement neuropsychological tests of cognitive impairment and provide valuable clinical information to inform rehabilitation planning. Existing measures have been validated in the outpatient setting. Here, we sought to evaluate a 10-item, short-form of a C-IADL measure, Weekly Calendar Planning Activity (WCPA-10), in inpatients with stroke undergoing acute rehabilitation. The specific goal was to determine if the WCPA-10 could differentiate between stroke patients undergoing acute inpatient rehabilitation and healthy control individuals. We also explored whether the WCPA-10 would identify C-IADL limitations in stroke patients screened as having intact cognition. Seventy-seven stroke inpatients undergoing rehabilitation and 77 healthy control participants completed the WCPA-10, which involves entering a list of simulated, fictional appointments into a weekly schedule while keeping track of and adhering to multiple task rules and ignoring built-in obstacles and distractions. Compared to the control group, stroke patients had significantly worse accuracy, made more errors, used fewer cognitive strategies, followed fewer rules, took more time to complete the task, and were less efficient. 83% of stroke patients were less accurate than predicted by their age, and 64% used less strategies than their age prediction. Among 28 participants who screened as having “normal” cognitive function on the Montreal Cognitive Assessment, the majority had deficits on the WCPA-10. Our results provide initial support for use of a brief C-IADL assessment, WCPA-10, for individuals with stroke undergoing inpatient rehabilitation. They indicate that stroke patients have deficits in C-IADL accuracy, efficiency, and strategy use at this stage of stroke recovery. Results highlight the need to use performance based, functional cognitive assessments, even for those who perform well on cognitive screening tools.
A Deep Learning-Based Approach to Video-Based Eye Tracking for Human Psychophysics
Authors: Zdarsky Niklas , Treue Stefan , Esghaei Moein
Published: July 2021

Real-time gaze tracking provides crucial input to psychophysics studies and neuromarketing applications. Many of the modern eye-tracking solutions are expensive mainly due to the high-end processing hardware specialized for processing infrared-camera pictures. Here, we introduce a deep learning-based approach which uses the video frames of low-cost web cameras. Using DeepLabCut (DLC), an open-source toolbox for extracting points of interest from videos, we obtained facial landmarks critical to gaze location and estimated the point of gaze on a computer screen via a shallow neural network. Tested for three extreme poses, this architecture reached a median error of about one degree of visual angle. Our results contribute to the growing field of deep-learning approaches to eye-tracking, laying the foundation for further investigation by researchers in psychophysics or neuromarketing.
The Effect of Social Distance on Intertemporal Choice of Reward Processing: An Event-Related Potentials Study
Authors: Tang Shulin , Guo Jie , Li Bing , Song Zhikai
Published: July 2021

Social factors can affect the processing of intertemporal choice, but the influence of social distance on the rewarding process of intertemporal choice is unclear. Therefore, by designing a novel cognitive resource competition paradigm for undifferentiated intertemporal choice, this article aims to explore the influence of social distance on intertemporal choice reward processing at the electrophysiological level. It was found that compared with the stranger condition, P3a is greater in the friend condition, which means social distance is evaluated in the early stage. In addition, different brain regions in the early stages are taking charge of processing the soon-but-small (SS) and later-but-lager (LL) reward in intertemporal choice. There is an interaction effect between social distance (friend vs. stranger) and intertemporal choice (SS reward vs. LL reward) on P3b. Under friend conditions, the P3b induced by LL reward is more positive than SS reward. Under the condition of choosing the LL reward, the P3b induced by friend is more positive than stranger. This result shows that in the latter stage of reward processing, the evaluation process of time discounting is less sensitive in LL reward for friend caused by lack of cognitive resources which is occupied when dealing with social distance in advance, and thus the degree of time discount was reduced. These findings demonstrate that P3b is the key index of time discounting and immediate and delayed rewards are valued in different brain regions.
Differences in Alzheimer’s Disease and Related Dementias Pathology Among African American and Hispanic Women: A Qualitative Literature Review of Biomarker Studies
Authors: Royse Sarah K. , Cohen Ann D. , Snitz Beth E. , Rosano Caterina
Published: July 2021

Introduction

The population of older adults with Alzheimer’s disease and Related Dementias (ADRD) is growing larger and more diverse. Prevalence of ADRD is higher in African American (AA) and Hispanic populations relative to non-Hispanic whites (nHW), with larger differences for women compared to men of the same race. Given the public health importance of this issue, we sought to determine if AA and Hispanic women exhibit worse ADRD pathology compared to men of the same race and nHW women. We hypothesized that such differences may explain the discrepancy in ADRD prevalence.

