bluuebunny/crossref_metadata_2025 huggingface dataset:
Title Achieving Integrated Self-Directed Cancer Aftercare (ASICA) for Melanoma: How a Digital Intervention to Support Total Skin Self-Examination Was Used By People Treated for Cutaneous Melanoma
Authors: Reilly Felicity , Contstable Lynda , Brant William , Rahman Kaz , Durrani Amer , Burroughs Nigel , Proby Charlotte , Allan Julia , Johnston Marie , Johnston Derek , Walter Fiona , Murchie Peter
Published: May 2021

BackgroundMelanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial.MethodsThis paper reports on process evaluation. Data on participants’ demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants’ demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved.Results Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up.ConclusionMelanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool.
Oncogenic BRAF Induces Whole-Genome Doubling Through Suppression of Cytokinesis
Authors: Darp Revati , Vittoria Marc , Ganem Neil , Ceol Craig
Published: May 2021

Melanomas and other solid tumors commonly have increased ploidy, with near-tetraploid karyotypes being most frequently observed. Such karyotypes have been shown to arise through whole-genome doubling events that occur during early stages of tumor progression. The generation of tetraploid cells via whole-genome doubling is proposed to allow nascent tumor cells the ability to sample various protumorigenic genomic configurations while avoiding the negative consequences that chromosomal gains or losses have in diploid cells. Whereas a high prevalence of whole-genome doubling events has been established, the means by which whole-genome doubling arises is unclear. Here, we find that BRAFV600E, the most common mutation in melanomas, can induce whole-genome doubling via cytokinesis failure in vitro and in a zebrafish melanoma model. Mechanistically, BRAFV600E causes decreased activation and localization of RhoA, a critical cytokinesis regulator. BRAFV600E activity during G1/S phases of the cell cycle is required to suppress cytokinesis. During G1/S, BRAFV600E activity causes inappropriate centriole amplification, which is linked in part to inhibition of RhoA and suppression of cytokinesis. Together these data suggest that common abnormalities of melanomas linked to tumorigenesis – amplified centrosomes and whole-genome doubling events – can be induced by oncogenic BRAF and other mutations that increase RAS/MAPK pathway activity.
Immune Cell Profiles of Metastatic HER2 Positive Breast Cancer Patients According To The Sites of Metastasis
Authors: Honkanen Tiia J , Luukkainen Milla E K , Tikkanen Antti , Karihtala Peeter , Mäkinen Markus , Väyrynen Juha P , Koivunen Jussi
Published: May 2021

Purpose: Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2 positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2 targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2 positive breast cancer treated with trastuzumab. Methods: We collected all (n=54) HER2 positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results: Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004 – 3.262), especially when presenting as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, liver metastases had low densities of CD3+ T-cells (p=0.030) and M1-like macrophages in their primary tumours (p=0.025). Of the other studied markers and sites, pulmonary metastases had low STAB1+ immunosuppressive macrophage density in their primary tumours.Conclusions: Our results suggest that the site of metastasis is associated with prognosis in HER2 positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.
Circulating Activated Immune Cells as a Potential Blood Biomarkers of Non-small Cell Lung Cancer Occurrence and Progression
Authors: Wang Yingyi , Zhou Na , Zhu Rui , Li Xiaoyuan , Sun Zhao , Yang Gao , Liu Wei , Meng Changting , Ge Yuping , Bai Chunmei , Li Taisheng , Liu Hongsheng
Published: May 2021

Background: Non-small cell lung cancer (NSCLC) has improved greatly in recent years. However, non-invasive early screening for carcinogenesis and progression are unclearly. The aim of this study was to explore the predictive value of peripheral blood immune cells in untreated NSCLC patients. Methods: We retrospectively enrolled 305 untreated NSCLC patients and 132 healthy participators from February 2016 to August 2019. Immune cells levels were performed by flow cytometry and blood routine tests. Results: NSCLC patients had lower levels of T lymphocytes, NK cells, CD8+ T cells, naïve CD4+/ CD4+, naïve CD4+ T cells and higher levels of CD4+ T cells, memory CD4+/CD4+, memory CD4+ T cells, CD4+CD28+/CD4+, CD4+CD28+ T cells, CD8+CD28+/CD8+, CD8+HLA-DR+/CD8+, CD8+HLA-DR+ T cells, CD8+CD38+/CD8+, CD8+CD38+ T cells and CD4+/CD8+ than those in controls. Cancer progression were negatively associated with levels of B cells, CD4+ T cells, naïve CD4+/CD4+, naïve CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+ T cells and positively associated with levels of NK cells, white blood cells (WBC), monocytes, neutrophils, eosinophils, basophils, monocytes to lymphocyte ratio (MLR), neutrophils to lymphocyte ratio (NLR), eosnophil to lymphocyte ratio (ELR), basophil to lymphocyte ratio (BLR), blood platelet to lymphocyte ratio (PLR) .Conclusions: Abnormal levels of NK cells, CD4+ T cells, naïve CD4+/CD4+, naïve CD4+ T cells, CD4+CD28+ T cells can be used as independently predictive biomarker for non-invasive early screening in NSCLC occurrence and progression.
Vibration Isolation With Passive Linkage Mechanisms
Authors: Feng Xiao , Jing Xingjian , Guo Yingqing
Published: May 2021

