bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoplasmic MSH2 Related to Genomic Deletions in the MSH2/EPCAM Genes in Colorectal Cancer Patients With Suspected Lynch Syndrome
Authors: Dong Lin , Zou Shuangmei , Jin Xianglan , Lu Haizhen , Zhang Ye , Guo Lei , Cai Jianqiang , Ying Jianming
Published: May 2021

Background

A large proportion of patients with Lynch syndrome (LS) have MSH2 abnormalities, but genotype-phenotype studies of MSH2 mutations in LS are still lacking. The aim of this study was to comprehensively analyze the clinicopathological characteristics and molecular basis of colorectal cancer (CRC) in patients with uncommon MSH2 cytoplasmic expression.

Methods

We retrospectively reviewed 4195 consecutive cases of CRC patients diagnosed between January 2015 and December 2017 at the Cancer Hospital Chinese Academy of Medical Sciences. Of the 4195 patients with CRC, 69 were indicated to have abnormal MSH2 expression through tumor immunohistochemical staining. Genetic tests, such as next-generation sequencing, large genomic rearrangement (LGR) analysis, microsatellite instability status analysis and genomic breakpoint analysis, were performed. Clinicopathological and molecular characteristics and clinical immunotherapy response were analyzed.

Results

Forty-five of 69 patients were identified to have LS with pathogenic germline mutations in MSH2 and/or EPCAM. Of these LS patients, 26.7% were confirmed to harbor large genomic rearrangements (LGRs). Of note, three tumors from two unrelated family pedigrees exhibited a rare cytoplasmic MSH2 staining pattern that was found in LS patients with EPCAM/MSH2 deletions. RNA analysis showed that two novel mRNA fusions of EPCAM and MSH2 resulted in the predicted protein fusion with MSH2 cytoplasmic localization. Analyses of genomic breakpoints indicated that two novel deletions of EPCAM and MSH2 originated from Alu repeat-mediated recombination events. Our study also provides clinical evidence for the beneficial effect of the PD-1 inhibitor pembrolizumab for CRC patients that exhibit cytoplasmic MSH2 staining.

Conclusion

Our study demonstrates that the rare cytoplasmic MSH2 staining pattern should be fully recognized by pathologists and geneticists. Given the specific genotype-phenotype correlation in LS screening, we advocate that all CRC patients with cytoplasmic MSH2 staining in histology should be screened for LGRs of EPCAM and MSH2.
Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference
Authors: Spohn Simon K. B. , Sachpazidis Ilias , Wiehle Rolf , Thomann Benedikt , Sigle August , Bronsert Peter , Ruf Juri , Benndorf Matthias , Nicolay Nils H. , Sprave Tanja , Grosu Anca L. , Baltas Dimos , Zamboglou Constantinos
Published: May 2021

Purpose

Multiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).

Patients and Methods

10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.

Results

Median overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 – 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 – 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.

Conclusion

Urethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.
Dual-Energy Computed Tomography-Based Radiomics to Predict Peritoneal Metastasis in Gastric Cancer
Authors: Chen Yong , Xi Wenqi , Yao Weiwu , Wang Lingyun , Xu Zhihan , Wels Michael , Yuan Fei , Yan Chao , Zhang Huan
Published: May 2021

Objective

To develop and validate a dual-energy computed tomography (DECT) derived radiomics model to predict peritoneal metastasis (PM) in patients with gastric cancer (GC).

Methods

This retrospective study recruited 239 GC (non-PM = 174, PM = 65) patients with histopathological confirmation for peritoneal status from January 2015 to December 2019. All patients were randomly divided into a training cohort (n = 160) and a testing cohort (n = 79). Standardized iodine-uptake (IU) images and 120-kV-equivalent mixed images (simulating conventional CT images) from portal-venous and delayed phases were used for analysis. Two regions of interest (ROIs) including the peritoneal area and the primary tumor were independently delineated. Subsequently, 1691 and 1226 radiomics features were extracted from the peritoneal area and the primary tumor from IU and mixed images on each phase. Boruta and Spearman correlation analysis were used for feature selection. Three radiomics models were established, including the R_IU model for IU images, the R_MIX model for mixed images and the combined radiomics model (the R_comb model). Random forest was used to tune the optimal radiomics model. The performance of the clinical model and human experts to assess PM was also recorded.

Results

Fourteen and three radiomics features with low redundancy and high importance were extracted from the IU and mixed images, respectively. The R_IU model showed significantly better performance to predict PM than the R_MIX model in the training cohort (AUC, 0.981 vs. 0.917, p = 0.034). No improvement was observed in the R_comb model (AUC = 0.967). The R_IU model was the optimal radiomics model which showed no overfitting in the testing cohort (AUC = 0.967, p = 0.528). The R_IU model demonstrated significantly higher predictive value on peritoneal status than the clinical model and human experts in the testing cohort (AUC, 0.785, p = 0.005; AUC, 0.732, p <0.001, respectively).

