bluuebunny/crossref_metadata_2025 huggingface dataset:
First Nationwide Molecular Screening Program in Spain for Patients With Advanced Breast Cancer: Results From the AGATA SOLTI-1301 Study
Authors: Pernas Sonia , Villagrasa Patricia , Vivancos Ana , Scaltriti Maurizio , Rodón Jordi , Burgués Octavio , Nuciforo Paolo , Canes Jordi , Paré Laia , Dueñas Marta , Vidal Maria , Cejalvo Juan Miguel , Perelló Antonia , Llommbard-Cussac Antonio , Dorca Joan , Montaño Alvaro , Pascual Tomás , Oliveira Mafalda , Ribas Gloria , Rapado Inmaculada , Prat Aleix , Ciruelos Eva
Published: November 2021

Background

The SOLTI-1301 AGATA study aimed to assess the feasibility of a multi-institutional molecular screening program to better characterize the genomic landscape of advanced breast cancer (ABC) and to facilitate patient access to matched-targeted therapies in Spain.

Methods

DNA sequencing of 74 cancer-related genes was performed using FFPE tumor samples in three different laboratories with three different gene panels. A multidisciplinary advisory board prospectively recommended potential targeted treatments. The primary objective was to determine the success of matching somatic DNA alteration to an experimental drug/drug class.

Results

Between September 2014 and July 2017, 305 patients with ABC from 10 institutions were enrolled. Tumor sequencing was successful in 260 (85.3%) patients. Median age was 54 (29-80); most tumors were hormone receptor-positive/HER2-negative (74%), followed by triple-negative (14.5%) and HER2-positive (11.5%). Ninety-seven (37%) tumor samples analyzed proceeded from metastatic sites. Somatic mutations were identified in 163 (62.7%) patients, mostly in PIK3CA (34%), TP53 (22%), AKT1 (5%), ESR1 (3%), and ERBB2 (3%) genes. Significant enrichment of AKT1 mutation was observed in metastatic versus primary samples (9% vs. 2%; p=0.01). Genome-driven cancer therapy was recommended in 45% (n=116) of successfully screened patients, 11% (n=13) of whom finally received it. Among these patients, 46.2% had a PFS of ≥6 months on matched therapy.

Conclusions

AGATA is the first nationwide molecular screening program carried out in Spain and we proved that implementing molecular data in the management of ABC is feasible. Although these results are promising, only 11% of the patients with genome-driven cancer therapy received it.
Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review
Authors: Guven Deniz C. , Sahin Taha K. , Kilickap Saadettin , Uckun Fatih M.
Published: November 2021

Introduction

After the results of phase III vaccine studies became available, the leading oncology societies recommended two doses of COVID-19 vaccination to all patients with cancer with no specific recommendation for tumor type and active treatments. However, the data on the COVID-19 vaccine efficacy in cancer patients is limited due to exclusion of cancer patients from most vaccine clinical trials. Therefore, we systemically reviewed the available evidence evaluating the antibody responses in cancer patients.

Methods

We conducted a systematic search from the Pubmed database and calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between cancer patients and controls using the Review Manager software, version 5.3.

Results

Our systematic search retrieved a total 27 studies and we included 17 studies with control arms in the analyses. Cancer patients had significantly lower seroconversion rates (37.3%) than controls (74.1%) (RD: -0.44, 95% CI: -0.52, -0.35, p<0.001) with first vaccine dose. After two doses, the seroconversion rates were 99.6% in control arm and 78.3% in cancer patients (RD: -0.19, 95% CI: -0.28, -0.10, p<0.001). The difference in seroconversion rates was more pronounced patients with hematologic malignancies (72.6%) (RD: -0.25, 95% CI: -0.27, -0.22, p<0.001) than patients with solid tumors (91.6%) (RD: -0.09, 95% CI: -0.13, -0.04, p<0.003) and patients in remission (RD: -0.10, 95% CI: -0.14, -0.06, p<0.001).

Conclusion

In conclusion, COVID-19 vaccine seroconversion rates were significantly lower in patients with hematological malignancies and patients under active treatment. Further research focusing on the approaches to improve vaccine efficacy and exploration of novel treatment options is urgently needed for these patients.
ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target
Authors: Cheng Xuan , Zhao Jian-Xiong , Dong Feng , Cao Xu-Chen
Published: November 2021

Distant metastasis is the principal cause of mortality for breast cancer patients. Targeting specific mutations that have been acquired during the evolution process of advanced breast cancer is a potential means of enhancing the clinical efficacy of treatment strategies. In metastatic breast cancer, ARID1A is the most prevalent mutation of the SWI/SNF complex, which regulates DNA repair, recombination, and gene transcription. The low expression of ARID1A is associated with poor disease-free survival and overall survival of patients with luminal A or HER2-rich breast cancer. In addition, ARID1A plays a prominent role in maintaining luminal characteristics and has an advantage for identifying responses to treatment, including endocrine therapies, HDAC inhibitors and CDK4/6 inhibitors. The therapeutic vulnerabilities initiated by ARID1A alterations encourage us to explore new approaches to cope with ARID1A mutant-related drug resistance or metastasis. In this review, we describe the mutation profiles of ARID1A in metastatic breast cancer and the structure and function of ARID1A and the SWI/SNF complex as well as discuss the potential mechanisms of ARID1A-mediated endocrine resistance and therapeutic potential.
Preoperative Systemic Inflammatory Biomarkers Are Independent Predictors of Disease Recurrence in ER+ HER2- Early Breast Cancer
Authors: Truffi Marta , Piccotti Francesca , Albasini Sara , Tibollo Valentina , Morasso Carlo Francesco , Sottotetti Federico , Corsi Fabio
Published: November 2021