Methods

We evaluated 932 articles that measured at least one of the following biomarkers of ADRD pathology in vivo and/or post-mortem: beta-amyloid (Aß), tau, neurodegeneration, and cerebral small vessel disease (cSVD). Criteria for inclusion were: (1) mean age of participants >65 years; (2) inclusion of nHW participants and either AA or Hispanics or both; (3) direct comparison of ADRD pathology between racial groups.

Results

We included 26 articles (Aß = 9, tau = 6, neurodegeneration = 16, cSVD = 18), with seven including sex-by-race comparisons. Studies differed by sampling source (e.g., clinic or population), multivariable analytical approach (e.g., adjusted for risk factors for AD), and cognitive status of participants. Aß burden did not differ by race or sex. Tau differed by race (AA < nHW), and by sex (women > men). Both severity of neurodegeneration and cSVD differed by race (AA > nHW; Hispanics < nHW) and sex (women < men). Among the studies that tested sex-by-race interactions, results were not significant.

Conclusion

Few studies have examined the burden of ADRD pathology by both race and sex. The higher prevalence of ADRD in women compared to men of the same race may be due to both higher tau load and more vulnerability to cognitive decline in the presence of similar Aß and cSVD burden. AA women may also exhibit more neurodegeneration and cSVD relative to nHW populations. Studies suggest that between-group differences in ADRD pathology are complex, but they are too sparse to completely explain why minority women have the highest ADRD prevalence. Future work should recruit diverse cohorts, compare ADRD biomarkers by both race and sex, and collect relevant risk factor and cognitive data.
Artificial Intelligence in the Imaging of Gastric Cancer: Current Applications and Future Direction
Authors: Qin Yun , Deng Yiqi , Jiang Hanyu , Hu Na , Song Bin
Published: July 2021

Gastric cancer (GC) is one of the most common cancers and one of the leading causes of cancer-related death worldwide. Precise diagnosis and evaluation of GC, especially using noninvasive methods, are fundamental to optimal therapeutic decision-making. Despite the recent rapid advancements in technology, pretreatment diagnostic accuracy varies between modalities, and correlations between imaging and histological features are far from perfect. Artificial intelligence (AI) techniques, particularly hand-crafted radiomics and deep learning, have offered hope in addressing these issues. AI has been used widely in GC research, because of its ability to convert medical images into minable data and to detect invisible textures. In this article, we systematically reviewed the methodological processes (data acquisition, lesion segmentation, feature extraction, feature selection, and model construction) involved in AI. We also summarized the current clinical applications of AI in GC research, which include characterization, differential diagnosis, treatment response monitoring, and prognosis prediction. Challenges and opportunities in AI-based GC research are highlighted for consideration in future studies.
Cancer Stemness Associated With Prognosis and the Efficacy of Immunotherapy in Adrenocortical Carcinoma
Authors: Shi Xiaoxi , Liu Yuanlin , Cheng Shuai , Hu Haidi , Zhang Jian , Wei Minjie , Zhao Lin , Xin Shijie
Published: July 2021

Background

Cancer stem cells (CSCs) have been proven to influence drug resistance, recurrence, and metastasis in tumors. Our study aimed to identify stemness-related prognostic biomarkers for new therapeutic strategies in adrenocortical carcinoma.

