bluuebunny/crossref_metadata_2025 huggingface dataset:
A rapid in vitro assay for evaluating the effects of acetylcholinesterase inhibitors and reactivators in the rat basolateral amygdala
Authors: Thinschmidt Jeffrey S. , Harden Scott W. , King Michael A. , Talton James D. , Frazier Charles J.
Published: November 2022

We established a novel brain slice assay to test the ability of acetylcholinesterase (AChE) reactivators to prevent ACh-induced M1 muscarinic acetylcholine receptor (mAChR) dependent hyperexcitability observed after exposure to the organophosphate (OP)-based AChE inhibitor and sarin surrogate 4-nitrophenyl isopropyl methylphosphonate (NIMP). Whole-cell patch clamp recordings were used to evaluate the response of pyramidal neurons in the rat basolateral amygdala (BLA) to brief (1 min) bath application of ACh (100 μM), either in control conditions, or after exposure to NIMP ± an AChE reactivator. Bath application of ACh produced atropine- and pirenzepine-sensitive inward currents in voltage clamped BLA pyramidal neurons, and increased the frequency of spontaneous EPSCs, suggesting robust activation of M1 mAChRs. Responses to ACh were increased ~3–5 fold in slices that had been preincubated in NIMP, and these effects were reversed in a concentration dependent manner by exposure to a commercially available AChE reactivator. The current work outlines a simple assay that can be used to evaluate the efficacy of both known and novel AChE reactivators in an area of the limbic system that likely contributes to seizures after acute exposure to OP-based AChE inhibitors.
Postoperative cerebral infarction after revascularization in patients with moyamoya disease: Incidence and risk factors
Authors: Wang Jiaxiong , Jiang Hanqiang , Tang Jinwei , Lin Chi , Ni Wei , Gu Yuxiang
Published: November 2022

Objectives

Cerebral infarction is the major complication of revascularization surgery in patients with moyamoya disease (MMD), and we analyzed the possible causes of cerebral infarction after revascularization surgery for MMD.

Methods

MMD patients who were admitted and underwent surgical revascularization at Shanghai Huashan Hospital from January 2019 to December 2021 were retrospectively analyzed.

Results

A total of 815 patients and 890 revascularization surgeries (677 first revascularization surgeries and 213 second revascularization surgeries) were included in this study; 453 (50.9%) were performed on the left side and 437 (49.1%) on the right side, with 779 (87.5%) combined procedures and 111 (12.5%) indirect bypasses included. The mean patient age at the time of these procedures was 44.6 ± 11.7 years (range 6–72 years). Postoperative cerebral infarctions were observed in 46 (5.17%) surgeries, among which 31 occurred after left hemisphere revascularization surgeries, with an incidence of 6.84%, and 15 occurred after right hemisphere revascularization surgeries, with an incidence of 3.43%. Of these, 30 (65.2%) occurred in the operated hemispheres, 2 (4.3%) in the contralateral hemisphere and 13 (28.3%) in the bilateral hemisphere. There were 11 cases of massive infarction (23.9%). The incidence of postoperative infarction in patients undergoing the first revascularization was 6% (41/677) and 2.3% (5/213) in the second revascularization surgeries. Initial presentation as infarction (P < 0.001), initial presentation as hemorrhage (P < 0.001), hypertension (P = 0.018), diabetes (P = 0.006), 1st or 2nd surgery and surgical side (P = 0.007) were found to be related to postoperative cerebral infarction. Initial presentation as infarction (OR = 2.934, 95% CI 1.453–5.928, P = 0.003), initial presentation as hemorrhage (OR = 0.149, 95% CI 0.035–0.641, P = 0.011), and 1st or 2nd surgery and surgical side (OR = 1.66, 95% CI 1.106–2.491, P = 0.014) were independently associated with cerebral infarction after revascularization surgeries.

Conclusions

In patients with MMD undergoing surgical revascularization, initial presentation as infarction and first revascularization surgery performed on the left hemisphere are independent risk factors for postoperative cerebral infarction, whereas initial presentation as hemorrhage is a protective factor.
Different Markov chains modulate visual stimuli processing in a Go-Go experiment in 2D, 3D, and augmented reality
Authors: Mugruza-Vassallo Carlos Andrés , Granados-Domínguez José L. , Flores-Benites Victor , Córdova-Berríos Luz
Published: November 2022

The introduction of Augmented Reality (AR) has attracted several developments, although the people’s experience of AR has not been clearly studied or contrasted with the human experience in 2D and 3D environments. Here, the directional task was applied in 2D, 3D, and AR using simplified stimulus in video games to determine whether there is a difference in human answer reaction time prediction using context stimulus. Testing of the directional task adapted was also done.

Research question: Are the main differences between 2D, 3D, and AR able to be predicted using Markov chains?

Methods: A computer was fitted with a digital acquisition card in order to record, test and validate the reaction time (RT) of participants attached to the arranged RT for the theory of Markov chain probability. A Markov chain analysis was performed on the participants’ data. Subsequently, the way certain factors influenced participants RT amongst the three tasks time on the accuracy of the participants was sought in the three tasks (environments) were statistically tested using ANOVA.