The host’s immune system plays a crucial role in determining the clinical outcome of many cancers, including breast cancer. Peripheral blood neutrophils and lymphocytes counts may be surrogate markers of systemic inflammation and potentially reflect survival outcomes. The aim of the present study is to assess the role of preoperative systemic inflammatory biomarkers to predict local or distant relapse in breast cancer. In particular we investigated ER+ HER2- early breast cancer, considering its challenging risk stratification. A total of 1,763 breast cancer patients treated at tertiary referral Breast Unit were reviewed. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios were assessed from the preoperative blood counts. Multivariate analyses for 5-years locoregional recurrence-free (LRRFS), distant metastases-free (DMFS) and disease-free survivals (DFS) were performed, taking into account both blood inflammatory biomarkers and clinical-pathological variables. Low NLR and high LMR were independent predictors of longer LRRFS, DMFS and DFS, and low PLR was predictive of better LRRFS and DMFS in the study population. In 999 ER+ HER2- early breast cancers, high PLR was predictive of worse LRRFS (HR 0.42, p=0.009), while high LMR was predictive of improved LRRFS (HR 2.20, p=0.02) and DFS (HR 2.10, p=0.01). NLR was not an independent factor of 5-years survival in this patients’ subset. Inflammatory blood biomarkers and current clinical assessment of the disease were not in agreement in terms of estimate of relapse risk (K-Cohen from -0.03 to 0.02). In conclusion, preoperative lymphocyte ratios, in particular PLR and LMR, showed prognostic relevance in ER+ HER2- early breast cancer. Therefore, they may be used in risk stratification and therapy escalation/de-escalation in patients with this type of tumor.
Feasibility and Safety of a Simple Non-cystoscopic Double-J Tube Removal Technique in Children
Authors: Bao Qiao , Lao Weihua , Shi Tong , Ouyang Keyu , Ma Sai , Zhang Wen , Lin Yankun
Published: November 2021

Objective: Double-J tube placement is an important procedure during upper urinary tract surgery. A primary drawback is the requirement of a second double-J tube removal under a cystoscope. Therefore, a simple and feasible alternative is required to remove the double-J tube without cystoscopy. The present study reported the feasibility and safety of a simple non-cystoscopic double-J tube removal technique.

Method: We retrospectively analysed children who underwent pyeloplasty and ureterovesical reimplantation between June 2015 and August 2021. A simple device (a catheter with a suture) was used to pull out the double-J tube. Patient characteristics, detailed surgical procedures, success and complication rates and reasons for failure were evaluated.

Result: A total of 613 children were included. The mean age of patients was 6.2 months (3 months−14 years). Non-endoscopic methods were used to remove the double-J tube in all except 6 patients (0.9%). Of the 6 patients who required ureteroscopy or cystoscopy, 4 had retraction of the double-J tube into the ureter, and 2 (0.6%) had bladder stones. Of the 613 patients, 479 (76.0%) required one attempt, 127 (20.1%) required two attempts and 19 (3.0%) required several attempts. No serious postoperative complications occurred in all patients. The most common complications were gross haematuria (22.5%), pain urinating (17.9%), difficulty in urinating (3.6%), foreskin injury (1.7%), and penile oedema (1.3%). No urethral strictures developed during the follow-up period.

Conclusion: The study results demonstrated that the modified and simple non-cystoscopic double-J tube removal technique is a safe and an effective alternative to cystoscopy in clinical practise.
Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4–BLT1 Axis
Authors: Gong Minmin , Duan Huiyan , Wu Fan , Ren Yanlin , Gong Jing , Xu Lijun , Lu Fuer , Wang Dingkun
Published: November 2021

Background: Chronic low-grade inflammation is recognized as a key pathophysiological mechanism of insulin resistance. Leukotriene B4 (LTB4), a molecule derived from arachidonic acid, is a potent neutrophil chemoattractant. The excessive amount of LTB4 that is combined with its receptor BLT1 can cause chronic low-grade inflammation, aggravating insulin resistance. Berberine (BBR) has been shown to relieve insulin resistance due to its anti-inflammatory properties. However, it is not clear whether BBR could have any effects on the LTB4–BLT1 axis.

Methods: Using LTB4 to induce Raw264.7 and HepG2 cells, we investigated the effect of BBR on the LTB4–BLT1 axis in the progression of inflammation and insulin resistance.

Results: Upon exposure to LTB4, intracellular insulin resistance and inflammation increased in HepG2 cells, and chemotaxis and inflammation response increased in RAW264.7 cells. Interestingly, pretreatment with BBR partially blocked these changes. Our preliminary data show that BBR might act on BLT1, modulating the LTB4–BLT1 axis to alleviate insulin resistance and inflammation.

