bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Late-Onset Lennox-Gastaut Syndrome Treated With Stereotactic Electroencephalography-Guided Radiofrequency Thermocoagulation Before Craniotomy
Authors: Li Sixian , Cai Xiaodong , Yao Chen , Wang Yuanqing , Xiao Xiaohua , Yang Huafeng , Yao Yi , Chen Lei
Published: June 2022

The onset of Lennox-Gastaut syndrome (LGS), a severe epilepsy syndrome, is typically before 8 years of age. Late-onset LGS (with onset in adolescence and adulthood) is relatively rare clinically and has some differences from classical LGS. Herein, we describe the case of a patient with late-onset LGS and provide a literature review of such cases. The patient had focal epilepsy onset at 8 years of age. After a 9-year evolution, he suffered seizures of different types and had a diagnosis of late-onset LGS. Drug treatment was ineffective. Nothing was found on stereotactic electroencephalography (SEEG) and magnetic resonance imaging (MRI) during the course of the disease. After the second presurgical evaluation, we found a suspicious focus on high-resolution structural MRI which was verified by SEEG at last. After SEEG-guided radiofrequency thermocoagulation (RFTC), his seizures were controlled, and his cognitive function and quality of living clearly improved. However, his seizures recurred 2 years later, and he underwent left occipital resection. Thereafter, his seizures have been controlled until now. This case emphasizes the importance of high-resolution structural MRI in the treatment of LGS. Furthermore, it suggests that late-onset LGS may be caused by focal lesions and evolve from focal epilepsy. Thus, characterizing the clinical symptoms and performing individualized electroencephalographic follow-up are both very important. Additionally, the clinical outcome in this case implies the value and limitations of RFTC in patients with epilepsy and a clear focal lesion. Moreover, this case further supports differences between late-onset and classical LGS in terms of clinical manifestation, cognitive changes, prognosis, and treatment.
Role of Ultrasound Imaging in the Prediction of TRIM67 in Brain Metastases From Breast Cancer
Authors: Xuan Zhidong , Ma Ting , Qin Yue , Guo Yajie
Published: June 2022

Objectives

Ultrasound (US) imaging is a relatively novel strategy to monitor the activity of the blood–brain barrier, which can facilitate the diagnosis and treatment of neurovascular-related metastatic tumors. The purpose of this study was to investigate the clinical significance of applying a combination of US imaging outcomes and the associated genes. This was performed to construct line drawings to facilitate the prediction of brain metastases arising from breast cancer.

Methods

The RNA transcript data from The Cancer Genome Atlas (TCGA) database was obtained for breast cancer, and the differentially expressed genes (DEGs) associated with tumor and brain tumor metastases were identified. Subsequently, key genes associated with survival prognosis were subsequently identified from the DEGs.

Results

Tripartite motif-containing protein 67 (TRIM67) was identified and the differential; in addition, the survival analyses of the TCGA database revealed that it was associated with brain tumor metastases and overall survival prognosis. Applying independent clinical cohort data, US-related features (microcalcification and lymph node metastasis) were associated with breast cancer tumor metastasis. Furthermore, ultrasonographic findings of microcalcifications showed correlations with TRIM67 expression. The study results revealed that six variables [stage, TRIM67, tumor size, regional lymph node staging (N), age, and HER2 status] were suitable predictors of tumor metastasis by applying support vector machine–recursive feature elimination. Among these, US-predicted tumor size correlated with tumor size classification, whereas US-predicted lymph node metastasis correlated with tumor N classification. The TRIM67 upregulation was accompanied by upregulation of the integrated breast cancer pathway; however, it leads to the downregulation of the miRNA targets in ECM and membrane receptors and the miRNAs involved in DNA damage response pathways.

Conclusions

The TRIM67 is a risk factor associated with brain metastases from breast cancer and it is considered a prognostic survival factor. The nomogram constructed from six variables—stage, TRIM67, tumor size, N, age, HER2 status—is an appropriate predictor to estimate the occurrence of breast cancer metastasis.
The Clustering Analysis of Time Properties in Patients With Cerebral Small Vessel Disease: A Dynamic Connectivity Study
Authors: Yin Wenwen , Zhou Xia , Li Chenchen , You Mengzhe , Wan Ke , Zhang Wei , Zhu Wenhao , Li Mingxu , Zhu Xiaoqun , Qian Yinfeng , Sun Zhongwu
Published: June 2022

Purpose

This study aimed to investigate the dynamic functional connectivity (DFC) pattern in cerebral small vessel disease (CSVD) and explore the relationships between DFC temporal properties and cognitive impairment in CSVD.

Methods

Functional data were collected from 67 CSVD patients, including 35 patients with subcortical vascular cognitive impairment (SVCI) and 32 cognitively unimpaired (CU) patients, as well as 35 healthy controls (HCs). The DFC properties were estimated by k-means clustering analysis. DFC strength analysis was used to explore the regional functional alterations between CSVD patients and HCs. Correlation analysis was used for DFC properties with cognition and SVD scores, respectively.

Results

The DFC analysis showed three distinct connectivity states (state I: sparsely connected, state II: strongly connected, state III: intermediate pattern). Compared to HCs, CSVD patients exhibited an increased proportion in state I and decreased proportion in state II. Besides, CSVD patients dwelled longer in state I while dwelled shorter in state II. CSVD subgroup analyses showed that state I frequently occurred and dwelled longer in SVCI compared with CSVD-CU. Also, the internetwork (frontal-parietal lobe, frontal-occipital lobe) and intranetwork (frontal lobe, occipital lobe) functional activities were obviously decreased in CSVD. Furthermore, the fractional windows and mean dwell time (MDT) in state I were negatively correlated with cognition in CSVD but opposite to cognition in state II.

