bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Computed Tomography Parameters in Coronavirus Disease 2019 Patients and Prediction of Respiratory Outcomes Using a Decision Tree
Authors: Kang Jieun , Kang Jiyeon , Seo Woo Jung , Park So Hee , Kang Hyung Koo , Park Hye Kyeong , Song Je Eun , Kwak Yee Gyung , Chang Jeonghyun , Kim Sollip , Kim Ki Hwan , Park Junseok , Choe Won Joo , Lee Sung-Soon , Koo Hyeon-Kyoung
Published: May 2022

Background

Chest computed tomography (CT) scans play an important role in the diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to describe the quantitative CT parameters in COVID-19 patients according to disease severity and build decision trees for predicting respiratory outcomes using the quantitative CT parameters.

Methods

Patients hospitalized for COVID-19 were classified based on the level of disease severity: (1) no pneumonia or hypoxia, (2) pneumonia without hypoxia, (3) hypoxia without respiratory failure, and (4) respiratory failure. High attenuation area (HAA) was defined as the quantified percentage of imaged lung volume with attenuation values between −600 and −250 Hounsfield units (HU). Decision tree models were built with clinical variables and initial laboratory values (model 1) and including quantitative CT parameters in addition to them (model 2).

Results

A total of 387 patients were analyzed. The mean age was 57.8 years, and 50.3% were women. HAA increased as the severity of respiratory outcome increased. HAA showed a moderate correlation with lactate dehydrogenases (LDH) and C-reactive protein (CRP). In the decision tree of model 1, the CRP, fibrinogen, LDH, and gene Ct value were chosen as classifiers whereas LDH, HAA, fibrinogen, vaccination status, and neutrophil (%) were chosen in model 2. For predicting respiratory failure, the decision tree built with quantitative CT parameters showed a greater accuracy than the model without CT parameters.

Conclusions

The decision tree could provide higher accuracy for predicting respiratory failure when quantitative CT parameters were considered in addition to clinical characteristics, PCR Ct value, and blood biomarkers.
Secretory Vesicle and Glucoamylase Distribution in Aspergillus niger and Macromorphology in Regions of Varying Shear Stress
Authors: Kunz Philipp , King Rudibert
Published: May 2022

In technical fermentations, filamentous microorganisms are exposed to different forms of mechanical stress, among which shear stress is prevalent in turbulent broths. Whereas small-scale bioreactors allow for realistic turbulent flow field conditions, they are not well-suited to investigate the fungal response to shear stress in more detail, as they only reveal the integral effect of a highly dynamic stress stimulus. Therefore, the widely used model system for producing constant, but rather low shear forces, the parallel plate flow chamber, is extended in this work by adding a backward-facing step (BFS). The BFS induces vortex shedding in the wake of the step and brings out distinct areas of different shear stress levels at the bottom of the chamber where mycelia grow. This allows for a stress-dependent analysis of growing cells using a confocal laser-scanning microscope. As the real stress cannot be measured in the experiment, the wall shear stress is estimated numerically using computational fluid dynamics (CFD). As a first application of the experimental setup, the relative biomass concentration, the relative amount of secretory vesicles and the relative amount of the chosen product glucoamylase produced by the filamentous fungus Aspergillus niger were measured. The obtained area scans show homogeneous mycelia growth in areas of low stress and cloud-like patterns downstream of the predicted flow reattachment length where high shear stress dominates. Quantitative analysis of the time course suggests that the amount of available secretory vesicles inside of A. niger decreases when the shear stress is increased, despite that no significant differences in biomass production could be found. In contrast, the highest level of glucoamylase was reached for intermediate volumetric flow rates, i.e., levels of shear stress.
Malaria-Transmitting Vectors Microbiota: Overview and Interactions With Anopheles Mosquito Biology
Authors: Djihinto Oswald Y. , Medjigbodo Adandé A. , Gangbadja Albert R. A. , Saizonou Helga M. , Lagnika Hamirath O. , Nanmede Dyane , Djossou Laurette , Bohounton Roméo , Sovegnon Pierre Marie , Fanou Marie-Joel , Agonhossou Romuald , Akoton Romaric , Mousse Wassiyath , Djogbénou Luc S.
Published: May 2022

Malaria remains a vector-borne infectious disease that is still a major public health concern worldwide, especially in tropical regions. Malaria is caused by a protozoan parasite of the genus Plasmodium and transmitted through the bite of infected female Anopheles mosquitoes. The control interventions targeting mosquito vectors have achieved significant success during the last two decades and rely mainly on the use of chemical insecticides through the insecticide-treated nets (ITNs) and indoor residual spraying (IRS). Unfortunately, resistance to conventional insecticides currently being used in public health is spreading in the natural mosquito populations, hampering the long-term success of the current vector control strategies. Thus, to achieve the goal of malaria elimination, it appears necessary to improve vector control approaches through the development of novel environment-friendly tools. Mosquito microbiota has by now given rise to the expansion of innovative control tools, such as the use of endosymbionts to target insect vectors, known as “symbiotic control.” In this review, we will present the viral, fungal and bacterial diversity of Anopheles mosquitoes, including the bacteriophages. This review discusses the likely interactions between the vector microbiota and its fitness and resistance to insecticides.
Tracing Lipid Metabolism by Alkyne Lipids and Mass Spectrometry: The State of the Art
Authors: Kuerschner Lars , Thiele Christoph
Published: May 2022

Lipid tracing studies are a key method to gain a better understanding of the complex metabolic network lipids are involved in. In recent years, alkyne lipid tracers and mass spectrometry have been developed as powerful tools for such studies. This study aims to review the present standing of the underlying technique, highlight major findings the strategy allowed for, summarize its advantages, and discuss some limitations. In addition, an outlook on future developments is given.
Identifying Cognitive Impairment in Elderly Using Coupling Functions Between Cerebral Oxyhemoglobin and Arterial Blood Pressure
Authors: Li Wenhao , Qu Guanwen , Huo Congcong , Hu Xiaoling , Xu Gongcheng , Li Huiyuan , Zhang Jingsha , Li Zengyong
Published: May 2022

Background

This study aimed to assess brain oxygenation status and cerebral autoregulation function in subjects with cognitive dysfunction.

