bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Dose Apatinib Combined With S-1 in Refractory Metastatic Colorectal Cancer: A Phase 2, Multicenter, Single-Arm, Prospective Study
Authors: Li Ning , Deng Wenying , Zhang Guifang , Du Yali , Guo Yanwei , Ma Yijie , Wei Chen , Bie Liangyu , Zhang Chi , Song Tao , Luo Suxia , Fang Baijun
Published: September 2021

Purpose

Apatinib is an approved third-line treatment for metastatic gastric cancer in China and demonstrates good safety, tolerability, and efficacy in other advanced solid tumors. The aim of this prospective, single-arm, multicenter, phase 2 study was to assess the efficacy and safety of low-dose apatinib combined with S-1 in the treatment of refractory mCRC.

Patients and Methods

Patients with refractory mCRC were enrolled and administered apatinib combined with S-1 until disease progression, patient decision to withdraw, or unacceptable toxic effects. The primary endpoint was investigator-evaluated progression-free survival (PFS) and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR).

Results

From December 2017 to December 2018, 30 patients were enrolled and 29 patients were eligible for the evaluation of efficacy and safety. The median PFS (mPFS) and OS (mOS) were 7.9 and 12.9 months, respectively. Exploratory analysis revealed that patients administered S-1 ≥ 70 days achieved longer mPFS and mOS. Four patients achieved a partial response, 22 achieved stable disease, and three had progressive disease, attributing to an ORR of 13.79% and a DCR of 89.66%. Ten grade 3 adverse events were reported and the frequency of each grade 3 adverse event was less than 5%. No grade 4 side events were observed.

Conclusions

These results indicated that apatinib combined with S-1 showed promising efficacy and manageable toxicity in patients with progressive mCRC after at least 2 prior lines of therapy, making it a promising therapeutic option for mCRC treatment.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT03397199, identifier NCT03397199.
Development and Validation of a Clinical Prognostic Nomogram for Esophageal Adenocarcinoma Patients
Authors: Shao Chen-ye , Yu Yue , Li Qi-fan , Liu Xiao-long , Song Hai-zhu , Shen Yi , Yi Jun
Published: September 2021

Background

Clinical staging is essential for clinical decisions but remains imprecise. We purposed to construct a novel survival prediction model for improving clinical staging system (cTNM) for patients with esophageal adenocarcioma (EAC).

Methods

A total of 4180 patients diagnosed with EAC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and included as the training cohort. Significant prognostic variables were identified for nomogram model development using multivariable Cox regression. The model was validated internally by bootstrap resampling, and then subjected to external validation with a separate cohort of 886 patients from 2 institutions in China. The prognostic performance was measured by concordance index (C-index), Akaike information criterion (AIC) and calibration plots. Different risk groups were stratified by the nomogram scores.

Results

A total of six variables were determined related with survival and entered into the nomogram construction. The calibration curves showed satisfied agreement between nomogram-predicted survival and actual observed survival for 1-, 3-, and 5-year overall survival. By calculating the AIC and C-index values, our nomogram presented superior discriminative and risk-stratifying ability than current TNM staging system. Significant distinctions in survival curves were observed between different risk subgroups stratified by nomogram scores.

Conclusion

The established and validated nomogram presented better risk-stratifying ability than current clinical staging system, and could provide a convenient and reliable tool for individual survival prediction and treatment strategy making.
Roles of Histone Deacetylases in Acute Myeloid Leukemia With Fusion Proteins
Authors: Zhang Juan , Gao Xuefeng , Yu Li
Published: September 2021

Accurate orchestration of gene expression is critical for the process of normal hematopoiesis, and dysregulation is closely associated with leukemogenesis. Epigenetic aberration is one of the major causes contributing to acute myeloid leukemia (AML), where chromosomal rearrangements are frequently found. Increasing evidences have shown the pivotal roles of histone deacetylases (HDACs) in chromatin remodeling, which are involved in stemness maintenance, cell fate determination, proliferation and differentiation, via mastering the transcriptional switch of key genes. In abnormal, these functions can be bloomed to elicit carcinogenesis. Presently, HDAC family members are appealing targets for drug exploration, many of which have been deployed to the AML treatment. As the majority of AML events are associated with chromosomal translocation resulting in oncogenic fusion proteins, it is valuable to comprehensively understand the mutual interactions between HDACs and oncogenic proteins. Therefore, we reviewed the process of leukemogenesis and roles of HDAC members acting in this progress, providing an insight for the target anchoring, investigation of hyperacetylated-agents, and how the current knowledge could be applied in AML treatment.
Adherence to the Porto Criteria Based on the Hungarian Nationwide Pediatric Inflammatory Bowel Disease Registry (HUPIR)
Authors: Müller Katalin E. , Dezsőfi Antal , Cseh Áron , Szűcs Dániel , Vass Noémi , Nemes Éva , Kadenczki Orsolya , Tárnok András , Szakos Erzsébet , Guthy Ildikó , Kovács Márta , Karoliny Anna , Czelecz Judit , Tokodi István , Tomsits Erika , Veres Gábor
Published: September 2021

Objectives: According to the Porto criteria, upper endoscopy and ileocolonoscopy with histology for patients with pediatric inflammatory bowel disease (pIBD) are recommended with small bowel imaging (SBI). We aimed to evaluate the adherence to the Porto criteria and biopsy sampling practice and to evaluate the diagnostic yield of magnetic resonance enterography (MRE) first time in a nationwide pIBD inception cohort.

