bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and management experience of schwannoma in extremities: Lessons learned from a 10-year retrospective study
Authors: Zhou Haiying , Yao Chengjun , Dong Yanzhao , Alhaskawi Ahmad , Wang Zewei , Lai Jingtian , Ezzi Sohaib Hasan Abdullah , Kota Vishnu Goutham , Abdulla Mohamed Hasan Abdulla Hasan , Lu Hui
Published: December 2022

Introduction

Schwannomas are the most common neoplastic lesions of the peripheral nerves when growing on the extremities, they usually have adverse effects on patients due to the exposed and functional nature of the region.

Methods

In the present single-center retrospective study, we included all patients with pathologically confirmed schwannoma located in extremities between 2011 and 2021 totaling 183 patients. Data on gender, age, duration history, clinical presentation, occurrence region, nerve affiliation, imaging data, modus operation, mass volume, immunohistochemistry, postoperative neurological function, and recurrence were collected.

Results

As in previous studies, patients were predominantly middle-aged with a mean age of 49.5, without gender preference and a male-to-female ratio of 1.2:1. Most patients are first seen for this disease, and only five of them are recurrent. The majority presented with an isolated (91.26%), asymptomatic (37.7%) mass, with tenderness (34.97%) being the second frequent complaint. 60% of lesions occurred in the upper extremity, more commonly on the left side (55.26%) than the right. The average duration of onset was 47.50 months. MRI is more sensitive for neurogenic tumors than ultrasound, as it owns 78.93% correct. In immunohistochemistry, the top three markers for positive labeling schwannoma are S-100 (98.95%), Ki67 (98.68%) and β-Catenin. 98.36% of patients underwent complete resection of the lesion, of which 14.44% required partial sacrifice of the nerve fibers. Thanks to the application of intraoperative peripheral nerve microscopic operation, only 6 patients showed symptoms of postoperative nerve injury, and 3 of them received second surgery. Intraoperative microscopic manipulation, preservation of the main nerve, and the need for reconstruction of the affected nerve fibers are some of the points worth noting.

Discussion

In summary, the possibility of schwannoma should not be overlooked in the identification of masses that occur in the upper extremities of the middle-aged population. Preoperative ultrasound and MR are useful for determining the nature of the mass, and S100, Ki67, and β-Catenin are sensitive to it. Surgical resection can achieve satisfying functional results and a low risk of nerve injury.
Estimating effective connectivity in Alzheimer's disease progression: A dynamic causal modeling study
Authors: Huang Jiali , Jung Jae-Yoon , Nam Chang S.
Published: December 2022

Introduction

Alzheimer's disease (AD) affects the whole brain from the cellular level to the entire brain network structure. The causal relationship among brain regions concerning the different AD stages is not yet investigated. This study used Dynamic Causal Modeling (DCM) method to assess effective connectivity (EC) and investigate the changes that accompany AD progression.

Methods

We included the resting-state fMRI data of 34 AD patients, 31 late mild cognitive impairment (LMCI) patients, 34 early MCI (EMCI) patients, and 31 cognitive normal (CN) subjects selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The parametric Empirical Bayes (PEB) method was used to infer the effective connectivities and the corresponding probabilities. A linear regression analysis was carried out to test if the connection strengths could predict subjects' cognitive scores.

Results

The results showed that the connections reduced from full connection in the CN group to no connection in the AD group. Statistical analysis showed the connectivity strengths were lower for later-stage patients. Linear regression analysis showed that the connection strengths were partially predictive of the cognitive scores.

Discussion

Our results demonstrated the dwindling connectivity accompanying AD progression on causal relationships among brain regions and indicated the potential of EC as a loyal biomarker in AD progression.
Liver fibrosis and retinal features in an older Mediterranean population: Results from the Salus in Apulia study
Authors: Lampignano Luisa , Niro Alfredo , Castellana Fabio , Bortone Ilaria , Zupo Roberta , Tirelli Sarah , Tatoli Rossella , Griseta Chiara , De Nucci Sara , Sila Annamaria , De Pergola Giovanni , Conte Caterina , Alessio Giovanni , Boscia Francesco , Sborgia Giancarlo ,   Eye Clinic Research Group, Giannelli Gianluigi , Sardone Rodolfo
Published: December 2022

Background

Age is a leading contributor to the liver fibrosis rate and a gradual deterioration of optical function, but this association in older populations is still under-explored. The present study aimed to explore the link between vascular and neural retinal characteristics and the risk of liver fibrosis in 731 older adults from the population-based Salus in Apulia study.

Methods

Retinal features were obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Liver fibrosis risk was taken as the fibrosis-4 (FIB-4) score. Generalized linear models (logistic regression) were used to estimate the association effect between each unit increase of OCT and OCT-A parameters as independent variables and a FIB-4 ≥ 2.67 score as an outcome. Generalized additive models were used to assess the non-linear association between OCT-A features and the linear FIB-4 score.

Results

Increased gangliar cell complex (GCC) thickness was inversely associated with a FIB-4 score above the cut-off in both the raw model (OR: 0.98; 95% CI: 0.96–0.99; SE: 0.01) and after adjustment for age, sex, education, hypertension, diabetes, total cholesterol, and triglycerides (OR: 0.98; 95% CI: 0.97–0.99; SE: 0.01).