Conclusions: Our study demonstrated that BBR treatment could reduce intracellular insulin resistance and inflammation of hepatic cells, as well as chemotaxis of macrophages induced by LTB4. BBR might interact with BLT1 and alter the LTB4–BLT1 signaling pathway. This mechanism might be a novel anti-inflammatory and anti-diabetic function of BBR.
Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade
Authors: Liao Li , Zhou Mengting , Wang Jing , Xue Xinyan , Deng Ying , Zhao Xingtao , Peng Cheng , Li Yunxia
Published: November 2021

Thrombosis is a general pathological phenomenon during severe disturbances to homeostasis, which plays an essential role in cardiovascular and cerebrovascular diseases. Leonurine (LEO), isolated from Leonurus japonicus Houtt, showes a crucial role in anticoagulation and vasodilatation. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated. Therefore, the antithrombotic effect of LEO was investigated in this study. Hematoxylin-Eosin staining was used to detect the thrombosis of zebrafish tail. Fluorescence probe was used to detect the reactive oxygen species. The biochemical indexes related to oxidative stress (lactate dehydrogenase, malondialdehyde, superoxide dismutase and glutathione) and vasodilator factor (endothelin-1 and nitric oxide) were analyzed by specific commercial assay kits. Besides, we detected the expression of related genes (fga, fgb, fgg, pkcα, pkcβ, vwf, f2) and proteins (PI3K, phospho-PI3K, Akt, phospho-Akt, ERK, phospho-ERK FIB) related to the anticoagulation and fibrinolytic system by quantitative reverse transcription and western blot. Beyond that, metabolomic analyses were carried out to identify the expressions of metabolites associated with the anti-thrombosis mechanism of LEO. Our in vivo experimental results showed that LEO could improve the oxidative stress injury, abnormal platelet aggregation and coagulation dysfunction induced by adrenalin hydrochloride. Moreover, LEO restored the modulation of amino acids and inositol metabolites which are reported to alleviate the thrombus formation. Collectively, LEO attenuates adrenalin hydrochloride-induced thrombosis partly via modulating oxidative stress, coagulation cascade and platelet activation and amino acid and inositol metabolites.
(-)-Epigallocatechin-3-gallate Ameliorates Intervertebral Disc Degeneration Through Reprogramming of the Circadian Clock
Authors: Mei Liangwei , Zheng Yi , Ma Teng , Xia Bing , Gao Xue , Hao Yiming , Luo Zhuojing , Huang Jinghui
Published: November 2021

The circadian clock is vital in the management of our daily physiological as well as metabolic processes. Disturbances of the clock can cause degenerative and age-related diseases. Increasing evidence has indicated that the intervertebral discs contain an internal biological clock related to degeneration. However, to date, no bioactive compounds have been found that can ameliorate intervertebral disc degeneration (IDD) by restoring the circadian clock. (-)-Epigallocatechin-3-gallate (EGCG) is a nutritious food with powerful antioxidant properties, as well as entraining biological clock to improve health. The purpose of this study was to determine whether the protective effects of EGCG on nucleus pulposus (NPCs) under oxidative stress is related to the circadian clock. First, we found that EGCG attenuated H2O2-induced extracellular matrix degradation in NPCs and inhibited H2O2-induced NPC apoptosis. Our in vivo experiments also confirmed this finding. Furthermore, EGCG attenuated H2O2-triggered dampening of phase shifts and daily oscillations in circadian clock gene transcription as well as protein expression levels. Intriguingly, core clock gene (Bmal1) knockdown notably blocked the protective effects of EGCG. To our knowledge, this study provides the first convincing evidence that EGCG prevents IDD in a Bmal1-dependent manner. In general, EGCG supplementation can be used as a nutritional prevention strategy for the rehabilitation of degenerative diseases related to the circadian clock.
Phillyrin for COVID-19 and Influenza Co-infection: A Potential Therapeutic Strategy Targeting Host Based on Bioinformatics Analysis
Authors: Lai Yanni , Han Tiantian , Lao Zizhao , Li Geng , Xiao Jianyong , Liu Xiaohong
Published: November 2021

Background: The risk of co-epidemic between COVID-19 and influenza is very high, so it is urgent to find a treatment strategy for the co-infection. Previous studies have shown that phillyrin can not only inhibit the replication of the two viruses, but also has a good anti-inflammatory effect, which is expected to become a candidate compound against COVID-19 and influenza.

Objective: To explore the possibility of phillyrin as a candidate compound for the treatment of COVID-19 and influenza co-infection and to speculate its potential regulatory mechanism.

Methods: We used a series of bioinformatics network pharmacology methods to understand and characterize the pharmacological targets, biological functions, and therapeutic mechanisms of phillyrin in COVID-19 and influenza co-infection and discover its therapeutic potential.

Results: We revealed potential targets, biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and upstream pathway activity of phillyrin against COVID-19 and influenza co-infection. We constructed protein–protein interaction (PPI) network and identified 50 hub genes, such as MMP9, IL-2, VEGFA, AKT, and HIF-1A. Furthermore, our findings indicated that the treatment of phillyrin for COVID-19 and influenza co-infection was associated with immune balance and regulation of hypoxia-cytokine storm, including HIF-1 signaling pathway, PI3K-Akt signaling pathway, Ras signaling pathway, and T cell receptor signaling pathway.

