bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation-based surgical education for glaucoma versus conventional training alone: the GLAucoma Simulated Surgery (GLASS) trial. A multicentre, multicountry, randomised controlled, investigator-masked educational intervention efficacy trial in Kenya, South Africa, Tanzania, Uganda and Zimbabwe
Authors: Dean William H , Buchan John , Gichuhi Stephen , Philippin Heiko , Arunga Simon , Mukome Agrippa , Admassu Fisseha , Lewis Karinya , Makupa William , Otiti Juliet , Kim Min J , Macleod David , Cook Colin , Burton Matthew J
Published: January 2021

Background/Aim

Glaucoma accounts for 8% of global blindness and surgery remains an important treatment. We aimed to determine the impact of adding simulation-based surgical education for glaucoma.

Methods

We designed a randomised controlled, parallel-group trial. Those assessing outcomes were masked to group assignment. Fifty-one trainee ophthalmologists from six university training institutions in sub-Saharan Africa were enrolled by inclusion criteria of having performed no surgical trabeculectomies and were randomised. Those randomised to the control group received no placebo intervention, but received the training intervention after the initial 12-month follow-up period. The intervention was an intense simulation-based surgical training course over 1 week. The primary outcome measure was overall simulation surgical competency at 3 months.

Results

Twenty-five were assigned to the intervention group and 26 to the control group, with 2 dropouts from the intervention group. Forty-nine were included in the final intention-to-treat analysis. Surgical competence at baseline was comparable between the arms. This increased to 30.4 (76.1%) and 9.8 (24.4%) for the intervention and the control group, respectively, 3 months after the training intervention for the intervention group, a difference of 20.6 points (95% CI 18.3 to 22.9, p<0.001). At 1 year, the mean surgical competency score of the intervention arm participants was 28.6 (71.5%), compared with 11.6 (29.0%) for the control (difference 17.0, 95% CI 14.8 to 19.4, p<0.001).

Conclusion

These results support the pursuit of financial, advocacy and research investments to establish simulation surgery training units and courses including instruction, feedback, deliberate practice and reflection with outcome measurement to enable trainee glaucoma surgeons to engage in intense simulation training for glaucoma surgery.

Trial registration number

PACTR201803002159198.
Differential associations between body mass index with diabetes and vision-threatening diabetic retinopathy in an adult Chinese population
Authors: Han Xiaotong , Jiang Yu , Niu Yong , Zhu Yongjuan , Huang Wenyong , He Mingguang
Published: January 2021

Purpose

To investigate the associations between body mass index (BMI) with diabetes mellitus (DM) and vision-threatening diabetic retinopathy (VTDR).

Methods

This was a longitudinal study which included DM-free participants aged ≥40 years from the Lingtou Eye Cohort Study at baseline (2008–2010). Physical and ocular examinations were performed at baseline and annual follow-ups under standardised protocol. Two 45° non-mydriatic colour digital retinal photographs were obtained for each eye at all study visits, and presence of VTDR at the 2016 follow-up was graded by a deep-learning algorithm (LableMe) with proved high accuracy for detection of VTDR.

Results

A total of 2934 participants were included with a mean (SD) age of 59.5 (7.3) years (58.3% men). Participants with incident DM (441/2934, 15%) were significantly older (p<0.001), had higher obesity levels (p<0.001), higher systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (p<0.001), fasting plasma glucose (FPG) (p<0.001), triglycerides (p=0.002) and high-density lipoprotein cholesterol (p<0.001), as compared with those without. Participants with incident VTDR (48/2934, 1.63%) were also older (p<0.001), had higher SBP (p=0.013) and FPG (p<0.001), but did not differ in baseline BMI, comparing with those without. Regression analysis showed that higher baseline BMI was significantly related to incident DM (p<0.005), but not incident VTDR, during the follow-up. Subgroup analysis among participants with incident DM also revealed no association between BMI and VTDR.

Conclusions

Higher baseline BMI increased the risk of incident DM, but was not related to the risk of VTDR in this adult Chinese population.
Improving National Intelligence for Public Health Preparedness: a methodological approach to finding local multi-sector indicators for health security
Authors: Erondu Ngozi A , Rahman-Shepherd Afifah , Khan Mishal S , Abate Ebba , Agogo Emmanuel , Belfroid Evelien , Dar Osman , Fehr Angela , Hollmann Lara , Ihekweazu Chikwe , Ikram Aamer , Iversen Bjorn Gunnar , Mirkuzie Alemnesh H , Rathore Tayyab Razi , Squires Neil , Okereke Ebere
Published: January 2021

