bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-Identification of Patient Subgroups in Uveal Melanoma
Authors: Nguyen Thi Hai Yen , Nguyen Tin , Nguyen Quang-Huy , Le Duc-Hau
Published: October 2021

Uveal melanoma (UM) is a comparatively rare cancer but requires serious consideration since patients with developing metastatic UM survive only for about 6–12 months. Fortunately, increasingly large multi-omics databases allow us to further understand cancer initiation and development. Moreover, previous studies have observed that associations between copy number aberrations (CNA) or methylation (MET) versus messenger RNA (mRNA) expression have affected these processes. From that, we decide to explore the effect of these associations on a case study of UM. Also, the current subtypes of UM display its weak association with biological phenotypes and its lack of therapy suggestions. Therefore, the re-identification of molecular subtypes is a pressing need. In this study, we recruit three omics profiles, including CNA, MET, and mRNA, in a UM cohort from The Cancer Genome Atlas (TCGA). Firstly, we identify two sets of genes, CNAexp and METexp, whose CNA and MET significantly correlated with their corresponding mRNA, respectively. Then, single and integrative analyses of the three data types are performed using the PINSPlus tool. As a result, we discover two novel integrative subgroups, IntSub1 and IntSub2, which could be a useful alternative classification for UM patients in the future. To further explore molecular events behind each subgroup, we identify their subgroup-specific genes computationally. Accordingly, the highest expressed genes among IntSub1-specific genes are mostly enriched with immune-related processes. On the other hand, IntSub2-specific genes are highly associated with cellular cation homeostasis, which responds effectively to chemotherapy using ion channel inhibitor drugs. In addition, we detect that the two integrative subgroups show different age-related risks and survival rates. These discoveries can influence the frequency of metastatic surveillance and support medical practitioners to choose an appropriate treatment regime.
A Novel MRI-Based Risk Stratification Algorithm for Predicting Postoperative Recurrence of Meningioma: More Benefits to Patients
Authors: Zhang Rufei , Chen Xiaodan , Cai Jialing , Jiang Peirong , Chen Yilin , Sun Bin , Song Yang , Lin Lin , Xue Yunjing
Published: October 2021

Pathological grading of meningioma is insufficient to predict recurrence after resection and to guide individualized treatment strategies. One hundred and thirty-three patients with meningiomas who underwent total resection were enrolled in this retrospective study. Univariate analyses were conducted to evaluate the association between factors and recurrence. Least absolute shrinkage and selection operator (Lasso) was used to further select variables to build a logistic model. The predictive efficiency of the model and WHO grade was compared by using receiver operating characteristic curve (ROC), decision curve analysis (DCA), and net reclassification improvement (NRI). Patients were given a new risk layer based on a nomogram. The recurrence of meningioma in different groups was observed through the Kaplan-Meier curve. Univariate analysis demonstrated that 11 risk factors were associated with prognosis (P < 0.05). The result of ROC proved that the quantified risk-scoring system (AUC = 0.853) had a higher benefit than pathological grade (AUC = 0.689, P = 0.011). The incidence of recurrence of the high risk cohort (69%) was significantly higher than that of the low risk cohort (9%) by Kaplan-Meier analysis (P < 0.001). And all patients who did not relapse in the high risk group received adjuvant radiotherapy. The novel risk stratification algorithm has a significant value for the recurrence of meningioma and can help in optimizing the individualized design of clinical therapy.
Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib
Authors: Scirocchi Fabio , Napoletano Chiara , Pace Angelica , Rahimi Koshkaki Hassan , Di Filippo Alessandra , Zizzari Ilaria Grazia , Nuti Marianna , Rughetti Aurelia
Published: October 2021

Cabozantinib (XL-184) is a multitarget tyrosine kinase inhibitor (TKI) targeting receptor tyrosine kinases (RTKs) involved in oncogenesis and angiogenesis. It is currently the standard therapy for medullary thyroid cancer (MTC), metastatic renal cell carcinoma (mRCC), and hepatocellular carcinoma (HCC). Combination of Cabozantinib with immunotherapy is now a standard treatment in metastatic renal cancer, and its efficacy is being tested in ongoing clinical trial in prostate cancer patients. Here, we report that Cabozantinib may exert an immunostimulatory role by inducing immunogenic stress of prostate cancer cells and directly modulating dendritic cells (DCs). Cabozantinib treatment arrested the cell cycle and triggered immunogenic cell death (ICD) in prostate cancer cells in vitro. Cabozantinib had a direct effect on DCs by the down-modulation of β-catenin and change in migratory and costimulatory phenotype of the DCs. These results may suggest possible immunomodulatory effects induced by Cabozantinib that could be exploited to optimize patient-tailored immunotherapeutic treatments.
Patient-Reported Outcomes-Guided Adaptive Radiation Therapy for Head and Neck Cancer
Authors: Weppler Sarah , Quon Harvey , Schinkel Colleen , Yarschenko Adam , Barbera Lisa , Harjai Nabhya , Smith Wendy
Published: October 2021

Purpose

To identify which patient-reported outcomes (PROs) may be most improved through adaptive radiation therapy (ART) with the goal of reducing toxicity incidence among head and neck cancer patients.

