bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-energy Pipelined Hardware Design for Approximate Medium Filter
Authors: Mahmoud Mervat M. A. , Elashkar Nahla E. , Draz Heba H.
Published: January 2023

Image and video processing algorithms are currently crucial for many applications. Hardware implementation of these algorithms provides higher speed for large computation applications. Removing noise is often a typical pre-processing step to enhance the results of later analysis and processing. Median filter is a typical nonlinear filter that is very commonly used for impulse noise elimination in digital image processing. This article suggests a low-energy median filter hardware design for battery-based hardware applications. An approximate solution with high accuracy is investigated to speed up the filtering operation, reduce the area, and consume less power/energy. Pipelining and parallelism are used to optimize the speed and power of this technique. Non-pipelined, two different pipelined structures, and two parallel architectures versions are designed. The design versions are implemented first with a Virtex-5 LX110T FPGA and then using the UMC 130nm standard cell ASIC technology. The selection and the even-odd sorting-based median filters are also implemented for an equitable comparison with the standard median filtering techniques. The suggested non-pipelined median filter design enhances the throughput 35% more than the highest investigated state of the art. The pipelining enhances the throughput to more than twice its value. Additionally, the parallel architecture decreases the area and the consumed power by around 40%. The simulation results reveal that one of the suggested designs significantly decreases the area, with the same speed as the fastest design in the literature, without noticeably degrading the accuracy, and a significant decrease in energy consumption by about 60%.
Multi-Level Visual Similarity Based Personalized Tourist Attraction Recommendation Using Geo-Tagged Photos
Authors: Chen Ling , Lyu Dandan , Yu Shanshan , Chen Gencai
Published: January 2023

Geo-tagged photo-based tourist attraction recommendation can discover users’ travel preferences from their taken photos, so as to recommend suitable tourist attractions to them. However, existing visual content-based methods cannot fully exploit the user and tourist attraction information of photos to extract visual features, and do not differentiate the significance of different photos. In this article, we propose multi-level visual similarity-based personalized tourist attraction recommendation using geo-tagged photos (MEAL). MEAL utilizes the visual contents of photos and interaction behavior data to obtain the final embeddings of users and tourist attractions, which are then used to predict the visit probabilities. Specifically, by crossing the user and tourist attraction information of photos, we define four visual similarity levels and introduce a corresponding quintuplet loss to embed the visual contents of photos. In addition, to capture the significance of different photos, we exploit the self-attention mechanism to obtain the visual representations of users and tourist attractions. We conducted experiments on two datasets crawled from Flickr, and the experimental results proved the advantage of this method.
Model-driven Cluster Resource Management for AI Workloads in Edge Clouds
Authors: Liang Qianlin , Hanafy Walid A. , Ali-Eldin Ahmed , Shenoy Prashant
Published: January 2023

Since emerging edge applications such as Internet of Things (IoT) analytics and augmented reality have tight latency constraints, hardware AI accelerators have been recently proposed to speed up deep neural network (DNN) inference run by these applications. Resource-constrained edge servers and accelerators tend to be multiplexed across multiple IoT applications, introducing the potential for performance interference between latency-sensitive workloads. In this article, we design analytic models to capture the performance of DNN inference workloads on shared edge accelerators, such as GPU and edgeTPU, under different multiplexing and concurrency behaviors. After validating our models using extensive experiments, we use them to design various cluster resource management algorithms to intelligently manage multiple applications on edge accelerators while respecting their latency constraints. We implement a prototype of our system in Kubernetes and show that our system can host 2.3× more DNN applications in heterogeneous multi-tenant edge clusters with no latency violations when compared to traditional knapsack hosting algorithms.
Report on the First International Workshop on Data Systems Education (DataEd '22)
Authors: Aivaloglou Efthimia , Fletcher George , Liut Michael , Miedema Daphne
Published: January 2023

This report summarizes the outcomes of the first international workshop on Data Systems Education: Bridging Education Practice with Education Research (DataEd '22). The workshop was held in conjunction with the SIGMOD '22 conference in Philadelphia, USA on June 17, 2022. The aim of the workshop was to provide a dedicated venue for presenting and and discussing data management systems education experiences and research by bringing together the database and the computing education research communities to share findings, to crosspollinate perspectives and methods, and to shed light on opportunities for mutual progress in data systems education. The program featured two keynote talks, ten research paper presentations, a discussion session, and an industry panel discussion. In this report, we present the workshop's main results, observations, and emerging research directions.
The World of Graph Databases from An Industry Perspective
Authors: Tian Yuanyuan
Published: January 2023

Rapidly growing social networks and other graph data have created a high demand for graph technologies in the market. A plethora of graph databases, systems, and solutions have emerged, as a result. On the other hand, graph has long been a well studied area in the database research community. Despite the numerous surveys on various graph research topics, there is a lack of survey on graph technologies from an industry perspective. The purpose of this paper is to provide the research community with an industrial perspective on the graph database landscape, so that graph researcher can better understand the industry trend and the challenges that the industry is facing, and work on solutions to help address these problems.
How Connected Are Our Conference Review Boards?
Authors: Bhowmick Sourav S.
Published: January 2023