Methods

The Montreal Cognitive Assessment (MoCA) was applied to divide the subjects into three groups: cognitive impairment (Group CI, 72.50 ± 10.93 y), mild cognitive impairment (Group MCI, 72.02 ± 9.90 y), and normal cognition (Group NC, 70.72 ± 7.66 y). Near-infrared spectroscopy technology and a non-invasive blood pressure device were used to simultaneously measure changes in cerebral tissue oxygenation signals in the bilateral prefrontal lobes (LPFC/RPFC) and arterial blood pressure (ABP) signals from subjects in the resting state (15 min). The coupling between ABP and cerebral oxyhemoglobin concentrations (Δ [O2Hb]) was calculated in very-low-frequency (VLF, 0.02–0.07 Hz) and low-frequency (LF, 0.07–0.2 Hz) bands based on the dynamical Bayesian inference approach. Pearson correlation analyses were used to study the relationships between MoCA scores, tissue oxygenation index, and strength of coupling function.

Results

In the interval VLF, Group CI (p = 0.001) and Group MCI (p = 0.013) exhibited significantly higher coupling strength from ABP to Δ [O2Hb] in the LPFC than Group NC. In the interval LF, coupling strength from ABP to Δ [O2Hb] in the LPFC was significantly higher in Group CI than in Group NC (p = 0.001). Pearson correlation results showed that MoCA scores had a significant positive correlation with the tissue oxygenation index and a significant negative correlation with the coupling strength from ABP to Δ [O2Hb].

Conclusion

The significantly increased coupling strength may be evidence of impaired cerebral autoregulation function in subjects with cognitive dysfunction. The Pearson correlation results suggest that indicators of brain oxygenation status and cerebral autoregulation function can reflect cognitive function. This study provides insights into the mechanisms underlying the pathophysiology of cognitive impairment and provides objective indicators for screening cognitive impairment in the elderly population.
Toward a Unified Analysis of the Brain Criticality Hypothesis: Reviewing Several Available Tools
Authors: Yu Chaojun
Published: May 2022

The study of the brain criticality hypothesis has been going on for about 20 years, various models and methods have been developed for probing this field, together with large amounts of controversial experimental findings. However, no standardized protocol of analysis has been established so far. Therefore, hoping to make some contributions to standardization of such analysis, we review several available tools used for estimating the criticality of the brain in this paper.
Deep Residual Convolutional Neural Networks for Brain–Computer Interface to Visualize Neural Processing of Hand Movements in the Human Brain
Authors: Fujiwara Yosuke , Ushiba Junichi
Published: May 2022

Concomitant with the development of deep learning, brain–computer interface (BCI) decoding technology has been rapidly evolving. Convolutional neural networks (CNNs), which are generally used as electroencephalography (EEG) classification models, are often deployed in BCI prototypes to improve the estimation accuracy of a participant's brain activity. However, because most BCI models are trained, validated, and testedviawithin-subject cross-validation and there is no corresponding generalization model, their applicability to unknown participants is not guaranteed. In this study, to facilitate the generalization of BCI model performance to unknown participants, we trained a model comprising multiple layers of residual CNNs and visualized the reasons for BCI classification to reveal the location and timing of neural activities that contribute to classification. Specifically, to develop a BCI that can distinguish between rest, left-hand movement, and right-hand movement tasks with high accuracy, we created multilayers of CNNs, inserted residual networks into the multilayers, and used a larger dataset than in previous studies. The constructed model was analyzed with gradient-class activation mapping (Grad-CAM). We evaluated the developed modelviasubject cross-validation and found that it achieved significantly improved accuracy (85.69 ± 1.10%) compared with conventional models or without residual networks. Grad-CAM analysis of the classification of cases in which our model produced correct answers showed localized activity near the premotor cortex. These results confirm the effectiveness of inserting residual networks into CNNs for tuning BCI. Further, they suggest that recording EEG signals over the premotor cortex and some other areas contributes to high classification accuracy.
Peripheral Nerve Innervation in Bilateral Cleft Hand Syndrome Elucidated by Ultrasound
Authors: Falco Pietro , Hovius Steven , van Alfen Nens
Published: May 2022

