bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation, Characterization and Application of Path Changing Switch based Arbiter PUF on FPGA as a lightweight Security Primitive for IoT
Authors: Mahalat Mahabub Hasan , Mandal Suraj , Mondal Anindan , Sen Bibhash , Chakraborty Rajat Subhra
Published: November 2021

Secure authentication of any
Internet-of-Things (IoT)
device becomes the utmost necessity due to the lack of specifically designed IoT standards and intrinsic vulnerabilities with limited resources and heterogeneous technologies. Despite the suitability of
arbiter physically unclonable function (APUF)
among other PUF variants for the IoT applications, implementing it on
field-programmable gate arrays (FPGAs)
is challenging. This work presents the complete characterization of the
path changing switch (PCS)

1

based APUF on two different families of FPGA, like Spartan-3E (90 nm CMOS) and Artix-7 (28 nm CMOS). A comprehensive study of the existing tuning concept for
programmable delay logic (PDL)
based APUF implemented on FPGA is presented, leading to establishment of its practical infeasibility. We investigate the entropy, randomness properties of the PCS based APUF suitable for practical applications, and the effect of temperature variation signifying the adequate tolerance against environmental variation. The XOR composition of PCS based APUF is introduced to boost performance and security. The robustness of the PCS based APUF against machine learning based modeling attack is evaluated, showing similar characteristics as the conventional APUF. Experimental results validate the efficacy of PCS based APUF with a little hardware footprint removing the paucity of lightweight security primitive for IoT.
Review—(Mn,Co)3O4-Based Spinels for SOFC Interconnect Coating Application
Authors: Zhu J. H. , Chesson D. A. , Yu Y. T.
Published: November 2021

With the reduction of solid oxide fuel cell (SOFC) operating temperature to the range of 600 °C–800 °C, Cr-containing ferritic alloys have become the preferred interconnect material, which unfortunately are susceptible to continuous scale growth and Cr volatility at the SOFC operating temperatures. The (Mn,Co)3O4 spinel system is widely regarded as the most effective coating for SOFC interconnect protection, due to its high thermal and electrical conductivity, adequate coefficient of thermal expansion, and excellent Cr blocking capability. This article reviews the physical and chemical properties of the (Mn,Co)3O4-based spinels; different types of coating precursors and deposition techniques; and the effects of spinel composition, quality and thickness on the coating performance. It is concluded that the spinel coating composition, quality, and thickness are more critical than the coating process in affecting the overall coating performance.
From skeletal muscle damage and regeneration to the hypertrophy induced by exercise: what is the role of different macrophage subsets?
Authors: Minari André Luis Araujo , Thomatieli-Santos Ronaldo V.
Published: November 2021

Macrophages are one of the top players when considering immune cells involved with tissue homeostasis. Recently, increasing evidence has demonstrated that macrophages could also present two major subsets during tissue healing: proliferative macrophages (M1-like), which are responsible for increasing myogenic cell proliferation, and restorative macrophages (M2-like), which are involved in the end of the mature muscle myogenesis. The participation and characterization of these macrophage subsets are critical during myogenesis to understand the inflammatory role of macrophages during muscle recovery and to create supportive strategies that can improve mass muscle maintenance. Indeed, most of our knowledge about macrophage subsets comes from skeletal muscle damage protocols, and we still do not know how these subsets can contribute to skeletal muscle adaptation. Thus, this narrative review aims to collect and discuss studies demonstrating the involvement of different macrophage subsets during the skeletal muscle damage/regeneration process, showcasing an essential role of these macrophage subsets during muscle adaptation induced by acute and chronic exercise programs.
Evaluation and resolution of many challenges of neural spike sorting: a new sorter
Authors: Hall Nathan J. , Herzfeld David J. , Lisberger Stephen G.
Published: November 2021

Electrophysiological recordings from multiple neurons across multiple channels pose great difficulty for spike sorting of single neurons. We propose methods that improve the ability to determine the number of individual neurons present in a recording and resolve near-simultaneous spike events from single neurons. We use ground-truth data sets to demonstrate the pros and cons of several current sorting algorithms and suggest strategies for determining the accuracy of spike sorting when ground-truth data are not available.
Sensing and decoding the neural drive to paralyzed muscles during attempted movements of a person with tetraplegia using a sleeve array
Authors: Ting Jordyn E. , Del Vecchio Alessandro , Sarma Devapratim , Verma Nikhil , Colachis Samuel C. , Annetta Nicholas V. , Collinger Jennifer L. , Farina Dario , Weber Douglas J.
Published: November 2021

A wearable electrode array and machine learning methods were used to record and decode myoelectric signals and motor unit firing in paralyzed muscles of a person with motor complete tetraplegia. The myoelectric activity and motor unit firing rates were task specific, even in the absence of visible motion, enabling accurate classification of attempted single-digit movements. This wearable system has the potential to enable people with tetraplegia to control assistive devices through movement intent.
Repetition effects in action planning reflect effector- but not hemisphere-specific coding
Authors: Seegelke Christian , Schonard Carolin , Heed Tobias
Published: November 2021