Dense co-authorship network formed by the review board members of a conference may adversely impact the quality and integrity of the review process. In this report, we shed light on the topological characteristics of such networks for three major data management conference venues. Our results show all these venues give rise to dense networks with a large giant component. We advocate to rethink the traditional way review boards are formed to mitigate the emergence of dense networks.
Next-Generation Estrogen Receptor–Targeted Therapeutics
Authors: Fernando Tharu M. , Moore Heather M. , Wongchenko Matthew J. , Metcalfe Ciara
Published: January 2023

Estrogen receptor (ER) α is expressed in the vast majority of breast cancers and is one of the most successfully prosecuted drug targets in oncology, with multiple classes of endocrine therapies approved for the treatment of ER+ breast cancer. These existing agents are highly active, both as single agents and as combination partners for other targeted therapies, and have significantly benefited patients. However, each of these standard-of-care (SOC) therapies has liabilities that allow for the reengagement of ER signaling as a mechanism of resistance. Data supporting the continued dependence of tumors on ER signaling following exposure to SOC agents have underpinned an extraordinary reenergizing of academic, biotechnology, and pharmaceutical groups pursuing next-generation ER-targeted therapies. The hypothesis that there remains an opportunity to bring further meaningful benefit to patients through fully optimized ER-targeted therapies is currently being investigated in the clinic.
The Blood-Brain Barrier: Implications for Experimental Cancer Therapeutics
Authors: Straehla Joelle P. , Reardon David A. , Wen Patrick Y. , Agar Nathalie Y.R.
Published: January 2023

The blood-brain barrier is critically important for the treatment of both primary and metastatic cancers of the central nervous system (CNS). Clinical outcomes for patients with primary CNS tumors are poor and have not significantly improved in decades. As treatments for patients with extracranial solid tumors improve, the incidence of CNS metastases is on the rise due to suboptimal CNS exposure of otherwise systemically active agents. Despite state-of-the art surgical care and increasingly precise radiation therapy, clinical progress is limited by the ability to deliver an effective dose of a therapeutic agent to all cancerous cells. Given the tremendous heterogeneity of CNS cancers, both across cancer subtypes andwithin a single tumor, and the range of diverse therapies under investigation, a nuanced examination of CNS drug exposure is needed. With a shared goal, common vocabulary, and interdisciplinary collaboration, the field is poised for renewed progress in the treatment of CNS cancers.
On the Biology and Therapeutic Modulation of Macrophages and Dendritic Cells in Cancer
Authors: Park Matthew D. , Belabed Meriem , Chen Steven T. , Hamon Pauline , Hegde Samarth , Mattiuz Raphaël , Marron Thomas U. , Merad Miriam
Published: January 2023

Myeloid cells represent a dominant cellular compartment of tumor lesions and play key roles in tumor inception, progression, metastasis, and response to treatment. Mononuclear phagocytes (MNPs), which include dendritic cells and macrophages, are unique among myeloid cells, as they not only shape both the broader composition and state of the tumor microenvironment but can also specifically instruct cancer-specific, T cell–mediated tumor cell killing, making them especially attractive targets for cancer treatment. Although MNPs remain difficult to modulate therapeutically, our understanding of MNP biology in the antitumor immune response has expanded significantly, offering hope for new possibilities in cancer immunotherapy. Here, we review the recent advances in our study of the cellular identity, molecular diversity, and spatial organization of MNPs in tumors, and we discuss the importance of tailoring therapeutic strategies to incorporate these new insights into cancer treatment design.
Soft Actuators and Robots Enabled by Additive Manufacturing
Authors: Wang Dong , Wang Jinqiang , Shen Zequn , Jiang Chengru , Zou Jiang , Dong Le , Fang Nicholas X. , Gu Guoying
Published: January 2023

Soft robotic systems are human friendly and can mimic the complex motions of animals, which introduces promising potential in various applications, ranging from novel actuation and wearable electronics to bioinspired robots operating in unstructured environments. Due to the use of soft materials, the traditional fabrication and manufacturing methods for rigid materials are unavailable for soft robots. 3D printing is a promising fabrication method for the multifunctional and multimaterial demands of soft robots, as it enables the personalization and customization of the materials and structures. This review provides perspectives on the manufacturing methods for various types of soft robotic systems and discusses the challenges and prospects of future research, including in-depth discussion of pneumatic, electrically activated, magnetically driven, and 4D-printed soft actuators and integrated soft actuators and sensors. Finally, the challenges of realizing multimaterial, multiscale, and multifunctional 3D-printed soft robots are discussed.
Biomaterials-Mediated Engineering of the Immune System
Authors: Backlund Coralie , Jalili-Firoozinezhad Sasan , Kim Byungji , Irvine Darrell J.
Published: January 2023

Modulation of the immune system is an important therapeutic strategy in a wide range of diseases, and is fundamental to the development of vaccines. However, optimally safe and effective immunotherapy requires precision in the delivery of stimulatory cues to the right cells at the right place and time, to avoid toxic overstimulation in healthy tissues or incorrect programming of the immune response. To this end, biomaterials are being developed to control the location, dose, and timing of vaccines and immunotherapies. Here we discuss fundamental concepts of how biomaterials are used to enhance immune modulation, and evidence from preclinical and clinical studies of how biomaterials-mediated immune engineering can impact the development of new therapeutics. We focus on immunological mechanisms of action and in vivo modulation of the immune system, and we also discuss challenges to be overcome to speed translation of these technologies to the clinic.
Photochemical Upconversion
Authors: Feng Jiale , Alves Jessica , de Clercq Damon M. , Schmidt Timothy W.
Published: January 2023