Results: Markov chains of order 1 and 2 successfully reproduced the average reaction time by participants in 3D and AR tasks, having only 2D tasks with the variance predicted with the current state. Moreover, a clear explanation of delayed RT in every environment was done. Mood and coffee did not show significant differences in RTs on a simplified videogame. Gender differences were found in 3D, where endogenous directional goals are in 3D, but no gender differences appeared in AR where exogenous AR buttons can explain the larger RT that compensate for the gender difference. Our results suggest that unconscious preparation of selective choices is not restricted to current motor preparation. Instead, decisions in different environments and gender evolve from the dynamics of preceding cognitive activity can fit and improve neurocomputational models.
Abdominal vagus nerve stimulation alleviates collagen-induced arthritis in rats
Authors: Payne Sophie C. , Romas Evange , Hyakumura Tomoko , Muntz Fenella , Fallon James B.
Published: November 2022

Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease. Despite therapeutic advances, a significant proportion of RA patients are resistant to pharmacological treatment. Stimulation of the cervical vagus nerve is a promising alternative bioelectric neuromodulation therapeutic approach. However, recent clinical trials show cervical vagus nerve stimulation (VNS) was not effective in a significant proportion of drug resistant RA patients. Here we aim to assess if abdominal vagus nerve stimulation reduces disease severity in a collagen-induced arthritis (CIA) rat model. The abdominal vagus nerve of female Dark Agouti rats was implanted and CIA induced using collagen type II injection. VNS (1.6 mA, 200 μs pulse width, 50 μs interphase gap, 27 Hz frequency) was applied to awake freely moving rats for 3 h/day (days 11–17). At 17 days following the collagen injection, unstimulated CIA rats (n = 8) had significantly worse disease activity index, tumor necrosis factor-alpha (TNF-α) and receptor activator of NFκB ligand (RANKL) levels, synovitis and cartilage damage than normal rats (n = 8, Kruskal–Wallis: P < 0.05). However, stimulated CIA rats (n = 5–6) had significantly decreased inflammatory scores and ankle swelling (Kruskal–Wallis: P < 0.05) compared to unstimulated CIA rats (n = 8). Levels of tumor necrosis factor-alpha (TNF-α) remained at undetectable levels in stimulated CIA rats while levels of receptor activator of NFκB ligand (RANKL) were significantly less in stimulated CIA rats compared to unstimulated CIA rats (P < 0.05). Histopathological score of inflammation and cartilage loss in stimulated CIA rats were no different from that of normal (P > 0.05). In conclusion, abdominal VNS alleviates CIA and could be a promising therapy for patients with RA.
Facial mask disturbs ocular exploration but not pupil reactivity
Authors: Rabadan Vivien , Ricou Camille , Latinus Marianne , Aguillon-Hernandez Nadia , Wardak Claire
Published: November 2022

Introduction

The COVID-19 pandemic has imposed to wear a face mask that may have negative consequences for social interactions despite its health benefits. A lot of recent studies focused on emotion recognition of masked faces, as the mouth is, with the eyes, essential to convey emotional content. However, none have studied neurobehavioral and neurophysiological markers of masked faces perception, such as ocular exploration and pupil reactivity. The purpose of this eye tracking study was to quantify how wearing a facial accessory, and in particular a face mask, affected the ocular and pupillary response to a face, emotional or not.

Methods

We used videos of actors wearing a facial accessory to characterize the visual exploration and pupillary response in several occlusion (no accessory, sunglasses, scarf, and mask) and emotional conditions (neutral, happy, and sad) in a population of 44 adults.

Results

We showed that ocular exploration differed for face covered with an accessory, and in particular a mask, compared to the classical visual scanning pattern of a non-covered face. The covered areas of the face were less explored. Pupil reactivity seemed only slightly affected by the mask, while its sensitivity to emotions was observed even in the presence of a facial accessory.

Discussion

These results suggest a mixed impact of the mask on attentional capture and physiological adjustment, which does not seem to be reconcilable with its strong effect on behavioral emotional recognition previously described.
Biological implications and clinical potential of invasion and migration related miRNAs in glioma
Authors: Guo Xin , Jiao Hengxing , Cao Lele , Meng Facai
Published: November 2022

Gliomas are the most common primary malignant brain tumors and are highly aggressive. Invasion and migration are the main causes of poor prognosis and treatment resistance in gliomas. As migration and invasion occur, patient survival and prognosis decline dramatically. MicroRNAs (miRNAs) are small, non-coding 21–23 nucleotides involved in regulating the malignant phenotype of gliomas, including migration and invasion. Numerous studies have demonstrated the mechanism and function of some miRNAs in glioma migration and invasion. However, the biological and clinical significance (including diagnosis, prognosis, and targeted therapy) of glioma migration and invasion-related miRNAs have not been systematically discussed. This paper reviews the progress of miRNAs-mediated migration and invasion studies in glioma and discusses the clinical value of migration and invasion-related miRNAs as potential biomarkers or targeted therapies for glioma. In addition, these findings are expected to translate into future directions and challenges for clinical applications. Although many biomarkers and their biological roles in glioma invasion and migration have been identified, none have been specific so far, and further exploration of clinical treatment is still in progress; therefore, we aimed to further identify specific markers that may guide clinical treatment and improve the quality of patient survival.
Anesthesia and developing brain: What have we learned from recent studies
Authors: Niu Yixuan , Yan Jia , Jiang Hong
Published: November 2022