Methods

One hundred fifty-five head and neck cancer patients receiving radical VMAT (chemo)radiotherapy (66-70 Gy in 30-35 fractions) completed the MD Anderson Symptom Inventory, MD Anderson Dysphagia Inventory (MDADI), and Xerostomia Questionnaire while attending routine follow-up clinics between June-October 2019. Hierarchical clustering characterized symptom endorsement. Conventional statistical approaches indicated associations between dose and commonly reported symptoms. These associations, and the potential benefit of interfractional dose corrections, were further explored via logistic regression.

Results

Radiotherapy-related symptoms were commonly reported (dry mouth, difficulty swallowing/chewing). Clustering identified three patient subgroups reporting: none/mild symptoms for most items (60.6% of patients); moderate/severe symptoms affecting some aspects of general well-being (32.9%); and moderate/severe symptom reporting for most items (6.5%). Clusters of PRO items broadly consisted of acute toxicities, general well-being, and head and neck-specific symptoms (xerostomia, dysphagia). Dose-PRO relationships were strongest between delivered pharyngeal constrictor Dmean and patient-reported dysphagia, with MDADI composite scores (mean ± SD) of 25.7 ± 18.9 for patients with Dmean <50 Gy vs. 32.4 ± 17.1 with Dmean ≥50 Gy. Based on logistic regression models, during-treatment dose corrections back to planned values may confer ≥5% decrease in the absolute risk of self-reported physical dysphagia symptoms ≥1 year post-treatment in 1.2% of patients, with a ≥5% decrease in relative risk in 23.3% of patients.

Conclusions

Patient-reported dysphagia symptoms are strongly associated with delivered dose to the pharyngeal constrictor. Dysphagia-focused ART may provide the greatest toxicity benefit to head and neck cancer patients, and represent a potential new direction for ART, given that the existing ART literature has focused almost exclusively on xerostomia reduction.
Target-Based Radiosensitization Strategies: Concepts and Companion Animal Model Outlook
Authors: Berry Matthew R. , Fan Timothy M.
Published: October 2021

External beam radiotherapy is indicated in approximately 50-60% of human cancer patients. The prescribed dose of ionizing radiation that can be delivered to a tumor is determined by the sensitivity of the normal surrounding tissues. Despite dose intensification provided by highly conformal radiotherapy, durable locoregional tumor control remains a clinical barrier for recalcitrant tumor histologies, and contributes to cancer morbidity and mortality. Development of target-based radiosensitization strategies that selectively sensitizes tumor tissue to ionizing radiation is expected to improve radiotherapy efficacy. While exploration of radiosensitization strategies has vastly expanded with technological advances permitting the precise and conformal delivery of radiation, maximal clinical benefit derived from radiotherapy will require complementary discoveries that exploit molecularly-based vulnerabilities of tumor cells, as well as the assessment of investigational radiotherapy strategies in animal models that faithfully recapitulate radiobiologic responses of human cancers. To address these requirements, the purpose of this review is to underscore current and emerging concepts of molecularly targeted radiosensitizing strategies and highlight the utility of companion animal models for improving the predictive value of radiotherapy investigations.
SnFe2O4 Nanozyme Based TME Improvement System for Anti-Cancer Combination Thermoradiotherapy
Authors: Zeng Wen , Liu Chunping , Wang Shuntao , Wang Ziqi , Huang Qinqin
Published: October 2021

High doses of radiotherapy (RT) are associated with resistance induction. Therefore, highly selective and controllable radiosensitizers are urgently needed. To address this issue, we developed a tin ferrite (SFO)-based tumor microenvironment (TME)-improved system (SIS) that can be used in combination with low-dose radiation. The SIS was delivered via intratumoral injection directly to the tumor site, where it was stored as a ration depot. Due to the photothermal properties of SFO, SIS steadily dissolved under near-infrared (NIR) laser irradiation. Simultaneously, the dual glutathione oxidase (GSH-OXD) and catalase (CAT) activities of the SFO nanozyme significantly lowered the content of GSH in tumor tissues and efficiently catalyzed the conversion of intracellular hydrogen peroxide to produce a large amount of oxygen (O2) for intracellular redox homeostasis disruption, thus reducing radiotherapy resistance. Our in vivo and in vitro studies suggested that combining the SIS and NIR irradiation with RT (2Gy) significantly reduced tumor proliferation without side effects such as inflammation. To conclude, this study revealed that SFO-based nanozymes show great promise as a catalytic, radiosensitizing anti-tumor therapy.
Transcriptional Control of Metastasis by Integrated Stress Response Signaling
Authors: Lu Si , Yang Li-Xian , Cao Zi-Jian , Zhao Jiang-Sha , You Jia , Feng Yu-Xiong
Published: October 2021