Conclusion: For the first time, we uncovered the potential targets and biological pathways of phillyrin for COVID-19 and influenza co-infection. These findings should solve the urgent problem of co-infection of COVID-19 and influenza that the world will face in the future, but clinical drug trials are needed for verification in the future.
A Study Based on Metabolomics, Network Pharmacology, and Experimental Verification to Explore the Mechanism of Qinbaiqingfei Concentrated Pills in the treatment of Mycoplasma Pneumonia
Authors: Liu Zheng , Huo Jin-hai , Dong Wen-ting , Sun Guo-dong , Li Feng-jin , Zhang Ya-nan , Qin Zhi-wei , pengna Jiang , Wang Wei-ming
Published: November 2021

Qinbaiqingfei concentrated pills (QB) are a commonly used medicine for the treatment of mycoplasma pneumonia in China, and the mechanism of action of QB needs to be studied further. Therefore, we use a combination of metabolomics and network pharmacology to clarify the mechanism of QB. Nontarget metabolomics studies were performed on rat serum, urine, and lung tissues, and 56 therapeutic biomarkers were found. Subsequently, the components of QB absorbed into the blood and lung tissues were clarified, and based on this finding, the core target of network pharmacology was predicted. The enrichment analysis of biomarkers–genes finally confirmed their close relationship with the NF-κB signaling pathway. By western blotting expression of the proteins in the lung tissue–related signaling pathways, it is finally confirmed that QB inhibits the NF-κB signaling pathway through SIRT1, IL-10 and MMP9, CTNNB1, EGFR, and other targets. It plays a role in regulating immunity, regulating metabolism, and treating diseases.
Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases
Authors: Ogawa Tomohisa , Tobishima Yu , Kamata Shizuka , Matsuda Youhei , Muramoto Koji , Hidaka Masafumi , Futai Eugene , Kuraishi Takeshi , Yokota Shinichi , Ohno Motonori , Hattori Shosaku
Published: November 2021

Snakebites are one of the major causes of death and long-term disability in the developing countries due to the presence of various bioactive peptides and proteins in snake venom. In Japan, the venom of the habu snake (Protobothrops flavoviridis) causes severe permanent damage due to its myonecrotic toxins. Antivenom immunoglobulins are an effective therapy for snakebites, and antivenom was recently developed with effective suppressive activity against myonecrosis induced by snake venom. To compare the properties of an antivenom having anti-myonecrotic activity with those of conventional antivenom with no anti-myonecrotic activity, this study applied focused proteomics analysis of habu venom proteins using 2D gel electrophoresis. As a target protein for antivenom immunoglobulins with anti-myonecrotic activity, we identified a thrombin-like serine protease, TLSP2 (TLf2), which was an inactive proteolytic isoform due to the replacement of the active site, His43 with Arg. Additionally, we identified the unique properties and a novel synergistic function of pseudoenzyme TLf2 as a myonecrosis-enhancing factor. To our knowledge, this is the first report of a function of a catalytically inactive snake serine protease.
New Insights Into the Effects of Individual Chinese Herbal Medicines on Chronic Kidney Disease
Authors: Shao Minghai , Ye Chaoyang , Bayliss George , Zhuang Shougang
Published: November 2021

The clinical and experimental study into the effects of Chinese herbal medicines on chronic kidney disease has evolved over the past 40 years with new insight into their mechanism and evidence of their clinical effects. Among the many traditional Chinese herbs examined in chronic renal disease, five were found to have evidence of sufficient clinical efficacy, high frequency of use, and well-studied mechanism. They are: Abelmoschus manihot and Huangkui capsule, Salvia miltiorrhiza and its components (tanshinone II A, salvianolic acid A and B); Rhizoma coptidis and its monomer berberine; Tripterygium wilfordii and its components (triptolide, tripterygium glycosides); Kudzu root Pueraria and its monomer Puerarin. These Chinese herbal medications have pharmaceutical effects against fibrosis, inflammation and oxidative stress and also promote renal repair and regeneration. This article reviews their clinical efficacy, anti-fibrotic effects in animal models, and molecular mechanism of action.
Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics
Authors: King Jasia , Giselbrecht Stefan , Truckenmüller Roman , Carlier Aurélie
Published: November 2021

Epithelial membrane transporter kinetics portray an irrefutable role in solute transport in and out of cells. Mechanistic models are used to investigate the transport of solutes at the organ, tissue, cell or membrane scale. Here, we review the recent advancements in using computational models to investigate epithelial transport kinetics on the cell membrane. Various methods have been employed to develop transport phenomena models of solute flux across the epithelial cell membrane. Interestingly, we noted that many models used lumped parameters, such as the Michaelis-Menten kinetics, to simplify the transporter-mediated reaction term. Unfortunately, this assumption neglects transporter numbers or the fact that transport across the membrane may be affected by external cues. In contrast, more recent mechanistic transporter kinetics models account for the transporter number. By creating models closer to reality researchers can investigate the downstream effects of physical or chemical disturbances on the system. Evidently, there is a need to increase the complexity of mechanistic models investigating the solute flux across a membrane to gain more knowledge of transporter-solute interactions by assigning individual parameter values to the transporter kinetics and capturing their dependence on each other. This change results in better pharmacokinetic predictions in larger scale platforms. More reliable and efficient model predictions can be made by creating mechanistic computational models coupled with dedicated in vitro experiments. It is also vital to foster collaborative efforts among transporter kinetics researchers in the modeling, material science and biological fields.
How to Establish a Minimal Invasive and Stable Carotid Artery Stenosis Rabbit Model? A Simple and Effective Carotid Artery Balloon Strain Technique
Authors: Liu Zhengli , Gong Maofeng , Zhao Boxiang , Gu Jianping , Su Haobo , Zhou Yangyi , Fu Guanqi , He Xu , Kong Jie
Published: November 2021

Background: The objective of this study is to establish a minimally invasive technique to create a stable carotid artery stenosis rabbit model. This article summarizes the specific methods and key points of this technology.

