bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular Disease and Risk of Incident Diabetes Mellitus: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Missikpode Celestin , Durazo-Arvizu Ramon , cooper richard , O'Brien Matthew , Castaneda Sheila , Talavera Gregory , Gallo Linda , Llabre Maria , Perera Marisa , Perreira Krista , Ricardo Ana , Pirzada Amber , Lash James , Daviglus Martha L
Published: February 2021

Introduction Studies have reported an association between cardiovascular disease (CVD) and risk of diabetes mellitus (DM). The mechanisms underlying this association remain unclear. We examined the association of CVD with incident DM and assessed the roles of weight gain and medication use as mediating factors. Methods Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) and Visit 2 (2014-2017) were used to compare incidence of DM among individuals with and without self-reported CVD at Visit 1. A total of 2081 individuals with self-reported CVD were matched to controls free of self-reported CVD at Visit 1 using 1:1 propensity score matching. Covariates included in the propensity model were sociodemographic characteristics, lifestyle factors, comorbid conditions, and study site. The effect of self-reported CVD on incident DM was examined using Generalized Estimating Equation. The mediating effects of weight gain and use of cardiovascular medications were evaluated. ResultsCovariate distributions were similar among individuals with and without self-reported CVD. The incidence of DM among persons with self-reported CVD was 15.6% vs. 12.7% among those without self-reported CVD. Compared to individuals without self-reported CVD, individuals with self-reported CVD had a 28% increased risk for incident DM (OR=1.28, 95%CI= 1.07, 1.52). The association between self-reported CVD and DM was mediated by the use of beta-blockers (proportion mediated=31%), statins (proportion mediated=24%), and diuretics (proportion mediated=8%). We found that weight gain did not explain the observed association.ConclusionsCardiovascular disease was associated with a significant increased risk of incident diabetes. The observed association was partially mediated by some medications used to manage CVD.
Comprehensive Assessment of Left Atrial and Ventricular Remodeling in Paroxysmal Atrial Fibrillation by Cardiovascular Magnetic Resonance Myocardial Extracellular Volume Fraction and Feature Tracking Strain
Authors: Yamada Akimasa , Hashimoto Naoki , Fujito Hidesato , Hatta Takumi , Saito Yuki , Otsuka Naoto , Wakamatsu Yuji , Arai Masaru , Watanabe Ryuta , Kurokawa Sayaka , Kitano Daisuke , Nagashima Koichi , Yoda Shunichi , Okumura Yasuo
Published: February 2021

Atrial fibrillation (AF) is a progressive disease that starts with structural or functional changes in the left atrium and left ventricle, and evolves from paroxysmal toward sustained forms. Early detection of structural or functional changes in the left atrium and left ventricle in the paroxysmal stage could be useful for identifying higher risk of progression to persistent AF and future cardio-cerebrovascular events. The aim of this study was to test the hypothesis that feature tracking (FT) left atrial (LA) strain and left ventricular (LV) extracellular volume fraction (ECV) derived from cardiovascular magnetic resonance (CMR) could detect the early changes of remodeling in the left atrium and ventricle in the stage of paroxysmal AF (PAF).Participants comprised 106 PAF patients (age, 66.1 ± 10.7 years; 66% male) who underwent clinical CMR before pulmonary vein isolation and 20 control subjects (age, 68.3 ± 8.6 years; 55% male). CMR-FT LA strain/phasic function and LV-ECV were compared between the PAF and control groups. Total and passive LA empty fraction (LAEF) and LA strain (corresponding to LA reservoir and conduit function) were decreased in the PAF group compared to the control group. However, active LAEF (corresponding to LA booster pump function) did not differ significantly between the PAF group (33.9 ± 10.9%) and control group (37.9 ± 13.3%, p = 0.15), while active LA strain (corresponding to LA booster pump function) was significantly decreased in the PAF group (11.4 ± 4.3 vs. 15.2 ± 5.6%, p = 0.002). LV-ECV was significantly greater in the PAF group (28.7 ± 2.8%) than in the control group (26.6 ± 2.0%, p = 0.002). In the PAF group, LV-ECV correlated significantly with E/e’ and LA volume index. Regarding LA strain, correlations were seen between LV-ECV and both reservoir function and conduit function.CMR-FT LA strain in combination with LV-ECV offers a potential imaging marker that identifies LA/LV remodeling including subtle LA booster pump dysfunction undetectable by conventional booster pump LAEF in the stage of PAF. These findings provide new insights into LA-LV interactions and further investigation regarding association between perpetuation of AF and LA functional remodeling in PAF patients.
Following De Novo Triglyceride Dynamics in Ovaries of Aedes Aegypti Mosquitoes
Authors: Tose Lilian Valadares , Weisbrod Chad R. , Michalkova Veronika , Nouzova Marcela , Noriega Fernando G. , Fernandez-Lima Francisco
Published: February 2021

