bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hospital-Based Independent Domestic Violence Advisor Service: Demand and Response During the COVID-19 Pandemic
Authors: Elvey Rebecca , Mason Thomas , Whittaker William
Published: August 2021

Background and aimRecent UK policy hasfocussed on improving support for victims of domestic violence and abuse (DVA), in healthcare settings. DVA victims attending hospital are often at highest risk of harm, yet DVA support in hospitals has been inadequate. A targeted service supportinghigh risk DVA victims, was implemented at a hospital Trust in North West England. The service was provided by Independent Domestic Violence Advisors (IDVAs).An evaluation exploredthe processes and outcomes associated with the service. The evaluation coincided with the COVID-19 pandemicand societal restrictions (lockdown), during which concern about DVA increased. This paper examines the hospital-based IDVA service during the COVID-19 period and addresses the research questions: What was the demand for the service? How did the service respond? What facilitated this response?MethodsA mixed-methods study was undertaken. Quantitative data on referrals to the service were examined using simple descriptive statistics and compared to other DVA services.Semi-structured interviews were undertaken with IDVAs and other hospital staff involved with the service and the data subjected to thematic analysis. ResultsThe quantitative analysis showed that referrals dropped at the start of lockdown, then increased and continued to rise; the qualitative findings reiterated this pattern. Referrals came from a range of departments across the Trust, with the majority from A&E. Pre-pandemic, the population supported by the service included higher proportions of males and people aged 40 and over than atother IDVA services; this continuedduring the pandemic. The qualitative findings indicated an effective, flexible response during the pandemic, enabled by strong working relationships and by using workarounds.ConclusionsThe hospital-based IDVA service provided a robust response to victims during the COVID-19 pandemic. Referrals increased during the firstlockdown and subsequent relaxing of restrictions. Locating the IDVAswithina team working across the organisation, and building good working relationships facilitatedan effective disclosure and referral route, which endured through social restrictions. The IDVAs supported high-risk victims who may otherwise not have been identified in traditional community-based DVA settings during the pandemic. Hospital-based IDVA services can broaden accessby supporting vulnerable, at risk populations whose needs may not be identified at other services.
Genomic Analysis of Molecular Bacterial Mechanisms of Resistance to Phage Infection
Authors: Ambroa Antón , Blasco Lucia , López María , Pacios Olga , Bleriot Inés , Fernández-García Laura , Ortiz-Cartagena Concha , Millard Andrew , Tomás María
Published: August 2021

BackgroundIn order to optimize phage therapy, we need to understand how bacteria evolve against phage attack. One of the main problems of the phage therapy is the appearance of bacterial resistance variants. The use of genomics to track antimicrobial resistance is increasingly developed and used in clinical laboratories. For that reason, it is important to consider, in an emerging future with phage therapy, to detect and avoid phage resistant strains, that can be overcomed by the analysis of metadata provided by WGS. Here, we identified genes associated with phage resistance in 18 Acinetobacter baumannii clinical strain belonging to the ST-2 clonal complex during a decade (Ab2000 vs 2010): 9 from 2000 and 9 from 2010.ResultsThe presence of genes putatively associated to phage resistance were detected. Genes detected were associated with an abortive infection system, restriction-modification system, genes predicted to be associated with defence systems but with unknown function and CRISPR-Cas system. Between 118 and 171 genes were found in the 18 clinical strains. On average, 26% of these genes were detected inside genomic islands (GIs) in the 2000 strains and 32% in 2010 strains. Furthermore, 38 potential CRISPR arrays in 17 of 18 of the strains were found, as well as 705 proteins associated with CRISPR-Cas systems.ConclusionsA moderately higher presence of these genes in the strains of the 2010 in comparison to those of the 2000 were found, especially those related to the R-M system and CRISPR-Cas system. The presence of these genes in GIs in a higher rate in the strains of the 2010 compared to those of the 2000 was also detected. WGS and bioinformatics could be powerful tools to avoid drawbacks when a personalized therapy is applied. In this study, it allows us to take care of the phage resistance in A. baumannii clinical strains to prevent a failure in a possible phage therapy.
Universe: the dynamics of the minimum and maximum expansion states
Authors: Petrakis Sócrates
Published: August 2021

Two hypotheses stand out in describing the evolution of the Universe. The predominant one predicts that the current expansion began at a certain instant and will not preserve any variation of energy that performs work; apparent flat Universe (Ω = 1) is advocated by relativistic calculations and observational data, with an end or thermal death at its maximum expansion (3D space). The other hypothesis considers that the Universe is cyclical (always alternating phases of expansion and contraction). This proposal aims to demonstrate that both hypotheses can be correct by not being distinct, but complementary. Supported by the immutability of physical laws, analyses of concepts such as space, mass, energy, gravity, spin, and entropy define an exclusive presence of 1D space in the minimum and maximum expansion states of the Universe. With our 3D space Universe created and existing between these extreme states, a complete universal evolution is outlined. More objectively, all the exposed dynamics complements the usual relativity. The concept of complete rest energy (1D space) was able to be applied, demonstrating that the evolution of the entire Universe is spatially dynamic in a perpetual time dimension, always recreating our Universe.
Evaluation of Different Imaging Modalities for Axillary Lymph Node Staging in Breast Cancer Patients to Provide A Personalized and Optimized Therapy Algorithm
Authors: Diessner Joachim , Anders Laura , Herbert Saskia , Kiesel Matthias , Bley Thorsten , Schlaiss Tanja , Sauer Stephanie , Wöckel Achim , Bartmann Catharina
Published: August 2021