Methods: Newly diagnosed pIBD cases (ages 0–18 years) are registered in the prospective, nationwide Hungarian Paediatric IBD Registry (HUPIR). We analyzed the diagnostic workup of patients recorded between the 1st of January 2007 and the 31st of December 2016.

Results: Data for diagnostic workup was available in 1,523 cases. Forty percent of the cases had complied with the Porto criteria. Adherence to the Porto criteria increased significantly from 20 to 57% (p < 0.0001) between 2007 and 2016. The most frequent reason for the incomplete diagnostic work-up was the lack of small bowel imaging (59%). In 2007, 8% of cases had a biopsy from all segments, and this rate reached 51% by 2016 (p < 0.0001). We analyzed the diagnostic yield of MRE in 113 patients (10.1%), who did not have any characteristic lesion for Crohn's disease. The MRE was positive for the small bowel in 44 cases (39%).

Conclusions: Adherence to the Porto criteria increased significantly during the 10-year period. This is the first study that reports multiple biopsy sampling as the less accepted recommendation. The diagnostic yield of MRE in patients without characteristic lesion for Crohn's disease is 39%.
Changes of Infant- and Family-Centered Care Practices Administered to Extremely Preterm Infants During Implementation of the NIDCAP Program
Authors: Klein Valérie , Zores-Koenig Claire , Dillenseger Laurence , Langlet Claire , Escande Benoît , Astruc Dominique , Le Ray Isabelle , Kuhn Pierre ,   Strasbourg NIDCAP Study group
Published: September 2021

Introduction:Many studies have evaluated the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP), but few studies have assessed changes in infant- and family-centered developmental care (IFCDC) practices during its implementation.

Objectives:The primary objective of this single center study was to investigate the impact of the implementation of the NIDCAP program on IFCDC practices used for management of extremely preterm infants (EPIs). The secondary objective was to determine during implementation the impact of this program on the short-term medical outcomes of all EPIs hospitalized at our center.

Methods:All EPIs (<28 weeks gestational age) who were hospitalized at Strasbourg University Hospital from 2007 to 2014 were initially included. Outborn infants were excluded. The data of EPIs were compared for three time periods: 2007 to 2008 (pre-NIDCAP), 2010 to 2011, and 2013 to 2014 (during-NIDCAP implementation) using appropriate statistical tests. The clinical and caring procedures used during the first 14 days of life were analyzed, with a focus on components of individualized developmental care (NIDCAP observations), infant pain management (number of painful procedures, clinical pain assessment), skin-to-skin contact (SSC; frequency, day of initiation, and duration), and family access and involvement in the care of their children (duration of parental presence, parental participation in care). The short-term mortality and morbidity at discharge were evaluated.

Results:We examined 228 EPIs who received care during the three time periods. Over time, painful procedures decreased, but pain evaluations, parental involvement in care, individualized observations, and SSC increased (allp< 0.01). In addition, the first SSC was performed earlier (p= 0.03) and lasted longer (p< 0.01). There were no differences in mortality and morbidity, but there were reductions in the duration of mechanical ventilation (p= 0.02) and the time from birth to first extubation (p= 0.02), and an increase of weight gain at discharge (p= 0.02).

Conclusion:NIDCAP implementation was accompanied by progressive, measurable, and significant changes in IFCDC strategies. There were, concomitantly, moderate but statistically significant improvements in multiple important outcome measures of all hospitalized EPI.
Whey Protein Lipid Concentrate High in Milk Fat Globule Membrane Components Inhibit Porcine and Human Rotavirus in vitro
Authors: Monaco Marcia H. , Gross Gabriele , Donovan Sharon M.
Published: September 2021

Background: The milk fat globule membrane (MFMG) is a complex milk component that has been shown to inhibit rotavirus (RV) binding to cell membranes in vitro. Herein, a whey protein lipid concentrate high in MFGM components (WPLC) and whey protein concentrate (WPC; control) were screened for anti-infective activity against porcine OSU and human Wa strains of RV in both the African Green Monkey kidney (MA104) and the human colorectal adenocarcinoma (Caco-2) cell lines.

Materials and Methods: Confluent cells were exposed to OSU or Wa RV in the presence of WPLC or WPC (control) at 0, 0.1, 0.5, 1.0, 2.5, or 5 mg/ml. Infectivity was detected by immunohistochemistry and expressed as % inhibition relative to 0 mg/ml. WPLC efficacy over WPC was expressed as fold-change. One-way ANOVA analyzed data for the independent and interactive effects of concentration, test material, and RV strain.

Results: Both WPLC and WPC exhibited concentration-dependent inhibition of human Wa and porcine OSU RV infectivity in MA104 and Caco-2 cells (p < 0.0001). WPLC was 1.5–4.8-fold more effective in reducing infectivity than WPC. WPLC efficacy was independent of RV strains, but varied between cell lines. WPLC and WPC at concentrations ≥0.5 mg/mL were most effective in reducing human Wa RV infectivity in MA104 cells (p < 0.0001).