Conclusion

DECT derived radiomics could serve as a non-invasive and easy-to-use biomarker to preoperatively predict PM for GC, providing opportunity for those patients to tailor appropriate treatment.
Circular RNAs in Hepatocellular Carcinoma: Emerging Functions to Clinical Significances
Authors: Zhang Yucheng , Wang Yali
Published: May 2021

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and carries high morbidity and mortality. Diagnosing HCC at an early stage is challenging. Therefore, finding new, highly sensitive and specific diagnostic biomarkers for the diagnosis and prognosis of HCC patients is extremely important. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed loop structures. They are characterized by remarkable stability, long half-life, abundance and evolutionary conservation. Recent studies have shown that many circRNAs are expressed aberrantly in HCC tissues and have important regulatory roles during the development and progression of HCC. Hence, circRNAs are promising biomarkers for the diagnosis and prognosis of HCC. This review: (i) summarizes the biogenesis, categories, and functions of circRNAs; (ii) focuses on current progress of dysregulated expression of circRNAs in HCC with regard to regulation of the tumor hallmarks, “stemness” of cancer cells, and immunotherapy; (iii) highlights circRNAs as potential biomarkers and therapeutic targets for HCC; and (iv) discusses some of the challenges, questions and future perspectives of circRNAs research in HCC.
A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer
Authors: Huang Peide , Li Fengyu , Mo Zongchao , Geng Chunyu , Wen Fang , Zhang Chunyan , Guo Jia , Wu Song , Li Lin , Brünner Nils , Stenvang Jan
Published: May 2021

To investigate the relationship between non-coding RNAs [especially circular RNAs (circRNAs)] and docetaxel resistance in breast cancer, and to find potential predictive biomarkers for taxane-containing therapies, we have performed transcriptome and microRNA (miRNA) sequencing for two established docetaxel-resistant breast cancer (DRBC) cell lines and their docetaxel-sensitive parental cell lines. Our analyses revealed differences between circRNA signatures in the docetaxel-resistant and -sensitive breast cancer cells, and discovered circRNAs generated by multidrug-resistance genes in taxane-resistant cancer cells. In DRBC cells, circABCB1 was identified and validated as a circRNA that is strongly up-regulated, whereas circEPHA3.1 and circEPHA3.2 are strongly down-regulated. Furthermore, we investigated the potential functions of these circRNAs by bioinformatics analysis, and miRNA analysis was performed to uncover potential interactions between circRNAs and miRNAs. Our data showed that circABCB1, circEPHA3.1 and circEPHA3.2 may sponge up eight significantly differentially expressed miRNAs that are associated with chemotherapy and contribute to docetaxel resistance via the PI3K-Akt and AGE-RAGE signaling pathways. We also integrated differential expression data of mRNA, long non-coding RNA, circRNA, and miRNA to gain a global profile of multi-level RNA changes in DRBC cells, and compared them with changes in DNA copy numbers in the same cell lines. We found that Chromosome 7 q21.12-q21.2 was a common region dominated by multi-level RNA overexpression and DNA amplification, indicating that overexpression of the RNA molecules transcribed from this region may result from DNA amplification during stepwise exposure to docetaxel. These findings may help to further our understanding of the mechanisms underlying docetaxel resistance in breast cancer.
Comparison of Percutaneous Radiofrequency Ablation for Subcapsular and Non-Subcapsular Colorectal Cancer Liver Metastases
Authors: Fan Hongjie , Wang Xiaoyan , Qu Jiali , Lu Wei , Xu Shufeng , Wu Xia , Xia Jingya , Zhang Yanhua , Sun Jihong , Yang Xiaoming
Published: May 2021

Purpose

To evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) for subcapsular colorectal cancer liver metastases (CLMs).

Materials and Methods

With the approval of the Institutional Review Board, the clinical data of CLM patients who underwent percutaneous RFA for the first time from August 2010 to August 2020 were continuously collected. All CLMs were divided into subcapsular and non-capsular groups. Baseline characteristic data, technical effectiveness, minimal ablative margin, complications, local tumor progression (LTP), and overall survival (OS) between the two groups were analyzed using the t-test or chi-square test. A Cox regression model was used to evaluate the prognostic factors of LTP.

Results

One hundred and ninety-nine patients (124 males; mean age, 60.2 years) with 402 CLMs (221 subcapsular; mean size, 16.0 mm) were enrolled in the study. Technical effectiveness was achieved in 93.5% (376/402) of CLMs, with a major complication rate of 5.5%. Compared with non-subcapsular tumors, the minimal ablative margin achieved in subcapsular CLM was smaller (χ2 = -8.047, P < 0.001). With a median follow-up time of 23 months (range, 3−96 months), 37.1% of the tumors had LTP. The estimated cumulative OS at 1, 3, and 5 years was 96.1%, 66.0%, and 44.2%, respectively. There were no statistically significant differences between the two groups in terms of technical effectiveness (χ2 = 0.484, P = 0.487), major complications (χ2 = 0.082, P = 0.775), local tumor progression-free survival (LTPFS) (χ2 = 0.881, P = 0.348), and OS (χ2 = 2.874, P = 0.090). Minimal ablative margin, tumor size (≥20 mm), and technical effectiveness were predictors of LTP (all P < 0.05).

