bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Transcranial Direct Current Stimulation and Monoclonal Antibodies Acting on the CGRP as a Combined Treatment for Migraine (TACTIC): Protocol for a Randomized, Double-Blind, Sham-Controlled Trial
Authors: Ornello Raffaele , Rosignoli Chiara , Caponnetto Valeria , Pistoia Francesca , Ferrara Michele , D'Atri Aurora , Sacco Simona 
Published: May 2022

BackgroundMigraine is a recurrent headache disorder that has a still unclear pathophysiology, involving several circuits of both the central and peripheral nervous system. Monoclonal antibodies acting on the calcitonin gene-related (CGRP) pathway (CGRP-MAbs) are the first drugs specifically designed for migraine; those drugs act peripherally on the trigeminal ganglion without entering the blood-brain barrier. Conversely, neuromodulation techniques such as transcranial direct current stimulation (tDCS) act centrally by increasing or decreasing the neuronal firing rate of brain cortical areas. The aim of the study will be to evaluate whether tDCS, in addition to CGRP-MAbs, is an effective add-on treatment in reducing headache frequency, intensity and acute medication use in patients with migraine. To demonstrate the biological effects of tDCS, the electroencephalographic (EEG) power changes after tDCS will be assessed.MethodsWe will include patients with migraine on treatment with CGRP-MAbs and reporting ≥8 monthly migraine days. During a prospective 28-day baseline period, patients will fill in a headache diary and questionnaires to evaluate migraine-related disability, anxiety and depressive symptoms, sleep quality, and health-related quality of life. Subjects will be randomly assigned in a 1:1 ratio to active or sham tDCS. The stimulation protocol will consist in five daily sessions, the cathodes will be applied bilaterally above the occipital areas, with the reference anode electrodes positioned above the primary motor areas. Before the first, and immediately after the last stimulation session, patients will perform a 10-min resting EEG recording. During a 28-day follow-up period following tDCS, patients will have to fill in a headache diary and questionnaires identical to those of the baseline period.DiscussionThis trial will evaluate the efficacy of an add-on treatment acting on the brain in patients with migraine, who are already treated with peripherally acting drugs, showing how tDCS acts in restoring the dysfunctional brain networks typical of the migraine patient.Clinical Trial RegistrationNCT05161871.
Global Trends and Hotspots in Trigeminal Neuralgia Research From 2001 to 2021: A Bibliometric Analysis
Authors: Zhu Ganggui , Fu Zaixiang , Su Sheng , Tang Yajuan , Liu Fuyi , Yu Wenhua 
Published: May 2022

BackgroundIn recent years, there have been an increasing number of studies on trigeminal neuralgia (TN). However, a scientific and comprehensive study of the current situation and trends in the field of TN research is lacking. The purpose of this study is to summarize and visualize the development, research hotspots, and future trends in TN based on a bibliometric approach.MethodsStudies on TN published from 2001 to 2021 were obtained from the Web of Science Core Collection (WoSCC). Bibliometrics, CiteSpace, and VOSviewer tools were used for bibliometric analysis and visualization.ResultsIn total, 4,112 documents were searched. The number of research articles in the field is generally on an upward trend, with the fastest growth in the number of articles from 2017 to 2020. Shanghai Jiao Tong University, Pittsburgh University, and Mayo Clinic are the three institutions with the most publications. Shiting Li and Zakrzewska JM are the most prolific author and top co-cited authors, respectively. The Journal of Neurosurgery is the most influential journal. The top 5 keywords in that time frame are TN, microvascular decompression, facial pain, stereotactic radiosurgery, and neuropathic pain.ConclusionThis is the first comprehensive scientific bibliometric analysis of the global research field on TN over the past 21 years, providing a meaningful reference for further exploration of topical issues and research trends in the field.
Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies
Authors: Jiang Maofen , Liu Chunjiao , Ding Dongxiao , Tian Hui , Yu Chaoqun 
Published: May 2022