As a central cellular program to sense and transduce stress signals, the integrated stress response (ISR) pathway has been implicated in cancer initiation and progression. Depending on the genetic mutation landscape, cellular context, and differentiation states, there are emerging pieces of evidence showing that blockage of the ISR can selectively and effectively shift the balance of cancer cells toward apoptosis, rendering the ISR a promising target in cancer therapy. Going beyond its pro-survival functions, the ISR can also influence metastasis, especially via proteostasis-independent mechanisms. In particular, ISR can modulate metastasis via transcriptional reprogramming, in the help of essential transcription factors. In this review, we summarized the current understandings of ISR in cancer metastasis from the perspective of transcriptional regulation.
PROTEA, A Southern African Multicenter Congenital Heart Disease Registry and Biorepository: Rationale, Design, and Initial Results
Authors: Aldersley Thomas , Lawrenson John , Human Paul , Shaboodien Gasnat , Cupido Blanche , Comitis George , De Decker Rik , Fourie Barend , Swanson Lenise , Joachim Alexia , Magadla Phaphama , Ngoepe Malebogo , Swanson Liam , Revell Alistair , Ramesar Raj , Brooks Andre , Saacks Nicole , De Koning Bianca , Sliwa Karen , Anthony John , Osman Ayesha , Keavney Bernard , Zühlke Liesl
Published: October 2021

Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or “cohort-prevalences” of CHD-subtypes with international findings.

Methods: PROTEA is a prospective multicenter CHD registry and biorepository. The initial cohort was recruited from seven hospitals in the Western Cape Province of South Africa from 1 April 2017 to 31 March 2019. All patients with structural CHD were eligible for inclusion. Descriptive data for the preliminary cohort are presented. In addition, cohort-prevalences (i.e., the proportion of patients within the cohort with a specific CHD-subtype) of 26 CHD-subtypes in PROTEA's pediatric cohort were compared with the cohort-prevalences of CHD-subtypes in two global birth-prevalence studies.

Results: The study enrolled 1,473 participants over 2 years, median age was 1.9 (IQR 0.4–7.1) years. Predominant subtypes included ventricular septal defect (VSD) (339, 20%), atrial septal defect (ASD) (174, 11%), patent ductus arteriosus (185, 11%), atrioventricular septal defect (AVSD) (124, 7%), and tetralogy of Fallot (121, 7%). VSDs were 1.8 (95% CI, 1.6–2.0) times and ASDs 1.4 (95% CI, 1.2–1.6) times more common in global prevalence estimates than in PROTEA's pediatric cohort. AVSDs were 2.1 (95% CI, 1.7–2.5) times more common in PROTEA and pulmonary stenosis and double outlet right ventricle were also significantly more common compared to global estimates. Median maternal age at delivery was 28 (IQR 23–34) years. Eighty-two percent (347/425) of mothers used no pre-conception supplementation and 42% (105/250) used no first trimester supplements.

Conclusions: The cohort-prevalence of certain mild CHD subtypes is lower than for international estimates and the cohort-prevalence of certain severe subtypes is higher. PROTEA is not a prevalence study, and these inconsistencies are unlikely the result of true differences in prevalence. However, these findings may indicate under-diagnosis of mild to moderate CHD and differences in CHD management and outcomes. This reemphasizes the need for robust CHD epidemiological research in the region.
Network Pharmacology–Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells
Authors: Zhang Yu-Zhu , Yang Jia-Yao , Wu Rui-Xian , Fang Chen , Lu Hai , Li Hua-Chao , Li Dong-Mei , Zuo Hua-Li , Ren Li-Ping , Liu Xiao-Yuan , Xu Rui , Wen Jia-Huai , Huang Hsien-Da , Hong Ri , Chen Qian-Jun
Published: October 2021

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell–related genes were identified. The drug–herb–active compound–target gene–disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.
Herbal Medicine Compared to Placebo for Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis
Authors: Kwon Chan-Young , Lee Boram , Lee Beom-Joon , Kim Kwan-Il , Jung Hee-Jae
Published: October 2021

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by irreversible airflow limitation. Many COPD patients use complementary and alternative modalities, including herbal medicines (HMs). This systematic review investigated the effectiveness and safety of HM in managing COPD symptoms compared to placebo. Nine electronic databases were searched to identify relevant randomized controlled trials (RCTs) up to February 12, 2021. The Cochrane risk of bias tool was used to assess the methodological qualities of the included studies. Primary outcomes were lung function parameters and exercise capacity. A meta-analysis was conducted to determine the effect size for homogeneous outcomes. Fourteen studies were included. There was low to very low quality evidence that HM significantly improved forced expiratory volume in 1  s (FEV1) (L), FEV1 (%) and 6-minute walk distance, as well as moderate quality evidence that HM significantly improved forced vital capacity (FVC) (L) compared to placebo. However, according to low quality evidence, there was no significant difference in FEV1/FVC (%) or vital capacity (L) between the groups. Low to moderate evidence suggests that HM has the potential to help improve some respiratory functions, COPD symptoms, and some aspects of quality of life in COPD patients compared to placebo. However, these findings are challenged by the poor methodological quality of the included studies, the heterogeneity of HMs used, and potential publication bias. Therefore, the findings could be significantly influenced by further larger, more rigorous RCTs on this topic. Moreover, it may also be recommended to develop standardized HMs focused on some individual herbs that are frequently used or expected to play an important role in patients with COPD, and to elucidate the underlying mechanisms.
Effect of CYP3A4 Inhibitors and Inducers on Pharmacokinetics and Pharmacodynamics of Saxagliptin and Active Metabolite M2 in Humans Using Physiological-Based Pharmacokinetic Combined DPP-4 Occupancy
Authors: Li Gang , Yi Bowen , Liu Jingtong , Jiang Xiaoquan , Pan Fulu , Yang Wenning , Liu Haibo , Liu Yang , Wang Guopeng
Published: October 2021

