bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association of Body Mass Index With the Risk of Pulmonary Hypertension in Adults: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Pu Shoufang , Yin Lidan , Wen Bi , He Juan
Published: January 2022

Backgrounds

Findings regarding the association of body mass index (BMI) with pulmonary hypertension (PH) are conflicting, and there is no systematic review and meta-analysis to summarize the results. Therefore, the purpose of this systematic review and meta-analysis is to assess this relationship.

Methods

To detect the relevant articles, PubMed, Scopus, and Google Scholar were searched until February 2021. Included essays were pooled using a random-effect model. Cochrane Q-test and I2-test was applied to assess between-study heterogeneity.

Results

Fourteen articles (eight cross-sectional and four cohort studies) were included in the meta-analysis. The meta-analysis of comparing highest vs. lowest BMI categories did not indicate a significant association between BMI and PH (Summary Effect Estimate: 1.59 (95% CI: 0.50, 5.07, I2 = 92.3). Furthermore, The summary risk estimate for a one-unit increment in BMI was 1.01 (95 % CI: 0.99, 1.03), with high heterogeneity, I2 = 73.5 %, P heterogeneity <0.001). Subgroup analysis showed significant positive association between BMI and the risk of PH in studies controlled for cofounders, and studies with higher sample sizes (≥2,000).

Conclusion

There is no significant association between BMI and risk of pulmonary hypertension. Further studies are required to confirm these findings.
Breath Stable Isotope Analysis Serves as a Non-invasive Analytical Tool to Demonstrate Dietary Changes in Adolescent Students Over Time
Authors: Mancuso Christy J. , Cornwall Collette M. , Robinson Swede , Valenzuela Luciano O. , Ehleringer James R.
Published: January 2022

Concern about adolescent diets, obesity, and the associated health risks have been growing in the United States. This inspired former First Lady Michelle Obama to spearhead the Healthy Hunger-Free Kids Act (HHFKA), which made changes to the national school lunch program by increasing servings of whole grains, fruits, and vegetables. Our study examined the variability of student carbohydrate sources throughout the day and before and after the implementation of HHFKA using a stable isotope dietary biomarker. This method uses carbon stable isotope values of exhaled CO2 breath (δ13Cbreath) and provides a quantitative, non-invasive measure. δ13Cbreath samples were collected throughout the day from students (n = 31) that attended a public high school in Salt Lake City, UT. δ13Cbreath measurements reflected the short-term carbohydrate inputs from the previous meal. Carbohydrate sources were not consistent throughout the day; most students had their lowest inputs of corn/sugar-based carbohydrates after lunch. We compared our results with an earlier study that had been conducted pre-HHFKA. After-lunch δ13Cbreath values decreased significantly between the two time points, suggesting an increase in whole grain, fruit, and vegetable carbohydrates in the lunch program. Our results demonstrated that δ13Cbreath measurements provide a valuable tool to examine carbohydrate sources in an individual's diet throughout the day. We believe that this tool could be beneficial to studies examining the relationship between sugar sweetened beverages, added sugars, and refined carbohydrates and health outcomes like diabetes and obesity in both adolescent and adult populations.
Association Between Non-obstructive Chronic Bronchitis and Incident Chronic Obstructive Pulmonary Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis
Authors: Wu Fan , Fan Huanhuan , Liu Jing , Li Haiqing , Zeng Weifeng , Zheng Silan , Tian Heshen , Deng Zhishan , Zheng Youlan , Zhao Ningning , Hu Guoping , Zhou Yumin , Ran Pixin
Published: January 2022

Background

Chronic bronchitis in patients with chronic obstructive pulmonary disease (COPD) is associated with poor respiratory health outcomes. However, controversy exists around whether non-obstructive chronic bronchitis (NOCB) is associated with airflow obstruction, lung function decline, and all-cause mortality in ever smoker or never smoker.

Research Question

This systematic review and meta-analysis aimed to clarify the relationship between NOCB and incident COPD, lung function decline, and all-cause mortality, and to quantify the magnitude of these associations.

Study Design and Methods

We searched PubMed, Embase, and Web of Science for studies published up to October 1, 2021. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Studies were included if they were original articles comparing incident COPD, lung function decline, and all-cause mortality in normal spirometry with and without chronic bronchitis. The primary outcomes were incident COPD and all-cause mortality. The secondary outcomes were respiratory disease-related mortality and lung function decline. Pooled effect sizes and 95% confidence intervals (CIs) were calculated using the random-effects model.

Results

We identified 17,323 related references and included 14 articles. Compared with individuals without NOCB, individuals with NOCB had an increased risk of incident COPD (odds ratio: 1.98, 95% CI: 1.21–3.22, I2 = 76.3% and relative risk: 1.44, 95%CI: 1.13–1.85, I2 = 56.1%), all-cause mortality (hazard ratio [HR]: 1.38, 95%CI: 1.26–1.51, I2 = 29.4%), and respiratory disease-related mortality (HR: 1.88, 95%CI: 1.37–2.59, I2 = 0.0%). Data on the decline in lung function could not be quantitatively synthesized, but the five articles that assessed the rate of decline in lung function showed that lung function declines faster in individuals with NOCB. The mean difference in the additional decline in forced expiratory volume in 1 s ranged from 3.6 to 23.2 mL/year.