Conclusion

RFA is a safe and effective technique for local tumor control of subcapsular CLMs.
Comparison of Two-Step Transient Evoked Otoacoustic Emissions and One-Step Automated Auditory Brainstem Response for Universal Newborn Hearing Screening Programs in Remote Areas of China
Authors: Sheng Haibin , Zhou Qian , Wang Qixuan , Yu Yun , Liu Lihua , Liang Meie , Zhou Xueyan , Wu Hao , Tang Xiangrong , Huang Zhiwu
Published: May 2021

Objective: To compare the hearing screening results of two-step transient evoked otoacoustic emissions (TEOAE) and one-step automatic auditory brainstem response (AABR) in non-risk newborns, and to explore a more suitable hearing screening protocol for infants discharged within 48 h after birth in remote areas of China.

Methods: To analyze the age effect on pass rate for hearing screening, 2005 newborns were divided into three groups according to screening time after birth: <24, 24–48, and 48–72 h. All subjects received TEOAE + AABR test as first hearing screen, and those who failed in any test were rescreened with TEOAE + AABR at 6 weeks after birth. The first screening results of AABR and TEOAE were compared among the three groups. The results of two-step TEOAE screening and one-step AABR screening were compared for newborns who were discharged within 48 h. The time spent on screening was recorded for TEOAE and AABR.

Results: The pass rate of TEOAE and AABR increased significantly with the increase of first screening time (P < 0.05), and the false positive rate decreased significantly with the increase of first screening time (P < 0.05). The failure rate of first screening of AABR within 48 h was 7.31%, which was significantly lower than that of TEOAE (9.93%) (P < 0.05). The average time spent on AABR was 12.51 ± 6.36 min, which was significantly higher than that of TEOAE (4.05 ± 1.56 min, P < 0.05). The failure rate of TEOAE two-step screening was 1.59%, which was significantly lower than one-step AABR.

Conclusions: Compared with TEOAE, AABR screening within 48 h after birth can reduce the failure rate and false positive rate of first screening. However, compared with TEOAE two-step screening, one-step AABR screening has higher referral rate for audiological diagnosis. In remote areas of China, especially in hospitals with high delivery rate, one-step AABR screening is not feasible, and two-step TEOAE screening protocol is still applicable to UNHS screening as more and more infants discharged within 48 h after birth.
Increased Risk of Kawasaki Disease in Infants Born of Mothers With Immune Disorders
Authors: Chu Hsiao-Wen , Lin Chien-Heng , Lin Ming-Chih , Hsu Ya-Chi
Published: May 2021

Introduction:Genetic susceptibility and immune dysregulation play important roles in the pathogenesis of Kawasaki disease (KD). However, it is still unclear whether KD causes immune disorder later in life or whether inherited susceptibility to immune disorders causes KD. The aim of this study was to elucidate whether inherited immune disease properties from mothers increase the risk of KD from a population-based perspective.

Method:Taiwan's National Health Insurance Research Database was the main data source in this study. Parents and children were linked using the Taiwan Maternal and Child Health Database. Patients diagnosed with KD and younger than 18 years from 2004 to 2015 were enrolled as the study population. The control group was randomly selected from individuals without the diagnosis of KD matched by age, index year, sex, and urbanization level at a ratio of 1 to 10. The prevalence of maternal autoimmune and allergic diseases was compared between groups.

Results:In total, 7,178 children were found to have been diagnosed with Kawasaki disease. Then 71,780 children matched by index year, gender, and urbanization were randomly selected to serve as the control group. Children born from mothers with asthma and allergic rhinitis had a higher risk of developing KD. Children of mothers with an autoimmune disorder had a significantly increased tendency to develop KD. Maternal numbers of autoimmune disorders showed a dose-dependent relationship with KD incidence.

Conclusion:This is the first population-based study to investigate maternal immune diseases and the risk of KD in their children. Children of mothers with immune disorders tend to have a higher risk of KD.
Renal Infarcts—A Perplexing Case in the Middle of the COVID-19 Pandemic
Authors: Plouffe Brett , Van Hooren Tamara , Barton Michelle , Nashid Nancy , Demirkaya Erkan , Norozi Kambiz , Rachinsky Irina , Delport Johan , Knauer Michael , Tole Soumitra , Filler Guido
Published: May 2021

Renal infarction is a rare finding in children. Associations between SARS-CoV-2 infections and thromboembolic events including renal infarcts have been described in adults. Although a similar association in children has not yet been described with this pandemic, the pediatric literature is still evolving with the recognition of new manifestations including the post-infectious Multisystem Inflammatory Syndrome in Children (MIS-C). We report the rare event of multiple renal infarcts in a 6-year-old boy manifesting several features of MIS-C 9 weeks following a self-limiting febrile illness characteristic of COVID-19. An underlying Factor V Leiden mutation was identified in this child but felt to be insufficient on its own to explain his clinical presentation. As SARS-CoV-2 testing was delayed, the failure to identify viral RNA or antibodies may not exclude the virus' potential role in precipitating the infarct in this host. Given that renal infarcts have been described in adult patients with COVID-19, reporting this perplexing case where SARS-CoV-2 may have played a role, may help identify this potential complication.
Cholesterol Stimulates the Transient Receptor Potential Melastatin 4 Channel in mpkCCDc14 Cells
Authors: Cai Yong-Xu , Zhang Bao-Long , Yu Miao , Yang Yan-Chao , Ao Xue , Zhu Di , Wang Qiu-Shi , Lou Jie , Liang Chen , Tang Liang-Liang , Wu Ming-Ming , Zhang Zhi-Ren , Ma He-Ping
Published: May 2021

