bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Pain in the Elderly: Mechanisms and Perspectives
Authors: Dagnino Ana P. A. , Campos Maria M.
Published: March 2022

Chronic pain affects a large part of the population causing functional disability, being often associated with coexisting psychological disorders, such as depression and anxiety, besides cognitive deficits, and sleep disturbance. The world elderly population has been growing over the last decades and the negative consequences of chronic pain for these individuals represent a current clinical challenge. The main painful complaints in the elderly are related to neurodegenerative and musculoskeletal conditions, peripheral vascular diseases, arthritis, and osteoarthritis, contributing toward poorly life quality, social isolation, impaired physical activity, and dependence to carry out daily activities. Organ dysfunction and other existing diseases can significantly affect the perception and responses to chronic pain in this group. It has been proposed that elderly people have an altered pain experience, with changes in pain processing mechanisms, which might be associated with the degeneration of circuits that modulate the descending inhibitory pathways of pain. Aging has also been linked to an increase in the pain threshold, a decline of painful sensations, and a decrease in pain tolerance. Still, elderly patients with chronic pain show an increased risk for dementia and cognitive impairment. The present review article is aimed to provide the state-of-art of pre-clinical and clinical research about chronic pain in elderly, emphasizing the altered mechanisms, comorbidities, challenges, and potential therapeutic alternatives.
Browsing Multiple Subjects When the Atlas Adaptation Cannot Be Achieved via a Warping Strategy
Authors: Rivière Denis , Leprince Yann , Labra Nicole , Vindas Nabil , Foubet Ophélie , Cagna Bastien , Loh Kep Kee , Hopkins William , Balzeau Antoine , Mancip Martial , Lebenberg Jessica , Cointepas Yann , Coulon Olivier , Mangin Jean-François
Published: March 2022

Brain mapping studies often need to identify brain structures or functional circuits into a set of individual brains. To this end, multiple atlases have been published to represent such structures based on different modalities, subject sets, and techniques. The mainstream approach to exploit these atlases consists in spatially deforming each individual data onto a given atlas using dense deformation fields, which supposes the existence of a continuous mapping between atlases and individuals. However, this continuity is not always verified, and this “iconic” approach has limits. We present in this study an alternative, complementary, “structural” approach, which consists in extracting structures from the individual data, and comparing them without deformation. A “structural atlas” is thus a collection of annotated individual data with a common structure nomenclature. It may be used to characterize structure shape variability across individuals or species, or to train machine learning systems. This study exhibits Anatomist, a powerful structural 3D visualization software dedicated to building, exploring, and editing structural atlases involving a large number of subjects. It has been developed primarily to decipher the cortical folding variability; cortical sulci vary enormously in both size and shape, and some may be missing or have various topologies, which makes iconic approaches inefficient to study them. We, therefore, had to build structural atlases for cortical sulci, and use them to train sulci identification algorithms. Anatomist can display multiple subject data in multiple views, supports all kinds of neuroimaging data, including compound structural object graphs, handles arbitrary coordinate transformation chains between data, and has multiple display features. It is designed as a programming library in both C++ and Python languages, and may be extended or used to build dedicated custom applications. Its generic design makes all the display and structural aspects used to explore the variability of the cortical folding pattern work in other applications, for instance, to browse axonal fiber bundles, deep nuclei, functional activations, or other kinds of cortical parcellations. Multimodal, multi-individual, or inter-species display is supported, and adaptations to large scale screen walls have been developed. These very original features make it a unique viewer for structural atlas browsing.
Managing Nutrition Impact Symptoms in Cancer Cachexia: A Case Series and Mini Review
Authors: Khorasanchi Adam , Nemani Srinidhi , Pandey Sudeep , Del Fabbro Egidio
Published: March 2022

Malnutrition is common in cancer patients and can occur throughout a patient’s disease course. The contributors to the clinical syndrome of cancer cachexia are often multifactorial, and produced by the cancer and associated pro-inflammatory response. Since cancer cachexia is a multifactorial syndrome, a multimodal therapeutic approach is ideal. A key component of therapy is identifying and managing symptom barriers to adequate oral intake, known as nutritional impact symptoms (NIS). NIS are associated with reduced intake and weight loss in patients with advanced cancer, and aggregate NIS are a predictor of survival in patients with Head and Neck Cancer and in patients undergoing surgery for esophageal cancer. Currently, there are no guidelines regarding the specific management of NIS in oncology patients. Experience from specialist centers suggest relatively simple assessments and inexpensive interventions are available for the diagnosis and treatment of NIS. We present three patient cases from a cachexia clinic, where NIS management decreased symptom burden and improved clinical outcomes such as weight and physical performance.
Effects of Oral Administration of Bamboo (Dendrocalamus membranaceus) Leaf Flavonoids on the Antioxidant Capacity, Caecal Microbiota, and Serum Metabolome of Gallus gallus domesticus
Authors: Cao Guangtian , Yu Yang , Wang Huixian , Liu Jinsong , Zhang Xiping , Yu Yue , Li Zhanming , Zhang Yan , Yang Caimei
Published: March 2022

