bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Brain Stimulation Complications in Patients With Parkinson’s Disease and Surgical Modifications: A Single-Center Retrospective Analysis
Authors: Xu Shuo , Wang Wenfei , Chen Si , Wu Qianqian , Li Chao , Ma Xiangyu , Chen Teng , Li Weiguo , Xu Shujun
Published: June 2021

Background

As a complication-prone operation, deep brain stimulation (DBS) has become the first-line surgical approach for patients with advanced Parkinson’s disease (PD). This study aimed to evaluate the incidence and risk factors of DBS-associated complications.

Methods

We have reviewed a consecutive series of patients with PD undergoing DBS procedures to describe the type, severity, management, and outcome of postoperative complications from January 2011 to December 2018. Both univariate and multivariate analyses were performed to identify statistically significant risk factors. We also described our surgical strategies to minimize the adverse events.

Results

A total of 225 patients underwent 229 DBS implantation procedures (440 electrodes), of whom 20 patients experienced 23 DBS-associated complications, including ten operation-related complications and 13 hardware-related ones. Univariate analysis elucidated that comorbid medical conditions (P = 0.024), hypertension (P = 0.003), early-stage operation (P < 0.001), and unilateral electrode implantation (P = 0.029) as risk factors for overall complications, or more specifically, operation-related complications demonstrated in the stratified analysis. In contrast, no risk factor for hardware-related complications was identified. Statistical significances of hypertension (OR = 3.33, 95% CI: 1.14–9.71, P = 0.027) and early-stage (OR = 11.04, 95% CI: 2.42–50.45, P = 0.002) were further validated via multivariate analysis. As the annual number of DBS procedures increased, the incidence of complications gradually decreased (R = −0.699, P < 0.01). Additionally, there was a strong correlation between surgical complications and unplanned readmission (R = 0.730, P < 0.01).

Conclusion

The importance of cumulative experience and relevant technique modifications should be addressed to prevent DBS-associated complications and unplanned readmission.
Visual Illusions in Radiology: Untrue Perceptions in Medical Images and Their Implications for Diagnostic Accuracy
Authors: Alexander Robert G. , Yazdanie Fahd , Waite Stephen , Chaudhry Zeshan A. , Kolla Srinivas , Macknik Stephen L. , Martinez-Conde Susana
Published: June 2021

Errors in radiologic interpretation are largely the result of failures of perception. This remains true despite the increasing use of computer-aided detection and diagnosis. We surveyed the literature on visual illusions during the viewing of radiologic images. Misperception of anatomical structures is a potential cause of error that can lead to patient harm if disease is seen when none is present. However, visual illusions can also help enhance the ability of radiologists to detect and characterize abnormalities. Indeed, radiologists have learned to exploit certain perceptual biases in diagnostic findings and as training tools. We propose that further detailed study of radiologic illusions would help clarify the mechanisms underlying radiologic performance and provide additional heuristics to improve radiologist training and reduce medical error.
Corticospinal vs Rubrospinal Revisited: An Evolutionary Perspective for Sensorimotor Integration
Authors: Olivares-Moreno Rafael , Rodriguez-Moreno Paola , Lopez-Virgen Veronica , Macías Martín , Altamira-Camacho Moisés , Rojas-Piloni Gerardo
Published: June 2021

The knowledge about how different subsystems participate and interplay in sensorimotor control is fundamental to understand motor deficits associated with CNS injury and movement recovery. The role of corticospinal (CS) and rubrospinal (RS) projections in motor control has been extensively studied and compared, and it is clear that both systems are important for skilled movement. However, during phylogeny, the emerging cerebral cortex took a higher hierarchical role controlling rubro-cerebellar circuits. Here, we present anatomical, neurophysiological, and behavioral evidence suggesting that both systems modulate complex segmental neuronal networks in a parallel way, which is important for sensorimotor integration at spinal cord level. We also highlight that, although specializations exist, both systems could be complementary and potentially subserve motor recovery associated with CNS damage.
Use-Dependent Prosthesis Training Strengthens Contralateral Hemodynamic Brain Responses in a Young Adult With Upper Limb Reduction Deficiency: A Case Report
Authors: Borrell Jordan A. , Copeland Christopher , Lukaszek Jessica L. , Fraser Kaitlin , Zuniga Jorge M.
Published: June 2021

The purpose of the current case study was to determine the influence of an 8-week home intervention training utilizing a partial hand prosthesis on hemodynamic responses of the brain and gross dexterity in a case participant with congenital unilateral upper-limb reduction deficiency (ULD). The case participant (female, 19 years of age) performed a gross manual dexterity task (Box and Block Test) while measuring brain activity (functional near-infrared spectroscopy; fNIRS) before and after an 8-weeks home intervention training. During baseline, there was a broad cortical activation in the ipsilateral sensorimotor cortex and a non-focalized cortical activation in the contralateral hemisphere, which was non-focalized, while performing a gross manual dexterity task using a prosthesis. After the 8-week home intervention training, however, cortical activation shifted to the contralateral motor cortex while cortical activation was diminished in the ipsilateral hemisphere. Specifically, the oxygenated hemodynamics (HbO) responses increased in the medial aspects of the contralateral primary motor and somatosensory cortices. Thus, these results suggest that an 8-week prosthetic home intervention was able to strengthen contralateral connections in this young adult with congenital partial hand reduction. This was supported by the case participant showing after training an increased flexor tone, increased range of motion of the wrist, and decreased times to complete various gross dexterity tasks. Changes in HbO responses due to the home intervention training follow the mechanisms of use-dependent plasticity and further guide the use of prostheses as a rehabilitation strategy for individuals with ULD.
CT-Based Radiomics Analysis for Preoperative Diagnosis of Pancreatic Mucinous Cystic Neoplasm and Atypical Serous Cystadenomas
Authors: Xie Tiansong , Wang Xuanyi , Zhang Zehua , Zhou Zhengrong
Published: June 2021

Objectives

To investigate the value of CT-based radiomics analysis in preoperatively discriminating pancreatic mucinous cystic neoplasms (MCN) and atypical serous cystadenomas (ASCN).