Repeated hand use facilitates the initiation of successive actions (repetition effect). This finding has been interpreted as evidence for effector-specific action plans. However, given that each hand is primarily controlled by the contralateral hemisphere, any differences might reflect effector-independent, hemisphere-specific rather than effector-specific processing. We dissociated these alternatives by asking participants to perform successive actions with hands and feet and provide novel evidence that repetition effects in limb use truly reflect effector-specific coding.
Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect
Authors: Takahashi Masayuki , Seki Mineaki , Nashimoto Masayuki , Kabuta Tomohiro
Published: November 2021

Although antisense oligonucleotide (ASO) therapeutics can be taken up by living cells without carrier molecules, a large part of incorporated ASOs are trapped in the endosomes and do not exert therapeutic effects. To improve their therapeutic effects, it would be important to elucidate the mechanism of cellular uptake and intracellular trafficking of ASOs. In this study, we investigated how SIDT1 affects cellular uptake and intracellular trafficking of ASOs. Fluorescence microscopic analysis suggested that most of naked ASOs are trafficked to the lysosomes via the endosomes. The data obtained from flow cytometry and fluorescence microscopy together showed that although the SIDT1 level barely affects the total cellular uptake of ASOs, it appears to affect the intracellular trafficking of ASOs. We also showed that SIDT1 exists mainly in the endoplasmic reticulum and that perturbing the normal level of SIDT1 suppresses the antisense effect of the naked ASO targeting miR-16.
Prevention of Acute Postoperative Pain in Breast Cancer: A Comparison between Opioids versus Ketamine in the Intraoperatory Analgesia
Authors: López Mirian , Padilla María Luz , García Blas , Orozco Javier , Rodilla Ana María
Published: November 2021

Background. Acute postoperative pain (APP) has a high incidence in breast surgery, and opioids are the most commonly used drugs for its management; however, they are not free from systemic side effects, which may increase comorbidity. In the past few years, opioid-free anaesthesia has been favoured with promising results. Methods. We conducted a descriptive study including 71 patients who underwent breast cancer surgery. The opioid group (n = 41) received fentanyl for induction, remifentanil for maintenance, and rescue morphine before waking up, whereas the ketamine group (n = 30) received a ketamine bolus for induction followed by continuous ketamine infusion during surgery. Later, the presence and intensity of pain were registered, using the Numeric Rating Scale (NRS 1–10) for pain, at different times in the recovery room, at 24 hours and at 3 months. Results. Administration of ketamine is more effective than opioid use for APP prevention in breast cancer surgery because the ketamine group presented with less pain than the opioid group (

p

 < 0.05) at all measured times. When there was pain, patients in the ketamine group gave a lower score to its intensity (

p

 < 0.05). Conclusions. Ketamine could reduce the incidence of APP in breast cancer surgery, compared to opioids.
Application of Gauss Mutation Genetic Algorithm to Optimize Neural Network in Image Painting Art Teaching
Authors: Xing Weiming , Zhang Jian , Zou Quan , Lin Jun
Published: November 2021

With the continuous application of the art industry in various fields, more and more people choose to systematically learn the knowledge of the art industry. In the art major, image painting is one of the important contents of the art major. How to improve students’ aesthetic quality and comprehensive professional quality is studied, in which the content learning of image painting art is the key. Therefore, we have carried out technical exploration and result analysis based on Gaussian mutation genetic algorithm to optimize the application of neural network in image painting art teaching. We use Gaussian mutation genetic algorithm to study the neural network optimized teaching cloud platform technology. Compared with the traditional algorithm, the algorithm proposed in this paper has more funny computational efficiency, being able to comprehensively evaluate and improve students’ aesthetic quality and comprehensive professional quality. Gaussian mutation genetic algorithm can effectively improve the knowledge search ability of the platform and the running speed of the teaching platform. In the future research in the field of art industry, neural network will optimize the teaching cloud platform technology, which has laid a solid foundation for improving students’ aesthetic quality and comprehensive professional quality.
A Model for Managing the Performance of CMMS Deployment in High‐Rise Office Buildings: A View from Lagos, Nigeria
Authors: Musa Shamsudeen , Nisham Musa Zairul , Chua Shirley Jin Lin
Published: November 2021

The development of high‐rise buildings is a current trend in developed cities to answer the challenges of population growth, adding aesthetic value, and optimal use of land. Lagos particularly is one of the fastest growing cities in the world with Gross Domestic Product (GDP) and Internally Generated Revenue (IGR) in Nigeria, which suggests the need for multiple complex buildings, and the need for their maintenance cannot be overemphasised. This maintenance aspect requires tremendous work due to the complexity attached and several strategies springing up. Different studies reveal that both performance measurements and factors are essential aspects in evaluating maintenance management. Thus, this study seeks to explore performance elements that could improve maintenance. Personnel attitude, maintenance policy, maintenance review, and maintenance implementation were measured relative to computerised maintenance management system (CMMS) performance. With a random sampling technique, a sample of 134 Facility Management (FM) practitioners involved in high‐rise office buildings was used to assess the effects of CMMS deployment. Results were analysed by Partial Least Squares Structural Equation Modelling (PLS‐SEM). Findings from this study highlighted an indirect effect size and a large predictive relevance of personnel attitude as a critical factor for a smooth maintenance execution procedure of 12.59% and a standard operating procedure (SOP) of 15.64% on maintenance implementation to contribute 28.36% to performance. This paper uncovers the place of personnel attitude in determining effective maintenance.
CaMK II Inhibition Attenuates ROS Dependent Necroptosis in Acinar Cells and Protects against Acute Pancreatitis in Mice
Authors: Zhu Qingtian , Hao Lu , Shen Qinhao , Pan Jiajia , Liu Weili , Gong Weijuan , Hu Lianghao , Xiao Weiming , Wang Mei , Liu Xinnong , Ding Yanbing , Lu Guotao
Published: November 2021