Bilateral cleft hand syndrome is a rare congenital malformation with complex anatomy. Previous reports have mainly focused on the description of bone and soft tissue abnormalities, but information about innervation is scarce. Knowledge of the peripheral nerve anatomy is helpful for surgical treatment, optimizing the reconstruction, and preventing iatrogenic damage. Following clinical assessment and conventional radiologic imaging, we used high-resolution ultrasound of both hands and forearms to image the peripheral nerves in a patient with severe bilateral cleft hand syndrome. The patient presented with two ulnar digits, a deformed thumb on the right, and a rudimentary thumb appendage on the left. In keeping with the tissue elements present and absent, we found a severe bilateral nerve size reduction of the median nerves, sparing the anterior interosseous nerve fascicles. The radial nerve and end branches were intact, and a slightly smaller ulnar nerve was found that ended in two digital branches to a single digit. Our study shows that in cleft hand syndrome the peripheral nervous system anatomy exactly reflects the presence and absence of the corresponding muscle and skin innervation areas. This information is helpful for planning a surgical-reconstructive approach and suggests a potential role for nerve ultrasound in the assessment of complex limb malformations.
Prediction of Early Mortality Among Children With Moderate or Severe Traumatic Brain Injury Based on a Nomogram Integrating Radiological and Inflammation-Based Biomarkers
Authors: Zhu Pingyi , Hussein Nimo Mohamed , Tang Jing , Lin Lulu , Wang Yu , Li Lan , Shu Kun , Zou Pinfa , Xia Yikai , Bai Guanghui , Yan Zhihan , Ye Xinjian
Published: May 2022

Inflammation-based scores have been increasingly used for prognosis prediction in neurological diseases. This study aimed to investigate the predictive value of inflammation-based scores combined with radiological characteristics in children with moderate or severe traumatic brain injury (MS-TBI). A total of 104 pediatric patients with MS-TBI were retrospectively enrolled and randomly divided into training and validation cohorts at a 7:3 ratio. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of prognosis in pediatric patients with MS-TBI. A prognostic nomogram was constructed, and its predictive performance was validated in both the training and validation cohorts. Sex, admission platelet-to-lymphocyte ratio, and basal cistern status from initial CT findings were identified as independent prognostic predictors for children with MS-TBI in multivariate logistic analysis. Based on these findings, a nomogram was then developed and its concordance index values were 0.918 [95% confidence interval (CI): 0.837–0.999] in the training cohort and 0.86 (95% CI: 0.70–1.00) in the validation cohort, which significantly outperformed those of the Rotterdam, Marshall, and Helsinki CT scores. The proposed nomogram, based on routine complete blood count and initial CT scan findings, can contribute to individualized prognosis prediction and clinical decision-making in children with MS-TBI.
Centromedian Nucleus of the Thalamus Deep Brain Stimulation for Genetic Generalized Epilepsy: A Case Report and Review of Literature
Authors: Agashe Shruti , Burkholder David , Starnes Keith , Van Gompel Jamie J. , Lundstrom Brian N. , Worrell Gregory A. , Gregg Nicholas M.
Published: May 2022

There is a paucity of treatment options for cognitively normal individuals with drug resistant genetic generalized epilepsy (GGE). Centromedian nucleus of the thalamus (CM) deep brain stimulation (DBS) may be a viable treatment for GGE. Here, we present the case of a 27-year-old cognitively normal woman with drug resistant GGE, with childhood onset. Seizure semiology are absence seizures and generalized onset tonic clonic (GTC) seizures. At baseline she had 4–8 GTC seizures per month and weekly absence seizures despite three antiseizure medications and vagus nerve stimulation. A multidisciplinary committee recommended off-label use of CM DBS in this patient. Over 12-months of CM DBS she had two GTC seizure days, which were in the setting of medication withdrawal and illness, and no GTC seizures in the last 6 months. There was no significant change in the burden of absence seizures. Presently, just two studies clearly document CM DBS in cognitively normal individuals with GGE or idiopathic generalized epilepsy (IGE) [in contrast to studies of cognitively impaired individuals with developmental and epileptic encephalopathies (DEE)]. Our results suggest that CM DBS can be an effective treatment for cognitively normal individuals with GGE and underscore the need for prospective studies of CM DBS.
Abnormal Dynamic Functional Connectivity in Patients With End-Stage Renal Disease
Authors: Li Xuekun , Yan Ruifang , Yue Zheng , Zhang Meng , Ren Jipeng , Wu Baolin
Published: May 2022

Dynamic functional connectivity (FC) analysis can capture time-varying properties of connectivity; however, studies focusing on dynamic FC in patients with end-stage renal disease (ESRD) are very limited. This is the first study to explore the dynamic aspects of whole-brain FC and topological properties in ESRD patients. Resting-state functional magnetic resonance imaging data were acquired from 100 ESRD patients [50 hemodialysis (HD) patients and 50 non-dialysis patients] and 64 healthy controls (HCs). Independent component analysis, a sliding-window approach and graph-theory methods were used to study the dynamic FC properties. The intrinsic brain FC were clustered into four configuration states. Compared with HCs, both patient groups spent longer time in State 3, in which decreased FC between subnetworks of the default mode network (DMN) and between the dorsal DMN and language network was observed in these patients, and a further reduction in FC between the DMN subnetworks was found in HD patients compared to non-dialysis patients. The number of transitions and the variability of global and local efficiency progressively decreased from that in HCs to that of non-dialysis patients to that of HD patients. The completion time of Trail Making Test A and Trail Making Test B positively correlated with the mean dwell time of State 3 and negatively correlated with the number of transitions in ESRD patients. Our findings suggest impaired functional flexibility of network connections and state-specific FC disruptions in patients with ESRD, which may underlie their cognitive deficits. HD may have an adverse effect on time-varying FC.
Tea Ingredients Have Anti-coronavirus Disease 2019 (COVID-19) Targets Based on Bioinformatics Analyses and Pharmacological Effects on LPS-Stimulated Macrophages
Authors: Wang Lei , Tao Qing , Wang Zhiguo , Shi Jianfeng , Yan Wei , Zhang Li , Sun Yaoxiang , Yao Xiaoming
Published: May 2022