Conclusion

Patients with CSVD accounted for a higher proportion and dwelled longer mean time in the sparsely connected state, while presented lower proportion and shorter mean dwell time in the strongly connected state, which was more prominent in SVCI. The changes in the DFC are associated with altered cognition in CSVD. This study provides a better explanation of the potential mechanism of CSVD patients with cognitive impairment from the perspective of DFC.
Systematic Review of Pre-injury Migraines as a Vulnerability Factor for Worse Outcome Following Sport-Related Concussion
Authors: Terry Douglas P. , Büttner Fionn , Huebschmann Nathan A. , Gardner Andrew J. , Cook Nathan E. , Iverson Grant L.
Published: June 2022

Background

Individuals with migraine disorders may be affected differently by concussions compared to individuals without migraine disorders. Prior studies on this topic have had mixed results. The purpose of this study was to systematically examine clinical outcomes following a sport-related concussion in athletes who have a pre-injury history of migraines.

Methods

All studies published prior to 15 May 2021 that examined pre-injury migraines as a possible predictor of clinical recovery from concussion were included. The search included (i) sport/athlete-related terms, (ii) concussion-related terms, and (iii) diverse predictor/modifier terms. After removing duplicates, 5,118 abstracts were screened, 538 full-text articles were reviewed, and 27 articles were included for narrative synthesis without meta-analysis (n = 25 with unique samples). Risk of bias was assessed using the domain-based Quality In Prognosis Studies (QUIPS) tool.

Results

Most studies did not find pre-injury migraines to be associated with concussion outcome, but several of these studies had small or very small sample sizes, as well as other methodological weaknesses. Risk of bias varied greatly across studies. Some of the larger, better-designed studies suggested pre-injury migraines may be a risk factor for worse concussion outcome. Most articles examined pre-injury migraines as an exploratory/secondary predictor of concussion outcome; very few were designed to examine migraine as the primary focus of the study. Migraine history was predominantly based on self-report and studies included minimal information about migraine (e.g., age of onset, frequency/severity, past treatment). Effect sizes were usually not reported or able to be calculated from reported study data.

Conclusion

There is some evidence to suggest that pre-injury migraines may be a vulnerability factor for a worse outcome following concussion, with studies having the lowest risk of bias reporting a positive association. Future studies should focus on improving methodological quality when assessing the relationship between pre-injury migraines and concussion outcome and better characterizing pre-injury migraine status.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128292, identifier: PROSPERO 2019 CRD42019128292.
The Effect of Neurofeedback on the Reaction Time and Cognitive Performance of Athletes: A Systematic Review and Meta-Analysis
Authors: Brito Michele Andrade de , Fernandes José Raimundo , Esteves Natã Sant'Anna , Müller Vanessa Teixeira , Alexandria Daniella Brito , Pérez Diego Ignacio Valenzuela , Slimani Maamer , Brito Ciro José , Bragazzi Nicola Luigi , Miarka Bianca
Published: June 2022

Our study evaluated the effect of training with neurofeedback (NFB) in improving athletes' reaction time and decision-making. A computerized search in PubMed, PsycINFO, Scielo, Web of Science, EMBASE, Scopus, BVS, and Cochrane databases was performed to identify studies published from 2011 to June 2021. The protocol was registered in PROSPERO. The quality of studies that was peer-reviewed and included was assessed using the Review Manager tool, Cochrane Risk of Bias, and design and reporting quality according to the CRED-nf checklist. Standard mean differences and 95% confidence intervals (CIs) were calculated and combined using a random-effects model. A total of 07 randomized controlled trials (RCTs) (173 athletes) met the inclusion criteria. Significant effects of NFB in the experimental group in relation to reaction time were found, indicating an improvement in sports performance [standardized mean difference (SMD) = −1.08; 95% CI = (−1.90, −0.25),p= 0.0009] and cognitive performance vs. decision-making with moderate effect [SMD = 1.12; 95% CI = (−0.40, 1.85),p= 0.0001]. However, the control group had a very small effect on cognitive performance [SMD = 0.19; 95% CI = (−0.20, 0.59),p= 0.086]. NFB could improve athletes' reaction time and decision-making, effectively increasing their performance in the sports field. Future studies should focus on standardized protocols for NFB training.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021258387.
Representation of Cone-Opponent Color Space in Macaque Early Visual Cortices
Authors: Du Xiao , Jiang Xinrui , Kuriki Ichiro , Takahata Toru , Zhou Tao , Roe Anna Wang , Tanigawa Hisashi
Published: June 2022

In primate vision, the encoding of color perception arises from three types of retinal cone cells (L, M, and S cones). The inputs from these cones are linearly integrated into two cone-opponent channels (cardinal axes) before the lateral geniculate nucleus. In subsequent visual cortical stages, color-preferring neurons cluster into functional domains within “blobs” in V1, “thin/color stripes” in V2, and “color bands” in V4. Here, we hypothesize that, with increasing cortical hierarchy, the functional organization of hue representation becomes more balanced and less dependent on cone opponency. To address this question, we used intrinsic signal optical imaging in macaque V1, V2, and V4 cortices to examine the domain-based representation of specific hues (here referred to as “hue domains”) in cone-opponent color space (4 cardinal and 4 intermediate hues). Interestingly, we found that in V1, the relative size of S-cone hue preference domain was significantly smaller than that for other hues. This notable difference was less prominent in V2, and, in V4 was virtually absent, resulting in a more balanced representation of hues. In V2, hue clusters contained sequences of shifting preference, while in V4 the organization of hue clusters was more complex. Pattern classification analysis of these hue maps showed that accuracy of hue classification improved from V1 to V2 to V4. These results suggest that hue representation by domains in the early cortical hierarchy reflects a transformation away from cone-opponency and toward a full-coverage representation of hue.
A Review of the Potential Effects of Melatonin in Compromised Mitochondrial Redox Activities in Elderly Patients With COVID-19
Authors: Su Wen-Lin , Wu Chia-Chao , Wu Shu-Fang Vivienne , Lee Mei-Chen , Liao Min-Tser , Lu Kuo-Cheng , Lu Chien-Lin
Published: June 2022