Understanding the molecular and biochemical basis of egg development is a central topic in mosquito reproductive biology. Lipids are a major source of energy and building blocks for the developing ovarian follicles. Ultra-High Resolution Mass Spectrometry (UHRMS) combined with in vivo metabolic labeling of follicle lipids with deuterated water (2H2O) can provide unequivocal identification of de novo lipid species during ovarian development. In the present study, we followed de novo triglyceride (TG) dynamics during the ovarian previtellogenic (PVG) stage (2-7 days post-eclosion) of female adult Aedes aegypti. The incorporation of stable isotopes from the diet was evaluated using liquid chromatography (LC) in tandem with the high accuracy (<0.3 ppm) and high mass resolution (over 1M) of a 14.5 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (14.5 T FT-ICR MS) equipped with hexapolar detection. LC-UHRMS provides effective lipid class separation and chemical formula identification based on the isotopic fine structure. The monitoring of stable isotope incorporation into de novo incorporated TGs suggests that ovarian lipids are consumed or recycled during the PVG stage, with variable time dynamics. These results provide further evidence of the complexity of the molecular mechanism of follicular lipid dynamics during oogenesis in mosquitoes.
Safety of Subclavian Venous Catheterization Using Anatomical Landmark Technique Versus Ultrasound-Guided Internal Jugular Central Venous Method Inserted in The Neuro-Intensive Care Unit
Authors: Eibach Michael , Kilinc Fatma , Gessler Florian , Strouhal Ulrich , Seifert Volker , Behmanesh Bedjan
Published: February 2021

Background:Central venous (CV) catheterization is one of the important interventions used for various purposes. Accordingly, this study aimed to compare the complication rates of internal jugular vein (IJV) assisted by ultrasound with those of subclavian vein (SCV) catheterization using the anatomical landmark technique.Methods:Prospective, nonrandomized, single center study. Data from patients undergoing central venous catheterization either via IJV or SCV were recorded. The overall complication rate as well as number of attempts and catheter misplacement were analyzed comparing both methodsResults:Data from 398 (IJV: 206; SCV:192) patients were analyzed. The rate of pneumothorax did not demonstrate a significant difference between the IJV (0.5 %) and SCV (2.1 %) groups, p = 0.2. The success rate on the first attempt was similar in both groups (64%; p = 1.0). More catheter misplacements were observed in the SCV group (4.7%) than in the IJV group (3%), p = 0.4.Conclusions:Our results demonstrated that the complication rates of anatomical landmark guided SCV is very low and comparable to US guided IJV method.
Effects of Different Straw Biochar Combined With Microbial Inoculants on Soil Environment of Ginseng
Authors: Qi Yuqi , Liu Haolang , Wang Jihong , Wang Yingping
Published: February 2021

Ginseng is an important cash crop. The long-term continuous cropping of ginseng causes the imbalance of soil environment and the exacerbation of soil-borne diseases, which affects the healthy development of ginseng industry. In this study, ginseng continuous cropping soil was treated with microbial inocula using broad-spectrum biocontrol microbial strain Frankia F1. Wheat straw, rice straw and corn straw were the best carrier materials for microbial inoculum. After treatment with microbial inoculum prepared with corn stalk biochar, the soil pH value, organic matter, total nitrogen, available nitrogen, available phosphorus, and available potassium were increased by 11.18%, 55.43%, 33.07%, 26.70%, 16.40%, and 9.10%, the activities of soil urease, catalase and sucrase increased by 52.73%, 16.80% and 43.80%, respectively. A Metagenomic showed that after the application of microbial inoculum prepared fromwith corn stalk biochar, soil microbial OTUs, Chao1 index, Shannon index, and Simpson index increased by 19.86%, 16.05%, 28.83%, and 3.16%, respectively. Three classes (Alphaproteobacteria, Gammaproteobacteria and Sphingobacteria) were the dominant bacteria in ginseng soil, and their abundance increased by 7.87%, 9.81% and 1.24%, respectively, after treatment with microbial inoculum (corn stalk biochar). Results indicated that the most effective treatment in ginseng soil ould be the combined application of corn stalk biochar and Frankia F1.
A Cross-Case Analysis of Developing Program Sustainability and Institutionalization in Early Stages of a Multisite Biomedical Student Diversity Initiative
Authors: Cobian Krystle Palma , Ramos Hector V.
Published: February 2021

Background: Grant funding often drives innovative programming in efforts to enhance diversity in biomedical fields, yet strategies for sustainability of grant-funded biomedical intervention are not well understood. Additionally, as funding agencies shift toward supporting institutional change to biomedical training, less is known about the extent to which sustainability strategies can support long-term institutionalization of the original goals of the grant-funded initiative. The purpose of this study is twofold: to identify strategies used by grant-funded programs for promoting sustainability, and to examine the interrelations between the concepts of sustainability and institutionalization during early stages of grant-funded biomedical career training efforts. Methods: We employed a multiple case study design and cross-case analysis using interviews of program administrators and participants from 10 undergraduate institutions that received Building Infrastructure Leading to Diversity (BUILD) awards funded by the National Institutes of Health (NIH).Results: BUILD sites engaged in the following strategies to develop program sustainability: 1) scaling and adapting to expand programmatic impact, 2) identifying additional funding and cost-cutting measures, 3) developing and maintaining infrastructure and structural operations, 4) leveraging relationships and with intra-and inter-institutional partners, and 5) and addressing hiring, policies, and reward systems at the institution. Senior administrative support supported program sustainability and early institutionalization, although we also identified situations where participants felt that they were on track for sustainable changes without administrative support or institutional change. Of the strategies identified, those that involve organizational and infrastructural changes contribute to early stages of institutionalization. Conclusions: This study provides evidence of distinctions and interrelations between program sustainability efforts and institutionalization of change efforts in that some programs employed sustainability strategies that also strived toward institutionalization. Findings indicate the importance of program administrators developing early sustainability plans that also lead to institutionalization, as well as an opportunity for funding agencies to develop technical assistance on sustainability, organizational change, and institutionalization as a resource to support program administrators’ efforts toward making lasting change on their campuses.
Safety, Pharmacokinetics, and Preliminary Efficacy of Talazoparib in Japanese Patients With Advanced Solid Tumors: Phase 1 Study
Authors: Naito Yoichi , Kuboki Yasutoshi , Ikeda Masafumi , Harano Kenichi , Matsubara Nobuaki , Toyoizumi Shigeyuki , Mori Yuko , Hori Natsuki , Nagasawa Takashi , Kogawa Takahiro
Published: February 2021