Conclusion

Our findings add to the growing volume of scientific literature demonstrating that liver fibrosis is associated with retinal neurodegeneration. This study raises a number of new questions, including whether OCT-A may be used to track the progression of metabolic abnormalities and define exact thresholds for predicting and classifying liver disease.
The protective effect of Buzhong Yiqi decoction on ischemic stroke mice and the mechanism of gut microbiota
Authors: Li Qianqian , Cao Mengxin , Wei Zijun , Mei Jianing , Zhang Yuechan , Li Man , Li Manlin , Zhang Yunyun , Wang Zhifei
Published: December 2022

Buzhong Yiqi decoction (BZYQD) has been developed for preventing or reducing the recurrence of ischemic stroke for a long time in China. However, the mechanism of action of the BZYQD is not completely understood. Our research aims to determine whether the mechanism of action of BZYQD is by regulating gut microbiota using 16SR RNA and fecal microbiota transplantation. In a cerebral ischemia mouse model, the results showed that prophylactic administration of BZYQD could reduce brain infarct volume and improve neurological function and behavior. The prophylactic administration of BZYQD could regulate intestinal microbiota and increase the abundance of butyrate-producing Prevotellaceae_NK3B31_group and probiotic Akkermansia in mice 72 h after surgery. Transplanting BZYQD-administered bacterial flora into antibiotic-depleted mice could reproduce the therapeutic effects of BZYQD. Overall, our study provided molecular insights into the mechanism and impact of BZYQD in the prevention of cerebral ischemic damage and highlighted the potential of regulation of intestinal microbiota as a therapeutic approach for ischemic stroke.
Creating a sustainable action-oriented engagement infrastructure—a UMN-MIDB perspective
Authors: Randolph Anita C. , Henry Alex , Hewitt Amy , Mejia Angie P. , Sethuraju Raj , DeJoseph Meriah , Koenig Melissa , Elison Jed T. , Fair Damien A.
Published: December 2022

Following the murder of George Floyd on May 25, 2020, Minneapolis represented the epicenter of protests that would reverberate internationally and re-instantiate a reckoning of the systemic and institutional racism that plagues American society. Also in the summer of 2020, and after several years of planning, the University of Minnesota (UMN) launched the Masonic Institute for the Developing Brain (MIDB), an interdisciplinary clinical and community research enterprise designed to create knowledge and engage all members of our community. In what follows, we describe the mission of the MIDB Community Engagement and Education (CEEd) Core and adjacent efforts within the UMN neuroscience and psychology community. Inherent to these efforts is the explicit attempt to de-center the dominant academic voice and affirm knowledge creation is augmented by diverse voices within and outside of traditional academic institutions. We describe several initiatives, including the Neuroscience Opportunities for Discovery and Equity (NODE) network, the NextGen Psych Scholars Program (NPSP), the Young Scientist Program, among others as exemplars of our approach. Developing and fortifying sustainable pathways for authentic community-academic partnerships are of central importance to enhance mutually beneficial scientific discovery. We posit that traditional academic approaches to community engagement to benefit the institution are severely constrained and perpetuate inherently exploitative power dynamics between academic institutions and communities.
Effects of N-methyl-D-aspartate receptor knockdown and hypoxia/reoxygenation injury on the neuronal proteome and transcriptome
Authors: He Jinting , Chen Kaili , Sui Yujie , Yang Qiwei
Published: December 2022

Introduction

Brain tissue is extremely sensitive to hypoxia/reoxygenation (H/R) injury, which can easily cause irreversible damage to neurons. H/R injury can induce neuronal apoptosis through glutamate-mediated excitotoxicity. N-methyl-d-aspartate receptor (NMDAR) is one of the main receptors of excitatory glutamate, and blocking NMDAR protects brain tissue from ischemic and hypoxic injury. However, NMDAR hypofunction can also cause psychotic symptoms or cognitive impairment. There is still a lack of systematic research on the changes in the proteome and transcriptome in neuronal cells under conditions of NMDAR hypofunction and H/R injury.

Methods

We compared the changes in the proteome, transcriptome and lncRNA expression levels in neurons after NMDAR knockdown and H/R by isobaric tags for relative and absolute quantitation (iTRAQ) and RNA sequencing (RNA-Seq).

Results

The results showed that the proteins Rps9, Rpl18 and Rpl15 and the lncRNAs XLOC_161072 and XLOC_065271 were significantly downregulated after NMDAR knockdown but upregulated after H/R; in contrast, the mRNAs Bank1 and Pcp4l1 and the lncRNAs XLOC_159404 and XLOC_031922 were significantly upregulated after NMDAR knockdown but downregulated after H/R.

Discussion

In this study, we demonstrated the characterization of protein, mRNA, and lncRNA expression profiles in neurons following NMDAR knockdown and H/R injury. These molecules are involved in multiple biological functions and signaling pathways, and their roles in neurons lacking NMDAR and subjected to H/R injury deserve further study. Additionally, we found that lncRNAs respond fastest to hypoxic stimulation and that Gapdh is not suitable as a reference protein for NMDAR-reduced neuron-related experiments.
Proteomic profiling reveals mitochondrial dysfunction in the cerebellum of transgenic mice overexpressing DYRK1A, a Down syndrome candidate gene
Authors: Ortega Mireia , De Toma Ilario , Fernández-Blanco Álvaro , Calderón Anna , Barahona Lucía , Trullàs Ramón , Sabidó Eduard , Dierssen Mara
Published: December 2022

Introduction

DYRK1A is a dual-specificity kinase that is overexpressed in Down syndrome (DS) and plays a key role in neurogenesis, neuronal differentiation and function, cognitive phenotypes, and aging. Dyrk1A has also been implicated in cerebellar abnormalities observed in association with DS, and normalization of Dyrk1A dosage rescues granular and Purkinje cell densities in a trisomic DS mouse model. However, the underlying molecular mechanisms governing these processes are unknown.