As a calcium‐regulated protein, CaMK II is closely related to cell death, and it participates in the development of pathological processes such as reperfusion injury, myocardial infarction, and oligodendrocyte death. The function of CaMK II activation in acute pancreatitis (AP) remains unclear. In our study, we confirmed that the expression of p‐CaMK II was increased significantly and consistently in injured pancreatic tissues after caerulein‐induced AP. Then, we found that KN93, an inhibitor of CaMK II, could mitigate the histopathological manifestations in pancreatic tissues, reduce serum levels of enzymology, and decrease oxidative stress products. Accordingly, we elucidated the effect of KN93 in vitro and found that KN93 had a protective effect on the pancreatic acinar cell necroptosis pathway by inhibiting the production of ROS and decreasing the expression of RIP3 and p‐MLKL. In addition, we identified the protective effect of KN93 on AP through another mouse model induced by pancreatic duct ligation (PDL). Together, these data demonstrated that CaMK II participates in the development of AP and that inhibiting CaMK II activation could protect against AP by reducing acinar cell necroptosis, which may provide a new idea target for the prevention and treatment of AP in the clinic.
Research on Mechanisms and Control Measures of Surrounding Rock Disaster in Large Section Roadway with Top Coal under the Influence of Tectonic Stress
Authors: Yu Yang , Lu Jianfei , Chen Dingchao , Pan Yuxin , Zhao Xiangqian , Chen Cheng
Published: November 2021

Based on the research background of large section roadway with top coal (LSRTC) in thick coal seam mining in Wangzhuang Coal Mine, Shanxi Province, China, catastrophe characteristics of the surrounding rock of the LSRTC were investigated and summarized. Based on the principle of damage mechanics, the critical size discriminant of the LSRTC was deduced, and the induction mechanism of section size effect and tectonic stress effect on the roadway surrounding rock disaster was revealed. Accordingly, the roadway surrounding rock control principle with the basic idea of “stabilizing and controlling top coal, reconstructing the coal wall, and limiting floor heave” was put forward, and the roadway surrounding rock stability control countermeasures with the core technology of “strong pressure support for roof + grouting reinforcement for two sides + bolt barrier for floor angle” were developed, which solved the surrounding rock control problem of the LSRTC under the action of tectonic stress and provided a useful reference for the difficult problem of roadway surrounding rock control under similar conditions.
Mathematical Analysis of the Role of HIV/HBV Latency in Hepatocytes
Authors: Nampala Hasifa , Jablonska-Sabuka Matylda , Singull Martin
Published: November 2021

The biggest challenge of treating HIV is rampant liver-related morbidity and mortality. This is, to some extent, attributed to hepatocytes acting as viral reservoirs to both HIV and HBV. Viral reservoirs harbour latent provirus, rendering it inaccessible by combinational antiretroviral therapy (cART) that is specific to actively proliferating virus. Latency reversal agents (LRA) such as Shock and kill or lock and block, aiming at activating the latently infected cells, have been developed. However, they are CD4+ cell-specific only. There is evidence that the low replication level of HIV in hepatocytes is mainly due to the latency of the provirus in these cells. LRA are developed to reduce the number of latently infected cells; however, the impact of the period viral latency in hepatocytes especially, during HIV/HBV coinfection, needs to be investigated. Viral coinfection coupled with lifelong treatment of HIV/HBV necessitates investigation for the optimal control strategy. We propose a coinfection mathematical model with delay and use optimal control theory to analyse the effect of viral latency in hepatocytes on the dynamics of HIV/HBV coinfection. Analytical results indicate that HBV cannot take a competitive exclusion against HIV; thus, the coinfection endemic equilibrium implies chronic HBV in HIV-infected patients. Numerical and analytical results indicate that both HIV and HBV viral loads are higher with longer viral latency period in hepatocytes, which indicates the need to upgrade LRA to other non-CD4+ cell viral reservoirs. Higher viral load caused by viral latency coupled with the effects of cART partly explains why liver-related complications are the leading cause of mortality in HIV-infected persons.
A Modified Nonsmooth Levenberg–Marquardt Algorithm for the General Mixed Complementarity Problem
Authors: Song Linsen , Gao Yan
Published: November 2021