The COVID-19 epidemic is the latest evidence of critical gaps in our collective ability to monitor country-level preparedness for health emergencies. The global frameworks that exist to strengthen core public health capacities lack coverage of several preparedness domains and do not provide mechanisms to interface with local intelligence. We designed and piloted a process, in collaboration with three National Public Health Institutes (NPHIs) in Ethiopia, Nigeria and Pakistan, to identify potential preparedness indicators that exist in a myriad of frameworks and tools in varying local institutions. Following a desk-based systematic search and expert consultations, indicators were extracted from existing national and subnational health security-relevant frameworks and prioritised in a multi-stakeholder two-round Delphi process. Eighty-six indicators in Ethiopia, 87 indicators in Nigeria and 51 indicators in Pakistan were assessed to be valid, relevant and feasible. From these, 14–16 indicators were prioritised in each of the three countries for consideration in monitoring and evaluation tools. Priority indicators consistently included private sector metrics, subnational capacities, availability and capacity for electronic surveillance, measures of timeliness for routine reporting, data quality scores and data related to internally displaced persons and returnees. NPHIs play an increasingly central role in health security and must have access to data needed to identify and respond rapidly to public health threats. Collecting and collating local sources of information may prove essential to addressing gaps; it is a necessary step towards improving preparedness and strengthening international health regulations compliance.
Elevated levels of prostaglandin E2in the tears of patients with severe allergic conjunctivitis and primary cultured conjunctival cells are suppressed by ketotifen and dexamethasone
Authors: Yamanishi Ryutaro , Okada Naoko , Shimizu Eisuke , Fujishima Hiroshi
Published: January 2021

Objective

We examined the production of prostaglandin E2(PGE2), which is the key prostaglandin involved in inflammatory disorders of the ocular surface. Tears and conjunctival fibroblasts were evaluated in order to assess allergic inflammation and the effect of specific drugs.

Methods and analysis

PGE2was measured in tears from both patients and normal volunteers. Primary cultures of human conjunctival fibroblasts were incubated with interleukin (IL)-4 and tumour necrosis factor (TNF)-α with or without ketotifen fumarate or dexamethasone. The culture supernatants were removed 24 hours after exposure and the concentrations of PGE2were quantified by ELISA.

Results

Significantly higher levels of PGE2were observed in the tears of patients with severe allergic conjunctivitis than in those with post-surgical inflammation (p=0.02), and this production was reduced by eye drops. Stimulation with IL-4 and TNF-α induced the generation of PGE2in supernatants of conjunctival fibroblasts, and this production was significantly downregulated by ketotifen fumarate or steroids.

Conclusion

PGE2may participate in the pathogenesis of severe ocular allergic disease, and both ketotifen fumarate and steroid reduce the production of PGE2.
Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers
Authors: Chiu Han-Mo , Jen Grace Hsiao-Hsuan , Wang Ying-Wei , Fann Jean Ching-Yuan , Hsu Chen-Yang , Jeng Ya-Chung , Yen Amy Ming-Fang , Chiu Sherry Yueh-Hsia , Chen Sam Li-Sheng , Hsu Wen-Feng , Lee Yi-Chia , Wu Ming-Shiang , Wu Chien-Yuan , Jou Yann-Yuh , Chen Tony Hsiu-Hsi
Published: January 2021

Objective

To measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening.

Design

A prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features.

Results

FIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80).

Conclusion

A large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.
MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor immune microenvironment in triple-negative breast cancer
Authors: Yamashita Nami , Long Mark , Fushimi Atsushi , Yamamoto Masaaki , Hata Tsuyoshi , Hagiwara Masayuki , Bhattacharya Atrayee , Hu Qiang , Wong Kwok-Kin , Liu Song , Kufe Donald
Published: January 2021

Background

Immune checkpoint inhibitors (ICIs) have had a profound impact on the treatment of many tumors; however, their effectiveness against triple-negative breast cancers (TNBCs) has been limited. One factor limiting responsiveness of TNBCs to ICIs is a lack of functional tumor-infiltrating lymphocytes (TILs) in ‘non-inflamed’ or ‘cold’ tumor immune microenvironments (TIMEs), although by unknown mechanisms. Targeting MUC1-C in a mouse transgenic TNBC tumor model increases cytotoxic tumor-infiltrating CD8+ T cells (CTLs), supporting a role for MUC1-C in immune evasion. The basis for these findings and whether they extend to human TNBCs are not known.

Methods

Human TNBC cells silenced for MUC1-C using short hairpin RNAs (shRNAs) were analyzed for the effects of MUC1-C on global transcriptional profiles. Differential expression and rank order analysis was used for gene set enrichment analysis (GSEA). Gene expression was confirmed by quantitative reverse-transcription PCR and immunoblotting. The The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were analyzed for effects of MUC1 on GSEA, cell-type enrichment, and tumor immune dysfunction and exclusion. Single-cell scRNA-seq datasets of TNBC samples were analyzed for normalized expression associations between MUC1 and selected genes within tumor cells.

Results

Our results demonstrate that MUC1-C is a master regulator of the TNBC transcriptome and that MUC1-C-induced gene expression is driven by STAT1 and IRF1. We found that MUC1-C activates the inflammatory interferon (IFN)-γ-driven JAK1→STAT1→IRF1 pathway and induces the IDO1 and COX2/PTGS2 effectors, which play key roles in immunosuppression. Involvement of MUC1-C in activating the immunosuppressive IFN-γ pathway was extended by analysis of human bulk and scRNA-seq datasets. We further demonstrate that MUC1 associates with the depletion and dysfunction of CD8+ T cells in the TNBC TIME.