Conclusions: WPLC decreased infectivity of two strains for RV which differ in their dependency on sialic acid for binding to cells. Inhibition was observed in the most commonly used cell type for RV infectivity assays (MA104) and an intestinal cell line (Caco-2). An effect on virus infectivity might be a potential mechanisms of action contributing to beneficial effects of supplementation of infant formula with MGFM reducing the risk of infections and consequently diarrhea incidence in infants.
Melatonin Alleviates Renal Injury in Mouse Model of Sepsis
Authors: Chen Liyang , Han Zhijian , Shi Zhiguang , Liu Chao , Lu Qiulun
Published: September 2021

Melatonin (N-acetyl-5-methoxytryptamine; MLT) has been shown to have a renal-protective effect against kidney injury. However, the mechanisms underlying the protective role of MLT in sepsis-induced renal injury are yet to be revealed. In this study, MLT alleviated renal dysfunction with the increase of BUN (blood urea nitrogen) and SCR (serum creatinine) and reduction of fibrosis in the CLP (cecal ligation puncture) model. RNA-seq analysis showed that MLT repressed the oxidant stress in response to kidney injury. Our in vitro study showed that MLT suppresses LPS-induced accumulation of ROS (reactive oxygen species) production via SOD2 downregulation and Nox4 upregulation in HK-2 cells. Furthermore, we found that MLT alleviated the inflammatory response, with the mRNA-level reduction of Il-1α, Il-1β, Mcp-1, and Tgf-β1. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced acute kidney injury, the results showed that MLT alleviated renal damage by regulating the production of ROS.
Is Curcumin at the Threshold of Therapeutic Effectiveness on Patients with Colon Cancer?—A Systematic Review
Authors: Shafei Laila Khaled Ismael Abdelgawad , Mohamed Ibrahim Mohamed Izham , Billa Nashiru
Published: September 2021

Curcumin, obtained from curcuma longa, has been the subject of decades of scientific investigation on its therapeutic usefulness. It is reported to possess several therapeutic properties, of which anti-colon cancer is of interest in this review. Clinically however, curcumin has yet to firm up its place among established anti-colon cancer therapeutic contenders. We aimed to systematically review prevailing clinical evidence on the role of curcumin in colon cancer treatment. The review drawing from literature on clinical studies indicates fairly long term tolerability. No regression of tumor was reported when curcumin was the sole intervention. Increase in p53 level expression was reported in a placebo controlled study but no reduction in PGE2 or 5HETE. Pharmacokinetic data on healthy humans indicate that formulated curcumin delivery systems present significantly higher systemic bioavailability. It appears therefore that the clinical use of curcumin can potentially be realized only through appropriate formulation interventions.

Systematic Review Registration: [website], identifier [registration number]
Lcz696 Alleviates Myocardial Fibrosis After Myocardial Infarction Through the sFRP-1/Wnt/β-Catenin Signaling Pathway
Authors: Liu Jing , Zheng Xuehui , Zhang Chen , Zhang Chunmei , Bu Peili
Published: September 2021

Background: Lcz696 (ARNI, angiotensin receptor–neprilysin inhibitor; sacubitril/valsartan) shows an inhibitory effect on fibrosis after myocardial infarction (MI). However, the underlying signaling mechanisms are poorly understood. The Wnt/β-catenin signaling pathway is activated after MI and participates in the process of myocardial fibrosis. Here, we aimed to assess the efficacy of ARNI for alleviating myocardial fibrosis after MI and hypothesized that ARNI alleviates myocardial fibrosis by inhibiting the Wnt/β-catenin signaling pathway and overexpressing sFRP-1, an inhibitor of the Wnt/β-catenin signaling pathway.

Methods: Mice randomized at 1 week post-MI were administered lcz696 (60 mg/kg, n = 21), valsartan (30 mg/kg, n = 19), or corn oil (n = 13) orally for 4 weeks, while the sham-operated group received vehicle (corn oil, n = 19). Cardiac function and extent of myocardial fibrosis were measured. Western blotting and quantitative real-time polymerase chain reaction were used to detect the expression of Wnt/β-catenin pathway-related proteins. Furthermore, primary myocardial fibroblasts were stimulated with angiotensin II (Ang II) and cultured with lcz696 and the sFRP-1 inhibitor way316606 to detect the expression of Wnt/β-catenin pathway proteins.

Results: Both lcz696 and valsartan alleviated myocardial fibrosis and improved cardiac function, but lcz696 had superior efficiency compared to valsartan. Furthermore, β-catenin expression was inhibited and sFRP-1 was overexpressed after drug treatment, which could be significantly improved by lcz696 in mice. In addition, lcz696 inhibited β-catenin expression in AngII-stimulated myocardial fibroblasts, and β-catenin expression increased after the inhibition of sFRP-1.

Conclusion: ARNI alleviated cardiac fibrosis and cardiac remodeling by inhibiting the Wnt/β-catenin signaling pathway. In addition, ARNI can lead to overexpression of sFRP-1, which is an inhibitor of the Wnt/β-catenin signaling pathway. These results indicate a new therapeutic target of ARNI to improve myocardial fibrosis and prevent myocardial remodeling.
Population Pharmacokinetics of Rituximab in Pediatric Patients With Frequent-Relapsing or Steroid-Dependent Nephrotic Syndrome
Authors: Chen Yewei , Shen Qian , Dong Min , Xiong Ye , Xu Hong , Li Zhiping
Published: September 2021

Objectives: Rituximab is frequently used off-label for the treatment of frequent-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS), but the relapse rate remained high and the dosing regimen varied widely. The objective of this study was to characterize rituximab pharmacokinetics (PK) in pediatric patients with FRNS/SDNS, and to investigate the differences in rituximab PK between patients with FRNS/SDNS and other disease populations.