We aimed to develop a physiological-based pharmacokinetic and dipepidyl peptidase 4 (DPP-4) occupancy model (PBPK-DO) characterized by two simultaneous simulations to predict pharmacokinetic (PK) and pharmacodynamic changes of saxagliptin and metabolite M2 in humans when coadministered with CYP3A4 inhibitors or inducers. Ketoconazole, delavirdine, and rifampicin were selected as a CYP3A4 competitive inhibitor, a time-dependent inhibitor, and an inducer, respectively. Here, we have successfully simulated PK profiles and DPP-4 occupancy profiles of saxagliptin in humans using the PBPK-DO model. Additionally, under the circumstance of actually measured values, predicted results were good and in line with observations, and all fold errors were below 2. The prediction results demonstrated that the oral dose of saxagliptin should be reduced to 2.5 mg when coadministrated with ketoconazole. The predictions also showed that although PK profiles of saxagliptin showed significant changes with delavirdine (AUC 1.5-fold increase) or rifampicin (AUC: a decrease to 0.19-fold) compared to those without inhibitors or inducers, occupancies of DPP-4 by saxagliptin were nearly unchanged, that is, the administration dose of saxagliptin need not adjust when there is coadministration with delavirdine or rifampicin.
Lactate Dehydrogenase A or B Knockdown Reduces Lactate Production and Inhibits Breast Cancer Cell Motility in vitro
Authors: Khajah Maitham A. , Khushaish Sarah , Luqmani Yunus A.
Published: October 2021

Background: Lactate dehydrogenase (LDH) plays an important role in cancer pathogenesis and enhanced expression/activity of this enzyme has been correlated with poor prognosis. In this study we determined the expression profile of LDH-A and B in normal as well as in endocrine-resistant and -responsive breast cancer cells and the effect of their knockdown on LDH activity, lactate production, proliferation and cell motility.

Methods: Knockdown experiments were performed using siRNA and shRNA. The expression profile of LDH and signaling molecules was determined using PCR and western blotting. Intracellular LDH activity and extracellular lactate levels were measured by a biochemical assay. Cell motility was determined using wound healing, while proliferation was determined using MTT assay.

Results: LDH-A was expressed in all of the tested cell lines, while LDH-B was specifically expressed only in normal and endocrine-resistant breast cancer cells. This was correlated with significantly enhanced LDH activity and lactate production in endocrine resistant breast cancer cells when compared to normal or endocrine responsive cancer cells. LDH-A or -B knockdown significantly reduced LDH activity and lactate production, which led to reduced cell motility. Exogenous lactate supplementation enhanced cell motility co-incident with enhanced phosphorylation of ERK1/2 and reduced E-cadherin expression. Also, LDH-A or -B knockdown reduced ERK 1/2 phosphorylation.

Conclusion: Enhanced cell motility in endocrine resistant breast cancer cells is at least in part mediated by enhanced extracellular lactate levels, and LDH inhibition might be a promising therapeutic target to inhibit cancer cell motility.
Integrating Molecular Biomarker Inputs Into Development and Use of Clinical Cancer Therapeutics
Authors: Louie Anna D. , Huntington Kelsey , Carlsen Lindsey , Zhou Lanlan , El-Deiry Wafik S.
Published: October 2021

Biomarkers can contribute to clinical cancer therapeutics at multiple points along the patient’s diagnostic and treatment course. Diagnostic biomarkers can screen or classify patients, while prognostic biomarkers predict their survival. Biomarkers can also predict treatment efficacy or toxicity and are increasingly important in development of novel cancer therapeutics. Strategies for biomarker identification have involved large-scale genomic and proteomic analyses. Pathway-specific biomarkers are already in use to assess the potential efficacy of immunotherapy and targeted cancer therapies. Judicious application of machine learning techniques can identify disease-relevant features from large data sets and improve predictive models. The future of biomarkers likely involves increasing utilization of liquid biopsy and multiple samplings to better understand tumor heterogeneity and identify drug resistance.
Cordycepin Decreases Ischemia/Reperfusion Injury in Diabetic Hearts via Upregulating AMPK/Mfn2-dependent Mitochondrial Fusion
Authors: Yu Houyou , Hong Xin , Liu Lihua , Wu Yangpeng , Xie Xuemei , Fang Guoxiang , Zhi Shaomin
Published: October 2021