ObjectiveThe present network meta-analysis (NMA) was conducted to summarize the direct and indirect evidence of common programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors including avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab for the treatment of non-small cell lung cancer (NSCLC) patients and further to determine the optimal therapeutic regimen.MethodsWe performed a systematic literature search to identify all potentially eligible studies in PubMed, Embase, and the Cochrane Library until August 7, 2021. The primary outcome was overall survival (OS), and the second outcome was treatment-related adverse events (TRAEs). We used random-effects model to conduct direct and network meta-analyses, which were performed by using RevMan 5.3 and R version 3.6.1, respectively.ResultsDirect meta-analysis suggested that atezolizumab, cemiplimab, nivolumab, or pembrolizumab significantly improved OS compared with chemotherapy (CT), and NMA further established that atezolizumab [hazard ratio (HR), 0.77; 95% CrI, 0.62–0.96], nivolumab (HR, 0.75; 95% CrI, 0.62–0.93), or pembrolizumab (HR, 0.71; 95% Credible interval (Crl), 0.57–0.89) significantly and cemiplimab (HR, 0.68; 95% CrI, 0.46–1.02) numerically improved OS compared with CT. Meanwhile, NMA also indicated that cemiplimab was numerically superior to other PD-1/PD-L1 agents. Moreover, avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab were found to have fewer TRAEs compared with CT in direct meta-analysis, which were supported by the results from the NMA. Meanwhile, surface under the cumulative ranking curve (SUCRA) and ranking probability suggested that cemiplimab provided the most favorable balance between efficacy and safety, with the first ranking for the OS.ConclusionsBased on available evidence, cemiplimab may have the most favorable risk–benefit ratio for NSCLC patients compared with other common therapeutic management. However, future research with a large-scale, high-quality, and mature follow-up is needed to further determine which agents should be preferentially selected for NSCLC patients due to the limitations of our NMA and variations of eligible studies in treatment line and PD-L1 status.
The Aging-Related Prognostic Signature Reveals the Landscape of the Tumor Immune Microenvironment in Head and Neck Squamous Cell Carcinoma
Authors: Chen Fang , Gong Xin , Xia Meng , Yu Feng , Wu Jian , Yu Chaosheng , Li Junzheng 
Published: May 2022

BackgroundNumerous studies have shown that the aging microenvironment played a huge impact on tumor progression. However, the clinical prognostic value of aging-related risk signatures and their effects on the tumor immune microenvironment (TIME) in head and neck squamous cell carcinoma (HNSCC) remains largely unclear. This study aimed to identify novel prognostic signatures based on aging-related genes (AGs) and reveal the landscape of the TIME in HNSCC.MethodsDifferentially expressed AGs were identified using the gene set enrichment analysis (GSEA). The prognostic risk model of AGs was established by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. The independent prognostic value of the risk model and the correlations of the prognostic signature with immune score, tumor immune cell infiltration, and immune checkpoints were systematically analyzed.ResultsA prognostic risk model of four AGs (BAK1, DKK1, CDKN2A, and MIF) was constructed and validated in the training and testing datasets. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed that the four-AG risk signature possessed an accurate predictive value for the prognosis of patients with HNSCC. Correlation analysis revealed that the risk score was negatively associated with immune score and immune cell infiltration level while positively correlated with immune checkpoint blockade (ICB) response score. Patients of the high-risk subtype contained higher infiltration levels of resting natural killer (NK) cells, M0 macrophages, M2 macrophages, and resting mast cells while having lower infiltration levels of memory B cells, CD8+ T cells, follicular helper T cells, regulatory T cells (Tregs), and activated mast cells than did those of the low-risk subtype. The expressions of CTLA4, PDCD1, and TIGIT were downregulated while the PDCD1LG2 expression was upregulated in the high-risk subtype compared to those in the low-risk subtype. Furthermore, the four selected AGs in the risk model were demonstrated to possess important functions in immune cell infiltration and ICB response of HNSCC.ConclusionsThe aging-related risk signature is a reliable prognostic model for predicting the survival of HNSCC patients and provides potential targets for improving outcomes of immunotherapy.
Synergistic Radiosensitization Mediated by Chemodynamic Therapy via a Novel Biodegradable Peroxidases Mimicking Nanohybrid
Authors: Zhang Jun , Jiang Dazhen , Lyu Meng , Ren Shiqi , Zhou Yunfeng , Cao Zhen 
Published: May 2022