Purpose The prognostic importance of lymph node infiltration in breast cancer patients before and after neoadjuvant therapy has increased significantly in recent years. For that reason, the reliable detection of tumor-infiltrated axillary lymph nodes at the time of diagnosis plays a decisive role in further therapy. We therefore focused on the sensitivity of different pretherapeutic imaging modalities (sonography, mammography, computed tomography [CT] and magnetic resonance imaging [MRI]) in nodal positive breast cancer patients and aimed to find out whether cross-sectional imaging techniques (MRI, CT) could improve sensitivity for pretherapeutic axillary staging compared to conventional imaging such as mammography and sonography. Methods Breast cancer patients with tumor-infiltrated axillary lymph nodes between 2014 and 2020 having a surgery for breast cancer were included in the study. Results All included 382 breast cancer patients had received conventional imaging, while 52.61% of the patients had received cross-sectional imaging. The sensitivity of the combination of all imaging modalities was 68.89%. The combination of MRI and CT showed 63.83% and the combination of sonography and mammography showed 36.11% sensitivity.Conclusion We could demonstrate that cross-sectional imaging can improve the sensitivity of the detection of tumor-infiltrated axillary lymph nodes in breast cancer patients. Considering the increasing importance of neoadjuvant and post-neoadjuvant therapeutic algorithms, the reliable detection of tumor-infiltrated lymph nodes gains increasing importance. Only the safe detection of tumor-infiltrated lymph nodes at the time of diagnosis enables the evaluation of the response to neoadjuvant therapy and thereby allows access to prognosis–improving post-neoadjuvant therapies.
The Role of Synovial Fluid Aspiration in Shoulder Joint Infections
Authors: Streck Laura Elisa , Forster Johannes , von Hertzberg-Boelch Sebastian Philipp , Reichel Thomas , Rudert Maximilian , Rueckl Kilian
Published: August 2021

Background: Joint aspiration with analysis of synovial fluid white blood cell count (WBC) and microbiological culture is a widely established aspect in the diagnosis of shoulder joint infections (SJI). In case of a two stage revision for SJI, joint aspiration before re-/implantation of an total shoulder arthroplasty (TSA) was used to rule out persistent infection for years but its value is under debate. Shoulder specific data on all aspects is rare. The current study aims to answer the following research questions: Joint aspiration has an insufficient predictive value in the diagnosis of SJI in (1) initial workup and (2) before definite arthroplasty with polymethylmethacrylate (PMMA)-Spacer in place. Methods: This retrospective evaluation investigates 35 patients that were treated for SJI with a two staged implantation of a TSA after debridement and implantation of an PMMA-Spacer. Joint aspirations were performed preoperatively (PA) and before re‑/implantation of the prosthesis while spacer was in place (interstage aspiration, IA). Samples were taken for microbiological culture and analysis of WBC. Sensitivity and specificity were calculated with reference to intraoperative microbiological samples. Receiver Operating Characteristic (ROC), Area-Under-Curve analysis (AUC) and calculation of the Youden index were performed to find optimum cut-off for WBC. Results: The sensitivity of microbiological cultures from PA was 58.3% and the specificity was 88.9%. The mean WBC was 27 800 leucocytes/mm3 (range 400-96 300). The maximum Youden index (0.857) was a cut-off of 2600 leucocytes/mm³ with a sensitivity of 85.7% and a specificity of 100.0%. The sensitivity and specificity of IA were 0.0% and 88.5%, respectively. Conclusions: PA is likely to miss Cutibacteria spp. Cuand CoNS and cannot rule out infection for sure. However, we recommend PA for its advantages of targeted antibiotic therapy in case of germ identification. Empiric antibiotic therapy should therefore cover these bacteria even if aspiration showed negative microbiological cultures. In contrast, diagnostic value of IA does not qualify for routine use. Trial registration: The study was approved by the ethic committee of the author`s institution (registration number 235/16-mk). The patients gave written informed consent to their inclusion in the study.
Prostate cancer histopathology with label-free multispectral deep UV microscopy quantifies phenotypes of tumor grade and aggressiveness
Authors: Soltani Soheil , Ojaghi Ashkan , Qiao Hui , Kaza Nischita , Li Xinyang , Dai Qionghai , Osunkoya Adeboye , Robles Francisco
Published: August 2021