The consumption of bamboo leaf flavonoids (BLFs) as novel dietary antioxidants has increased owing to their beneficial biological and pharmacological functions. This study assessed the in vivo effects of BLFs on antioxidant capacity, as well as caecal microbiota, serum metabolome, and health status. The Gallus gallus domesticus model and the oral administration approach were used with four treatment groups (basal diet, basal diet with 20 mg bacitracin/kg, basal diet with 50 mg BLF/kg, and basal diet with 250 mg BLF/kg). Ultra-high-performance liquid chromatography triple-quadrupole mass spectrometry analysis indicated that vitexin, fumaric acid, orientin, isoorientin, and p-coumaric acid were the predominant BLF components. From days 1 to 21, BLF increased the average daily gain and decreased the feed:gain of broilers. Moreover, BLF enhanced the serum antioxidant capacity and immune responses. Further, 16S rRNA sequencing showed that BLF modulated the caecal microbial community structure, which was dominated by Betaproteobacteriales, Erysipelatoclostridium, Parasutterella, Lewinella, Lactobacillus, and Candidatus Stoquefichus in BLF broilers. Among the 22 identified serum metabolites in BLF broilers, sphinganine, indole-3-acetaldehyde retinol, choline, 4-methylthio-2-oxobutanoic acid, and L-phenylalanine were recognised as biomarkers. In summary, BLFs appeared to modulate the caecal microbiome, alter the serum metabolome, and indirectly improve antioxidant capacity and health status.
Gene Promoter-Methylation Signature as Biomarker to Predict Cisplatin-Radiotherapy Sensitivity in Locally Advanced Cervical Cancer
Authors: Contreras-Romero Carlos , Pérez-Yépez Eloy-Andrés , Martinez-Gutierrez Antonio Daniel , Campos-Parra Alma , Zentella-Dehesa Alejandro , Jacobo-Herrera Nadia , López-Camarillo César , Corredor-Alonso Guillermo , Martínez-Coronel Jaime , Rodríguez-Dorantes Mauricio , de León David Cantu , Pérez-Plasencia Carlos
Published: March 2022

Despite efforts to promote health policies focused on screening and early detection, cervical cancer continues to be one of the leading causes of mortality in women; in 2020, estimated 30,000 deaths in Latin America were reported for this type of tumor. While the therapies used to treat cervical cancer have excellent results in tumors identified in early stages, those women who are diagnosed in locally advanced and advanced stages show survival rates at 5 years of <50%. Molecular patterns associated with clinical response have been studied in patients who present resistance to treatment; none of them have reached clinical practice. It is therefore necessary to continue analyzing molecular patterns that allow us to identify patients at risk of developing resistance to conventional therapy. In this study, we analyzed the global methylation profile of 22 patients diagnosed with locally advanced cervical cancer and validated the genomic results in an independent cohort of 70 patients. We showed that BRD9 promoter region methylation and CTU1 demethylation were associated with a higher overall survival (p = 0.06) and progression-free survival (p = 0.0001), whereas DOCK8 demethylation was associated with therapy-resistant patients and a lower overall survival and progression-free survival (p = 0.025 and p = 0.0001, respectively). Our results suggest that methylation of promoter regions in specific genes may provide molecular markers associated with response to treatment in cancer; further investigation is needed.
Immune Infiltration and Clinical Outcome of Super-Enhancer-Associated lncRNAs in Stomach Adenocarcinoma
Authors: Peng Li , Peng Jiang-Yun , Cai Dian-Kui , Qiu Yun-Tan , Lan Qiu-Sheng , Luo Jie , Yang Bing , Xie Hai-Tao , Du Ze-Peng , Yuan Xiao-Qing , Liu Yue , Yin Dong
Published: March 2022

Super-enhancers (SEs) comprise large clusters of enhancers that highly enhance gene expression. Long non-coding RNAs (lncRNAs) tend to be dysregulated in cases of stomach adenocarcinoma (STAD) and are vital for balancing tumor immunity. However, whether SE-associated lncRNAs play a role in the immune infiltration of STAD remains unknown. In the present study, we identified SE-associated lncRNAs in the H3K27ac ChIP-seq datasets from 11 tumor tissues and two cell lines. We found that the significantly dysregulated SE-associated lncRNAs were strongly correlated with immune cell infiltration through the application of six algorithms (ImmuncellAI, CIBERSORT, EPIC, quantiSeq, TIMER, and xCELL), as well as immunomodulators and chemokines. We found that the expression of SE-associated lncRNA TM4SF1-AS1 was negatively correlated with the proportion of CD8+ T cells present in STAD. TM4SF1-AS1 suppresses T cell-mediated immune killing function and predicts immune response to anti-PD1 therapy. ChIP-seq, Hi-C and luciferase assay results verified that TM4SF1-AS1 was regulated by its super-enhancer. RNA-seq data showed that TM4SF1-AS1 is involved in immune and cancer-related processes or pathways. In conclusion, SE-associated lncRNAs are involved in the tumor immune microenvironment and act as indicators of clinical outcomes in STAD. This study highlights the importance of SE-associated lncRNAs in the immune regulation of STAD.
Multiparametric MRI-Based Radiomics Model for Predicting H3 K27M Mutant Status in Diffuse Midline Glioma: A Comparative Study Across Different Sequences and Machine Learning Techniques
Authors: Guo Wei , She Dejun , Xing Zhen , Lin Xiang , Wang Feng , Song Yang , Cao Dairong
Published: March 2022

Objectives

The performance of multiparametric MRI-based radiomics models for predicting H3 K27M mutant status in diffuse midline glioma (DMG) has not been thoroughly evaluated. The optimal combination of multiparametric MRI and machine learning techniques remains undetermined. We compared the performance of various radiomics models across different MRI sequences and different machine learning techniques.