Photochemical upconversion is a process whereby two lower-energy photons are converted into a higher-energy photon by sensitized triplet–triplet annihilation. While recent interest in this process has been motivated by improving the efficiencies of solar cells, many applications are being explored. In this review, we address the underlying physicochemical phenomena that are responsible for photochemical upconversion. We review their kinetics, and the requirements for annihilators and sensitizers to design efficient upconversion systems. We discuss the spin physics of the bi-excitonic interactions and how the spin character of the triplet pairs can fundamentally limit the upconversion efficiency and give rise to the magnetic field effect on delayed photoluminescence. Finally, we address light-matter coupling phenomena that could be employed to enhance photochemical upconversion.
Tuning the Performance of Nanofiller Reinforced Phosphorylated Chitosan-Based Proton Exchange Membrane
Authors: Ahmed Saad , Tao Zhengyuan , Zhang Hao , Ahmed Naveed , Gulzar Haroon , Wang Jianli
Published: January 2023

In this study, a one-step method was enforced for the phosphorylation of chitosan (CS) using ATMP, and later amino functionalized multiwalled carbon nanotubes (MWCNTs-NH2) were used for the fabrication of PCS/N-MWCNTs membranes. The phosphorylation of CS and later PCS/N-MWCNTs nanocomposite membranes were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). They were also evaluated for their mechanical properties, water uptake, area swelling ratio, ion-exchange capacity (IEC), and proton conductivity. Interfacial interaction among an -NH2 group of MWCNTs and -phosphonic acid as well as the -NH2 group of PCS provided extra sites for proton transfer, thus improving the proton conductivity of PCS/N-MWCNTs membranes. These results revealed that the incorporation of N-MWCNTs into PCS chains lowers PCS chain mobility and ultimately improved the thermal and mechanical properties of the composite membranes. The proton conductivity of the composite membrane with 5 wt.% of N-MWCNTs at 80 °C was 0.045 S.cm−1. Thus, PCS/N-MWCNTs nanocomposite membranes as a PEM can be used in fuel cells. With this advantage, the N-MWCNTs-filled hydrogen fuel cell outperforms compared to PCS filled membrane.
BDNF-induced phrenic motor facilitation shifts from PKCθ to ERK dependence with mild systemic inflammation
Authors: Agosto-Marlin Ibis M. , Nikodemova Maria , Dale Erica A. , Mitchell Gordon S.
Published: January 2023

We demonstrate that even mild systemic inflammation shifts signaling mechanisms giving rise to BDNF-induced phrenic motor plasticity. This finding has important experimental, biological, and translational implications, particularly since BDNF-dependent spinal plasticity is being translated to restore breathing and nonrespiratory movements in diverse clinical disorders, such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS).
Molecular Targets of Shenqi Dihuang, A Traditional Chinese Herbal
Medicine, and Its Potential Role in Renal Cell Carcinoma Therapy
Authors: Chen Xinglin , Zhang Tongtong , Zhan Xiangyang , Zang Xinyue , Zhai Xinyu , Wan Zhong , Ge Minyao , Tan Mingyue , Gu Jianyi , Xu Dongliang
Published: January 2023

Chinese herbal medicine (CHM), which includes herbal slices and proprietary
products, is widely used in China. Shenqi Dihuang (SQDH) is a traditional
Chinese medicine (TCM) formula with ingredients that affect tumor growth.
Despite recent advances in prognosis, patients with renal cell carcinoma (RCC)
cannot currently receive curative treatment. The present study aimed to explore
the potential target genes closely associated with SQDH. The gene expression
data for SQDH and RCC were obtained from the TCMSP and TCGA databases. The
SQDH-based prognostic prediction model reveals a strong correlation between RCC
and SQDH. In addition, the immune cell infiltration analysis indicated that SQDH
might be associated with the immune response of RCC patients. Based on this, we
successfully built the prognostic prediction model using SQDH-related genes. The
results demonstrated that CCND1 and NR3C2 are closely associated with the
prognosis of RCC patients. Finally, the pathways enrichment analysis revealed
that response to oxidative stress, cyclin binding, programmed cell death, and
immune response are the most enriched pathways in CCND1. Furthermore,
transcription regulator activity, regulation of cell population proliferation,
and cyclin binding are closely associated with the NR3C2.
Population- and Gender-Based Investigation for Prevalence of Helicobacter pylori in Dhamar, Yemen
Authors: Almashhadany Dhary A. , Mayas Sara M. , Mohammed Hero I. , Hassan Abdulwahed A. , Khan Izhar U. H.
Published: January 2023