Interpretation

Individuals with NOCB are at a higher risk of incident COPD and all-cause mortality than individuals without NOCB, highlighting the crucial need for strategies to screen for and reduce NOCB risk.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/ PROSPERO, identifier CRD42020202837
Comparison of Efficacy of Anti-interleukin-17 in the Treatment of Psoriasis Between Caucasians and Asians: A Systematic Review and Meta-Analysis
Authors: Zhang Danyi , Qiu Jianing , Liao Xing , Xiao Yi , Shen Minxue , Deng Yaxiong , Jing Danrong
Published: January 2022

Background

Interleukin-17 (IL-17) monoclonal antibody drugs have been increasingly significant in the treatment of psoriasis, but it is not clear whether the efficacy is equivalent across ethnicities.

Objective

To explore the differences of short-term efficacy of IL-17 inhibitors between Caucasians and Asians.

Methods

The pooled log risk ratio (logRR) between the groups was estimated. The meta-regression analysis on the logRR was performed, with the proportion of Caucasian patients as the covariate. The subgroup analysis was performed by specific IL-17 inhibitors.

Results

Of the 1,569 potentially relevant studies, sixteen randomized controlled trials (RCTs) were included. For the Psoriasis Area and Severity Index 75 (PASI 75) response at week 12, the pooled logRR of the Asian group and the Caucasian group was 2.81 (95% CI: 2.27–3.35, p < 0.001) and 2.93 (95% CI: 2.71–3.16, p < 0.001), respectively, indicating no significant difference of efficacy between Asians and Caucasians. The meta-regression analysis did not show an association of the proportion of Caucasians with the effect size (β = 0.3203, p = 0.334). In the subgroup analysis, the comparison results of secukinumab were consistent with the main analysis.

Limitations

Only the short-term efficacy was explored. The data from Asian countries were limited.

Conclusions

The short-term efficacy of IL-17 inhibitors in the treatment of psoriasis has no significant difference between Caucasians and Asians.

Systematic Review Registration

PROSPERO, identifier CRD42020201994, https://www.crd.york.ac.uk/prospero/.
Prognostic Value of Ki-67 Index in Patients With Endometrial Stromal Sarcoma
Authors: Meng Yu , Quan Quan , Zhang Fenfen , Liu Yao , Ren Siling , Mu Xiaoling
Published: January 2022

Objective

The Ki-67 index is used to evaluate cell proliferation activity, which is related to tumor progression, metastasis, and prognosis. We aimed to explore the prognostic value of Ki-67 index in endometrial stromal sarcoma and to explore the optimal cut-off value of Ki-67 index for predicting recurrent endometrial stromal sarcoma.

Methods

A total of 82 patients with endometrial stromal sarcoma who were treated in our hospital were collected. Clinicopathological data of these patients were retrospectively analyzed. Ki-67 index was detected by the immunohistochemical method. Receiver operating characteristic curve and the Youden index were performed to determine the optimal cut-off value of Ki-67 index for predicting recurrent endometrial stromal sarcoma. The Cox regression was performed to analyze risk factors affecting prognosis of endometrial stromal sarcoma. The Kaplan–Meier method and Log-rank test were performed to analyze the survival of patients.

Results

The optimal cut-off value of Ki-67 index for predicting recurrent endometrial stromal sarcoma was 35%. The results of univariate analysis showed that high Ki-67 index (≥35%) was statistically significantly bound up with shorter progress free survival and overall survival. The results of multivariate analysis showed that Ki-67 index (P = 0.001) and ovarian preservation (P = 0.040) were independent prognostic factors of progress free survival.

Conclusions

A Ki-67 index cut-off of 35% was optimal for predicting recurrent endometrial stromal sarcoma. Ki-67 index may be a useful prognostic marker in endometrial stromal sarcoma.
Advances in Dry Eye Disease Examination Techniques
Authors: Wu Yaying , Wang Chunyang , Wang Xin , Mou Yujie , Yuan Kelan , Huang Xiaodan , Jin Xiuming
Published: January 2022

Dry eye-related ocular surface examination is very important in the diagnosis and treatment of dry eye disease. With the recent advances in science and technology, dry eye examination techniques have progressed rapidly, which has greatly improved dry eye diagnoses and treatment. However, clinically, confusion remains about which examination to choose, how to ensure the repeatability of the examination, and how to accurately interpret the examination results. In this review, we systematically evaluate previous examinations of dry eye, analyze the latest views and research hotspots, and provide a reference for the diagnosis and management of dry eye.
Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence
Authors: Almansour Nahlah Makki
Published: January 2022

Triple-negative breast cancer (TNBC) is a kind of breast cancer that lacks estrogen, progesterone, and human epidermal growth factor receptor 2. This cancer is responsible for more than 15–20% of all breast cancers and is of particular research interest as it is therapeutically challenging mainly because of its low response to therapeutics and highly invasive nature. The non-availability of specific treatment options for TNBC is usually managed by conventional therapy, which often leads to relapse. The focus of this review is to provide up-to-date information related to TNBC epidemiology, risk factors, metastasis, different signaling pathways, and the pathways that can be blocked, immune suppressive cells of the TNBC microenvironment, current and investigation therapies, prognosis, and the role of artificial intelligence in TNBC diagnosis. The data presented in this paper may be helpful for researchers working in the field to obtain general and particular information to advance the understanding of TNBC and provide suitable disease management in the future.
ADHD and Neurodegenerative Disease Risk: A Critical Examination of the Evidence
Authors: Becker Sara , Sharma Manu J. , Callahan Brandy L.
Published: January 2022