This study is to present a novel way to achieve superior passive vibration isolation by employing a specially-designed and compact linkage mechanism. The proposed anti-vibration system has beneficial nonlinear inertia, inspired by swinging motion of human arms, and is constructed with an adjustable nonlinear stiffness system inspired by animal or human leg skeleton. It is shown with comprehensive theoretical analysis and consequently validated by a series of well-designed experiments that the nonlinear stiffness, nonlinear damping and nonlinear inertia of the proposed system are very helpful for significantly reducing natural frequency and enhancing damping effect in a beneficial nonlinear way. This results in excellent vibration isolation performance with lower resonant frequency and resonant peak of faster decay rate. This study provides an innovative solution to a cost-efficient vibration control demanded in various engineering systems.
Magma flux of silicic supereruptions from the Afro-Arabian large igneous province
Authors: Thines Jennifer , Ukstins Ingrid , Wall Corey , Schmitz Mark
Published: May 2021

The Main Silicics phase of the Afro-Arabian large igneous province preserves some of the largest volcanic eruptions on Earth, with six units totaling >8,600 km3 dense rock equivalent (DRE). The large volumes of rapidly emplaced individual eruptions present a case study for examining the tempo of generation and emplacement of voluminous silicic magmas. We use high-precision 206Pb/238U zircon dating to differentiate individual eruption ages and show that the largest sequentially dated eruptions occurred within a timeframe of 48 ± 34 kyr (29.755 ± 0.023 Ma to 29.707 ± 0.025 Ma), yielding a maximum magma flux of 3.09 x 10-1 km3/yr for 4,339 km3 DRE and making this sequence the highest known flux of silicic volcanism on Earth. The Main Silicics phase of volcanism occurred within a timeframe of 130 ± 150 kyr (29.80 ± 0.80 Ma to 29.67 ± 0.13 Ma), yielding a maximum magma flux of 3.05 x 10-2 km3/yr. We also provide a robust tie-point for calibration of the geomagnetic polarity timescale by integrating recalculated 40Ar/39Ar data with our high-precision 206Pb/238U ages to yield new constraints on the duration of the C11n.1r Subchron.
Role of Cassava CC-type Glutaredoxin MeGRXC3 in Regulating Sensitivity to Mannitol-Induced Osmotic Stress Dependent on its Nuclear Activity
Authors: Ruan Meng-Bin , Yu Xiao-Ling , Guo Xin , Zhao Ping-Juan , Peng Ming
Published: May 2021

BackgroundWe previously identified six drought-inducible CC-type glutaredoxins in cassava cultivars, however, less is known about their potential role in the molecular mechanism by which cassava adapted to abiotic stress. ResultsHerein, we investigate one of cassava drought-responsive CC-type glutaredoxins, namely MeGRXC3, that involved in regulation of mannitol-induced inhibition on seed germination and seedling growth in transgenic Arabidopsis. MeGRXC3 overexpression up-regulates several stress-related transcription factor genes, such as PDF1.2, ERF6, WRKY40, and WRKY53 in Arabidopsis. Protein interaction assays show that MeGRXC3 interacts with Arabidopsis TGA2 and TGA5 in the nucleus. Eliminated nuclear localization of MeGRXC3 failed to result mannitol-induced inhibition of seed germination and seedling growth in transgenic Arabidopsis. Mutation analysis of MeGRXC3 indicates the importance of conserved motifs for its transactivation activity in yeast. Additionally, these motifs are also indispensable for its functionality in regulating mannitol-induced inhibition of seed germination and enhancement of the stress-related transcription factors in transgenic Arabidopsis.Conclusions﻿MeGRXC3 overexpression confers mannitol sensitivity in transgenic Arabidopsis possibly through interaction with TGA2/5 in the nucleus, and nuclear activity of MeGRXC3 is required for its function.
Novel Er3+ doped heavy metals-oxyfluorophosphate glass as a blue emitter
Authors: Saeed Aly , Sobaih S. , Abu-raia W. , Abdelghany A. , Heikel Sh.
Published: May 2021