Among 35 species of genus Helicobacter, H. pylori is the most common causative agent of human gastritis, peptic ulcer, and gastric cancer. The infection can spread through direct human-to-human contact, fecal–oral route, and contaminated water. The study was designed to investigate the rate of prevalence of H. pylori in the population of Dhamar, Yemen. In this one-year study, 460 including 250 male and 210 female stool specimens were collected between January to December 2020 in Dhamar Governorate, Yemen. Of the total 460, 215 rural (male: n = 120 and female: n = 95) and 245 urban (male: n = 130 and female: n = 115) specimens were investigated for identification of H. pylori by serological test using Helicobacter pylori stool antigen (HpSA) test. In addition, for comparing an improved recovery of H. pylori, conventional culture-based isolation was also carried out using three selective media. Modified Campy-blood Agar (MCA), Belo Horizonte Agar (BHA), and Egg yolk Emulsion (EYE) medium supplemented with antimicrobial agents including vancomycin (10 mg/L), cefsulodin (5 mg/L), trimethoprim (5 mg/L), and amphotericin B (5 mg/L) and isolates were phenotypically characterized. The HpSA test results revealed that of the total 460 specimens, 89 (19.3%) were positive for H. pylori with relatively low in male (n = 43; 17.2%) as compared to the female (n = 46; 21.9%) specimens. After 3–10 days of incubation, H. pylori was recovered at a variable rate on each selective (MCA: 16.5%; BHA: 15.0%; EYE: 13.0%) media. However, culture-based assay results showed less recovery (n = 81; 17.6%) with no significant difference among all selective media tested and between genders (male: n = 39; 15.6%; female: n = 42; 20.0%). The infection rate was comparatively higher in rural (n = 45; 20.9%) as compared to urban (n = 36; 14.7%) population. Overall, the study data showed the prevalence of infection in both genders of all age groups. The present study showed a relatively high rate of infection of H. pylori in the Dhamar population. The serological identification and culture-based methods are important for rapid detection, aid in treatment, and developing policies for the control and eradication of H. pylori infection and to prevent the disease in different age groups in Yemen.
Berberine in Sepsis: Effects, Mechanisms, and Therapeutic Strategies
Authors: Lv Tingxia , Zhang Chunpan , Hu Lan , Wang Chao , Li Shirong , Wang He , Qi Wenjie
Published: January 2023

Sepsis is defined as a dysregulated immune response to infection that leads to multiple organ dysfunction. To date, though a growing body of knowledge has gained insight into the clinical risk factors, pathobiology, treatment response, and recovery methods, sepsis remains a significant concern and clinical burden. Therefore, further study is urgently needed to alleviate the acute and chronic outcomes. Berberine (BBR), a traditional Chinese medicine with multiple actions and mechanisms, has been investigated in cellular and rodent animal models of sepsis mainly based on its anti-inflammatory effect. However, the practical application of BBR in sepsis is still lacking, and it is imperative to systematically summarize the study of BBR in sepsis. This review summarized its pharmacological activities and mechanisms in septic-related organ injuries and the potential BBR-based therapeutic strategies for sepsis, which will provide comprehensive references for scientific research and clinical application.
On Powers and Roots of Split Octonions
Authors: Akbıyık Mücahit
Published: January 2023

In this article, we obtain the polar forms for two types of split octonions. We calculate De Moivre’s formulas for all polar forms of split octonions. Thus, we give thenth−powers and roots of split octonions and the matrix representation of split octonions. In addition, we present an illustrative example with Matlab codes.
Analysis of Determinants of Economic Efficiency in Honey Production in Horo Guduru Zone, Ethiopia: Stochastic Dual Cost Frontier Model Approach
Authors: Tesema Tolesa , Adugna Megersa
Published: January 2023

Honey production is generating employment and source of income in the rural area of Ethiopia. However, its productivity was low. The objective of this study was to measure the economic efficiency of honey production in Ethiopia’s Horo Guduru Wollega Zone and their limiting factors. To achieve the above-mentioned objective, the study employed a survey methodology using a structured questionnaire tool, and the data were collected from 396 households. Both descriptive and econometric data analysis methods are employed. Dual cost was used to measure the levels of economic efficiency and the Tobit model to identify the determinants of economic efficiency in the study area. In this regard, the analysis relied on a cross-sectional data collected from 396 sample farm households. The mean economic efficiency was 44%. This demonstrates that the farmers in the study area have to decrease production cost by 56% to achieve 100% economic efficiency level. From the determinants of economic efficiency family size, extension services, training, beekeeping experience, and family size are significant technical efficiency variables for honey producers. The study suggests policies to address economic inefficiencies by increasing the number of hives, extending the best performers’ experience by increasing the frequency of extension contacts on honey production, facilitating and expanding credit service in the study area, making bee forage access simple, and increasing forest coverage on the land area in line with the current policy of Ethiopia. Additionally, since farmers in the study area spend their time guarding the honey from damage by ants and monkeys, labor that utilizes technology must be made available in the study area.
Technology for Fundamental Improvement of an Extremely Low-Quality Video Signal for Use in Fine Focusing and Astigmatism Correction in Scanning Electron Microscopy
Authors: Oho Eisaku , Yamazaki Sadao , Suzuki Kazuhiko
Published: January 2023

This study describes important techniques for production of a series of video signals for use in fine focusing operations and near-perfect astigmatism correction in the general-purpose scanning electron microscopy (SEM) field. These techniques can enhance the stability of the signal greatly when used for focusing. As two particularly important fundamental techniques, SEM image acquisition with priority given to the signal-to-noise ratio and signal reinforcement based on the active image processing concept were utilized fully. The performance improvement was evaluated using the case of a previously reported support system for fine focusing and astigmatism correction based on image covariance. The method is almost completely robust against noise within practical limits and allows for focusing and astigmatism correction for even extremely noisy SEM images. The results of this study may be useful not only in the SEM field but also in many fields that use weak signals.
The Effect of Spinal Muscle Fatigue and Psychosocial Factors on Pressure-Pain Threshold in Healthy Adults
Authors: Mais Susan , Smith Jo Armour
Published: January 2023