Diabetes mellitus is considered to be a major risk factor for cardiovascular disease, the most common cause of death in diabetes. However, therapeutic strategies for myocardial protection in patients with diabetes are still limited. Cordycepin is a traditional Tibetan medicine with a long history of widespread use, and exerts a wide range of anti-tumor, anti-inflammatory, and anti-oxidative effects. In recent years, although the therapeutic potential of cordycepin has attracted the attention of researchers, it remains unknown whether cordycepin plays a protective role in myocardial ischemia/reperfusion (MI/R) injury in diabetic patients. Here, using a diabetic mouse model, we found that cordycepin protected diabetic hearts from MI/R injury by promoting mitochondrial fusion and Mfn2 expression. Our in vitro results showed that cordycepin enhanced Mfn2-medicated mitochondrial fusion, improved mitochondrial function, and reduced cardiomyocyte apoptosis in high-glucose/high-fat cultured simulated ischemia/reperfusion cardiomyocytes. Furthermore, we found that knockout of Mfn2 significantly blocked the cardioprotective effects of cordycepin in diabetic mice. Finally, an AMPK-dependent pathway was found to upregulate Mfn2 expression upon cordycepin treatment, indicating that cordycepin protected diabetic hearts via AMPK/Mfn2-dependent mitochondrial fusion. Collectively, our study firstly demonstrated that cordycepin could be a potential cardioprotective agent for MI/R injury, and we established a novel mechanism by which upregulated AMPK/Mfn2-dependent mitochondrial fusion contributes to the cardioprotective role of cordycepin.
Serum Amyloid A Correlates With the Osteonecrosis of Femoral Head by Affecting Bone Metabolism
Authors: Peng Xiaoyuan , Ma Yiyang , Wang Qiyang , Gao Yanchun , Li Guangyi , Jiang Chenyi , Gao Yun , Feng Yong
Published: October 2021

Osteonecrosis of femoral head (ONFH) is a progressive hip joint disease without disease-modifying treatment. Lacking understanding of the pathophysiological process of ONFH has become the humper to develop therapeutic approach. Serum amyloid A (SAA) is an acute phase lipophilic protein during inflammation and we found that SAA is increased for the first time in the serum of ONFH patients through proteomic studies and quantitatively verified by ELISA. Treating rBMSCs with SAA inhibited the osteogenic differentiation via Wnt/β-catenin signaling pathway deactivation and enhanced the adipogenic differentiation via MAPK/PPARγ signaling pathway activation. Finally, bilateral critical-sized calvarial-defect rat model which received SAA treated rBMSCs demonstrated reduction of bone formation when compared to untreated rBMSCs implantation control. Hence, SAA is a vital protein in the physiological process of ONFH and can act as a potential therapeutic target to treat ONFH.
Graphene Based Triboelectric Nanogenerators Using Water Based Solution Process
Authors: Domingos Ismael , Neves Ana I. S. , Craciun Monica F. , Alves Helena
Published: October 2021

A rapid development in personal electronics has raised challenging requirements for portable and sustainable power sources. For example, in wearable technologies, the concept of wearable body area network brings body motion and vital signs monitoring together in synergy. For this, a key aspect is sustainable portable energy, available anywhere, at any time, as generated by triboelectric nanogenerators (TENG). This technology usually demands high-cost processes and materials and still suffer from low power output, as well as unstable output values due to charge generating stimulus with variable intensities. In this work, we present TENGs using shear exfoliated graphene as electrodes as well as active triboelectric layer deposited by a simple solution process. Graphene in combination with polymers such as polydimethylsiloxane (PDMS) were used to produce TENG devices using low-cost solution processing methods. Device electrical power generation was tested with a cyclic physical stimulus for better control and understanding of device output. The triboelectric response of these materials showed open circuit voltages (Voc) and short-circuit currents (Isc)of approximately 233 V and 731 nA respectively when stimulated at 1.5 Hz. A power density of 13.14 μW/cm2 under a load of 200 MΩ was achieved, which can be 40 times higher when compared to devices made with aluminum and PDMS. These results demonstrate the potential of solution process for low-cost triboelectric devices for self-sustainable wearable portable nanogenerators on health and security applications using contact and positional sensors.
Overview of Fibre Optic Sensing Technology in the Field of Physical Ocean Observation
Authors: Wang Li , Wang Yong jie , Song Sanming , Li Fang
Published: October 2021