Methods: The experiment studied a rabbit that was anesthetized through the vein. After the femoral artery was exposed, a minimally invasive needle was used to puncture the femoral artery, then the sheath was placed into the artery. We primarily put a catheter in the ascending aorta for angiography and then used a PT2 guidewire for super-selection. The PT2 guidewire was retained, and a balloon was placed in the right common carotid artery (CCA) through a guidewire to inflate it three times. Six rabbits in the 2- (2W) and 4-week (4W) groups were examined at 14 and 28 days, respectively. The rabbits in the control group received angiography at the beginning and 28 days later but without balloon injury. After angiography assessment, specimens of right CCA were dissected. Pathological and immunohistochemical examinations were performed on the collected specimens, and iFlow analysis was performed as well.

Results: All the 18 animals which survived were observed. The rabbits in the 2W and 4W groups showed stenosis of the right CCA. Digital subtraction angiography showed the diameter was lower than that in the control group (1.04 ± 0.1, 0.71 ± 0.12, and 1.83 ± 0.08 mm in 2W, 4W, and control group, P < 0.05). Pathology also suggested carotid stenosis and obvious intimal hyperplasia. The results of immunohistochemistry showed that α-smooth muscle actin was highly expressed in the 2W and 4W groups, and the integrated optical density (IOD) value was higher than that in the control group (14,807.11 ± 1,822.3, 22,245.96 ± 1,212.82, and 6,537.16 ± 1,186.62 in the 2W, 4W, and control group, P < 0.05). Meanwhile, a cluster of differentiation 31 (CD31) was low expressed in the 2W and 4W groups, and the IOD value was lower than that in the control group (519.14 ± 44.4, 1,029.64 ± 98.48, and 1,502.05 ± 88.79 in the 2W, 4W, and control group, P < 0.05), which suggested endothelial damage and partial repair. The analysis by iFlow showed that the time-to-peak after balloon strain in the 2W and 4W groups were longer than that in the control group.

Conclusion: We established a minimally invasive, effective, and safe method to establish a carotid artery stenosis rabbit model. The highlights of this technology were the application of minimally invasive methods, reducing surgical bleeding, infection, and related complications. This technology avoided the influence of tissue around CCA in the traditional carotid artery balloon injury model, which might lead to more accurate treatment outcomes.
Differential Effects of ‘Vaping’ on Lipid and Glucose Profiles and Liver Metabolic Markers in Obese Versus Non-obese Mice
Authors: Chen Hui , Li Gerard , Chan Yik Lung , Zhang Hui Emma , Gorrell Mark D. , Pollock Carol A. , Saad Sonia , Oliver Brian G.
Published: November 2021

Tobacco smoking increases the risk of metabolic disorders due to the combination of harmful chemicals, whereas pure nicotine can improve glucose tolerance. E-cigarette vapour contains nicotine and some of the harmful chemicals found in cigarette smoke at lower levels. To investigate how e-vapour affects metabolic profiles, male Balb/c mice were exposed to a high-fat diet (HFD, 43% fat, 20kJ/g) for 16weeks, and e-vapour in the last 6weeks. HFD alone doubled fat mass and caused dyslipidaemia and glucose intolerance. E-vapour reduced fat mass in HFD-fed mice; only nicotine-containing e-vapour improved glucose tolerance. In chow-fed mice, e-vapour increased lipid content in both blood and liver. Changes in liver metabolic markers may be adaptive responses rather than causal. Future studies can investigate how e-vapour differentially affects metabolic profiles with different diets.
Manual Therapy With Rest as a Treatment for Established Inflammation and Fibrosis in a Rat Model of Repetitive Strain Injury
Authors: Barbe Mary F. , Panibatla Siva Tejaa , Harris Michele Y. , Amin Mamta , Dorotan Jocelynne T. , Cruz Geneva E. , Bove Geoffrey M.
Published: November 2021

Background: Repetitive strain injuries caused by repetitive occupational work are difficult to prevent for multiple reasons. Therefore, we examined the effectiveness of manual therapy (MT) with rest to treat the inflammation and fibrosis that develops through the performance of a repetitive task. We hypothesized that this treatment would reduce task-induced sensorimotor declines and neuromuscular inflammation.

Methods: Twenty-nine female Sprague-Dawley rats performed a reaching and lever-pulling task for 14weeks. All ceased performing the task at 14weeks. Ten were euthanized at this timepoint (TASK). Nine received manual therapy to their upper extremities while resting 7weeks (MTR); 10 were assigned to rest alone (REST). Ten additional food restricted rats were included that neither performed the task nor received manual therapy (FRC).