Background: Talazoparib is a poly(ADP-ribose) polymerase enzyme inhibitor. This open-label, non-randomized, phase 1 study of talazoparib investigated the safety, pharmacokinetics, and preliminary antitumor activity in Japanese patients with locally advanced or metastatic solid tumors, regardless of mutations in DNA damage repair-related genes, who are resistant to/ineligible for standard therapies.Methods: Patients received talazoparib dosed orally at 0.75 or 1 mg once daily using a modified 3+3 dose-escalation scheme. Primary endpoint was dose-limiting toxicities during the first cycle of talazoparib.Results: Nine patients (median age 62.0 years) were included: 3 and 6 patients at the 0.75 and 1.0 mg once-daily dose level, respectively. No dose-limiting toxicities were reported. The most commonly reported treatment-emergent adverse events (≥2 patients) were anemia, stomatitis, maculopapular rash, platelet count decreased, neutrophil count decreased, and alanine aminotransferase increased. Three patients had grade ≥3 treatment-emergent adverse events (anemia, brain metastases [1 patient each], and neutrophil and white blood cell count decreased [same patient]). Two patients temporarily discontinued treatment due to a treatment-emergent adverse event, and 1 patient required a dose reduction for neutrophil count decreased (all at 1 mg once daily). Talazoparib exposure (Cmax and AUC) after single and multiple dosing was slightly higher proportionally with talazoparib 1 mg than talazoparib 0.75 mg. The overall disease control rate was 44.4%, including 2 patients with stable disease. The recommended phase 2 dose of talazoparib was established as 1 mg once daily.Conclusions: Single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors. Clinical Trial Register: clinicalTrials.govClinical Registration Number: NCT03343054 (November 17, 2017)
Promoting Economic Growth and Environmental Sustainability Through Energy Efficiency: Evidence From Indonesia
Authors: Tenrini Rita Helbra , Damayanty Sofia Arie , Setyawan Dhani , Setiawan Hadi , Rakhmindyarto Rakhmindyarto
Published: February 2021

Indonesia has set a unilateral greenhouse gas emissions (GHG) emissions reduction target by 29% and conditional targets with international support of up to 41%, compared to the business as usual by 2030. This paper aims to formulate energy conservation policies to increase productivity and promote economic growth in Indonesia. Indonesia's energy conservation policy has multiple aspects: supporting energy security, commitment to GHG emission reduction, state budget efficiency, and improving productivity and competitiveness. Using Social Accounting Matrix (SAM), this study found evidence that energy efficiency saving will positively affect ecological sustainability and economic agents in the five targeted sectors: energy, waste, industrial processes, product use, agriculture, and forestry. Further, the Corporate Social Responsibility (CSR) policy provides positive effects in increasing economic growth and reducing income disparities.
Aging and MPTP-Sensitivity Depend on Molecular and Ultrastructural Signatures of Astroglia and Microglia in Mice Substantia Nigra
Authors: Abhilash PL , Bharti Upasna , Philip Mariamma , Rashmi Santhosh Kumar , Raju Trichur R , Kutty Bindu M , Sagar BK Chandrasekhar , Alladi Phalguni Anand
Published: February 2021

BackgroundBoth astroglia and microglia show region-specific distribution pattern in the central nervous system and often maladapt to age-associated alterations within their niche. Studies on autopsied substantia nigra of Parkinson’s disease (PD) patients and experimental models propose gliosis as a trigger for neuronal loss. Epidemiological studies propose an ethnic bias in PD prevalence, since Caucasians are more susceptible than non-whites living in Asia and Africa. Similarly, different mice strains are variably sensitive to the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). We had earlier likened divergent MPTP-sensitivity of C57BL/6J and CD-1 mice with differential susceptibility to PD, based on differences in neuronal numbers.MethodsHere we examined whether the variable susceptibility was also incumbent to inter-strain differences in the glial features in the substantia nigra pars compacta (SNpc) of C57BL/6J and CD-1 mice. We performed unbiased stereology to quantify iba-1 immunoreactive microglia and s100β immunopositive astroglia on immunohistochemically stained sections. Further, ELISA based estimation of pro- inflammatory and anti-inflammatory cytokines was supplemented with estimation of enzymes like fractalkine, hemeoxygenase, and monoamine oxidases A and B. Electron microscopy was performed to compare the effects on the organelles.ResultsStereological counts showed more microglia and fewer astrocytes in the substantia nigra of MPTP-susceptible normal C57BL/6J mice, which suggests persistence of an immune-vigilant state. MPTP caused induction of microgliosis and astrogliosis in both strains, suggesting the involvement of these cells in pathogenesis. ELISA of pro-inflammatory cytokines in the ventral-midbrain revealed augmentation of TNF-α and IL-6 at middle-age in both strains that reduced at old-age, suggesting middle-age as a critical, inflamm-aging associated time-point. TNF-α levels were persistently high in C57BL/6J, through aging and post-MPTP; while IL-6 and IL-1β were upregulated at old-age. CD-1 had higher levels of anti-inflammatory cytokine TGF-β. MPTP-challenge caused upregulation of enzymes MAO-A, MAO-B and iNOS in both strains. Post-MPTP enhancement in fractalkine and hemeoxygenase-1, may be neuronal compensatory signals. Lastly, ultrastructural observations of elongated mitochondria in astroglia and microglia vis-à-vis the shrunken ones in neurons, suggest upscaling of their functions with neurotoxic consequences.ConclusionsThus, astroglia and microglia play a critical role in modulating aging and the susceptibility of an individual to PD.
Novel Variants in DNAH9 Lead to Nonsyndromic Severe Asthenozoospermia
Authors: Tang Dongdong , Sha Yanwei , Gao Yang , Zhang Jingjing , Cheng Huiru , Zhang Junqiang , Ni Xiaoqing , Wang Chao , Xu Chuan , Geng Hao , He Xiaojin , Cao Yunxia
Published: February 2021