Methods

A total of 102 patients with pathologically confirmed DMG were retrospectively enrolled (27 with H3 K27M-mutant and 75 with H3 K27M wild-type). Radiomics features were extracted from eight sequences, and 18 feature sets were conducted by independent combination. There were three feature matrix normalization algorithms, two dimensionality-reduction methods, four feature selectors, and seven classifiers, consisting of 168 machine learning pipelines. Radiomics models were established across different feature sets and machine learning pipelines. The performance of models was evaluated using receiver operating characteristic curves with area under the curve (AUC) and compared with DeLong’s test.

Results

The multiparametric MRI-based radiomics models could accurately predict the H3 K27M mutant status in DMG (highest AUC: 0.807–0.969, for different sequences or sequence combinations). However, the results varied significantly between different machine learning techniques. When suitable machine learning techniques were used, the conventional MRI-based radiomics models shared similar performance to advanced MRI-based models (highest AUC: 0.875–0.915 vs. 0.807–0.926; DeLong’s test, p > 0.05). Most models had a better performance when generated with a combination of MRI sequences. The optimal model in the present study used a combination of all sequences (AUC = 0.969).

Conclusions

The multiparametric MRI-based radiomics models could be useful for predicting H3 K27M mutant status in DMG, but the performance varied across different sequences and machine learning techniques.
Thymidine Kinase 1 Drives Skin Cutaneous Melanoma Malignant Progression and Metabolic Reprogramming
Authors: Zuo Sipeng , Wang Huixue , Li Lin , Pan Hui , Lu Linna
Published: March 2022

Background

Thymidine kinase 1 (TK1) is a cell cycle-dependent kinase that catalyzes the addition of a gamma-phosphate group to thymidine. The protumorigenic role of TK1 has been reported in various malignancies. However, the role of TK1 in skin cutaneous melanoma (SKCM) remains unclear. This study aimed to explore the molecular function of TK1 in SKCM progression.

Methods

Bioinformatics data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Subcutaneous xenografts were established to observe the effect of TK1 knockdown on the proliferation of SKCM cells in vivo. RNA sequencing (RNA-seq; deposited in Sequence Read Archive, SRX10950283-SRX10950285 for A375 control cells and SRX10950286-SRX10950288 for TK1-silenced A375 cells) and immunoprecipitation–mass spectrometry (IP-MS) were used to analyze TK1-related genes and pathways. Seahorse XF Cell Mito tests and glycolysis stress assays were conducted for metabolic testing.

Results

TK1 was upregulated in malignant SKCM compared to that in normal tissues and cell lines. Elevated expression of TK1 was associated with poor prognosis. In vitro and in vivo assays demonstrated that TK1 promoted the proliferation and migration of SKCM cells. Moreover, TK1 was strongly associated with multiple intracellular metabolic pathways, facilitating cell mitochondrial respiration and glycolysis in SKCM malignant progression.

Conclusions

TK1 drives SKCM malignant progression and supports metabolic reprogramming, indicating that TK1 serves as a therapeutic target for SKCM.
High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 1: Perfusion and Diffusion Techniques
Authors: Henriksen Otto M. , del Mar Álvarez-Torres María , Figueiredo Patricia , Hangel Gilbert , Keil Vera C. , Nechifor Ruben E. , Riemer Frank , Schmainda Kathleen M. , Warnert Esther A. H. , Wiegers Evita C. , Booth Thomas C.
Published: March 2022

Objective

Summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments.

Methods

Experts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics).

Results

High-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motion, and other microstructural modeling approaches also allow treatment response assessment; more robust data are required to validate these alone or when applied to post-processing methodologies.