Developed P2O5-ZnO-PbO-WO3-NaF glasses containing Er3+ ions were prepared by the melt/casting procedures. X-ray diffraction patterns confirmed the amorphicity of the prepared materials. The density and Fourier Transform Infrared FTIR spectroscopy showed that Er3+ ions play a modifier role and the studied glasses have low phonon energy. The observed decrease in the measured glass transition temperature indicates that the decrease in the bonding strength of the studied glass structure. The studied glass has a high thermal stability. Vickers microhardness results showed the weakening of the glass network. Measured UV-Vis absorption spectra exhibited several bands in the ultraviolet and visible regions. The studied glass has a high refractive index. The metallization criterion showed that the studied glasses have an insulating behavior. The metallization criterion values of the present glasses are in the range of nonlinear optical materials. Under 320 nm excitation wavelength, the studied glass generates three blue bands at 446, 457, and 473 nm. The CIE-1931 chromaticity diagram coordinates confirmed the blue emission of the prepared glass. According to the obtained results, the produced glasses have a high potential for using as efficient luminescence materials for photonic devices in the blue region.
CRISPR/Cas9 assisted gene targeting efficiently inhibits bovine herpesvirus-1 replication
Authors: Deol Pallavi , Mahajan Sonalika , Nandi Sukdeb , Chander Vishal , Chaple Ashwini R. , Ganie Saima M , S. Bindu , Agrawal Ravikant , Singh Karam Pal , gupta Vivek kumar , Singh Raj kumar , Sharma Gaurav Kumar
Published: May 2021

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/ CRISPR associated protein (cas) are now being accepted as a highly specific method of gene editing. Among many other applications, CRISPR/cas has an immense potential to be used as antivirals. In this study, we successfully demonstrated CRISPR/Cas9 mediated inhibition of Bovine Herpes virus -1 (BHV-1) replication. BHV-1 causes economically important diseases in bovines with establishment of latency. Six essential genes and one non-essential gene of BHV-1 were targeted to assess the impact on virus replication. Inhibition of UL52, circ, and UL27 genes showed promising results, whereas the other three genes US6, UL18, and UL34 resulted in lower level of inhibition. Non-specific gene editing in host and virus was in-silico evaluated and was demonstrated by inhibition of virus induced apoptosis. Successful editing of one viral non-essential gene without any alterations in virus replication demonstrated the potential of CRISPR/Cas9 in replicating viral genome. Complete abrogation of virus replication was observed transiently (~24 hours post-transfection/hpt) when transfected with short lived in-vitro transcribed sgRNAs. Whereas, under constant expression of sgRNAs through plasmid, complete inhibition of virus replication was observed till ~72 hours post-infection. Complete inhibition of replication was also observed with in-vitro transcribed sgRNA when booster dose of sgRNA was trasnfected at 24hpt. It has been speculated that constant expression with plasmid based delivery may result in off-target activity which can be ruled out with short lived in-vitro transcribed sgRNA.
LDL mediated delivery of Paclitaxel and MRI imaging probes for personalized medicine applications
Authors: Rakhshan Sahar , Alberti Diego , Stefania Rachele , Bitonto Valeria , Crich Simonetta Geninatti
Published: May 2021

Background: The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by flow cytometry analysis. Results. PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 °C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel kabi (PTX Kabi) used in clinical applications. Tumour cells uptake was initially assessed by ICP-MS and MRI on B16-F10 cell line. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone. Conclusions. LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents. For the first time the anon invasive “in vivo” determination of the amount of PTX accumulated in the tumour was possible, thanks to the use of theranostic agents of natural origin.
Towards realistic modeling of plasmonic nanostructures: the comparative study to determine the impact of optical effects on solar cell improvement
Authors: Haidari Gholamhosain
Published: May 2021

Plasmonic structures may improve cell performance in a variety of ways. More accurate determining the optical influence, unlike ideal simulations, requires modeling closer to experimental cases. In this modeling, nonregular nanostructures were chosen and for simulation divided into three groups and some modes. For each mode, different sizes of nanoparticles were randomly selected which could result in pre-determined average particle size and standard deviation. By 3D-FDTD, the optical plasmonic properties of that mode in solar cell structure were investigated when nanostructure was added to the buffer/active layer of the organic solar cell. The far and near-field results were used to compare the plasmonic behavior, relying on the material and geometry. By detailed simulations, the Al and approximately Ag nanostructure at the interface of the ZnO/active layer can improve OSC performance optically, especially by the near-field effect. Unlike Au and relatively Ag, the Al nanostructured sample showed less parasitic absorption loss.
Comparison between Synthetic Oil Lubricants for Reducing Fretting Degradation in Lightly Loaded Gold-Plated Contacts
Authors: Chaudhary Rishabh , Kaushik Lovlesh , Azarian Michael H. , Pecht Michael
Published: May 2021