Conclusions

These findings demonstrate that MUC1-C integrates activation of the immunosuppressive IFN-γ pathway with depletion of TILs in the TNBC TIME and provide support for MUC1-C as a potential target for improving TNBC treatment alone and in combination with ICIs. Of translational significance, MUC1-C is a druggable target with chimeric antigen receptor (CAR) T cells, antibody-drug conjugates (ADCs) and a functional inhibitor that are under clinical development.
Prognostic value of left ventricular mitral annular longitudinal displacement obtained by tissue Doppler imaging in patients with heart failure with reduced ejection fraction
Authors: Sengeløv Morten , Jørgensen Peter Godsk , Bruun Niels Eske , Olsen Flemming Javier , Fritz-Hansen Thomas , Biering-Sørensen Tor
Published: January 2021

Background

Tissue Doppler imaging (TDI) can be used to measure the mitral annular longitudinal displacement (LD) during systole. However, the prognostic utility of global and regional LD in patients with heart failure with reduced ejection fraction (HFrEF) is unknown.

Methods

Echocardiographic examinations from 907 patients with HFrEF were analysed obtaining conventional echocardiographic measurements. Regional LD was obtained from colour TDI projections in six mitral annular regions and global LD was calculated as an average.

Results

Mean age was 67 years, 26.9% were women and mean left ventricular ejection fraction was 27%. During a median follow-up period of 40 months, 150 (16.5 %) patients died. The risk of dying increased with decreasing tertile of global LD and was approximately five times higher for patients in the lowest tertile compared with the highest (1. tertile vs 3. tertile, HR 4.9, 95% CI: 3.0 to 7.9, p<0.001).

Global LD was a significant independent predictor of mortality after adjusting for age, gender, body mass index, pacemaker, heart rate, atrial fibrillation, diabetes and conventional echocardiographic measures and global longitudinal strain: HR 1.16 (95% CI: 1.00 to 1.34, p=0.044) per 1 mm decrease.

For regional measures, inferior LD was also a significant independent predictor in the multivariable model: HR 1.16 (95% CI: 1.04 to 1.29, p=0.006) and adding inferior LD to the conventional measures yielded a significant increase in Harrell’s C-statistic (95% CI: 0.75 to 0.78, p=0.009).

Conclusion

In patients with HFrEF, global and inferior LD are independent predictors of all-cause mortality. Furthermore, inferior LD proved to be a significant prognosticator when compared with all the conventional echocardiographic parameters.
Roles of adiponectin and leptin signaling-related microRNAs in the preventive effects of calorie restriction in mammary tumor development
Authors: Dogan Soner , Cicekdal Munevver B. , Ozorhan Umit , Karabiyik Goktug , Kazan Busra T. , Ekici Isin D. , Yilmaz Bayram , Demirel Pinar B. , Coban Ilker , Tuysuz Emre Can , Kuskucu Aysegul , Bayrak Omer F. , Cleary Margot P. , Tuna Bilge G.
Published: January 2021

Calorie restriction (CR) is suggested to prevent the development of mammary tumors (MTs); however, the mechanism remains to be clarified. We aimed to determine the microRNA (miRNA) profile in mice applied to 2 different CR protocols; chronic (CCR) and intermittent (ICR) and follow the MT development. In addition, the roles of miRNAs involved in adiponectin and/or leptin signaling pathways were investigated. Mice were divided into 3 groups: ad-libitum (AL), CCR, or ICR, which comprised 3 weeks of AL feeding followed by 1 week of 60% CR in a cyclic manner. Blood and tissue collection were performed at weeks 10, 17/18, 49/50 and 81/82. Long-term CCR provided better protection compared with ICR for MT development with a delay in the MT occurrence. Adiponectin expression in mammary fat pad were significantly higher in CCR group compared with AL. Using GeneChip Array, 250 of 3195 miRNAs were differentially expressed among the dietary groups. Thirteen of 250 miRNAs were related to adiponectin and/or leptin signaling genes. Results were verified by reverse transcription polymerase chain reaction. Specifically, miR-326-3p, miR-500-3p and miR-129-5p, which are related to adiponectin and/or leptin signaling, may play important roles in the preventive effects of CR in MT development and in ageing. Thus, these miRNAs might be putative biomarkers to target for diagnostic and treatment purposes.

Novelty: Type of CR and micro RNA interaction is related to ageing. miR-326-3p, miR-500-3p and miR-129-5p expression levels were differentially expressed in MT development and in ageing. The genes associated with adiponectin and/or leptin signaling pathways are regulated by certain miRNAs in the protective effects of CR.
A ground-state complex between methyl viologen and the fluorescent whitening agent 4,4′-bis(2-sulfostyryl)-biphenyl disodium salt: a fluorescence spectroscopy study
Authors: Armstrong Emily J. , Galas Henry , Wylie R. Stephen , Zohrehvand Shiva , Stam Jan van , Evans Christopher H.
Published: January 2021