Methods

A total of 103 MCN and 113 ASCN patients who underwent surgery were retrospectively enrolled. A total of 764 radiomics features were extracted from preoperative CT images. The optimal features were selected by Mann-Whitney U test and minimum redundancy and maximum relevance method. The radiomics score (Rad-score) was then built using random forest algorithm. Radiological/clinical features were also assessed for each patient. Multivariable logistic regression was used to construct a radiological model. The performance of the Rad-score and the radiological model was evaluated using 10-fold cross-validation for area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy.

Results

Ten screened optimal features were identified and the Rad-score was then built based on them. The radiological model was built based on four radiological/clinical factors. In the 10-fold cross-validation, the Rad-score was proved to be robust and reliable (average AUC: 0.784, sensitivity: 0.847, specificity: 0.745, PPV: 0.767, NPV: 0.849, accuracy: 0.793). The radiological model performed slightly less well in classification (average AUC: average AUC: 0.734 sensitivity: 0.748, specificity: 0.705, PPV: 0.732, NPV: 0.798, accuracy: 0.728.

Conclusions

The CT-based radiomics analysis provided promising performance for preoperatively discriminating MCN from ASCN and showed good potential in improving diagnostic power, which may serve as a novel tool for guiding clinical decision-making for these patients.
Normalization of Enzyme Expression and Activity Regulating Vitamin A Metabolism Increases RAR-Beta Expression and Reduces Cellular Migration and Proliferation in Diseases Caused by Tuberous Sclerosis Gene Mutations
Authors: Abdelwahab Elhusseiny Mohamed Mahmoud , Bovari-Biri Judit , Smuk Gabor , Harko Tunde , Fillinger Janos , Moldvay Judit , Krymskaya Vera P. , Pongracz Judit E.
Published: June 2021

Background

Mutation in a tuberous sclerosis gene (TSC1 or 2) leads to continuous activation of the mammalian target of rapamycin (mTOR). mTOR activation alters cellular including vitamin A metabolism and retinoic acid receptor beta (RARβ) expression. The goal of the present study was to investigate the molecular connection between vitamin A metabolism and TSC mutation. We also aimed to investigate the effect of the FDA approved drug rapamycin and the vitamin A metabolite retinoic acid (RA) in cell lines with TSC mutation.

Methods

Expression and activity of vitamin A associated metabolic enzymes and RARβ were assessed in human kidney angiomyolipoma derived cell lines, primary lymphangioleiomyomatosis (LAM) tissue derived LAM cell lines. RARβ protein levels were also tested in primary LAM lung tissue sections. TaqMan arrays, enzyme activities, qRT-PCRs, immunohistochemistry, immunofluorescent staining, and western blotting were performed and analysed. The functional effects of retinoic acid (RA) and rapamycin were tested in a scratch and a BrDU assay to assess cell migration and proliferation.

Results

Metabolic enzyme arrays revealed a general deregulation of many enzymes involved in vitamin A metabolism including aldehyde dehydrogenases (ALDHs), alcohol dehydrogenases (ADHs) and Cytochrome P450 2E1 (CYP2E1). Furthermore, RARβ downregulation was a characteristic feature of all TSC-deficient cell lines and primary tissues. Combination of the two FDA approved drugs -RA for acute myeloid leukaemia and rapamycin for TSC mutation- normalised ALDH and ADH expression and activity, restored RARβ expression and reduced cellular proliferation and migration.

Conclusion

Deregulation of vitamin A metabolizing enzymes is a feature of TSC mutation. RA can normalize RARβ levels and limit cell migration but does not have a significant effect on proliferation. Based on our data, translational studies could confirm whether combination of RA with reduced dosage of rapamycin would have more beneficial effects to higher dosage of rapamycin monotherapy meanwhile reducing adverse effects of rapamycin for patients with TSC mutation.
The Prognostic Value of Preoperative Serum Tumor Markers in Non-Small Cell Lung Cancer Varies With Radiological Features and Histological Types
Authors: Chen Haiqing , Fu Fangqiu , Zhao Yue , Wu Haoxuan , Hu Hong , Sun Yihua , Zhang Yawei , Xiang Jiaqing , Zhang Yang
Published: June 2021

Objectives

To assess the association between common-used serum tumor markers and recurrence of lung adenocarcinoma and squamous cell carcinoma separately and determine the prognostic value of serum tumor markers in lung adenocarcinoma featured as ground glass opacities.

Methods

A total of 2,654 non-small cell lung cancer patients undergoing surgical resection between January 2008 and September 2014 were analyzed. The serum levels of carcinoma embryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carbohydrate antigen 199 (CA199) were tested preoperatively. Survival analyses were performed with COX proportional hazard regression.