This paper presents a comparison between the performances of two chemistries of synthetic oil lubricants, polyalphaolefins (PAOs) and perfluoropolyethers (PFPEs) when applied on gold-plated electrical contacts operating at contact loads of 9.8 cN and experiencing fretting-induced degradation. Performance assessment was done using the contact resistance and coefficient of friction behavior and the surface’s response to fretting in the presence of different types of lubricants within the two chemistries. It was found that the PAOs improved the fretting performance of the lightly loaded contacts, and statistically, were at least fifty times more reliable for a longer duration of fretting cycles than the PFPEs, suggesting their suitability for low contact load applications. At low loads, PFPEs underwent contact separation due to hydrodynamic lubrication, and the behavior was more observable among the PFPEs having higher kinematic viscosities. On the contrary, viscous PAOs had improved fretting performance and delayed time to contact failure than less viscous PAOs. The applied lubricant film thickness also contributed to the contact’s performance, and it was found that increasing the thickness of the PFPE films advanced contact failures, while the PAO film postponed contact’s time to failure.
Comparison of Laminoplasty and Posterior Fusion Surgery for Cervical Ossification of Posterior Longitudinal Ligament
Authors: Nakashima Hiroaki , Imagama Shiro , Yoshii Toshitaka , Egawa Satoru , Sakai Kenichiro , Kusano Kazuo , Nakagawa Yukihiro , Hirai Takashi , Wada Kanichiro , Katsumi Keiichi , Fujii Kengo , Kimura Atsushi , Furuya Takeo , Kanchiku Tsukasa , Nagamoto Yukitaka , Oshima Yasushi , Nagoshi Narihito , Ando Kei , Takahata Masahiko , Mori Kanji , Nakajima Hideaki , Murata Kazuma , Matsunaga Shunji , Kaito Takashi , Yamada Kei , Kobayashi Sho , Kato Satoshi , Ohba Tetsuro , Inami Satoshi , Fujibayashi Shunsuke , Katoh Hiroyuki , Kanno Haruo , Li Yuanying , Yatsuya Hiroshi , Koda Masao , Kawaguchi Yoshiharu , Takeshita Katsushi , Matsumoto Morio , Yamazaki Masashi , Okawa Atsushi
Published: May 2021

This prospective multicenter study formed by the Japanese Ministry of Health, Labour and Welfare at 27 institutions aimed to compare postoperative outcomes between laminoplasty (LM) and posterior fusion (PF) for cervical ossification of the posterior longitudinal ligament (OPLL). Controversy exists regarding the role of instrumented fusion in the context of posterior surgical decompression for OPLL. Among the 479 patients enrolled, 189 (137 and 52 patients with LM and PF, respectively) were included and evaluated using the Japanese Orthopaedic Association (JOA) scores, the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiographical measurements. Basic demographic and radiographical data were reviewed, and the propensity to choose a surgical procedure was calculated. Preoperatively, patient backgrounds, radiographical measurements (K-line or cervical alignment on X-ray, OPLL occupation ratio on computed tomography, and increased signal intensity change on magnetic resonance imaging), or clinical status (JOA score and JOACMEQ) after adjustments showed no significant differences. The overall risk of perioperative complications was lower in LM (odds ratio [OR] 0.40, p = 0.006), and C5 palsy was significantly lower in LM (OR 0.11, p = 0.0002) than in PF. The range of motion (20.91° ± 1.05° and 9.38° ± 1.24°, p < 0.0001) in patients with PF was significantly smaller than in those with LM. However, multivariable logistic regression analysis showed no significant difference in JOA score, JOA recovery rate, or JOACMEQ improvement at two years. In contrast, OPLL progression was greater in LM group than in the PF group (OR 2.73, p = 0.0002). LM and PF for cervical myelopathy due to OPLL resulted in comparable postoperative outcomes at two years after surgery.
Delayed Fluorescence from Inverted Singlet and Triplet Excited States for Efficient Organic Light-Emitting Diodes
Authors: Miyajima Daigo , Aizawa Naoya , Pu Yong-Jin , Nihonyanagi Atsuko , Ibuka Ryotaro , Inuzuka Hiroyuki , Dhara Barun , Koyama Yuki , Araoka Fumito
Published: May 2021

Hund’s multiplicity rule states that for a given electronic configuration, a higher spin state has a lower energy. Rephrasing this rule for molecular excited states predicts a positive energy gap between spin-singlet and spin-triplet excited states, which has been consistent with numerous experimental observations over almost a century. Here, we report a fluorescent molecule that disobeys Hund’s rule, possessing a negative singlet–triplet energy gap of –11 meV. The energy inversion of the singlet and triplet excited states results in delayed fluorescence with short time constants of 0.2 μs, which anomalously decrease with decreasing temperature due to the emissive singlet character of the lowest-energy excited state. Organic light-emitting diodes using this molecule exhibited a fast transient electroluminescence decay with a peak external quantum efficiency of 17%, demonstrating potential implications for optoelectronic devices, including displays, lighting, and lasers.
Impact of The Distal Resection Margin On Local Recurrence After Neoadjuvant Chemoradiation and Rectal Excision For Locally Advanced Rectal Cancer
Authors: Song Seung Ho , Park Jun Seok , Choi Gyu-Seog , Seo An Na , Park Soo Yeun , Kim Hye Jin , Lee Sung-Min , Yoon Ghilsuk
Published: May 2021