Conclusion

Considerable progress has been made in the development of these monitoring biomarkers. Many techniques are in their infancy, whereas others have generated a larger body of evidence for clinical application.
Roles of Plasmacytoid Dendritic Cells in Gastric Cancer
Authors: Yang Jinpu , Liu Xia , Cheng Yiwen , Zhang Jingchen , Ji Feng , Ling Zongxin
Published: March 2022

Gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer in humans worldwide. Helicobacter pylori infection is the most important causative factor of gastric carcinogenesis, and activates host innate and adaptive immune responses. As key constituents of the tumor immune microenvironment, plasmacytoid dendritic cells (pDCs) are increasingly attracting attention owing to their potential roles in immunosuppression. We recently reported that pDCs have vital roles in the development of immunosuppression in GC. Clarifying the contribution of pDCs to the development and progression of GC may lead to improvements in cancer therapy. In this review, we summarize current knowledge regarding immune modulation in GC, especially the roles of pDCs in GC carcinogenesis and treatment strategies.
Cancer Neoantigens: Challenges and Future Directions for Prediction, Prioritization, and Validation
Authors: Borden Elizabeth S. , Buetow Kenneth H. , Wilson Melissa A. , Hastings Karen Taraszka
Published: March 2022

Prioritization of immunogenic neoantigens is key to enhancing cancer immunotherapy through the development of personalized vaccines, adoptive T cell therapy, and the prediction of response to immune checkpoint inhibition. Neoantigens are tumor-specific proteins that allow the immune system to recognize and destroy a tumor. Cancer immunotherapies, such as personalized cancer vaccines, adoptive T cell therapy, and immune checkpoint inhibition, rely on an understanding of the patient-specific neoantigen profile in order to guide personalized therapeutic strategies. Genomic approaches to predicting and prioritizing immunogenic neoantigens are rapidly expanding, raising new opportunities to advance these tools and enhance their clinical relevance. Predicting neoantigens requires acquisition of high-quality samples and sequencing data, followed by variant calling and variant annotation. Subsequently, prioritizing which of these neoantigens may elicit a tumor-specific immune response requires application and integration of tools to predict the expression, processing, binding, and recognition potentials of the neoantigen. Finally, improvement of the computational tools is held in constant tension with the availability of datasets with validated immunogenic neoantigens. The goal of this review article is to summarize the current knowledge and limitations in neoantigen prediction, prioritization, and validation and propose future directions that will improve personalized cancer treatment.
Dosimetric Evaluation of Incidental Irradiation to the Internal Mammary Chain After Surgery in Breast Cancer Patients
Authors: Wang Wei , Sun Tao , Meng Yingtao , Xu Min , Zhang Yingjie , Shao Qian , Song Yuanfang , Li Jianbin
Published: March 2022

Background and Purpose

The low rate of internal mammary node (IMN) recurrence was attributed to systemic therapy and internal mammary chain (IMC) coverage by the tangential fields of irradiation. This study aimed to evaluate the incidental irradiation dose to the IMC in breast cancer patients after surgery and to estimate the clinical predictive parameters affecting the magnitude of the IMC.

Materials and Methods

A total of 138 patients treated with postmastectomy radiotherapy and 210 patients undergoing radiotherapy after breast-conserving surgery (BCS) in our hospital were retrospectively analyzed. The mean dose (Dmean) to the IMC and the first to third intercostal spaces of IMC levels (ICS1–3) were evaluated. We evaluated the IMC coverage according to the type of surgery and whether the ipsilateral supraclavicular fossa (SCF) was included in the irradiation field.

Results

The incidental radiation dose to the IMC was 29.69 Gy, and the dose delivered to the IMC, ICS1, and ICS2 showed a greater coverage in the modified radical mastectomy (MRM) group when compared with the BCS group (32.85 vs. 27.1 Gy, 26.6 vs. 12.5 Gy, 34.63 vs. 30.42 Gy). The dose delivered to ICS3 showed no difference between the MRM and BCS groups (37.41 vs. 36.24 Gy). Furthermore, 131 patients (37.64%) received radiotherapy to the chest wall and ipsilateral SCF. In the univariate analysis, both surgery type and SCF irradiation were parameters affecting the Dmean of incidental radiation to the IMC (r = −0.179, P = 0.001; r = −0.175, P = 0.001). In the multivariate analysis, surgery type was the only correlative factor that affected incidental radiation dose to the IMC (r = –3.534, P = 0.000).

Conclusion

The real influencing factor of incidental dose to the IMC was the surgery form rather than the accession of SCF irradiation.
NcRNA-Mediated High Expression of HMMR as a Prognostic Biomarker Correlated With Cell Proliferation and Cell Migration in Lung Adenocarcinoma
Authors: Jiang Xiulin , Tang Lin , Yuan Yixiao , Wang Juan , Zhang Dahang , Qian Kebao , Cho William C. , Duan Lincan
Published: March 2022

Background

Hyaluronan-mediated motility receptor (HMMR) plays a pivotal role in cell proliferation in various cancers, including lung cancer. However, its function and biological mechanism in lung adenocarcinoma (LUAD) remain unclear.

Methods

Data on HMMR expression from several public databases were extensively analyzed, including the prognosis of HMMR in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using DAVID and gene set enrichment analysis (GSEA) software. The correlation between HMMR expression and immune cell infiltration was analyzed in the Tumor Immune Estimation Resource (TIMER) database, and the gene and protein networks were examined using the GeneMANIA and STRING databases. Experimentally, the expression of HMMR in LUAD and lung cancer cell lines was determined using immunohistochemistry and quantitative RT-PCR assays. Besides, the function of HMMR on cancer cell proliferation and migration was examined using cell growth curve and colony formation, Transwell, and wound healing assays.