Results

Among patients with lung adenocarcinoma, elevated preoperative serum CEA(HR=1.246, 95%CI:1.043-1.488, P=0.015), CYFRA21-1(HR=1.209, 95%CI:1.015-1.441, P=0.034) and CA125(HR=1.361, 95%CI:1.053-1.757, P=0.018) were significantly associated with poorer recurrence free survival (RFS). Elevated preoperative serum CA199 predicted worse RFS in patients diagnosed with lung squamous cell carcinoma (HR=1.833, 95%CI: 1.216-2.762, P=0.004). Preoperative serum CYFRA21-1(HR=1.256, 95%CI:1.044-1.512, P=0.016) and CA125(HR=1.373, 95%CI: 1.050-1.795, P=0.020) were independent prognostic factors for patients with adenocarcinoma presenting as solid nodules while serum CEA (HR=2.160,95%CI:1.311-3.558, P=0.003) and CA125(HR=2.475,95%CI:1.163-5.266, P=0.019) were independent prognostic factors for patients with adenocarcinoma featured as ground glass opacities.

Conclusions

The prognostic significances of preoperative serum tumor markers in non-small cell lung cancer were associated with radiological features and histological types.
Subtype-Based Analysis of Cell-in-Cell Structures in Esophageal Squamous Cell Carcinoma
Authors: Wang Yuqi , Niu Zubiao , Zhou Lulin , Zhou Yongan , Ma Qunfeng , Zhu Yichao , Liu Mengzhe , Shi Yinan , Tai Yanhong , Shao Qiuju , Ge Jianlin , Hua Jilei , Gao Lihua , Huang Hongyan , Jiang Hong , Sun Qiang
Published: June 2021

Cell-in-cell (CIC) structures are defined as the special structures with one or more cells enclosed inside another one. Increasing data indicated that CIC structures were functional surrogates of complicated cell behaviors and prognosis predictor in heterogeneous cancers. However, the CIC structure profiling and its prognostic value have not been reported in human esophageal squamous cell Carcinoma (ESCC). We conducted the analysis of subtyped CIC-based profiling in ESCC using “epithelium-macrophage-leukocyte” (EML) multiplex staining and examined the prognostic value of CIC structure profiling through Kaplan-Meier plotting and Cox regression model. Totally, five CIC structure subtypes were identified in ESCC tissue and the majority of them was homotypic CIC (hoCIC) with tumor cells inside tumor cells (TiT). By univariate and multivariate analyses, TiT was shown to be an independent prognostic factor for resectable ESCC, and patients with higher density of TiT tended to have longer post-operational survival time. Furthermore, in subpopulation analysis stratified by TNM stage, high TiT density was associated with longer overall survival (OS) in patients of TNM stages III and IV as compared with patients with low TiT density (mean OS: 51 vs 15 months, P = 0.04) and T3 stage (mean OS: 57 vs 17 months, P=0.024). Together, we reported the first CIC structure profiling in ESCC and explored the prognostic value of subtyped CIC structures, which supported the notion that functional pathology with CIC structure profiling is an emerging prognostic factor for human cancers, such as ESCC.
Prognostic Biomarkers on a Competitive Endogenous RNA Network Reveals Overall Survival in Triple-Negative Breast Cancer
Authors: Qin Wenxing , Qi Feng , Li Jia , Li Ping , Zang Yuan-Sheng
Published: June 2021

The objective of this study was to construct a competitive endogenous RNA (ceRNA) regulatory network using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with triple-negative breast cancer (TNBC) and to construct a prognostic model for predicting overall survival (OS) in patients with TNBC. Differentially expressed lncRNAs, miRNAs, and mRNAs in TNBC patients from the TCGA and Metabric databases were examined. A prognostic model based on prognostic scores (PSs) was established for predicting OS in TNBC patients, and the performance of the model was assessed by a recipient that operated on a distinctive curve. A total of 874 differentially expressed RNAs (DERs) were screened, among which 6 lncRNAs, 295 miRNAs and 573 mRNAs were utilized to construct targeted and coexpression ceRNA regulatory networks. Eight differentially expressed genes (DEGs) associated with survival prognosis, DBX2, MYH7, TARDBP, POU4F1, ABCB11, LHFPL5, TRHDE and TIMP4, were identified by multivariate Cox regression and then used to establish a prognostic model. Our study shows that the ceRNA network has a critical role in maintaining the aggressiveness of TNBC and provides comprehensive molecular-level insight for predicting individual mortality hazards for TNBC patients. Our data suggest that these prognostic mRNAs from the ceRNA network are promising therapeutic targets for clinical intervention.
Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma
Authors: Wadowski Benjamin , Bueno Raphael , De Rienzo Assunta
Published: June 2021

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with limited therapeutic options beyond surgery and cytotoxic chemotherapy. The success of immune checkpoint inhibition has been found to correlate with expression of immune-related genes such as CD274 (PD-L1) in lung and other solid cancers. However, only a small subset of MPM patients respond to checkpoint inhibition, and this response has been varied and unpredictable across several clinical trials. Recent advances in next-generation sequencing (NGS) technology have improved our understanding of the molecular features of MPM, also with respect to its genetic signature and how this impacts the immune microenvironment. This article will review current evidence surrounding the interplay between MPM genetics, including epigenetics and transcriptomics, and the immune response.
Case Report: Vemurafenib Treatment in Brain Metastases of BRAFS365L-Mutant Lung Papillary Cancer by Genetic Sequencing of Cerebrospinal Fluid Circulating Tumor DNA Detection
Authors: Jiang Jianing , Gao Jinqi , Wang Gang , Lv Jinyan , Chen Wenting , Ben Jing , Wang Ruoyu
Published: June 2021