Identifying prostate cancer patients that are harboring aggressive forms of prostate cancer remains a significant clinical challenge. To help address this problem, we develop an approach based on multispectral deep-ultraviolet (UV) microscopy that provides novel quantitative insight into the aggressiveness and grade of this disease. First, we find that UV spectral signatures from endogenous molecules give rise to a phenotypical continuum that differentiates critical structures of thin tissue sections with subcellular spatial resolution, including nuclei, cytoplasm, stroma, basal cells, nerves, and inflammation. Further, we show that this phenotypical continuum can be applied as a surrogate biomarker of prostate cancer malignancy, where patients with the most aggressive tumors show a ubiquitous glandular phenotypical shift. Lastly, we adapt a two-part Cycle-consistent Generative Adversarial Network to translate the label-free deep-UV images into virtual hematoxylin and eosin (H&E) stained images. Agreement between the virtual H&E images and the gold standard H&E-stained tissue sections is evaluated by a panel of pathologists who find that the two modalities are in excellent agreement. This work has significant implications towards improving our ability to objectively quantify prostate cancer grade and aggressiveness, thus improving the management and clinical outcomes of prostate cancer patients. This same approach can also be applied broadly in other tumor types to achieve low-cost, stain-free, quantitative histopathological analysis.
Existence and Stability of the Periodic Orbits Induced by Grazing Bifurcation in a Cantilever Beam System with Single Rigid Impacting Constraint
Authors: Liu Run , Yue Yuan , Xie Jianhua
Published: August 2021

Grazing which can induce many nonclassical bifurcations, is a special dynamic phenomenon in some non-smooth dynamical systems such as vibro-impact systems with clearance. In this paper, the existence and stability of the periodic orbits induced by the grazing bifurcation in a cantilever beam system with impacts are uncovered. Firstly, the Poincaré mapping of the system is obtained by the discontinuous mapping method. Secondly, the periodic orbits are determined by means of shooting method, and Jacobian matrix in the case of non-impact is obtained subsequently. Thirdly, for various impacting patterns, a combination of inhomogeneous equations and inequations is obtained to determine the existence of period orbits after grazing. Furthermore, the stability criterion of the grazing-induced periodic orbits is given. Numerical results verify the effectiveness of theoretical analysis. What’s more, we also give a conjecture about the relationship between eigenvalues and the type of periodic orbits when eigenvalues are imaginary numbers.
Assessing the Transition From Pre-Clerkship to Clerkship in a Four-Year Medical Program: Recommendations for Future Success
Authors: Mistry Neel , de Laplante Stefan , Campbell Craig Murray
Published: August 2021

Background: The transition from pre-clerkship to clinical clerkship is a pivotal moment for medical students. At the University of Ottawa Faculty of Medicine, Unit IV and the Link Block are designed to facilitate this transition. Improvements to the current curriculum, specifically in Unit IV, may better prepare students for clerkship. We aimed to summarize existing literary evidence on the transition to clerkship and collect student feedback to generate recommendations for success with regard to clerkship preparedness at the University of Ottawa Faculty of Medicine. Methods: We conducted a literature search using PubMed, MEDLINE, ERIC, and CINAHL for studies evaluating the transition to clerkship in a four-year medical program. Using this data, we created two different versions of our survey (pre-transition and post-transition) for dissemination to second, third, and fourth-year medical students, plus MD/PhD students, in the Anglophone and Francophone stream. The survey was open for three weeks from October 10 to October 31, 2020, with weekly reminders to all eligible participants. Microsoft Excel 2016 was used for data analysis. Results: We obtained 176 respondents, of which 158 (70% Anglophone and 30% Francophone) were included in the analysis. The majority of students were in the MD2023 cohort (40%) and had completed a 4-year Bachelor’s degree (61%) prior to medical school. Students in the post-transition group were less anxious about the transition to clerkship than their junior colleagues, although differences between streams were marginal. The most notable difference concerning Entrustable Professional Activities was in terms of obtaining a complete history and performing a physical examination, with the post-transition cohort reporting increased competency compared to the pre-transition cohort in the Anglophone stream (2.9/5.0 pre-transition vs. 3.3/5.0 post-transition, +0.33 difference, p<0.05). Top two stressors for incoming clerks were a lack of clinical skills or experience, and lack of clarity around clerkship roles, responsibilities, and expectations.Conclusion: There is limited training to facilitate a seamless transition for incoming clerks at the University of Ottawa Faculty of Medicine. Changes can be made at the pre-clerkship level in the form of small-group orientation sessions, formative OSCEs, accelerated review of pre-clerkship material, and clerkship simulation sessions.
Age-Related Differences in Auditory Statistical Learning of Complex Speech Streams: Evidence From ERPs
Authors: Soares Ana Paula , Gutiérrez-Domínguez Francisco-Javier , Lages Alexandrina , Oliveira Helena M. , Vasconcelos Margarida , Jiménez Luis
Published: August 2021

Statistical learning (SL), the ability to pick up regularities in the sensory environment, is a fundamental skill that allows us to structure the world in a regular and predictable way. Although extensive evidence has been gathered from children and adults, the changes that SL might undergo throughout development remain contentious, particularly in the auditory modality (aSL) with linguistic materials. Here, we collected Event-Related Potentials (ERPs) while 5 years-old children and young adults (university students) were exposed to a complex speech stream in which eight three-syllable nonsense words - four with high (1.0) and four with low (.50) transitional probabilities were embedded to further examine how aSL works under less predictable conditions and to enhance age-related differences in the neural correlates of aSL. Moreover, to ascertain how previous knowledge of the to-be-learned regularities might also affect the results, participants performed the aSL task, firstly, under implicit and, subsequently, under explicit conditions. Although behavioral signs of aSL were observed only for adult participants, ERP data showed evidence of aSL in both groups, as indexed by modulations in the N100 and N400 components. A detailed analysis of the neural responses suggests, however, that adults and children rely on different mechanisms to assist aSL.
Can We Be at Peace With Unsolvable Suffering? A Qualitative Study Exploring the Effectiveness of Supportive Communication and Resilience Building
Authors: Nagano Hiroaki , Chida Keiko , Ozawa Taketoshi
Published: August 2021