Methods

To shed light on the effects of Dyrk1A overexpression in the cerebellum, here we investigated the cerebellar proteome in transgenic Dyrk1A overexpressing mice in basal conditions and after treatment with green tea extract containing epigallocatechin-3-gallate (EGCG), a DYRK1A inhibitor.

Results and Discussion

Our results showed that Dyrk1A overexpression alters oxidative phosphorylation and mitochondrial function in the cerebellum of transgenic mice. These alterations are significantly rescued upon EGCG-containing green tea extract treatment, suggesting that its effects in DS could depend in part on targeting mitochondria, as shown by the partially restoration by the treatment of the increased mtDNA copy number in TG non-treated mice.
Transcriptome-wide association study reveals cholesterol metabolism gene Lpl is a key regulator of cognitive dysfunction
Authors: Hu Wei , Liu Jian , Hu Yaorui , Xu Qingling , Deng Tingzhi , Wei Mengna , Lu Lu , Mi Jia , Bergquist Jonas , Xu Fuyi , Tian Geng
Published: December 2022

Cholesterol metabolism in the brain plays a crucial role in normal physiological function, and its aberrations are associated with cognitive dysfunction. The present study aimed to determine which cholesterol-related genes play a vital role in cognitive dysfunction and to dissect its underlying molecular mechanisms using a systems genetics approach in the BXD mice family. We first systematically analyzed the association of expression of 280 hippocampal genes related to cholesterol metabolism with cognition-related traits and identified lipoprotein lipase (Lpl) as a critical regulator. This was further confirmed by phenome-wide association studies that indicate Lpl associated with hippocampus volume residuals and anxiety-related traits. By performing expression quantitative trait locus mapping, we demonstrate that Lpl is strongly cis-regulated in the BXD hippocampus. We also identified ∼3,300 genes significantly (p < 0.05) correlated with the Lpl expression. Those genes are mainly involved in the regulation of neuron-related traits through the MAPK signaling pathway, axon guidance, synaptic vesicle cycle, and NF-kappa B signaling pathway. Furthermore, a protein–protein interaction network analysis identified several direct interactors of Lpl, including Rab3a, Akt1, Igf1, Crp, and Lrp1, which indicates that Lpl involves in the regulation of cognitive dysfunction through Rab3a-mediated synaptic vesicle cycle and Akt1/Igf1/Crp/Lrp1-mediated MAPK signaling pathway. Our findings demonstrate the importance of the Lpl, among the cholesterol-related genes, in regulating cognitive dysfunction and highlighting the potential signaling pathways, which may serve as novel therapeutic targets for the treatment of cognitive dysfunction.
Phase angle derived from bioelectrical impedance analysis as a marker for predicting sarcopenia
Authors: Wu Haotian , Ding Ping'an , Wu Jiaxiang , Yang Peigang , Tian Yuan , Zhao Qun
Published: December 2022

Sarcopenia is commonly defined as the age-related loss of muscle mass and function and may be caused by several factors, such as genetics, environmental conditions, lifestyle, drug use, and, in particular, comorbidities. People with pre-existing conditions are more likely to develop sarcopenia and subsequently have a less favorable prognosis. Recently, phase angle (PhA), which is derived from bioelectrical impedance analysis (BIA), has received a great deal of attention, and numerous studies have been carried out to examine the relationship between PhA and sarcopenia in different conditions. Based on these studies, we expect that PhA could be used as a potential marker for sarcopenia in the future.
Fluorescent advanced glycation end products in type 2 diabetes and its association with diabetes duration, hemoglobin A1c, and diabetic complications
Authors: Liu Rui , Zhang Mengyao , Xu Li , Liu Jingjin , Yang Pingan , Li Min , Qin Jie
Published: December 2022

Background

Fluorescent advanced glycation end products (fAGEs) are generated through the Maillard reaction between reducing sugars and amino compounds. fAGEs accumulation in human bodies have been confirmed to be related to many chronic diseases. To date, the correlations between serum fAGEs levels and clinical parameters or carotid intima media thickness (CIMT) in patients with T2DM remain unclear. Thus, this study aimed to investigate the relationship between serum AGEs levels and clinical parameters or CIMT in patients with T2DM.

Method

A total of 131 patients with diabetes and 30 healthy controls were enrolled. Patients were divided into three groups according to diabetes duration, including ≤5, 5–10, and ≥10 years. Serum fAGEs, protein oxidation products, clinical parameters, and CIMT were determined.

Results

The result showed that levels of fAGEs and protein oxidation products increased with the increasing duration of diabetics. Pearson correlation coefficients of fAGEs versus hemoglobin A1c (HbA1c) were >0.5 in patients with diabetes duration ≥10 years. A continued increase in fAGEs might cause the increase of HbA1c, urinary albumin/creatinine ratio (UACR) and CIMT in patients with T2DM.