This study explores the quenching of the dianionic fluorescent whitening agent, NFW, by various substances, including methyl viologen (MV), in water and in the presence of beta-cyclodextrin (β-CD). Results of a fluorescence spectroscopic examination of the β-CD–NFW system are presented. It was found that NFW forms a 1:1 inclusion complex with β-CD with an association constant of 2540 ± 380 M−1. The included NFW fluorescent state is protected by the β-CD cavity from a range of water-based quenchers (neutral, anionic, and cationic). Quenching proceeds near the diffusion-controlled limit in water for the quenchers tested with the exception of the dicationic MV. Methyl viologen is an extremely efficient quencher of NFW fluorescence with a nominal K SV ∼ 5.0 × 103 M−1 in water alone, corresponding to a nominal k q of ∼ 4 × 1012 M−1 s−1, which exceeds the diffusion-controlled limit in this solvent. The quenching efficiency of MV is strongly suppressed in the presence of 10 mM β-CD (K SV = 105 ± 12 M−1) and in the presence of NaCl (K SV = 106 ± 9 M−1 at 0.5 M salt). In the absence of CD or salt, there is a strong contribution from static quenching in the MV system; the presence of these additives suppresses the static quenching. Various results suggest the static quenching is due to formation of a ground-state complex between the dianion NFW and the dication MV.
Baby tyrannosaurid bones and teeth from the Late Cretaceous of western North America1
Authors: Funston Gregory F. , Powers Mark J. , Whitebone S. Amber , Brusatte Stephen L. , Scannella John B. , Horner John R. , Currie Philip J.
Published: January 2021

Tyrannosaurids were the apex predators of Late Cretaceous Laurasia and their status as dominant carnivores has garnered considerable interest since their discovery, both in the popular and scientific realms. As a result, they are well studied and much is known of their anatomy, diversity, growth, and evolution. In contrast, little is known of the earliest stages of tyrannosaurid development. Tyrannosaurid eggs and embryos remain elusive, and juvenile specimens — although known — are rare. Perinatal tyrannosaurid bones and teeth from the Campanian–Maastrichtian of western North America provide the first window into this critical period of the life of a tyrannosaurid. An embryonic dentary (cf. Daspletosaurus) from the Two Medicine Formation of Montana, measuring just 3 cm long, already exhibits distinctive tyrannosaurine characters like a “chin” and a deep Meckelian groove, and reveals the earliest stages of tooth development. When considered together with a remarkably large embryonic ungual from the Horseshoe Canyon Formation of Alberta, minimum hatchling size of tyrannosaurids can be roughly estimated. A perinatal premaxillary tooth from the Horseshoe Canyon Formation likely pertains to Albertosaurus sarcophagus and it shows small denticles on the carinae. This tooth shows that the hallmark characters that distinguish tyrannosaurids from other theropods were present early in life and raises questions about the ontogenetic variability of serrations in premaxillary teeth. Sedimentary and taphonomic similarities in the sites that produced the embryonic bones provide clues to the nesting habits of tyrannosaurids and may help to refine the prospecting search image in the continued quest to discover baby tyrannosaurids.
A Theoretical Analysis of Physical Properties and Half-Metallic Stability under Pressure Effect of the ScNiCrZ (Z=Ga, Al, In) Heusler Alloys
Authors: Rabah I. E. , Rached H. , Rabah M. , Rached D. , Benkhettou N.
Published: January 2021

The aim purpose of this study is to investigate the structural, elastic, magnetic, electronic properties and half-metallic stability under pressure of ScNiCrZ ([Formula: see text], Ga and In) quaternary Heusler alloys using full-potential linear muffin-tin orbital (FP-LMTO) method within the gradient generalized approximation (GGA) for exchange, and correlation potential. In order to evaluate the stability of our compounds, the formation energy, and elastic constants have been evaluated. The results showed that our compounds have ferromagnetic ground states and are energetically more stable in type-[Formula: see text] configuration. True half-metallic ferromagnetic behavior with 100% spin polarization at Fermi level [Formula: see text] with high Curie temperature [Formula: see text], and very interesting bandgap in the minority spin are obtained for the three alloys. The calculated total magnetic moment [Formula: see text] for all three alloys is consistent with Slater[Formula: see text]Pauling rule. The half-metallicity is maintained over a wide range of lattice constants making these alloys promising for spintronic, and magneto-electronics applications.
The time I stole $10,000 from Bell Labs
Authors: Limoncelli Thomas A.
Published: January 2021

Why DevOps encourages us to celebrate outages.
Issues arise when time goes digital
Authors: Hill Robin K.
Published: January 2021

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Robin K. Hill considers why time can be "a pesky problem for computing."
Let's not dumb down the history of computer science
Authors: Knuth Donald E. , Shustek Len
Published: January 2021

Donald Knuth on the best way to recognize the history of computer science.
GeoHumanities 2020 workshop report
Authors: Moncla Ludovic , Murrieta-Flores Patricia , Brando Carmen
Published: January 2021

This article reports on the 4th ACM SIGSPATIAL Workshop on Geospatial Humanities, held in conjunction with the 28th ACM SIGSPATIAL International Conference on Advances in Geographic Information Systems. The article outlines the objectives of the workshop, and briefly describes the technical program.
The 3rd ACM SIGSPATIAL International Workshop on Advances in Resilient and Intelligent Cities
Authors: Kar Bandana , Ye Xinyue , Mohebbi Shima , Fu Guangtao
Published: January 2021