We have shown that cholesterol regulates the activity of ion channels in mouse cortical collecting duct (CCD) mpkCCDc14 cells and that the transient receptor potential melastatin 4 (TRPM4) channel is expressed in these cells. However, whether TRPM4 channel is regulated by cholesterol remains unclear. Here, we performed inside-out patch-clamp experiments and found that inhibition of cholesterol biosynthesis by lovastatin significantly decreased, whereas enrichment of cholesterol with exogenous cholesterol significantly increased, TRPM4 channel open probability (Po) by regulating its sensitivity to Ca2+ in mpkCCDc14 cells. In addition, inside-out patch-clamp data show that acute depletion of cholesterol in the membrane inner leaflet by methyl-β-cyclodextrin (MβCD) significantly reduced TRPM4 Po, which was reversed by exogenous cholesterol. Moreover, immunofluorescence microscopy, Western blot, cell-surface biotinylation, and patch clamp analysis show that neither inhibition of intracellular cholesterol biosynthesis with lovastatin nor application of exogenous cholesterol had effect on TRPM4 channel protein abundance in the plasma membrane of mpkCCDc14 cells. Sucrose density gradient centrifugation studies demonstrate that TRPM4 was mainly located in cholesterol-rich lipid rafts. Lipid-protein overlay experiments show that TRPM4 directly interacted with several anionic phospholipids, including PI(4,5)P2. Depletion of PI(4,5)P2 with either wortmannin or PGE2 abrogated the stimulatory effects of exogenous cholesterol on TRPM4 activity, whereas exogenous PI(4,5)P2 (diC8-PI(4,5)P2, a water-soluble analog) increased the effects. These results suggest that cholesterol stimulates TRPM4 via a PI(4,5)P2-dependent mechanism.
Restricting Glutamine Uptake Enhances NSCLC Sensitivity to Third-Generation EGFR-TKI Almonertinib
Authors: Liu Yaming , Ge Xianming , Pang Jinlong , Zhang Yuhan , Zhang Hao , Wu Hongyan , Fan Fangtian , Liu Hao
Published: May 2021

The emergence of secondary resistance is the main failure cause of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a targeted therapy for non-small cell lung cancer (NSCLC). EGFR mutations of NSCLC cells can markedly increase glutamine transporter (SLC1A5) expression, thereby increasing glutamine metabolism. Glutamine metabolites can activate EGFR downstream signals, including mTOR, ERK1/2, STAT3, etc., which is an important cause for the decreased sensitivity of NSCLC to EGFR-TKIs. CCK8 and Annexin V/PI assays were conducted to detect the effects of Almonertinib and/or V9302 on the proliferation and apoptosis of NSCLC cells. Proteomics was used to determine the effect of Almonertinib on energy metabolism-related proteins in NSCLC. siRNA transfection was performed to study the effect of SLC1A5 down-regulation on cell proliferation. In addition, the effects of drugs on colony formation capacity were determined by colony formation assay. Immunofluorescence and Western blot were utilized to detect the apoptosis- and autophagy-related proteins expression. DAPI staining was utilized to detect the effect of drugs on the nucleus. Transmission electron microscope was used to observe the changes of submicroscopic structure such as autophagosomes and nucleus of cells. mCherry-GFP-LC3B tandem fluorescent protein was to used to detect the level of autophagy flux. Tumor-bearing nude mouse model was utilized to detect the effect of V9302 on the anti-tumor effect of Almonertinib in vivo. As a result, Almonertinib suppressed H1975 and A549 cell proliferation depended on its dosage and treatment duration, and it also induced apoptosis. A549 cells with wild-type EGFR had lower sensitivity to Almonertinib. The expression of SLC1A5 was up-regulated by stimulating with low concentration of Almonertinib in NSCLC cells. SLC1A5 was highly expressed in A549 cells with wild-type EGFR. Glutamine deletion or SLC1A5 inhibition/silencing inhibited the proliferation of NSCLC cells, and decreased cellular glutamine uptake. The combination of SLC1A5 inhibitor V9302 and Almonertinib had a synergistic inhibitory effect on the proliferation of NSCLC. V9302 enhanced the effect of Almonertinib in apoptosis-inducing in NSCLC cells. The combination of V9302 and Almonertinib might induce apoptosis by inhibiting autophagy.
Basal Pressure Variations Induced by a Turbulent Flow Over a Wavy Surface
Authors: Claudin Philippe , Louge Michel , Andreotti Bruno
Published: May 2021