In this review, we undertake a critical appraisal of eight published studies providing first evidence that a history of attention-deficit/hyperactivity disorder (ADHD) may increase risk for the later-life development of a neurodegenerative disease, in particular Lewy body diseases (LBD), by up to five-fold. Most of these studies have used data linked to health records in large population registers and include impressive sample sizes and adequate follow-up periods. We identify a number of methodological limitations as well, including potential diagnostic inaccuracies arising from the use of electronic health records, biases in the measurement of ADHD status and symptoms, and concerns surrounding the representativeness of ADHD and LBD cohorts. Consequently, previously reported risk associations may have been underestimated due to the high likelihood of potentially missed ADHD cases in groups used as “controls”, or alternatively previous estimates may be inflated due to the inclusion of confounding comorbidities or non-ADHD cases within “exposed” groups that may have better accounted for dementia risk. Prospective longitudinal studies involving well-characterized cases and controls are recommended to provide some reassurance about the validity of neurodegenerative risk estimates in ADHD.
Opportunities and Challenges for Nanotherapeutics for the Aging Population
Authors: Hunt Nicholas J. , McCourt Peter A. G. , Kuncic Zdenka , Le Couteur David G. , Cogger Victoria C.
Published: January 2022

Nanotherapeutics utilize the properties of nanomaterials to alter the pharmacology of the drugs and therapies being transported, leading to changes in their biological disposition (absorption, distribution, cellular uptake, metabolism and elimination) and ultimately, their pharmacological effect. This provides an opportunity to optimize the pharmacology of drugs, particularly for those that are dependent on hepatic action. Old age is associated with changes in many pharmacokinetic processes which tend to impair drug efficacy and increase risk of toxicity. While these age-related changes are drug-specific they could be directly addressed using nanotechnology and precision targeting. The benefits of nanotherapeutics needs to be balanced against toxicity, with future use in humans dependent upon the gathering of information about the clearance and long-term safety of nanomaterials.
HybridMouse: A Hybrid Convolutional-Recurrent Neural Network-Based Model for Identification of Mouse Ultrasonic Vocalizations
Authors: Goussha Yizhaq , Bar Kfir , Netser Shai , Cohen Lior , Hel-Or Yacov , Wagner Shlomo
Published: January 2022

Mice use ultrasonic vocalizations (USVs) to convey a variety of socially relevant information. These vocalizations are affected by the sex, age, strain, and emotional state of the emitter and can thus be used to characterize it. Current tools used to detect and analyze murine USVs rely on user input and image processing algorithms to identify USVs, therefore requiring ideal recording environments. More recent tools which utilize convolutional neural networks models to identify vocalization segments perform well above the latter but do not exploit the sequential structure of audio vocalizations. On the other hand, human voice recognition models were made explicitly for audio processing; they incorporate the advantages of CNN models in recurrent models that allow them to capture the sequential nature of the audio. Here we describe the HybridMouse software: an audio analysis tool that combines convolutional (CNN) and recurrent (RNN) neural networks for automatically identifying, labeling, and extracting recorded USVs. Following training on manually labeled audio files recorded in various experimental conditions, HybridMouse outperformed the most commonly used benchmark model utilizing deep-learning tools in accuracy and precision. Moreover, it does not require user input and produces reliable detection and analysis of USVs recorded under harsh experimental conditions. We suggest that HybrideMouse will enhance the analysis of murine USVs and facilitate their use in scientific research.
Enriching the Study Population for Ischemic Stroke Therapeutic Trials Using a Machine Learning Algorithm
Authors: Maharjan Jenish , Ektefaie Yasha , Ryan Logan , Mataraso Samson , Barnes Gina , Shokouhi Sepideh , Green-Saxena Abigail , Calvert Jacob , Mao Qingqing , Das Ritankar
Published: January 2022

Background

Strokes represent a leading cause of mortality globally. The evolution of developing new therapies is subject to safety and efficacy testing in clinical trials, which operate in a limited timeframe. To maximize the impact of these trials, patient cohorts for whom ischemic stroke is likely during that designated timeframe should be identified. Machine learning may improve upon existing candidate identification methods in order to maximize the impact of clinical trials for stroke prevention and treatment and improve patient safety.

Methods

A retrospective study was performed using 41,970 qualifying patient encounters with ischemic stroke from inpatient visits recorded from over 700 inpatient and ambulatory care sites. Patient data were extracted from electronic health records and used to train and test a gradient boosted machine learning algorithm (MLA) to predict the patients' risk of experiencing ischemic stroke from the period of 1 day up to 1 year following the patient encounter. The primary outcome of interest was the occurrence of ischemic stroke.

Results

After training for optimization, XGBoost obtained a specificity of 0.793, a positive predictive value (PPV) of 0.194, and a negative predictive value (NPV) of 0.985. The MLA further obtained an area under the receiver operating characteristic (AUROC) of 0.88. The Logistic Regression and multilayer perceptron models both achieved AUROCs of 0.862. Among features that significantly impacted the prediction of ischemic stroke were previous stroke history, age, and mean systolic blood pressure.