Methods: Fourteen pediatric patients received rituximab for FRNS/SDNS treatment were enrolled in a prospective, open-label, single-center PK study. A population PK model of rituximab was developed and validated, and PK parameters were derived for quantitative evaluation.

Results: A two-compartment PK model best described the data. Body surface area was the most significant covariate for both central clearance (CL) and apparent central volume of distribution (V1). Patients with FRNS/SDNS exhibited a clinically relevant increase in rituximab CL compared to patient population with non-Hodgkin’s lymphoma (NHL).

Conclusion: This pilot study indicated that higher doses or more frequent regimens of rituximab may be required for optimal therapeutic effects in patients with FRNS/SDNS. Further clinical studies with more patients are warranted to confirm this result.
Rituximab Therapy for Primary Sjögren’s Syndrome
Authors: Chen Yi Han , Wang Xin Yu , Jin Xin , Yang Zi , Xu Jianguang
Published: September 2021

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune diseases of the connective tissues, characteristic of the presentation of keratoconjunctivitis sicca and xerostomia. A cardinal pathogenetic feature of SS is B-cell hyperactivity, which has invited efforts on optimal B-cell targeted therapy, whereas conventional corticosteroids and disease-modifying antirheumatic drugs (DMARDs) are restricted to symptomatic relief. As per the first EULAR recommendation for pSS patients published in 2020, regimens with monoclonal antibodies targeting B cells may be initiated in patients with severe, refractory systemic disease, notably rituximab (RTX), a mouse-derived monoclonal antibody that targets CD20 antigen and contributes to B-cell depletion. Nonetheless, the data available from clinical trials with RTX are often controversial. Despite the lack of promising results from two large RCTs, several positive clinical efficacies were demonstrated. This current review addressed the efficacy and safety of clinical trials available and elucidated the potential of RTX on the immune system, especially B and T cells. Furthermore, plausible explanations for the discrepancy in clinical data were also presented.
PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy
Authors: Liu Jinhua , Chen Zichao , Li Yaqun , Zhao Wenjie , Wu JiBiao , Zhang Zhen
Published: September 2021

Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of cancer and has become an important immune checkpoint in recent years, so understanding the mechanism of PD1/PDL1 action is of great significance for combined immunotherapy and patient prognosis. The inhibitors of PD1/PDL1 have shown clinical efficacy in many tumors, for example, blockade of PD1 or PDL1 with specific antibodies enhances T cell responses and mediates antitumor activity. However, some patients are prone to develop drug resistance, resulting in poor treatment outcomes, which is rooted in the insensitivity of patients to targeted inhibitors. In this paper, we reviewed the mechanism and application of PD1/PDL1 checkpoint inhibitors in tumor immunotherapy. We hope that in the future, promising combination therapy regimens can be developed to allow immunotherapeutic tools to play an important role in tumor treatment. We also discuss the safety issues of immunotherapy and further reflect on the effectiveness of the treatment and the side effects it brings.
Albuca Bracteate Polysaccharides Synergistically Enhance the Anti-Tumor Efficacy of 5-Fluorouracil Against Colorectal Cancer by Modulating β-Catenin Signaling and Intestinal Flora
Authors: Yuan Xinyu , Xue Jiao , Tan Yingxia , Yang Qingguo , Qin Ziyan , Bao Xiaodong , Li Shengkai , Pan Liangliang , Jiang Ziqing , Wang Yu , Lou Yongliang , Jiang Lei , Du Jimei
Published: September 2021

The first-line treatment for colorectal cancer (CRC) is 5-fluorouracil (5-FU). However, the efficacy of this treatment is sometimes limited owing to chemoresistance as well as treatment-associated intestinal mucositis and other adverse events. Growing evidence suggests that certain phytochemicals have therapeutic and cancer-preventing properties. Further, the synergistic interactions between many such plant-derived products and chemotherapeutic drugs have been linked to improved therapeutic efficacy. Polysaccharides extracted from Albuca bracteata (Thunb.) J.C.Manning and Goldblatt (ABP) have been reported to exhibit anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, murine CRC cells (CT26) and a murine model of CRC were used to examine the anti-tumor properties of ABP and explore the mechanism underlying the synergistic interactions between ABP and 5-FU. Our results revealed that ABP could inhibit tumor cell proliferation, invasion, and migratory activity in vitro and inhibited tumor progression in vivo by suppressing β-catenin signaling. Additionally, treatment with a combination of ABP and 5-FU resulted in better outcomes than treatment with either agent alone. Moreover, this combination therapy resulted in the specific enrichment of Ruminococcus, Anaerostipes, and Oscillospira in the intestinal microbiota and increased fecal short-chain fatty acid (SCFA) levels (acetic acid, propionic acid, and butyric acid). The improvement in the intestinal microbiota and the increase in beneficial SCFAs contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Together, these data suggest that ABP exhibits anti-neoplastic activity and can effectively enhance the efficacy of 5-FU in CRC treatment. Therefore, further research on the application of ABP in the development of novel anti-tumor drugs and adjuvant compounds is warranted and could improve the outcomes of CRC patients.
Herb-Induced Liver Injury Related to Reynoutria multiflora (Thunb.) Moldenke: Risk Factors, Molecular and Mechanistic Specifics
Authors: Zhai Xing-Ran , Zou Zheng-Sheng , Wang Jia-Bo , Xiao Xiao-He
Published: September 2021