Results

In this study, we found that HMMR was elevated in LUAD and that its high expression was associated with poor clinicopathological features and adverse outcomes in LUAD patients. Furthermore, our results demonstrated that the expression of HMMR was positively correlated with immune cell infiltration and immune modulation. Interestingly, diverse immune cell infiltration affects the prognosis of LUAD. In the functional assay, depletion of HMMR significantly repressed the cancer cell growth and migration of LUAD. Mechanically, we found that that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR in LUAD. Depletion of TMPO-AS1 and overexpression of let-7b-5p could result in the decreased expression of HMMR in LUAD cells. Furthermore, we found that TMPO-AS1 was positively correlated with HMMR, yet negatively correlated with let-7b-5p expression in LUAD.

Conclusions

Our findings elucidated that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR, which may be considered as a biomarker to predict prognosis in LUAD.
An Assisted Diagnosis Model for Cancer Patients Based on Federated Learning
Authors: Ma Zezhong , Zhang Meng , Liu Jiajia , Yang Aimin , Li Hao , Wang Jian , Hua Dianbo , Li Mingduo
Published: March 2022

Since the 20th century, cancer has been a growing threat to human health. Cancer is a malignant tumor with high clinical morbidity and mortality, and there is a high risk of recurrence after surgery. At the same time, the diagnosis of whether the cancer is in situ recurrence is crucial for further treatment of cancer patients. According to statistics, about 90% of cancer-related deaths are due to metastasis of primary tumor cells. Therefore, the study of the location of cancer recurrence and its influencing factors is of great significance for the clinical diagnosis and treatment of cancer. In this paper, we propose an assisted diagnosis model for cancer patients based on federated learning. In terms of data, the influencing factors of cancer recurrence and the special needs of data samples required by federated learning were comprehensively considered. Six first-level impact indicators were determined, and the historical case data of cancer patients were further collected. Based on the federated learning framework combined with convolutional neural network, various physical examination indicators of patients were taken as input. The recurrence time and recurrence location of patients were used as output to construct an auxiliary diagnostic model, and linear regression, support vector regression, Bayesling regression, gradient ascending tree and multilayer perceptrons neural network algorithm were used as comparison algorithms. CNN’s federated prediction model based on improved under the condition of the joint modeling and simulation on the five types of cancer data accuracy reached more than 90%, the accuracy is better than single modeling machine learning tree model and linear model and neural network, the results show that auxiliary diagnosis model based on the study of cancer patients in assisted the doctor in the diagnosis of patients, As well as effectively provide nutritional programs for patients and have application value in prolonging the life of patients, it has certain guiding significance in the field of medical cancer rehabilitation.
A Polydopamine-Coated Platinum Nanoplatform for Tumor-Targeted Photothermal Ablation and Migration Inhibition
Authors: Zou Xianwen , Ma Guiqi , Zhu Pengyu , Cao Yutao , Sun Xiao , Wang Haijun , Dong Jian
Published: March 2022

In this work, Arg-Gly-Asp (RGD) peptide-coupled polydopamine-modified mesoporous platinum nanoparticles (mPt@PDA-RGD NPs) were developed for targeted photothermal therapy (PTT) and migration inhibition of SKOV-3 cells. mPt@PDA-RGD NPs with obvious core/shell structure demonstrated high photothermal performance under 808-nm near-infrared (NIR) laser irradiation. mPt@PDA-RGD NPs with favorable biocompatibility exhibited remarkable SKOV-3 inhibition ability under NIR laser irradiation. Moreover, compared to mPt@PDA NPs, the RGD-functionalized NPs achieved more tumor uptake and PTT performance, which was attributed to the specific interaction between RGD of NPs and αvβ3 integrin overexpressed by SKOV-3. Importantly, cell scratch experiments indicated that the photothermal effect of mPt@PDA-RGD NPs can effectively inhibit the migration of surviving SKOV-3 cells, which was assigned to disturbance of the actin cytoskeleton of SKOV-3. Thus, mPt@PDA-RGD NPs presented great potential for targeted tumor photothermal ablation and migration inhibition.
Peripapillary Choroidal Vascularity and Visual Correlates in Non-Arteritic Anterior Ischemic Optic Neuropathy Using Swept-Source Optical Coherence Tomography
Authors: Lu Edward S. , Katz Raviv , Miller John B. , Gaier Eric D.
Published: March 2022

Introduction

The peripapillary choroid shares a blood supply with and is directly apposed to the optic nerve, and therefore may contribute to the pathogenesis of non-arteritic anterior ischemic optic neuropathy (NAION). Prior studies evaluating peripapillary choroidal thickness (PCT) or choroidal vascularity index (CVI; the ratio of the perfused area to total choroid area) have produced mixed results. None investigated the relationship between PCT and CVI or demonstrated functional correlates. We hypothesized that greater PCT and lower CVI would correlate with visual function in patients presenting with NAION.

Methods

Seventeen eyes with NAION (9 acute, 8 non-acute) and 6 unaffected “fellow” eyes in 13 patients, and 18 eyes in 18 age-matched control subjects were imaged using swept-source optical coherence tomography (SS-OCT) prospectively between 2017-2018. Mean PCT and CVI measurements were compared across groups and with respect to corresponding automated perimetric performance at the same visit.