Melatonin, an endogenous indoleamine, is an antioxidant and anti-inflammatory molecule widely distributed in the body. It efficiently regulates pro-inflammatory and anti-inflammatory cytokines under various pathophysiological conditions. The melatonin rhythm, which is strongly associated with oxidative lesions and mitochondrial dysfunction, is also observed during the biological process of aging. Melatonin levels decline considerably with age and are related to numerous age-related illnesses. The signs of aging, including immune aging, increased basal inflammation, mitochondrial dysfunction, significant telomeric abrasion, and disrupted autophagy, contribute to the increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These characteristics can worsen the pathophysiological response of the elderly to SARS-CoV-2 and pose an additional risk of accelerating biological aging even after recovery. This review explains that the death rate of coronavirus disease (COVID-19) increases with chronic diseases and age, and the decline in melatonin levels, which is closely related to the mitochondrial dysfunction in the patient, affects the virus-related death rate. Further, melatonin can enhance mitochondrial function and limit virus-related diseases. Hence, melatonin supplementation in older people may be beneficial for the treatment of COVID-19.
Characterizing Adolescents' Dietary Intake by Taste: Results From the UK National Diet and Nutrition Survey
Authors: Bawajeeh Areej , Zulyniak Michael A. , Evans Charlotte E. L. , Cade Janet E.
Published: June 2022

The taste of foods is a key factor for adolescents' food choices and intakes, yet, exploring taste characteristics of adolescents' diet is limited. Using food records for 284 adolescents (10–19 years old) from the National Diet and Nutrition Survey (NDNS), year 9 (2016–2017), we classified diets according to taste. Tastes for each food consumed were generated from a previous survey that asked participants to allocate one main taste to each food. Responses from that survey were processed and included in a Hierarchical Cluster Analysis (HCA) to identify taste clusters. The resulting tastes were then applied to the adolescents' food records in the NDNS. For each individual, the total weight of food per day for each taste was calculated. A linear regression model was used to explore dietary intakes from each taste. Findings reveal that adolescents' daily energy intake was highest (34%) from foods that taste sweet. Sweet foods were the main calorie contributors at breakfast and daytime snacking, while energy intake from neutral-tasting foods was higher at lunch and dinner. Sweet food intake was significantly positively associated with higher energy, sugar, and fat intakes. For each percentage increase in sweet foods, energy increased by 10 kcal/d (95% CI 6, 15; P < 0.01). Savory food intake was lower in carbohydrates and sugars; with neutral food consumption inversely associated with energy, carbohydrate, sugars, saturated and total fat. Higher salty food intake was linked to higher saturated fat as well as sodium consumption. Sweet and neutral foods dominate the UK adolescent diet, followed by savory tastes. Balancing the contributions of different tasting foods could assist in improving adolescent diet quality.
Citrus Consumption and Risk of Melanoma: A Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Fang Xuexian , Han Dan , Yang Jun , Li Fulun , Sui Xinbing
Published: June 2022

Background

Epidemiological studies of citrus consumption in relation to melanoma risk have yielded conflicting results. This meta-analysis was performed to investigate the dose-response association between citrus consumption and risk of melanoma.

Methods

Relevant prospective cohort studies were identified by searching PubMed, Embase, Scopus, and Web of Science databases up to February 28th, 2022. Results from individual studies were pooled using a random-effects model.

Results

Five prospective studies, with 8,836 melanoma cases and 977,558 participants, were included in the meta-analysis. A significantly increased risk of melanoma was associated with the highest categories of either total citrus products (RR: 1.20; 95% CI: 1.01–1.42) or citrus fruit consumption (1.15; 1.04–1.28), but consumption of citrus juice was not associated with melanoma risk (1.08; 0.97–1.21). The dose-response analyses revealed that for per 1 serving/day increase in total citrus or citrus fruit consumption, the risk of melanoma increased by 9 and 12%, respectively. An inverted U-shaped curvilinear relationship, but not linear association, was observed between citrus juice consumption and melanoma risk.

Conclusions

Citrus consumption was generally associated with a greater risk of malignant melanoma. Our findings may have important public health implications with respect to preventing melanoma.
Attenuation of Postharvest Browning in Rambutan Fruit by Melatonin Is Associated With Inhibition of Phenolics Oxidation and Reinforcement of Antioxidative Process
Authors: Wei Dongling , Yang Jiali , Xiang Yue , Meng Lanhuan , Pan Yonggui , Zhang Zhengke
Published: June 2022