Turbulent flows over wavy surfaces give rise to the formation of ripples, dunes and other natural bedforms. To predict how much sediment these flows transport, research has focused mainly on basal shear stress, which peaks upstream of the highest topography, and has largely ignored the corresponding pressure variations. In this article, we reanalyze old literature data, as well as more recent wind tunnel results, to shed a new light on pressure induced by a turbulent flow on a sinusoidal surface. While the Bernoulli effect increases the velocity above crests and reduces it in troughs, pressure exhibits variations that lag behind the topography. We extract the in-phase and in-quadrature components from streamwise pressure profiles and compare them to hydrodynamic predictions calibrated on shear stress data.
Arterial Stiffness: Effects of Anticancer Drugs Used for Breast Cancer Women
Authors: Novo Giuseppina , Di Lisi Daniela , Manganaro Roberta , Manno Girolamo , Lazzara Simone , Immordino Federico Angelo , Madaudo Cristina , Carerj Scipione , Russo Antonio , Incorvaia Lorena , Zito Concetta
Published: May 2021

Purpose: It is well known that anticancer drugs used for treating breast cancer can cause cardiac toxicity, and less is known about vascular toxicity. The aim of this study was to assess subclinical vascular effects of anthracyclines and trastuzumab (TRZ) in women treated for breast cancer.

Methods: We enrolled 133 female patients with breast cancer undergoing adjuvant treatment with anthracycline-containing chemotherapy (CT) followed by taxane (paclitaxel/docetaxel) + TRZ. Patients underwent a standard echocardiography including measurement of left ventricular ejection fraction and global longitudinal strain at baseline and at follow-up. Vascular toxicity was evaluated by measuring brachial blood pressure (BP) and arterial stiffness indices (pulse wave velocity and Beta stiffness index) at T0 (baseline), T1 (3 months), T2 (6 months), and T3 (12 months).

Results: Arterial stiffness indices were significantly increased at T1 in patients treated with anthracycline-containing CT (PWV 5.5 m/s IQR 5.15–6.4 at T0 vs. PWV 6.7 m/s IQR 5.6–7.2 at T1, p < 0.05; Beta index PWV 6.7 IQR 5.25–6.65 at T0, PWV 8.35 IQR 6.5–10.15 at T1, p < 0.05) but not at T2 and T3, when treatment with anthracyclines was stopped and patients were under treatment with taxane and TRZ. Blood pressure values did not significantly change during follow-up.

Conclusion: Changes in arterial stiffness parameters occur early after starting treatment with anthracyclines, and they seem to be reversible if anthracycline treatment is stopped. These changes are not influenced by blood pressure values modifications. Therefore, in breast cancer women, anthracyclines seem to cause early reversible subclinical vascular injury.
Sex and Response to Cardioprotective Conditioning Maneuvers
Authors: Querio Giulia , Geddo Federica , Antoniotti Susanna , Gallo Maria Pia , Penna Claudia
Published: May 2021

Ischemic heart disease (IHD) is a multifactorial pathological condition strictly related to genetic, dietary, and lifestyle factors. Its morbidity and mortality rate represent one of the most important pathological issues that today involve younger people in a stronger way than in the past. IHD clinical outcomes are difficult to treat and have a high economic impact on health care. So prevention of this pathological condition through cardioprotective maneuvers represents the first line of intervention, as already underlined by several animal and human studies. Even if the time of intervention is important to prevent severe outcomes, many studies highlight that sex-dependent responses are crucial for the result of cardioprotective procedures. In this scenario sexual hormones have revealed an important role in cardioprotective approach, as women seem to be more protected toward cardiac insults when compared to male counterparts. The aim of this mini review is to show the molecular pathways involved in cardioprotective protocols and to elucidate how sexual hormones can contribute in ameliorating or worsening the physiological responses to IHD.
Screening of Reference Genes for RT-qPCR in Chicken Adipose Tissue and Adipocytes
Authors: Na Wei , Wang Yuxiang , Gong Pengfei , Zhang Xinyang , Zhang Ke , Zhang Hui , Wang Ning , Li Hui
Published: May 2021

Reverse transcription quantitative real-time PCR is the most commonly used method to detect gene expression levels. In experiments, it is often necessary to correct and standardize the expression level of target genes with reference genes. Therefore, it is very important to select stable reference genes to obtain accurate quantitative results. Although application examples of reference genes in mammals have been reported, no studies have investigated the use of reference genes in studying the growth and development of adipose tissue and the proliferation and differentiation of preadipocytes in chickens. In this study, GeNorm, a reference gene stability statistical algorithm, was used to analyze the expression stability of 14 candidate reference genes in the abdominal adipose tissue of broilers at 1, 4, and 7 weeks of age, the proliferation and differentiation of primary preadipocytes, as well as directly isolated preadipocytes and mature adipocytes. The results showed that the expression of the TATA box binding protein (TBP) and hydroxymethylbilane synthase (HMBS) genes was most stable during the growth and development of abdominal adipose tissue of broilers, the expression of the peptidylprolyl isomerase A (PPIA) and HMBS genes was most stable during the proliferation of primary preadipocytes, the expression of the TBP and RPL13 genes was most stable during the differentiation of primary preadipocytes, and the expression of the TBP and HMBS genes was most stable in directly isolated preadipocytes and mature adipocytes. These results provide reference bases for accurately detecting the mRNA expression of functional genes in adipose tissue and adipocytes of chickens.
Management After Windstorm Affects the Composition of Ectomycorrhizal Symbionts of Regenerating Trees but Not Their Mycorrhizal Networks
Authors: Veselá Petra , Vašutová Martina , Edwards-Jonášová Magda , Holub Filip , Fleischer Peter , Cudlín Pavel
Published: May 2021