Results: Confirming previous experiments, TASK rats showed behavioral changes (forepaw mechanical hypersensitivity, reduced grip strength, lowered forelimb/forepaw agility, and noxious cold temperature sensitivity), reduced median nerve conduction velocity (NCV), and pathological tissue changes (myelin degradation, increased median nerve and muscle inflammation, and collagen production). Manual therapy with rest (MTR) ameliorated cold sensitivity seen in REST rats, enhanced muscle interleukin 10 (IL-10) more than in REST rats, lead to improvement in most other measures, compared to TASK rats. REST rats showed improved grip strength, lowered nerve inflammation and degraded myelin, and lowered muscle tumor necrosis factor alpha (TNFα) and collagen I levels, compared to TASK rats, yet maintained lowered forelimb/forepaw agility and NCV, and increased neural fibrosis.

Conclusion: In our model of repetitive motion disorder, manual therapy during rest had modest effects on behavioral, histological, and physiological measures, compared to rest alone. These findings stand in contrast to the robust preventive effects of manual therapy in this same model.
A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1
Authors: Jeon Eun Yeong , Baek Seung Eun , Kim Ji On , Choi Jong Min , Jang Eun Jeong , Kim Chi Dae
Published: November 2021

Migration of vascular smooth muscle cells (VSMCs) plays an essential role in the development of vascular remodeling in the injured vasculatures. Previous studies have identified high-mobility group box 1 (HMGB1) as a principal effector mediating vascular remodeling; however, the mechanisms involved have not been fully elucidated. Thus, this study investigated the role of HMGB1 on VSMC migration and the underlying molecular mechanisms involved. VSMCs were ex plant cultured using rat thoracic aorta, and the cellular migration was measured using wound-healing assay. Osteopontin (OPN) mRNA and protein were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. The OPN promoter was cloned into pGL3 basic to generate a pLuc-OPN-2284 construct. Migration of VSMCs stimulated with HMGB1 (100ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100–300ng/ml), a neutralizing monoclonal antibody for OPN as well as in cells deficient of OPN. In VSMCs stimulated with HMGB1, OPN mRNA and protein levels were significantly increased in association with an increased promotor activity of OPN gene. Putative-binding sites for activator protein 1 (AP-1) and CCAAT/enhancer-binding protein beta (C/EBPβ) in the indicated promoter region were suggested by TF Search, and the HMGB1-induced expression of OPN was markedly attenuated in cells transfected with siRNA for AP-1. VSMC stimulated with HMGB1 also showed an increased expression of AP-1. Results of this study suggest a pivotal role for AP-1-induced OPN expression in VSMC migration induced by HMGB1. Thus, the AP-1-OPN signaling axis in VSMC might serve as a potential therapeutic target for vascular remodeling in the injured vasculatures.
SuperSour: A New Strategy for Breeding Superior Citrus Rootstocks
Authors: Bowman Kim D. , McCollum Greg , Albrecht Ute
Published: November 2021

Citrus crops have a long history of cultivation as grafted trees on selected rootstock cultivars, but all current rootstocks have significant limitations and traditional methods of rootstock breeding take at least 2–3 decades to develop and field test new rootstocks. Citrus production in the United States, and other parts of the world, is impaired by a wide range of biotic and abiotic problems, with especially severe damage caused by the disease huanglongbing (HLB) associated withCandidatusLiberibacter asiaticus. All major commercial citrus scion cultivars are damaged by HLB, but tree tolerance is significantly improved by some rootstocks. To overcome these challenges, the USDA citrus breeding program has implemented a multi-pronged strategy for rootstock breeding that expands the diversity of germplasm utilized in rootstock breeding, significantly increases the number of new hybrids evaluated concurrently, and greatly reduces the time from cross to potential cultivar release. We describe the key components and methodologies of this new strategy, termed “SuperSour,” along with reference to the historical favorite rootstock sour orange (Citrus aurantium), and previous methods employed in citrus rootstock breeding. Rootstock propagation by cuttings and tissue culture is one key to the new strategy, and by avoiding the need for nucellar seeds, eliminates the 6- to 15-year delay in testing while waiting for new hybrids to fruit. In addition, avoiding selection of parents and progeny based on nucellar polyembryony vastly expands the potential genepool for use in rootstock improvement. Fifteen new field trials with more than 350 new hybrid rootstocks have been established under the SuperSour strategy in the last 8 years. Detailed multi-year performance data from the trials will be used to identify superior rootstocks for commercial release, and to map important traits and develop molecular markers for the next generation of rootstock development. Results from two of these multi-year replicated field trials with sweet orange scion are presented to illustrate performance of 97 new hybrid rootstocks relative to four commercial rootstocks. Through the first 7 years in the field with endemic HLB, many of the new SuperSour hybrid rootstocks exhibit greatly superior fruit yield, yield efficiency, canopy health, and fruit quality, as compared with the standard rootstocks included in the trials.
Different Metabolic Roles for Alternative Oxidase in Leaves of Palustrine and Terrestrial Species
Authors: Del-Saz Nestor Fernandez , Douthe Cyril , Carriquí Marc , Ortíz Jose , Sanhueza Carolina , Rivas-Medina Alicia , McDonald Allison , Fernie Alisdair R. , Ribas-Carbo Miquel , Gago Jorge , Florez-Sarasa Igor , Flexas Jaume
Published: November 2021