Objective. Pain sensitivity decreases following isometric exercise. It is not clear whether this exercise-induced hypoalgesia (EIH) occurs to the same extent in men and women. It is also unclear if the effect is systemic or local to the exercised musculature. The aim of our study was to investigate whether fatiguing isometric exercise of the spinal and hip extensors would result in increased pressure pain threshold (PPT) at sites local to and remote from the exercised muscles in healthy men and women and whether there is a relationship between central sensitization, psychosocial factors, and PPT. Subjects. 35 healthy adults (age 27.1 ± 4.5 years, 22 women). Methods. This was a within-subjects cohort study. Participants completed questionnaires quantifying central sensitization, pain catastrophizing, sleepiness/insomnia, anxiety, and depression. PPT was assessed at the lumbar and thoracic paraspinals, hamstrings, gastrocnemius, wrist, and third digit before and immediately after participants performed the Biering–Sorensen test to failure. Results. PPT increased postexercise in the thoracic paraspinals, hamstrings, and gastrocnemius in men and women and in the lumbar paraspinals in men only but did not change at the wrist and digit sites. A lower average PPT at baseline was associated with a higher central sensitization scores. A greater increase in average PPT postfatigue was significantly associated with higher average PPT at baseline. Conclusions. Exercise-induced hypoalgesia occurs at sites overlying the muscles involved in fatiguing exercise, but not at remote sites, and is more evident in males than females. The magnitude of EIH depends upon baseline PPT. Even in healthy individuals, greater central sensitization is associated with lower baseline PPT.
Revealing the Mineralogical and Petrographic Signs of Fluid-Related Processes in the Kelebia Basement Area (Szeged Basin, S Hungary): A Case Study of Alpine Prograde Metamorphism in a Permo-Triassic Succession
Authors: Varga Andrea , Pál-Molnár Elemér , Raucsik Béla
Published: January 2023

The Szeged Basin (S Hungary) occupies a relatively central position within the European Alpine–Carpathian–Dinaride orogenic belt. An ongoing controversy about the tectonic position of the study area indicates that its evolution is still not fully understood; however, several important hydrocarbon occurrences are known in the fractured basement reservoirs. The main aim of this contribution is to investigate the petrographic features and possible Alpine metamorphic conditions of volcanic/volcanoclastic and siliciclastic rocks from the Kelebia basement area. Due to the outcrop conditions and poor exposure, study samples are obtained from cores and core chips resulting from oil exploration. Based on an evaluation of petrographic (including also cathodoluminescence analysis) and microstructural features, joined with mineralogical and metamorphic data such as “illite crystallinity” and K-white mica crystallite size obtained by X-ray powder diffractometry (XRPD), a very low- to low-grade (ca. 300°C) Alpine metamorphic imprint of this portion of the basement can be proposed. Several deformation characteristics (deformation lamellae in quartz, deformation twins in dolomite, fragmented porphyroclasts, and strain shadows) were recognized in the studied samples, showing a weakly to moderately developed disjunctive foliation in the Permian rocks, as well as quartz veinlets, microcracks, and fluid inclusion planes in the Lower Triassic sandstones. Most likely, one of the Cretaceous orogenic events, namely, the “Turonian” phase (Early–Late Cretaceous nappe stacking), resulted in the prograde greenschist facies metamorphism in the study area, instead of the burial depth. We propose that the Permo-Triassic cover succession was also affected by shearing episodes accompanied by fluid migrations along the contact zone between the tectonic units. The scientific approach and dataset provided here are examples of how the application of XRPD parameters of phyllosilicates and micropetrographic observations can help to understand the evolution of an orogen and improve knowledge about the basement structure.
Redundant Signaling as the Predominant Mechanism for Resistance to Antibodies Targeting the Type-I Insulin-Like Growth Factor Receptor in Cells Derived from Childhood Sarcoma
Authors: Shackleford Terry J. , Hariharan Seethalakshmi , Vaseva Angelina V. , Alagoa Karina , Espinoza Maricruz , Bid Hemant K. , Li Fuyang , Zhong Haihong , Phelps Doris A. , Roberts Ryan D. , Cam Hakan , London Cheryl A. , Guttridge Denis C. , Chen Yidong , Rao Manjeet , Shiio Yuzuru , Houghton Peter J.
Published: January 2023

Antibodies targeting insulin-like growth factor 1 receptor (IGF-1R) induce objective responses in only 5% to 15% of children with sarcoma. Understanding the mechanisms of resistance may identify combination therapies that optimize efficacy of IGF-1R–targeted antibodies. Sensitivity to the IGF-1R–targeting antibody TZ-1 was determined in rhabdomyosarcoma and Ewing sarcoma cell lines. Acquired resistance to TZ-1 was developed and characterized in sensitive Rh41 cells. The BRD4 inhibitor, JQ1, was evaluated as an agent to prevent acquired TZ-1 resistance in Rh41 cells. The phosphorylation status of receptor tyrosine kinases (RTK) was assessed. Sensitivity to TZ-1 in vivo was determined in Rh41 parental and TZ-1–resistant xenografts. Of 20 sarcoma cell lines, only Rh41 was sensitive to TZ-1. Cells intrinsically resistant to TZ-1 expressed multiple (>10) activated RTKs or a relatively less complex set of activated RTKs (∼5). TZ-1 decreased the phosphorylation of IGF-1R but had little effect on other phosphorylated RTKs in all resistant lines. TZ-1 rapidly induced activation of RTKs in Rh41 that was partially abrogated by knockdown of SOX18 and JQ1. Rh41/TZ-1 cells selected for acquired resistance to TZ-1 constitutively expressed multiple activated RTKs. TZ-1 treatment caused complete regressions in Rh41 xenografts and was significantly less effective against the Rh41/TZ-1 xenograft. Intrinsic resistance is a consequence of redundant signaling in pediatric sarcoma cell lines. Acquired resistance in Rh41 cells is associated with rapid induction of multiple RTKs, indicating a dynamic response to IGF-1R blockade and rapid development of resistance. The TZ-1 antibody had greater antitumor activity against Rh41 xenografts compared with other IGF-1R–targeted antibodies tested against this model.
Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody
Authors: Niwa Yuki , Adachi Keito , Tabata Kimiyo , Ishida Ryoga , Hotta Koichiro , Ishida Tomomi , Mano Yuji , Ozawa Yoichi , Minoshima Yukinori , Funahashi Yasuhiro , Semba Taro
Published: January 2023