Background Asthenozoospermia is one of the most common causes of male infertility, and its genetic etiology is poorly understood. DNAH9 is a core component of outer dynein arms in cilia and flagellum. It was reported that variants of DNAH9 (OMIM: 603330) might cause primary ciliary dyskinesia (PCD). However, variants in DNAH9 lead to nonsyndromic severe asthenozoospermia have yet to be reported.Methods Whole exome sequencing (WES) was performed for two individuals with nonsyndromic severe asthenozoospermia from two non-consanguineous families, and Sanger sequencing was performed to verify the identified variants and parental origins. Sperm routine analysis, sperm vitality rate and sperm morphology analysis were performed according the WHO guidelines 2010 (5th edition). Transmission electron microscopy (TEM, TECNAI-10, 80 kV, Philips, Holland) was used to observe ultrastructures of sperm tail. Quantitative realtime-PCR and immunofluorescence staining were performed to detect the expression of DNAH9-mRNA and location of DNAH9-protein. Furthermore, assisted reproductive procedures were applied.Results By WES and Sanger sequencing, compound heterozygous DNAH9 (NM_001372.4) variants were identified in the two individuals with nonsyndromic severe asthenozoospermia (F1 II-1: c.302dupT, p.Leu101fs*47 / c.6956A>G, p.Asp2319Gly; F2 II-1: c.6294T>A, p.Phe2098Leu / c.10571T>A, p.Leu3524Gln). Progressive rates less than 1% with normal sperm morphology rates and normal vitality rates were found in both of the two subjects. No respiratory phenotypes, situs inversus or other malformations were found by detailed medical history, physical examination and lung CT scans etc. Moreover, the expression of DNAH9-mRNA was significantly decreased in sperm from F1 II-1. And expression of DNAH9 is lower in sperm tail by immunofluorescence staining in F1 II-1 compared with normal control. Notably, by intracytoplasmic sperm injection (ICSI), F1 II-1 and his partner successfully achieved clinical pregnancy. Conclusions We identified DNAH9 as a novel pathogenic gene for nonsyndromic severe asthenospermia, and ICSI can contribute to favorable pregnancy outcomes for these patients.
Women's Knowledge and Attitude Towards Cervical Cancer Preventive Measures and Associated Factors in South Gondar Zone, Amhara Region, North Central Ethiopia: a Cross-sectional Study
Authors: Tafere Yilkal , Jemere Tezera , Desalegn Tsion , Melak Addisu
Published: February 2021

Background: The aim of the current research was to assess women's knowledge and attitudes towards cervical cancer preventions in South Gondar zone. Methods: A community-based cross-sectional study was carried out in South Gondar zone, Ethiopia. A total of 844 women aged 18 and above have participated in the current study. Binary and multivariable logistic models were used to assess predictors of women’s knowledge and attitude towards cervical cancer.Results: About 66% of the women had heard about cervical cancer. The percentage of women who heard about cervical cancer was 66%. Regarding the main source of information of respondents, 75.4% were heard from health professionals. Sixty two point four percent of women knew at least one preventive measure and 82.6% of participants knew at least one symptom or sign. Among study participants, 25% and 64% had good knowledge, and favorable attitude towards cervical cancer prevention measures, respectively. Being reside in rural (AOR= .21, 95%CI; .18, .34), not attending formal education (AOR = 0.50, 95% CI: 0.3, 0.75), low income (AOR = .57, 95% CI: .43, .81) and having <4 children ((AOR = .8, 95% CI: .60–.86) were negatively associated with knowledge toward cervical cancer prevention measures Conclusion: This study found the majority of the respondents had poor knowledge about cervical cancer prevention measures. The majority of the study participants had favorable attitudes regarding cervical cancer prevention. Living in rural areas, not attending any formal education low income and having less than four children was negatively associated with respondents' knowledge towards cervical cancer prevention measures. There is needed to scale up cervical cancer prevention measures and services
Swarm Shedding in Networks of Self-propelled Agents
Authors: Hindes Jason , Edwards Victoria , Kasraie Klimka Szwaykowska , Stantchev George , Schwartz Ira B.
Published: February 2021