Anesthesia is unavoidable in surgical procedures. However, whether the general anesthetics are neurotoxic to immature brains remains undefined. Neurodevelopmental impairment induced by anesthesia has been a critical health issue and topic of concern. This review summarizes recent progress made in clinical and preclinical studies to provide useful suggestions and potential therapeutic targets for the protection of the immature brain. On the one hand, clinical researchers continue the debate about the effect of single and multiple exposures to anesthesia on developing brains. On the other hand, preclinical researchers focus on exploring the mechanisms of neurotoxic effects of general anesthesia on immature brains and seeking novel solutions. Rodent models have always been used in preclinical studies, but it is still unclear whether the mechanisms observed in rodent models have clinical relevance. Compared with these models, non-human primates (NHPs) are more genetically similar to humans. However, few research institutions in this area can afford to use NHP models in their studies. One way to address both problems is by combining single-cell sequencing technologies to screen differential gene expression in NHPs and perform in vivo validation in rodents. The mechanism of anesthesia-induced neurotoxicity still requires further elucidation in primates.
Preparation and characterization of chitosan/whey isolate protein active film containing TiO2 and white pepper essential oil
Authors: Wang Ying , Wang Ji , Lai Jing , Zhang Xin , Wang Yongliang , Zhu Yingchun
Published: November 2022

Active packaging films are designed to improve quality and extend the food shelf life by incorporating functional active ingredients into biopolymer films. This study developed a bioactive film based on chitosan (CS) and whey isolated protein (WPI) incorporated with 0.01 wt% TiO2and 0.1 wt% white pepper essential oil (WPEO). The physicochemical properties of the prepared film were also evaluated comprehensively. The results showed that water solubility and water vapor permeability of the film incorporated with TiO2and WPEO were 25.09% and 0.0933 g mm m–2h–1KPa–1, respectively, which were significantly higher than those of other films (P< 0.05). In addition, the UV barrier properties of films incorporating TiO2and WPEO have improved. The films were characterized by Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The FTIR results showed interactions between TiO2and WPEO with CS/WPI compound, and the SEM results indicated a good incorporation of TiO2into the composite films. The antioxidative and antibacterial properties of films were significantly enhanced by incorporating WPEO. According to results, the developed biocomposite film can be considered as a packaging material.
Meta-analysis of omega-3 polyunsaturated fatty acids on immune functions and nutritional status of patients with colorectal cancer
Authors: Yue Tinghui , Xiong Kai , Deng Jia , Hu Wenting , Tan Tianying , Li Shuangshuang , Yang Tao , Xiao Tianbao
Published: November 2022

This meta-analysis assessed the clinical significance of omega-3 polyunsaturated fatty acids (PUFAs) in the management of patients with colorectal cancer (CRC) after radical resection. We comprehensively searched electronic databases, such as EMBASE, PubMed, MEDLINE and Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Database (CBM), Wanfang Electronic Database, and VIP Medical Information System (VIP) from inception to 10 April 2022. Randomized controlled trials (RCTs) of omega-3 PUFAs and conventional nutrition or blank treatments were selected. The following were evaluated in the pooled analysis: immune function-related indices (IgA, IgG, IgM, CD3+, CD4+, CD8+, and ratio of CD4+/CD8+), nutritional status-related indices [total protein (TP), albumin (ALB), and prealbumin (PA)], and their corresponding 95% confidence intervals (CIs). Next, we conducted heterogeneity detection, sensitivity analysis, contour-enhanced funnel plot to detect possible publication bias, and meta-regression analysis. In all, 20 studies, including 1,613 patients (809 in the omega-3 PUFAs group and 804 in the control group), were selected in the final analysis. The results of the pooled analysis showed that omega-3 PUFAs significantly increased the humoral immune function indices, including IgA [standardized mean difference (SMD) = 0.54, 95% CI 0.10–0.99], IgM (SMD = 0.52, 95% CI 0.05–0.99), IgG (SMD = 0.65, 95% CI 0.47–0.84); T cell immune function indices, including CD3+ (SMD = 0.73, 95% CI 0.54–0.92), CD4+ (SMD = 0.76, 95% CI 0.53–0.98), and ratio of CD4+/CD8+ (SMD = 0.66, 95% CI 0.39–0.92). However, CD8+ was markedly reduced after intervention of omega-3 PUFAs (SMD = –0.28, 95% CI –0.66–0.09). In addition, pooled analysis indicated that omega-3 PUFAs markedly improved the nutritional status indicators, including TP (SMD = 0.53, 95% CI 0.17–0.88), ALB (SMD = 0.43, 95% CI 0.15–0.70), and PA (SMD = 0.46, 95% CI 0.01–0.90). The meta-regression analysis revealed that the covariates of the small sample affected the robustness and credibility of the CD4+ results. Conclusively, this study suggested that omega-3 PUFAs have the potential to be used as a valid immunonutritional therapy/support for treating patients with CRC postoperatively. This meta-analysis protocol was registered in PROSPERO (no. CRD42021288487).