Eribulin is a microtubule dynamics inhibitor with tumor microenvironment modulation activity such as vascular remodeling activity. Here, we investigated antitumor and immunomodulatory activities of eribulin and its liposomal formulation (eribulin-LF) as monotherapies or in combination with anti–programmed death 1 (PD-1) Ab. The antitumor activity of eribulin or eribulin-LF as monotherapy or in combination with anti–PD-1 Ab was examined in a P-glycoprotein–knockout 4T1 model. Eribulin and eribulin-LF showed stronger antitumor activity in immunocompetent mice compared with immunodeficient mice, indicating that they have immunomodulatory activity that underlies its antitumor activity. Combination therapy of eribulin and eribulin-LF with anti–PD-1 Ab showed antitumor activity, and the combination activity of eribulin-LF with anti–PD-1 Ab was observed at a lower dose and longer interval of administration compared with that using eribulin. To examine the immunomodulatory activity of eribulin and eribulin-LF and its underlying mechanisms, we performed flow cytometry, IHC, and gene expression profiling. IHC and flow cytometry revealed that eribulin-LF increased microvessel density and intratumoral populations of cytotoxic T cells and natural killer cells rather than eribulin. Gene expression profiling demonstrated that eribulin-LF induces IFNγ signaling. Furthermore, IHC also showed that eribulin-LF increased infiltration of CD8-positive cells together with increased CD31-positive cells. Eribulin-LF also increased ICAM-1 expression, which is essential for lymphocyte adhesion to vascular endothelial cells. In conclusion, eribulin showed combination antitumor activity with anti–PD-1 Ab via immunomodulation due to its vascular remodeling activity, and the liposomal formulation showed improved antitumor activity over the standard formulation.
Focused Ultrasound Thalamotomy: Correlation of Postoperative Imaging with Neuropathological Findings
Authors: Blitz Sarah E. , Torre Matthew , Chua Melissa M.J. , Christie Sarah L. , McDannold Nathan J. , Cosgrove G. Rees
Published: January 2023

Magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) is a rapidly developing technique used for tremor relief in tremor-predominant Parkinson’s disease (PD) and essential tremor that has demonstrated successful results. Here, we describe the neuropathological findings in a woman who died from a fall 10 days after successful MRgFUS for tremor-predominant PD. Histological analysis demonstrates the characteristic early postoperative MRI findings including 3 distinct zones on T2-weighted imaging: (1) a hypointense core, (2) a hyperintense region with hypointense rim, and (3) a slightly hyperintense, poorly marginated surrounding area. Histopathological analyses also demonstrate the suspected cellular processes composing each of these regions including central hemorrhagic necrosis with surrounding cytotoxic edema and a rim of mostly unaffected vasogenic edema with some reactive and reparative processes. Overall, this case demonstrates the correlation of postoperative imaging findings with the subacute neuropathological findings after MRgFUS for PD.
COVID-19 Stigma Correlates with Burnout among Healthcare Workers: Evidence from Healthcare Workers Practicing in Saudi Arabia
Authors: Alnahdi Omar S. , Albuqaytah Faisal A. , Alotaibi Najla , Afeef Marwah A. , Natto Zuhair S. , Subahi Razin H.
Published: January 2023

Introduction: COVID-19-related stigma is the level of stigma associated with being involved with the pandemic. It has been reported that a significant number of healthcare workers experienced anxiety, depression, stigmatization, physical violence, harassment during the COVID-19 pandemic; even the families of the healthcare workers were victims of discrimination and stigmatization. The aim of our study was to determine the prevalence of COVID-19-related stigma among the healthcare workers in Saudi Arabia and to assess the COVID-19-related stigma, its associated factors, and burnout correlate. Methods: Web-based, self-administered questionnaire has been sent to healthcare workers’ official emails through the internal communication department in the targeted hospitals. It includes the COVID-19-related stigma-validated scale “E16-COVID19-S” and two questions relative to the full Maslach Burnout Inventory assessing the burnout. The required sample is 377 based on the sample size calculation with a response rate of 50%. Results: A total of 407 responses were received from the targeted population. Of them, 49.4% scored high on the COVID-19-related stigma scale. The correlation between the COVID-19-related stigma and burnout was found to be moderately positive and statistically significant (rs = 0.515, p= <0.001). Conclusion: It has been found that gender, workplace capacity, ever taking COVID-19 test during the pandemic had a significant impact on scoring high on the COVID-19-related stigma scale. Moreover, there is a correlation between being stigmatized during the pandemic and being burned out.
Management Strategy for Gallbladder Polypoid Lesions: Results of a 5-Year Single-Center Cohort Study
Authors: Tian Feng , Ma Yu-xin , Liu Yi-fan , Liu Wei , Hong Tao , He Xiao-dong , Qu Qiang
Published: January 2023