As is well known, the mixed complementarity problem is equivalent to a nonsmooth equation by using a median function. By investigating the generalized Jacobi of a composite vector-valued maximum function, a nonsmooth Levenberg–Marquardt algorithm is proposed in this paper. In the present algorithm, we adopt a new LM parameter form and discuss the local convergence rate under the local error bound condition, which is weaker than nonsingularity. Finally, the numerical experiments and the application for the real-time pricing in smart grid illustrate the effectiveness of the algorithm.
Mei Symmetry and Conservation Laws for Time-Scale Nonshifted Hamilton Equations
Authors: Zhang Yi
Published: November 2021

The Mei symmetry and conservation laws for time-scale nonshifted Hamilton equations are explored, and the Mei symmetry theorem is presented and proved. Firstly, the time-scale Hamilton principle is established and extended to the nonconservative case. Based on the Hamilton principles, the dynamic equations of time-scale nonshifted constrained mechanical systems are derived. Secondly, for the time-scale nonshifted Hamilton equations, the definitions of Mei symmetry and their criterion equations are given. Thirdly, Mei symmetry theorems are proved, and the Mei-type conservation laws in time-scale phase space are driven. Two examples show the validity of the results.
Multiobjective Optimization Method and Application of Tolerance Allocation for the Steam Turbine Based on Cooperative Game Theory
Authors: Li Li-li , Chen Kun , Gao Jian-min , Liu Jun-kong , Gao Zhi-yong , Wang Man-xian
Published: November 2021

Aiming at the optimization problem of multiple objectives with contradictions and conflicts in the process of allocating the tolerance for complex products, taking advantage of the features of coordinating, and balancing contradictions and conflicts of cooperative game theory, this paper uses cooperative game theory to solve the multiobjective optimization problem of tolerance allocation. The quality requirements and cost requirements of assembly products are used as the game decision parties, and the fuzzy clustering method is used to group the design variables of tolerance allocation problem of the steam turbine to form the strategic space of game parties. Take the quality level and cost level of the assembly product as the optimization goals, complete the calculation of the utilities of the two game parties, and establish the multiobjective optimization model of tolerance allocation based on cooperative game theory. Finally, the Shapley value method based on cooperative game theory, the Nash equilibrium method based on noncooperative game theory, and the traditional single‐objective optimization method with the quality as the constraint and the cost as the optimization objective are used to solve the tolerance allocation problem of steam turbine. The solution results show that the method of cooperative game realized the balance, coordination, and comprehensive optimization of the quality and cost from the perspective of collective interests, overcame the shortcomings of the traditional single‐objective optimization method, and obtained better result than the Nash equilibrium method.
Adaptation of Cowpea (Vigna unguiculata (L.) Walp.) to Water Deficit during Vegetative and Reproductive Phases Using Physiological and Agronomic Characters
Authors: Ezin Vincent , Tosse Artoche Gloria Christelle , Chabi Ifagbémi Bienvenue , Ahanchede Adam
Published: November 2021

Cowpea (Vigna unguiculata (L.) Walp.) is an important commodity in West Africa. Its seeds are a valuable source of protein, vitamins, and income for humans. However, cowpea cultivation in Benin faces climatic constraints such as water stress caused by a prolonged absence of rain during the rainy season. Thus, this work aims at selecting cowpea varieties that can be cultivated in times of drought without compromising their yields and yield components. Twenty cowpea varieties were used, including 17 improved cultivars and 3 landraces. The experiment was conducted at the International Institute of Tropical Agriculture in Benin and laid at a split-plot design with four replicates. Each genotype was exposed to three water treatments: fully irrigated control, vegetative stress (when plants were 23 days old, drought stress was imposed for 30 days), and reproductive stress (once the first flowers were observed, water stress was imposed for 30 days). The results showed that photochemical yield, chlorophyll content, and relative water content were reduced under water deficit at the vegetative and reproductive stages. But there were no significant differences in proline content among cowpea varieties. Agronomic traits such as number of days to flowering, number of pods, yield per plant, the weight of 100 seeds, and harvest time showed significant differences under water stress. Overall, the landraces and cultivars including Kpodjiguegue, KVX 61-1, and IT 06-K-242-3 were the most tolerant to drought stress at the vegetative and reproductive stages and could potentially be used in breeding programs to improve drought tolerance of cowpeas.
Recognizing Unmet Need in the Era of Targeted Therapy for CLL/SLL: “What's Past Is Prologue” (Shakespeare)
Authors: Mato Anthony R. , Davids Matthew S. , Sharman Jeff , Roeker Lindsey E. , Kay Neil , Kater Arnon P. , Rogers Kerry , Thompson Meghan C. , Rhodes Joanna , Goy Andre , Skarbnik Alan , Schuster Stephen J. , Tam Constantine S. , Eyre Toby A. , O'Brien Susan , Nabhan Chadi , Lamanna Nicole , Sun Clare , Shadman Mazyar , Pagel John M. , Ujjani Chaitra , Brander Danielle , Coombs Catherine C. , Jain Nitin , Cheah Chan Y. , Brown Jennifer R. , Seymour John F. , Woyach Jennifer A.
Published: November 2021