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288487], identifier [CRD42021288487].
Case report: Complex paraneoplastic syndromes in thymoma with nephrotic syndrome, cutaneous amyloidosis, myasthenia gravis, and Morvan’s syndrome
Authors: Liu Huiqin , Dong Zeqin , Zhang Milan , Pang Rui , Xu Jiajia , He Pan , Mei Wenli , Zhang Shuai , You Guanqiao , Li Wei
Published: November 2022

Background

Apart from myasthenia gravis (MG), thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes (PNSs). Here, we report on a rare case presenting with four different PNSs, namely, MG, membranous nephropathy, cutaneous amyloidosis, and Morvan’s syndrome associated with thymoma.

Case presentation

A middle-aged man was frequently hospitalized because of nephrotic syndrome (stage I membranous nephropathy), cutaneous amyloidosis, and MG with acetylcholine receptor (AChR) antibody and titin antibody positivity. Chest CT showed a thymic mass in the left anterior mediastinum, and he received intravenous immunoglobulin (IVIG), methylprednisolone pulse therapy, thoracoscopic thymoma resection, and radiotherapy. Postoperative pathological examination revealed a type B2 thymoma. During the perioperative stage, his electrocardiogram (ECG) showed myocardial infarction-like ECG changes; however, his levels of cardiac enzymes and troponin were normal, and he had no symptoms of precardiac discomfort. Six months after thymectomy, his nephrotic syndrome and MG symptoms were relieved; however, he presented with typical manifestations of Morvan’s syndrome, including neuromyotonia, severe insomnia, abnormal ECG activity, and antibodies against leucine-rich glioma-inactivated 1 (LGI1) and γ-amino-butyric acid-B receptor (GABABR). His symptoms did not improve after repeated IVIG and steroid therapies. Finally, he received low-dose rituximab, and his symptoms gradually resolved.

Conclusion

This case serves to remind us that apart from MG, thymoma is also associated with other autoimmune PNSs such as membranous nephropathy, cutaneous amyloidosis, and Morvan’s syndrome. Autoimmune PNSs can present concurrently with or after surgical or medical therapy for thymoma. For Morvan’s syndrome post-thymectomy with LGI1 antibody positivity, B-cell depletion therapy such as intravenous rituximab is an effective treatment.
The magic bullet: Niclosamide
Authors: Jiang Haowen , Li Albert M. , Ye Jiangbin
Published: November 2022

The term ‘magic bullet’ is a scientific concept proposed by the German Nobel laureate Paul Ehrlich in 1907, describing a medicine that could specifically and efficiently target a disease without harming the body. Oncologists have been looking for a magic bullet for cancer therapy ever since. However, the current therapies for cancers—including chemotherapy, radiation therapy, hormone therapy, and targeted therapy—pose either pan-cytotoxicity or only single-target efficacy, precluding their ability to function as a magic bullet. Intriguingly, niclosamide, an FDA-approved drug for treating tapeworm infections with an excellent safety profile, displays broad anti-cancer activity in a variety of contexts. In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK. Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1. We recently discovered that niclosamide ethanolamine (NEN) reprograms cellular metabolism through its uncoupler function, consequently remodeling the cellular epigenetic landscape to promote differentiation. Inspired by the promising results from the pre-clinical studies, several clinical trials are ongoing to assess the therapeutic effect of niclosamide in cancer patients. This current review summarizes the functions, mechanism of action, and potential applications of niclosamide in cancer therapy as a magic bullet.
MR image reconstruction from undersampled data for image-guided radiation therapy using a patient-specific deep manifold image prior
Authors: Grandinetti Jace , Gao Yin , Gonzalez Yesenia , Deng Jie , Shen Chenyang , Jia Xun
Published: November 2022

Introduction

Recent advancements in radiotherapy (RT) have allowed for the integration of a Magnetic Resonance (MR) imaging scanner with a medical linear accelerator to use MR images for image guidance to position tumors against the treatment beam. Undersampling in MR acquisition is desired to accelerate the imaging process, but unavoidably deteriorates the reconstructed image quality. In RT, a high-quality MR image of a patient is available for treatment planning. In light of this unique clinical scenario, we proposed to exploit the patient-specific image prior to facilitate high-quality MR image reconstruction.

Methods

Utilizing the planning MR image, we established a deep auto-encoder to form a manifold of image patches of the patient. The trained manifold was then incorporated as a regularization to restore MR images of the same patient from undersampled data. We performed a simulation study using a patient case, a real patient study with three liver cancer patient cases, and a phantom experimental study using data acquired on an in-house small animal MR scanner. We compared the performance of the proposed method with those of the Fourier transform method, a tight-frame based Compressive Sensing method, and a deep learning method with a patient-generic manifold as the image prior.

Results

In the simulation study with 12.5% radial undersampling and 15% increase in noise, our method improved peak-signal-to-noise ratio by 4.46dB and structural similarity index measure by 28% compared to the patient-generic manifold method. In the experimental study, our method outperformed others by producing reconstructions of visually improved image quality.
Prognostic significance of CDC20 expression in malignancy patients: A meta-analysis
Authors: Xian Feng , Yang Xuegang , Xu Guohui
Published: November 2022

Background

Cell Division Cycle Protein 20(CDC20) is reported to promote cancer initiation, progression and drug resistance in many preclinical models and is demonstrated in human cancer tissues. However, the correlation between CDC20 and cancer patients’ prognosis has not yet been systematically evaluated. Therefore, this present meta-analysis was performed to determine the prognostic value of CDC20 expression in various malignancy tumors.