Conclusion

MLAs have the potential to more accurately predict the near risk of ischemic stroke within a 1-year prediction window for individuals who have been hospitalized. This risk stratification tool can be used to design clinical trials to test stroke prevention treatments in high-risk populations by identifying subjects who would be more likely to benefit from treatment.
Targeting α-Synuclein in Parkinson's Disease by Induced Pluripotent Stem Cell Models
Authors: Spathopoulou Angeliki , Edenhofer Frank , Fellner Lisa
Published: January 2022

Parkinson's disease (PD) is a progressive, neurodegenerative disorder characterized by motor and non-motor symptoms. To date, no specific treatment to halt disease progression is available, only medication to alleviate symptoms can be prescribed. The main pathological hallmark of PD is the development of neuronal inclusions, positive for α-synuclein (α-syn), which are termed Lewy bodies (LBs) or Lewy neurites. However, the cause of the inclusion formation and the loss of neurons remain largely elusive. Various genetic determinants were reported to be involved in PD etiology, including SNCA, DJ-1, PRKN, PINK1, LRRK2, and GBA. Comprehensive insights into pathophysiology of PD critically depend on appropriate models. However, conventional model organisms fall short to faithfully recapitulate some features of this complex disease and as a matter-of-fact access to physiological tissue is limiting. The development of disease models replicating PD that are close to human physiology and dynamic enough to analyze the underlying molecular mechanisms of disease initiation and progression, as well as the generation of new treatment options, is an important and overdue step. Recently, the establishment of induced pluripotent stem cell (iPSC)-derived neural models, particularly from genetic PD-variants, developed into a promising strategy to investigate the molecular mechanisms regarding formation of inclusions and neurodegeneration. As these iPSC-derived neurons can be generated from accessible biopsied samples of PD patients, they carry pathological alterations and enable the possibility to analyze the differences compared to healthy neurons. This review focuses on iPSC models carrying genetic PD-variants of α-syn that will be especially helpful in elucidating the pathophysiological mechanisms of PD. Furthermore, we discuss how iPSC models can be instrumental in identifying cellular targets, potentially leading to the development of new therapeutic treatments. We will outline the enormous potential, but also discuss the limitations of iPSC-based α-syn models.
In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea
Authors: Nelson Lacey , Lovett Braeden , Johns J. Dixon , Gu Shoujun , Choi Dongseok , Trune Dennis , Hoa Michael
Published: January 2022

Background

Treatment of many types of hearing instability in humans, including sudden sensorineural hearing loss, Meniere's disease, and autoimmune inner ear disease, rely heavily on the utilization of corticosteroids delivered both by oral and transtympanic routes. Despite this use, there is heterogeneity in the response to treatment with corticosteroids in humans with these diseases. The mechanisms by which corticosteroids exert their effect and the cell types in which they exert their effects in the inner ear remain poorly characterized. In this study, we localize steroid-responsive genes to cochlear cell types using previously published transcriptome datasets from the mammalian cochlea.

Methods

Steroid-responsive genes were localized to specific cochlear cell types using existing transcriptome datasets from wild-type mammalian cochlea exposed to systemic and transtympanic steroids, as well as previously published single-cell and single-nucleus RNA-sequencing datasets from the mammalian cochlea. Gene ontology (GO) analysis of differentially expressed genes (DEGs) was performed using PANTHER to investigate cellular processes implicated in transtympanic vs. systemic steroid action in the cochlea.

Results

Steroid-responsive genes were localized to specific cell types and regions in the cochlea including the stria vascularis, organ of Corti, and spiral ganglion neurons (SGN). Analyses demonstrate differential prevalence of steroid-responsive genes. GO analysis demonstrated steroid-responsive DEGs in the SGN to be associated with angiogenesis, apoptosis, and cytokine-mediated anti-inflammatory pathways.

Conclusions

Single-cell and single-nucleus transcriptome datasets localize steroid-responsive genes to specific regions in the cochlea. Further study of these regionally-specific steroid-responsive genes may provide insight into the mechanisms of and clinical response to corticosteroids in diseases of hearing instability.
Analgesia in the Neurosurgical Intensive Care Unit
Authors: Kvolik Slavica , Koruga Nenad , Skiljic Sonja
Published: January 2022

Acute pain in neurosurgical patients is an important issue. Opioids are the most used for pain treatment in the neurosurgical ICU. Potential side effects of opioid use such as oversedation, respiratory depression, hypercapnia, worsening intracranial pressure, nausea, and vomiting may be problems and could interfere with neurologic assessment. Consequently, reducing opioids and use of non-opioid analgesics and adjuvants (N-methyl-D-aspartate antagonists, α2 -adrenergic agonists, anticonvulsants, corticosteroids), as well as non-pharmacological therapies were introduced as a part of a multimodal regimen. Local and regional anesthesia is effective in opioid reduction during the early postoperative period. Among non-opioid agents, acetaminophen and non-steroidal anti-inflammatory drugs are used frequently. Adverse events associated with opioid use in neurosurgical patients are discussed. Larger controlled studies are needed to find optimal pain management tailored to neurologically impaired neurosurgical patients.
Case Report: Triphasic Waves in a 9-Year-Old Girl With Anti-NMDAR Encephalitis
Authors: Zhang Ke , Xu Shuang , Zhou Yalan , Su Tangfeng
Published: January 2022

Background

Triphasic waves (TWs) are mainly described in association with metabolic encephalopathy, especially hepatic encephalopathy. Now, as different conditions including non-metabolic and structural abnormalities have been reported to be associated with TWs, the presence of TWs becomes a non-specific finding for metabolic encephalopathy.

Case Presentation

We report the first case of anti-NMDAR encephalitis in a 9-year-old girl presenting with TWs on EEG. The TWs background EEG lasted for about 12 h on the 40th day of the disease course. No epileptic wave was found during a series of EEG examinations. The child was discharged from the hospital and no neurological sequelae remained after a six-month follow-up.