BackgroundSuper-aging, along with high death rates and limited social resources in Japan, has created an urgent need to assume responsibility for the wellbeing of older adults and patients who have reached the end of life in the local community. MethodsFrom January 2019 to December 2020, we held six workshops with the same contents of interpersonal assistance using the teaching materials provided by End-of-Life Care (ELC) Association. The study session lasted for 180 minutes: the first 90 minutes entailed a presentation on supportive communication. The last 90 minutes were centered on role-playing. The objective of the supportive communication was not to understand the other person perfectly but to lead suffering people to think of supporters an understanding people.The participants were asked to perform reflective journal writing immediately following each session to record their experiences and describe what they learned. We applied thematic analysis to the journal entries to identify key themes based on Kolb’s ELT (experiential learning theory). For the three-month follow-up, semi-structured interviews were conducted with each participant to assess their self-perceived changes.ResultsReflective journal writing was completed by 152 participants. Using thematic analysis of the journal content immediately following the workshop, we identified two domains and 10 key themes based on participants’ perceptions. Participants realized the importance of using listening techniques, such as repetition and silence and understanding another person. Some mentioned they could ease their sense of weakness when helping those who are suffering, and that this awareness could be applied to work, grief care, and daily life.Three months post-experience interviews were completed with 28 of the original 152 participants who had completed reflective journal writing. Two domains and six key themes were generated. Some of the participants continued to practice listening with repetition and silence. Some of them also asked questions that could help strengthen the support for the sufferers. Changes in relationships between the participants and patients were identified. ConclusionUsing role-playing to teach supportive communication, such as listening attentively and accepting others by practicing repetition, silence, and asking, may be effective in encouraging supporters to confidently engage with people experiencing incurable suffering.
The Value of Colorectal Filling Contrast Ultrasonography in Diagnosing Paediatric Juvenile Polyps
Authors: Zhang Min , Lin Hai , Wu Tang Na , Hu Jie , Fu Sheng Xin , Jing Xiang Xiang , Qin Ling Ling
Published: August 2021

Objectives: To describe a facilitated procedure of colorectal filling contrast ultrasonography (CFCUS) and investigate its potential role in the assessment of paediatric juvenile polyps. Methods: The general information, clinical symptoms, ultrasound image characteristics, and colonoscopy findings of 101 children with clinical signs of colorectal polyps admitted to our hospital between May 2018 and May 2021 were retrospectively reviewed. All children underwent conventional transabdominal ultrasonography (CTUS), and CFCUS before colonoscopy, and the latter served as the gold standard. Chi-squared tests and Mann-Whitney U tests were used for the statistical analysis. Results: Forty-five children with fifty-two colorectal polyps were diagnosed by colonoscopy. Ten polyps had false-negative results on CTUS, six of which were detected by CFCUS. The sensitivity, specificity, positive predictive value, and negative predictive value of CFCUS vs CTUS was 92.3% vs 80.7%, 100% vs 100%, 100% vs 100%, 93.3% vs 84.8%, respectively. The maximum diameter of polyps (mean ± standard deviation) missed by CTUS was significantly smaller than that detected by CTUS (7.50±2.12 mm [range 4–12 mm] vs. 19.62±7.89 mm [range 6–41 mm], P<0.0001). A significant difference was observed between CTUS and CFCUS. The difference between CTUS and CFCUS regarding the detection rate of polyps with a diameter < 1 cm (P=0.031). A statistical difference was observed in the detection rate of polyps (P=0.031), and pedicles (P<0.001) between CTUS and CFCUS. The Kappa values for the assessment of Yamada’s classification between CTUS and colonoscopy and CFCUS and colonoscopy were 0.51 and 0.84, respectively. Six colonic polyps were accompanied by a punctate hyperechoic area on the surface, which may be suggestive of a correlation with erosion and bleeding findings.Conclusion: CFCUS can increase the detection rate of polyps and pedicles, especially polyps with diameters <1 cm, and accurately evaluate Yamada’s classification, providing useful preoperative information for colonoscopy.
Simulation-based Analysis of Ultra Thin-body Double Gate Ferroelectric TFET for an Enhanced Electric Performance
Authors: GOPAL GIRDHAR , varma Tarun
Published: August 2021