BRAF mutations, primarily sensitizing mutations, such as BRAFV600E, have been proven to response to the BRAF inhibitor, Dabrafenib combined with trametinib therapy, but there have been no data demonstrating that it has activity against NSCLC-related brain metastases (BM). How patients harboring BRAFS365L mutation (a rare mutation following BRAFV600E-inhibitor treatment) in NSCLC is unknown. Vemurafenib, another BRAF inhibitor, can reverse the resistance that develops with the BRAFS365L mutation following dabrafenib combined with trametentinib treatment in melanoma, but none has been reported in NSCLC. Lung papillary cancer, as a rare typing, occupies about 4% of NSCLC. Hence, we reported the first case of a patient with BM of lung papillary carcinoma harboring a BRAFV600E mutation who benefited from dabrafenib combined with trametinib, and following the development of the BRAFS365L mutation, vemurafenib remained an effective therapeutic option. Moreover, we found that the next-generation sequencing (NGS) of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) may potentially provide more accurate information about intracranial lesions than ctDNA in the blood serum, which will be a better detection method.
An Improved Detection of Circulating Tumor DNA in Extracellular Vesicles-Depleted Plasma
Authors: Sun Li , Du Meijun , Kohli Manish , Huang Chiang-Ching , Chen Xiaoxiang , Xu Mu , Shen Hongbing , Wang Shukui , Wang Liang
Published: June 2021

Circulating tumor DNA (ctDNA) in plasma has been used as a biomarker for cancer detection and outcome prediction. In this study, we collected the five precipitates (fractions 1–5) and leftover supernatant plasma component (fraction 6) by a sequential centrifugation in plasma samples from nine small cell lung cancer (SCLC) patients. The fractions 3, 5 and 6 were large vesicles, exosomes and extracellular vesicles (EVs)-depleted plasma, respectively. Fragment size analysis using DNAs from these fractions showed dramatical differences from a peak of 7–10 kb in fraction 1 to 140–160 bp in fraction 6. To determine ctDNA content, we performed whole genome sequencing and applied copy number-based algorithm to calculate ctDNA percentage. This analysis showed the highest ctDNA content in EV-depleted plasma (average = 27.22%), followed by exosomes (average = 22.09%) and large vesicles (average = 19.70%). Comparatively, whole plasma, which has been used in most ctDNA studies, showed an average of 23.84% ctDNA content in the same group of patients. To further demonstrate higher ctDNA content in fraction 6, we performed mutational analysis in the plasma samples from 22 non-small cell lung cancer (NSCLC) patients with known EGFR mutations. This analysis confirmed higher mutation detection rates in fraction 6 (14/22) than whole plasma (10/22). This study provides a new insight into potential application of using fractionated plasma for an improved ctDNA detection.
The 46, XX Ovotesticular Disorder of Sex Development With Xq27.1q27.2 Duplication Involving the SOX3 Gene: A Rare Case Report and Literature Review
Authors: Zhuang Jianlong , Chen Chunnuan , Li Jia , Jiang Yuying , Wang Junyu , Wang Yuanbai , Zeng Shuhong , Lin Yiming , Xie Yingjun
Published: June 2021

Background: Very few reports are available on human XX ovotesticular disorder of sex development involving SOX3 gene duplication. Here we aim to present a rare case of SOX3 gene duplication in a person from the Chinese population who exhibits XX ovotesticular disorder of sex development.

Case Presentation: A 7-year-old Chinese individual from Fujian province in Southeast China was recruited. The patient presented 46, XX karyotype, absence of sex-determining region Y, and was diagnosed with XX ovotesticular disorder of sex development. Furthermore, SNP array analysis demonstrated that the patient had a 2.2-Mb duplication in the Xq27.1q27.2 region (arr[hg19]Xq27.1q27.2:139,499,778-141,777,782) involving the SOX3 gene. Additionally, no SOX3 duplication was observed in the parents or the sibling, who displayed none of the clinical features.

Conclusion: We identified the first case of SOX3 duplication in a Chinese individual who exhibits ovotesticular disorder of sex development. Our study strengthens the link between the SOX3 duplication and XX ovotesticular disorder of sex development and indicates that SOX3 is the evolutionary antecedent of sex-determining region Y.
In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis
Authors: Liu Xiaolu , Fan Yuling , Du Lipeng , Mei Zhigang , Fu Yang
Published: June 2021