The advancements in sensor technology and ubiquity of connected devices has enabled the generation of large volume of disparate, dynamic and geographically distributed data both by scientific communities and citizens. With astonishing technological innovations and convergence, there have been major changes in peoples daily activities and social interactions. These innovations have contributed to the establishment of smart and connected cities. A smart city is forward-looking, progressive, and has the potential to provide high-quality life. A resilient city can preserve its activities and bounce back to its previous stage or to a new normal in the face of an emergency while meeting the daily activities and needs of its citizens. It is imperative to improve our understanding of Resilient and Intelligent Cities in order to leverage these new technologies to tackle the challenges ranging from climate change, public health, traffic congestion, economic growth, to digital divide, social equity, political movements, and cultural conflicts, among others.
The 2nd ACM SIGSPATIAL International Workshop on Spatial Gems
Authors: Krumm John , Shahabi Cyrus , Züfle Andreas
Published: January 2021

Researchers and practitioners working with spatial data often develop fundamental new techniques they would like to share with their community. These are not necessarily new research results, not yet in any textbook, but they are interesting, self-contained techniques for doing something useful in the domain of spatial data. We call these techniques "spatial gems".
A La2O3-NPs/ZnO/MEMS SO2 Gas Sensor
Authors: Hsueh Ting-Jen , Lee Shih-Hsien
Published: January 2021

This study uses the structure of a MEMS gas sensor to fabricate a La2O3-NPs/ZnO/MEMS SO2 gas sensor. La2O3 nanoparticles (La2O3-NPs) with an average diameter of about 20 nm are produced by ultrasonic wave grinding. For SO2 gas, the La2O3-NPs/ZnO/MEMS gas sensor has a greater sensor response to 400 ppb SO2 gas at an operating temperature of 342 °C than a ZnO/MEMS gas sensor or a La2O3-NPs/MEMS gas sensor. This result demonstrates that the large 44% sensor response is due to the ZnO thin film with La2O3 nanoparticles. The experimental results also show that the ZnO thin film acts as an electronic transmission path. The sensors exhibit a higher sensitivity to SO2 than other gases (NO2, CO, CO2) at the optimal operating temperature of 342 °C. The reproducibility experiment shows that the La2O3-NPs/ZnO/MEMS SO2 gas sensor is stable.
A Novel Framework Design of Network Intrusion Detection Based on Machine Learning Techniques
Authors: Zhang Chongzhen , Chen Yanli , Meng Yang , Ruan Fangming , Chen Runze , Li Yidan , Yang Yaru
Published: January 2021

Traditional machine learning-based intrusion detection often only considers a single algorithm to identify intrusion data, lack of the flexibility method, low detection rate, no handing high-dimensional data, and cannot solve these problems well. In order to improve the performance of intrusion detection system, a novel general intrusion detection framework was proposed in this paper, which consists of five parts: preprocessing module, autoencoder module, database module, classification module, and feedback module. The data processed by the preprocessing module are compressed by the autoencoder module to obtain a lower-dimensional reconstruction feature, and the classification result is obtained through the classification module. Compressed features of each traffic are stored in the database module which can both provide retraining and testing for the classification module and restore these features to the original traffic for postevent analysis and forensics. For evaluation of the framework performance proposed, simulation was conducted with the CICIDS2017 dataset to the real traffic of the network. As the experimental results, the accuracy of binary classification and multiclass classification is better than previous work, and high-level accuracy was reached for the restored traffic. At the last, the possibility was discussed on applying the proposed framework to edge/fog networks.
The First Case Report of Ectopic Hepatic Tissue in a Guinea Pig
Authors: Kimura Tohru , Inaka Kengo
Published: January 2021

Ectopic hepatic tissue is an extremely rare developmental abnormality in human beings. Although this lesion is likewise rare in veterinary medicine and there were sparse reports in several species such as dogs, cats, cows, and calves, we incidentally encountered ectopic hepatic tissue in a guinea pig. In the case of guinea pigs, we report for the first time the occurrence of ectopic hepatic tissue implanted in the gallbladder. The healthy guinea pig remained asymptomatic, and its macroscopic findings also showed no abnormalities. Hematological examinations exhibited moderate decreases in white cell counts, hemoglobin concentrations, and packed cell volume ratio. Serum biochemical examinations showed decreases in total protein and albumin and increases in glucose levels, alkaline phosphatase, lactate dehydrogenase, creatine kinase, and γ-glutamyl transpeptidase. There were slight changes in electrolytes (Cl, Ca, and Mg) and inorganic phosphorus, indicating minor deviations from physiologic ranges. An increase in TBIL concentrations was not found in this examination. Histopathological examination revealed the presence of normal hepatic structures (hepatocytes and hepatic cords) within the wall of the normal gallbladder. The vascular and bile duct structures and portal triads were not observed in the ectopic hepatic tissue. In conclusion, this microectopic hepatic tissue in a guinea pig was characterized by the embedded structures of hepatic tissues, without foreign body reaction.
Preclinical Evaluation and Phase Ib Study of Prexasertib, a CHK1 Inhibitor, and Samotolisib (LY3023414), a Dual PI3K/mTOR Inhibitor
Authors: Hong David S. , Moore Kathleen N. , Bendell Johanna C. , Karp Daniel D. , Wang Judy S. , Ulahannan Susanna V. , Jones Suzanne , Wu Wenjuan , Donoho Gregory P. , Ding Yan , Capen Andrew , Wang Xuejing , Bence Lin Aimee , Patel Manish R.
Published: January 2021

Purpose:

Prexasertib, a checkpoint kinase 1 inhibitor (CHK1), exhibited modest monotherapy antitumor activity in previous studies. Preclinical data were generated to support the clinical combination of prexasertib + samotolisib, a PI3K/mTOR inhibitor.