The alternative oxidase pathway (AOP) is associated with excess energy dissipation in leaves of terrestrial plants. To address whether this association is less important in palustrine plants, we compared the role of AOP in balancing energy and carbon metabolism in palustrine and terrestrial environments by identifying metabolic relationships between primary carbon metabolites and AOP in each habitat. We measured oxygen isotope discrimination during respiration, gas exchange, and metabolite profiles in aerial leaves of ten fern and angiosperm species belonging to five families organized as pairs of palustrine and terrestrial species. We performed a partial least square model combined with variable importance for projection to reveal relationships between the electron partitioning to the AOP (τa) and metabolite levels. Terrestrial plants showed higher values of net photosynthesis (AN) and τa, together with stronger metabolic relationships between τa and sugars, important for water conservation. Palustrine plants showed relationships between τa and metabolites related to the shikimate pathway and the GABA shunt, to be important for heterophylly. Excess energy dissipation via AOX is less crucial in palustrine environments than on land. The basis of this difference resides in the contrasting photosynthetic performance observed in each environment, thus reinforcing the importance of AOP for photosynthesis.
Genome-Wide Investigation of the NAC Transcription Factor Family in Miscanthus sinensis and Expression Analysis Under Various Abiotic Stresses
Authors: Nie Gang , Yang Zhongfu , He Jie , Liu Aiyu , Chen Jiayi , Wang Shuan , Wang Xia , Feng Guangyan , Li Dandan , Peng Yan , Huang Linkai , Zhang Xinquan
Published: November 2021

The NAC transcription factor family is deemed to be a large plant-specific gene family that plays important roles in plant development and stress response. Miscanthus sinensis is commonly planted in vast areas of marginal lang as forage, ornamental grass, or bioenergy crop which demand a relatively high resistance to abiotic stresses. The recent release of a draft chromosome-scale assembly genome of M. sinensis provided a basic platform for the genome-wide investigation of NAC proteins. In this study, a total of 261 M. sinensis NAC genes were identified and a complete overview of the gene family was presented, including gene structure, conserved motif compositions, chromosomal distribution, and gene duplications. Results showed that gene length, molecular weights (MW), and theoretical isoelectric points (pI) of NAC family were varied, while gene structure and motifs were relatively conserved. Chromosomal mapping analysis found that the M. sinensis NAC genes were unevenly distributed on 19 M. sinensis chromosomes, and the interchromosomal evolutionary analysis showed that nine pairs of tandem duplicate genes and 121 segmental duplications were identified, suggesting that gene duplication, especially segmental duplication, is possibly associated with the amplification of M. sinensis NAC gene family. The expression patterns of 14 genes from M. sinensis SNAC subgroup were analyzed under high salinity, PEG, and heavy metals, and multiple NAC genes could be induced by the treatment. These results will provide a very useful reference for follow-up study of the functional characteristics of NAC genes in the mechanism of stress-response and potential roles in the development of M. sinensis.
Applying Bayesian Belief Networks to Assess Alpine Grassland Degradation Risks: A Case Study in Northwest Sichuan, China
Authors: Zhou Shuang , Peng Li
Published: November 2021

Grasslands are crucial components of ecosystems. In recent years, owing to certain natural and socio-economic factors, alpine grassland ecosystems have experienced significant degradation. This study integrated the frequency ratio model (FR) and Bayesian belief networks (BBN) for grassland degradation risk assessment to mitigate several issues found in previous studies. Firstly, the identification of non-encroached degraded grasslands and shrub-encroached grasslands could help stakeholders more accurately understand the status of different types of alpine grassland degradation. In addition, the index discretization method based on the FR model can more accurately ascertain the relationship between grassland degradation and driving factors to improve the accuracy of results. On this basis, the application of BBN not only effectively expresses the complex causal relationships among various variables in the process of grassland degradation, but also solves the problem of identifying key factors and assessing grassland degradation risks under uncertain conditions caused by a lack of information. The obtained result showed that the accuracies based on the confusion matrix of the slope of NDVI change (NDVIs), shrub-encroached grasslands, and grassland degradation indicators in the BBN model were 85.27, 88.99, and 74.37%, respectively. The areas under the curve based on the ROC curve of NDVIs, shrub-encroached grasslands, and grassland degradation were 75.39% (P < 0.05), 66.57% (P < 0.05), and 66.11% (P < 0.05), respectively. Therefore, this model could be used to infer the probability of grassland degradation risk. The results obtained using the model showed that the area with a higher probability of degradation (P > 30%) was 2.22 million ha (15.94%), with 1.742 million ha (78.46%) based on NDVIs and 0.478 million ha (21.54%) based on shrub-encroached grasslands. Moreover, the higher probability of grassland degradation risk was mainly distributed in regions with lower vegetation coverage, lower temperatures, less potential evapotranspiration, and higher soil sand content. Our research can provide guidance for decision-makers when formulating scientific measures for alpine grassland restoration.
Distinctive Traits for Drought and Salt Stress Tolerance in Melon (Cucumis melo L.)
Authors: Chevilly Sergio , Dolz-Edo Laura , Martínez-Sánchez Gema , Morcillo Luna , Vilagrosa Alberto , López-Nicolás José M. , Blanca José , Yenush Lynne , Mulet José M.
Published: November 2021