We aimed to evaluate whether a short distal resection margin (< 1 cm) was associated with local recurrence in patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy. Patients with rectal cancer who underwent preoperative chemoradiotherapy followed by curative surgery were divided into two groups based on the distal resection margin (≥ 1 cm and < 1 cm). In total, 507 patients were analyzed. The median follow-up duration was 48.9 months. The 3-year local recurrence rates were 2% and 8% in the ≥ 1 cm and < 1 cm groups, respectively (p < 0.001). Multivariable analysis revealed that a distal resection margin of < 1 cm was a significant risk factor for local recurrence (p = 0.008). Subgroup analysis revealed that a distal resection margin of < 1 cm was not an independent risk factor for local recurrence in the ypT0–1 group. However, among patients with tumor stages ypT2–4, the cumulative 3-year incidences of local recurrence were 2.3% and 9.8% in the ≥ 1 cm and < 1 cm groups, respectively (p = 0.001). A distal resection margin of < 1 cm might influence local recurrence rates in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy, especially in patients with tumor stages ypT2–4.
Integrating Health Literacy into a Theory-Based Drug-Use Prevention Program: A Quasi-Experimental Study Among Junior High Students in Taiwan.
Authors: LIN Li-Chen , GUO Jong-Long , Huang Chiu-Mieh , Hsu Hsiao-Pei , LIAO Jung-Yu , LIN Cheng-Yu
Published: May 2021

BackgroundIn Taiwan, illegal drug use is a critical health problem during adolescence. Schools play a vital role in preventing students’ illegal drug use. Accordingly, we developed and evaluated a school-based, drug-use prevention program integrating the theory of planned behavior (TPB) and health literacy for junior high school students.MethodsWe recruited 648 junior high school students from 14 selected schools: N= 323 in the experimental group, N= 325 in the comparison group. The experimental group received ten 45-minute sessions of a theory-based drug-use prevention program. The comparison group received traditional didactic teaching and drug refusal skill training. We used a generalized estimating equation (GEE) to analyze data.ResultsResults of paired t-tests indicated that drug-use health literacy and TPB-related variables improved in the experimental group. The GEE analyses indicated that participants in the experimental group also demonstrated significantly improved health literacy (p < 0.001) compared to the comparison group, especially for functional (p< 0.001) and critical health literacy (p = 0.017). The experimental group also showed significant post-intervention improvement in terms of subjective norm scores (p = 0.024). Conclusion﻿Study results demonstrated the effectiveness of a drug-use prevention program on health literacy and subjective norm by integrating the TPB and health literacy. These results could support the future implementation of drug-use prevention programs for junior high school students on a larger scale.
Hierarchical Coordinated Anti-Jamming Channel Access in Clustering Networks: A Multi-Leader Multi-Follower Stackelberg Game Approach
Authors: Xu Yifan , Chen Jin , Feng Zhibin , Yao Kailing , Li Guoxin , Song Fei , Fang Gui
Published: May 2021

This paper mainly investigates the multi-user coordinated anti-jamming problem in clustering communication networks. In such kinds of networks, there exist multiple clusters, and multiple users who communicate with their receivers simultaneously. Besides, a malicious jammer persistently attacks channels with wide-band and dynamic changing jamming signals. To cope with these challenges brought by the large-scale clustering network and the dynamic wide-band jamming, a hierarchical coordinated anti-jamming approach is proposed, and a multi-leader multi-follower Stackelberg game is introduced to model the anti-jamming problem. In detail, cluster heads act as leaders, and select available frequency bands to avoid jamming attacks. While users in each cluster act as followers, and select corresponding channels distributedly and independently. Moreover, it is proved that there exist multiple Stackelberg Equilibriums (SEs) in the proposed game. To obtain SEs, a hierarchical coordinated anti-jamming channel access (HCACA) algorithm is designed. Simulation results illustrate that the proposed approach is effective to cope with the dynamic wide-band jamming attacks. Furthermore, it is also depicted that the proposed approach outperforms the distributed anti-jamming comparative approach in terms of convergence speed.
Comparison of Safety and Efficacy of Warfarin Versus Rivaroxaban in Northern Chinese Patients With Different CHA2DS2-VASc Score
Authors: Xu Shiwei , Guo Yuanyuan , Li Xianghui , dong zengxiang , Hai Xin
Published: May 2021

Purpose: Although many researches have indicated the anticoagulant effect of warfarin and rivaroxaban in atrial fibrillation (AF) patients, the comparison of these drugs on safety and efficacy in northern Chinese patients with different CHA2DS2-VASc Score is unclear. We aim to compare the safety and efficacy of warfarin versus rivaroxaban in northern Chinese AF patients with different CHA2DS2-VASc Score subgroups. Methods: 387 AF patients were recruited in the study. Of these, one group patients (n=194) were receiving warfarin, and the other group patients (n=193) were receiving rivaroxaban. Follow-up data were collected for one year, which included adherence, bleeding and ischemic stroke (IS) events. Results: There was better adherence in rivaroxaban-treated group than warfarin-treated group. The events of bleeding decreased with increased score in warfarin-treated group. Patients with score 2-3, had better adherence and less stroke events in warfarin-treated group. The events of bleeding and stroke was not significantly different in rivaroxaban-treated group at different score. Conclusions: We found that there was better adherence and less bleeding and stroke events in rivaroxaban-treated group than warfarin-treated group with different CHA2DS2-VASc score. There is better choice for northern Chinese patients to select rivaroxaban in the anticoagulative treatment of AF, regardless of economic factors.
Rapidly Dissolving Microneedle Patch of Amphotericin-B for Intracorneal Fungal Infections.
Authors: Albadr Alyaa A. , Tekko Ismaiel A. , Vora Lalitkumar K. , Ali Ahlam A. , Laverty Garry , Donnelly Ryan F. , Thakur Raghu Raj
Published: May 2021