Fiber optic sensors are expected to be an auxiliary measurement tool in the field of ocean observation due to their small size, easy networking, intrinsic immunity to electromagnetic interference, and many other advantages. In recent years, the research around fiber optic sensing technology in the field of physical ocean observation has received increasing attention from researchers. According to the different measurement objects and measurement principles, the focus is on the seawater temperature sensor based on fiber grating, seawater salinity sensor, seawater pressure sensor, seawater salinity sensor based on multi-core optical fiber, seawater salinity sensor based on Michelson and Mach-Zehnder interferometry, seawater pressure sensor based on Fabry-Perot cavity, fiber optic temperature salinity and depth sensors based on resonant and coupling technology, flow velocity sensor based on multi-core optical fiber and fiber optic turbulence sensors based on thermal dissipation and turbulent kinetic energy dissipation. The test methods and test results of various sensors are analyzed, and the advantages and disadvantages of the technologies are pointed out. Prospects for the application of fiber optic sensors in physical ocean observation are presented.
Self-Assembly of Porous Structures From a Binary Mixture of Lobed Patchy Particles
Authors: Paul Sanjib , Vashisth Harish
Published: October 2021

We report simulation studies on the self-assembly of a binary mixture of snowman and dumbbell shaped lobed particles. Depending on the lobe size and temperature, different types of self-assembled structures (random aggregates, spherical aggregates, liquid droplets, amorphous wire-like structures, amorphous ring structures, crystalline structures) are observed. At lower temperatures, heterogeneous structures are formed for lobed particles of both shapes. At higher temperatures, homogeneous self-assembled structures are formed mainly by the dumbbell shaped particles, while the snowman shaped particles remain in a dissociated state. We also investigated the porosities of self-assembled structures. The pore diameters in self-assemblies increased with an increase in temperature for a given lobe size. The particles having smaller lobes produced structures with larger pores than the particles having larger lobes. We further investigated the effect of σ, a parameter in the surface-shifted Lennard-Jones potential, on the self-assembled morphologies and their porosities. The self-assembled structures formed at a higher σ value are found to produce larger pores than those at a lower σ.
Distribution of Cardiac and Renal Corin and Proprotein Convertase Subtilisin/Kexin-6 in the Experimental Model of Cardio-Renal Syndrome of Various Severities
Authors: Khoury Emad E. , Fokra Ahmad , Kinaneh Safa , Knaney Yara , Aronson Doron , Abassi Zaid
Published: October 2021

Congestive heart failure (CHF) often leads to progressive cardiac hypertrophy and salt/water retention. However, its pathogenesis remains largely unclarified. Corin, a cardiac serine protease, is responsible for converting proANP and proBNP to biologically active peptides. Although the involvement of corin in cardiac hypertrophy and heart failure was extensively studied, the alterations in corin and proprotein convertase subtilisin/kexin-6 (PCSK6), a key enzyme in the conversion of procorin to corin, has not been studied simultaneously in the cardiac and renal tissues in cardiorenal syndrome. Thus, this study aims to examine the status of PCSK6/corin in the cardiac and renal tissues of rats with CHF induced by the creation of aorto-caval fistula (ACF). We divided rats with ACF into two subgroups based on the pattern of their urinary sodium excretion, namely, compensated and decompensated. Placement of ACF led to cardiac hypertrophy, pulmonary congestion, and renal dysfunction, which were more profound in the decompensated subgroup. Corin immunoreactive peptides were detected in all heart chambers at the myocyte membranal and cytosolic localization and in the renal tissue, especially in the apical membrane of the proximal tubule, mTAL, and the collecting duct. Interestingly, the expression and abundance of corin in both the cardiac ventricles and renal tissues were significantly increased in compensated animals as compared with the decompensated state. Noteworthy, the abundance of PCSK6 in these tissues followed a similar pattern as corin. In contrast, furin expression was upregulated in the cardiac and renal tissues in correlation with CHF severity. We hypothesize that the obtained upregulation of cardiac and renal PCSK6/corin in rats with compensated CHF may represent a compensatory response aiming at maintaining normal Na+ balance, whereas the decline in these two enzymes may contribute to the pathogenesis of avid sodium retention, cardiac hypertrophy, and blunted atrial natriuretic peptide/brain natriuretic peptide actions in decompensated CHF.
Fully-Coupled FSI Computational Analyses in the Ascending Thoracic Aorta Using Patient-Specific Conditions and Anisotropic Material Properties
Authors: Vignali Emanuele , Gasparotti Emanuele , Celi Simona , Avril Stéphane
Published: October 2021

Computational hemodynamics has become increasingly important within the context of precision medicine, providing major insight in cardiovascular pathologies. However, finding appropriate compromise between speed and accuracy remains challenging in computational hemodynamics for an extensive use in decision making. For example, in the ascending thoracic aorta, interactions between the blood and the aortic wall must be taken into account for the sake of accuracy, but these fluid structure interactions (FSI) induce significant computational costs, especially when the tissue exhibits a hyperelastic and anisotropic response. The objective of the current study is to use the Small On Large (SOL) theory to linearize the anisotropic hyperelastic behavior in order to propose a reduced-order model for FSI simulations of the aorta. The SOL method is tested for fully-coupled FSI simulations in a patient-specific aortic geometry presenting an Ascending Thoracic Aortic Aneurysm (aTAA). The same model is also simulated with a fully-coupled FSI with non-linear material behavior, without SOL linearization. Eventually, the results and computational times with and without the SOL are compared. The SOL approach is demonstrated to provide a significant reduction of computational costs for FSI analysis in the aTAA, and the results in terms of stress state distribution are comparable. The method is implemented in ANSYS and will be further evaluated for clinical applications.
Thermal Performance Curves Are Shaped by Prior Thermal Environment in Early Life
Authors: Rebolledo Adriana P. , Sgrò Carla M. , Monro Keyne
Published: October 2021