Methods

A thorough database search was performed in EMBASE, PubMed, Cochrane Library and Web of Science from inception to May 2022. Stata14.0 Software was used for the statistical analysis. The pooled hazard ratios(HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival (OS), recurrence-free survival (RFS), distant-metastasis free survival (DMFS). Qualities of the included literature were assessed by JBI Critical appraisal checklist. Egger’s test was used to assess publication bias in the included studies.

Results

Ten articles were selected, and 2342 cancer patients were enrolled. The cancer types include breast, colorectal, lung, gastric, oral, prostate, urothelial bladder cancer, and hepatocellular carcinoma. The result showed strong significant associations between high expression of CDC20 and endpoints: OS (HR 2.52, 95%CI 2.13-2.99; HR 2.05, 95% CI 1.50-2.82, respectively) in the multivariate analysis and in the univariate analysis. Also, high expression of CDC20 was significantly connected with poor RFS (HR 2.08, 95%CI 1.46-2.98) and poor DMFS (HR 4.49, 95%CI 1.57-12.85). The subgroup analysis was also performed, which revealed that CDC20 upregulated expression was related to poor OS in non-small cell lung cancer (HR 2.40, 95% CI 1.91-3.02).

Conclusions

This meta-analysis demonstrated that highly expressing CDC20 was associated with poor survival in human malignancy tumors. CDC20 may be a valuable prognostic predictive biomarker and a potential therapeutic target in various cancer parents.
Obinutuzumab plus chlorambucil versus ibrutinib in previously untreated chronic lymphocytic leukemia patients without TP53 disruptions: A real-life CLL campus study
Authors: Visentin Andrea , Mauro Francesca Romana , Catania Gioachino , Fresa Alberto , Vitale Candida , Sanna Alessandro , Mattiello Veronica , Cibien Francesca , Sportoletti Paolo , Gentile Massimo , Rigolin Gian Matteo , Quaglia Francesca Maria , Murru Roberta , Gozzetti Alessandro , Molica Stefano , Marchetti Monia , Pravato Stefano , Angotzi Francesco , Cellini Alessandro , Scarfò Lydia , Reda Gianluigi , Coscia Marta , Laurenti Luca , Ghia Paolo , Foà Robin , Cuneo Antonio , Trentin Livio
Published: November 2022

One of the main issues in the treatment of patients with chronic lymphocytic leukemia (CLL) deals with the choice between continuous or fixed-duration therapy. Continuous ibrutinib (IB), the first-in-class BTK inhibitor, and obinutuzumab-chlorambucil (G-CHL) are commonly used therapies for elderly and/or comorbid patients. No head-to-head comparison has been carried out. Within the Italian campus CLL network, we performed a retrospective study on CLL patients without TP53 disruption treated with IB or G-CHL as first-line therapy. Patients in the G-CHL arm had a higher CIRS score and the worst renal function. The overall response rates between the G-CHL and IB arms were similar, but more complete remissions (CRs) were achieved with G-CHL (p = 0.0029). After a median follow-up of 30 months, the progression-free survival (PFS, p = 0.0061) and time to next treatment (TTNT, p = 0.0043), but not overall survival (OS, p = 0.6642), were better with IB than with G-CHL. Similar results were found after propensity score matching and multivariate analysis. While PFS and TTNT were longer with IB than with G-CHL in IGHV unmutated patients (p = 0.0190 and 0.0137), they were superimposable for IGHV mutated patients (p = 0.1900 and 0.1380). In the G-CHL arm, the depth of response (79% vs. 68% vs. 38% for CR, PR and SD/PD; p < 0.0001) and measurable residual disease (MRD) influenced PFS (78% vs. 53% for undetectable MRD vs. detectable MRD, p = 0.0203). Hematological toxicities were common in the G-CHL arm, while IB was associated with higher costs. Although continuous IB provides better disease control in CLL, IGHV mutated patients and those achieving an undetectable MRD show a marked clinical and economic benefit from a fixed-duration obinutuzumab-based treatment.
Hallmarks of cancer: The insulin-like growth factors perspective
Authors: Werner Haim , LeRoith Derek
Published: November 2022

The identification of a series of attributes or hallmarks that are shared by virtually all cancer cells constitutes a true milestone in cancer research. The conceptualization of a catalogue of common genetic, molecular, biochemical and cellular events under a unifying Hallmarks of Cancer idea had a major impact in oncology. Furthermore, the fact that different types of cancer, ranging from pediatric tumors and leukemias to adult epithelial cancers, share a large number of fundamental traits reflects the universal nature of the biological events involved in oncogenesis. The dissection of a complex disease like cancer into a finite directory of hallmarks is of major basic and translational relevance. The role of insulin-like growth factor-1 (IGF1) as a progression/survival factor required for normal cell cycle transition has been firmly established. Similarly well characterized are the biochemical and cellular activities of IGF1 and IGF2 in the chain of events leading from a phenotypically normal cell to a diseased one harboring neoplastic traits, including growth factor independence, loss of cell-cell contact inhibition, chromosomal abnormalities, accumulation of mutations, activation of oncogenes, etc. The purpose of the present review is to provide an in-depth evaluation of the biology of IGF1 at the light of paradigms that emerge from analysis of cancer hallmarks. Given the fact that the IGF1 axis emerged in recent years as a promising therapeutic target, we believe that a careful exploration of this signaling system might be of critical importance on our ability to design and optimize cancer therapies.
The prognosis of bladder cancer is affected by fatty acid metabolism, inflammation, and hypoxia
Authors: Xiao Yu , Yang Junfeng , Yang Maolin , Len Jinjun , Yu Yanhong
Published: November 2022