The management of chronic lymphocytic leukemia (CLL) has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to multiple classes. Symptomatic patients previously treated with a BTK inhibitor (BTKi) and venetoclax represent a new and rapidly growing unmet need in CLL. Here, we define unmet needs in a modern treatment context. We also critically review the literature for PI3K inhibitors and chemoimmunotherapy and lack of data to support their utility following BTKis and venetoclax. Finally, we suggest opportunities to ensure the continued innovation for patients with CLL.
Association of Neutrophil-to-Lymphocyte Ratio with Efficacy of First-Line Avelumab plus Axitinib vs. Sunitinib in Patients with Advanced Renal Cell Carcinoma Enrolled in the Phase 3 JAVELIN Renal 101 Trial
Authors: Bilen Mehmet A. , Rini Brian I. , Voss Martin H. , Larkin James , Haanen John B.A.G. , Albiges Laurence , Pagliaro Lance C. , Voog Eric G. , Lam Elaine T. , Kislov Nikolay , McGregor Bradley A. , Lalani Aly-Khan A. , Huang Bo , di Pietro Alessandra , Krulewicz Stan , Robbins Paul B. , Choueiri Toni K.
Published: November 2021

Purpose:

To evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and efficacy of avelumab plus axitinib or sunitinib.

Experimental Design:

Adult patients with untreated advanced renal cell carcinoma (RCC) with a clear-cell component, ≥1 measurable lesions, Eastern Cooperative Oncology Group performance status of 0 or 1, fresh or archival tumor specimen, and adequate renal, cardiac, and hepatic function were included. Retrospective analyses of the association between baseline NLR and progression-free survival (PFS) and overall survival (OS) in the avelumab plus axitinib or sunitinib arms were performed using the first interim analysis of the phase 3 JAVELIN Renal 101 trial (NCT02684006). Multivariate Cox regression analyses of PFS and OS were conducted. Translational data were assessed to elucidate the underlying biology associated with differences in NLR.

Results:

Patients with below-median NLR had longer observed PFS with avelumab plus axitinib [stratified HR, 0.85; 95% confidence interval (CI), 0.634–1.153] or sunitinib (HR, 0.56; 95% CI, 0.415–0.745). In the avelumab plus axitinib or sunitinib arms, respectively, median PFS was 13.8 and 11.2 months in patients with below-median NLR, and 13.3 and 5.6 months in patients with median-or-higher NLR. Below-median NLR was also associated with longer observed OS in the avelumab plus axitinib (HR, 0.51; 95% CI, 0.300–0.871) and sunitinib arms (HR, 0.30; 95% CI, 0.174–0.511). Tumor analyses showed an association between NLR and key biological characteristics, suggesting a role of NLR in underlying mechanisms influencing clinical outcome.

Conclusions:

Current data support NLR as a prognostic biomarker in patients with advanced RCC receiving avelumab plus axitinib or sunitinib.
Characterization of Novel α-Mangostin and Paeonol Derivatives With Cancer-Selective Cytotoxicity
Authors: Nunna Suneetha , Huang Ying-Pei , Rasa Mahdi , Krepelova Anna , Annunziata Francesco , Adam Lisa , Käppel Sandra , Hsu Ming-Hua , Neri Francesco
Published: November 2021

α-Mangostin (aMan) and Paeonol (Pae) have shown anticancer and anti-inflammatory properties. However, these two natural compounds have no clinical value because of their low solubility and low membrane permeability. In this study, we screened chemically synthesized derivatives from these two natural compounds as potential novel chemicals that increase cancer cell cytotoxicity over nontransformed human cells. We found that two derivative compounds, named α-Mangostin-1 (aMan1) and Paeonol-1 (Pae1) more efficiently and more specifically induced cytotoxicity in HCT116, HT29, and SW48 colorectal cancer cell lines than the parental compounds. Both aMan1 and Pae1 arrested HCT116 cells in the G1 phase and HT29 and SW48 cells in the G2–M phase of the cell cycle. Both aMan1 and Pae1 induced apoptosis in human colorectal cancer cells, through a caspase-dependent mechanism. aMan1 and Pae1 induced selective transcriptional responses in colorectal cancer cells involving genes related to metabolic stress and DNA damage response signaling pathways. Finally, experiments on primary colon organoids showed that both derivatives were able to kill cancer-derived organoids without affecting the viability of organoids derived from healthy tissue, where the parental compounds and the currently used chemotherapeutic drug irinotecan failed. In conclusion, our findings expand the knowledge of natural compound derivatives as anticancer agents and open new avenues of research in the derivation of lead compounds aimed at developing novel chemotherapeutic drugs for colorectal cancer treatment that selectively target cancer, but not healthy cells.
Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Antitumor Activity
Authors: Dong Yiyu , Gong Yongxing , Kuo Fengshen , Makarov Vladimir , Reznik Ed , Nanjangud Gouri J. , Aras Omer , Zhao Huiyong , Qu Rui , Fagin James A. , Sherman Eric J. , Xu Bin , Ghossein Ronald , Chan Timothy A. , Ganly Ian
Published: November 2021