Conclusions

TWs are not specific to metabolic encephalopathy, but can also occur in children with autoimmune encephalitis. This case achieved a good prognosis after the early initiation of immunotherapy.
DHA Suppresses Hepatic Lipid Accumulation via Cyclin D1 in Zebrafish
Authors: Ding Qianwen , Hao Qiang , Zhang Qingshuang , Yang Yalin , Olsen Rolf Erik , Ringø Einar , Ran Chao , Zhang Zhen , Zhou Zhigang
Published: January 2022

With the widespread use of high-fat diets (HFDs) in aquaculture, fatty livers are frequently observed in many fish species. The aim of this study was to investigate if docosahexaenoic acid (DHA) could be used to reduce the fatty liver in zebrafish generated by a 16% soybean oil-HFD over 2 weeks of feeding. The DHA was added to iso-lipidic HFD at 0.5, 1.0, and 2.0% of diet. Supplementation of DHA reduced growth and feed efficiency in a dose dependent manner being lowest in the HFDHA2.0 group. Hepatic triglyceride (TG) in zebrafish fed 0.5% DHA-supplemented HFD (HFDHA0.5) was significantly lower than in the HFD control. Transcriptional analyses of hepatic genes showed that lipid synthesis was reduced, while fatty acid β-oxidation was increased in the HFDHA0.5 group. Furthermore, the expression of Cyclin D1 in liver of zebrafish fed HFDHA0.5 was significantly reduced compared to that in fish fed HFD. In zebrafish liver cells, Cyclin D1 knockdown and blocking of Cyclin D1-CDK4 signal led to inhibited lipid biosynthesis and elevated lipid β-oxidation. Besides, DHA-supplemented diet resulted in a rich of Proteobacteria and Actinobacteriota in gut microbiota, which promoted lipid β-oxidation but did not alter the expression of Cyclin D1 in germ-free zebrafish model. In conclusion, DHA not only inhibits hepatic lipid synthesis and promotes lipid β-oxidation via Cyclin D1 inhibition, but also facilitates lipid β-oxidation via gut microbiota. This study reveals the lipid-lowering effects of DHA and highlights the importance of fatty acid composition when formulating fish HFD.
Protective Effects of Bile Acids Against Hepatic Lipid Accumulation in Hybrid Grouper Fed a High-Lipid Diet
Authors: Xu Jia , Li Xiaoyue , Yao Xinzhou , Xie Shiwei , Chi Shuyan , Zhang Shuang , Cao Junming , Tan Beiping
Published: January 2022

Bile acids (BAs) usually display growth-promoting and lipid-lowering properties when supplemented to the diet. The effects of a high-lipid diet (HD) and BAs supplementation on growth performance and lipid deposition of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) was evaluated in this study. Compared to the control diet (CD), the HD did not significantly affect the fish growth performance, but it promoted lipid deposition, as revealed by a significantly higher crude lipid content of the whole body, muscle, and liver. Among the HD supplemented with taurocholic acid (BD) groups, and compared to the HD, fish fed dietary supplementation of BAs at 900 mg kg−1 exhibited the best growth performance and lowest hepatic lipid deposition. In most BD groups, the content of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in serum, as well as the content of total cholesterol in the liver, were decreased, whereas the content of high-density lipoprotein cholesterol in serum was increased. In addition, the most strongly influenced pathways between the control, HD, and B3D groups were fatty acid biosynthesis, insulin signaling pathway, and AMPK signaling pathway. The improvement of lipid metabolism induced by the supplementation of BAs may be attributed to decreased expression of lipogenesis genes and proteins (enzymes), and increased lipolysis. In conclusion, dietary supplementation of BAs at 900 mg kg−1 promoted growth performance and reduced lipid accumulation, whereas BAs supplementation improved the hepatic lipid metabolism by enhancing hepatic lipolysis, inhibiting lipogenesis, and regulating associated transcriptional factors in hybrid grouper.
Development and Validation of a Prognostic Index Based on Genes Participating in Autophagy in Patients With Lung Adenocarcinoma
Authors: Wu Zi-Xuan , Huang Xuyan , Cai Min-Jie , Huang Pei-Dong , Guan Zunhui
Published: January 2022

Background

Lung adenocarcinoma (LUAD) is a deadly respiratory system malignancy with poor prognosis. Autophagy is essential for the beginning, development, and therapy resistance of cancer. However, the expression of genes participating in autophagy in LUAD and their associations with prognosis remain unclear.

Methods

Predictive genes participating in autophagy in LUAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were investigated. TCGA and GEO cohorts were divided into two risk groups, while the low-risk group having a longer overall survival (OS) time. This article aims to point out the interaction between genes participating in autophagy and immune function, immune checkpoints, and m6a in LUAD. The prediction model was designed for exploring least absolute shrinkage and selection operator (LASSO) regression. It has been revealed that gene expression and autophagy are inextricably connected.

Results

Genes participating in autophagy were shown to be somewhat overexpressed in the high-risk group even though no different clinical symptoms were present, indicating that they might be used in a model to predict LUAD prognosis. The majority of genes participating in autophagy prognostic signatures controlled immunological and tumor-related pathways, according to gene set enrichment analysis (GSEA). KRT6A, KYNU, IGFBP1, DKK1, PKP2, PLEK2, GAPDH, FLNC, and NTSR1 might be related to the oncology process for LUAD patients. CERS4, CMAHP, and PLEKHB1 have been identified as being associated with low risk in patients with LUAD. Furthermore, the immune function and m6a gene expression differed significantly between the two groups.