Background

The prognosis of bladder cancer (BC) is poor, and there is no effective personalized management method for BC patients at present. Developing an accurate model is helpful to make treatment plan and prognosis analysis for BC patients. Endogenous fatty acid metabolism causes cancer cells to become hypoxic, and the coexistence of hypoxia and inflammation is often characteristic of cancer. All three together influence the tumor immune microenvironment, treatment, and prognosis of BC.

Methods

We used The Cancer Genome Atlas-Bladder Urothelial Carcinoma (TCGA-BLAC) cohorts as a train group to build a risk model based on fatty acid metabolism, hypoxia and inflammation-related gene signatures and performed external validation with GSE13507, GSE31684, and GSE39281 cohorts. We validated the model to correlate with the clinicopathological characteristics of patients, created an accuracy nomogram, and explored the differences in immune microenvironment and enrichment pathways.

Results

We found significant differences in overall survival and progression-free survival between high- and low-risk groups, and patients in the low-risk group had a better prognosis than those in the high-risk group. In the train group, the AUCs for predicting overall survival at 1, 3, and 5 years were 0.745, 0.712, and 0.729, respectively. The 1-, 3-, and 5-year overall survival AUCs were 0.589, 0.672, and 0.666 in the external validation group, respectively. The risk score independently predicted the prognosis of BC patients with AUCs of 0.729. In addition, there was a significant correlation between risk scores and BC clinicopathological features and, in the GSE13507 cohort, we observed that BC progression and deeper invasion were associated with higher risk scores. Risk scores were highly correlated with coproptosis, pyroptosis, m7G, immune checkpoint-related genes, and immune microenvironment. In addition, we found that patients in the low-risk group responded better to immunotherapy, whereas patients in the high-risk group were more sensitive to commonly used chemotherapy drugs.

Conclusion

Our findings provide new treatment decisions for BC, and can effectively predict the prognosis of BC patients, which is helpful for the management of BC patients.
Biological and clinical review of IORT-induced wound fluid in breast cancer patients
Authors: Jeibouei Shabnam , Shams Forough , Mohebichamkhorami Fariba , Sanooghi Davood , Faal Bahareh , Akbari Mohammad Esmaeil , Zali Hakimeh
Published: November 2022

Intraoperative radiotherapy (IORT) has become a growing therapy for early-stage breast cancer (BC). Some studies claim that wound fluid (seroma), a common consequence of surgical excision in the tumor cavity, can reflect the effects of IORT on cancer inhibition. However, further research by our team and other researchers, such as analysis of seroma composition, affected cell lines, and primary tissues in two-dimensional (2D) and three-dimensional (3D) culture systems, clarified that seroma could not address the questions about IORT effectiveness in the surgical site. In this review, we mention the factors involved in tumor recurrence, direct or indirect effects of IORT on BC, and all the studies associated with BC seroma to attain more information about the impact of IORT-induced seroma to make a better decision to remove or remain after surgery and IORT. Finally, we suggest that seroma studies cannot decipher the mechanisms underlying the effectiveness of IORT in BC patients. The question of whether IORT-seroma has a beneficial effect can only be answered in a trial with a clinical endpoint, which is not even ongoing.
Inter-subject variability of pleasant pain relief using a data-driven approach in healthy volunteers
Authors: Henri Catherine , Marchand Serge , Giguère Charles-Édouard , Léonard Guillaume , Potvin Stéphane
Published: November 2022

Background

The offset of a painful and unpleasant sensation can elicit pleasure. This phenomenon, namely pleasant pain relief (PPR), is attracting growing interest in research. While the cold pressor test (CPT) has been frequently used to study the inhibition of pain by the administration of another painful stimulation (inhibitory conditioned pain modulation; ICPM), a preliminary study from our research team has shown that CPT can also elicit a robust and long-lasting PPR. However, its effects on pain relief and inhibition vary greatly between subjects. Although substantial research has been carried out on inter-individual variability in the case of ICPM, the same cannot be said of PPR. Therefore, the current study sought to identify clusters of healthy volunteers with similar dynamic pain responses during the CPT, using a data-driven approach, and to investigate the inter-subject variability for PPR and ICPM.

Methods

One hundred and twenty-two healthy volunteers were recruited. A sequential ICPM paradigm was carried out with CPT (water at 10°C) and a Peltier Thermode to evaluate pain intensity and unpleasantness. Moreover, PPR was measured for four minutes at CPT offset. Statistical analyses were performed using group-based trajectory modelling.