The Ultrathin body double gate FE layer TFET(UTB-DG-FE-TFET) is proposed and investigated in this work. Electrical performance parameters such as surface potential ψ(x), electrical field, drain current, sub-threshold swing, threshold voltage, and I on /I off ratio are further analyzed using simulation-based analysis. Integration of Si: HFO 2 ferroelectric layer on top and bottom surfaces make the structure that provides negative capacitance, higher on current, enormous surface potential, peak electric field, and improvement in SS with degradation in off Current. The suggested design is evaluated in comparison with FE-TFET and standard TFET devices. Finally, the impact of device geometry variants like ferroelectric layer thickness (t fe ), intrinsic channel thickness t si , interfacial layer types, interfacial layer thickness (t ox ) and channel length L c on transfer characteristics are investigated through 2D TCAD Sentaurus Simulator for a clear validation of its optimization. The recommended work demonstrates that it is a suitable device enabling superior performance and helpful in ultra-low-power applications.
Preparation of Ni-La/Al2O3-CeO2-Bamboo Charcoal Catalyst and its Application in Co-pyrolysis of Straw and Plastic for Hydrogen Production
Authors: Zhang YiRan , Li Jianfen , Li Bolin , Li Zeshan , He Yun , Qin Zhenhua , Gao Rongyi
Published: August 2021

The developed Ni-La/Al2O3-CeO2-Bamboo charcoal (ACB) catalyst was applied to the co-pyrolysis of straw and plastic to produce hydrogen in a horizontal quartz tube pyrolysis furnace. In this study, the effects of the mixing ratio of straw and plastic, the presence and stability of the catalyst on the co-pyrolysis hydrogen production were investigated. Experiment showed that the addition of PE can increase the yield of H2 within a certain range, and the best mass ratio of 5:5 was found. In the co-pyrolysis process with the participation of the catalysts, the macromolecular tar can be cracked into combustible gases such as H2, and the H2 yield could be increased to 332.2ml/g (Ni-La/ACB) is much higher than 68.87ml/g without catalyst. Compared with Ni/ACB, Ni-La/ACB had been increased the alkalinity by adding La element and enhanced the carbon deposition resistance of the catalyst, which makes the catalyst maintain higher stability. This was also confirmed in stability test experiments.
A Case Report of Ichthyosis Uteri
Authors: Liu Zhouying , Liu Dongge
Published: August 2021

Background: Ichthyosis uteri is a rare condition in which the entire surface of the endometrium is replaced by squamous epithelium. The condition often is considered as benign, despite anaplastic and dysplastic changes have been reported. Case presentation: A 36-year-old female present with extensive squamous metaplasia and dispersed normal endometrium. The case displayed with a benign ichthyosis uteri showing heavy keratinization without dysplasia. The cervix showed no dysplastic changes without HPV infection. Conclusion: We conclude that a benign ichthyosis uteri was not associated with HPV infection.
The Preclinical Evaluation of Self-Replicating RNA Oral Vaccine to Simultaneously Neutralize Both SARS-CoV-2 Delta and Alpha Variants
Authors: Mohammadi Abbas , Jebali Ali
Published: August 2021

The aim of this study was to design an oral vaccine based on self-replicating RNA lipid nanoparticle (saRNA LNP) to neutralize SARS-CoV-2 Delta (B.1.617 lineage) and Alpha (B.1.1.7 lineage) variants. Before immunization of mice with saRNA LNP, we saw the high expression of S-protein at both mRNA and protein levels after transfection of HEK293T/17 with saRNA LNP. After immunization of BALB/c mice with saRNA LNP at 0.1-10 μg, a high quantity of SARS-CoV-2 specific IgG, IgG1, IgG2a, and IgA was seen with a dose-dependent and Th1/Th2 skewing response in serum of vaccinated mice. We also found that the secreted antibodies could neutralize SARS-CoV-2 Delta (B.1.617 lineage) and Alpha (B.1.1.7 lineage) variants. Splenocytes from vaccinated mice re-stimulated with SARS-CoV-2 peptides had high IFN-γ, IL-6, and TNF- α secretion. Although the preclinical study confirmed the efficacy of saRNA LNP against SARS-CoV-2, its efficacy and safety must be evaluated in clinical trials.
Effects of Metformin on Bone-derived Mesenchymal Stromal Cell–breast Cancer Cell Line Interactions
Authors: Teufelsbauer Maryana , Lang Clemens , Plangger Adelina , Rath barbara , Moser Doris , Staud Clemens , Radke Christine , Neumayer Christoph , Hamilton Gerhard
Published: August 2021

Metformin is used to treat patients with diabetes mellitus and that was found to lower the incidence of cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC) and their breast cancer cell line interactions. BM-MSCs were tested for growth stimulation and migration controlling activity on four breast cancer cell lines employing MTT tests, migration scratch tests and assays of the expression of adipokines in Western Blot arrays. Compared to breast cancer cell lines, metformin significantly inhibited the proliferation of BM-MSC lines. Pretreatment of BM-MSCs with metformin showed variable effects on breast cancer cell lines depending on the specific BM-MSC cancer line combination. Metformin significantly impaired the migration of MDA-MB-231 and MDA-MB-436 in response to conditioned media (CM) of drug pretreated BM-MSCs. Metformin-induced alterations of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. The anticancer activities of metformin seem to be the result of direct and indirect mechanisms. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the anticancer effects of this drug in breast cancer patients.
Predicting Response to Immunotherapy Plus Chemotherapy in Patients with Esophageal Squamous Cell Carcinoma Using Non-Invasive Radiomic Biomarkers
Authors: Zhu Ying , Yao Wang , Xu Bing-Chen , Lei Yi-Yan , Guo Qi-Kun , Liu Li-Zhi , Li Hao-Jiang , Xu Min , Yan Jing , Chang Dan-Dan , Feng Shi-Ting , Zhu Zhihua
Published: August 2021