Patients and Methods:

Prexasertib + samotolisib was first evaluated in triple-negative breast cancer (TNBC) cells, MDA-MB-231 orthotopic xenograft tumors, and TNBC patient–derived xenograft (PDX) mouse models. In the phase Ib trial, following dose escalation, the initial expansion arm (E1, solid tumors) explored prexasertib 105 mg/m2 intravenously every 14 days + samotolisib 200 mg orally twice daily. Subsequent expansion arms evaluated samotolisib 150 mg twice daily in patients carrying PIK3CA mutations (E2, solid tumors) or with TNBC (E3). Safety and antitumor activity were assessed.

Results:

Prexasertib + samotolisib inhibited cell proliferation in TNBC lines and primary tumor growth in the MDA-MB-231 model. Prexasertib + samotolisib exhibited synergistic or additive effects in 30 of 38 PDX single-mouse (“n = 1”) models, and provided rationale for clinical evaluation. In the phase Ib study, 53 patients were enrolled (escalation, n = 13; E1, n = 9; E2, n = 15; and E3, n = 16). No dose-limiting toxicities (DLT) were observed during escalation; however, DLT-equivalent toxicities were observed in E1, leading to samotolisib dose reduction (150 mg twice daily) in E2/E3. Common treatment-related adverse events were leukopenia/neutropenia (94.3%), thrombocytopenia (62.3%), and nausea (52.8%). During escalation, 2 patients achieved partial response for an overall response rate (ORR) of 15.4%, and ORRs were 13.3% for E2 (PIK3CA) and 25% for E3 (TNBC).

Conclusions:

Prexasertib + samotolisib showed antitumor activity in preclinical models and preliminary efficacy in heavily pretreated patients. The clinical combination was associated with toxicity, suggesting supportive measures may be required. However, these data may inform future trials using other CHK1 and PI3K pathway inhibitors.
Abiraterone Acetate Induces CREB1 Phosphorylation and Enhances the Function of the CBP-p300 Complex, Leading to Resistance in Prostate Cancer Cells
Authors: Pan Wenting , Zhang Zhouwei , Kimball Hannah , Qu Fangfang , Berlind Kyler , Stopsack Konrad H. , Lee Gwo-Shu Mary , Choueiri Toni K. , Kantoff Philip W.
Published: January 2021

Purpose:

Abiraterone acetate (AA), an inhibitor of cytochrome P450 17alpha-hydroxylase/17, 20 lyase, is an FDA-approved drug for advanced prostate cancer. However, not all patients respond to AA, and AA resistance ultimately develops in patients who initially respond. We aimed to identify AA resistance mechanisms in prostate cancer cells.

Experimental Design:

We established several AA-resistant cell lines and performed a comprehensive study on mechanisms involved in AA resistance development. RNA sequencing and phospho-kinase array screenings were performed to discover that the cAMP-response element CRE binding protein 1 (CREB1) was a critical molecule in AA resistance development.

Results:

The drug-resistant cell lines are phenotypically stable without drug selection, and exhibit permanent global gene expression changes. The phosphorylated CREB1 (pCREB1) is increased in AA-resistant cell lines and is critical in controlling global gene expression. Upregulation of pCREB1 desensitized prostate cancer cells to AA, while blocking CREB1 phosphorylation resensitized AA-resistant cells to AA. AA treatment increases intracellular cyclic AMP (cAMP) levels, induces kinases activity, and leads to the phosphorylation of CREB1, which may subsequently augment the essential role of the CBP/p300 complex in AA-resistant cells because AA-resistant cells exhibit a relatively higher sensitivity to CBP/p300 inhibitors. Further pharmacokinetics studies demonstrated that AA significantly synergizes with CBP/p300 inhibitors in limiting the growth of prostate cancer cells.

Conclusions:

Our studies suggest that AA treatment upregulates pCREB1, which enhances CBP/p300 activity, leading to global gene expression alterations, subsequently resulting in drug resistance development. Combining AA with therapies targeting resistance mechanisms may provide a more effective treatment strategy.
Multifocal Langerhans Cell Histiocytosis: A Unique Presentation of Eosinophilic Granuloma with Intracranial Extension, Massive Lymphadenopathy, and Epstein-Barr Viral Infection in an Adolescent Female
Authors: Foster Kent Wade , Robinson Shamika Kayo , Tung-Hahn Eleanor , Gibbons George , Cruse Carl Wayne , Mudaliar Kumaran , Tung Rebecca , Kim Wendy
Published: January 2021

We report the case of an otherwise healthy 17-year-old female who presented for surgical removal of an enlarging “atypical cyst” on her scalp. During subtotal excision, only friable serosanguinous translucent ribbons of tissue were found. A histopathologic diagnosis of Langerhans cell histiocytosis (LCH) was rendered and imaging studies revealed extradural invasion of the tumor. Within weeks, the patient also developed progressive lymphadenopathy with grossly elevated levels of Epstein-Barr virus viral capsid antigen antibody levels. This report aims to highlight a unique presentation of LCH with discussion of workup, management, and avoidance of potential surgical complications.
Altered Immune Regulation of Dendritic Cells and Enhanced Cytokine Production of T Cells in the Pathogenesis of Eosinophilic Chronic Rhinosinusitis
Authors: Kawakami Kaori , Miyasaka Tomomitsu , Ohno Isao , Ohta Nobuo , Masuda-Suzuki Chiaki , Tateda Yutaka , Kusano Yusuke , Shoji Fumi , Kitaya Shiori , Nakamura Yutaka , Arikawa Tomohiro , Kawano Tasuku , Takayanagi Motoaki , Takahashi Tomoko
Published: January 2021