Hurthle cell carcinomas (HCCs) are refractory to radioactive iodine and unresponsive to chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic thyroid cancer. Our previous study on the genomic landscape of HCCs identified a high incidence of disruptions of mTOR pathway effectors. Here, we report a detailed analysis of mTOR signaling in cell line and patient-derived xenograft mouse models of HCCs. We show that mTOR signaling is upregulated and that targeting mTOR signaling using mTOR inhibitors suppresses tumor growth in primary tumors and distant metastasis. Mechanistically, ablation of mTOR signaling impaired the expression of p-S6 and cyclin A2, resulting in the decrease of the S phase and blocking of cancer cell proliferation. Strikingly, mTOR inhibitor treatment significantly reduced lung metastatic lesions, with the decreased expression of Snail in xenograft tumors. Our data demonstrate that mTOR pathway blockade represents a novel treatment strategy for HCC.
Application of Hans Algorithm for Subcategorization of Diffuse Large B-Cell Lymphoma in Fine-Needle Aspiration Biopsy Cytology
Authors: Rohilla Manish , Garg Sumit , Bal Amanjit , Das Ashim , Gupta Nalini , Dey Pranab , Srinivasan Radhika
Published: November 2021

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with remarkably variable clinical presentation and outcome. Hans algorithm subclassified DLBCL into prognostically distinct molecular subtypes by using immunohistochemistry (IHC). Fine-needle aspiration biopsy cytology (FNABC) is a first-line diagnostic modality in lymphadenopathy. The study aims to perform IHC on FNABC cell blocks (CBs) for subclassifying according to the Hans algorithm and correlate with case-matched histopathology. Methods: This was a retrospective study carried out between January 2017 and December 2019. All DLBCL FNABC cases with CBs and smears and which had follow-up histopathology were included in the study. Detailed cytomorphological evaluation and CD10, B-cell lymphoma 6 (BCL6), and multiple myeloma oncogene 1 IHCs were performed on CBs. The cases are divided into 3 distinct molecular subtypes based on the Hans algorithm as germinal centre B-cell (GCB), activated B-cell (ABC), and unclassified subtypes. The results were compared with the final histopathology. Results: A total of 44 cases were diagnosed as DLBCL, and 33 cases with sufficient material for further IHC were included in the study. Twelve cases were of the GCB type, 19 were of the ABC type, and 2 remained unclassified. Follow-up histopathology was available in 20 cases. Overall, histopathological concordance was found in 95% of cases (19/20). The single discordant case was classified as GCB on FNABC and was ABC on histopathology. Conclusion: FNABC with CBs is an acceptable alternative to biopsy for providing a complete diagnosis of DLBCL as per the current WHO classification.
Activation of the Hedgehog and Wnt/β-Catenin Signaling Pathways in Basal Cell Carcinoma
Authors: Takada Tomoaki
Published: November 2021

In basal cell carcinoma (BCC) tumorigenesis, interaction between Hedgehog (Hh) and Wnt/β-catenin (Wnt) signaling pathways has been investigated, but not completely elucidated. Here, a case of sporadic BCC in an 80-year-old man is presented, and the effectiveness of SMO inhibitors in case of relapse is predicted. The aim of this study was to determine whether the SMO inhibitors can be effective in treating this individual should the tumor recur in the future. Immunohistochemistry (IHC) was performed in a tumor and the adjacent skin tissue from the patient. IHC within the same BCC tissue specimen revealed that Glioma-associated oncogene 1 (GLI1) and Smoothened (SMO) in the Hh signaling pathway and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in the Wnt signaling pathway were overexpressed. Hh and Wnt signaling pathways were activated. These findings suggest that the patient might be resistant to treatment with SMO inhibitors because of the interaction between Hh and Wnt signaling pathways. Overexpression of GLI1 leads to transcriptional activation, making it an attractive molecular target for anticancer therapy owing to the downstream effectors of the cascade.
Variations in Radioiodine Therapy in Europe: Decision-Making after Total Thyroidectomy
Authors: Forrer Flavio , Fischer Galina Farina , Maas Ole , Giovanella Luca , Hoffmann Martha , Iakovou Ioannis , Luster Markus , Mihailovic Jasna , Petranovic Ovčariček Petra , Vrachimis Alexis , Zerdoud Slimane , Putora Paul Martin
Published: November 2021