Methods

RNA-seq data and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA). The stemness indexes, mDNAsi and mRNAsi, were calculated to classify all samples into low-score and high-score groups. Two algorithms, based on the R language, ESTIMATE and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to assess the immune cell infiltration states of adrenocortical carcinoma patients. Weighted Gene Co-expression Network Analysis (WGCNA) was used to find genes that were related to the stemness of cancer. By bioinformatics methods, the correlations between biomarkers capable of predicting immune checkpoint inhibitors (ICIs) responses and stemness of cancer were explored.

Results

High-mRNAsi predicted shorter overall survival (OS) and a higher metastatic trend in adrenocortical carcinoma (ACC) patients. Compared with the low-mRNAsi group, the high-mRNAsi group had a lower ImmuneScore and StromalScroe. Twenty-two stemness-related prognostic genes were obtained by WGCNA, which focused on the function of the cell cycle and cell mitosis. Immune cell infiltration, especially CD8+T cell, increased in the low-mRNAsi group compared with the high-mRNAsi group. Lower expression of PD-L1, CTLA-4, and TIGHT was evaluated in the high-mRNAsi group.

Conclusions

ACC patients with high-mRNAsi have poor prognosis and less immune cell infiltration. Combined with the finding of lower expression of CTLA-4, TIGHT, and PD-L1 in the high-mRNAsi group, we came to the conclusion that stemness index is a potential biomarker to predict the effectiveness of ICIs.
Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial–Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis
Authors: Zhang Linling , Ke Jingjing , Min Shengping , Wu Nan , Liu Fei , Qu Zhen , Li Wei , Wang Hongtao , Qian Zhongqing , Wang Xiaojing
Published: July 2021

Background

Tumor cells initiate hypoxia-induced mechanisms to fuel cell proliferation, invasion, and metastasis, largely mediated by low O2-responsive Hypoxia-Inducible Factor 1 Alpha (HIF-1α). Therefore, hyperbaric oxygen therapy (HBO) is now being studied in cancer patients, but its impact upon non-small-cell lung cancer (NSCLC) cell metabolism remains uncharacterized.

Methods

We employed the NSCLC cell lines A549 and H1299 for in vitro studies. Glucose uptake, pyruvate, lactate, and adenosine triphosphate (ATP) assays were used to assess aerobic glycolysis (Warburg effect). A quantitative glycolytic flux model was used to analyze the flux contributions of HIF-1α-induced glucose metabolism genes. We used a Lewis lung carcinoma (LLC) murine model to measure lung tumorigenesis in C57BL/6J mice.

Results

HBO suppressed hypoxia-induced HIF-1α expression and downstream HIF-1α signaling in NSCLC cells. One HIF-1α-induced glucose metabolism gene—Phosphofructokinase, Platelet (PFKP)—most profoundly enhanced glycolytic flux under both low- and high-glucose conditions. HBO suppressed hypoxia-induced PFKP transactivation and gene expression via HIF-1α downregulation. HBO’s suppression of the Warburg effect, suppression of hyperproliferation, and suppression of epithelial-to-mesenchymal transition (EMT) in hypoxic NSCLC cell lines is mediated by the HIF-1α/PFKP axis. In vivo, HBO therapy inhibited murine LLC lung tumor growth in a Pfkp-dependent manner.

Conclusions

HBO’s repression of the Warburg effect, repression of hyperproliferation, and repression of EMT in hypoxic NSCLC cells is dependent upon HIF-1α downregulation. HIF-1α’s target gene PFKP functions as a central mediator of HBO’s effects in hypoxic NSCLC cells and may represent a metabolic vulnerability in NSCLC tumors.
Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response
Authors: Olmos Manuel , Glajzer Jacek , Büntemeyer Tjark-Ole , Frohwitter Gesche , Ries Jutta , Eckstein Markus , Hecht Markus , Lutz Rainer , Kesting Marco Rainer , Weber Manuel
Published: July 2021

Background

The treatment of oral cancer remains challenging due to its infiltrative nature and a high tendency for tumour relapse leading to an overall poor prognosis. In the case of early recurrence, the patient’s prognosis deteriorates dramatically, with survival rate dropping to below 30%. Minimal improvements in survival trends in recurrent and advanced stage tumours have been reported in recent decades. Neoadjuvant immunotherapy may represent a new therapeutic approach changing the standard of care in advanced oral cancer therapy.