Rambutan is a famous tropical fruit with a unique flavor and considerable economic value. However, the high vulnerability to postharvest browning leads to a short shelf life of rambutan fruit. Melatonin (MT) is an excellent bioactive molecule that possesses the potential to improve the storability of the harvested crops. In this study, the physiological mechanism of exogenous MT in affecting pericarp browning and senescence of postharvest rambutan fruit was investigated. Experimental results showed that the application of MT at 0.125 mmol L–1 appreciably retarded the advancement of pericarp browning and color parameters (L*, a*, and b*). MT treatment inhibited the increase in membrane relative electrolytes leakage (REL) while lowering the accumulation of reactive oxygen species (ROS) (■O2– and H2O2) and malonaldehyde (MDA). Reduced phenolics oxidation, as indicated by higher contents of total phenolics, flavonoids, and anthocyanins along with fewer activities of peroxidase (POD) and polyphenol oxidase (PPO), was detected in MT fruit compared with control fruit. MT treatment maintained the cellular redox state by inducing antioxidant enzyme activity and reinforcing the ascorbate-glutathione (AsA-GSH) cycle. Furthermore, the ultrastructural observation revealed that the spoilage of cellular and subcellular structures was milder in MT fruit than that in control fruit. The results suggest that MT could ameliorate the browning and senescence of rambutan fruit by inhibiting phenolic oxidation and enhancing the antioxidative process.
Investigation Into Environmental Selenium and Arsenic Levels and Arseniasis Prevalence in an Arsenic-Affected Coal-Burning Area
Authors: Bai Ai-Mei , Li Qian , Li Yue , Fan Zhong-Xue , Li Xiao-Qian , Tan Wen-Hong , Cao Dong-Yuan , Kang Yi-Jun
Published: June 2022

This study aims to explore whether selenium (Se) concentration correlates with arseniasis in a high-arsenic coal area in the southern Shaanxi Province, China. Herein, an epidemiological investigation was conducted among 100 arsenic (As)-poisoned patients in Ziyang County, an area with high soil As and Se levels. Fifty healthy subjects were selected from areas without endemic As poisoning. The subjects in the high-As coal area were diagnosed with either normal, suspicious, mild, moderate, or severe As poisoning. Local coal, water, soil, corn, and pepper samples, as well as hair, blood, and urine samples of subjects and patients were collected and analyzed for their As and Se contents. The contents of As and Se in coal, soil, corn, pepper, and hair samples from Ziyang County were significantly higher than those in the control area. The As content of hair in Ziyang County positively correlated with As poisoning, whereas the Se content of hair and urine negatively correlated with As poisoning. The Se content in the body was negatively correlated with the degree of As poisoning, indicating that Se may accelerate the metabolism and decumulation of As and antagonize As toxicity.
The Effects of Different Induction Chemotherapy Cycles and Adjuvant Chemotherapy on the Survival Outcomes of Patients With Locally Advanced Nasopharyngeal Carcinoma
Authors: Liao Shu , Diao Yunlian , Ling Qingyuan , Xiong Zhijuan , Deng Wenxin , Zhang Ping , Zhang Congkai , Ying Ying , Zhong Xiaojun , Zhang Wei
Published: June 2022

Objective

This study investigated whether differences in the induction chemotherapy (IC) cycle number and adjuvant chemotherapy (AC) affect survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

Methods

The survival outcomes of 386 consecutive LA-NPC patients treated between January 2015 and March 2018 were retrospectively analyzed. Univariate and multivariate analyses were used to compare treatment groups defined by IC< 3 or ≥3 IC cycles followed by radiotherapy with or without AC (i.e., IC<3+AC, IC<3+non-AC, IC≥3+AC, and IC≥3+non-AC groups).

Results

The median follow-up time was 53 months (range: 2-74 months) and the median number of IC cycles was 2 (range: 1-6 cycles). The 3-year overall survival (OS) rate was significantly higher in patients with IC≥3 cycles compared to IC<3 cycles (95.7% vs. 90.3%, P=0.020). Multivariate analysis indicated that the IC cycle number is an independent factor for OS (hazard ratio=0.326, P=0.007). Furthermore, patients in the IC<3+AC group had a better OS rate than those in the IC<3+non-AC group (91.6% vs. 79.1%, P=0.030), indicating that AC positively affected OS in patients with IC<3. However, no significant difference in the OS rate was found between IC≥3+non-AC and IC≥3+AC groups (92.1% vs. 94.6%, P =0.550).

Conclusion

The IC cycle number appears to be an independent prognostic factor for higher OS in LA-NPC patients who received ≥3 cycles. Sequential AC after IC plus radiotherapy may improve OS in patients with IC<3 cycles.
Dissecting the Roles of PDCD4 in Breast Cancer
Authors: Cai Qian , Yang Hsin-Sheng , Li Yi-Chen , Zhu Jiang
Published: June 2022

The human programmed cell death 4 (PDCD4) gene was mapped at chromosome 10q24 and encodes the PDCD4 protein comprised of 469 amino acids. PDCD4 inhibits protein translation PDCD4 inhibits protein translation to suppress tumor progression, and its expression is frequently decreased in breast cancer. PDCD4 blocks translation initiation complex by binding eIF4AviaMA-3 domains or by directly binding 5’ mRNA internal ribosome entry sites with an RNA binding domain to suppress breast cancer progression and proliferation. Numerous regulators and biological processes including non-coding RNAs, proteasomes, estrogen, natural compounds and inflammation control PDCD4 expression in breast cancer. Loss of PDCD4 expression is also responsible for drug resistance in breast cancer. HER2 activation downregulates PDCD4 expression by activating MAPK, AKT, and miR-21 in aromatase inhibitor-resistant breast cancer cells. Moreover, modulating the microRNA/PDCD4 axis maybe an effective strategy for overcoming chemoresistance in breast cancer. Down-regulation of PDCD4 is significantly associated with short overall survival of patients, which suggests that PDCD4 may be an independent prognostic marker for breast cancer.
Emerging Role of Helicobacter pylori in the Immune Evasion Mechanism of Gastric Cancer: An Insight Into Tumor Microenvironment-Pathogen Interaction
Authors: Li Zhifang , Zhang Wenqing , Bai Jinyang , Li Jing , Li Hong
Published: June 2022