Introduction: Eosinophilic chronic rhinosinusitis (ECRS) is a refractory chronic disease defined by recurrent nasal polyps with severe eosinophilic infiltration. This is mainly due to enhanced type 2-dominant immune responses, but the underlying mechanism is still not fully understood. Objective and Methods: In the present study, we aimed to determine the characteristics of dendritic cells (DCs) and cytokine profiles of T cells in the peripheral blood of individuals with ECRS and age- and sex-matched healthy controls (HC). Results and Conclusion: The ratios of myeloid (m)DC1s to DCs and PD-L1+ mDC1s to mDC1s were higher in ECRS patients than in HC. The proportions of plasmacytoid (p)DCs in DCs, and human leukocyte antigen-DR+ pDCs and ILT3+ pDCs in pDCs were lower in ECRS patients than in HC. In a characterization of T cells, IL-4+CD4+, IFN-γ+CD4+, IL-4+IFN-γ+CD4+, IL-4+Foxp3+CD4+, IFN-γ+Foxp3+CD4+, IFN-γ+IL-4−Foxp3−CD4+, IL-4+CD8+, IL-4+IFN-γ+CD8+, and IL-4+Foxp3+CD8+ T-cell populations were significantly higher in ECRS patients than in HC. These results suggest that the enhanced immune regulation of mDC1, diminished capacity of pDCs, and increased proportion of the T-cell phenotypes in peripheral blood might be factors in ECRS pathogenesis.
Moxibustion for Essential Hypertension and Hypertensive Symptoms: A Systematic Review of 18 Randomized Controlled Trials
Authors: Zhou Xu , Wu Qingni , Liu Meilu , Zhu Weifeng , Ren Qing , Wang Yanping , Sun Xin , Chen Jianrong
Published: January 2021

Introduction: This systematic review aims to update the evidence for moxibustion for essential hypertension. Methods: Randomized controlled trials (RCTs) comparing moxibustion versus lifestyle intervention or moxibustion plus antihypertensive drugs versus antihypertensive drugs alone were searched in 9 databases up to March 29, 2020. In meta-analyses, mean difference (MD) and proportional odds ratio (pOR) with 95% confidence intervals (CIs) was pooled for continuous and ordinal outcomes, respectively. Results: Eighteen RCTs were included, involving 1,460 patients. Moxibustion decreased systolic (MD –7.85 mm Hg, 95% CI –9.69 to –6.00, p < 0.00001, I2 = 46%) and diastolic (MD –4.09 mm Hg, 95% CI –5.45 to –2.73, p < 0.0001, I2 = 56%) blood pressures and improved the response to hypotensive treatment (pOR 2.37, 95% CI 1.49–3.75, p = 0.0003, I2 = 57%) significantly more than did the control treatment. Moxibustion also significantly relieved headache and dizziness but the effects changed to be statistically nonsignificant after excluding RCTs with a high risk of bias. Moxibustion did not significantly relieve insomnia and anxiety. No adverse events were reported. Conclusions: Based on the current low to moderate quality evidence, our study suggests that moxibustion may have effects on reducing blood pressure. The effects of moxibustion on typical hypertension symptoms and the long-term safety of moxibustion remain uncertain.
Amplified and quantum based brain storm optimization algorithms for real power loss reduction
Authors: Lenin Kanagasabai
Published: January 2021

In this work Amplified Brain Storm Optimization (ABS) algorithm and Quantum based Brain Storm (QBS) Optimization Algorithm is used for solving optimal reactive power problem. In the projected amplified Brain storm optimization algorithm Hamiltonian cycle has been applied to improve the search abilities and also to avoid of trap in local optimal solution. A node is arbitrarily chosen from the graph as the preliminary point to form a Hamiltonian cycle. At generation t and t+1, Lt and Lt+1 are the length of Hamiltonian cycle correspondingly. In the QBS algorithm a Quantum state of an idea is illustrated by a wave function as an alternative of the position modernized only in Brain storm optimization algorithm. Monte Carlo simulation method is used, to measure the position for each idea from the quantum state to the traditional one. Proposed Amplified Brain Storm Optimization (ABS) algorithm and Quantum based Brain Storm (QBS) Optimization Algorithm has been tested in standard IEEE 57 bus test system and simulation results show the projected algorithms reduced the real power loss effectively.
Investigation of 22 kV silane cure TR-EPR cable
Authors: Agustin Fernando , Kalam Akhtar , Zayegh Aladin
Published: January 2021