Conclusion

Our study suggested that levels of fAGEs could be considered as an indicator for duration of diabetics and carotid atherosclerosis. Diabetes duration and smoking might have a synergistic effect on the increment of fAGEs levels, as evidence by the results of correlation analysis in patients with long-duration diabetics (≥10 years) and smoking. The determination of fAGEs might be helpful to advance our knowledge on the overall risk of complications in patients with T2DM.
Biological function, mediate cell death pathway and their potential regulated mechanisms for post-mortem muscle tenderization of PARP1: A review
Authors: Li Rong , Luo Ruiming , Luo Yulong , Hou Yanru , Wang Jinxia , Zhang Qian , Chen Xueyan , Hu Lijun , Zhou Julong
Published: December 2022

Tenderness is a key attribute of meat quality that affects consumers’ willingness to purchase meat. Changes in the physiological environment of skeletal muscles following slaughter can disrupt the balance of redox homeostasis and may lead to cell death. Excessive accumulation of reactive oxygen species (ROS) in the myocytes causes DNA damage and activates poly ADP-ribose polymerase 1 (PARP1), which is involved in different intracellular metabolic pathways and is known to affect muscle tenderness during post-slaughter maturation. There is an urgent requirement to summarize the related research findings. Thus, this paper reviews the current research on the protein structure of PARP1 and its metabolism and activation, outlines the mechanisms underlying the function of PARP1 in regulating muscle tenderness through cysteine protease 3 (Caspase-3), oxidative stress, heat shock proteins (HSPs), and energy metabolism. In addition, we describe the mechanisms of PARP1 in apoptosis and necrosis pathways to provide a theoretical reference for enhancing the mature technology of post-mortem muscle tenderization.
Determinants of nutritional status among pregnant women in East Shoa zone, Central Ethiopia
Authors: Wakwoya Ermias Bekele , Belachew Tefera , Girma Tsinuel
Published: December 2022

Background

Undernutrition is an insufficient intake of energy and nutrients to meet an individual's needs to maintain good health. Undernutrition during pregnancy severely affects the health of mothers and her baby. Globally it contributes directly or indirectly to 3.5 million maternal deaths annually. This study aimed to determine the level of undernutrition and identify factors associated with undernutrition among pregnant women attending public health facilities in the East Shoa Zone, Central Ethiopia.

Methods

Institution-based cross-sectional study was conducted among 472 randomly selected pregnant women from June to August 2021. Sociodemographic, obstetrics, and knowledge related data were collected using a structured interviewer-administered questionnaire, and maternal nutritional status was measured using the Mid Upper Arm Circumference (MUAC). The collected data were entered to EPI-info version 3.5.4 and then exported to SPSS for windows version 26.0 software for analysis. Multivariable regression analysis was fitted to identify determinants of undernutrition. An adjusted odds ratio with 95% confidence intervals and a p-value < 0.05 was considered a statistically significant.

Results

The prevalence of undernutrition among pregnant women was 13.9% [95% CI: 11.0–17.4]. On multivariable logistic regression model after adjusting background variables, wealth (AOR: 4.9, 95% CI 1.34–18.20), women's decision making power (AOR: 3.31, 95% CI 1.18–7.79), and nutritional counseling (AOR: 3.53, 95% CI 1.29–9.60) were independently associated with nutritional status of pregnant women.

Conclusion

Findings indicated that significant number of pregnant women in the study were undernourished. Higher wealth index, nutritional counseling, and women's decision-making power were inversely associated with undernutrition. The findings imply the need for economic empowerment of women, enhancing decision-making ability of women and routine and consistent nutritional counseling to decrease undernutrition among pregnant women.
Increased PD-1+Foxp3+ γδ T cells associate with poor overall survival for patients with acute myeloid leukemia
Authors: Zheng Jiamian , Qiu Dan , Jiang Xuan , Zhao Yun , Zhao Haotian , Wu Xiaofang , Chen Jie , Lai Jing , Zhang Wenbin , Li Xutong , Li Yangqiu , Wu Xiuli , Jin Zhenyi
Published: December 2022

Problems

γδ T cells are essential for anti-leukemia function in immunotherapy, however, γδ T cells have different functional subsets, including regulatory cell subsets expressing the Foxp3. Whether they are correlated with immune-checkpoint mediated T cell immune dysfunction remains unknown in patients with acute myeloid leukemia (AML).

Methods

In this study, we used RNA-seq data from 167 patients in TCGA dataset to analyze the correlation between PD-1 and FOXP3 genes and these two genes’ association with the prognosis of AML patients. The expression proportion of Foxp3+/PD-1+ cells in γδ T cells and two subgroups Vδ1 and Vδ2 T cells were performed by flow cytometry. The expression level of FOXP3 and PD-1 genes in γδ T cells were sorted from peripheral blood by MACS magnetic cell sorting technique were analyzed by quantitative real-time PCR.

Results

We found that PD-1 gene was positively correlated with FOXP3 gene and highly co-expressed PD-1 and FOXP3 genes were associated with poor overall survival (OS) from TCGA database. Then, we detected a skewed distribution of γδ T cells with increased Vδ1 and decreased Vδ2 T cell subsets in AML. Moreover, significantly higher percentages of PD-1+ γδ, Foxp3+ γδ, and PD-1+Foxp3+ γδ T cells were detected in de novo AML patients compared with healthy individuals. More importantly, AML patients containing higher PD-1+Foxp3+ γδ T cells had lower OS, which might be a potential therapeutic target for leukemia immunotherapy.