Chronic fungal infection of the cornea could lead to blindness if not treated properly. Topical AMP-B is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea leads to poor bioavailability. Microneedles (MNs) are emerging as a minimally-invasive method to enhance ocular drug delivery. Therefore, this study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA) based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays' reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs as microdevice successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MNs arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch.
Optimization of Mycoremediation Potential of A Fungi: Aspergillus Ochraceus Strain
Authors: Ozyurek Sezen Bilen , Avcioglu Nermin Hande , Bilkay Isil Seyis
Published: May 2021

Mycoremediation is an important process that targets the removal of petroleum hydrocarbons by fungi. Accordingly, colorimetric method was used in the preliminary investigation of petroleum degradation with ten fungal strains as Aspergillus ochraceus, Aspergillus parasiticus, Aspergillus niger, Fusarium acuminatum, Fusarium graminearum, Fusarium equiseti, Fusarium oxysporum, Paecilomyces lilac, Penicillium crustosum, and Penicillium chrysogenum. Petroleum degradation of spore suspension, live biomass (fungal pellet and disc) and cell-free culture supernatant of the potent A. ochraceus strain were determined by gravimetric analysis. It was obtained that the fungal disc (94%) was more successful than the spore suspension (87%) in petroleum degradation under optimized conditions as pH:5.0, 1% of petroleum concentration, %5 (v/v) of inocum concentration, 1 g/100mL of inoculum amount and 7 days of incubation period. The degradation rate constant and half-life period of spore suspension were calculated as 0.291 day− 1 and t1/2 = 0.340 and of fungal disc were 0.401 day− 1 and t1/2 = 0.247. 7.5% and 10% (v/v) concentration of cell-free culture supernatant were achieved more than 80% of petroleum removal. However, the cell-free culture supernatant was not as effective as fungal disc. According to GC/MS analysis, the fungal disc of A. ochraceus strain degraded long chain n-alkanes such as C35 and C36 more effectively than n-alkanes in the range of C22-C34. Drop-collapse and oil-spreading methods showed that A. ochraceus is a good biosurfactant producer. This study clearly pointed out that Aspergillus ochraceus NRRL 3174 strain with high its removal capacity can be used as an effective agent in petroleum bioremediation process.
A Novel miRNA Y-56 Mediates The Proliferation of Porcine Skeletal Muscle Satellite Cells By Targeting IGF-1R
Authors: Song Jie , Hao Linlin , Zeng Xiangfang , Yang Rui , Qiao Shiyan , Wang Chunli , Yu Hao , Wang Siyao , Jiao Yingying , Liu Songcai , Cheng Yunyun
Published: May 2021

Background: The skeletal muscle phenotype of the Bama Xiang pig (BM) is significantly different from the Landrace pig (LP). Uncovering the mechanism of porcine skeletal muscle growth will be of great significance to elucidate the mechanism of the different formation. As the key post-transcriptional regulators, miRNAs play an indispensable role in skeletal muscle development. The proliferation of skeletal muscle satellite cells not only maintain the muscle stem cell population, but also provide a large number of muscle derived cells. Thus, the goal of this study is to explore the effects of a novel miRNA Y-56 on the porcine skeletal muscle satellite cells (PSCs). Results: Firstly, we found that Y-56 was highly expressed in porcine muscle tissues, and its expression was higher in the BM than the LP. The EdU staining and CCK-8 assays results showed that increased levels of Y-56 suppressed cell proliferation, whereas decreased levels of Y-56 resulted in the opposite consequences. Furthermore, flow cytometry results showed that overexpression of Y-56 significantly reduced the percentage of S-phase cells, and the qRT-PCR and western blotting results showed that the expression levels of cyclin dependent kinase 2 (CDK4), proliferating cell nuclear antigen (PCNA) and Cyclin D1 were significantly inhibited. Moreover, downregulation of Y-56 increased the number of S-phase cells and the expression of CDK, PCNA and Cyclin D1. Furtherly, we identified that insulin like growth factor-1 receptor (IGF-1R) was a direct target of Y-56. Consistently, overexpression of IGF-1R promoted the cell proliferation of the PSCs, and increased the number of S-phase cells, as well as up-regulated the expressions of CDK4, PCNA and Cyclin D1. Meanwhile, knock-down of IGF-1R was associated with the opposite tend. Finally, overexpression of IGF-1R partially reversed the inhibition of cell proliferation of the PSCs, the decrease of the percentage of S-phase cells and down-regulation of the expression levels of CDK4, PCNA and Cyclin D1, which caused by overexpression of Y-56. Conclusion: Collectively, our findings suggested that Y-56 represses proliferation and cell cycle process of the PSCs through several biological mechanisms involving downregulation of IGF-1R.
Diagnosis, Treatment of Type I Autoimmune Pancreatitis and Management of Relapse and Side Effects After Steroid Treatment
Authors: Tang Neng , Dou Xiaolin , Liu Guodong , You Xing , Ou Zhenglin , Ke Mujing , Yi Xiaoping , Ji Liandong
Published: May 2021