PurposeReactive oxygen species (ROS) are practically essential in radiotherapy to damage cancer cells; however, they are always inadequate for some malignant entities. Here, we designed a biodegradable mesoporous silica decorated with hemin and glucose oxidase (GOD@Hemin-MSN) to generate a chemodynamic therapy in order to enhance the killing capacity of radiotherapy.MethodsMesoporous silica, as an outstanding drug carrier, can deliver hemin and glucose oxidase to the tumor site. With high level of metabolism activity, cancer cells are abundant in glucose, which can be oxidized into H2O2 by glucose oxidase (GOD) on site. The generated H2O2 is subsequently converted into intracellular ROS, especially hydroxyl radical within the tumor microenvironment, by hemin, which has mimetic peroxidase properties. By this means, the ROS can be supplemented or enriched to facilitate the killing of tumor cells.ResultsThe chemodynamic therapy induced by GOD@Hemin-MSN produced quantities of ROS, which compensated for their inadequacy as a result of radiotherapy, and exhibited remarkable antitumor efficacy, with a tumor inhibition rate of 91.5% in A549 tumor-bearing mice.ConclusionThis work has validated GOD@Hemin-MSN as a radiosensitizer in chemodynamic therapy, which showed biocompatibility and potential for translational application.
Clinical Experience and Management Strategy of Retroperitoneal Tumor With Venous Tumor Thrombus Involvement
Authors: Liu Zhuo , Ge Liyuan , Liu Lei , Zhao Xun , Chen Kewei , Li Yuxuan , Aili Abudureyimujiang , Lu Min , Pei Xinlong , Han Dengyang , Zhang Shudong , Ma Lulin 
Published: May 2022

BackgroundThis study aims to report the surgical management, complications, and outcomes for patients with retroperitoneal tumor and venous thrombus.MethodsWe retrospectively analyzed 19 cases of retroperitoneal tumor with venous tumor thrombus from August 2015 to March 2021. A new tumor thrombus PUTH-RT grading system was proposed on the basis of the characteristics of the surgical techniques.ResultsTwo cases of PUTH-RT-1a, two cases of PUTH-RT-1b, six cases of PUTH-RT-2, six cases of PUTH-RT-3, and three cases of PUTH-RT-4 were included. Surgeries were successfully performed in all 19 patients. Among them, five cases (26.3%) were operated via a completely laparoscopic approach and 13 cases (68.4%) via an open approach. One case (5.3%) was converted from laparoscopic to open approach. Five cases (26.3%) experienced postoperative complications. All patients were followed for a median of 14 months. Cancer-associated death occurred in three cases. Distant metastases occurred in seven cases.ConclusionsWe propose a new tumor thrombus grading system based on the anatomical characteristics of retroperitoneal tumors with venous tumor thrombus. Retroperitoneal tumor resection and removal of venous tumor thrombi are safe and effective for the treatment of such diseases.
OGG1 Inhibition Triggers Synthetic Lethality and Enhances The Effect of PARP Inhibitor Olaparib in BRCA1-Deficient TNBC Cells
Authors: Baquero Juan Miguel , Marchena-Perea Erik , Mirabet Rocío , Torres-Ruiz Raúl , Blanco-Aparicio Carmen , Rodríguez-Perales Sandra , Helleday Thomas , Benítez-Buelga Carlos , Benítez Javier , Osorio Ana 
Published: May 2022

BackgroundPARP1 plays a critical role in the base excision repair (BER) pathway, and PARP1 inhibition leads to specific cell death, through a synthetic lethal interaction, in the context of BRCA1/2 deficiency. To date, up to five different PARP inhibitors (PARPi), have been approved, nevertheless, the acquisition of resistance to PARPi is common and there is increasing interest in enhancing responses and expand their use to other tumour types.MethodsWe hypothesized that other BER members could be additional synthetic lethal partners with mutated BRCA genes. To test this, we decided to evaluate the glycosylase OGG1 as a potential candidate, by treating BRCA1 proficient and deficient breast cancer cells with PARPi olaparib and the OGG1 inhibitor TH5478.ResultsKnocking out BRCA1 in triple-negative breast cancer cell lines causes hypersensitivity to the OGG1 inhibitor TH5487. Besides, TH5487 enhances the sensitivity to the PARP inhibitor olaparib, especially in the context of BRCA1 deficiency, reflecting an additive interaction.DiscussionThese results provide the first evidence that OGG1 inhibition is a promising new synthetic lethality strategy in BRCA1-deficient cells, and could lead to a new framework for the treatment of hereditary breast and ovarian cancer.
AQP5 Is a Novel Prognostic Biomarker in Pancreatic Adenocarcinoma
Authors: Chen Guo , Song Haiyang , Yang Zelong , Du Tianshu , Zheng Yu , Lu Zifan , Zhang Kunpeng , Wei Di 
Published: May 2022