Conclusion

A significant increase in the PD-1+Foxp3+ γδ T cell subset in AML was associated with poor clinical outcome, which provides predictive value for the study of AML patients.
A case report of CIC–DUX4 fusion-positive sarcoma in the pelvic cavity with targeted next-generation sequencing results
Authors: Wu Qian , He Ying
Published: December 2022

CIC–DUX4 fusion-positive sarcoma is a subtype of undifferentiated small round cell sarcoma that is rarely reported. As far as we know, less than 200 cases have been reported worldwide to date. The clinicopathologic characteristics of this kind of tumor are non-specific, which makes it difficult to be diagnosed. Therefore, more cases are required to enrich the diagnosis and treatment experience. Here, we present a 17-year-old Asian girl diagnosed with CIC–DUX4 fusion-positive sarcoma after targeted next-generation sequencing. Her clinical manifestation was abdominal pain. Furthermore, a mass in the pelvic cavity and massive ascites were found after an imaging examination. After resection, the mass was sent to the pathology department for a definite diagnosis, and the micromorphology showed an undifferentiated sarcoma with massive necrosis. The tumor cells were round to spindle with clear to eosinophilic cytoplasm and vesicular nuclei. Rhabdoid cells and myxoid mesenchyme were focally shown. Immunohistochemical staining showed diffusely positive for vimentin, cyclin D1, Fli-1, and WT-1 and very focally positive for CD99. Moreover, the targeted next-generation sequencing also revealed other genetic changes in this tumor including LongInDel of POLE, copy number variation of CD79, low tumor mutational burden, and microsatellite stability. With a follow-up time of 6 months, the patient survived the disease and received chemotherapy routinely. This report presented a rare primary site CIC–DUX4 fusion-positive sarcoma (CDS) and revealed novel genetic changes that enrich the manifestation, histology, and cytogenetic scales of this rare sarcoma. In addition, we have summarized the clinicopathologic characteristics of this tumor by reviewing the literature to have a better understanding of CIC–DUX4 fusion-positive sarcomas, which may be helpful for diagnosis and treatment.
Predictive value of PD-L1 expression in response to immune checkpoint inhibitors for esophageal cancer treatment: A systematic review and meta-analysis
Authors: Noori Maryam , Yousefi Amir-Mohammad , Zali Mohammad Reza , Bashash Davood
Published: December 2022

Background

Programmed death-ligand-1 (PD-L1) molecule is a well-known predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in several cancers. Present systematic review and meta-analysis aimed at investigating the role of PD-L1 in predicting the effectiveness of programmed death-1 (PD-1)/PD-L1 inhibitors in patients suffering from esophageal cancer.

Methods

We searched PubMed, Scopus, Web of Science, and EMBASE databases as of March 25, 2022, for retrieving the potential relevant randomized controlled trials (RCTs). The pooled hazard ratios (HR) and the corresponding 95% confidence intervals (95%CIs) were calculated for the outcomes of overall survival (OS) and progression-free survival (PFS). The primary objective was to investigate the association between PD-1/PD-L1 inhibitors vs. control agents and treatment efficacy in terms of OS in patients with esophageal tumor expressing different values of PD-L1 based on combined-positive score (CPS) and tumor proportion score (TPS). The secondary outcome was the pooled risk of PFS.

Results

Eleven studies with a total of 5,418 participants were included. While there was no difference in the OS of CPS<1 patients in the intervention and the control group, patients bearing esophageal tumors with a CPS≥1 (HR 0.65, 0.56-0.74) treated by ICIs showed a significant improvement in OS relative to the control agents. Accordingly, patients with CPS<5 (HR 0.75, 0.58-0.98), CPS≥5 (HR 0.64, 0.53-0.77), CPS<10 (HR 0.86, 0.76-0.98), and CPS≥10 (HR 0.65, 0.56-0.75) had improved OS; however, a significant longer OS was observed in cases who expressed higher values of CPS=10 (p=0.018). In terms of TPS, a significant greater benefit in prolonging the OS came from TPS≥1% PD-L1 expressing tumors in comparison to TPS<1% tumors, suggesting this cut-off as another predictor of PD-1/PD-L1 inhibitors efficacy. Notably, in the subgroup analysis when the cut-off value of CPS=10 or TPS=1% was selected, Nivolumab was the best ICI that improved the survival of PD-L1 positive patients. In patients with negative PD-L1 expression, Toripalimib is the only ICI which could prolong the OS of patients with the cut-off value of CPS=10.

Conclusion

Among patients suffering from esophageal cancer, PD-L1 CPS=10 and TPS=1% expression thresholds seem to be predictive of a lower rate of mortality when PD-1/PD-L1 inhibitors are administrated; however, further large-scale trials are required for confirming the findings of the present study.
A novel nomogram model combining CT texture features and urine energy metabolism to differentiate single benign from malignant pulmonary nodule
Authors: Shen Jing , Du Hai , Wang Yadong , Du Lina , Yang Dong , Wang Lingwei , Zhu Ruiping , Zhang Xiaohui , Wu Jianlin
Published: December 2022

Objective

To investigate a novel diagnostic model for benign and malignant pulmonary nodule diagnosis based on radiomic and clinical features, including urine energy metabolism index.

Methods

A total of 107 pulmonary nodules were prospectively recruited and pathologically confirmed as malignant in 86 cases and benign in 21 cases. A chest CT scan and urine energy metabolism test were performed in all cases. A nomogram model was established in combination with radiomic and clinical features, including urine energy metabolism levels. The nomogram model was compared with the radiomic model and the clinical feature model alone to test its diagnostic validity, and receiver operating characteristic (ROC) curves were plotted to assess diagnostic validity.