EPR-insulated cables for distribution power network are not commonly used in Australia. This is due to the higher DDF of common EPR cables when compared with XLPE that contributes to the power loss and economics in transmitting electricity. This led to the development of EPR called TR-EPR with significantly lower DDF and uses silane curing process to address concerns about cost-effectiveness. The thermal behavior of low DDF silane cure TR-EPR is investigated for 30 months of exposure to the maximum operating temperature of material. The physical changes in the samples throughout the long-term aging are examined to create an opportunity to model the expected life cycle of TR-EPR cable under thermal stress. The cross-linking characteristics of TR-EPR cable are also examined by ambient curing that simulates the storage condition for unused cable and by cable heating process that simulates the condition when the cable is energized. The results are tabulated for a better understanding of the time for the material to cross-link at various conditions. The improved partial discharge values after cross-linking are also presented.
Single switch Z source/quasi Z source DC-DC converters
Authors: Saravanan V , Sabitha M , Bindu V , K M Venkatachalam , Arumugam M
Published: January 2021

This paper analyzes a family of high step up single switch switched capacitor boost converters and Z-source/quasi Z-source dc-dc converters to provide high output dc voltage gain, a proper choice for photovoltaic applications. The operating principles, parameters design guideline of these converters are presented along with simulation results.
Epithelial Sodium Channel and Salt-Sensitive Hypertension
Authors: Mutchler Stephanie M. , Kirabo Annet , Kleyman Thomas R.
Published: January 2021

The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.
Longitudinal Changes of Input Impedance, Pulse Wave Velocity, and Wave Reflection in a Middle-Aged Population
Authors: Campos-Arias Daime , De Buyzere Marc L. , Chirinos Julio A. , Rietzschel Ernst R. , Segers Patrick
Published: January 2021

The changes experienced by the arterial system due to the aging process have been extensively studied but are incompletely understood. Within-subject patterns of changes in regards to input impedance and wave reflection parameters have not been assessed. The Asklepios study is a longitudinal population study including healthy (at onset) middle-aged subjects, with 974 males and 1052 females undergoing 2 rounds of measurements of applanation tonometry and ultrasound, 10.15±1.40 years apart. Carotid-femoral pulse wave velocity, aortic input impedance, and wave reflection parameters were assessed, and linear mixed-effects models were used to evaluate their longitudinal trajectories and determinants. Overall, the effective 10-year increase in pulse wave velocity was less than expected from first round cross-sectional data, and pulse wave velocity was found to accelerate more in women than in men. Interestingly, the increase in pulse wave velocity was not paralleled by a decrease in arterial volume compliance, particularly in younger males. Aortic root characteristic impedance decreased with age in younger subjects while it increased for the older subjects in the study. These changes suggest that aortic dilation and elongation may play an important role determining the longitudinal age-related changes in impedance parameters in middle-age. Wave reflection decreased with aging, whereas resistance increased in women and decreased in men. We conclude that the effective impact of aging on arterial system properties, in a middle-aged population, is not well reflected by cross-sectional studies. Future studies should assess the interaction between geometric remodeling and wall stiffening as determinants of pulsatile hemodynamics.
Stroke in Women
Authors: Kapral Moira K. , Bushnell Cheryl
Published: January 2021

Sex differences exist in the epidemiology, care, and outcomes of stroke. This article highlights recent advances in our understanding of sex and gender differences in the benefits of endovascular therapy, outcomes after stroke and transient neurological events, and the potential to prevent stroke in women with a history of hypertensive disorders of pregnancy.
Reality-Assisted Evolution of Soft Robots through Large-Scale Physical Experimentation: A Review
Authors: Howison Toby , Hauser Simon , Hughes Josie , Iida Fumiya
Published: January 2021

We introduce the framework of reality-assisted evolution to summarize a growing trend towards combining model-based and model-free approaches to improve the design of physically embodied soft robots. In silico, data-driven models build, adapt, and improve representations of the target system using real-world experimental data. By simulating huge numbers of virtual robots using these data-driven models, optimization algorithms can illuminate multiple design candidates for transference to the real world. In reality, large-scale physical experimentation facilitates the fabrication, testing, and analysis of multiple candidate designs. Automated assembly and reconfigurable modular systems enable significantly higher numbers of real-world design evaluations than previously possible. Large volumes of ground-truth data gathered via physical experimentation can be returned to the virtual environment to improve data-driven models and guide optimization. Grounding the design process in physical experimentation ensures that the complexity of virtual robot designs does not outpace the model limitations or available fabrication technologies. We outline key developments in the design of physically embodied soft robots in the framework of reality-assisted evolution.
Jane Austen
Authors: Bartlett Nora
Published: January 2021

This volume presents an exhilarating and insightful collection of essays on Jane Austen – distilling the author’s deep understanding and appreciation of Austen’s works across a lifetime. The volume is both intra- and inter-textual in focus, ranging from perceptive analysis of individual scenes to the exploration of motifs across Austen’s fiction.

Full of astute connections, these lively discussions hinge on the study of human behaviour – from family relationships to sickness and hypochondria – highlighting Austen’s artful literary techniques and her powers of human observation.

Jane Austen: Reflections of a Reader by (the late) Nora Bartlett is a brilliant contribution to the field of Jane Austen studies, both in its accessible style (which preserves the oral register of the original lectures), and in its foregrounding of the reader in a warm, compelling and incisive conversation about Austen’s works. As such, it will appeal widely to all lovers of Jane Austen, whether first-time readers, students or scholars.