Introduction: Controversy remains about the classification, differential diagnosis, and treatment strategy for gallbladder polypoid lesions (GPLs). This study sought to explore the individualized treatment strategy for GPLs. Methods: We retrospectively studied 642 consecutive patients with GPLs from January 2015 to May 2020. Univariate and multivariable analyses were performed to explore the potential risk factors for neoplastic polyps. The outcome of laparoscopic gallbladder-preserving polypectomy (GPP) was evaluated and compared with that of laparoscopic cholecystectomy (LC). Results: Of 642 enrolled patients, 572 underwent LC, and 70 underwent GPP. Pathologically, the majority of GPLs were cholesterol polyps (68.4%), followed by adenomyomatosis (19.9%), benign adenoma (7.3%), adenocarcinoma (3.6%), and rare pathological types (0.8%). Additionally, 66.3% (379/572) of the LC cases were classified as non-neoplastic, and 33.7% (193/572) neoplastic polyps. Multivariate analysis demonstrated that single polyps (OR 1.956, 95% CI: 1.121–3.412; p = 0.018), polyps located at the gallbladder fundus (OR 4.326, 95% CI: 2.179–8.591; p < 0.001), polyps not less than 14 mm (OR 2.833, 95% CI: 1.614–4.973; p < 0.001), and polyps with a broad base (OR 4.173, 95% CI: 1.743–9.990; p = 0.001) were independent risk factors for neoplastic polyps. The 5-year prospective results after GPP showed that the 1-year and 3-year polyp recurrence rates were 13.2% and 23.4%, respectively. Conclusion: The majority of GPLs are cholesterol or other benign lesions without malignant potential. LC is the main treatment procedure for GPLs with a high neoplastic risk. GPP is potentially feasible and could be an alternative management strategy for a group of GPLs patients who meet the selection criteria.
Bioenergy Treatment for Improving Well-Being: A Meta-Analysis
Authors: Walach Harald , Marmann Peter
Published: January 2023

Background: Bioenergy treatment devices for self-treatment with the aim to improve well-being are widely available, have become popular, and are used by a rather large number of persons. Yet, a systematic analysis of the assumed effect of these devices has not yet been conducted. We meta-analyzed eight very similar studies of the Healy device to assess the joint effect size. Method: Eight studies with similar designs, some active controlled and some wait-list controlled, testing the Healy bioenergy device, were meta-analyzed. They were conducted by the producer of the device for quality assurance and further development of the application. An additional literature search revealed no additional, independent studies. Result: The overall effect size across studies, combining all active arms and averaging outcome measures, is Hedge’s g = 0.757 (random effects model, I2 = 85.8; z = 6.57; p < 0.0001). The stronger active intervention against control yields a heterogeneous g = 0.825 (random effects, I2 = 82.5; z = 7.77; p < 0.0001). Active treatments against each other result in a significant g = 0.29 (fixed effects, I2 = 0.0; z = 8.34; p < 0.0001). Discussion: The highest effect sizes are produced by a measure of coherence, followed by the WHO5 well-being questionnaire, the Perceived Stress Scale, with the Measure Your Own Medical Outcome Profile, resulting in the smallest effect size. Heterogeneity can be partially explained by the type of control, with active control producing smaller and wait-list control producing larger outcomes. Another source of heterogeneity is the sequencing of studies. Effect sizes grew for three studies, which were similar, and then fell and remained very similar for the rest of the studies. A limitation of this analysis is the fact that all studies were conducted by the R and D Department of the producer of the device. Conclusion: In this meta-analysis, the Healy device showed considerable effects, improving general well-being in healthy individuals. Nonetheless, an independent confirmation of these findings would be desirable. Moreover, the potential mechanisms of effect of the bioenergy device remain unclear, and further studies addressing this research question are warranted.
Conceptual design and simulation study of an autonomous indoor medical waste collection robot
Authors: Shaju Shawn , George Thomas , Francis Jithin Kunnath , Joseph Manu , Thomas Mervin Joe
Published: January 2023

Solid waste management is one of the critical challenges seen everywhere, and the coronavirus disease (COVID-19) pandemic has only worsened the problems in the safe disposal of infectious waste. This paper outlines a design for a mobile robot that will intelligently identify, grasp, and collect a group of medical waste items using a six-degree of freedom (DoF) arm, You Only Look Once (YOLO) neural network, and a grasping algorithm. Various designs are generated before running simulations on the selected virtual model using Robot Operating System (ROS) and Gazebo simulator. A lidar sensor is also used to map the robot's surroundings and navigate autonomously. The robot has good scope for waste collection in medical facilities, where it can help create a safer environment.
On solving the kinematics and controlling of origami box-shaped robot
Authors: Thai Phuong Thao , Nguyen Ngoc Hai
Published: January 2023