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology approach and molecular docking in silico were applied to uncover the potential multicomponent synergetic effect and molecular mechanisms. The targets of ingredients in GQD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM) database, while the UC targets were retrieved from Genecards, therapeutic target database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The topological parameters of Protein-Protein Interaction (PPI) data were used to screen the hub targets in the network. The possible mechanisms were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the active compounds and hub targets. Network pharmacology analysis successfully identified 77 candidate compounds and 56 potential targets. The targets were further mapped to 20 related pathways to construct a compound-target-pathway network and an integrated network of GQD treating UC. Among these pathways, PI3K-AKT, HIF-1, VEGF, Ras, and TNF signaling pathways may exert important effects in the treatment of UC via inflammation suppression and anti-carcinogenesis. In the animal experiment, treatment with GQD and sulfasalazine (SASP) both ameliorated inflammation in UC. The proinflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by UC were significantly decreased by GQD and SASP. Moreover, the protein expression of EGFR, PI3K, and phosphorylation of AKT were reduced after GQD and SASP treatment, and there was no significance between the GQD group and SASP group. Our study systematically dissected the molecular mechanisms of GQD on the treatment of UC using network pharmacology, as well as uncovered the therapeutic effects of GQD against UC through ameliorating inflammation via downregulating EGFR/PI3K/AKT signaling pathway and the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6.
The Membrane Cholesterol Modulates the Interaction Between 17-βEstradiol and the BK Channel
Authors: Granados Sara T. , Latorre Ramon , Torres Yolima P.
Published: June 2021

BK channels are composed by the pore forming α subunit and, in some tissues, is associated with different accessory β subunits. These proteins modify the biophysical properties of the channel, amplifying the range of BK channel activation according to the physiological context. In the vascular cells, the pore forming BKα subunit is expressed with the β1 subunit, where they play an essential role in the modulation of arterial tone and blood pressure. In eukaryotes, cholesterol is a structural lipid of the cellular membrane. Changes in the ratio of cholesterol content in the plasma membrane (PM) regulates the BK channel activation altering its open probability, and hence, vascular contraction. It has been shown that the estrogen 17β-Estradiol (E2) causes a vasodilator effect in vascular cells, inducing a leftward shift in the V0.5 of the GV curve. Here, we evaluate whether changes in the membrane cholesterol concentration modify the effect that E2 induces on the BKα/β1 channel activity. Using binding and electrophysiology assays after cholesterol depletion or enrichment, we show that the cholesterol enrichment significantly decreases the expression of the α subunit, while cholesterol depletion increased the expression of that α subunit. Additionally, we demonstrated that changes in the membrane cholesterol cause the loss of the modulatory effect of E2 on the BKα/β1 channel activity, without affecting the E2 binding to the complex. Our data suggest that changes in membrane cholesterol content could affect channel properties related to the E2 effect on BKα/β1 channel activity. Finally, the results suggest that an optimal membrane cholesterol content is essential for the activation of BK channels through the β1 subunit.
Constraints of Weight Loss as a Marker of Bariatric Surgery Success: An Exploratory Study
Authors: Gil Saulo , Goessler Karla , Dantas Wagner S. , Murai Igor Hisashi , Merege-Filho Carlos Alberto Abujabra , Pereira Rosa Maria R. , de Cleva Roberto , Santo Marco Aurélio , Kirwan John P. , Roschel Hamilton , Gualano Bruno
Published: June 2021

Purpose

The aim of this exploratory study was to investigate whether the degree of weight loss properly reflects improvements in cardiometabolic health among patients who underwent Roux-en-Y gastric bypass.

Methods

In this ancillary analysis from a clinical trial, patients were clustered into tertiles according to the magnitude of the percentage weight loss (1st tertile: “higher weight loss”: −37.1 ± 5.8%; 2nd tertile: “moderate weight loss”: −29.7 ± 1.4%; 3rd tertile: “lower weight loss”: −24.2 ± 2.3%). Delta changes (9 months after surgery-baseline) in clustered cardiometabolic risk (i.e., blood pressure index, fasting glucose, high-density lipoprotein [HDL] and triglycerides [TG]), glycated hemoglobin (HbA1c), homeostasis model assessment (HOMA-IR), and C-reactive protein (CRP) were calculated.

Results

A total of 42 patients who had complete bodyweight data (age = 40 ± 8 year; BMI = 47.8 ± 7.1 kg/m2) were included. Surgery led to substantial weight loss (−37.9 ± 11.3 kg, P < 0,001), and clinically significant improvements in blood pressure index (−17.7 ± 8.2 mmHg, P < 0.001), fasting glucose (−36.6 ± 52.5 mg/dL, P < 0.001), HDL (9.4 ± 7.1 mg/dL, P < 0.001), TG (−35.8 ± 44.1 mg/dL P < 0,001), HbA1c (−1.2 ± 1.6%, P < 0.001), HOMA-IR (−4.7 ± 3.9 mg/dL, P < 0.001) and CRP (−8.5 ± 6.7 μg/mL P < 0.001). Comparisons across tertiles revealed no differences for cardiometabolic risk score, fasting glucose, HbAc1, HOMA-IR, blood pressure index, CRP, HDL, and TG (P > 0.05 for all). Individual variable analysis confirmed cardiometabolic improvements across the spectrum on weight-loss. There were no associations between weight loss and any dependent variable.