Background: Autoimmune pancreatitis (AIP) is a rare disease, have a dramatic response to steroid therapy, but the relapse rates(RRs) is very high, and the side effects of steroid therapy are inevitable. The aim of this study is to focus on the management of relapse and side effects. Methods: A single-centre, retrospective, cohort study of the type Ⅰ AIP patients admitted to Xiangya Hospital Central South University from September 2008 to September 2019 conducted. Collection and retrospectively analyzed the clinicopathologic data and outcomes of these patients. Results: 82 patients were included, 73.2% were histologically confirmed. 78.0% treated by medications: 62.5% prednisolone, 37.5% prednisolone plus cyclophosphamide. The RRs of the two group have no significant difference (35.0% vs 29.2%, P = 0.630). Increasing the dosage of prednisolone, the effective rate of the prednisolone treatment and prednisolone plus cyclophosphamide treatment relapsed patients were 78.57% and 71.43%, respectively. The side effects were DM in 12.5%; central obesity in 15.6%; hyperlipidemia in 18.8%; gastric ulcer in 6.3%; osteoporosis in 9.4%; bone fracture in 1.6%. For those side effects patients performed low dose prednisolone and expectant treatment have a ideal results. Conclusions: Increasing the dose of prednisolone can effectively treat relapsed patients. Low dose steroid and expectant treatment should be performed when side effects arised.
Potential Influence of Factors For Genu Valgus With Hereditary Multiple Exostoses
Authors: Liu Ya , Fang Jianfeng , Liu Yao , Zhang Zheng , Wang Xiaodong , Guo Zhixiong , Zhang Fuyong
Published: May 2021

The authors have requested that this preprint be removed from Research Square.
Modified Techniques Versus Hadfield’s Procedure in Patients With Periductal Mastitis
Authors: Dalci Kubilay , Gumus Serdar , Saritas Ahmet Gokhan , Gul Mehmet Onur , Rencuzogullari Ahmet , Akcam Atilgan Tolga , Ulku Abdullah , Ergin Melek , Sakman Gurhan
Published: May 2021

Background: Periductal mastitis (PM) is a rare disease characterized by chronic inflammation of the terminal mammary ducts. Complete removal of the terminal canals with Hadfield’s operation applied in the treatment carries various complication risks. This study is designed to evaluate the effectiveness of modified techniques and compare them with the Hadfield operation.Methods: Twenty women who underwent surgery due to PM between January 2012 and December 2019 were retrospectively analyzed. Types of PM were determined. All patients were operated on with three different incisions (Hadfield’s operation with periareolar incision, periareolar combined with radial incision, and round block incision). Results: The age mean 37.5±6.5 years (range:24-49). Sixty percent of patients had type three PM. For the affected duct excision, a classic Hadfield’s operation with periareolar incision was performed in 11 patients, periareolar incision combined with radial incision was performed in 7 patients. The round block method was performed on two patients. Seroma was observed in only one of the patients who underwent the modified technique. In Hadfield’s procedure, NAC retraction (n:2), seroma (n:1), and hematoma (n:1) were seen. The follow-up period was 12±1.5 months. Recurrence occurred in two patients, and both had Hadfield’s procedures. Conclusions: The main principle of surgical treatment is excision of the affected canal with a clear margin. In PM treatment, The round block method and periareolar incision combined radial incision modifications of the Hadfield procedure reduce complications and recurrence risk.
Designing Highly Multiplex PCR Primer Sets with Simulated Annealing Design using Dimer Likelihood Estimation (SADDLE)
Authors: Zhang David , Xie Nina , Wang Michael , Song Ping , Wang Yifan , Yang Yuxia , Luo Junfeng
Published: May 2021