Nowadays, there are various research on transformable robot. The use of origami pattern for transformable robot can be found in many research. The disadvantages of traditional origami model are the suitable material for folding is zero thickness, complicated patterns and overconstrained mechanism. In this paper, the idea of designing 1 degree-of-freedom box-shaped robot is proposed and two types of robot design have been analyzed. The first design is the waterbomb robot, that uses the traditional origami pattern. The second model takes the Sarrus linkage as the main mechanism for the mobile robot. In both designs, only one motor is required for the transformation of the robot, making the robot light-weight and portable. This paper analyzes the kinematic and dynamic properties of two transformable robots by using MATLAB. The comparison of the torque required for forming 3D shape has been done for optimizing robot design. Finally, the real model optimized design is introduced to illustrate the proposed method. 
Prediction Model Based on Easily Available Markers for Aberrant Cardiac Remodeling in Women After Pregnancy
Authors: Mohseni-Alsalhi Zenab , B.N.J. Janssen Emma , Delmarque Jil , van Kuijk Sander M.J. , Spaanderman Marc E.A. , Ghossein-Doha Chahinda
Published: January 2023

BACKGROUND:

Preeclampsia is strongly associated with left ventricular concentric remodeling (LVCR) and left ventricular hypertrophy (LVH) up to 10 years after delivery. This predisposes to heart failure later in life. Adequate detection and prediction of LVCR or LVH is expected to decrease the risk of developing clinical heart failure within this high-risk female population. Therefore, we developed and internally validated a prediction model for aberrant cardiac remodeling in formerly pregnant women.

METHODS:

This large cohort study included women with a history of preeclampsia or normotensive pregnancy within a postpartum interval of 6 months to 30 years. Cardiovascular assessment was performed, including echocardiography, 30-minute blood pressure measurements, and circulating biomarkers. Aberrant cardiac remodeling based on echocardiographic findings was defined as either LVCR or LVH. Discriminative performance was evaluated by the area under the receiver operating characteristic curve.

RESULTS:

A total of 1397 women were included, of which 139 (10%) with LVCR or LVH (mean±SD age, 43±9 years) and 1258 (90%) without LVCR or LVH (40±8 years). The final prediction model was established based on the predictors age, waist circumference, systolic blood pressure, glycated hemoglobin, antihypertensive medication use, and early onset preeclampsia (yes/no). After internal validation, the prediction model showed accurate discriminative ability with an area under the receiver operating characteristic curve of 0.702 (95% CI, 0.657–0.756).

CONCLUSIONS:

Based on the conventional predictors, we developed a prediction model for women who are on average 8 to 12 years postpartum. Internal validation showed accurate discriminative ability. Upon external validation, this model may aid clinicians to initiate further diagnostic testing or clinical follow-up.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02347540.
Long‐Term Visit‐to‐Visit Glycemic Variability as a Predictor of Major Adverse Limb and Cardiovascular Events in Patients With Diabetes
Authors: Hsu Jung‐Chi , Yang Yen‐Yun , Chuang Shu‐Lin , Huang Kuan‐Chih , Lee Jen‐Kuang , Lin Lian‐Yu
Published: January 2023

Background

Peripheral arterial disease (PAD) is a severe complication in patients with type 2 diabetes. Glycemic variability (GV) is associated with increased risks of developing microvascular and macrovascular diseases. However, few studies have focused on the association between GV and PAD.

Methods and Results

This cohort study used a database maintained by the National Taiwan University Hospital, a tertiary medical center in Taiwan. For each individual, GV parameters were calculated, including fasting glucose coefficient of variability (FGCV) and hemoglobin A1c variability score (HVS). Multivariate Cox regression models were constructed to estimate the relationships between GV parameters and composite scores for major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs). Between 2014 and 2019, a total of 45 436 adult patients with prevalent type 2 diabetes were enrolled for analysis, and GV was assessed during a median follow‐up of 64.4 months. The average number of visits and time periods were 13.38 and 157.87 days for the HVS group and 14.27 and 146.59 days for the FGCV group, respectively. The incidence rates for cardiac mortality, PAD, and critical limb ischemia (CLI) were 5.38, 20.11, and 2.41 per 1000 person‐years in the FGCV group and 5.35, 20.32, and 2.50 per 1000 person‐years in HVS group, respectively. In the Cox regression model with full adjustment, the highest FGCV quartile was associated with significantly increased risks of MALEs (hazard ratio [HR], 1.57 [95% CI, 1.40–1.76];
P
<0.001) and MACEs (HR, 1.40 [95% CI, 1.25–1.56];
P
<0.001). Similarly, the highest HVS quartile was associated with significantly increased risks of MALEs (HR, 1.44 [95% CI, 1.28–1.62];
P
<0.001) and MACEs (HR, 1.28 [95% CI, 1.14–1.43];
P
<0.001). The highest FGCV and HVS quartiles were both associated with the development of PAD and CLI (FGCV: PAD [HR, 1.57;
P
<0.001], CLI [HR, 2.19;
P
<0.001]; HVS: PAD [HR, 1.44;
P
<0.001], CLI [HR, 1.67;
P
=0.003]). The Kaplan‐Meier analysis showed significantly higher risks of MALEs and MACEs with increasing GV magnitude (log‐rank
P
<0.001).

Conclusions

Among individuals with diabetes, increased GV is independently associated with the development of MALEs, including PAD and CLI, and MACEs. The benefit of maintaining stable glycemic levels for improving clinical outcomes warrants further studies.