Results

Four trajectories (groups) were identified for CPT pain intensity and unpleasantness ratings with varying levels of tonic pain and pain sensitization (e.g., temporal summation). PPR scores were correlated with both pain ratings trajectories (p < 0.001). On the other hand, no differences were found between groups regarding ICPM efficacy (percentage pain inhibition).

Discussion

This study has provided a first step into the investigation of PPR and ICPM interindividual variability. Using a data-driven approach, it was shown that PPR at CPT offset differs between clusters of participants identified based on dynamic pain intensity and unpleasantness responses from CPT. Thus, it was brought to light that both the levels of tonic pain and pain sensitization underlie individual differences in PPR. The lack of correlation between CPT pain trajectories and ICPM efficacy may be explained by the hypotheses that eliciting ICPM requires only a certain threshold of stimulation which doesn’t need to be noxious. In the future, studies on the inter-subject variability of PPR in large samples of chronic pain patients are warranted.
Health-related quality of life in adult patients with asthma according to asthma control and severity: A systematic review and meta-analysis
Authors: Oh Byeong-Chan , Lee Ju-Eun , Nam Jin Hyun , Hong Ji-Yoon , Kwon Sun-Hong , Lee Eui-Kyung
Published: November 2022

Background:The utility values are increasingly being used in economic evaluations and health policy decision making. This study aims to conduct a systematic literature review and meta-analysis of the utility values for asthma, particularly with respect to severity and asthma control.

Materials and methods:A literature search was conducted using the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for studies published until July, 2020, reporting the utilities of adult asthma. We extracted utility values derived by nine indirect and four direct utility instruments. Meta-analyses were performed for each utility instrument according to health states based on the level of asthma control and severity.

Results:Fifty-two eligible studies were included in our systematic review, of which forty studies were used in the meta-analyses. Among the 13 utility instruments, the most used was EQ-5D-3L, whereas EQ-5D-5L showed the narrowest 95% confidence interval (95% CI, 0.83–0.86) of pooled utility. The pooled utility of asthma declined with worsening control levels and severity. The pooled utility value of EQ-5D-3L was 0.72 (95% CI, 0.63–0.80) for uncontrolled, 0.82 (95% CI, 0.75–0.88) for partly controlled, and 0.87 (95% CI, 0.84–0.90) for well-controlled asthma.

Conclusion:Our study shows that EQ-5D-3L and EQ-5D-5L are appropriate for economic evaluations in terms of availability and variability of information, respectively. Asthma patients had poorer utility values with worsened severity and level of asthma control. This study will be useful for health economists conducting economic evaluations of asthma treatments.
Similarities between maternal and fetal RR interval tachograms and their association with fetal development
Authors: Widatalla Namareq , Khandoker Ahsan , Alkhodari Mohanad , Koide Kunihiro , Yoshida Chihiro , Kasahara Yoshiyuki , Kimura Yoshitaka , Saito Masatoshi
Published: November 2022

An association between maternal and fetal heart rate (HR) has been reported but, so far, little is known about its physiological implication and importance relative to fetal development. Associations between both HRs were investigated previously by performing beat-by-beat coupling analysis and correlation analysis between average maternal and fetal HRs. However, studies reporting on the presence of similarities between maternal and fetal HRs or RR intervals (RRIs) over the short term (e.g., 5-min) at different gestational ages (GAs) are scarce. Here, we demonstrate the presence of similarities in the variations exhibited by maternal and fetal RRl tachograms (RRITs). To quantify the same similarities, a cross-correlation (CC) analysis between resampled maternal and fetal RRITs was conducted; RRITs were obtained from non-invasive electrocardiogram (ECG). The degree of similarity between maternal and fetal RRITs (bmfRRITs) was quantified by calculating four CC coefficients. CC analysis was performed for a total of 330 segments (two 5-min segments from 158 subjects and one 5-min from 14 subjects). To investigate the association of the similarity bmfRRITs with fetal development, the linear correlation between the calculated CC coefficients and GA was calculated. The results from the latter analysis showed that similarities bmfRRITs are common occurrences, they can be negative or positive, and they increase with GA suggesting the presence of a regulation that is associated with proper fetal development. To get an insight into the physiological mechanisms involved in the similarity bmfRRITs, the association of the same similarity with maternal and fetal HR variability (HRV) was investigated by comparing the means of two groups in which one of them had higher CC values compared to the other. The two groups were created by using the data from the 158 subjects where fetal RRI (fRRI) calculation from two 5-min ECG segments was feasible. The results of the comparison showed that the maternal very low frequency (VLF) HRV parameter is potentially associated with the similarity bmfRRITs implying that maternal hormones could be linked to the regulations involved in the similarity bmfRRITs. Our findings in this study reinforce the role of the maternal intrauterine environment on fetal development.
Impact of mental health, job insecurity, and COVID-19 symptoms on protective behavior changes among White, Black, and other minorities in the US
Authors: Sun Yingying , Wang Ping , Tang Jun
Published: November 2022

Introduction

Job insecurity such as loss of jobs or reduced wages has become a serious social problem in the US since COVID-19 started. Combined with psychological distress and experience of COVID-19 symptoms, the changes of people’s protective behaviors vary across states in the US.