Results

Analysis of variance showed significantly greater PCT (NAION: 278 ± 65 μm, Fellow: 221 ± 50 μm, Control: 158 ± 27 μm, p<0.001) and lower CVI (NAION: 0.35 ± 0.03, Fellow: 0.35 ± 0.04, Control: 0.38 ± 0.02, p<0.005) in patients with NAION compared to control subjects. Bonferroni-corrected pairwise comparisons showed greater PCT and lower CVI in NAION-affected eyes compared to control eyes (p values<0.008), and no significant differences in PCT or CVI between NAION and fellow eyes (p values>0.06). PCT was negatively correlated with CVI among unaffected fellow eyes (r=-0.8, p<0.05), but not among acute NAION eyes (r=-0.1, p>0.7), non-acute NAION eyes (r=0.1, p>0.7), or controls (r=-0.3, p>0.2). Nasal CVI was positively correlated with mean deviation scores in non-acute NAION (r=0.8, p<0.02), but not among fellow unaffected eyes (r=0.8, p>0.05) or acutely affected NAION eyes (r=-0.3, p>0.4). Mean and temporal PCT correlated with pattern standard deviation scores among unaffected fellow eyes (r=0.8, p<0.04; r=0.9, p<0.03), but not among acute NAION eyes (r=-0.2, p>0.5; r=-0.1, p>0.7) or non-acute NAION eyes (r=0.1, p>0.7; r=0.05, p>0.9).

Conclusion

NAION and unaffected fellow eyes demonstrate increased choroidal thicknesses and reduced vascular density. Perimetric performance is directly associated with vascular density among non-acutely affected eyes with NAION. Ongoing work will provide further insights into these structure-function relationships with pathogenic and pathophysiologic relevance.
Case Report: Severe Acute Pulmonary COVID-19 in a Teenager Post Autologous Hematopoietic Stem Cell Transplant
Authors: van der Velden Fabian J. S. , van Delft Frederik , Owens Stephen , Llevadias Judit , McKean Michael , Pulford Lindsey , Taha Yusri , Williamson Grace , Campbell-Hewson Quentin , Hambleton Sophie , Payne Rebecca , Duncan Christopher , Johnston Catriona , Spegarova Jarmila , Emonts Marieke
Published: March 2022

Pulmonary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally described as mild, and SARS-CoV-2 infection in immunocompromised children are observed as generally mild as well. A small proportion of pediatric patients will become critically ill due to (cardio)respiratory failure and require intensive care treatment. We report the case of a teenager with Hodgkin's lymphoma who acquired SARS-CoV-2 (detected by PCR) on the day of her autologous stem cell transplant and developed acute respiratory distress syndrome, successfully treated with a combination of antivirals, immunomodulation with steroids and biologicals, and ECMO.
Quantification of Fetal Renal Function Using Fetal Urine Production Rate and Its Reflection on the Amniotic and Fetal Creatinine Levels During Pregnancy
Authors: Ezuruike Udoamaka , Blenkinsop Alexander , Pansari Amita , Abduljalil Khaled
Published: March 2022

Adequate prediction of fetal exposure of drugs excreted by the kidney requires the incorporation of time-varying renal function parameters into a pharmacokinetic model. Published data on measurements of fetal urinary production rate (FUPR) and creatinine at various gestational ages were collected and integrated for prediction of the fetal glomerular filtration rate (GFR). The predicted GFR values were then compared to neonatal values recorded at birth. Collected data for FUPR across different gestational ages using both 3D (N = 517) and 2D (N = 845) ultrasound methods showed that 2D techniques yield significantly lower estimates of FUPR than 3D (p < 0.0001). A power law function was shown to best capture the change in FUPR with fetal age (FA) for both 2D (FUPR2D(mLmin)=0.000169  FA2.19); and 3D (FUPR3D (mLmin)= 3.21×10-7 FA4.21) data. The predicted FUPR based on the observed 3D data was shown to be strongly linearly related (R2 = 0.95) to measured values of amniotic creatinine concentration (N = 664). The FUPR3D data together with creatinine levels in the fetal urine and serum resulted in median predicted fetal GFR values of 0.47, 1.2, 2.5, and 4.9 ml/min at 23, 28, 33, and 38 weeks of fetal age (50% CV), respectively. These values are in good agreement with neonatal values observed immediately at birth. The derived FUPR and creatinine functions can be utilized to assess fetal renal maturation and predict fetal renal clearance.
DNA Methylation Aberrant in Atherosclerosis
Authors: Dai Yao , Chen Danian , Xu Tingting
Published: March 2022