The role of radioiodine therapy (RIT) (used as ablation therapy or adjuvant therapy) following total thyroidectomy for differentiated thyroid cancer (DTC) changed. Major revisions of the American Thyroid Association (ATA) Guidelines in 2015 resulted in significant differences in treatment recommendations in comparison to the European Association of Nuclear Medicine (EANM) 2008 guidelines. Recently, we presented the effects on daily practice for RIT among Swiss Nuclear Medicine centres. We now performed a study at the European level and hypothesized that there is also considerable variability among European experts. We performed a decision-tree-based analysis of management strategies from all members of the EANM thyroid committee to map current practice among experts. We collected data on whether or not RIT is administered, on which criteria these decisions are based and collected details on treatment activities and patient preparation. Our study shows discrepancies for low-risk DTC, where “follow-up only” is recommended by some experts, while RIT with significant doses is used by other experts. E.g., for pT1b tumours without evidence of metastases, the level of agreement for the use of RIT is as low as 50%. If RIT is administered, activities of I-131 range from 1.1 GBq to 3.0 GBq. In other constellations (e.g., pT1a), experts diverge from current clinical guidelines as up to 75% administer RIT in certain cases. For intermediate and high-risk patients, RIT is generally recommended. However, dosing and treatment preparation (rhTSH vs. thyroid hormone withdrawal) vary distinctly. In comparison to the Swiss study, the general level of agreement is higher among the European experts. The recently proposed approach on the use of RIT, based on integrated post-surgery assessment (Martinique article) and results of ongoing prospective randomized studies are likely to reduce uncertainty in approaching RIT treatment. In certain constellations, consensus identified among European experts might be helpful in formulating future guidelines.
Multiple Social Vulnerabilities to Health Disparities and Hypertension and Death in the REGARDS Study
Authors: King Jordan B. , Pinheiro Laura C. , Bryan Ringel Joanna , Bress Adam P. , Shimbo Daichi , Muntner Paul , Reynolds Kristi , Cushman Mary , Howard George , Manly Jennifer J. , Safford Monika M.
Published: November 2021

Social vulnerabilities increase the risk of developing hypertension and lower life expectancy, but the effect of an individual’s overall vulnerability burden is unknown. Our objective was to determine the association of social vulnerability count and the risk of developing hypertension or dying over 10 years and whether these associations vary by race. We used the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) and included participants without baseline hypertension. The primary exposure was the count of social vulnerabilities defined across economic, education, health and health care, neighborhood and built environment, and social and community context domains. Among 5425 participants of mean age 64±10 SD years of which 24% were Black participants, 1468 (31%) had 1 vulnerability and 717 (15%) had ≥2 vulnerabilities. Compared with participants without vulnerabilities, the adjusted relative risk ratio for developing hypertension was 1.16 (95% CI, 0.99–1.36) and 1.49 (95% CI, 1.20–1.85) for individuals with 1 and ≥2 vulnerabilities, respectively. The adjusted relative risk ratio for death was 1.55 (95% CI, 1.24–1.93) and 2.30 (95% CI, 1.75–3.04) for individuals with 1 and ≥2 vulnerabilities, respectively. A greater proportion of Black participants developed hypertension and died than did White participants (hypertension, 38% versus 31%; death, 25% versus 20%). The vulnerability count association was strongest in White participants (
P
value for vulnerability count×race interaction: hypertension=0.046, death=0.015). Overall, a greater number of socially determined vulnerabilities was associated with progressively higher risk of developing hypertension, and an even higher risk of dying over 10 years.
Increased Collagen Turnover Is a Feature of Fibromuscular Dysplasia and Associated With Hypertrophic Radial Remodeling: A Pilot, Urine Proteomic Study
Authors: Latosinska Agnieszka , Bruno Rosa Maria , Pappaccogli Marco , Bacca Alessandra , Beauloye Christophe , Boutouyrie Pierre , Khettab Hakim , Staessen Jan A , Taddei Stefano , Toubiana Laurent , Vikkula Miikka , Mischak Harald , Persu Alexandre
Published: November 2021

Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alterations in medium-sized, but not large artery geometry and mechanics. The study included 33 patients with mostly multifocal, renal FMD who underwent in depth arterial exploration using ultra-high frequency ultrasound. The cohort was separated in a training set of 23 patients with FMD from Belgium and an independent test set of 10 patients with FMD from Italy. For each set, controls matched 2:1 were selected from the Human Urinary Proteome Database. The specificity of the classifier was tested in 700 additional controls from general population studies, patients with chronic kidney disease (n=66) and coronary artery disease (n=31). Three hundred thirty-five urinary peptides, mostly related to collagen turnover, were identified in the training cohort and combined into a classifier. When applying in the test cohort, the area under the receiver operating characteristic curve was 1.00, 100% specificity at 100% sensitivity. The classifier maintained a high specificity in additional controls (98.3%), patients with chronic kidney (90.9%) and coronary artery (96.8%) diseases. Furthermore, in patients with FMD, the proteomic score was positively associated with radial wall thickness and wall cross-sectional area. In conclusion, a proteomic score has the potential to discriminate between patients with FMD and controls. If confirmed in a wider and more diverse cohort, these findings may pave the way for a noninvasive diagnostic test of FMD.
Molecular Biomarkers and Drug Targets in Brain Arteriovenous and Cavernous Malformations: Where Are We?
Authors: Venugopal Vani , Sumi S.
Published: November 2021

Vascular malformations of the brain (VMB) comprise abnormal development of blood vessels. A small fraction of VMBs causes hemorrhages with neurological morbidity and risk of mortality in patients. Most often, they are symptomatically silent and are detected at advanced stages of disease progression. The most common forms of VMBs are arteriovenous and cavernous malformations in the brain. Radiopathological features of these diseases are complex with high phenotypic variability. Early detection of these malformations followed by preclusion of severe neurological deficits such as hemorrhage and stroke is crucial in the clinical management of patients with VMBs. The technological advances in high-throughput omics platforms have currently infused a zest in translational research in VMBs. Besides finding novel biomarkers and therapeutic targets, these studies have withal contributed significantly to the understanding of the etiopathogenesis of VMBs. Here we discuss the recent advances in predictive and prognostic biomarker research in sporadic and familial arteriovenous malformations as well as cerebral cavernous malformations. Furthermore, we analyze the clinical applicability of protein and noncoding RNA-based molecular-targeted therapies which may have a potentially key role in disease management.
Pentecostal Theology, Identity Politics, and Racialized Xenophobia: Claiming A New Social Order
Authors: Hankela Elina
Published: November 2021