Methods

This research investigated racial differences in the COVID-19 related factors among White, Black, and other minorities in the US, and examined how mental health mediated the impact of job insecurity on protective behaviors, and how the COVID-19 symptoms moderated the mediation effect of mental health. The 731 valid responses in a cross-sectional survey from May 23 to 27, 2020, in the US were analyzed with independent sample t-tests, Pearson’s chi-square tests, and path analysis.

Results

The findings showed that there were significant differences in job insecurity and Nonpharmaceutical Interventions (NPIs) practice among White, Black, and other minorities. Job insecurity was significantly negatively associated with NPIs practice and was significantly positively associated with mental health. Mental health significantly partially mediated the effect of job insecurity on NPIs practice, in that job insecurity is a better predictor of NPIs practice for individuals with worse mental health than that for individuals with better mental health. Experience of COVID-19 symptoms moderates the mediation effect of mental health on the relationship between job insecurity and NPIs practice, in that mental health is a better predictor of NPIs practice for individuals with a higher experience of COVID-19 symptoms than for individuals with a lower experience of COVID-19 symptoms.

Discussion

The findings in this study shed lights on psychological and behavioral studies of people’s behavior changes during a pandemic. The study indicates the importance of treating mental health to promote protective behaviors during a pandemic, as well as advocating for employees by identifying the needs for those whose jobs were negatively impacted the most.
It’s time to talk fathers: The impact of paternal depression on parenting style and child development during the COVID-19 pandemic
Authors: Roberts Joshua Paul , Satherley Rose-Marie , Iles Jane
Published: November 2022

This study aimed to understand the relationship between paternal depression, parenting behavior and child developmental outcomes during the SARS-CoV-2 (COVID) pandemic. In addition, the paternal experience of the pandemic, such as the impact of lockdowns, was explored. Fathers of children aged 6–11 years old (n= 87) were recruited for an online cross-sectional survey. Data was collected through questionnaires and open-ended comments. Regression analysis indicated a higher level of self-reported depressive symptomology in fathers more severely impacted by the pandemic across financial, familial and health domains. Further, COVID-19 impact, but not paternal depression, was linked to fewer authoritative parenting behaviors, characterized as lower warmth and responsiveness. Paternal pandemic impact and depression symptoms were independently predictive of child cognitive scores, and both were associated with emotional and behavioral outcomes. A content analysis of open-ended responses from fathers noted that concerns for their children, work and mental health were most prevalent during the pandemic. However, several responders also reported no change or positive facets of lockdowns related to the pandemic. These finds are discussed in the context of a possible behavioural mechanism of action accounting for the effect of these factors on child development. Clinical implications include targeted interventions for at risk groups as well as psychoeducation for fathers that acknowledge difference in paternal coping and support seeking.
The implications of inefficient markets for executive pay comparison: The case of China and Poland
Authors: Liu Yanqiu , Liu Hanmin
Published: November 2022

Although there is a large volume of literature on executive compensation, few of these studies have focused on executive pay comparisons and even fewer on the antecedents of executive pay comparisons. This paper fills this gap in executive pay comparison literature by beginning with executive pay comparison behaviors, and then the elements that influence executive pay comparison behaviors are discussed. A questionnaire survey found that executive pay comparison behaviors exist in both China and Poland. Furthermore, the findings show that the factors influencing executive pay comparison behaviors are different in the two countries. In China, there is a significant relationship between executive pay comparison behaviors and the dysfunctional agent market, herd mentality. And in Poland, there is a significant relationship between executive pay comparison behaviors and the ineffectiveness of government intervention, herd mentality. The implications of the study are also discussed.
The anti-anxiety drug lorazepam changes implicit behaviors but not explicit evaluations of sense of agency under authoritative pressure: A functional magnetic resonance imaging study
Authors: Chen Chenyi , Martínez Róger Marcelo , Chen Yu-Chun , Fan Yang-Teng , Cheng Yawei
Published: November 2022

Previous research on coercion has neglected the fact that agents under authoritative pressure may also suffer from coercive power, which can trigger anxiety-like emotional negativity on its victims. Furthermore, high levels of neuroticism and/or anxiety have been found to be associated with the compliance of various forms of social pressure. In this study, we investigate the effects of the anxiolytic GABAA (gamma-Aminobutyric acid) modulator, lorazepam, on behavioral and neural responses to coercive power. Here, we applied a virtual obedience to authority paradigm alongside lorazepam administration (versus placebo), and during functional magnetic resonance imaging scanning. Our results show that lorazepam administration exerted differential effects on the reaction times (RTs) when initiating harming versus helping behaviors, with longer harming RTs compared to helping RTs, despite comparable subjective ratings regarding perceived coercion. Coercive harming significantly increased activity in the amygdala, hippocampus, orbitofrontal cortex, and dorsolateral prefrontal cortex (dlPFC). Lorazepam administration decreased amygdala and hippocampus activity, but increased dlPFC and right temporoparietal junction activations. The lower activity in the hippocampus predicted higher ratings for perceived coercion. Furthermore, lorazepam significantly decreased the functional connectivity of the hippocampus with the dlPFC during coercive harming. In conclusion, we provide evidence –by incorporating multimodal indices, including neuroimaging, neuropharmacological interventions, and behavioral assessments– to posit that the GABAA agonist, lorazepam, might aid as a possible intervention in service of coping strategies against coercion.