Results

The nomogram was established using a logistic regression algorithm to combine radiomic features and clinical characteristics including urine energy metabolism results. The predictive performance of the nomogram was evaluated using the area under the ROC and calibration curve, which showed the best performance, area under the curve (AUC) = 0.982, 95% CI = 0.940–1.000, compared to clinical and radiomic models in the testing cohort. The clinical benefit of the model was assessed using the decision curve analysis (DCA) and using the nomogram for benign and malignant pulmonary nodules, and preoperative prediction of benign and malignant pulmonary nodules using nomograms showed better clinical benefit.

Conclusion

This study shows that a coupled model combining CT imaging features and clinical features (including urine energy metabolism) in combination with the nomogram model has higher diagnostic performance than the radiomic and clinical models alone, suggesting that the combination of both methods is more advantageous in identifying benign and malignant pulmonary nodules.
Theranostic digital twins for personalized radiopharmaceutical therapies: Reimagining theranostics via computational nuclear oncology
Authors: Rahmim Arman , Brosch-Lenz Julia , Fele-Paranj Ali , Yousefirizi Fereshteh , Soltani Madjid , Uribe Carlos , Saboury Babak
Published: December 2022

This work emphasizes that patient data, including images, are not operable (clinically), but that digital twins are. Based on the former, the latter can be created. Subsequently, virtual clinical operations can be performed towards selection of optimal therapies. Digital twins are beginning to emerge in the field of medicine. We suggest that theranostic digital twins (TDTs) are amongst the most natural and feasible flavors of digitals twins. We elaborate on the importance of TDTs in a future where ‘one-size-fits-all’ therapeutic schemes, as prevalent nowadays, are transcended in radiopharmaceutical therapies (RPTs). Personalized RPTs will be deployed, including optimized intervention parameters. Examples include optimization of injected radioactivities, sites of injection, injection intervals and profiles, and combination therapies. Multi-modal multi-scale images, combined with other data and aided by artificial intelligence (AI) techniques, will be utilized towards routine digital twinning of our patients, and will enable improved deliveries of RPTs and overall healthcare.
The mechanisms and roles of melatonin in gastrointestinal cancer
Authors: Gong Yong-Qiang , Hou Fu-Tao , Xiang Cai-Ling , Li Cheng-Long , Hu Guo-Huang , Chen Chao-Wu
Published: December 2022

Gastrointestinal (GI) cancer is a global health problem with wide lesions and numerous cases. The increased morbidity and mortality of GI cancer is a socio-economic challenge for decades to come. Melatonin, a nature indolamine, exerts a crucial role in molecular interactions involved in multiple functional and physiological processes. Increasing evidence indicates that melatonin can modulate GI tract, decrease the occurrence of GI cancer, and enhance the sensitivity to chemoradiotherapy. However, little is known about the exact role of melatonin in anti-carcinogenesis. In this review, we discuss the action of the beneficial effects of melatonin in GI carcinogenesis. Furthermore, we compile the understanding of the role of melatonin in GI cancer, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), and pancreatic cancer (PC). In addition, the potential therapeutic application and clinical evaluation of melatonin in GI cancer are also discussed.
Detection of circulating KRAS mutant DNA in extracellular vesicles using droplet digital PCR in patients with colon cancer
Authors: Choi Jeesoo , Cho Ho Yeon , Jeon Jeongseok , Kim Kyung-A , Han Yoon Dae , Ahn Joong Bae , Wortzel Inbal , Lyden David , Kim Han Sang
Published: December 2022

Background

Extracellular vesicles secreted by tumor cells contain double-stranded DNA called extracellular vesicle DNA (evDNA). EvDNA is genomic DNA that reflects cancer driver mutations. However, the significance of evDNA analysis in the diagnosis and surveillance of colon cancer remains unclear. This study aimed to investigate the clinical utility of extracellular vesicles and evDNA isolated from the plasma of colon cancer patients harboring KRAS G12D and G13D mutations.

Methods

Cell-free DNA (cfDNA) and evDNA were collected from the plasma of 30 patients with colon cancer. KRAS mutation status (G12D and G13D) was detected using a droplet digital polymerase chain reaction assay (ddPCR). Sensitivity and specificity were evaluated in patients with wild-type KRAS tumors. Mutation status was correlated with carcinoembryonic antigen (CEA) levels and overall survival (OS).

Results

Thirty cfDNA and evDNA pairs showed a KRAS fractional abundance (FA) ranging from 0 to 45.26% and 0 to 83.81%, respectively. When compared with eight wild-type KRAS samples, cfDNA exhibited 70% sensitivity and 100% specificity, whereas evDNA achieved 76.67% sensitivity and 100% specificity. The concentration of evDNA was significantly lower than that of cfDNA, but it obtained a higher FA than cfDNA, while showing a positive correlation with CEA.

Conclusions

Our findings demonstrate the feasibility of evDNA as a complementary tool to aid current methods of patient evaluation in the diagnosis and surveillance of colon cancer.
A tumor microenvironment preoperative nomogram for prediction of lymph node metastasis in bladder cancer
Authors: Chen Zhenghao , Qin Chuan , Wang Gang , Shang Donghao , Tian Ye , Yuan Lushun , Cao Rui
Published: December 2022

Background

Growing evidence suggests that tumor metastasis necessitates multi-step microenvironmental regulation. Lymph node metastasis (LNM) influences both pre- and post-operative bladder cancer (BLCA) treatment strategies. Given that current LNM diagnosis methods are still insufficient, we intend to investigate the microenvironmental changes in BLCA with and without LNM and develop a prediction model to confirm LNM status.