Conclusions

Genes participating in autophagy are connected to the development and progression of LUAD. LUAD patients’ prognoses are often foreseen utilizing matched prognostic models. Genes participating in autophagy in LUAD may be therapeutic targets that ought to be investigated more.
First-Line Tyrosine Kinase Inhibitors Combined With Local Consolidative Radiation Therapy for Elderly Patients With Oligometastatic Non-Small Cell Lung Cancer Harboring EGFR Activating Mutations
Authors: Hu Xiaolong , Li Hongqi , Kang Xiaoli , Wang Xuan , Pang Haifeng , Liu Chen , Zhang Jianchun , Wang Yingjie
Published: January 2022

Objective

The aim of this study was to investigate the efficacy and safety of combined applications of local consolidative radiation therapy (LCRT) and first-line tyrosine kinase inhibitors (TKIs) for the treatment of primary tumors and oligometastatic sites in oligometastatic NSCLC harboring Epidermal Growth Factor Receptor (EGFR) activating mutations.

Patients and Methods

Elderly patients with oligometastatic NSCLC (≤5 metastases) harboring EGFR activating mutations at the time of diagnosis were identified. They were treated with first-line TKIs alone or in combination with LCRT. Progression‐free survival (PFS) and overall survival (OS) were estimated through the Kaplan–Meier method.

Results

A total of 122 elderly patients were enrolled between February 2010 and January 2018. Among them, 41.0% (n = 50) received TKIs combined with LCRT (TKIs + LCRT group), whereas 59.0% (n = 72) received TKIs monotherapy (TKIs alone group). Patients were followed up for a median length of 34 months (ranging from 7.0 to 64 months). The median PFS in TKIs + LCRT group was 17 months (95%CI: 15.37–18.63), which was significantly longer than that of the TKIs-alone group (12 months; 95%CI: 11.05–12.95) (p <0.001). Median OS in TKIs + LCRT group was 38 months (95%CI: 35.61–40.39), while that of the TKIs-alone group was 29 months (95%CI: 26.86–31.14) (p <0.001). Multivariate analyses revealed that LCRT, one to two metastases, and good ECOG PS were independent predictors for better PFS (p <0.001, p = 0.004, and p = 0.027). Moreover, LCRT, good ECOG PS, and T1-2 stage were independent predictors for better OS (p <0.001, p = 0.007 and p = 0.007). Most of the patients suffered from grade 1 to 2 toxicities, and treatment-related deaths were not recorded.

Conclusion

First-line TKIs combined with LCRT may improve survival outcomes for elderly patients with oligometastatic NSCLC harboring EGFR activating mutations. This approach was not associated with much toxicity, therefore, it can be used for the treatment of elderly patients with oligometastatic disease.
Construction and Multicenter Diagnostic Verification of Intelligent Recognition System for Endoscopic Images From Early Gastric Cancer Based on YOLO-V3 Algorithm
Authors: Yao Zhendong , Jin Tao , Mao Boneng , Lu Bo , Zhang Yefei , Li Sisi , Chen Weichang
Published: January 2022

Introduction

Endoscopy is an important tool for the diagnosis of early gastric cancer. Therefore, a combination of artificial intelligence and endoscopy has the ability to increase the speed and efficiency of early gastric cancer diagnosis. YOU ONLY LOOK ONCE (YOLO) is an advanced object detection depth neural network algorithm that has not been widely used in gastrointestinal image recognition.

Objective

We developed an artificial intelligence system herein referred to as “EGC-YOLO” for the rapid and accurate diagnosis of endoscopic images from early gastric cancer.

Methods

More than 40000 gastroscopic images from 1653 patients in Yixing people’s Hospital were used as the training set for the system, while endoscopic images from the other two hospitals were used as external validation test sets. The sensitivity, specificity, positive predictive value, Youden index and ROC curve were analyzed to evaluate detection efficiencies for EGC-YOLO.

Results

EGC-YOLO was able to diagnose early gastric cancer in the two test sets with a high superiority and efficiency. The accuracy, sensitivity, specificity and positive predictive value for Test Sets 1 and 2 were 85.15% and 86.02%, 85.36% and 83.02%, 84.41% and 92.21%, and 95.22% and 95.65%, respectively. In Test Sets 1 and 2, the corresponding Threshold-values were 0.02, 0.16 and 0.17 at the maximum of the Youden index. An increase in Threshold-values was associated with a downward trend in sensitivity and accuracy, while specificity remained relatively stable at more than 80%.

Conclusions

The EGC-YOLO system is superior for the efficient, accurate and rapid detection of early gastric cancer lesions. For different data sets, it is important to select the appropriate threshold-value in advance to achieve the best performance of the EGC-YOLO system.
Caffeine Therapy for Apnea of Prematurity: Role of the Circadian CLOCK Gene Polymorphism
Authors: Guo Hong-Li , Long Jia-Yi , Hu Ya-Hui , Liu Yun , He Xin , Li Ling , Xia Ying , Ding Xuan-Sheng , Chen Feng , Xu Jing , Cheng Rui
Published: January 2022