Herbal medicine is widely used in Asia as well as the west. Hepatotoxicity is one of the most severe side effects of herbal medicine which is an increasing concern around the world. Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb., PM) is the most common herb that can cause herb-induced liver injury (HILI). The recent scientific and technological advancements in clinical and basic research are paving the way for a better understanding of the molecular aspects of PM-related HILI (PM-HILI). This review provides an updated overview of the clinical characteristics, predisposing factors, hepatotoxic components, and molecular mechanisms of PM-HILI. It can also aid in a better understanding of HILI and help in further research on the same.
Impact of Cation Stoichiometry on the Crystalline Structure and Superconductivity in Nickelates
Authors: Li Yueying , Sun Wenjie , Yang Jiangfeng , Cai Xiangbin , Guo Wei , Gu Zhengbin , Zhu Ye , Nie Yuefeng
Published: September 2021

The recent discovery of superconductivity in infinite-layer nickelate films has aroused great interest since it provides a new platform to explore the mechanism of high-temperature superconductivity. However, superconductivity only appears in the thin film form and synthesizing superconducting nickelate films is extremely challenging, limiting the in-depth studies on this compound. Here, we explore the critical parameters in the growth of high-quality nickelate films using molecular beam epitaxy. We found that stoichiometry is crucial in optimizing the crystalline structure and realizing superconductivity in nickelate films. In precursor NdNiO3 films, optimal stoichiometry of cations yields the most compact lattice while off-stoichiometry of cations causes obvious lattice expansion, influencing the subsequent topotactic reduction and the emergence of superconductivity in infinite-layer nickelates. Surprisingly, in-situ reflection high energy electron diffraction indicates that some impurity phases always appear once Sr ions are doped into NdNiO3 although the X-ray diffraction data are of high quality. While these impurity phases do not seem to suppress the superconductivity, their impacts on the electronic and magnetic structure deserve further studies. Our work demonstrates and highlights the significance of cation stoichiometry in the superconducting nickelate family.
Actively Controlled Frequency-Agile Fano-Resonant Metasurface for Broadband and Unity Modulation
Authors: Yang Ruisheng , Fu Quanhong , Fan Yuancheng , Xu Jing , Zhu Wei , Cai Weiqi , Zhang Fuli
Published: September 2021

The active control to the local resonant mode of metasurface is a promising route for improving the operation bandwidth limitation of metasurface. Here, we propose and experimentally demonstrated the active tunabilities in a frequency-agile Fano-resonant metasurface. The metasurface with a pair of asymmetric split ring resonators is integrated with double varactor diodes for active control of the sharp Fano resonance. It is found that the sharp Fano-type spectrum appears due to the near-field interferences between the collective electric and magnetic dipole modes. The physical insight is revealed through local field analysis, multipole decomposition and temporal coupled-mode theory. It is also found that the metasurface can be employed as a broadband and unity modulator. Hopefully, our results could inspire sophisticated electrically controlled photonic devices with novel functions.
Characterizing the Layer Structures of the Lacquerware From the Palace Museum by Terahertz Imaging in Reflection Geometry
Authors: Zhang Hongfei , Zhao Yuanmeng , Li Chenyu , Zhang Cunlin
Published: September 2021

Chinese lacquerware is an important invention of arts and crafts in China. In this study, Chinese lacquerware is characterized using terahertz reflectometric imaging. The lacquerware studied herein comprises an ornamental wood panel covered by multiple layers of lacquers to portray motifs. For characterizing lacquerware, a terahertz time-domain spectroscopic reflectometric imaging system is proposed. The role of the proposed terahertz imaging system in highlighting the interface between layers during stratigraphic buildup in reflection geometry is proved. The proposed system provides a universal method for assessing the structural information of lacquered objects in a contactless and non-invasive manner; moreover, it provides two-dimensional images, subsurface three-dimensional images, and stratigraphic images (b-scans) in a contactless and non-invasive manner. Using the proposed system, we examine the buried layers of the lacquerware, including faults in the wooden layer and damages in the lacquerware. Research shows the promising prospects of terahertz time-domain spectroscopic reflectometric imaging as a non-destructive detection technique suited to lacquerware.
Characterization of Atrial Propagation Patterns and Fibrotic Substrate With a Modified Omnipolar Electrogram Strategy in Multi-Electrode Arrays
Authors: Riccio Jennifer , Alcaine Alejandro , Rocher Sara , Martinez-Mateu Laura , Laranjo Sergio , Saiz Javier , Laguna Pablo , Martínez Juan Pablo
Published: September 2021

Introduction: The omnipolar electrogram method was recently proposed to try to generate orientation-independent electrograms. It estimates the electric field from the bipolar electrograms of a clique, under the assumption of locally plane and homogeneous propagation. The local electric field evolution over time describes a loop trajectory from which omnipolar signals in the propagation direction, substrate and propagation features, are derived. In this work, we propose substrate and conduction velocity mapping modalities based on a modified version of the omnipolar electrogram method, which aims to reduce orientation-dependent residual components in the standard approach.