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused millions of deaths and lacks treatment. Although several studies have focused on the major component of green tea, epigallocatechin 3-gallate (EGCG), which is efficient in preventing COVID-19, systemic analyses of the anti-COVID-19 potential of green tea remain insufficient. Here, we co-analyzed the target genes of tea ingredients and COVID-19 signature genes and found that epigallocatechin 3-acetalbehyde was capable of reversing the major molecular processes of COVID-19 (MAPK and NF-κB activation). These findings were further supported by Western blotting (WB), immunofluorescence, and quantitative polymerase chain reaction (qPCR) in LPS-stimulated macrophages. Moreover, using molecular docking analysis, we identified three tea ingredients ((-)-catechin gallate, D-(+)-cellobiose, and EGCG) that may interact with the vital SARS-CoV-2 protein, 5R84, compared with the qualified 5R84 ligand WGS. Thus, our results indicated that tea ingredients have the potential to treat COVID-19 by suppressing the COVID-19 signature genes and interacting with the vital SARS-CoV-2 protein.
Effect of High Ratio of n-6/n-3 PUFAs on Depression: A Meta-Analysis of Prospective Studies
Authors: Wang Yuanyuan , Dong Lirong , Pan Da , Xu Dengfeng , Lu Yifei , Yin Shiyu , Wang Shaokang , Xia Hui , Liao Wang , Sun Guiju
Published: May 2022

Objective

The aim of this systematic review and meta-analysis was to examine the association between high ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) and depression.

Methods

The authors conducted a meta-analysis of research articles on the association of high ratio of n-6/n-3 PUFAs with the risk of depression published in the online article database on PubMed, Embase, Cochrane library as of December 2021. Pooled odds ratios (OR) were calculated using random effects models. Publication bias was assessed visually by funnel plots and statistically by the Egger’s and Begg’s tests.

Results

Finally, 12 studies included in this systematic review and meta-analysis with a total of 66,317 participants (including 4,173 individuals with depression condition). The pooled results showed that high ratio of n-6/n-3 PUFAs might be positively associated with depression [OR = 1.21, 95% confidence intervals (CIs): 1.04∼1.41]. The I2 test indicated that there was a substantial statistical heterogeneity across the included studies (I2 = 54.38%, P = 0.01). Subgroup analysis showed that high ratio of n-6/n-3 PUFAs in blood had no significant association with depression (OR = 1.15, 95%CI: 0.88∼1.50), while high ratio of n-6/n-3 PUFAs in dietary supplements was positively associated with depression (OR = 1.32, 95%CI: 1.16∼1.51).

Conclusion

This meta-analysis confirmed the association between high ratio of n-6/n-3 PUFAs and the risk of depression. High ratio of n-6/n-3 PUFAs in dietary supplementation was positively associated with depression, but had no significant association in the blood. This study suggested that lowering the dietary intake of the ratio of n-6/n-3 PUFAs would be beneficial in the prevention of depression.
Beneficial Actions of Essential Fatty Acids in Streptozotocin-Induced Type 1 Diabetes Mellitus
Authors: Shen Junhui , Zhang Li , Wang Yuanqi , Chen Zhiqing , Ma Jian , Fang Xiaoyun , Das Undurti N. , Yao Ke
Published: May 2022

The essential fatty acids (EFA), n3 alpha-linolenic acid (ALA), and n6 linoleic acid (LA) are of benefit in diabetes mellitus, but their mechanisms of action are unknown. We, therefore, examined the effects of EFAs on the metabolism, gut microbiota, and inflammatory and retinal histopathology indices in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) animals, and we assessed the levels of vitreal lipoxin A4 (LXA4)—derived from LA—in subjects with diabetic retinopathy (DR). STZ-induced T1DM rats received LA or ALA 100 μg/day intraperitoneally on alternate days for 21 days, and their blood glucose; lipid profile; plasma, hepatic, and retinal fatty acid profiles (by gas chromatography); retinal histology; activities of hepatic and retinal desaturases; and inflammatory markers (by qRT-PCR) were evaluated. Gut microbiota composition was assayed by 16S rDNA sequencing technology of the fecal samples, and their short-chain fatty acids and bile acids were assayed by gas chromatography, liquid chromatography coupled with tandem mass spectrometry, respectively. The human vitreal fatty acid profiles of subjects with proliferative DR and LXA4 levels were measured. LA and ALA significantly improved the plasma glucose and lipid levels; increased the abundance of Ruminococcaceae (the ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010, and Ruminococcus_1 (the LA-treated group) bacteria; enhanced acetate and butyrate levels; and augmented fecal and hepatic concentrations of cholic acid, chenodeoxycholic acid, and tauro ursodeoxycholic acid in ALA- and LA-treated animals. Significant STZ-induced decreases in plasma LA, gamma-linolenic acid, arachidonic acid, and ALA levels reverted to near normal, following LA and ALA treatments. Significant changes in the expression of desaturases; COX-2, 5-LOX, and 12-LOX enzymes; and cytokines in T1DM were reverted to near normal by EFAs. DR subjects also had low retinal LXA4 levels. The results of the present study show that ALA and LA are of significant benefit in reversing metabolism, gut microbiota, and inflammatory and retinal index changes seen in T1DM, suggesting that EFAs are of benefit in diabetes mellitus.
Dietary Magnesium Intake Ameliorates the Association Between Household Pesticide Exposure and Type 2 Diabetes: Data From NHANES, 2007–2018
Authors: Huang Jungao , Hu Liqin , Yang Juan
Published: May 2022

Aims/Hypothesis

This study aimed to explore whether household pesticide exposure in the general population increased the risk of developing type 2 diabetes and whether intake of dietary magnesium could lower type 2 diabetes from household pesticide exposure.