Case Presentation

We describe the case of a woman in her late 30’s who presented in mid-2019 with oral squamous cell carcinoma (OSCC) localized to the floor of the mouth. After initial R0 resection, selective neck dissection, and adjuvant brachytherapy, an early recurrence of OSCC located between the hyoid bone and the mandible was diagnosed at the end of 2019. An off-label treatment regimen was performed with neoadjuvant use of Pembrolizumab 19 days prior to salvage surgery. Radiological and histological assessment of T-cell and programmed cell death protein 1 ligand 1 (PD-L1) expression was performed before and after checkpoint inhibitor application. Neoadjuvant immunotherapy resulted in increased T-cell infiltration and PD-L1 expression, as well as a significant tumour necrosis rate. One cycle of Pembrolizumab led to significant regressive tumour changes with increases in immune infiltration, sclerosis, and necrosis of 75% of the tumour mass with only 25% vital tumour cells remaining. By June 2020, the patient remained without recurrence.

Conclusions

The case presented outlines the potential effects of neoadjuvant immunotherapy in recurrent or advanced OSCC prior to definitive surgical tumour treatment. The benefit of additional adjuvant treatment after histologic response will be discussed. The case is also analysed considering ongoing clinical trials of neoadjuvant immunotherapy for head and neck malignancies.
Population-Based Cohort of Children With Parapneumonic Effusion and Empyema Managed With Low Rates of Pleural Drainage
Authors: Moral Luis , Toral Teresa , Clavijo Agustín , Caballero María , Canals Francisco , Forniés María José , Moral Jorge , Revert Raquel , Lucas Raquel , Huertas Ana María , González María Cristina , García-Avilés Belén , Belda Mónica , Marco Nuria
Published: July 2021

Introduction: The most appropriate treatment for parapneumonic effusion (PPE), including empyema, is controversial. We analyzed the experience of our center and the hospitals in its reference area after adopting a more conservative approach that reduced the use of chest tube pleural drainage (CTPD).

Methods: Review of the clinical documentation of all PPE patients in nine hospitals from 2010 to 2018.

Results: A total of 318 episodes of PPE were reviewed; 157 had a thickness of <10 mm. The remaining 161 were 10 mm or thicker and were subdivided into three increasing sizes: PE+1, PE+2, and PE+3. There was a strong relationship between the size of the effusion and complicated effusion/empyema, defined by its appearance on imaging studies or by the physical or bacteriological characteristics of the pleural fluid. The size of effusion was also strongly related to the duration of fever and intravenous treatment and was the best independent predictor of the length of hospital stay (LHS) (p < 0.001). CTPD was placed in 2.9% of PE+1 patients, 19.3% of PE+2, and 63.9% of PE+3 (p < 0.001). The referral of patients with PE+1 decreased over time (p = 0.033), as did the use of CTPD in the combined PE+1/PE+2 group (p = 0.018), without affecting LHS (p = 0.814). There were no changes in the use of CTPD in the PE+3 group (p = 0.721).

Conclusions: The size of the PPE is strongly correlated with its severity and with LHS. Most patients can be treated with antibiotics alone.
Case Report: Changes in Cytokine Kinetics During the Course of Disease in a Japanese Patient With Multisystem Inflammatory Syndrome in Children
Authors: Takasago Satoshi , Sakai Aiko , Sugiyama Masaya , Mizokami Masashi , Hamada Hiromichi , Ishizaka Yukihito , Miyoshi-Akiyama Tohru , Matsunaga Akihiro , Ueno Mikako , Shichino Hiroyuki , Mizukami Ayumi
Published: July 2021