Due to ongoing climate change, forests are expected to face significant disturbances more frequently than in the past. Appropriate management is intended to facilitate forest regeneration. Because European temperate forests mostly consist of trees associated with ectomycorrhizal (ECM) fungi, understanding their role in these disturbances is important to develop strategies to minimize their consequences and effectively restore forests. Our aim was to determine how traditional (EXT) and nonintervention (NEX) management in originally Norway spruce (Picea abies) forests with an admixture of European larch (Larix decidua) affect ECM fungal communities and the potential to interconnect different tree species via ECM networks 15 years after a windstorm. Ten plots in NEX and 10 plots in EXT with the co-occurrences of Norway spruce, European larch, and silver birch (Betula pendula) were selected, and a total of 57 ECM taxa were identified using ITS sequencing from ECM root tips. In both treatments, five ECM species associated with all the studied tree species dominated, with a total abundance of approximately 50% in the examined root samples. Because there were no significant differences between treatments in the number of ECM species associated with different tree species combinations in individual plots, we concluded that the management type did not have a significant effect on networking. However, management significantly affected the compositions of ECM symbionts of Norway spruce and European larch but not those of silver birch. Although this result is explained by the occurrence of seedlings and ECM propagules that were present in the original forest, the consequences are difficult to assess without knowledge of the ecology of different ECM symbionts.
Splitting the Difference: Heterogeneous Soil Moisture Availability Affects Aboveground and Belowground Reserve and Mass Allocation in Trembling Aspen
Authors: Hart Ashley T. , Merlin Morgane , Wiley Erin , Landhäusser Simon M.
Published: May 2021

When exploring the impact of resource availability on perennial plants, artificial treatments often apply conditions homogeneously across space and time, even though this rarely reflects conditions in natural systems. To investigate the effects of spatially heterogeneous soil moisture on morphological and physiological responses, trembling aspen (Populus tremuloides) saplings were used in a split-pot experiment. Following the division of the root systems, saplings were established for a full year and then subjected to either heterogeneous (portion of the root system exposed to non-lethal drought) or homogeneous (whole root system exposed to non-lethal drought or well-watered) treatments. Above- and belowground growth and non-structural carbohydrate (NSC) reserves (soluble sugars and starch) were measured to determine how allocation of reserves and mass between and within organs changed in response to variation in soil moisture availability. In contrast to saplings in the homogeneous drought treatment, which experienced reduced shoot growth, leaf abscission and fine root loss, saplings exposed to the heterogeneous conditions maintained similar aboveground growth and increased root system allocation compared to well-watered saplings. Interestingly under heterogeneous soil moisture conditions, the portion of the root system that was resource limited had no root dieback and increased carbon reserve concentrations, while the portion of the root system that was not resource limited added new roots (30% increase). Overall, saplings subjected to the heterogeneous soil moisture regime over-compensated belowground, both in mass and NSC reserves. These results indicate that the differential allocation of mass or reserves between above- and belowground organs, but also within the root system can occur. While the mechanisms and processes involved in these patterns are not clear, these responses could be interpreted as adaptations and acclimations to preserve the integrity of the entire sapling and suggests that different portions of plant organs might respond autonomously to local conditions. This study provides further appreciation of the complexity of the mechanisms by which plants manage heterogeneous conditions and offers evidence that spatial and temporal variability of resource availability, particularly belowground, needs to be accounted for when extrapolating and modeling stress responses at larger temporal and spatial scales.
(Sympathy for) the Devil You Know: Openness, Psychological Entropy, and the Case of the Incumbency Advantage
Authors: Ramey Adam J. , Klingler Jonathan D. , Hollibaugh Gary E.
Published: May 2021

Why do some individuals prefer lesser-known, riskier experiences over more well-known options in life? In this paper, we focus on the case of the electoral advantage to incumbency, and the role that psychological entropy reduction can play in undermining that advantage among individuals who lack simplifying heuristics, such as party brand loyalty. We build on recent work in political psychology, applying a more general political psychology framework linking the Big Five personality trait of Openness to a compulsion to gather and process information. Using data from the 2014 and 2016 Cooperative Congressional Election Studies, we find more Open respondents are more willing to vote for more uncertain House challengers at higher rates, but only among Independent respondents who are unable to rely on partisan cues to simplify the psychological entropy presented by such challengers. This suggests Openness captures relative preferences for encountering and reducing psychological entropy rather than traditionally defined risk preferences.
Factor Structure of the “Top Ten” Positive Emotions of Barbara Fredrickson
Authors: Roth Leopold Helmut Otto , Laireiter Anton-Rupert
Published: May 2021