Methods

For this cross-sectional study, we obtained the data of 9,187 United States adults from the National Health and Nutrition Examination Surveys, 2007–2018. Participants were subdivided into two groups based on the amount of daily dietary magnesium in the population: low group: <175 mg/day and high group: ≥175 mg/day. Using multivariable logistic regression analysis, we evaluated the relationship between pesticide exposure in the home and type 2 diabetes.

Results

Compared to those unexposed at home, individuals who were exposed to pesticides in their households had a relatively higher odds ratio for type 2 diabetes (OR = 1.22, 95% CI: 1.04–1.44). The association of pesticide exposure in the home with the incidence of type 2 diabetes was different for low and high dietary magnesium groups, OR = 1.66, 95% Cl: 1.19-2.33 vs. OR = 1.1, 95% Cl: 0.92–1.32, respectively. An interaction (P = 0.035) between household pesticide exposure and magnesium intake, suggested that high dietary magnesium intake may reduce the risk of developing type 2 diabetes from pesticide exposure.

Conclusions

Household pesticide exposure in the general population is associated with an elevated risk of type 2 diabetes. We report for the first time possible clinical relevance in that high magnesium intake may ameliorate the increased risk of type 2 diabetes from pesticide exposure.
Structural Elucidation, Modification, and Structure-Activity Relationship of Polysaccharides in Chinese Herbs: A Review
Authors: Wang Bei , Yan Lingling , Guo Shuchen , Wen Ling , Yu Mengli , Feng Liang , Jia Xiaobin
Published: May 2022

Chinese herbal polysaccharides (CHPs) are natural polymers composed of monosaccharides, which are widely found in Chinese herbs and work as one of the important active ingredients. Its biological activity is attributed to its complex chemical structure with diverse spatial conformations. However, the structural elucidation is the foundation but a bottleneck problem because the majority of CHPs are heteropolysaccharides with more complex structures. Similarly, the studies on the relationship between structure and function of CHPs are even more scarce. Therefore, this review summarizes the structure-activity relationship of CHPs. Meanwhile, we reviewed the structural elucidation strategies and some new progress especially in the advanced structural analysis methods. The characteristics and applicable scopes of various methods are compared to provide reference for selecting the most efficient method and developing new hyphenated techniques. Additionally, the principle structural modification methods of CHPs and their effects on activity are summarized. The shortcomings, potential breakthroughs, and developing directions of the study of CHPs are discussed. We hope to provide a reference for further research and promote the application of CHPs.
Identification of Novel Pyroptosis-Related Gene Signatures to Predict Prostate Cancer Recurrence
Authors: Li Chun , Zhu Jie , Du Hexi , Liang Chaozhao
Published: May 2022

Prostate cancer (PCa) is a common malignant type of urogenital tract tumor with poor prognosis. Despite therapeutic advances, the recurrence and mortality rates of PCa have continued to increase with poor prognoses. Pyroptosis, also known as inflammatory cell necrosis, is a recently identified type of programmed cell death that can regulate the invasiveness, differentiation, proliferation, and metastasis of tumor cells; thus, it has a profound effect on the prognosis of patients with tumors. However, the relationship between pyroptosis and PCa remains unclear. We first identified 25 pyroptosis-related genes (PRGs) that were differentially expressed between PCa tissues and matched normal tissues in The Cancer Genome Atlas (TCGA) cohort. Based on the expression levels of 25 PRGs, PCa patients were clearly divided into two clusters and 17 PRGs were found to be significantly different between the two clusters, suggesting probable roles for these genes in the progression and recurrence of PCa. Therefore, the GSE40272 dataset with recurrence follow-up information was used to verify their value. Univariate analysis suggested that 5/17 genes were associated with recurrence, the number of genes did not decrease after least absolute shrinkage and selection operator (LASSO) regression analysis, and 5 PRGs constituted the risk score formula. Low-risk and high-risk subgroups identified using the recurrence model showed different disease-free survival (DFS) times (P<0.001) and the risk score of five PRGs was a factor of independence for recurrence in patients with PCa. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that these pathways, and comprising PRGs might be closely related to carcinogenesis and invasion of tumors, tumor microenvironment, and immune response. In conclusion, the expression signatures of PRGs play an important role in predicting PCa recurrence.
Prostate Surface Distension and Tumor Texture Descriptors From Pre-Treatment MRI Are Associated With Biochemical Recurrence Following Radical Prostatectomy: Preliminary Findings
Authors: Shiradkar Rakesh , Ghose Soumya , Mahran Amr , Li Lin , Hubbard Isaac , Fu Pingfu , Tirumani Sree Harsha , Ponsky Lee , Purysko Andrei , Madabhushi Anant
Published: May 2022

Objective

To derive and evaluate the association of prostate shape distension descriptors from T2-weighted MRI (T2WI) with prostate cancer (PCa) biochemical recurrence (BCR) post-radical prostatectomy (RP) independently and in conjunction with texture radiomics of PCa.

Methods

This retrospective study comprised 133 PCa patients from two institutions who underwent 3T-MRI prior to RP and were followed up with PSA measurements for ≥3 years. A 3D shape atlas-based approach was adopted to derive prostate shape distension descriptors from T2WI, and these descriptors were used to train a random forest classifier (CS) to predict BCR. Texture radiomics was derived within PCa regions of interest from T2WI and ADC maps, and another machine learning classifier (CR) was trained for BCR. An integrated classifier CS+R was then trained using predictions from CS and CR. These models were trained on D1 (N = 71, 27 BCR+) and evaluated on independent hold-out set D2 (N = 62, 12 BCR+). CS+R was compared against pre-RP, post-RP clinical variables, and extant nomograms for BCR-free survival (bFS) at 3 years.