BackgroundPancreatic adenocarcinoma (PAAD) is a highly malignant tumor with a poor prognosis. The identification of effective molecular markers is of great significance for diagnosis and treatment. Aquaporins (AQPs) are a family of water channel proteins that exhibit several properties and play regulatory roles in human carcinogenesis. However, the association between Aquaporin-5 (AQP5) expression and prognosis and tumor-infiltrating lymphocytes in PAAD has not been reported.MethodsAQP5 mRNA expression, methylation, and protein expression data in PAAD were analyzed using GEPIA, UALCAN, HAP, METHSURV, and UCSC databases. AQP5 expression in PAAD patients and cell lines from our cohort was examined using immunohistochemistry and Western blotting. The LinkedOmics database was used to study signaling pathways related to AQP5 expression. TIMER and TISIDB were used to analyze correlations among AQP5, tumor-infiltrating immune cells, and immunomodulators. Survival was analyzed using TCGA and Kaplan–Meier Plotter databases.ResultsIn this study, we investigated AQP5 expression in PAAD and determined whether the expression of AQP5 is a strong prognostic biomarker for PAAD. We searched and analyzed public cancer databases (GEO, TCGA, HAP, UALCAN, GEPIA, etc.) to conclude that AQP5 expression levels were upregulated in PAAD. Kaplan–Meier curve analysis showed that high AQP5 expression positively correlated with poor prognosis. Using TIMER and TISIDB, we found that the expression of AQP5 was associated with different tumor-infiltrating immune cells, especially macrophages. We found that hypomethylation of the AQP5 promoter region was responsible for its high expression in PAAD.ConclusionsAQP5 can serve as a novel biomarker to predict prognosis and immune infiltration in PAAD.
Maternal Resilience and Postpartum Depression at the Neonatal Intensive Care Unit
Authors: Mautner Eva , Stern Christina , Avian Alexander , Deutsch Maria , Fluhr Herbert , Greimel Elfriede 
Published: May 2022

BackgroundThe neonatal intensive care unit causes maternal stress and postpartum depressive symptoms in preterm and term mothers. Personal resources like maternal resilience are usually not considered in counselling these women.ObjectiveThis study aims to evaluate the resilience and differences in postpartum depression after admission of newborns at the neonatal intensive care unit.MethodsThis prospective pilot study was conducted in a single teaching hospital in Austria from December 2016 until December 2018. Sixty women completed two internationally validated questionnaires, the Edinburgh Postnatal Depression Scale (EPDS) to evaluate depressive symptoms and the Resilience Scale RS-13 to measure maternal resilience during the postpartum period (3 to 10 days postpartum). Additionally, women answered two open questions about burdens and relief.ResultsTwenty women (34%) showed lower resilience scores. The 39 high-resilient women (66%) showed significantly less depression (p = 0.005). Women reported social support from their partner (n = 15), health professionals and psychologists (n = 15), family and friends (n = 12), and child-specific relief, e.g., spending time with the newborn and involvement in care (n = 7) as the most helpful variable during the first postpartum period.ConclusionThe experience of having a newborn at the neonatal intensive care unit is a challenging event for women. Women have different resilience parameters. Mothers with lower resilience will benefit from social support and emotional health-promoting activities.
Molecular Basis Underlying Hepatobiliary and Renal Excretion of Phenolic Acids of Salvia miltiorrhiza Roots (Danshen)
Authors: Lu Jun-Lan , Zeng Xue-Shan , Zhou Xin , Yang Jun-Ling , Ren Ling-Ling , Long Xin-Yu , Wang Feng-Qing , Olaleye Olajide E. , Tian Nan-Nan , Zhu Ya-Xuan , Dong Jia-Jia , Jia Wei-Wei , Li Chuan 
Published: May 2022