Standard-dose caffeine citrate has been routinely prescribed for apnea of prematurity (AOP) management; however, some preterm infants respond well to the therapy while others do not. The AOP phenotype has been attributed solely to the immature control of the respiratory system consequent to preterm birth, but there are also important genetic influences. Based on our previous report, we tested the hypothesis that the human circadian locomotor output cycles kaput (CLOCK) gene polymorphisms play a role in the response to caffeine citrate therapy in preterm infants. We also studied the interactions of the circadian clock with aryl hydrocarbon receptor (AHR) signaling pathways in preterm babies who received caffeine citrate. This single-center study collected data from 112 preterm infants (<35 weeks gestational age) between July 2017 and July 2018, including apnea-free (n = 48) and apneic (n = 64) groups. Eighty-eight candidate single nucleotide polymorphisms (SNPs) were tested using the MassARRAY system. Association analysis was performed using the PLINK Whole Genome Data Analysis Toolset and SNPStats software. Linkage disequilibrium (LD) and haplotype analyses were performed using Hapview software. No significant intergroup differences in allele distributions or genotype frequencies of CYP1A2, CYP3A4, CYP3A5, and CYP3A7 were detected in our study on preterm babies. Two more SNPs in AHR were found to be associated with determining the response to caffeine citrate therapy in our pediatric patients. Of the 46 candidate SNPs in the CLOCK gene, 26 were found to be associated with determining the response to caffeine treatment in these babies. Interestingly, a significant association was retained for 18 SNPs in the CLOCK gene after false discovery rate correction. Moreover, strong LD formed in those variants in AHR, ADORA2A, and CLOCK genes was confirmed to be significantly associated with a better response to standard-dose caffeine therapy. In summary, CLOCK gene polymorphisms play a role in determining the response to caffeine therapy in premature neonates with AOP. However, whether the AHR and CLOCK signaling pathways crosstalk with each other during caffeine treatment remains largely unclear. Future clinical studies including more immature babies and basic research are needed to explore the mechanism by which circadian rhythms affect the response to caffeine therapy.
Recent Progress of RGD Modified Liposomes as Multistage Rocket Against Cancer
Authors: Sheikh Afsana , Alhakamy Nabil A. , Md Shadab , Kesharwani Prashant
Published: January 2022

Cancer is a life-threatening disease, contributing approximately 9.4 million deaths worldwide. To address this challenge, scientific researchers have investigated molecules that could act as speed-breakers for cancer. As an abiotic drug delivery system, liposomes can hold both hydrophilic and lipophilic drugs, which promote a controlled release, accumulate in the tumor microenvironment, and achieve elongated half-life with an enhanced safety profile. To further improve the safety and impair the off-target effect, the surface of liposomes could be modified in a way that is easily identified by cancer cells, promotes uptake, and facilitates angiogenesis. Integrins are overexpressed on cancer cells, which upon activation promote downstream cell signaling and eventually activate specific pathways, promoting cell growth, proliferation, and migration. RGD peptides are easily recognized by integrin over expressed cells. Just like a multistage rocket, ligand anchored liposomes can be selectively recognized by target cells, accumulate at the specific site, and finally, release the drug in a specific and desired way. This review highlights the role of integrin in cancer development, so gain more insights into the phenomenon of tumor initiation and survival. Since RGD is recognized by the integrin family, the fate of RGD has been demonstrated after its binding with the acceptor’s family. The role of RGD based liposomes in targeting various cancer cells is also highlighted in the paper.
Construction of the Enterococcal Strain Expressing Immunogenic Fragment of SARS-Cov-2 Virus
Authors: Suvorov Alexander , Gupalova Tatiana , Desheva Yulia , Kramskaya Tatiana , Bormotova Elena , Koroleva Irina , Kopteva Olga , Leontieva Galina
Published: January 2022

Contemporary SARS-Cov-2 pandemic, besides its dramatic global influence on the human race including health care systems, economies, and political decisions, opened a window for the global experiment with human vaccination employing novel injectable vaccines providing predominantly specific IgG response with little knowledge of their impact on the mucosal immunity. However, it is widely accepted that protection against the pathogens at the gates of the infection - on mucosal surfaces—predominantly rely on an IgA response. Some genetically modified bacteria, including probiotics, represent attractive vehicles for oral or nasal mucosal delivery of therapeutic molecules. Probiotic-based vaccines for mucous membranes are easy to produce in large quantities; they have low cost, provide quite a long T-cell memory, and gut IgA response to oral vaccines is highly synchronized and strongly oligoclonal. Here we present a study demonstrating construction of the novel SARS-Cov-2 vaccine candidate employing the gene fragment of S1 SARS-Cov-2 gene. This DNA fragment was inserted in frame into major pili protein gene with d2 domain of enterococcal operon encoding for pili. The DNA sequencing proved the presence of the insert in enterococcal genome. RNA transcription, immunoprecipitation, and immune electron microscopy with human sera obtained from the SARS-Cov-2 patients demonstrated expression of SARS-Cov-2 antigens in bacteria. Taken together the data obtained allowed considering this genetically modified probiotic strain as an interesting candidate for vaccine against SARS-Cov-2.
Pharmacological Treatment of Secondary Lymphedema
Authors: Brown Stav , Dayan Joseph H. , Coriddi Michelle , Campbell Adana , Kuonqui Kevin , Shin Jinyeon , Park Hyeung Ju , Mehrara Babak J. , Kataru Raghu P.
Published: January 2022