Method

"Estimation of Stromal and Immune cells in Malignant Tumors using Expression data" (ESTIMATE) algorithm was used to characterize the tumor microenvironment pattern of TCGA-BLCA cohort, and dimension reduction, feature selection, and StrLNM signature construction were accomplished using least absolute shrinkage and selection operator (LASSO) regression. StrLNM signature was combined with the genomic mutation to establish an LNM nomogram by using multivariable logistic regression. The performance of the nomogram was evaluated in terms of calibration, discrimination, and clinical utility. The testing set from the TCGA-BLCA cohort was used for internal validation. Moreover, three independent cohorts were used for external validation, and BLCA patients from our cohort were also used for further validation.

Results

The StrLNM signature, consisting of 22 selected features, could accurately predict LNM status in the TCGA-BLCA cohort and several independent cohorts. The nomogram performed well in discriminating LNM status, with the area under curve (AUC) of 75.1% and 65.4% in training and testing datasets from the TCGA-BLCA cohort. Furthermore, the StrLNM nomogram demonstrated good calibration with p >0.05 in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis (DCA) revealed that the StrLNM nomogram had a high potential for clinical utility. Additionally, 14 of 22 stably expressed genes were identified by survival analysis and confirmed by qPCR in BLCA patient samples in our cohort.

Conclusion

In summary, we developed a nomogram that included an StrLNM signature and facilitated the preoperative prediction of LNM status in BLCA patients.
Antipsychotic exposure is an independent risk factor for breast cancer: A systematic review of epidemiological evidence
Authors: Gao Zheng , Xi Yin , Shi Hekai , Ni Jiyuan , Xu Wei , Zhang Kaili
Published: December 2022

Background

The effect of antipsychotics on breast cancer remains controversial.

Materials and methods

Embase, Scopus, PubMed, Web of Science, Cochrane Library, and Hebei Medical University Library were used for the literature search. Observational studies with original data for the effects of antipsychotics on breast cancer were used. Studies of bed quality, those with inadequate sample size, incomplete follow-up works, or studies that did not meet the criteria were excluded. Meta-analysis was performed using R version 4.1.2. The odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the proportion of breast cancer in different groups. To detect possible sources of heterogeneity, subgroup and meta-regression analyses were employed.

Results

Pooled data from 11 relevant studies with 1,499,001 participants suggested that individuals exposed to antipsychotics were more likely to suffer from breast cancer than those who were not exposed (OR, 1.23; 95% CI, 1.04–1.47). No significant difference in breast cancer prevalence between the atypical and typical antipsychotic groups was found (OR, 1.23; 95% CI, 0.93–1.63). Prolactin (PRL)-increasing and PRL-sparing antipsychotics posed a similar risk of breast cancer (OR, 1.13; 95% CI, approximately 0.97–1.31). Furthermore, the use of antipsychotics is attributed to increased mortality in patients with breast cancer (OR, 1.54; 95% CI, 1.29–1.82). Those exposed to antipsychotics at the maximum dose were more likely to suffer from breast cancer than those exposed to the minimum dose.

Conclusions

Antipsychotic exposure is an independent risk factor for breast cancer. No significant difference in the risk of breast cancer between typical and atypical antipsychotics was noted. Those exposed to antipsychotics at higher doses are more likely to suffer from breast cancer. Moreover, the use of antipsychotics is attributed to increased mortality in patients with breast cancer. PRL-increasing and PRL-sparing antipsychotics pose a similar risk of breast cancer.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022307624.
Incidence, etiology, sociodemographic and clinical characterization of acute respiratory failure in pediatric patients at a high-altitude city: A multicenter cohort study
Authors: Vargas Muñoz Sarha M. , De Vivero Haddad Sara , Beltran Aldo M. , Bonilla Gonzalez Carolina , Naranjo Vanegas Melisa , Moreno-Lopez Sergio , Rueda-Guevara Paola , Barrera Pedro , Piñeros Juan Gabriel , Mejía Luz Marina , Mesa María Lucia , Restrepo-Gualteros Sonia , Baquero Castañeda Olga Lucía , Ramírez Varela Andrea
Published: December 2022

Background

Acute respiratory failure is a life-threatening medical condition, associated with a variety of conditions and risk factors, including acute respiratory diseases which are a frequent cause of pediatric morbidity and mortality worldwide. In Colombia, the literature related to ARF is scarce.

Objective

To determine the incidence, causes, and sociodemographic and clinical characteristics of ARF in three hospitals in Bogota, a high-altitude city located in Colombia, during the COVID-19 pandemic.

Methods

A multicenter prospective cohort study called the FARA cohort was developed between April 2020 – December 2021. Patients older than one month and younger than 18 years with respiratory distress who developed ARF were included.

Results

685 patients with respiratory distress were recruited in 21 months. The incidence density of ARF was found to be 41.7 cases per 100 person-year CI 95%, (37.3–47.7). The median age was 4.5 years.. Most of the patients consulted during the first 72 h after the onset of symptoms. Upon admission, 67.2% were potentially unstable. The most frequent pathologies were asthma, bronchiolitis, pneumonia, and sepsis. At admission, 75.6% of the patients required different oxygen delivery systems, 29,5% a low-flow oxygen system, 36,8% a high-flow oxygen system, and 9,28% invasive mechanical ventilation. SARS-COV-2, respiratory syncytial virus, rhinovirus/enterovirus, and adenovirus were the most frequently isolated viral agents. The coinfection cases were scarce.