In order to contribute to the consolidation in the field ofPositive Psychology, we reinvestigated the factor structure of top 10 positive emotions of Barbara Fredrickson. Former research in experimental settings resulted in a three-cluster solution, which we tested withexploratoryandconfirmatorymethodology against different factor models. Within our non-experimental data (N= 312), statistical evidence is presented, advocating for a single factor model of the 10 positive emotions. Different possible reasons for the deviating results are discussed, as well as the theoretical significance to various subfields inPositive Psychology(e.g., therapeutical interventions). Furthermore, the special role ofawewithin the study and its implications for further research in the field are discussed.
Moving Beyond Disciplinary Silos Towards a Transdisciplinary Model of Wellbeing: An Invited Review
Authors: Mead Jessica , Fisher Zoe , Kemp Andrew H.
Published: May 2021

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues such as inequality and anthropogenic climate change. Accordingly, there have been increasing calls for a broader conceptualisation of wellbeing. Here we impose an interpretative framework on previously published literature and theory, and present a theoretical framework that brings into focus the multifaceted determinants of wellbeing and their interactions across multiple domains and levels of scale. We define wellbeing as positive psychological experience, promoted by connections to self, community and environment, supported by healthy vagal function, all of which are impacted by socio-contextual factors that lie beyond the control of the individual. By emphasising the factors within and beyond the control of the individual and highlighting how vagal function both affects and are impacted by key domains, the biopsychosocial underpinnings of wellbeing are explicitly linked to a broader context that is consistent with, yet complementary to, multi-levelled ecological systems theory. Reflecting on the reciprocal relationships between multiple domains, levels of scale and related social contextual factors known to impact on wellbeing, our GENIAL framework may provide a foundation for a transdisciplinary science of wellbeing that has the potential to promote the wellbeing of individuals while also playing a key role in tackling major societal challenges.
A Systematic Review of the Characteristics and Efficacy of Recovery Training for Mental Health Staff: Implications for Supported Accommodation Services
Authors: McPherson Peter , Lloyd-Evans Brynmor , Dalton-Locke Christian , Killaspy Helen
Published: May 2021

Evidence suggests a link between recovery-oriented practise and service user outcomes in supported accommodation settings. Current clinical guidelines recommend recovery training for supported accommodation staff, however evidence relating to the effectiveness of this type of training is unclear. This review aimed to describe and compare the characteristics and efficacy of existing recovery training packages for mental health staff. The appropriateness and applicability of the interventions was considered in relation to UK supported accommodation services. Initial search processes returned 830 papers. After duplicate removal, inclusion and exclusion criteria were applied to 489 papers, leaving a final sample of seven papers. Data were reviewed using a narrative synthesis approach. The reviewed papers showed variation in the aims, frequency, and duration of the training interventions, although all included content consistent with the five-domains of the CHIME model. All interventions used direct, in-person teaching, and prioritised interactive, experiential learning, however a number were limited by the absence of feedback, the use of one-off, rather than repeated/follow-up sessions, and a reliance on classroom-based, rather than in-vivo, training. There was limited evidence to suggest a consistent effect of training on staff or service user outcomes, and there was no clear association between the delivery and design characteristics of the interventions and reported outcomes. In considering the development of recovery training for supported accommodation staff, little guidance can be taken from the reviewed literature. Any training package must be developed with consideration of the unique contextual and organisational characteristics of these services. The authors recommend viewing training as one component of a broader goal of service transformation.
Childhood and Adulthood Severe Stressful Experiences and Biomarkers Related to Glucose Metabolism: A Possible Association?
Authors: Tosato Sarah , Bonetto Chiara , Lopizzo Nicola , Cattane Nadia , Barcella Mara , Turco Giorgia , Ruggeri Mirella , Provasi Stefania , Tomassi Simona , Dazzan Paola , Cattaneo Annamaria
Published: May 2021

Background: No study investigated the association between stress exposure in different stages of life and metabolic dysfunction.

Aim: We explore the association between stress exposure and several biomarkers related to glucose metabolism (insulin, c-peptide, GIP, GLP-1, glucagon) in a group of 72 healthy individuals.

Method: We used the Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and a modified version of the Life Events Scale to define exposure to stress, according to four categories: no exposure to childhood trauma (CT) nor to stressful life events (SLEs) (46%), only to CT (25%), only to SLEs (21%), to both (8%).

Results: We found that c-peptide (p = 0.006) and insulin (p = 0.002) levels differed among the four categories: 0.77 ng/ml (SD 0.27) and 0.21 ng/ml (SD 0.06) for none, 0.77 (SD 0.37) and 0.20 (SD 0.08) for only SLEs, 0.88 (SD 0.39) and 0.27 (SD 0.12) for only CT, 1.33 (SD 0.57) and 0.40 (SD 0.28) for both, respectively. The highest levels of biomarkers were found in subjects exposed to both CT and SLEs.