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that is reportedly linked to coronavirus disease 2019. Affected patients present with gastrointestinal symptoms and cardiovascular dysfunction, in addition to Kawasaki disease-like features, suggesting the potential for overlapping disease mechanisms. Kawasaki disease has been reported among individuals of East Asian ethnicities, whereas there is minimal clinical literature regarding the occurrence of MIS-C among individuals of Asian ethnicities. A few reports thus far have described changes in cytokine kinetics during the course of disease in patients with MIS-C. We followed the temporal cytokine kinetics in a 9-year-old Japanese girl who exhibited a classical trajectory of MIS-C. The patient exhibited right cervical swelling and pain, abdominal pain, vomiting, and lip reddening, which developed 31 days after she was diagnosed with severe acute respiratory syndrome coronavirus-2 infection. The patient was diagnosed with Kawasaki disease on her fifth day of illness; because she fulfilled the criteria for MIS-C, she was also diagnosed with this disease on her fifth day of illness. Her fever rapidly resolved upon administration of intravenous immunoglobulin, aspirin, and prednisolone. On the patient's sixth day of illness, she developed acute myocarditis, which was treated with two diuretics and one vasodilator; the myocarditis ameliorated within a few days. Analyses of temporal kinetics for 71 serum cytokines revealed several patterns of cytokine changes that were consistent with the patient's clinical course of disease. Importantly, there was a clear distinction between cytokines that did and did not decrease rapidly following post-treatment fever resolution. These findings may be useful for the assessment of disease status and selection of therapy in patients with similar symptoms; they may also provide insights for basic and clinical research regarding MIS-C.
Switching and Discontinuation Pattern of Biologic Disease-Modifying Antirheumatic Drugs and Tofacitinib for Patients With Rheumatoid Arthritis in Taiwan
Authors: Li Ko-Jen , Chang Chia-Li , Hsin Chih-Yi , Tang Chao-Hsiun
Published: July 2021

Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease characterized by persistent joint synovial inflammation and swelling, leading to cartilage damage and bone erosion. This retrospective, longitudinal study is to evaluate the treatment patterns of biologic-naïve RA patients receiving index biologic disease-modifying antirheumatic drug (bDMARD) and tofacitinib by the data of Taiwan National Healthcare Insurance Claims and the Death Registry between 2012 and 2017. Drug survival and treatment patterns were determined by investigating the occurrence of switching and discontinuation from index treatment. At baseline, 70.0% of patients used tumor necrosis factor inhibitors (TNFi) bDMARD with the majority taking etanercept (27.0%) or adalimumab (26.2%). During the follow-up period, 40.0% (n = 3,464) of index users switched (n = 1,479) or discontinued (n = 1,985) the treatment with an average incidence rate of 0.18 per patient-year. Among the six index treatment groups, drug survival was the lowest for adalimumab and highest for tocilizumab. When compared with etanercept, only adalimumab had a higher cumulative probability of switching/discontinuation (adjusted HR = 1.17, 95% CI: 1.08–1.28), whereas golimumab, non-TNFi bDMARDs and tofacitinib were significantly less probable to switch or discontinue. For patients switching the index treatment, tocilizumab (31.2%) and tofacitinib (23.4%) were the main regimens being switched to. In addition, 48.2% of patients who discontinued the index treatment received further retreatment, and 63.8–77.0% of them were retreated with same agent. In conclusion, this population-based study found that TNFi were the preferred agents as the index treatments during 2012–2017. Non-TNFi and tofacitinib were more common second-line agents being switched to. Nearly half of discontinued patients received retreatment, with a majority receiving the same agent.
Effects of Tranexamic Acid on Hemorrhage Control and Deep Venous Thrombosis Rate After Total Knee Arthroplasty: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Ling Tao , Zhao Zhihu , Xu Wenwen , Ge Weihong , Huang Lingli
Published: July 2021

Background: Total knee arthroplasty (TKA) surgery has a lot of complications, especially hemorrhage, which can be controlled via tranexamic acid (TXA). The guidelines endorse the integration of TXA interventions in the management of TKA-induced complications. However, uncertainty surrounds the effects of different TXA therapies. This frequentist model network meta-analysis (NMA) aims to compare hemorrhage control and deep venous thrombosis (DVT) rate of different TXA therapies in TKA.