Objectives: To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI+CT) in patients with advanced esophageal squamous cell carcinoma (ESCC).Methods: A total of 64 patients with advance ESCC receiving first-line ICI+CT at two center between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. Results: Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p=0.0059) in the training cohort, and significantly better (p<0.0001) in the validation cohort. The 2D corrected radiomics model yielded the optimal performance and was used to build the nomogram. The calibration curve of the radiomics model demonstrated good agreement between prediction and observation and the decision curve analysis confirmed the clinical utility. Conclusions: The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI+CT.
Long-Term Time Trends in Reactivated Herpes Simplex Infections and Treatment in Sweden.
Authors: Lindman Karin Lopatko , Lockman-Lundgren Judith , Weidung Bodil , Olsson Jan , Elgh Fredrik , Lövheim Hugo
Published: August 2021

Background: Our aim was to describe the annual prevalence of herpes simplex virus (HSV) reactivation in relation to solar ultraviolet (UV) radiation and antiviral drug use in the Swedish adult population. Methods: The study comprised 2,879 anti-HSV-1 immunoglobulin (Ig) G positive subjects from five different cohorts who had donated serum from 1988–2010. The sera were analyzed for anti-HSV IgM using enzyme-linked immunosorbent assay. Associations between the presence of anti-HSV IgM antibodies, the apolipoprotein E ε4 allele and the serum sampling year were assessed by logistic regression. Seasonality of anti-HSV IgM was evaluated in a UV radiation model. Data of antiviral drugs for the entire Swedish population were compiled from two different nationwide databases: the Swedish Prescribed Drug Register and the Swedish Association of the Pharmaceutical Industry. Results: Cross-sectional and longitudinal analyses indicated that the prevalence of anti-HSV IgM antibodies declined between 1988 and 2010 (odds ratio [OR] = 0.912, P < .001), while the total annual use of antiviral drugs in Sweden gradually increased from 1984 to 2017. Higher UV radiation was associated with higher prevalence of anti-HSV IgM antibodies (OR = 1.071, P = .043). Conclusion: The declining time trend of HSV reactivation coincides with a steady increase of antiviral drug use, indicating improved control of HSV reactivation in the Swedish adult population.
DNA Methylation and Asthma Acquisition During and Post-Adolescence, an Epigenome-Wide Longitudinal Study.
Authors: Rathod Aniruddha , Zhang Hongmei , Arshad Hasan , Ewart Susan , Relton Caroline , Karmaus Wilfried , Holloway John
Published: August 2021

Background- While the majority of asthma starts in early childhood, asthma onset in some individuals occurs during adolescence or in adulthood. However, the pathogenesis of later onset asthma as well as the observed sex specificity are not well understood. Objective- We hypothesized that DNAm at specific CpG sites measured before disease onset, either in pre- or post-adolescence would be associated with asthma acquisition both during adolescence and in later adulthood. Methods- Subjects from the Isle of Wight Birth Cohort (IOWBC) were included. DNAm in blood at ages 10 (pre-adolescence) and 18 (post-adolescence), and asthma acquisition from age 10-18, and 18-26 years was studied. To improve statistical power, we first screened epigenome-wide CpGs based on the association of DNAm at 10 years with asthma acquisition from 10-18 years. Logistic regression with repeated measures were then applied to the CpGs that survived screening to examine the associations of pre-adolescence DNAm with asthma acquisition from pre-to post-adolescence, and post-adolescence DNAm with asthma acquisition from post-adolescence to adulthood. The effect of DNAm on asthma acquisition at different transition period was evaluated using interaction terms. The ALSPAC birth cohort was used for independent replication. For biological assessment of identified CpGs, pathway enrichment analysis and Differentially Methylated Regions were assessed. Results- Significant interaction effects of DNAm and transition period (10-18 or 18-26 years) on asthma acquisition were found for 17 CpGs in males and 98 CpGs in females (FDR=0.05) in IOWBC. Consistent interaction effects were observed for 9 CpGs in males and 53 CpGs in females in ALSPAC. For CpGs not showing interaction effects (i.e., effect of DNAm is stable over time), association with asthma acquisition was found for 38 CpGs in males and 52 CpGs in females in IOWBC. Of these 90 CpGs, at 13 CpG in males and 37 CpG in females, consistent direction of associations was observed in ALSPAC. Genes that the identified CpGs were mapped to, e.g., AKAP1 and ENO1, have shown to be associated with asthma. Conclusion- DNAm at specific CpGs is associated with asthma acquisition and such association is likely to be sex and transition period specific.
TGF-β-Induced CCR8 Promoted Macrophage Transdifferentiation into Myofibroblast-Like Cells
Authors: Liu Haijun , Guan Qingzhou , Zhao Peng , Li Jiansheng
Published: August 2021