Conclusion: Our preliminary results seem to suggest that CT might be specifically associated with a dysfunction of glucose metabolism, which might increase the risk of poorer health outcomes in adulthood. This association seems to be even stronger in individuals additionally exposed to SLEs in adulthood. In conclusion, if confirmed in other studies, subjects exposed to both CT and SLEs appear the most vulnerable individuals, for whom preventative interventions, such as healthy lifestyle education programs, might ameliorate the risk of developing metabolic abnormalities.
Monocyte Transcriptional Profiling Highlights a Shift in Immune Signatures Over the Course of Illness in Schizophrenia
Authors: Melbourne Jennifer K. , Rosen Cherise , Chase Kayla A. , Feiner Benjamin , Sharma Rajiv P.
Published: May 2021

With advanced understanding of the intricate interplay between the immune and central nervous systems in neurological and neuropsychiatric illness, there is renewed interest in the potential contribution of immune dysregulation to the development and progression of schizophrenia. To inform this line of inquiry requires a more nuanced understanding of specific immune changes throughout the course of illness. Here, we utilized a genome-wide sequencing approach to transcriptionally profile circulating monocytes in participants with chronic schizophrenia. These myeloid cells, isolated from whole blood samples, are highly plastic with potentially important disease-modifying functions. Differential gene expression and gene set enrichment analyses, focusing on established monocyte phenotypic signatures, including those related to proinflammatory (“M1-like”) and protective or tissue remodeling (“M2-like”) functions, were carried out. We demonstrate an overall enrichment of both “M1-like” (interferon-alpha, interferon-gamma, lipopolysaccharide acute) and “M2-like” (endotoxin tolerance, glucocorticoid acute) monocyte signatures in the participants with schizophrenia compared to non-psychiatric controls. There was no enrichment of the “M1-like” chronic stress signature or the “M2-like” interleukin-4 signature. Using the Molecular Signatures Database Hallmark gene sets list, the “interferon response” was most strongly enriched in schizophrenia compared to controls. Additionally, an exploratory subgroup analysis based on illness duration suggests a shift in monocyte phenotype with illness progression. Specifically, the “M1-like” interferon-gamma signature shows decreased enrichment accompanied by increased enrichment of opposing “M2-like” signatures in participants with a medium illness duration shifting to a strong enrichment of interferon response signatures only in participants with a long illness duration. These findings related to circulating immune cell phenotype have potentially important implications for understanding the role of immune dysregulation in schizophrenia and are a critical consideration for future study design and immune-targeting treatment strategies.
Cognitive Empathy and Longitudinal Changes in Temporo-Parietal Junction Thickness in Schizophrenia
Authors: Karpouzian-Rogers Tatiana , Cobia Derin , Petersen Julie , Wang Lei , Mittal Vijay A. , Csernansky John G. , Smith Matthew J.
Published: May 2021

Objective: Deficits in cognitive empathy are well-documented in individuals with schizophrenia and are related to reduced community functioning. The temporoparietal junction (TPJ) is closely linked to cognitive empathy. We compared the relationship between baseline cognitive empathy and changes in TPJ thickness over 24 months between individuals with schizophrenia and healthy controls.

Methods: Individuals with schizophrenia (n = 29) and healthy controls (n = 26) completed a cognitive empathy task and underwent structural neuroimaging at baseline and approximately 24 months later. Symmetrized percent change scores were calculated for right and left TPJ, as well as whole-brain volume, and compared between groups. Task accuracy was examined as a predictor of percent change in TPJ thickness and whole-brain volume in each group.

Results: Individuals with schizophrenia demonstrated poorer accuracy on the cognitive empathy task (p < 0.001) and thinner TPJ cortex relative to controls at both time points (p = 0.01). In schizophrenia, greater task accuracy was uniquely related to less thinning of the TPJ over time (p = 0.02); task accuracy did not explain changes in left TPJ or whole-brain volume. Among controls, task accuracy did not explain changes in right or left TPJ, or whole-brain volume.

Conclusions: Our findings suggest that greater cognitive empathy may explain sustained integrity of the right TPJ in individuals with schizophrenia, suggesting a contributory substrate for the long-term maintenance of this process in psychosis. Cognitive empathy was not related to changes in whole-brain volume, demonstrating the unique role of the TPJ in cognitive empathy.
Under COVID-19 Pandemic: A Quasi-Experimental Trial of Observation on Diabetes Patients' Health Behavior Affected by the Pandemic From a Coaching Intervention Program
Authors: Lin Ching-Ling , Huang Li-Chi , Chang Yao-Tsung , Chen Ruey-Yu , Yang Shwu-Huey
Published: May 2021

Introduction: The aim of this study was to explore the impact of diabetes self-management and HbA1c affected by the COVID-19 pandemic and the epidemic prevention work.

Methods: This quasi-experimental study collected a pooled data from a randomized-control study between February and May 2020 in which 114 participants who presented type 2 diabetes were recruited. The intervention group had health coaching and usual care, whereas the control had usual care only. The main outcome variables of this observation study were the change of HbA1c, physical activity, and eating out behavior within this time interval.

Results: We found that the eating out behavior of both groups had decreased, and if a health coach helped the patients set physical activity goals in the two groups, the physical activity behavior will not be impacted due to the pandemic.

Conclusions: While every country is focusing on COVID-19 pandemic prevention, especially when strict home quarantine measures and social distancing are adopted, reminding and assisting chronic patients to maintain good self-management behavior may lessen the social and medical system burdens caused by the deterioration of chronic conditions due to the excessive risk prevention behavior and the epidemic prevention work.

Trial Registration:www.isrctn.com, identifier number: ISRCTN14167790, date: 12 July, 2019.