Methods: Articles were searched with the PubMed, Embase, Cochrane Library, and Web of Science from 1966 to October 2020. Randomized controlled trials (RCTs) comparing different TXA therapies, or with placebo in patients with TKA were included. Two investigators independently conducted article retrievals and data collection. The outcome was total blood loss and DVT rate. Effect size measures were mean differences (MDs), or odds ratios (ORs) with 95% confidence intervals (CIs). We conducted a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses were performed in Stata software or R software. The study protocol was registered with PROSPERO, number CRD42020202404.

Results: We identified 1 754 citations and included 81 studies with data for 9 987 patients with TKA. Overall, all TXA therapies were superior to placebo for total blood loss in TKA. Of all TXA therapies, M therapy (IV/IV infusion + oral TXA > 3g) was most effective for total blood loss (MD=−688.48, −1084.04–−328.93), followed by F therapy (IV TXA ≥ 15 mg/kg or 1 g three times). TXA therapies in this study are not associated with the increase of DVT risk.

Conclusions: TXA therapies in this study are effective and safe for the treatment of TKA-induced complications. M therapy (IV/IV infusion + oral TXA > 3 g) may be the most effective TXA therapy for hemorrhage control. TXA therapies in this study do not increase DVT risk. Considering hemorrhage control and DVT rate simultaneously, F therapy (IV TXA ≥ 15 mg/kg or 1 g three times) may be suggested to apply for TKA, and this study may provide a crucial clue to future TXA use.
Bicyclol Alleviates Signs of BDL-Induced Cholestasis by Regulating Bile Acids and Autophagy-Mediated HMGB1/p62/Nrf2 Pathway
Authors: Zhao Jingwen , Ran Maojuan , Yang Ting , Chen Liwei , Ji Peixu , Xu Xiuxiu , Zhang Lu , Sun Siyuan , Liu Xin , Zhou Simin , Zhou Lu , Zhang Jie
Published: July 2021

Cholestasis is a liver disease characterized by the accumulation of toxic bile salts, bilirubin, and cholesterol, resulting in hepatocellular damage. Recent findings have revealed several key steps of cholestasis liver injury including the toxicity of bile acids and accumulation of proinflammatory mediator. In this study, we investigated the protective effect of bicyclol in cholestasis caused by bile duct ligation (BDL), as well as relevant mechanisms. Bicyclol attenuated liver damage in BDL mice by increasing the levels of hydrophilic bile acid such as α-MCA and β-MCA, regulating bile acid-related pathways and improving histopathological indexes. High-mobility group box 1 (HMGB1) is an extracellular damage-associated molecular pattern molecule which can be used as biomarkers of cells and host defense. Bicyclol treatment decreased extracellular release of HMGB1. In addition, HMGB1 is also involved in regulating autophagy in response to oxidative stress. Bicyclol promoted the lipidation of LC3 (microtubule-associated protein 1 light chain 3)-Ⅱ to activate autophagy. The nuclear factor, E2-related factor 2 (Nrf2) and its antioxidant downstream genes were also activated. Our results indicate that bicyclol is a promising therapeutic strategy for cholestasis by regulating the bile acids and autophagy-mediated HMGB1/p62/Nrf2 pathway.
Once Weekly Whole-Body Electromyostimulation Enhances Muscle Quality in Men: Data of the Randomized Controlled Franconian Electromyostimulation and Golf Study
Authors: Zink-Rückel Carina , Chaudry Oliver , Engelke Klaus , Ghasemikaram Mansour , Kohl Matthias , Uder Michael , Kemmler Wolfgang
Published: July 2021