Results

CS+R resulted in a higher AUC (0.75) compared to CR (0.70, p = 0.04) and CS (0.69, p = 0.01) on D2 in predicting BCR. On univariable analysis, CS+R achieved a higher hazard ratio (2.89, 95% CI 0.35–12.81, p < 0.01) compared to other pre-RP clinical variables for bFS. CS+R, pathologic Gleason grade, extraprostatic extension, and positive surgical margins were associated with bFS (p < 0.05). CS+R resulted in a higher C-index (0.76 ± 0.06) compared to CAPRA (0.69 ± 0.09, p < 0.01) and Decipher risk (0.59 ± 0.06, p < 0.01); however, it was comparable to post-RP CAPRA-S (0.75 ± 0.02, p = 0.07).

Conclusions

Radiomic shape descriptors quantifying prostate surface distension complement texture radiomics of prostate cancer on MRI and result in an improved association with biochemical recurrence post-radical prostatectomy.
Social Media Listening to Understand the Lived Experience of Individuals in Europe With Metastatic Breast Cancer: A Systematic Search and Content Analysis Study
Authors: Mazza Manuelita , Piperis Maria , Aasaithambi Sathyaraj , Chauhan Jyoti , Sagkriotis Alexandros , Vieira Claudia
Published: May 2022

Background

Despite a wealth of real-world data on metastatic breast cancer (mBC), insights into the lived experience are lacking. This study aimed to explore how the lived experience of mBC is described on social media.

Methods

A predefined search string identified posts relevant to the lived experience of mBC from Twitter, patient forums, and blogs across 14 European countries. The final data set was analyzed using content analysis.

Results

A total of 76,456 conversations were identified between November 1, 2018, and November 30, 2020. Twitter was the most commonly used social media platform across all 76,456 conversations from the raw data set (n = 61,165; 80%). Automated and manual relevancy checks followed by a final random sampling filter identified 820 conversations for content analysis. The majority of data from the raw data set was generated from the United Kingdom (n = 31,346; 41%). From this final data set, 61% of posts were authored by patients, 15% by friends and/or family members of patients, and 14% by caregivers. A total of 686 conversations described the patient journey (n = 686/820; 84%); 64% of these (n = 439) concerned breast cancer treatment, with approximately 40% of discussions regarding diagnosis and tests (n = 274/686) and less than 20% of discussions surrounding disease management (n = 123/686; 18%). Key themes relating to a lack of effective treatment, prolonged survival and associated quality of life, debilitating consequences of side effects, and the social impacts of living with mBC were identified.

Conclusions

The findings from this study provided an insight into the lived experience of mBC. While retrospective data collection inherently limits the amount of demographic or clinical information that can be obtained from the population sample, social media listening studies offer training to healthcare professionals in communication, the importance of quality of life, organization of healthcare, and even the design of clinical trials. As new targeted therapies are gradually incorporated into clinical practice, innovative technologies, such as social media listening, have the potential to support regulatory procedures and drug toxicity monitoring, as well as provide the patient voice in the regulation of new and existing medicines.
The Alteration of T-Cell Heterogeneity and PD-L1 Colocalization During dMMR Colorectal Cancer Progression Defined by Multiplex Immunohistochemistry
Authors: Yan Hongkai , Li Yaqi , Wang Xiaoyu , Qian Juanjuan , Xu Midie , Peng Junjie , Huang Dan
Published: May 2022

Background

Immune checkpoint inhibitors (ICIs) are quickly becoming key instruments in the treatment of mismatch repair-deficient (dMMR) colorectal cancers (CRCs). Despite their clinical value, ICIs have several limitations associated with their use. Only approximately 15% of all CRCs have a dMMR status, and the overall response rate of ICIs is approximately 40%. The mechanism of ICI resistance is not clear, and its study is limited by the lack of information available on the characterization of the immune microenvironment during the progression from early- to advanced-stage dMMR CRC.

Methods

We used multiplex immunohistochemistry (mIHC) with two panels, each containing five markers, to simultaneously analyze the proportions of immune microenvironment constituents in 59 patients with advanced-stage dMMR CRC and 24 patients with early-stage dMMR CRC. We detected immune cell–associated signatures in the epithelial and stromal regions and evaluated the predictive value of these immune molecules. Student’s t-tests, Mann–Whitney U tests, Cox proportional hazards regression modeling, univariate Cox modeling, and Kaplan–Meier estimation were used to analyze immune cell proportions and survival data.

Results

We observed significantly higher proportions of CD8+ cytotoxic T cells (CD8+) (p = 0.001), CD8+ memory T cells (CD8+CD45RO+) (p = 0.032), and CD4+ regulatory T cells (CD4+FOXP3+) (p = 0.011) in the advanced-stage dMMR CRCs than in the early-stage dMMR CRCs. Furthermore, CD3+ T cells with PD-L1 colocalization (CD3+PD-L1+) (p = 0.043) and CD8+ T cells with PD-L1 colocalization (CD8+PD-L1+) (p = 0.005) were consistently more numerous in patients in the advanced stage than those in the early stage. Our analyses revealed that a high proportion of CD3+PD-1+ T cells was an independent prognostic factor of overall survival (OS) [hazard ratios (HR) = 9.6, p < 0.001] and disease-free survival (DFS) (HR = 3.7, p = 0.010) in patients in the advanced stage.