Background: Idiopathic pulmonary fibrosis (IPF) is an unknown interstitial disease characterized by tissue fibrosis for which there currently is no effective treatment. Macrophages, as the main immune cells in lung tissue, are involved in the whole process of pulmonary fibrosis. In recent years, intercellular transformation has been widespread concerned in pulmonary fibrosis researchers. The macrophages which have flexible heterogeneity and plasticity participate in different physiological processes of the body. Cell chemokine receptor 8 (CCR8) expressed in a variety of cells plays a significant chemotactic role in inducing cell activation and migration. And it could also promote the differentiation of macrophages under certain environmental conditions. The current study is intended to explore the role of CCR8 in macrophage transdifferentiation into myofibroblast cells in idiopathic pulmonary fibrosis.Methods: We conducted experiments using Ccr8-specific small interfering RNA (siRNA), autophagy inhibitor (3-methyladenine,3-MA) and agonist (rapamycin) to explore the underlying mechanisms of macrophage transdifferentiation into myofibroblast cells in TGF-β induced pulmonary fibrosis. Results: The results indicated that TGF-β treatment increased the CCR8 protein level in a time- and a dose-dependent manner in MH-S, as well as macrophage transdifferentiation-related markers, including Vimentin, Collagen 1, and a-SMA, and cell migration. In addition, levels of autophagy were enhanced in macrophages treated with TGF-β. We found that 3-MA, an autophagy inhibitor decreased the expression levels of macrophage transdifferentiation-related markers and attenuated the cell migration. Furthermore, inhibition of CCR8 through using Ccr8-specific siRNA reduced the levels of autophagy and macrophage transdifferentiation-related markers, and inhibited the cell migration. Enhancing autophagy with rapamycin attenuated the inhibition effect of Ccr8-specific siRNA on macrophage migration and the increase of myofibroblast marker proteins.Conclusions: Our findings showed that the macrophages exposed to TGF-β had the potential to transdifferentiate into myofibroblasts and CCR8 was involved in the process. The effect of CCR8 in TGF-β-induced macrophage transdifferentiation occurs mainly through autophagy. Targeting the CCR8 may become a novel therapeutic strategy for the treatment of IPF.
A Virtual Laboratory Based on Full-Field Crystal Plasticity Simulation to Characterize the Multiscale Mechanical Properties of AHSS
Authors: Ma Hongyue , Li Yangqi , Zhang Haiming , Li Qian , Chen Fei , Cui Zhenshan
Published: August 2021

In this work, we proposed a virtual laboratory based on full-field crystal plasticity simulation to track plastic anisotropy and to calibrate yield functions for multi-phase metals. The virtual laboratory, minimally, only requires easily accessible EBSD data for constructing the high-resolved microstructural representative volume element and macroscopic flow stress data for identifying the micromechanical parameters of constituent phases. An inverse simulation method based on global optimization scheme was developed for parameters identification, and a nonlinear least-squares method was employed to calibrate the yield functions. Various mechanical tests of an advanced high strengthening steel (DP980) sheet under different loading conditions were conducted to validate the virtual laboratory. Three well-known yield functions, the quadratic Hill48, Yld91, and Yld2004-18p, were selected as the validation benchmarks. All the studied functions, calibrated by numerous stress points under arbitrary loading conditions, successfully captured both the deformation and strength anisotropies. Furthermore, the full-field CP modeling well correlates the microscopic deformation mechanism and plastic heterogeneity to the macro-mechanical behavior of the sheet. The proposed virtual laboratory, which is readily extended with physically based CP model, could be a versatile tool to explore and predict the mechanical property and plastic anisotropy of advanced multi-phase metals.
Geo-Analysis: The Distribution of Community Health Workers in Relation to the HIV Prevalence in Kwazulu-Natal Province, South Africa
Authors: Khumalo Gugulethu Eve , Ntuli S , Lutge E , Mashamba-Thompson T P
Published: August 2021

Background: The Ward Based Primary Health Care Outreach Team (WBPHCOT) policy framework states that community health workers (CHW)s should be distributed mainly according to poverty lines for each catchment population. We aimed to describe the spatial distribution of CHWs in relation to the HIV prevalence which has been associated with poverty in previous studies.Methods: We utilized geographic information system (GIS) method to visualize the distribution of CHWs in relation to HIV prevalence in KwaZulu-Natal (KZN) districts. Dot density mapping, was used to visualize the random distribution of CHWs in relation to HIV prevalence in the districts. The districts’ HIV prevalence, number of PLWH, CHW: PLWH ratio and poverty scores were mapped using choropleth mapping. MapInfo 17, a GIS software was used to map geospatial presentation of the data.Results: Ten out of 11 KZN districts had more than a required CHW:PLWH ratio of 1:160-267, which indicates a significant shortage of CHWs regardless of the HIV prevalence or poverty scores. Furthermore, our findings showed extensive geospatial heterogeneity with no clear pattern in the distribution CHWs in relation to the HIV prevalence and poverty scores in the districts Conclusion: This finding represents inequalities in the provision of HIV services by the CHWs. It is critical to strengthen response to the HIV epidemic through the well informed and justified distribution of CHWs especially to the poor districts.
The Trunk Rotation May Reduce Lung Volume and Respiratory Muscle Strength Prominently in Female Than Male
Authors: Takahata Miki , Osawa Miho , Hoshina Mizuki , Yamaki Michiyasu , Sato Toshiaki
Published: August 2021