Lymphedema is a chronic disease that results in swelling and decreased function due to abnormal lymphatic fluid clearance and chronic inflammation. In Western countries, lymphedema most commonly develops following an iatrogenic injury to the lymphatic system during cancer treatment. It is estimated that as many as 10 million patients suffer from lymphedema in the United States alone. Current treatments for lymphedema are palliative in nature, relying on compression garments and physical therapy to decrease interstitial fluid accumulation in the affected extremity. However, recent discoveries have increased the hopes of therapeutic interventions that may promote lymphatic regeneration and function. The purpose of this review is to summarize current experimental pharmacological strategies in the treatment of lymphedema.
A Repurposed Drug Screen for Compounds Regulating Aquaporin 5 Stability in Lung Epithelial Cells
Authors: Villandre John , White Virginia , Lear Travis B. , Chen Yanwen , Tuncer Ferhan , Vaiz Emily , Tuncer Beyza , Lockwood Karina , Camarco Dan , Liu Yuan , Chen Bill B. , Evankovich John
Published: January 2022

Aquaporin 5 (AQP5) is expressed in several cell types in the lung and regulates water transport, which contributes to barrier function during injury and the composition of glandular secretions. Reduced AQP5 expression is associated with barrier dysfunction during acute lung injury, and strategies to enhance its expression are associated with favorable phenotypes. Thus, pharmacologically enhancing AQP5 expression could be beneficial. Here, we optimized a high-throughput assay designed to detect AQP5 abundance using a cell line stably expressing bioluminescent-tagged AQP5. We then screened a library of 1153 compounds composed of FDA-approved drugs for their effects on AQP5 abundance. We show compounds Niclosamide, Panobinostat, and Candesartan Celexitil increased AQP5 abundance, and show that Niclosamide has favorable cellular toxicity profiles. We determine that AQP5 levels are regulated in part by ubiquitination and proteasomal degradation in lung epithelial cells, and mechanistically Niclosamide increases AQP5 levels by reducing AQP5 ubiquitination and proteasomal degradation. Functionally, Niclosamide stabilized AQP5 levels in response to hypotonic stress, a stimulus known to reduce AQP5 levels. In complementary assays, Niclosamide increased endogenous AQP5 in both A549 cells and in primary, polarized human bronchial epithelial cells compared to control-treated cells. Further, we measured rapid cell volume changes in A549 cells in response to osmotic stress, an effect controlled by aquaporin channels. Niclosamide-treated A549 cell volume changes occurred more rapidly compared to control-treated cells, suggesting that increased Niclosamide-mediated increases in AQP5 expression affects functional water transport. Taken together, we describe a strategy to identify repurposed compounds for their effect on AQP5 protein abundance. We validated the effects of Niclosamide on endogenous AQP5 levels and in regulating cell-volume changes in response to tonicity changes. Our findings highlight a unique approach to screen for drug effects on protein abundance, and our workflow can be applied broadly to study compound effects on protein abundance in lung epithelial cells.
Metabolomic Fingerprint of Behavioral Changes in Response to Full-Spectrum Cannabis Extracts
Authors: Maayah Zaid H. , Raposo Pamela J. F. , Silver Heidi , Mandal Rupasri , Ellis Lee , Alam Abrar S. , Takahara Shingo , Ferdaoussi Mourad , Mathewson Kyle E. , Eurich Dean T. , Fouad Karim , Wishart David S. , Dyck Jason R. B.
Published: January 2022

Numerous existing full-spectrum cannabis extract products have been used in clinical trials for the treatment of various diseases. Despite their efficacy, the clinical use of some of these full-spectrum cannabis extracts is limited by behavioral side effects such as cognitive dysfunction and impaired motor skills. To better understand what constitutes cannabis-induced behavioral effects, our objective was to identify a novel panel of blood-based metabolites that are predictive, diagnostic, and/or prognostic of behavioral effects.

At 8 weeks of age, male rats were randomly assigned to groups and were gavage fed with full-spectrum cannabis extract (tetrahydrocannabinol/cannabidiol (THC/CBD) along with all other cannabis compounds, 15 mg/kg), broad-spectrum cannabis extract (CBD along with all other cannabis compounds, 15 mg/kg), or vehicle oil. Four hours after being gavage fed, behavioral assessments were determined using the open field test and the elevated plus maze. Following these assessments, serum was collected from all rats and the serum metabolites were identified and quantified by LC–MS/MS and 1H NMR spectroscopy.

We found that only rats treated with full-spectrum cannabis extract exhibited behavioral changes. Compared to vehicle-treated and broad-spectrum extract–treated rats, full-spectrum extract–treated rats demonstrated higher serum concentrations of the amino acid phenylalanine and long-chain acylcarnitines, as well as lower serum concentrations of butyric acid and lysophosphatidylcholines. This unique metabolomic fingerprint in response to cannabis extract administration is linked to behavioral effects and may represent a biomarker profile of cannabis-induced behavioral changes. If validated, this work may allow a metabolomics-based decision tree that would aid in the rapid diagnosis of cannabis-induced behavioral changes including cognitive impairment.
Remote Chemical Sensing by SERS with Self-Assembly Plasmonic Nanoparticle Arrays on a Fiber
Authors: Zhang Xin , Zhang Kunyi , von Bredow Hasso , Metting Christopher , Atanasoff George , Briber Robert M. , Rabin Oded
Published: January 2022

An optical fiber was modified at the tip with a self-assembled plasmonic metamaterial that acts as a miniature surface-enhanced Raman spectroscopy (SERS) substrate. This optical fiber-based device co-localizes the laser probe signal and the chemical analyte at a distance remote from the spectrometer, and returns the scattered light signal to the spectrometer for analysis. Remote SERS chemical detection is possible in liquids and in dried samples. Under laboratory conditions, the analyte SERS signal can be separated from the background signal of the fiber itself and the solvent. An enhancement factor greater than 35,000 is achieved with a monolayer of the SERS marker 4-aminothiophenol.