Whole-body electromyostimulation (WB-EMS) is commercially advertised as a time-efficient resistance-type exercise technology. Indeed, the commercial, non-medical setting applies 20 min of WB-EMS only once a week. However, this setting conflicts with the approved scientific approach of higher training frequencies. Using data from an ongoing study on WB-EMS and golf performance as a vehicle, we evaluate the effect of once weekly WB-EMS on changes of fatty muscle infiltration, as a crucial parameter of muscle quality. Fifty-four moderately physically active male amateur golfers 18–70 years old were randomly allocated to a WB-EMS (n = 27) with a standard setting of once weekly 20 min and a non-WB-EMS control group (CG, n = 27). Intermuscular adipose tissue (IMAT) volume and intrafascial muscle tissue (MT) volume per unit of intrafascial volume as determined by magnetic resonance imaging were used to characterize muscle quality. Intention to treat analysis with multiple imputation was applied. WB-EMS was conducted at the participants’ homes; thus, the attendance rate was close to 100%. After 16 weeks of intervention, we observed increases in volume-adjusted IMAT (p = 0.040) and decreases in MT (p = 0.206) in the CG. IMAT decreased in the WB-EMS group (p = 0.215), while MT increased significantly (p = 0.032). Of importance, group difference (i.e., “effects”) for intra-group changes in volume-adjusted IMAT (effect size: d´ = 0.66; p = 0.028) and MT (d´ = 0.70; p = 0.020) was significant for both parameters. Once weekly WB-EMS application significantly affects muscle quality of the mid-thigh in moderately active, healthy men 18–70 years old.
The Well-being and Instructional Experiences of K-12 Music Educators: Starting a New School Year During a Pandemic
Authors: Parkes Kelly A. , Russell Joshua A. , Bauer William I. , Miksza Peter
Published: July 2021

In adapting to remote emergency teaching modes during pandemic-imposed conditions, teachers’ instruction has changed dramatically. Early research indicates that the well-being of music teachers has suffered during the COVID-19 pandemic and that high levels of depression are widespread. The purpose of this survey study was to assess the continued psychological well-being of music teachers working amid a global pandemic based upon previous research we conducted during the Spring 2020 semester when most teachers in the United States were forced into emergency remote teaching. A secondary purpose was to explore the ways that pandemic conditions have affected music teachers’ sense of safety at work and their current teaching situations. Our questionnaire consisted of sections pertaining to (1) demographic and institutional information, (2) well-being and depression, (3) instructional format and preparedness, (4) teaching efficacy compared to the start of the pandemic, and (5) potential positive outcomes of the pandemic-imposed adjustments. In total, 1,325 music teachers responded to our survey. Overall, the participants reported poorer well-being than both published norms and the sample of participants in our previous study. In addition, 17% reported mild depression, 25% reported moderate depression, and 24% reported severe extremely severe levels of depression. Summaries of the participants instructional experiences and their implications for music education are discussed within.
The Relationship Between Crime-Related Television Viewing and Perceptions of the Death Penalty: Results of a Large Cross-Sectional Survey Study
Authors: Till Benedikt , Arendt Florian , Niederkrotenthaler Thomas
Published: July 2021

Background:According to cultivation theory, distorted representations of social reality on television can lead to distorted perceptions of reality among viewers. For example, the death penalty has been abolished in most Western countries a long time ago, but is often portrayed or mentioned in US crime shows, which are very popular outside the United States. Previous research suggests that the amount of television viewing can be associated with erroneous perceptions of the use of the death penalty—even when the death penalty is not used in the respective country. Unfortunately, available evidence on this association is inconclusive.

Methods:In a cross-sectional web-based survey, we used quota-based sampling techniques to recruit 1,002 individuals representative of the Austrian population in terms of gender, age, education, and region of residence. We asked about their weekly amount of television viewing and use of US crime dramas and measured their beliefs on the use of the death penalty in Austria.

Results:Although television viewing in general was not associated with erroneous perceptions of the death penalty (i.e., no overall across-the-board cultivation effect), data analysis provided supporting evidence for the idea of a genre-specific cultivation effect: The more US crime shows participants watched, the more likely they were to mistakenly believe that the death penalty is used in Austria. This association held true even after controlling for the gender, age, and education of participants.

Conclusion:The finding that watching US crime shows, which are based on social reality in the United States, is associated with Austrian viewers' confusion with regards to perceptions of the death penalty is consistent with the genre-specific cultivation hypothesis. Some viewers may be guided more by mediated reality than by actual social reality.