It is known that gender affect pulmonary function, associated with anatomical differences between male and female. However, the effects of trunk rotation on respiratory variables and its differences between males and females remain unclear. We examined the effects of gender and physical characteristics on postural changes in healthy young people. In this study, 9 males and 11 females (22 ± 1 year old for both males and females) were enrolled. We measure the vital capacity (VC), inspiratory capacity (IC), tidal volume (VT), expiratory reserve volume (ERV), inspiratory reserve volume (IRV), and force vital capacity (FVC) and respiratory muscle (PImax and PEmax) with rest posture in the sitting position (rest posture) in sitting position and 30° trunk rotation both genders in the sitting position (rotational posture). The value of VC, IC, ERV, IRV, FVC, or FEV1.0 for males were significantly higher than that for females in both postures. In both genders, the VC, ERV, FVC, FEV1.0, and PEmax values in the rotational posture were significantly lower than that in the rest posture. Further, in females, there was a significant decrease in PImax in the rotational posture compared with the resting posture.This study indicated that trunk rotation may limit pulmonary function prominently in female than in male. These finding may provide important insights on gender differences in respiration in daily living.
Novel Field Effect Photodiode to Control the Output Photocurrent and Fast Optical Switching
Authors: Sharafi Foad , Orouji Ali A. , Soroosh Mohammad
Published: August 2021

This paper presents a novel device named Field Effect Photodiode (FEPD) to overcome the inherent drawbacks of PIN Photodiode (PIN-PD) and having an accurate control of the output photocurrent either applying the regular PIN-PD as a fast optical switch that provides a desire I ON /I OFF ratio for optical applications in the nanoscale regime. The proposed device combines a Metal Semiconductor Field Effect Transistor (MESFET) and a regular PIN-PD device that can convert the incident light with photon energy greater than the semiconductor’s bandgap to the regulated photocurrent by changing the gates bias which mounted over the absorption region. Our work include additional models such as bandgap narrowing, Shockley–Read–Hall (SRH), Auger (AUGER), the dependence of the carrier mobility on the doping concentration, Lombardi mobility model (CVT), Fermi statistic dependence (FERMIDIRAC), and Lateral electric field-dependent mobility. To extract and illustrate the electrical and optical results of both the regular PIN-PD and the proposed FEPD in this work, we have used TCAD tools as a semiconductor simulator.
Production of α-glucosidase Inhibitor in the Intestines by Bacillus Licheniformis
Authors: Kim Hee-Woong , Lee Deug-Chan , Rhee Hae-Ik
Published: August 2021

Alpha-glucosidase (EC.3.2.1.20) is involved in the absorption of monosaccharides in the small intestine of animals. We aimed to find a microorganism capable of proliferating in the intestine and producing α-glucosidase inhibitor. We developed a strain capable of forming spores from dry grass and growing in an anaerobic environment was selected as Bacillus lichenformis. Mixing spores of this strain with a high-fat diet and high-carbohydrate diet, it was confirmed that the weight gain was significantly reduced than the high-calorie diet group without spores. Furthermore it was confirmed that Bacillus lichenformis administered as spores efficiently proliferated in the intestine and consistently produced α-glucosidase inhibitor by securing a constant amount of the strain and α-glucosidase inhibitor in feces after a certain period. This study shows an efficient process in which microorganisms capable of proliferating in the intestine directly produce and supply specific secondary metabolites in the intestine.
Evaluation of Small Intestinal Motility in a Rat Model of Irritable Bowel Syndrome
Authors: Sato Masamichi , Kudo Takahiro , Arai Nobuyasu , Kyodo Reiko , Hosoi Kenji , Sakaguchi Keita , Ikuse Tamaki , Jimbo Keisuke , Ohtsuka Yoshikazu , Shimizu Toshiaki
Published: August 2021

Background: The correlation between small intestinal motility alteration and irritable bowel syndrome (IBS) is not well evaluated. Aims: To assess the small intestinal and colonic transits in an IBS rat model with restraint stress and determine the role of small intestinal motility in the IBS pathophysiology.Methods: Restraint stress was utilized to make adolescent IBS rat models that were evaluated for clinical symptoms, including stool frequency and diarrhea. The small intestinal motility and transit rate were also evaluated. The amounts of mRNA encoding corticotropin-releasing hormone, mast cell, and serotonin (5-Hydroxytryptamine; 5-HT) receptor 3a were quantified using real-time polymerase chain reaction (PCR); the 5-HT expression was evaluated using immunostaining.Results: Restraint stress significantly increased the number of fecal pellet outputs, stool water content, and small intestinal motility in the IBS rat models. There was no difference in real-time PCR results, but immunostaining analysis revealed that 5-HT expression in the small intestine was significantly increased in the IBS rat models.Conclusions: In the adolescent rat model of IBS with restraint stress, we observed an increase in small intestinal and colonic motility. In the small intestine, enhanced 5-HT secretion in the distal portion may be involved in increasing the small intestinal motility.