Conclusions

This multicenter study, the FARA cohort, developed at 2,600 meters above sea level, shows the first data on incidence, etiology, sociodemographic and clinical characterization in a pediatric population with ARF that also concurs with the COVID-19 pandemic. These results, not only have implications for public health but also contribute to the scientific and epidemiological literature on a disease developed at a high altitude.
Glucocorticoid induced adrenal insufficiency in children: Morning cortisol values to avoid LDSST
Authors: Laulhé Margaux , Dumaine Cécile , Chevenne Didier , Leye Fallou , Faye Albert , Dozières Blandine , Strullu Marion , Viala Jérome , Hogan Julien , Houdouin Véronique , Léger Juliane , Simon Dominique , Carel Jean-Claude , Storey Caroline , Guilmin-Crépon Sophie , Martinerie Laetitia
Published: December 2022

Objectives

Glucocorticoid-induced adrenal insufficiency (GI-AI) is a common side effect of glucocorticoid therapy. However, its diagnosis currently relies on the realization of a Low Dose Short Synacthen Test (LD-SST) that requires an outpatient hospital and several blood samples. Our goal was to evaluate whether morning cortisol values could predict the response to LD-SST, in children, to avoid useless dynamic tests and facilitate diagnosis of glucocorticoid induced adrenal insufficiency.

Study Design

We recorded data of 91 pediatric patients who underwent a LD-SST in our center between 2016 and 2020 in a retrospective observational study. We selected LD-SST realized following administration of supra-physiologic doses of glucocorticoids during more than 3 weeks and performed at least four weeks after treatment was stopped. Adrenal deficiency was defined as a plasma cortisol concentration inferior to 500 nmol/l at LD-SST.

Results

Glucocorticoid-induced adrenal insufficiency was diagnosed in 60% of our cohort. Morning cortisol values were predictive of the response to the LD-SST (AUC ROC 0.78). A plasma cortisol concentration of less than 144 nmol/l predicted glucocorticoid induced adrenal insufficiency with a specificity of 94% and a value over 317 nmol/l predicted recovery of the HPA axis with a sensitivity of 95%. We did not find any other predictive factor for glucocorticoid-induced adrenal insufficiency.

Conclusions

Morning cortisol values can safely assess recovery of the HPA axis in children treated chronically with glucocorticoids. Using these thresholds, more than 50% of LD-SST could be avoided in children.
Pharmacovigilance of triazole antifungal agents: Analysis of the FDA adverse event reporting system (FAERS) database
Authors: Zhou Jianxing , Wei Zipeng , Xu Baohua , Liu Maobai , Xu Ruichao , Wu Xuemei
Published: December 2022

Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in the clinic, multiple Adverse Events (AE) are still reported each year. Objective: We aimed to characterize the distribution of Adverse Events associated with Triazole antifungal drugs in different systems and to identify Important Medical Events (IME) signals for Triazole antifungal drugs. Methods: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was queried for Adverse Events related to Triazole antifungal drugs from 2012 to 2022. The Adverse Events caused by all other drugs and non-TAD antifungal drugs were analyzed as references. Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to evaluate the association between Triazole antifungal drugs and Important Medical Events. Visual signal spectrum is mapped to identify potential adverse reaction signals. Results: Overall, 10,262 Adverse Events were reported to be associated with Triazole antifungal drugs, of which 5,563 cases were defined as Important Medical Events. Common adverse drug reactions (ADR) mentioned in the instructions such as delirium and hypokalemia were detected, as well as unlabeled ADRs such as rhabdomyolysis and hepatitis fulminant. Cholestasis, drug-induced liver injury, QT interval prolongation and renal impairment have notable signals in all Triazole antifungal drugs, with 50 percent of patients developing a severe clinical outcome. Isavuconazole had the lowest signal intensity and demonstrated a superior safety profile. Conclusion: Most results are generally consistent with previous studies and are documented in the prescribing instructions, but some IMEs are not included, such as hepatitis fulminant. Additional pharmaco-epidemiological or experimental studies are required to validate the small number of unlabeled ADRs. TAD-related Important Medical Eventshave a considerable potential to cause clinically serious outcomes. Clinical use of Triazole antifungal drugs requires more attention.
A review of recent advances in exosomes and allergic rhinitis
Authors: Zheng Zhong , Yu Yangyang
Published: December 2022

Allergic rhinitis is a chronic inflammatory disease of nasal mucosa caused by the presence of IgE after exposure to allergens, characterized by nasal irritation, hypersecretion of the nasal passages and sneezing, which frequently occurs in children and adolescents. There has been an increase in allergic rhinitis over the past few years due to air pollution. Exosomes have been discovered to be nano-sized vesicles, which contain a wide range of substances, including proteins and nucleic acids, numerous studies indicates that exosomes play a vital role in cells communication. Recently there have been more and more studies exploring the role of exosomes in allergic rhinitis. Therefore, here we will present a comprehensive review of the research on exosomes and their role in allergic rhinitis for the purpose of providing new understanding of potential value of exosomes applied to the treatment of allergic rhinitis.