Helicobacter pylori (H. pylori) infection is the strongest causative factor of gastric cancer. Growing evidence suggests that the complex crosstalk of H. pylori and the tumor microenvironment (TME) exerts a profound influence on gastric cancer progression. Hence, there is emerging interest to in-depth comprehension of the mechanisms of interplay between H. pylori and the TME. This review discusses the regulatory mechanisms underlying the crosstalk between H. pylori infection and immune and stromal cells, including tumor-associated macrophages (TAMs), neutrophils, dendritic cells, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, B and T cells, cancer associated fibroblasts (CAFs), and mesenchymal stem cells (MSCs), within the TME. Such knowledge will deepen the understanding about the roles of H. pylori in the immune evasion mechanism in gastric cancer and contribute to the development of more effective treatment regimens against H. pylori-induced gastric cancer.
Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma
Authors: Ollila Hely , Mäyränpää Mikko I. , Paavolainen Lassi , Paajanen Juuso , Välimäki Katja , Sutinen Eva , Wolff Henrik , Räsänen Jari , Kallioniemi Olli , Myllärniemi Marjukka , Ilonen Ilkka , Pellinen Teijo
Published: June 2022

Background

Pleural mesothelioma (MPM) is an aggressive malignancy with an average patient survival of only 10 months. Interestingly, about 5%–10% of the patients survive remarkably longer. Prior studies have suggested that the tumor immune microenvironment (TIME) has potential prognostic value in MPM. We hypothesized that high-resolution single-cell spatial profiling of the TIME would make it possible to identify subpopulations of patients with long survival and identify immunophenotypes for the development of novel treatment strategies.

Methods

We used multiplexed fluorescence immunohistochemistry (mfIHC) and cell-based image analysis to define spatial TIME immunophenotypes in 69 patients with epithelioid MPM (20 patients surviving ≥ 36 months). Five mfIHC panels (altogether 21 antibodies) were used to classify tumor-associated stromal cells and different immune cell populations. Prognostic associations were evaluated using univariate and multivariable Cox regression, as well as combination risk models with area under receiver operating characteristic curve (AUROC) analyses.

Results

We observed that type M2 pro-tumorigenic macrophages (CD163+pSTAT1−HLA-DRA1−) were independently associated with shorter survival, whereas granzyme B+ cells and CD11c+ cells were independently associated with longer survival. CD11c+ cells were the only immunophenotype increasing the AUROC (from 0.67 to 0.84) when added to clinical factors (age, gender, clinical stage, and grade).

Conclusion

High-resolution, deep profiling of TIME in MPM defined subgroups associated with both poor (M2 macrophages) and favorable (granzyme B/CD11c positivity) patient survival. CD11c positivity stood out as the most potential prognostic cell subtype adding prediction power to the clinical factors. These findings help to understand the critical determinants of TIME for risk and therapeutic stratification purposes in MPM.
Role of Pneumonectomy in T1–4N2M0 Non-Small Cell Lung Cancer: A Propensity Score Matching Analysis
Authors: Wang Suyu , Wang Qing , Zhu Wanli , Wei Juan , Feng Di , Lv Xin , Liu Meiyun
Published: June 2022

Background

N2 stage disease constitutes approximately 20%–30% of all non-small cell lung cancer (NSCLC). Concurrently, surgery remains the first-choice treatment for patients with N2 NSCLC if feasible. However, the role of pneumonectomy in N2 NSCLC has rarely been investigated and remains controversial.

Methods

We enrolled 26,798 patients with T1–4N2M0 NSCLC (stage IIIA/IIIB) from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. We compared the overall survival (OS) and cancer-specific survival (CSS) between patients who received pneumonectomy and those who did not receive surgery. The Kaplan–Meier method, Cox regression analyses, and propensity score matching (PSM) were applied to demonstrate the effect of pneumonectomy.

Results

Patients receiving pneumonectomy had a significantly better OS and CSS than those without pneumonectomy both before [adjusted-HR (95% CI): 0.461 (0.425–0.501) for OS, 0.444 (0.406–0.485) for CSS] and after PSM [adjusted-HR (95% CI): 0.499 (0.445–0.560) for OS, 0.457 (0.405–0.517) for CSS] with all p-values <0.001. Subgroup analysis demonstrated concordant results stratified by demographic or clinicopathological variables. In sensitivity analysis, no significant difference was observed between patients receiving single pneumonectomy and chemoradiotherapy without surgery in OS and CSS both before [unadjusted-HR (95% CI): 1.016 (0.878–1.176) for OS, 0.934 (0.794–1.099) for CSS, p = 0.832] and after PSM [unadjusted-HR (95% CI): 0.988 (0.799–1.222) for OS, 0.938 (0.744–1.182) for CSS] with all p-values >0.4.