Phenolic acids are cardiovascular constituents (originating from the Chinese medicinal herb Salvia miltiorrhiza root/Danshen) of DanHong and many other Danshen-containing injections. Our earlier pharmacokinetic investigation of DanHong suggested that hepatic and/or renal uptake of the Danshen compounds was the crucial steps in their systemic elimination. This investigation was designed to survey the molecular basis underlying hepatobiliary and renal excretion of the Danshen compounds, i.e., protocatechuic acid, tanshinol, rosmarinic acid, salvianolic acid D, salvianolic acid A, lithospermic acid, and salvianolic acid B. A large battery of human hepatic and renal transporters were screened for transporting the Danshen compounds and then characterized for the uptake kinetics and also compared with associated rat transporters. The samples were analyzed by liquid chromatography/mass spectrometry. Because the Danshen phenolic acids are of poor or fairly good membrane permeability, their elimination via the liver or kidneys necessitates transporter-mediated hepatic or renal uptake from blood. Several human transporters were found to mediate hepatic and/or renal uptake of the Danshen compounds in a compound-molecular-mass-related manner. Lithospermic acid and salvianolic acid B (both &gt;500 Da) underwent systemic elimination, initiated by organic anion-transporting polypeptide (OATP)1B1/OATP1B3-mediated hepatic uptake. Rosmarinic acid and salvianolic acids D (350–450 Da) underwent systemic elimination, initiated by OATP1B1/OATP1B3/organic anion transporter (OAT)2-mediated hepatic uptake and by OAT1/OAT2-mediated renal uptake. Protocatechuic acid and tanshinol (both &lt;200 Da) underwent systemic elimination, initiated by OAT1/OAT2-mediated renal uptake and OAT2-mediated hepatic uptake. A similar scenario was observed with the rat orthologs. The investigation findings advance our understanding of the disposition of the Danshen phenolic acids and could facilitate pharmacokinetic research on other Danshen-containing injections.
Involvement of the SIRT1/PGC-1α Signaling Pathway in Noise-Induced Hidden Hearing Loss
Authors: Liu Yu-Hui , Jiang Yi-Hong , Li Cong-Cong , Chen Xue-Min , Huang Li-Gui , Zhang Min , Ruan Bai , Wang Xiao-Cheng 
Published: May 2022

Objective: To establish an animal model of noise-induced hidden hearing loss (NIHHL), evaluate the dynamic changes in cochlear ribbon synapses and cochlear hair cell morphology, and observe the involvement of the SIRT1/PGC-1α signaling pathway in NIHHL.Methods: Male guinea pigs were randomly divided into three groups: control group, noise exposure group, and resveratrol treatment group. Each group was divided into five subgroups: the control group and 1 day, 1 week, 2 weeks, and 1 month post noise exposure groups. The experimental groups received noise stimulation at 105 dB SPL for 2 h. Hearing levels were examined by auditory brainstem response (ABR). Ribbon synapses were evaluated by inner ear basilar membrane preparation and immunofluorescence. The cochlear morphology was observed using scanning electron microscopy. Western blotting analysis and immunofluorescence was performed to assess the change of SIRT1/PGC-1α signaling. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), ATP and SIRT1 activity were measured using commercial testing kits.Results: In the noise exposure group, hearing threshold exhibited a temporary threshold shift (TTS), and amplitude of ABR wave I decreased irreversibly. Ribbon synapse density decreased after noise exposure, and the stereocilia were chaotic and then returned to normal. The expression and activity of SIRT1 and PGC-1α protein was lower than that in the control group. SOD, CAT and ATP were also influenced by noise exposure and were lower than those in the control group, but MDA showed no statistical differences compared with the control group. After resveratrol treatment, SIRT1 expression and activity showed a significant increase after noise exposure, compared with the noise exposure group. In parallel, the PGC-1α and antioxidant proteins were also significantly altered after noise exposure, compared with the noise exposure group. The damage to the ribbon synapses and the stereocilia were attenuated by resveratrol as well. More importantly, the auditory function, especially ABR wave I amplitudes, was also promoted in the resveratrol treatment group.Conclusion: The SIRT1/PGC-1α signaling pathway and oxidative stress are involved in the pathogenesis of NIHHL and could be potential therapeutical targets in the future.