Methods: A simulated electrical propagation in 2D, with a tissue including a circular patch of diffuse fibrosis, was used for validation. Unipolar electrograms were calculated in a multi-electrode array, also deriving bipolar electrograms along the two main directions of the grid. Simulated bipolar electrograms were also contaminated with real noise, to assess the robustness of the mapping strategies against noise. The performance of the maps in identifying fibrosis and in reproducing unipolar reference voltage maps was evaluated. Bipolar voltage maps were also considered for performance comparison.

Results: Results show that the modified omnipolar mapping strategies are more accurate and robust against noise than bipolar and standard omnipolar maps in fibrosis detection (accuracies higher than 85 vs. 80% and 70%, respectively). They present better correlation with unipolar reference voltage maps than bipolar and original omnipolar maps (Pearson's correlations higher than 0.75 vs. 0.60 and 0.70, respectively).

Conclusion: The modified omnipolar method improves fibrosis detection, characterization of substrate and propagation, also reducing the residual sensitivity to directionality over the standard approach and improving robustness against noise. Nevertheless, studies with real electrograms will elucidate its impact in catheter ablation interventions.
Effects of Thermal Acclimation on the Tolerance of Bactrocera zonata (Diptera: Tephritidae) to Hydric Stress
Authors: Ben-Yosef Michael , Verykouki Eleni , Altman Yam , Nemni-Lavi Esther , Papadopoulos Nikos T. , Nestel David
Published: September 2021

Insects, similarly to other small terrestrial invertebrates, are particularly susceptible to climatic stress. Physiological adjustments to cope with the environment (i.e., acclimation) together with genetic makeup eventually determine the tolerance of a species to climatic extremes, and constrain its distribution. Temperature and desiccation resistance in insects are both conditioned by acclimation and may be interconnected, particularly for species inhabiting xeric environments. We determined the effect of temperature acclimation on desiccation resistance of the peach fruit fly (Bactrocera zonata, Tephritidae) – an invasive, polyphagous pest, currently spreading through both xeric and mesic environments in Africa and the Eurasian continent. Following acclimation at three constant temperatures (20, 25, and 30°C), the survival of adult flies deprived of food and water was monitored in extreme dry and humid conditions (<10 and >90% relative humidity, respectively). We found that flies acclimated at higher temperatures were significantly heavier, and contained more lipids and protein. Acclimation temperature significantly and similarly affected the survival of males and females at both high and low humidity conditions. In both cases, flies maintained at 30°C survived longer compared to 20 and 25°C – habituated counterparts. Regardless of the effect of acclimation temperature on survival, overall life expectancy was significantly shortened when flies were assayed under desiccating conditions. Additionally, our experiments indicate no significant difference in survival patterns between males and females, and that acclimation temperature had similar effects after both short (5–10 days) and long (11–20 days) acclimation periods. We conclude that acclimation at 30°C prolongs the survival of B. zonata, regardless of ambient humidity levels. Temperature probably affected survival through modulating feeding and metabolism, allowing for accumulation of larger energetic reserves, which in turn, promoted a greater ability to resist starvation, and possibly desiccation as well. Our study set the grounds for understanding the phenotypic plasticity of B. zonata from the hydric perspective, and for further evaluating the invasion potential of this pest.
Detecting Pathogen Exposure During the Non-symptomatic Incubation Period Using Physiological Data: Proof of Concept in Non-human Primates
Authors: Davis Shakti , Milechin Lauren , Patel Tejash , Hernandez Mark , Ciccarelli Greg , Samsi Siddharth , Hensley Lisa , Goff Arthur , Trefry John , Johnston Sara , Purcell Bret , Cabrera Catherine , Fleischman Jack , Reuther Albert , Claypool Kajal , Rossi Franco , Honko Anna , Pratt William , Swiston Albert
Published: September 2021

Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First, we seek to determine the upper limits of early warning detection through physiological measurements. Second, we investigate whether the detected physiological response is specific to the pathogen. Third, we explore the feasibility of extending early warning detection with wearable devices.

Research Methods: For the first objective, we developed a supervised random forest algorithm to detect pathogen exposure in the asymptomatic period prior to overt symptoms (fever). We used high-resolution physiological telemetry data (aortic blood pressure, intrathoracic pressure, electrocardiograms, and core temperature) from non-human primate animal models exposed to two viral pathogens: Ebola and Marburg (N = 20). Second, to determine reusability across different pathogens, we evaluated our algorithm against three independent physiological datasets from non-human primate models (N = 13) exposed to three different pathogens: Lassa and Nipah viruses and Y. pestis. For the third objective, we evaluated performance degradation when the algorithm was restricted to features derived from electrocardiogram (ECG) waveforms to emulate data from a non-invasive wearable device.