Conclusion

Weight loss following bariatric surgery does not correlate with improvements in cardiovascular risk factors. These findings suggest that weight loss alone may be insufficient to assess the cardiometabolic success of bariatric surgery, and the search for alternate proxies that better predict surgery success are needed.
Proerythroblast Cells of Diamond-Blackfan Anemia Patients With RPS19 and CECR1 Mutations Have Similar Transcriptomic Signature
Authors: Karaosmanoglu Beren , Kursunel M. Alper , Uckan Cetinkaya Duygu , Gumruk Fatma , Esendagli Gunes , Unal Sule , Taskiran Ekim Z.
Published: June 2021

Diamond Blackfan Anemia (DBA) is an inherited bone marrow (BM) failure syndrome, characterized by a paucity of erythroid differentiation. DBA is mainly caused by the mutations in ribosomal protein genes, hence classified as ribosomopathy. However, in approximately 30% of patients, the molecular etiology cannot be discovered. RPS19 germline mutations caused 25% of the cases. On the other hand, CECR1 mutations also cause phenotypes similar to DBA but not being a ribosomopathy. Due to the blockade of erythropoiesis in the BM, we investigated the transcriptomic profile of three different cell types of BM resident cells of DBA patients and compared them with healthy donors. From BM aspirates BM mononuclear cells (MNCs) were isolated and hematopoietic stem cells (HSC) [CD71–CD34+ CD38mo/lo], megakaryocyte–erythroid progenitor cells (MEP) [CD71–CD34+ CD38hi] and Proerythroblasts [CD71+ CD117+ CD38+] were sorted and analyzed with a transcriptomic approach. Among all these cells, proerythroblasts had the most different transcriptomic profile. The genes associated with cellular stress/immune responses were increased and some of the transcription factors that play a role in erythroid differentiation had altered expression in DBA proerythroblasts. We also showed that gene expression levels of ribosomal proteins were decreased in DBA proerythroblasts. In addition to these, colony formation assay (CFU-E) provided functional evidence of the failure of erythroid differentiation in DBA patients. According to our findings that all patients resembling both RPS19 and CECR1 mutations have common transcriptomic signatures, it may be possible that inflammatory BM niche may have a role in DBA pathogenesis.
Gene Flow Risks From Transgenic Herbicide-Tolerant Crops to Their Wild Relatives Can Be Mitigated by Utilizing Alien Chromosomes
Authors: Song Xiaoling , Yan Jing , Zhang Yuchi , Li Hewei , Zheng Aiqin , Zhang Qingling , Wang Jian , Bian Qing , Shao Zicheng , Wang Yu , Qiang Sheng
Published: June 2021

Integration of a transgene into chromosomes of the C-genomes of oilseed rape (AACC, 2n = 38) may affect their gene flow to wild relatives, particularly Brassica juncea (AABB, 2n = 36). However, no empiric evidence exists in favor of the C-genome as a safer candidate for transformation. In the presence of herbicide selections, the first- to fourth-generation progenies of a B. juncea × glyphosate-tolerant oilseed rape cross [EPSPS gene insertion in the A-genome (Roundup Ready, event RT73)] showed more fitness than a B. juncea × glufosinate-tolerant oilseed rape cross [PAT gene insertion in the C-genome (Liberty Link, event HCN28)]. Karyotyping and fluorescence in situ hybridization–bacterial artificial chromosome (BAC-FISH) analyses showed that crossed progenies from the cultivars with transgenes located on either A- or C- chromosome were mixoploids, and their genomes converged over four generations to 2n = 36 (AABB) and 2n = 37 (AABB + C), respectively. Chromosome pairing of pollen mother cells was more irregular in the progenies from cultivar whose transgene located on C- than on A-chromosome, and the latter lost their C-genome-specific markers faster. Thus, transgene insertion into the different genomes of B. napus affects introgression under herbicide selection. This suggests that gene flow from transgenic crops to wild relatives could be mitigated by breeding transgenic allopolyploid crops, where the transgene is inserted into an alien chromosome.
Relationships Between Leaf Carbon and Macronutrients Across Woody Species and Forest Ecosystems Highlight How Carbon Is Allocated to Leaf Structural Function
Authors: Xing Kaixiong , Zhao Mingfei , Niinemets Ülo , Niu Shuli , Tian Jing , Jiang Yuan , Chen Han Y. H. , White Philip J. , Guo Dali , Ma Zeqing
Published: June 2021

Stoichiometry of leaf macronutrients can provide insight into the tradeoffs between leaf structural and metabolic investments. Structural carbon (C) in cell walls is contained in lignin and polysaccharides (cellulose, hemicellulose, and pectins). Much of leaf calcium (Ca) and a fraction of magnesium (Mg) were further bounded with cell wall pectins. The macronutrients phosphorus (P), potassium (K), and nitrogen (N) are primarily involved in cell metabolic functions. There is limited information on the functional interrelations among leaf C and macronutrients, and the functional dimensions characterizing the leaf structural and metabolic tradeoffs are not widely appreciated. We investigated the relationships between leaf C and macronutrient (N, P, K, Ca, Mg) concentrations in two widespread broad-leaved deciduous woody species Quercus wutaishanica (90 individuals) and Betula platyphylla (47 individuals), and further tested the generality of the observed relationships in 222 woody eudicots from 15 forest ecosystems. In a subsample of 20 broad-leaved species, we also analyzed the relationships among C, Ca, lignin, and pectin concentrations in leaf cell walls. We found a significant leaf C–Ca tradeoff operating within and across species and across ecosystems. This basic relationship was explained by variations in the share of cell wall lignin and pectin investments at the cell scale. The C–Ca tradeoffs were mainly driven by soil pH and mean annual temperature and precipitation, suggesting that leaves were more economically built with less C and more Ca as soil pH increased and at lower temperature and lower precipitation. However, we did not detect consistent patterns among C–N, and C–Mg at different levels of biological organization, suggesting substantial plasticity in N and Mg distribution among cell organelles and cell protoplast and cell wall. We observed two major axes of macronutrient differentiation: the cell-wall structural axis consisting of protein-free C and Ca and the protoplasm metabolic axis consisting of P and K, underscoring the decoupling of structural and metabolic elements inherently linked with cell wall from protoplasm investment strategies. We conclude that the tradeoffs between leaf C and Ca highlight how carbon is allocated to leaf structural function and suggest that this might indicate biogeochemical niche differentiation of species.
Magnesium Application Promotes Rubisco Activation and Contributes to High-Temperature Stress Alleviation in Wheat During the Grain Filling
Authors: Shao Yuhang , Li Shiyu , Gao Lijun , Sun Chuanjiao , Hu Jinling , Ullah Attiq , Gao Jingwen , Li Xinxin , Liu Sixi , Jiang Dong , Cao Weixing , Tian Zhongwei , Dai Tingbo
Published: June 2021