Understanding swarm pattern-formation is of great interest because it occurs naturally in many physical and biological systems, and has artificial applications in robotics. In both natural and engineered swarms, agent communication is typically local and sparse. This is because, over a limited sensing or communication range, the number of interactions an agent has is much smaller than the total possible number. A central question for self-organizing swarms interacting through sparse networks is whether or not collective motion states can emerge where all agents have stable and coherent dynamics. In this work we introduce the phenomenon of swarm shedding in which weakly-connected agents are ejected from stable milling patterns in self-propelled swarming networks with finite-range interactions. We show that swarm shedding can be localized around a few agents, or delocalized, and entail a simultaneous ejection of all agents in a network. Despite the complexity of milling motion in complex networks, we successfully build mean-field theory that accurately predicts both milling state dynamics and shedding transitions. The latter are described in terms of saddle-node bifurcations that depend on the range of communication, the inter-agent interaction strength, and the network topology.
Analysis of Hepatocellular Carcinoma Stereotactic Body Radiation Therapy Dose Prescription Method Using Uncomplicated Tumour Control Probability Model
Authors: Cheung Michael L M , Kan Monica W K , Chan Anthony T C
Published: February 2021

Background: This work was to establish an uncomplicated tumour control probability (UTCP) model using Hepatocellular Carcinoma Stereotactic Body Radiation Therapy (HCC SBRT) clinical data in our institution. The model was then used to analyze the treatment outcome of the current dose prescription method and to seek the opportunity for improvement.Methods: A tumour control probability (TCP) model was generated based on local clinical data using the maximum likelihood method. A UTCP model was then formed by combining the established TCP model with the normal tissue complication probability (NTCP) model based on the study by Dawson et al. The authors investigated the dependence of maximum achievable UTCP on tumor mean biological effective dose (BED) at various ratio between tumour mean biological effective dose (BED) and normal liver mean BED (T/N BED ratios). A new term uncomplicated tumour control efficiency (UTCE) was also introduced to analyze the outcome. A UTCE value of 1 implied that the theoretical maximum UTCP for the corresponding T/N BED ratio was achieved.Results: The UTCE of the HCC SBRT patients based on the current dose prescription method was found to be 0.90±0.08. It was found that the UTCE could be increased to 0.99±0.03 by using a new dose prescription scheme, for which the UTCP could be maximized while keeping the NTCP value smaller than 5 %. Conclusion: The treatment outcome of the current HCC SBRT in our institution was analyzed using a UTCP model established based on local clinical data. It was shown that there could be a potential to increase the prescription dose of HCC SBRT. A new dose prescription scheme was proposed to achieve better treatment outcome.
Safety of Radiotherapy in Patients with Cardiac Implantable Electronic Devices
Authors: Han Donghoon , Lee Ji Hyun , Cho Youngjin , Oh Il-Young
Published: February 2021

Background: Patients with cardiac implantable electronic devices (CIEDs) usually have multiple comorbidities, and some require radiotherapy (RTx) for cancer treatment. However, the effect of RTx in patients with CIEDs is unclear. We aimed to examine the effectiveness of RTx in patients with CIEDs, and share our real-world clinical experience in this population.Methods: We recruited patients with a pacemaker or implantable cardioverter-defibrillator who underwent RTx between April 2009 and August 2019. RTx and CIED interrogation data were collected from electronic medical records. Patients who received an RTx cardiology consultation and CIED interrogation before and after RTx were assigned to the proper consultation (PC) group. All others were enrolled in the no-consultation (NC) group. Results: Out of 23 patients, 3 (13.0%) and 20 (87.0%) patients were assigned to the PC and NC groups, respectively. The most common RTx sites were the abdomen and pelvis (34.8%). The mean cumulative dose was 50.1 ± 11.7 Gy, and the mean beam energy was 10.3 ± 4.01 mV. The PC and NC groups showed no significant difference in cumulative dose (51.5 ± 12.1 vs. 45.3 ± 3.9, p=0.19) or beam energy (10.4 ± 4.03 vs. 7.0 ± 1.41, p=0.08). There was no significant between-group difference in any pre-RTx CIED parameter. Two patients died during the study period; both were in the NC group. The relationship between death and device malfunction was not clear in either case.Conclusions: Patients with CIEDs frequently do not receive a cardiology consultation before RTx. Although radiotherapy-related CIED complications occur stochastically and are difficult to predict, cooperation between the cardiology and radiation therapy departments, and regular device follow-up are necessary for the safety of these patients.
Neoadjuvant Chemoradiotherapy in Patients With Unresectable Locally Advanced Sigmoid Colon Cancer: Clinical Feasibility and Outcome
Authors: Niu Shao-Qing , Li Rong-Zhen , Yuan Yan , Xie Wei-Hao , Wang Qiao-Xuan , Chang Hui , Lu Zhen-Hai , Ding Pei-Rong , Li Li-Ren , Wu Xiao-Jun , Zeng Zhi-Fan , Xiao Wei-Wei , Gao Yuan-Hong
Published: February 2021