Conclusion

For patients with T1–4N2M0 NSCLC (stage IIIA/IIIB), pneumonectomy is an independent protective factor of OS and should be considered when applicable.
Advances in the Study of circRNAs in Hematological Malignancies
Authors: Du Jingyi , Jia Feiyu , Wang Lijuan
Published: June 2022

Circular RNAs (circRNAs) are non–protein-coding RNAs that have a circular structure and do not possess a 5` cap or 3` poly-A tail. Their structure is more stable than that of linear RNAs, and they are difficult to deform via hydrolysis. Advancements in measurement technology such as RNA sequencing have enabled the detection of circRNAs in various eukaryotes in both in vitro and in vivo studies. The main function of circRNAs involves sponging of microRNAs (MiRNAs) and interaction with proteins associated with physiological and pathological processes, while some circRNAs are involved in translation. circRNAs act as tumor suppressors or oncogenes during the development of many tumors and are emerging as new diagnostic and prognostic biomarkers. They also affect resistance to certain chemotherapy drugs such as imatinib. The objective of this review is to investigate the expression and clinical significance of circRNAs in hematological malignancies. We will also explore the effect of circRNAs on proliferation and apoptosis in hematological malignancy cells and their possible use as biomarkers or targets to determine prognoses. The current literature indicates that circRNAs may provide new therapeutic strategies for patients with hematologic malignancies.
Radiomics-Based Machine Learning Models for Predicting P504s/P63 Immunohistochemical Expression: A Noninvasive Diagnostic Tool for Prostate Cancer
Authors: Liu Yun-Fan , Shu Xin , Qiao Xiao-Feng , Ai Guang-Yong , Liu Li , Liao Jun , Qian Shuang , He Xiao-Jing
Published: June 2022

Objective

To develop and validate a noninvasive radiomic-based machine learning (ML) model to identify P504s/P63 status and further achieve the diagnosis of prostate cancer (PCa).

Methods

A retrospective dataset of patients with preoperative prostate MRI examination and P504s/P63 pathological immunohistochemical results between June 2016 and February 2021 was conducted. As indicated by P504s/P63 expression, the patients were divided into label 0 (atypical prostatic hyperplasia), label 1 (benign prostatic hyperplasia, BPH) and label 2 (PCa) groups. This study employed T2WI, DWI and ADC sequences to assess prostate diseases and manually segmented regions of interest (ROIs) with Artificial Intelligence Kit software for radiomics feature acquisition. Feature dimensionality reduction and selection were performed by using a mutual information algorithm. Based on screened features, P504s/P63 prediction models were established by random forest (RF), gradient boosting decision tree (GBDT), logistic regression (LR), adaptive boosting (AdaBoost) and k-nearest neighbor (KNN) algorithms. The performance was evaluated by the area under the ROC curve (AUC) and accuracy.

Results

A total of 315 patients were enrolled. Among the 851 radiomic features, the 32 top features were derived from T2WI, in which the gray-level run length matrix (GLRLM) and gray-level cooccurrence matrix (GLCM) features accounted for the largest proportion. Among the five models, the RF algorithm performed best in general evaluations (microaverage AUC=0.920, macroaverage AUC=0.870) and provided the most accurate result in further sublabel prediction (the accuracies of label 0, 1, and 2 were 0.831, 0.831, and 0.932, respectively). In comparative sequence analyses, T2WI was the best single-sequence candidate (microaverage AUC=0.94 and macroaverage AUC=0.78). The merged datasets of T2WI, DWI, and ADC yielded optimal AUCs (microaverage AUC=0.930 and macroaverage AUC=0.900).

Conclusions

The radiomic-based RF classifier has the potential to be used to evaluate the presurgical P504s/P63 status and further diagnose PCa noninvasively and accurately.
Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer
Authors: Luo Chenyi , Wang Peipei , He Siqi , Zhu Jingjing , Shi Yuanyuan , Wang Jianxun
Published: June 2022

Breast cancer is the most commonly diagnosed cancer (estimated 2.3 million new cases in 2020) and the leading cause of cancer death (estimated 685,000 deaths in 2020) in women globally. Breast cancers have been categorized into four major molecular subtypes based on the immunohistochemistry (IHC) expression of classic hormone and growth factor receptors including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as a proliferation marker Ki-67 protein expression. Triple-negative breast cancer (TNBC), a breast cancer subtype lacking ER, PR, and HER2 expression, is associated with a high metastatic potential and poor prognosis. TNBC accounts for approximately only 15%–20% of new breast cancer diagnoses; it is responsible for most breast cancer–related deaths due to the lack of targeted treatment options for this patient population, and currently, systemic chemotherapy, radiation, and surgical excision remain the major treatment modalities for these patients with TNBC. Although breast cancer patients in general do not have a robust response to the immunotherapy, a subset of TNBC has been demonstrated to have high tumor mutation burden and high tumor-infiltrating lymphocytes, resembling the features observed on melanoma or lung cancers, which can benefit from the treatment of immune checkpoint inhibitors (ICIs). Therefore, the immunogenic nature of this aggressive disease has presented an opportunity for the development of TNBC-targeting immunotherapies. The recent US Food and Drug Administration approval of atezolizumab in combination with the chemotherapeutic agent nab-paclitaxel for the treatment of PD-L1-positive unresectable, locally advanced, or metastatic TNBC has led to a new era of immunotherapy in TNBC treatment. In addition, immunotherapy becomes an active research area, both in the cancer biology field and in the oncology field. In this review, we will extend our coverage on recent discoveries in preclinical research and early results in clinical trials from immune molecule-based therapy including cytokines, monoclonal antibodies, antibody–drug conjugates, bi-specific or tri-specific antibodies, ICIs, and neoantigen cancer vaccines; oncolytic virus-based therapies and adoptive immune cell transfer–based therapies including TIL, chimeric antigen receptor-T (CAR-T), CAR-NK, CAR-M, and T-cell receptor-T. In the end, we will list a series of the challenges and opportunities in immunotherapy prospectively and reveal novel technologies such as high-throughput single-cell sequencing and CRISPR gene editing-based screening to generate new knowledges of immunotherapy.
Nomogram for Estimating the Risks of Intestinal Ischemia and Necrosis in Neonates With Midgut Volvulus: A Retrospective Study
Authors: Guan Xisi , Wang Zhe , He Qiuming , Lv Junjian , Yu Jiakang , Zhong Wei
Published: June 2022

Background

Delayed diagnosis and inaccurate judgment of the severity of the disease may be the principal reasons for the poor prognosis associated with neonatal midgut volvulus. We aimed to develop a nomogram model that timely assesses the risks of intestinal ischemia and necrosis in the neonate with midgut volvulus.