Understanding links between thermal performance and environmental variation is necessary to predict organismal responses to climate change, and remains an ongoing challenge for ectotherms with complex life cycles. Distinct life stages can differ in thermal sensitivity, experience different environmental conditions as development unfolds, and, because stages are by nature interdependent, environmental effects can carry over from one stage to affect performance at others. Thermal performance may therefore respond to carryover effects of prior thermal environments, yet detailed insights into the nature, strength, and direction of those responses are still lacking. Here, in an aquatic ectotherm whose early planktonic stages (gametes, embryos, and larvae) govern adult abundances and dynamics, we explore the effects of prior thermal environments at fertilization and embryogenesis on thermal performance curves at the end of planktonic development. We factorially manipulate temperatures at fertilization and embryogenesis, then, for each combination of prior temperatures, measure thermal performance curves for survival of planktonic development (end of the larval stage) throughout the performance range. By combining generalized linear mixed modeling with parametric bootstrapping, we formally estimate and compare curve descriptors (thermal optima, limits, and breadth) among prior environments, and reveal carryover effects of temperature at embryogenesis, but not fertilization, on thermal optima at completion of development. Specifically, thermal optima shifted to track temperature during embryogenesis, while thermal limits and breadth remained unchanged. Our results argue that key aspects of thermal performance are shaped by prior thermal environment in early life, warranting further investigation of the possible mechanisms underpinning that response, and closer consideration of thermal carryover effects when predicting organismal responses to climate change.
Chronic Sleep Restriction While Minimizing Circadian Disruption Does Not Adversely Affect Glucose Tolerance
Authors: Yuan Robin K. , Zitting Kirsi-Marja , Duffy Jeanne F. , Vujovic Nina , Wang Wei , Quan Stuart F. , Klerman Elizabeth B. , Scheer Frank A. J. L. , Buxton Orfeu M. , Williams Jonathan S. , Czeisler Charles A.
Published: October 2021

Insufficient sleep, which has been shown to adversely affect metabolism, is generally associated with prolonged exposure to artificial light at night, a known circadian disruptor. There is growing evidence suggesting that circadian disruption adversely affects metabolism, yet few studies have attempted to evaluate the adverse metabolic effects of insufficient sleep while controlling for circadian disruption. We assessed postprandial glucose and insulin responses to a standard breakfast meal in healthy adults (n = 9) who underwent 3 weeks of chronic sleep restriction (CSR) in a 37-day inpatient study while minimizing circadian disruption by maintaining the same duration of light exposure each study day. We compared these results to findings from an earlier inpatient study which used a forced desynchrony (FD) protocol to assess the influence of 3 weeks of CSR combined with recurrent circadian disruption (RCD) on glycemic control in healthy adults (n = 21). CSR combined with RCD resulted in significantly elevated postprandial plasma glucose levels (p < 0.0001), while CSR with minimized circadian disruption had no adverse glycemic effects after 3 weeks of exposure (EXP). These results suggest that one mechanism by which sleep restriction impacts metabolism may be via concurrent circadian disruption.
Indirect Export of Reducing Equivalents From the Chloroplast to Resupply NADP for C3 Photosynthesis—Growing Importance for Stromal NAD(H)?
Authors: Krämer Moritz , Kunz Hans-Henning
Published: October 2021

Plant productivity greatly relies on a flawless concerted function of the two photosystems (PS) in the chloroplast thylakoid membrane. While damage to PSII can be rapidly resolved, PSI repair is complex and time-consuming. A major threat to PSI integrity is acceptor side limitation e.g., through a lack of stromal NADP ready to accept electrons from PSI. This situation can occur when oscillations in growth light and temperature result in a drop of CO2 fixation and concomitant NADPH consumption. Plants have evolved a plethora of pathways at the thylakoid membrane but also in the chloroplast stroma to avoid acceptor side limitation. For instance, reduced ferredoxin can be recycled in cyclic electron flow or reducing equivalents can be indirectly exported from the organelle via the malate valve, a coordinated effort of stromal malate dehydrogenases and envelope membrane transporters. For a long time, the NADP(H) was assumed to be the only nicotinamide adenine dinucleotide coenzyme to participate in diurnal chloroplast metabolism and the export of reductants via this route. However, over the last years several independent studies have indicated an underappreciated role for NAD(H) in illuminated leaf plastids. In part, it explains the existence of the light-independent NAD-specific malate dehydrogenase in the stroma. We review the history of the malate valve and discuss the potential role of stromal NAD(H) for the plant survival under adverse growth conditions as well as the option to utilize the stromal NAD(H) pool to mitigate PSI damage.
Development and Validation of a Multi-Dimensional Measure of Activity-Based Working Behaviors
Authors: Bäcklander Gisela , Fältén Rebecca , Bodin Danielsson Christina , Toivanen Susanna , Richter Anne
Published: October 2021