Background: Patients with locally advanced sigmoid colon cancer (LASCC) have limited treatment options and a dismal prognosis with poor quality of life. This prospective study aimed to further evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by surgery as treatment for select patients with unresectable LASCC.Methods: We studied patients with unresectable LASCC who received NACRT between November 2010 and April 2019. The NACRT regimen consisted of intensity modulated radiotherapy (IMRT) of 50 Gy to the gross tumor and positive lymphoma nodes and 45 Gy to the clinical target volume. Capecitabine‑based chemotherapy was administered every 3 weeks. Surgery was scheduled 6–8 weeks after radiotherapy.Results: Seventy‑two patients were enrolled in this study. Patients had a regular follow-up (median, 41.1 months; range, 8.3–116.5 months). Seventy‑one patients completed NACRT, and sixty-five completed surgery. Resection with microscopically negative margins (R0 resection) was achieved in 64 patients (88.9%). Pathologic complete response was observed in 15 patients (23.1%), and multivisceral resection was necessary in 38 patients (58.3%). The cumulative probability of 3-year overall survival and disease‑free survival were 75.8% and 70.7%, respectively.Conclusion: For patients with unresectable LASCC, neoadjuvant chemoradiotherapy is feasible, surgery can be performed safely and may result in increased survival and organ preservation rates.
Family-centered Approach to Monitoring Children’s Development in a Paediatric Outpatient Setting: Feasibility Study From Pakistan
Authors: Rasheed Muneera A. , Mughis Waliyah , Elahi Kinza N , Hasan Babar S.
Published: February 2021

Background: The purpose of the study was to design and test the feasibility of a recent guideline of family-centered psychosocial support as an approach to developmental monitoring in a pediatric outpatient setting.Methods: The patient experience team at a private tertiary care hospital leveraged an on-going patient and family-centric initiative in the service to implement the intervention. The intervention delivery model was designed using the theory of change model and entailed the following i) the service providers: paediatricians but with support from psychology trainee volunteers to address time constraints; ii) monitoring form: Survey of Well-Being of Young Children (SWYC) being feasible and designed for regular developmental monitoring as parent report; iii) family support intervention: the Care for Child Development module to enhance parent-child interactions given team’s successful experience with inpatient children; iv) timing: utilize wait time to also enhance families’ experience and v) reinforcement: reinforced by the paediatrician in the consultation visit to capitalize on the established rapport and relationship with families. All families with children under 5 years 5 months of age in selected clinics (acute care, complex care, developmental issues) were eligible. The study was evaluated for acceptability and implementation feasibility. Families were interviewed about their experience; trainees provided a written narrative while physicians provided feedback on email. These were thematically analyzed using an inductive approach.Results: A total 182 families were administered the SWYC with 54% children detected for further review on cognitive milestones and 76% on social-emotional milestones. Forty-eight families were interviewed regarding their experience with the intervention. They reported the monitoring process to be useful and important for them as parents indicating acceptability. Paediatricians and trainees found the intervention to be important for parents and children’s health also requesting further understanding about child’s functioning. The trainees further expressed the experience to be significant for their own learning.Conclusion: The authors conclude that the intervention model for a family-centric approach to monitoring was acceptable to the families and the service providers. The intervention when implemented using a robust behaviour change framework can enhance feasibility.
The Influence of Hypoglycemia on the Specific Quality of Life in Type 2 Diabetes Mellitus: a Comparative Cross-sectional Study of Diabetics With and Without Hypoglycemia in Xi'an, China
Authors: Chao Wu , Yiling Ge , Xinyan Zhang , Mingchao Liu , Chunni Heng , Linyuan Zhang , Yanling Du , Shizhe He , Lei Shang , Hongjuan Lang
Published: February 2021

Purpose This study aims to explore the incidence of hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and the influence of hypoglycemia on the specific quality of life in T2DM patients.Methods It was a comparative cross-sectional study consisting of 519 T2DM patients in Xi'an, China and patients were investigated by self-reported hypoglycemia and specific quality of life questionnaires during September 2019 to January 2020. Descriptive analysis, t-test, Chi-square test, hierarchical regression analysis and stepwise multiple regression analysis were used to assess the influence of hypoglycemia on the specific quality of life. Results The incidence of hypoglycemia in T2DM patients was 32.18%. The mean score of specific quality of life in diabetes without hypoglycemia was 57.33±15.36 and was 61.56±17.50 in those with hypoglycemia, which indicated that hypoglycemia had a serious impact on the quality of life diabetics (t＝-5.172, p＝0.000). In the Univariate analysis of specific quality of life, age, education background, marital status, living status, duration of diabetes, monthly income per capita were independent and significant factors associated with specific quality of life of two groups of T2DM patients (P<0.05). In the hierarchical regression analysis, the duration of the diabetes more than 11 years and the frequency of hypoglycemia more than 6 times in half a year entered the equation of specific quality of life of 519 diabetics respectively (P<0.001). In multiple linear regression analysis, age, marital status and income both entered the regression equation of quality of life of the two groups (P<0.05).Conclusion Hypoglycemia will have a serious impact on the quality of life of T2DM patients. In order to improve the living quality in diabetics, effective measurements should be taken to strengthen the management of blood glucose and avoid hypoglycemia.
Quality of Life and Its Contributors Among Adults With Late-onset Pompe Disease in China
Authors: Chen Shanquan , Wang Jingxuan , Zhu Jianfeng , Chung Roger Yat-Nork , Dong Dong
Published: February 2021