Results: First, our cross-validated random forest classifier provides a mean early warning of 51 ± 12 h, with an area under the receiver-operating characteristic curve (AUC) of 0.93 ± 0.01. Second, our algorithm achieved comparable performance when applied to datasets from different pathogen exposures – a mean early warning of 51 ± 14 h and AUC of 0.95 ± 0.01. Last, with a degraded feature set derived solely from ECG, we observed minimal degradation – a mean early warning of 46 ± 14 h and AUC of 0.91 ± 0.001.

Conclusion: Under controlled experimental conditions, physiological measurements can provide over 2 days of early warning with high AUC. Deviations in physiological signals following exposure to a pathogen are due to the underlying host’s immunological response and are not specific to the pathogen. Pre-symptomatic detection is strong even when features are limited to ECG-derivatives, suggesting that this approach may translate to non-invasive wearable devices.
A Hybrid Approach for Cardiac Blood Flow Vortex Ring Identification Based on Optical Flow and Lagrangian Averaged Vorticity Deviation
Authors: Yang Ke , Wu Shiqian , Samuel Oluwarotimi W. , Zhang Hui , Ghista Dhanjoo N. , Yang Di , Wong Kelvin K. L.
Published: September 2021

Objective: The measurement of cardiac blood flow vortex characteristics can help to facilitate the analysis of blood flow dynamics that regulates heart function. However, the complexity of cardiac flow along with other physical limitations makes it difficult to adequately identify the dominant vortices in a heart chamber, which play a significant role in regulating the heart function. Although the existing vortex quantification methods can achieve this goal, there are still some shortcomings: such as low precision, and ignoring the center of the vortex without the description of vortex deformation processes. To address these problems, an optical flow Lagrangian averaged vorticity deviation (Optical flow-LAVD) method is proposed.

Methodology: We examined the flow within the right atrium (RA) of the participants’ hearts, by using a single set of scans pertaining to a slice at two-chamber short-axis orientation. Toward adequate extraction of the vortex ring characteristics, a novel approach driven by the Lagrangian averaged vorticity deviation (LAVD) was implemented and applied to characterize the trajectory integral associated with vorticity deviation and the spatial mean of rings, by using phase-contrast magnetic resonance imaging (PC-MRI) datasets as a case study. To interpolate the time frames between every larger discrete frame and minimize the error caused by constructing a continuous velocity field for the integral process of LAVD, we implemented the optical flow as an interpolator and introduced the backward warping as an intermediate frame synthesis basis, which is then used to generate higher quality continuous velocity fields.

Results: Our analytical study results showed that the proposed Optical flow-LAVD method can accurately identify vortex ring and continuous velocity fields, based on optical flow information, for yielding high reconstruction outcomes. Compared with the linear interpolation and phased-based frame interpolation methods, our proposed algorithm can generate more accurate synthesized PC-MRI.

Conclusion: This study has developed a novel Optical flow-LAVD model to accurately identify cardiac vortex rings, and minimize the associated errors caused by the construction of a continuous velocity field. Our paper presents a superior vortex characteristics detection method that may potentially aid the understanding of medical experts on the dynamics of blood flow within the heart.
Social Jetlag Is Associated With Impaired Metabolic Control During a 1-Year Follow-Up
Authors: Mota Maria Carliana , Silva Catarina Mendes , Balieiro Laura Cristina Tibiletti , Fahmy Walid Makin , Marqueze Elaine Cristina , Moreno Claudia Roberta de Castro , Crispim Cibele Aparecida
Published: September 2021

Previous studies have identified social jetlag (SJL) as a risk factor for non-communicable chronic diseases (NCCDs), but its association with metabolic control over time is unclear in the literature. Therefore, we examined the influence of SJL on metabolic parameters and blood pressure (BP) in patients with NCCDs over a 1-year follow-up. This retrospective, longitudinal study included 625 individuals (age: 56.0 +12.0 years; 76% female) with NCCDs [type 2 diabetes mellitus (TD2), systemic arterial hypertension (SHA), obesity, or dyslipidemia]. SJL was calculated based on the absolute difference between mid-sleep time on weekends and weekdays. Current metabolic parameters and BP of the patients were compared with data from a year prior. Generalized estimating equations (GEE) and multiple linear regression analyses were used to examine the association among SJL, metabolic parameters, and BP. Multiple linear regression analyses adjusted for confounders showed that SJL was positively associated with the delta difference of fasting glucose (β = 0.11, p = 0.02) and triglyceride levels (β = 0.09, p = 0.04) among all subjects with NCCDs, and with fasting glucose (β = 0.30, p = 0.0001) and triglyceride levels (β = 0.22, p = 0.01) in the TD2 group. GEE analysis demonstrated an isolated effect of SJL on diastolic BP. High SJL impaired clinical and metabolic control in individuals with NCCDs, leading to a worse profile after a 1-year follow-up, particularly among type II diabetics.
Physicochemical and Functional Characterization of Female Reproductive Fluids: A Report of the First Two Infants Born Following Addition of Their Mother's Fluids to the Embryo Culture Media
Authors: Canha-Gouveia Analuce , Prieto-Sánchez Maria Teresa , Sánchez-Ferrer Maria Luisa , Mollá Marta , Martínez-Soto Juan Carlos , París-Oller Evelyne , Soriano-Úbeda Cristina , Landeras José , Coy Pilar
Published: September 2021