Melon (Cucumis melo L.) is a crop with important agronomic interest worldwide. Because of the increase of drought and salinity in many cultivation areas as a result of anthropogenic global warming, the obtention of varieties tolerant to these conditions is a major objective for agronomical improvement. The identification of the limiting factors for stress tolerance could help to define the objectives and the traits which could be improved by classical breeding or other techniques. With this objective, we have characterized, at the physiological and biochemical levels, two different cultivars (sensitive or tolerant) of two different melon varieties (Galia and Piel de Sapo) under controlled drought or salt stress. We have performed physiological measurements, a complete amino acid profile and we have determined the sodium, potassium and hormone concentrations. This has allowed us to determine that the distinctive general trait for salt tolerance in melon are the levels of phenylalanine, histidine, proline and the Na+/K+ ratio, while the distinctive traits for drought tolerance are the hydric potential, isoleucine, glycine, phenylalanine, tryptophan, serine, and asparagine. These could be useful markers for breeding strategies or to predict which varieties are likely perform better under drought or salt stress. Our study has also allowed us to identify which metabolites and physiological traits are differentially regulated upon salt and drought stress between different varieties.
Acceptance of Sexual Interest in Minors in Self-Referred Individuals Under Treatment – An Exploratory Pilot Study
Authors: Lampalzer Ute , Tozdan Safiye , von Franqué Fritjof , Briken Peer
Published: November 2021

Some therapists/scientists argue that “acceptance” of sexual interest in minors (SIM), i.e., the integration of the sexual preference into the individual self-concept, is a prerequisite for dealing with SIM in a responsible way. However, if one assumes that – even in some persons – SIM might change over time, “acceptance” could also run counter to therapeutic targets because the motivation to change as well as the specific self-efficacy for modifying SIM might be reduced. This exploratory pilot study analyzes the relationship between acceptance of SIM and (1) dynamic risk for contact sexual reoffending, (2) SIM and frequency of the use of child/adolescent (sexual abuse) imagery, (3) frequency of sexual desire/behavior toward children/adolescents, and (4) the change of the level of acceptance of SIM during the course of treatment. The majority of the participants (N= 79) was not exclusively interested in children (85%) and used child pornography but did not commit child sexual abuse (54%). Acceptance of SIM, frequency of the use of child/adolescent (sexual abuse) imagery and frequency of sexual desire/behavior toward children/adolescents are assessed via self-report questionnaires, dynamic risk for contact sexual reoffending is measured by STABLE-2007. Pretreatment data are analyzed via Spearman’s correlation (N= 79). Intragroup analysis compares acceptance of SIM from pre- and posttreatment (n= 35). There was no correlation between acceptance of SIM and dynamic risk for contact sexual reoffending. However, there was a medium, positive correlation between acceptance of SIM and the frequency of the use of legal imagery of children, a positive correlation between the item “My inclination is an integral part of my personality” and the frequency of the use of legal imagery of children, and a positive correlation between acceptance of SIM and the frequency of sexual activities with minors. Acceptance of SIM did not change during the course of treatment. The results suggest that “acceptance” of SIM has to be discussed in a differentiated way, i.e., as possibly being associated with positive and negative outcomes as well.
“Brain Fog” by COVID-19 or Alzheimer’s Disease? A Case Report
Authors: Matias-Guiu Jordi A. , Delgado-Alonso Cristina , Yus Miguel , Polidura Carmen , Gómez-Ruiz Natividad , Valles-Salgado María , Ortega-Madueño Isabel , Cabrera-Martín María Nieves , Matias-Guiu Jorge
Published: November 2021

Cognitive symptoms after COVID-19 have been increasingly recognized several months after the acute infection and have been designated as “brain fog.” We report a patient with cognitive symptoms that started immediately after COVID-19, in which cerebrospinal fluid biomarkers were highly suggestive of Alzheimer’s disease. Our case highlights the need to examine patients with cognitive symptoms following COVID-19 comprehensively. A detailed assessment combining clinical, cognitive, and biomarker studies may help disentangle the underlying mechanisms associated with cognitive dysfunction in each case. The investigation of neurodegenerative processes in an early stage, especially in older patients, is probably warranted.
The Relationship Between Emotional Intelligence and Diabetes Management: A Systematic Review
Authors: Pérez-Fernández Aida , Fernández-Berrocal Pablo , Gutiérrez-Cobo María José
Published: November 2021

Diabetes has been associated with affective disorders which complicate the management of the disease. Emotional intelligence (EI), or the ability to perceive, facilitate, understand, and regulate emotions, has shown to be a protective factor of emotional disorders in general population. The main objective of this study was to systematically review the role of the EI construct in Type 1 and Type 2 diabetics and to observe how EI is related to biological and psychological variables. Comprehensive searches were conducted in PubMed, Scopus, PsycInfo, and Cochrane without time limitations, for studies examining the link between diabetes and EI. A total of 12 eligible studies were selected according to the inclusion criteria. We divided the results into four sections: (1) EI and hemoglobin glycosylated (HbA1c), (2) EI training effects, (3) differences in EI between persons with diabetes and without diabetes, and (4) EI and psychological adjustment and well-being. The results showed negative correlations between EI and HbA1c, positive effects of EI training on quality of life, anxiety, and glycemic control, no differences in EI between people with diabetes and healthy individuals, and, finally, negative correlations between EI and different psychological variables such as diabetes-related anxiety and distress, and positive correlations with quality of life, well-being, and marital satisfaction. This systematic review offers a starting point for a theoretical and practical understanding of the role played by EI in the management of diabetes and reveals that EI is a promising protective factor for biological and psychological variables in this population.