The design of highly multiplex PCR primers to amplify and enrich many different DNA sequences is increasing in biomedical importance as new mutations and pathogens are identified. One major challenge in the design of highly multiplex PCR primer sets is the large number of potential primer dimer species that grows quadratically with the number of primers to be designed. Simultaneously, there are exponentially many choices for multiplex primer sequence selection, resulting in systematic evaluation approaches being computationally intractable. Here, we present and experimentally validate Simulated Annealing Design using Dimer Likelihood Estimation (SADDLE), a stochastic algorithm for design of highly multiplex PCR primer sets that minimize primer dimer formation. Our approach uses a rapidly computable Loss function to approximate the degree of primer dimer formation within a primer set, and randomly swaps primers in the set with alternative candidates using a simulated annealing algorithm. In a 96-plex PCR primer set (192 primers), we show that we can reduce the fraction of primer dimers from 90.7% in a naively designed PCR primer set to 4.9% in our optimized primer set. Running the optimized 96-plex primer set on FFPE DNA samples from cancer patients, we likewise observe a low fraction of primer dimer reads. Even when scaling to 384-plex (768 primers), the PCR primer set designed by our algorithm maintains low primer dimer fraction. In addition to NGS, we also show that our SADDLE-designed multiplex primer sets can be used in qPCR settings to allow highly multiplexed detection of gene fusions in cDNA, with a single-tube assay comprising 60 primers detecting 56 distinct gene fusions recurrently observed in lung cancer.
Amplified Antitumor Efficacy By A Targeted Drugs Retention and Chemosensitization Strategies-Based “Combo” Nanoagent Together With PD-L1 Blockade In Reversing Multidrug Resistance
Authors: Jiang Weixi , Su Lei , Ao Meng , Guo Xun , Cheng Chen , Luo Yuanli , Xie Zhuoyan , Wang Xingyue , Wang Junrui , Liu Shuling , Cao Yang , Li Pan , Wang Zhigang , Ran Haitao , Ren Jianli , Zhou Zhiyi
Published: May 2021

Background: Recent studies have demonstrated that multidrug resistance (MDR) plays a critical role in the low efficiency of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results: In this study, we fabricated a “combo” nanoagent equipped with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape that enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to relieve the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that the versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumor. Conclusion: This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors compared to an equivalent dose of free paclitaxel by using multiple MDR reversing strategies.
Cooperative interaction between ERα and the EMT-inducer ZEB1 reprograms breast cancer cells for metastasis
Authors: Ghahhari Nastaran , Sznurkowska Magdalena , Hulo Nicolas , Bernasconi Lilia , Aceto Nicola , Picard Didier
Published: May 2021

The epithelial to mesenchymal transition (EMT) has been proposed to contribute to the metastatic spread of breast cancer cells. EMT-promoting transcription factors determine a continuum of different EMT states. In contrast, estrogen receptor α (ERα) helps to maintain the epithelial phenotype of breast cancer cells and its expression is crucial for effective endocrine therapies. Determining whether and how EMT-associated transcription factors such as ZEB1 modulate ERα signaling during early stages of EMT could promote the discovery of novel therapeutic approaches to suppress metastasis. We have discovered that, shortly after induction of EMT and while cells are still epithelial, ZEB1 modulates ERα-mediated transcription induced by estrogen or cAMP signaling in breast cancer cells. Based on these findings and our ex vivo and xenograft results, we suggest that the functional interaction between ZEB1 and ERα may alter the tissue tropism of metastatic breast cancer cells towards bone.
Health-promoting Prisons in the Female Estate: An Analysis of Prison Inspection Data
Authors: James Woodall , Charlotte Freeman , Louise Warwick-Booth
Published: May 2021

Background: Women in prison has comparatively greater health needs than men, often compounded by structures and policies within the prison system. The notion of a ‘health-promoting’ prison is a concept which has been put forward to address health inequalities and health deterioration in prisons. It has, however, not been fully discussed in relation to women in prison. The paper aims to distil the learning and evidence in relation to health promotion in female prisons using prison inspection reports of women’s prisons in England and Wales. Methods: Prison inspection reports are one way of ascertaining the contemporary situation in prisons. Prison inspections are often unannounced and use a myriad of methods to draw conclusions around various aspects of prison life. Thirteen prison inspection reports were analysed thematically focusing on health promotion within the institutions. Two analysts conducted the work using NVivo 12. Results: Five core thematic areas were identified during the analysis of the reports. Saliently, a joined-up approach to health promotion was not a common feature in the prisons and indeed the focus tended to be on screening and ‘lifestyle issues’ rather than a concern for the underlying determinants of health. There was often an absence of a strategic approach to health promotion. There were some good examples of the democratic inclusion of women in prison in shaping services, but this was not widespread and often tokenistic. There were some examples of inequity and the inspection reports from a small number of institutions, illustrated that the health needs of some women remained unmet. Conclusions: The paper suggests that there is potentially some work before conditions in women’s prisons could be described as ‘health-promoting’, although there are some examples of individual prisons demonstrating good practice. The health promoting prison movement has, implicitly at least, focused on the needs of men in prison and this has been to the exclusion of the female prison population. This does lead to several challenges and the potential for exacerbating health challenges faced by an already marginalised and vulnerable group. Greater focus on the health promotion needs of women in prison is required.