Inhibited photosynthesis caused by post-anthesis high-temperature stress (HTS) leads to decreased wheat grain yield. Magnesium (Mg) plays critical roles in photosynthesis; however, its function under HTS during wheat grain filling remains poorly understood. Therefore, in this study, we investigated the effects of Mg on the impact of HTS on photosynthesis during wheat grain filling by conducting pot experiments in controlled-climate chambers. Plants were subjected to a day/night temperature cycle of 32°C/22°C for 5 days during post-anthesis; the control temperature was set at 26°C/16°C. Mg was applied at the booting stage, with untreated plants used as a control. HTS reduced the yield and net photosynthetic rate (Pn) of wheat plants. The maximum carboxylation rate (VCmax), which is limited by Rubisco activity, decreased earlier than the light-saturated potential electron transport rate. This decrease in VCmax was caused by decreased Rubisco activation state under HTS. Mg application reduced yield loss by stabilizing Pn. Rubisco activation was enhanced by increasing Rubisco activase activity following Mg application, thereby stabilizing Pn. We conclude that Mg maintains Rubisco activation, thereby helping to stabilize Pn under HTS.
Mutations of the Genomes Uncoupled 4 Gene Cause ROS Accumulation and Repress Expression of Peroxidase Genes in Rice
Authors: Li Rui-Qing , Jiang Meng , Huang Jian-Zhong , Møller Ian Max , Shu Qing-Yao
Published: June 2021

The Genomes Uncoupled 4 (GUN4) is one of the retrograde signaling genes in Arabidopsis and its orthologs have been identified in oxygenic phototrophic organisms from cyanobacterium to higher plants. GUN4 is involved in tetrapyrrole biosynthesis and its mutation often causes chlorophyll-deficient phenotypes with increased levels of reactive oxygen species (ROS), hence it has been speculated that GUN4 may also play a role in photoprotection. However, the biological mechanism leading to the increased ROS accumulation in gun4 mutants remains largely unknown. In our previous studies, we generated an epi-mutant allele of OsGUN4 (gun4epi), which downregulated its expression to ∼0.5% that of its wild-type (WT), and a complete knockout allele gun4-1 due to abolishment of its translation start site. In the present study, three types of F2 plant derived from a gun4-1/gun4epi cross, i.e., gun4-1/gun4-1, gun4-1/gun4epi and gun4epi/gun4epi were developed and used for further investigation by growing them under photoperiodic condition (16 h/8 h light/dark) with low light (LL, 100 μmol photons m–2 s–1) or high light (HL, 1000 μmol photons m–2 s–1). The expression of OsGUN4 was light responsive and had two peaks in the daytime. gun4-1/gun4-1-F2 seeds showed defective germination and died within 7 days. Significantly higher levels of ROS accumulated in all types of OsGUN4 mutants than in WT plants under both the LL and HL conditions. A comparative RNA-seq analysis of WT variety LTB and its gun4epi mutant HYB led to the identification of eight peroxidase (PRX)-encoding genes that were significantly downregulated in HYB. The transcription of these eight PRX genes was restored in transgenic HYB protoplasts overexpressing OsGUN4, while their expression was repressed in LTB protoplasts transformed with an OsGUN4 silencing vector. We conclude that OsGUN4 is indispensable for rice, its expression is light- and oxidative-stress responsive, and it plays a role in ROS accumulation via its involvement in the transcriptional regulation of PRX genes.
Interference of Illusory Contour Perception by a Distractor
Authors: Yang Junkai , Sui Lisen , Wu Hongyuan , Wu Qian , Mei Xiaolin , Wu Xiang
Published: June 2021

The visual system is capable of recognizing objects when object information is widely separated in space, as revealed by the Kanizsa-type illusory contours (ICs). Attentional involvement in perception of ICs is an important topic, and the present study examined whether and how the processing of ICs is interfered with by a distractor. Discrimination between thin and short deformations of an illusory circle was investigated in the absence or presence of a central dynamic patch, with difficulty of discrimination varied in three levels (easy, medium, and hard). Reaction time (RT) was significantly shorter in the absence compared to the presence of the distractor in the easy and medium conditions. Correct rate (CR) was significantly higher in the absence compared to the presence of the distractor in the easy condition, and the magnitude of the difference between CRs of distracted and non-distracted responses significantly reduced as task difficulty increased. These results suggested that perception of ICs is more likely to be vulnerable to distraction when more attentional resources remain available. The present finding supports that attention is engaged in perception of ICs and that distraction of IC processing is associated with perceptual load.
Importance Calculation of Customer Requirements for Incremental Product Innovation
Authors: Geng Lisha , Shi Xiaofei , Zu Liran , Chai Meiqun , Xing Jinge
Published: June 2021