Atherosclerosis (AS) is a pathological process involving lipid oxidation, immune system activation, and endothelial dysfunction. The activated immune system could lead to inflammation and oxidative stress. Risk factors like aging and hyperhomocysteinemia also promote the progression of AS. Epigenetic modifications, including DNA methylation, histone modification, and non-coding RNA, are involved in the modulation of genes between the environment and AS formation. DNA methylation is one of the most important epigenetic mechanisms in the pathogenesis of AS. However, the relationship between the progression of AS and DNA methylation is not completely understood. This review will discuss the abnormal changes of DNA methylation in AS, including genome-wide hypermethylation dominating in AS with an increase of age, hypermethylation links with methyl supply and generating hyperhomocysteinemia, and the influence of oxidative stress with the demethylation process by interfering with the hydroxyl-methylation of TET proteins. The review will also summarize the current status of epigenetic treatment, which may provide new direction and potential therapeutic targets for AS.
Predictive Simulations in Preclinical Oncology to Guide the Translation of Biologics
Authors: Dong Shujun , Nessler Ian , Kopp Anna , Rubahamya Baron , Thurber Greg M.
Published: March 2022

Preclinical in vivo studies form the cornerstone of drug development and translation, bridging in vitro experiments with first-in-human trials. However, despite the utility of animal models, translation from the bench to bedside remains difficult, particularly for biologics and agents with unique mechanisms of action. The limitations of these animal models may advance agents that are ineffective in the clinic, or worse, screen out compounds that would be successful drugs. One reason for such failure is that animal models often allow clinically intolerable doses, which can undermine translation from otherwise promising efficacy studies. Other times, tolerability makes it challenging to identify the necessary dose range for clinical testing. With the ability to predict pharmacokinetic and pharmacodynamic responses, mechanistic simulations can help advance candidates from in vitro to in vivo and clinical studies. Here, we use basic insights into drug disposition to analyze the dosing of antibody drug conjugates (ADC) and checkpoint inhibitor dosing (PD-1 and PD-L1) in the clinic. The results demonstrate how simulations can identify the most promising clinical compounds rather than the most effective in vitro and preclinical in vivo agents. Likewise, the importance of quantifying absolute target expression and antibody internalization is critical to accurately scale dosing. These predictive models are capable of simulating clinical scenarios and providing results that can be validated and updated along the entire development pipeline starting in drug discovery. Combined with experimental approaches, simulations can guide the selection of compounds at early stages that are predicted to have the highest efficacy in the clinic.
An Interactive City Choice Model and Its Application for Measuring the Intercity Interaction
Authors: Jia Xiang-Yu , Liu Er-Jian , Chen Chun-Yan , He Zhengbing , Yan Xiao-Yong
Published: March 2022

Measuring the interaction between cities is an important research topic in many disciplines, such as sociology, geography, economics, and transportation science. The traditional and most widely used spatial interaction model is the gravity model, but it requires the parameters to be artificially set. In this paper, we propose a parameter-free interactive city choice (ICC) model that measures intercity interaction from the perspective of individual choice behavior. The ICC model assumes that the probability of an individual choosing to interact with a city is proportional to the number of opportunities in the destination city and inversely proportional to the number of intervening opportunities between the origin city and the destination city, calculated using the travel time in the transportation network. The intercity interaction intensity can be obtained by calculating the product of this probability and the origin city’s population. We apply the ICC model to measure the interaction intensity among 339 cities in China and analyze the impact of changes in the Chinese land transportation network from 2005 to 2018 on the intercity and city interaction intensity. The results show that our model provides an alternative method for measuring the intercity interaction.
New Insights Into the Role of Inflammation in the Brain in Heart Failure
Authors: Badoer Emilio
Published: March 2022

Heart failure is a growing medical problem. Although the underlying aetiology of heart failure differs according to the phenotype, there are some common characteristics observed in patients with heart failure. These include an increased sympathetic nerve activity, an activated renin–angiotensin system, and inflammation. The mechanisms mediating the increased sympathetic activity are not completely understood but the central nervous system plays a major role. Activation of the renin–angiotensin system plays an active role in the remodelling of the heart and in fluid and electrolyte imbalance. The presence of a central renin–angiotensin system means that locally produced angiotensin in the brain may also play a key role in autonomic dysfunction seen in heart failure. Markers of inflammation in the heart and in the circulation are observed in patients diagnosed with heart failure. Circulating pro-inflammatory cytokines can also influence cardiac function further afield than just locally in the heart including actions within the brain to activate the sympathetic nervous system. Preclinical evidence suggests that targeting the pro-inflammatory cytokines would be a useful therapy to treat heart failure. Most clinical studies have been disappointing. This mini-review suggests that pro-inflammatory cytokines in the brain play a key role and there is a problem associated with access of effective doses of the drugs to the site of action in the brain. The recent advances in nanotechnology delivery techniques may provide exciting future technology to investigate the role of specific pro-inflammatory mediators as novel targets within the brain in the treatment of heart failure.
Resistance Training of Inspiratory Muscles After Coronary Artery Disease May Improve Obstructive Sleep Apnea in Outpatient Cardiac Rehabilitation: RICAOS Study
Authors: Labeix Pierre , Berger Mathieu , Zellag Amandine , Garcin Arnauld , Barthelemy Jean-Claude , Roche Frederic , Hupin David
Published: March 2022

Background

Obstructive sleep apnea (OSA) affects 5% of the adult population and its prevalence is up to 13 times higher in coronary artery disease (CAD) patients. However, OSA in this population is less symptomatic, leading to lower adherence to positive airway pressure (CPAP). While oropharyngeal exercise showed a significant decrease in apnea-hypopnea index (AHI) in patients with moderate OSA, there have been no studies testing the impact of specific inspiratory muscle training (IMT) for these patients. The aim of our study was to assess the effectiveness of IMT on AHI reduction in CAD patients with moderate OSA.