Materials and Methods

We retrospectively analyzed the clinical data from neonates with midgut volvulus who were admitted to Guangzhou Women and Children’s Medical Center from January 2009 to December 2019. Univariate and multivariate analyses were used to obtain independent factors to build a predictive model. The independent factors were used to develop the nomogram model.

Results

Heart rate, mean arterial pressure, serum C-reactive protein, serum sodium, serum albumin, and pH levels were independent predictors for intestinal ischemia and necrosis in patients with midgut volvulus. The area under the receiver operating characteristic curve (AUC) of the predictive model was 0.985 (95% confidence interval, 0.966–0.999; P < 0.001). The sensitivity was 90.48%, and the specificity was 93.10%. A nomogram model was established using the six independent predictors, with a C-index of 0.859 and a favorable consistency between the predicted and actual intestinal ischemia and necrosis rates according to the internal validation.

Conclusion

The constructed nomogram model could be a superior tool for predicting intestinal ischemia and necrosis in neonates with midgut volvulus.
Molecular Mechanism of Caffeine in Preventing Bronchopulmonary Dysplasia in Premature Infants
Authors: Tian Congliang , Li Danni , Fu Jianhua
Published: June 2022

Bronchopulmonary dysplasia (BPD) is a chronic respiratory complication commonly seen in premature infants. Following continuous advances in neonatal intensive care diagnosis and treatment technology, an increasing number of premature babies are being treated successfully. Despite these remarkable improvements, there has been no significant decline in the incidence of BPD; in fact, its incidence has increased as more extremely preterm infants survive. Therefore, in view of the impact of BPD on the physical and mental health of children and the increased familial and social burden on these children, early prevention of BPD is emphasized. In recent decades, the clinical application of caffeine in treating primary apnea in premature infants was shown not only to stimulate the respiratory center but also to confer obvious protection to the nervous and respiratory systems. Numerous clinical cross-sectional and longitudinal studies have shown that caffeine plays a significant role in the prevention and treatment of BPD, but there is a lack of overall understanding of its potential molecular mechanisms. In this review, we summarize the possible molecular mechanisms of caffeine in the prevention or treatment of BPD, aiming to better guide its clinical application.
Application of Pharmacokinetic/Pharmacodynamic Modeling to Bridge Mouse Antitumor Efficacy and Monkey Toxicology Data for Determining the Therapeutic Index of an Interleukin-10 Fc Fusion Protein
Authors: Yang Zheng , Loy James , Poirson Brian , Dai Yanshan , Rajendran Surendran , Xu Shihua , Spires Vanessa , Gururajan Murali , Lin Zheng , Arbanas Jaren , Carl Stephen , Pace Samantha , Wang Yun , Mehl John , Vasudevan Krishna , Spires Thomas , Novosiadly Ruslan , Coker Shodeinde , Perez Raymond , Covello Kelly , Morin Paul , Graziano Robert , Broz Miranda , Lehman-McKeeman Lois
Published: June 2022

Pharmacokinetic/pharmacodynamic (PK/PD) modeling was performed to quantitatively integrate preclinical pharmacology and toxicology data for determining the therapeutic index (TI) of an interleukin-10 (IL-10) fragment crystallizable (Fc) fusion protein. Mouse Fc fused with mouse IL-10 (mFc-mIL-10) was studied in mice for antitumor efficacy, and the elevation of interleukin-18 (IL-18) was examined as a PD biomarker. The in vivo mFc-mIL-10 EC50 for the IL-18 induction was estimated to be 2.4 nM, similar to the in vitro receptor binding affinity (Kd) of 3.2 nM. The IL-18 induction was further evaluated in cynomolgus monkeys, where the in vivo induction EC50 by a human IL-10 human Fc-fusion protein (hFc-hIL-10) was 0.08 nM vs. 0.3 nM measured as the in vitro Kd. The extent of the IL-18 induction correlated with mouse antitumor efficacy and was used to connect mouse efficacy to that in monkeys. The PD-based efficacious dose projected in monkeys was comparable to the results obtained using a PK-based method in which mouse efficacious exposure was targeted and corrected for affinity differences between the species. Furthermore, PK/PD relationships were developed for anemia and thrombocytopenia in monkeys treated with hFc-hIL-10, with thrombocytopenia predicted to be dose-limiting toxicity. Using quantitative pharmacology and toxicology information obtained through modeling work in the same species, the TI of hFc-hIL-10 in monkeys was determined to be 2.4 (vs. PD-based efficacy) and 1.2–3 (vs. PK-based efficacy), indicating a narrow safety margin. The model-based approaches were proven valuable to the developability assessment of the IL-10 Fc-fusion protein.
Prevalence of Polypharmacy and Potentially Inappropriate Medications Use in Elderly Chinese Patients: A Systematic Review and Meta-Analysis
Authors: Tian Fangyuan , Chen Zhaoyan , Wu Jinhui
Published: June 2022

Objectives: Polypharmacy and potentially inappropriate medication (PIM) use among elderly Chinese patients have not yet been investigated by systematic review and meta-analysis. The purposes of this study were to investigate the prevalence of polypharmacy and PIM use and the risk factors associated with PIM use in elderly Chinese patients.