Background: Pompe disease (PD) is a rare inherited disorder caused by the deficiency of acid-ɑ glucosidase, which leads to the impairment of organ and tissue functions and causes disabilities. As the first national survey on patients with late-onset PD (LOPD) in China, this study investigated the quality of life (QOL) of adult patients with LOPD in China and explored its contributors. Methods: Data were derived from a nation-based, cross-sectional, self-response survey on rare diseases in early 2018. Answers from 68 adult Chinese patients with LOPD were used for data analysis. QOL was measured using the World Health Organization Quality of Life: Brief Version (WHOQOL-BREF). Covariates included age, gender, education, employment, reliance on assistive devices, medication history, social support, and disease economic burden. Data were analyzed using linear regression in R.Results: For adult patients with LOPD, the average scores and standard deviations (SD) of the four dimensions of QOL were physical health=33.77 (SD=18.28), psychological health=43.81 (SD=21.70), environmental health=39.43 (SD=16.93), and social relationship=46.20 (SD=19.76); the scoring for each dimension was evaluated on a scale of 0 to 100. At the significance level of p<0.05, with increasing age, the patients experienced a significant decrease in physical health QOL (β=-0.75) and environmental health QOL (β=-0.79). Those who relied heavily on assistive devices had lower perceived physical health (β=-17.8), psychological health (β=-22.76), environmental health (β=-17.8), and social relationships (β=-22.12) than those who did not. A one-unit increase in the amount of social support, as a form of social interaction, led to a significant increase in physical health (β=0.28), psychological health (β=0.71), environmental health (β=0.72), and social relationships (β =0.70).Conclusion: Adult Chinese patients with LOPD had a lower physical health and QOL compared to their counterparts with other rare diseases. Being employed was found to affect the QOL of adult Chinese patients with LOPD in almost all dimensions. Encouraging adult Chinese patients with LOPD to be socially active and help them become more involved in social life might improve their QOL.
Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis
Authors: Offermanns Stefan , Wang ShengPeng , Shi Yue , Moeller Tanja , Stegmeyer Rebekka , Strilic Boris , Xu Liran , Yuan Zuyi , Wettschureck Nina , Vestweber Dietmar
Published: February 2021

The extravasation of leukocytes is a critical step during inflammation which requires the localized opening of the endothelial barrier. This process is initiated by the close interaction of leukocytes with various adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) on the surface of endothelial cells. It is still unclear how these initial processes induce downstream signaling events resulting in the opening of inter-endothelial junctions to allow leukocyte diapedesis. Here we show that mechanical forces induced by leukocyte-induced clustering of ICAM-1 and fluid shear stress exerted by the flowing blood synergistically activate the mechanosensitive cation channel PIEZO1 in endothelial cells. In human and mouse endothelial cells exposed to low flow, PIEZO1 mediates leukocyte-induced increases in [Ca2+]i and activation of downstream signaling events including phosphorylation of SRC, PYK2 and myosin light chain (MLC) leading to endothelial barrier opening. Mice with endothelium-specific loss of Piezo1 show decreased leukocyte extravasation in different inflammation models. We found that actin polymerization and actomyosin contraction induced by ICAM-1 clustering synergistically with fluid shear stress increase endothelial plasma membrane tension to activate PIEZO1. Our data reveal a mechanism by which leukocytes and the hemodynamic microenvironment synergize to mechanically activate endothelial PIEZO1 and subsequent downstream signaling to initiate leukocyte diapedesis.
Potent Mixed Backbone Antisense Oligonucleotide Safety Suppressed Expression of Mutant C9ORF72 Transcripts and Polypeptides: First in Human Pilot Study
Authors: Brown Robert , Tran Hélène , Moazami Michael , Yang Huiya , McKenna-Yasek Diane , Douthwright Catherine , PINTO Courtney , Metterville Jake , Shin Minwook , Sanil Nitasha , Dooley Craig , Puri Ajit , Weiss Alexandra , Wightman Nichols , Gray-Edwards Heather , Marosfoi Miklos , King Robert , Kenderdine Thomas , Fabris Dan , Bowser Robert , Watts Jonathan
Published: February 2021

Expansions of a G4C2 repeat in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating adult-onset neurodegenerative disorders. Proposed disease mechanisms include a gain of toxic functions of the G4C2 repeats, implying that selective reduction in levels of the repeat-containing transcripts would represent a treatment strategy for this disorder. In the present study, using C9-ALS/FTD patient derived cells and C9ORF72 BAC transgenic mice, we have generated and optimized antisense oligonucleotides (ASOs) that selectively blunt expression of G4C2 repeat containing transcripts in both the sense and anti-sense strands of C9ORF72 and effectively suppress tissue levels of polyGP dipeptides. In a single patient harboring mutant C9ORF72 with the G4C2 repeat expressions, repeated dosing by intrathecal delivery of the optimal ASO was well tolerated, leading to significant reductions in levels of CSF polyGP.
A Study on Interferential Tool Position Correcting Algorithm in Rough Machining of 3d Impeller Variable-axis Plunge Milling
Authors: Dong Lei , Wang Jie
Published: February 2021

The plunge milling method has remarkably improved the rough machining efficiency of 3D impeller channel. However, in conventional cutter position planning for plunge milling, interference at the end of every cutter position due to sudden increase of radial depth is inevitable, which may seriously compromise the service life of machine tool and cutter, as well as the cutting efficiency at the interferential phase. This study optimized the cutter axis vector for the tool path of conventional rough machining of 3D impeller variable -axis plunge milling to make the angle between the normal vector for workpiece surface at the cutter contact point and the cutter-axis vector of adjacent tool position increase gradually from outlet to inlet at the smallest scale. Based on this, an iterative algorithm for tool center position and safety height for the cutter was provided, thus making the hub allowance of the optimized tool path for plunge milling as small as possible without affecting the subsequent machining on the premise of avoiding the interferential phenomenon. Finally, the correctness of the proposed method was verified by relevant numerical examples.
Guanidinium and phosphonium scaffolds loaded with silver nanoparticles: synthesis, characterization, in vitro assessment of the antibacterial potential and toxicity
Authors: Gorbunova M. N. , Lemkina L.M. , Nechaev A.I.
Published: February 2021