Incremental product innovation is achieved by finding and solving problems of existing products. The importance of customer requirements reflects the severity of existing product problems, which points out the direction for incremental product innovation. In this research, the calculation process of customer requirement importance mainly includes three steps. Firstly, from the perspective of customers, the improvement gap analytical method is used to obtain the improvement and original importance of customer requirements by measuring customer perceived satisfaction and dissatisfaction. Secondly, from the perspective of industry experts, an improved interval grey number ranking method is proposed to calculate the basic importance of customer requirements, which can deal with the inadequate problem of the data provided by experts due to the limited number of experts. Finally, a multi-dimensional vector cosine method, which avoids the interference of subjectivity of importance weight calculation to the final importance, is proposed to integrate the importance data provided by customers and experts. A case of a water purifier is considered to illustrate the validity of the proposed process. This research improves existing calculation methods and proposes an integrated calculation process from three dimensions to calculate the final importance of customer requirements effectively.
Intolerance of Uncertainty and Fear of COVID-19 Moderating Role in Relationship Between Job Insecurity and Work-Related Distress in the Republic of Serbia
Authors: Blanuša Jelena , Barzut Vesna , Knežević Jasmina
Published: June 2021

The COVID-19 outbreak in Serbia was followed by strict restrictions that negatively affected the economy, particularly small size companies. The complete lockdown and the prohibition of certain services have led to an unstable employment situation. Only several studies investigated the job insecurity and its consequences during COVID-19 pandemic, and some of them highlight the fear of COVID-19 as a significant moderator of mental health. Other studies emphasize the huge effect that intolerance of uncertainty could have in explaining distress, especially during pandemic. In addition, intolerance of uncertainty was considered as a possible moderator of the relationship between the objective and subjective job threat, as well their consequences for mental health. This study aimed to examine the presence of job insecurity and work related distress in Serbia during the first wave of COVID-19. We wanted to measure the effect of the job insecurity on experienced work distress, as well the moderation potential of the intolerance of uncertainty as an individual-level and the fear of coronavirus as a situation-dependent variable. Five hundred and twenty five employed participants took part in an online study during the first wave of coronavirus infection in Serbia. To measure job insecurity, we used Perception of job insecurity scale (PJIS), while distress was assessed with Distress scale from 4DSQ. Fear of COVID-19 was measured on three items. The intolerance of uncertainty was measured by the IUS-11 scale. The results showed that 30.4% of the participants consider their employment as moderately or highly insecure, and 15.1% thought they can lose their jobs. 63.4% of participants expressed increased levels of distress. The moderation analysis revealed that the effect of job insecurity on distress can be moderated by interaction of intolerance of uncertainty and COVID-related fear. In general, distress scores were increasing with increasing job insecurity, intolerance of uncertainty and fear of COVID-19. This pattern is not observed only when fear and intolerance of uncertainty were both low, when job instability could not influence distress. This study also showed that emotional appraisal of the job threat had higher impact on distress than the perceived threat, that shed the light on the importance of considering general resilience capabilities as a protective factor in the work environment in the time of crisis.
Gender Differences in Transnational Brand Purchase Decision Toward Mixed Culture and Original Culture Advertisements: An fNIRS Study
Authors: Duan Lian , Ai Hui , Yang Lili , Xu Lianlian , Xu Pengfei
Published: June 2021

Culture strategy is very important for transnational brand marketing. Functional near-infrared spectroscopy (fNIRS) is a promising brain imaging modality for neuromarketing research. In the present study, we used fNIRS to explore the neural correlates of consumers’ purchase decision on different cross-culture marketing strategies. Forty Chinese participants watched transnational brands and products advertised with photographs of the brands’ original culture (the original culture advertisements) and advertised with photographs of Chinese culture (the mixed culture advertisements), respectively. The behavioral results showed that the female participants showed significantly higher purchase rate when watching the original culture advertisements than the mixed culture advertisements, whereas the male participants did not show significant preference between these two types. The fNIRS results further revealed that for the female participants, watching mixed culture advertisements evoked significant positive activation in the left dorsolateral prefrontal cortex and negative activation in the medial prefrontal cortex, which was not found in the male participants. These findings suggest possible cognitive and emotional differences between men and women in purchase decision making toward different cross-culture marketing strategy. The present study also demonstrates the great potential of fNIRS in neuromarketing research.
Fear of the Unknown: Does Fear of Terrorism Differ From Fear of Contracting COVID-19?
Authors: Shechory Bitton Mally , Laufer Avital
Published: June 2021

The aim of the study was to explore whether living under constant security threat would result in better coping and higher resilience when exposed to an unknown threat such as the COVID-19 pandemic. Thus, fear of COVID-19 and fear of terrorism as well as the associations with coping strategies and resilience were examined among Israelis living in conflict zones as well as Israelis living in the center, where exposure to security incidents is rare. Six hundred and fifteen Israeli adults (260 men and 356 women) were interviewed via the internet while Israel was under mandatory first lockdown. Fear of COVID-19 was found to be higher than fear of terrorism among both groups. those living in the conflict zones and those living in the central Israel. In contradiction to our assumption, we found that those who were living in a conflict zone did not exhibit higher levels of resilience and did not cope better when exposed to a new threat—even though they may be more skilled at handling prolonged exposure to a threat such as terrorism. A regression analysis indicated that the best predictor of both fear of COVID-19 and of terrorism is financial concerns—more than geographical area.