Conclusion

High numbers of CD8+ cytotoxic T cells and CD8+ memory T cells, which usually represent a cytotoxic function of the adaptive immune system and possibly enhanced inhibition factors, such as CD4+ regulatory T cells and PD-L1 colocalized T cells, were associated with the transformation of the immune microenvironment from the early stage to the advanced stage in dMMR CRCs. Furthermore, CD3+PD-1+ T cells are a prognostic factor for patients with dMMR.
Economic Analysis of Tissue-First, Plasma-First, and Complementary NGS Approaches for Treatment-Naïve Metastatic Lung Adenocarcinoma
Authors: Yang Szu-Chun , Lin Chien-Chung , Chen Yi-Lin , Su Wu-Chou
Published: May 2022

Background

To compare the testing costs and testing turnaround times of tissue-first, plasma-first, and complementary next-generation sequencing (NGS) approaches in patients with treatment-naïve metastatic lung adenocarcinoma.

Materials and Methods

We developed a decision tree model to compare three different approaches. Patients were entered into the model upon cancer diagnosis and those with both insufficient tissue specimens and negative liquid-based NGS were subjected to tissue re-biopsy. Actionable gene alterations with the U.S. Food and Drug Administration (FDA)-approved therapies included epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement, ROS proto-oncogene 1 (ROS1) rearrangement, B-Raf proto-oncogene (BRAF) V600E mutation, rearranged during transfection (RET) gene rearrangement, mesenchymal-epithelial transition factor (MET) mutation, neurotrophic tyrosine receptor kinase (NTRK) gene rearrangement, K-Ras proto-oncogene (KRAS) G12C mutation, and human epidermal growth factor receptor 2 (HER2) mutation. Model outcomes were testing costs, testing turnaround times, and monetary losses taking both cost and time into consideration. We presented base-case results using probabilistic analysis. Stacked one-way and three-way sensitivity analyses were also performed.

Results

In terms of testing costs, tissue-first approach incurred US$2,354($1,963–$2,779) and was the most cost-efficient strategy. Complementary approach testing turnaround time (days) of 12.7 (10.8 to 14.9) was found as the least time-consuming strategy. Tissue-first, complementary, and plasma-first approaches resulted in monetary losses in USD of $4,745 ($4,010–$5,480), $6,778 ($5,923–$7,600), and $7,006 ($6,047–$7,964) respectively, and identified the same percentage of patients with appropriate FDA-approved therapies. Costs for liquid-based NGS, EGFR mutation rates, and quantity of tissue specimens were the major determinants in minimizing monetary loss. Plasma-first approach would be the preferable strategy if its testing price was reduced in USD to $818, $1,343, and $1,869 for populations with EGFR mutation rates of 30%, 45%, and 60% respectively.

Conclusion

The tissue-first approach is currently the best strategy in minimizing monetary loss. The complementary approach is an alternative for populations with a low EGFR mutation rate. The plasma-first approach becomes increasingly preferable as EGFR mutation rates gradually increase.
Impact of Baseline Muscle Mass and Myosteatosis on the Development of Early Toxicity During First-Line Chemotherapy in Patients With Initially Metastatic Pancreatic Cancer
Authors: Hong Sun , Kim Kyung Won , Park Hyo Jung , Ko Yousun , Yoo Changhoon , Park Seo Young , Khang Seungwoo , Jeong Heeryeol , Lee Jeongjin
Published: May 2022

Objectives

Although chemotherapy is the only treatment option for metastatic pancreatic cancer (PDAC), patients frequently encounter adverse events during chemotherapy leading deterioration of patients’ quality of life and treatment interruption. We evaluated the role of baseline CT-assessed body composition in predicting early toxicity during first cycle of the first-line chemotherapy in patients with metastatic PDAC.

Methods

This retrospective study included 636 patients with initially metastatic PDAC who underwent first-line chemotherapy from January 2009 to December 2019. Chemotherapy regimen, baseline laboratory data, and body composition parameters acquired from baseline CT were obtained. The skeletal muscle index (SMI) was used to identify patients with a low muscle mass (SMI < 41 cm2/m2 for women, and < 43 cm2/m2 [body mass index < 25 cm/kg2] or < 53 cm2/m2 [body mass index ≥ 25 cm/kg2] for men), and myosteatosis was defined as low-attenuated muscle area divided by skeletal muscle area (LAMA/SMA index) ≥ 20%. Univariate and multivariable binary logistic regression analyses were performed using bootstrapping with 500 interactions to identify predictors of grade 3–4 toxicity and any treatment-modifying toxicity which led to a dose reduction, delayed administration, drug skip or discontinuation.

Results

During the first cycle of the first-line chemotherapy, grade 3–4 toxicity and treatment-modifying toxicity occurred in 160 patients (25.2%) and in 247 patients (38.8%), respectively. The presence of both low muscle mass and myosteatosis was significantly associated with the occurrence of both grade 3-4 toxicity (odd ratio [OR], 1.73; 95% confidence interval [CI], 1.14–2.63) and treatment-modifying toxicity (OR, 1.83; 95% CI, 1.26–2.66) whereas low muscle mass alone did not.