Most work on activity-based working centers on the physical environment and digital technologies enabling flexible working. While important, we believe the key components for implementing activity-based working are employee and manager behaviors. To measure the degree of enactment of activity-based work, based on workshops with experienced practitioners as well as previous literature, we have developed and validated a behavior-focused measure of activity-based working behaviors. In our initial sample (Sample 1,N= 234), three subscales were identified: task – environment crafting, workday planning, and social needs prioritization. In the replication sample (Sample 2,N= 434), this model also showed adequate fit. Moreover, task – environment crafting was related to general health and lower stress in sample 1 (multi-organization sample), but not in the single-organization sample (sample 2). Workday planning was associated with higher concentration in both samples and in the second sample with general health and work engagement; the latter was also related to social needs prioritization.
Auditory Processing of Non-speech Stimuli by Children in Dual-Language Immersion Programs
Authors: Jones Chloe , Collin Elizabeth , Kepinska Olga , Hancock Roeland , Caballero Jocelyn , Zekelman Leo , Vandermosten Maaike , Hoeft Fumiko
Published: October 2021

Perception of low-level auditory cues such as frequency modulation (FM) and rise time (RT) is crucial for development of phonemic representations, segmentation of word boundaries, and attunement to prosodic patterns in language. While learning an additional language, children may develop an increased sensitivity to these cues to extract relevant information from multiple types of linguistic input. Performance on these auditory processing tasks such as FM and RT by children learning another language is, however, unknown. Here we examine 92 English-speaking 7–8-year-olds in the U.S. and their performance in FM and RT perceptual tasks at the end of their second year in Cantonese or Spanish dual-language immersion compared to children in general English education programs. Results demonstrate that children in immersion programs have greater sensitivity to FM, but not RT, controlling for various factors. The immersion program students were also observed to have better phonological awareness performance. However, individual differences in FM sensitivity were not associated with phonological awareness, a pattern typically observed in monolinguals. These preliminary findings suggest a possible impact of formal language immersion on low-level auditory processing. Additional research is warranted to understand causal relationships and ultimate impact on language skills in multilinguals.
Are Personality-Based Intellectual Styles Culture Specific or Universal?
Authors: Zhang Li-fang
Published: October 2021

Traditionally, it had been commonly believed that individuals in the same culture have personalities distinct from those of individuals in other cultures. This article examines this belief by critically reviewing relevant literature generated from two of the most widely investigated personality-based style constructs in the field of intellectual styles: the Jungian personality styles and the career personality styles proposed by Holland. It aims at answering the question of whether personality-based intellectual styles are culture specific or they are universal. To achieve this aim, based on the two broad cultural systems derived from Hofstede's model of four cultural dimensions and two major style types from Zhang and Sternberg's threefold model of intellectual styles, two research hypotheses were made. To test the hypotheses, two types of empirical literature centered on each of the two personality-based styles are reviewed: (1) cross-cultural comparative studies; and (2) within-culture studies investigating the association of the two style constructs with other human attributes and outcomes. Results suggest that although personality-based styles are related to culture, they cannot be culture specific; rather, they are fundamentally universal. These findings carry scientific value and have practical implications for education and beyond.
Ability to Consolidate Instances as a Proxy for the Association Among Reading, Spelling, and Math Learning Skill
Authors: Marinelli Chiara Valeria , Angelelli Paola , Martelli Marialuisa , Trenta Mara , Zoccolotti Pierluigi
Published: October 2021

Learning skills (as well as disorders) tend to be associated; however, cognitive models typically focus either on reading, spelling or maths providing no clear basis for interpreting this phenomenon. A recent new model of learning cognitive skills proposes that the association among learning skills (and potentially the comorbidity of learning disorders) depends in part from the individual ability to consolidate instances (taken as a measure of rate of learning). We examined the performance of typically developing fifth graders over the acquisition of a novel paper-and-pencil task that could be solved based on an algorithm or, with practice, with reference to specific instances. Our aim was to establish a measure of individual rate of learning using parameters envisaged by the instance theory of automatization by Logan and correlate it to tasks requiring knowledge of individual items (e.g., spelling words with an ambiguous transcription) or tasks requiring the application of a rule or an algorithm (e.g., spelling non-words). The paper-and-pencil procedure yielded acquisition curves consistent with the predictions of the instance theory of automatization (i.e., they followed a power function fit) both at a group and an individual level. Performance in tasks requiring knowledge of individual items (such as doing tables or the retrieval of lexical representations) but not in tasks requiring the application of rules or algorithms (such as judging numerosity or spelling through sublexical mapping) was significantly predicted by the learning parameters of the individual power fits. The results support the hypothesis that an individual dimension of “ability to consolidate instances” contributes to learning skills such as reading, spelling, and maths, providing an interesting heuristic for understanding the comorbidity across learning disorders.