Methods

We included patients with CAD involved in a cardiac rehabilitation program and presenting an AHI between 15 and 30. Patients were randomized in a 1:1 allocation to a control group (CTL – classic training) or an IMT group (classic training + IMT). IMT consisted in 60 deep inspirations a day, 6 days a week, into a resistive load device set at 70% of the maximum inspiratory pressure (MIP). After 6 weeks, we compared AHI, neck circumference, Epworth Sleepiness Scale, Pittsburgh Sleep Quality index, and quality of life with the 12-item Short Form Survey before and after rehabilitation.

Results

We studied 45 patient (60 ± 9 y, BMI = 27 ± 6 kg.m−2). The IMT group (n = 22) significantly improved MIP ( p < 0.05) and had a significant decrease in AHI by 25% (−6.5 ± 9.5, p = 0.02). In the CTL group (n = 23), AHI decreased only by 3.5% (−0.7 ± 13.1; p = 0.29). Between groups, we found a significant improvement in MIP ( p = 0.003) and neck circumference ( p = 0.01) in favor of the IMT group. However, we did not find any significant improvement of AHI in the IMT group compared to CTL ( p = 0.09).

Conclusion

A specific IMT during cardiac rehabilitation contributes to reduce significantly AHI in CAD patients with moderate OSA. Magnitude of the decrease in OSA severity could be enhanced according to implementation of specific IMT in this population.
Rapid and Selective Absorption of Plant Defense Compounds From the Gut of a Sequestering Insect
Authors: Yang Zhi-Ling , Seitz Fabian , Grabe Veit , Nietzsche Sandor , Richter Adrian , Reichelt Michael , Beutel Rolf , Beran Franziska
Published: March 2022

Many herbivorous insects exploit defense compounds produced by their host plants for protection against predators. Ingested plant defense compounds are absorbed via the gut epithelium and stored in the body, a physiological process that is currently not well understood. Here, we investigated the absorption of plant defense compounds from the gut in the horseradish flea beetle, Phyllotreta armoraciae, a specialist herbivore known to selectively sequester glucosinolates from its brassicaceous host plants. Feeding experiments using a mixture of glucosinolates and other glucosides not found in the host plants showed a rapid and selective uptake of glucosinolates in adult beetles. In addition, we provide evidence that this uptake mainly takes place in the foregut, whereas the endodermal midgut is the normal region of absorption. Absorption via the foregut epithelium is surprising as the apical membrane is covered by a chitinous intima. However, we could show that this cuticular layer differs in its structure and overall thickness between P. armoraciae and a non-sequestering leaf beetle. In P. armoraciae, we observed a thinner cuticle with a less dense chitinous matrix, which might facilitate glucosinolate absorption. Our results show that a selective and rapid uptake of glucosinolates from the anterior region of the gut contributes to the selective sequestration of glucosinolates in P. armoraciae.
Stem Trait Spectra Underpin Multiple Functions of Temperate Tree Species
Authors: Yang Shanshan , Sterck Frank J. , Sass-Klaassen Ute , Cornelissen J. Hans C. , van Logtestijn Richard S. P. , Hefting Mariet , Goudzwaard Leo , Zuo Juan , Poorter Lourens
Published: March 2022

A central paradigm in comparative ecology is that species sort out along a slow-fast resource economy spectrum of plant strategies, but this has been rarely tested for a comprehensive set of stem traits and compartments. We tested how stem traits vary across wood and bark of temperate tree species, whether a slow-fast strategy spectrum exists, and what traits make up this plant strategy spectrum. For 14 temperate tree species, 20 anatomical, chemical, and morphological traits belonging to six key stem functions were measured for three stem compartments (inner wood, outer wood, and bark). The trait variation was explained by major taxa (38%), stem compartments (24%), and species within major taxa (19%). A continuous plant strategy gradient was found across and within taxa, running from hydraulic safe gymnosperms to conductive angiosperms. Both groups showed a second strategy gradient related to chemical defense. Gymnosperms strongly converged in their trait strategies because of their uniform tracheids. Angiosperms strongly diverged because of their different vessel arrangement and tissue types. The bark had higher concentrations of nutrients and phenolics whereas the wood had stronger physical defense. The gymnosperms have a conservative strategy associated with strong hydraulic safety and physical defense, and a narrow, specialized range of trait values, which allow them to grow well in drier and unproductive habitats. The angiosperm species show a wider trait variation in all stem compartments, which makes them successful in marginal- and in mesic, productive habitats. The associations between multiple wood and bark traits collectively define a slow-fast stem strategy spectrum as is seen also for each stem compartment.