Conclusions

The presence of both low muscle mass and myosteatosis assessed on baseline CT may be used to predict early chemotherapy-related toxicity in patients with metastatic PDAC.
Risk Factors of Non-en Bloc Resection and Non-R0 Resection During Endoscopic Resection in the Treatment of Superficial Duodenal Epithelial Lesions
Authors: Fu Shifeng , Gong Jian , Zhou Mei , Wang Yongjun , Liu Deliang , Tan Yuyong
Published: May 2022

Background

Superficial duodenal epithelial lesions are precancerous lesions of duodenal carcinoma. Upper gastrointestinal endoscopy has been widely used in the screening and treatment of this disease. This article will collect the data of patients who underwent endoscopic resection of superficial duodenal epithelial lesions in our hospital from 2010 to 2021, aiming to describe the efficacy and safety of endoscopic resection, as well as to explore the risk factors of non-en bloc resection and non-R0 resection.

Methods

Patients who underwent endoscopic resection for superficial duodenal epithelial lesions in our hospital from January 2010 to September 2021 were selected. The curative effect was expressed by the en bloc resection rate and R0 resection rate. The safety was expressed by intra- or postoperative complications, such as bleeding and perforation. The potential risk factors of curative effect were analyzed by logistic regression.

Results

A total of 137 patients were included. The en bloc resection rate was 95.62% (131/137), R0 resection rate was 91.97% (126/137), the postoperative bleeding rate was 2.19% (3/137), and no postoperative perforation was found. The histology result of ectopic gastric mucosa was the risk factor of non-en bloc resection (OR: 8.86, 95% CI: 1.38-56.92); the lesion size ≥2 cm was the risk factor of non-R0 resection (OR: 12.55, 95% CI: 2.95-53.38).

Conclusion

Endoscopic resection is a safe and effective method for the treatment of superficial duodenal epithelial lesions. The histology result of ectopic gastric mucosa was the risk factor of non-en bloc resection and the lesion size ≥2 cm was the risk factor of non-R0 resection.
High-Metastatic Melanoma Cells Promote the Metastatic Capability of Low-Metastatic Melanoma Cells via Exosomal Transfer of miR-411-5p
Authors: Chen Hao , Zeng Bin , Li Xiaoshuang , Zhao Qiting , Liu Doudou , Chen Yuting , Zhang Yuhan , Wang Jianyu , Xing H. Rosie
Published: May 2022

Melanoma is characterized by high rate of metastasis and mortality. Effective management of metastatic melanoma depends on renewed mechanistic understanding underlying melanoma progression and metastasis. The role of exosomes in mediating the interactions between cancer cells and the metastatic microenvironment is at the forefront of cancer research. Previous researches on the function of exosomes in metastasis have been primarily focused on tumor cell-derived exosomes in modifying the biological functions of stromal cells. Whether the cancer cells at the involved organ can modify the metastatic capability of each other has not been demonstrated. In this study, a paired M14 melanoma derivative cell line, i.e., M14-OL and POL, that we established and characterized were employed. Oligo-metastatic (M14-OL) and poly-metastatic (M14-POL) cell line were generated from three consecutive rounds of in vivo selection and passage. They exhibit high (POL cells) and low (OL cells) metastatic colonization efficiency in vivo, respectively. We show that exosomal crosstalk between metastatic cancer cells is a new mechanism of cancer metastasis. High-metastatic melanoma cells (POL) can augment the metastatic colonization capability of the low-metastatic melanoma cells (OL). POL achieves this goal by utilizing its exosomes to deliver functional miRNAs, in this case, miR-411-5p, to the OL cell. Upon entering OL cells, exosomal miR-411-5p enhance metastatic colonization efficiency by activation of the ERK signaling pathway. Moreover, miR-411-5p expression is higher in cancer tissues of other cancer types (colon, lung, rectum) compared with that of respective normal tissues. The clinical relevance of the present finding merits future investigations.
Oncolytic Adenoviral Vector-Mediated Expression of an Anti-PD-L1-scFv Improves Anti-Tumoral Efficacy in a Melanoma Mouse Model
Authors: Vitale Maria , Scialò Filippo , Passariello Margherita , Leggiero Eleonora , D’Agostino Anna , Tripodi Lorella , Gentile Laura , Bianco Andrea , Castaldo Giuseppe , Cerullo Vincenzo , De Lorenzo Claudia , Pastore Lucio
Published: May 2022

Oncolytic virotherapy is an emerging therapeutic approach based on replication-competent viruses able to selectively infect and destroy cancer cells, inducing the release of tumor-associated antigens and thereby recruiting immune cells with a subsequent increase in antitumoral immune response. To increase the anticancer activity, we engineered a specific oncolytic adenovirus expressing a single-chain variable fragment of an antibody against PD-L1 to combine blockage of PD-1/PD-L1 interaction with the antitumoral activity of Onc.Ad5. To assess its efficacy, we infected B16.OVA cells, a murine model of melanoma, with Ad5Δ24 -anti-PD-L1-scFv and then co-cultured them with C57BL/6J naïve splenocytes. We observed that the combinatorial treatments were significantly more effective in inducing cancer cell death. Furthermore, we assessed the efficacy of intratumoral administrations of Ad5Δ24-anti-PD-L1-scFv in C57BL/6J mice engrafted with B16.OVA and compared this treatment to that of the parental Ad5Δ24 or placebo. Treatment with the scFv-expressing Onc.Ad induced a marked reduction of tumor growth concerning the parental Onc.Ad. Additionally, the evaluation of the lymphocytic population infiltrating the treated tumor reveals a favorable immune profile with an enhancement of the CD8+ population. These data suggest that Onc.Ad-mediated expression of immune checkpoint inhibitors increases oncolytic virotherapy efficacy and could be an effective and promising tool for cancer treatments, opening a new way into cancer therapy.