Culture media supplemented with reproductive fluids (RF) have been used in livestock species, improving the efficiency and quality of in vitro produced embryos. However, usefulness in humans is still unknown. In this study, we collected human reproductive fluids (HRFs) ex vivo (from 25 patients undergoing abdominal hysterectomy plus bilateral salpingectomy) and in vivo (from 31 oocyte donors). Afterward, protocols to evaluate their osmolality, pH, total protein concentration, endotoxin level, and sterility were optimized, establishing security ranges for their use as natural additives. In addition, a functional assay was developed with bovine embryos grown in vitro in a medium supplemented with 1% of collected HRFs. Finally, a proof of concept was performed with six patients on post ovulation day 2 to evaluate the full-term viability of embryos grown in media supplemented with autologous uterine fluid, collected under in vivo conditions. Two of the embryos resulted in successful pregnancy and delivery of healthy babies. In conclusion, this study establishes a complete quality control sheet of HRFs as additives for embryo culture media and shows first preliminary data on obtaining healthy offspring derived from embryos grown in media supplemented with HRFs.
Thalidomide Suppresses Angiogenesis Through the Signal Transducer and Activator of Transcription 3/SP4 Signaling Pathway in the Peritoneal Membrane
Authors: Zhu Nan , Wang Ling , Guo Huimin , Jia Jieshuang , Gu Lijie , Wang Xuan , Yang Man , Guan Haochen , Yuan Weijie
Published: September 2021

Peritoneal angiogenesis is the key pathophysiological factor that limits peritoneal ultrafiltration during peritoneal dialysis (PD) in uremic patients. Thalidomide has been confirmed to inhibit angiogenesis by inhibiting the secretion of vascular endothelial growth factor (VEGF), but the exact mechanism by which thalidomide inhibits vascular proliferation during PD is still unclear. Here, the objective of the present study was to investigate whether the reduction in VEGF production by human peritoneal mesothelial cells (HPMCs) was controlled by thalidomide. Stimulation of HPMCs with IL-6 in combination with soluble IL-6 receptor (sIL-6R) promoted VEGF expression and secretion, but these effects were attenuated by thalidomide treatment through a transcriptional mechanism that involved signal transducer and activator of transcription 3 (STAT3) and SP4. Conditioned medium from HPMCs cultured with thalidomide inhibited angiogenic endothelial tube formation, which could be further blocked by silencing SP4 and promoted by overexpressing SP4. In vivo, induction of peritoneal angiogenesis in sham rats, sham+PD rats, 5/6 nephrectomy (5/6Nx) rats, 5/6Nx+PD rats, and 5/6Nx+PD rats intraperitoneally treated with thalidomide showed that thalidomide was involved in the control of several key endothelial–specific targets, including VEGFR2, VEGFR3, SP4, and STAT3 expression and new vessel formation, confirming the role of thalidomide and STAT3/SP4 signaling in these processes. Taken together, these findings identify a novel mechanism that links thalidomide, STAT3/SP4 signaling, and angiogenesis in the peritoneal membrane.
Effects of Four Lipid Metabolism-Related Polymorphisms on Body Composition Improvements After 12 Weeks of High-Intensity Interval Training and Dietary Energy Restriction in Overweight/Obese Adult Women: A Pilot Study
Authors: Andrade-Mayorga Omar , Díaz Erik , Salazar Luis A.
Published: September 2021

Background: Polymorphisms in lipid metabolism-related genes have been associated with obesity and body composition, but these have been scarcely described concerning the magnitude of the response to exercise interventions in the overweight/obese population.

Objective: To evaluate the association of perilipin 1 (PLIN1; rs1052700 and rs2304795), lipoprotein lipase (rs283), and adrenoceptor beta 3 (rs4994) polymorphisms with high and low responders (LoRes) to fat mass reduction after 12 weeks of high-intensity interval training (HIIT) and dietary energy restriction in overweight/obese adult women. In addition, we examined the effect of these genetic variants on body composition changes.

Methods: Forty-three unrelated overweight/obese adult women were incorporated and genotyped, of which 30 women (age = 27.4 ± 7.9 years; BMI = 29.9 ± 3.3 kg/m2) successfully completed the 12-week supervised HIIT program plus an individually prescribed home hypocaloric diet.

Results: An association was observed between the PLIN1 rs1052700 polymorphism with high and LoRes (χ2 = 8.138; 2 df; p = 0.01). Moreover, after the intervention, the carriers of TT genotype of PLIN1 rs1052700 as compared to AA and AT showed a greater reduction in absolute fat mass (Δ: −5.1 ± 1.8 vs. − 1.8 ± 1.4 vs. − 2.1 ± 2.3 kg; p = 0.04). The effect size of this fat mass reduction between TT and AT genotypes was a mean difference of −3.01 kg [95%IC − 4.88– − 1.1], and between TT and AA genotypes was −3.29 kg [95%IC − 4.86– − 1.65]. No differences were observed for other polymorphisms investigated.

Conclusion: These results suggest that the rs1052700 (14995A>T) polymorphism of the PLIN1 gene is associated with a differential response to fat mass reduction after a 12-week intervention in overweight/obese adult women. In addition, women with the TT genotype of this genetic variant showed greater changes in fat mass than AA and AT genotypes. However, further studies are needed to confirm these findings.