Methods: Databases including PubMed, EMBase, and Web of Science were searched to collect studies which used Chinese criteria, Beers criteria, or STOPP criteria to evaluate the PIM status of elderly Chinese patients from inception to August 2021 (PROSPERO Code No: CRD42021262821). Observational studies reporting the prevalence of polypharmacy and PIM use in elderly Chinese patients were meta-analyzed. The pooled prevalence and risk ratio (RR) were calculated with a 95% confidence interval (CI).

Results: A total of 8 articles involving 4,558,786 patients were included. The overall prevalence of polypharmacy (concomitant use of more than 5 medicines) and PIM use pooled by meta-analysis in Chinese older patients was 48% (95% CI: 0.17, 0.79, p = 0.003) (inpatients 73%, outpatients 23%) and 39% (95% CI: 0.25, 0.54, p < 0.001) (inpatients 50%, outpatients 29%), respectively. Polypharmacy (RR: 2.03, 95% CI: 1.13, 3.64) was significantly associated with PIM use.

Conclusion: This meta-analysis demonstrated a high prevalence of polypharmacy and PIM use among elderly patients in China. Affected by the quantity and quality of the included studies, the aforementioned conclusions need to be confirmed by large samples and high-quality studies.
Curcumenol Mitigates the Inflammation and Ameliorates the Catabolism Status of the Intervertebral Discs In Vivo and In Vitro via Inhibiting the TNFα/NFκB Pathway
Authors: Yang Xiao , Li Baixing , Tian Haijun , Cheng Xiaofei , Zhou Tangjun , Zhao Jie
Published: June 2022

Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is accredited to the release of inflammatory cytokines followed by biomechanical and structural deterioration. In our study, we used a plant-derived medicine, curcumenol, to treat IVDD. A cell viability test was carried out to evaluate the possibility of using curcumenol. RNA-seq was used to determine relative pathways involved with curcumenol addition. Using TNFα as a trigger of inflammation, the activation of the NF-κB signaling pathway and expression of the MMP family were determined by qPCR and western blotting. Nucleus pulposus (NP) cells and the rats’ primary NP cells were cultured. The catabolism status was evaluated by an ex vivo model. A lumbar instability mouse model was carried out to show the effects of curcumenol in vivo. In general, RNA-seq revealed that multiple signaling pathways changed with curcumenol addition, especially the TNFα/NF-κB pathway. So, the NP cells and primary NP cells were induced to suffer inflammation with the activated TNFα/NF-κB signaling pathway and increased expression of the MMP family, such as MMP3, MMP9, and MMP13, which would be mitigated by curcumenol. Owing to the protective effects of curcumenol, the height loss and osteophyte formation of the disc could be prevented in the lumbar instability mouse model in vivo.
Pipersentan: A De Novo Synthetic Endothelin Receptor Antagonist that Inhibits Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension
Authors: Zhang Zeyu , Liu Chunlei , Bai Yongyi , Li Xin , Gao Xiaojian , Li Chen , Guo Ge , Chen Si , Sun Mingzhuang , Liu Kang , Li Yang , He Kunlun
Published: June 2022

Background: Although major advances have been made in the pathogenesis and management of pulmonary arterial hypertension (PAH), the endothelin system is still considered to play a vital role in the pathology of PAH due to its vasoconstrictive action. Endothelin receptor antagonists (ERAs), either as monotherapy or in combination with other drugs, have attracted much attention in the treatment of this lethal disease, and research is continuing.

Methods: A novel ERA, pipersentan 5-(1,3-Benzodioxol-5-yl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-N-(2-methoxyethylsulfamoyl)pyrimidin-4-amine, was recently synthesized and the physicochemical characterizations and the pharmacology both in vitro and in vivo were studied.

Results: This orally administered ERA can both competitively and selectively inhibit the binding of endothelin-1 (ET-1) to its receptors with good physicochemical characteristics. Pipersentan efficaciously antagonized the effects of ET-1 on pulmonary artery smooth muscle cell proliferation, migration and calcium mobilization and effectively improved right ventricular hypertrophy and pulmonary arterial pressure in both monocrotaline- and hypoxia-induced pulmonary hypertension (PH) rat models.

Conclusions: This profile identifies pipersentan as a new agent for treating ET-1 system activation-related PH.
Neuroinflammation Involved in Diabetes-Related Pain and Itch
Authors: Fang Xiao-Xia , Wang Heng , Song Hao-Lin , Wang Juan , Zhang Zhi-Jun
Published: June 2022

Diabetes mellitus (DM) is a global epidemic with increasing incidence, which results in diverse complications, seriously affects the patient quality of life, and brings huge economic burdens to society. Diabetic neuropathy is the most common chronic complication of DM, resulting in neuropathic pain and chronic itch. The precise mechanisms of diabetic neuropathy have not been fully clarified, hindering the exploration of novel therapies for diabetic neuropathy and its terrible symptoms such as diabetic pain and itch. Accumulating evidence suggests that neuroinflammation plays a critical role in the pathophysiologic process of neuropathic pain and chronic itch. Indeed, researchers have currently made significant progress in knowing the role of glial cells and the pro-inflammatory mediators produced from glial cells in the modulation of chronic pain and itch signal processing. Here, we provide an overview of the current understanding of neuroinflammation in contributing to the sensitization of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, we also summarize the inflammation mechanisms that contribute to the pathogenesis of diabetic itch, including activation of glial cells, oxidative stress, and pro-inflammatory factors. Targeting excessive neuroinflammation may provide potential and effective therapies for the treatment of chronic neuropathic pain and itch in DM.