New silver nanocomposites based on polysulfones of 2,2-diallyl-1,1,3,3-tetraethylguanidiniumchloride [poly(AGC-SO2)], tris(diethylamino)diallylaminophosphonium tetrafluoroborate [poly(DAAP-BF4-SO2)] and chloride [poly(DAAP-Cl-SO2)] have been developed. UV- spectroscopy, SEM and XRD techniques were used to characterize the formation of silver nanoparticles in copolymers. Antibacterial action of new silver nanocomposites on S. epidermidis 33 and Escherichia coli (planktonic cells and biofilms) was studied. The silver nanocomposites strongly inhibited biofilms formation of S. epidermidis 33 and Escherichia coli. The silver nanocomposites based on phosphonium polysulfones have a significant cytotoxic activity against RD and MS line cells.
Docosahexaenoic Acid and Lactoferrin Effects on the Brain and Placenta in a Rabbit Model of Intrauterine Growth Restriction 
Authors: Illa Miriam , Pla Laura , Loreiro Carla , Miranda Cristina , Mayol Montse , Kühne Britta Anna , Barenys Marta , Eixarch Elisenda , Gratacós Eduard
Published: February 2021

Intrauterine growth restriction (IUGR) is associated with suboptimal perinatal outcomes and neurodevelopment in the offspring. We hypothesize that prenatal supplementation with docosahexaenoic acid (DHA) or lactoferrin (Lf) would ameliorate these consequences. At 25 days of gestation, IUGR was surgically induced in pregnant rabbits, which were randomized as follows: no treatment, or DHA or Lf administration. DHA or Lf were administrated orally once per day. Five days later, animals were delivered obtaining controls, untreated IUGR, IUGR treated with DHA and IUGR treated with Lf, and the associated placentas. At postnatal day 1, a functional evaluation was performed and, thereafter, brains were obtained. Neuronal arborization in the prefrontal cortex and the density of pre-oligodendrocytes in the corpus callosum were then evaluated. Untreated IUGR pups presented a higher percentage of stillbirth, lower birth weight, and poorer neurobehavioral performance in comparison with control pups, and these are associated with structural changes in brain and placenta. Regarding treated IUGR animals, although no significant improvements were detected in perinatal data, functional and structural effects were observed in either the brain or the placenta. DHA and Lf supplements in a rabbit model of IUGR were related to neurodevelopmental improvements and an amelioration of the placental changes.
Enhancing Machine Learning Algorithms to Assess Rock Burst Phenomena
Authors: Papadopoulos Dimitrios , Benardos Andreas
Published: February 2021

One of the main challenges that deep mining faces is the occurrence of rockburst phenomena. Rockburst risk assessment with the use of machine learning is currently gaining increased attention, due to the fact that outperforms the widely used empirical approaches. However, the limited and imbalanced instance records, combined with the multiparametric nature of the phenomenon, can lead to unstable estimations. This study focuses on the enhancement of the prediction performance of five machine learning algorithms, including Decision Trees, Naïve Bayes, K-Nearest Neighbor, Random Forest and Logistic Regression, by utilizing the oversampling technique SMOTE (Synthetic Minority Oversampling TEchnique).The initial database consists of 249 rockburst incidents, from which approximately 70% was used as the training set and the remaining 30% as the test set. Parametric analyses were conducted regarding different indicator combinations, such as the maximum tangential stress, the rock’s uniaxial compressive and tensile strength, the stress coefficient, two brittleness coefficients and the elastic energy index. The models were trained with the original dataset and afterwards a gradual increase of the database with synthetic instances was made until the obtainment of a balanced dataset. Subsequently the creation of synthetic instances was continued until the real incidents used for training and the synthetic incidents were of the same amount. The results from the following analysis show that SMOTE technique has a considerable effect in the evaluation metrics of the models, even after the balancing of the dataset, and can be a valuable asset for the rockburst prediction.
Bark-stripping of Common Buckthorn by Goats During Managed Browsing on Bur Oak Savannas
Authors: Mundahl Neal , Walsh Ryan
Published: February 2021

Goats are being used increasingly to manage woody invasive plants in woodland habitats, but their specific impacts on those plants over a period of time during active, periodic browsing has not been documented. This study investigated bark-stripping by goats browsing on common buckthorn in savanna habitats, focusing on possible size-selective feeding and the cumulative effects of repeated, periodic browsing over a 3-year period. When surveyed after the first browsing period, bark was stripped selectively on buckthorn stems 20 to 60 mm in diameter. Approximately 60% of all stripped stems were completely girdled, but only 14-17% of stems were bark-stripped. After five browsing periods, 66% of standing stems displayed bark stripping and 39% were completely girdled. Buckthorn densities were reduced by 90% compared to the first browsing period, the decline resulting mostly from consumption of foliage and terminal shoots of small (<20 mm) buckthorn and bark-stripping resulting in top-kill in intermediate-sized (20-60 mm) plants. Large buckthorn (>60 mm) were largely unimpacted by goats. Relatively few (28%) seedling buckthorn were browsed by goats, although >90% of 2nd-year plants were browsed. Buckthorn can be managed in part via goat browsing, but repeated, periodic browsing over several to many years may be necessary to produce a significant impact, and other techniques will be needed to eliminate large, seed-producing plants.