Applying the methodological lens of ethnographic theology, the article argues that grounded Pentecostal theologies participate in reimagining a new social order, particularly in relation to racialized xenophobia. This argument is made in the specific context of two Pentecostal churches in Johannesburg, South Africa, both led and frequented by people who have come to Johannesburg from other parts of the African continent. The argument is outlined by unpacking three theological themes prominent in the collected ethnographic data: positive confession, Word-centred ecclesiology, and Christlike lifestyle. Taken together, these themes highlight a social conscience that other societal actors would do well to take seriously when considering combatting xenophobia. Overall, the article challenges the scholarly emphasis on Pentecostal theologies as uninterested in life-affirming structural change, building on Nimi Wariboko’s formulation of blackness, chosenness, and Nigerian Pentecostalism ‘that reads against the existing social order’ within the particular context of xenophobia in urban South Africa.
Human Rights, Islam, and Debates around CEDAW
Authors: Fazaeli Roja , Hanisek Joel
Published: November 2021

The article explores the tensions between FORB claims and the advancement of women’s rights in Muslim majority state contexts. Forms of Muslim majority state reservations to CEDAW are analysed in critical and comparative fashion. Iran’s historical engagement with CEDAW is studied for insight into how a purported theoretical conflict between CEDAW and FORB may be better understood in terms of the domestic and international politics of gender and power.
Kittsteiner’s History Out of Joint
Authors: Wimmer Mario
Published: November 2021

In this article, I portray both the “thinking historian” Heinz-Dieter Kittsteiner and his philosophical analysis of the unavailability of the historical process. In his book Out of Control (2004), Kittsteiner builds on Immanuel Kant’s concept of the historical sign to demonstrate how history is out of joint due to the contingent character of the historical process. This understanding demands a new theory of historical time and of historiographical practice, which I reconstruct through a close reading of a chapter of Kittsteiner’s book.
Hydroxycamptothecin Impedes the Mesenchymal Stem Cells (MSCs)-Triggered Migrative Features of Breast Cancer Cells via Suppressing the Protein Kinase B/Mitogen-Activated Protein Kinase (AKT/MAPK) Activation in Bone Marrowmesenchymal Stem Cells
Authors: Cheng Hong , Zhang Xin , Li Yinmou
Published: November 2021

The current study aimed to dissect the impacts and mechanisms of hydroxycamptothecin on breast cancer. Collect conditioned medium from MSCs cells to apply it into the co-culture system of breast cancer cells, which were pre-treated with hydroxycamptothecin. The cell counting kit was
employed to measure the proliferation potential of cells, while the phosphorylation degrees of AKT/MAPKrelated proteins were examined via Western blotting. Then the cellular migration was test by transwell. Finally, the transcriptional and translational levels of IL-6 and RANTES in cells were
detected by real-time PCR and enzyme-linked immunosorbent assay. HC could remarkably influence the interplay between MSC and breast malignant cells, reduce the MSC-activated migrative behavior of breast malignant cells and impede the capability of MSC to maintain the migration of cancer cells.
RANTES and IL-6 exerted a synergistic induction in the migrative feature of breast cancer cells. HC could retard the migrating activities of breast cancer cells via diminishing the RANTES and IL-6 levels. Hydroxycamptothecin could impede the proliferative and migrative activities of MSC, of
which the impediment was accompanied by an inhibitory impact on the secretory production of two growth factors IL-6 and RANTES from MSC, thereby enhancing the migration of breast malignant cells.
Austerity as Bureaucratic Violence: Understanding the Impact of (Neoliberal) Austerity on Disabled People in Sweden
Authors: Norberg Ida
Published: November 2021

Drawing on a framework offered by Bauman and literature from disability studies and other sociological areas, this article argues that the experience of austerity for disabled people in Sweden is one of bureaucratic violence, shaped by disablism. The article aims to broaden the sociological conceptualisation of bureaucratic violence to include disablist austerity within its purview. It utilises fieldwork data from interviews with disabled people in Sweden to explore how welfare bureaucracy isolates and dehumanises disabled people. It also examines how Swedish welfare bureaucracies obscure the impact of austerity on this population. Due to the convergence of neoliberalism and austerity in Sweden, the exploration of bureaucratic violence opens up important questions regarding the Social Darwinist elements in neoliberal theory. Ultimately, bureaucratic violence is a useful concept for sociologists for two reasons: it sheds austerity of its technocratic veneer and connects lived experiences of welfare reform to the lethal consequences of austerity.
the domestic workers’ strike: migrant women, social reproduction and contentious labour organising
Authors: Fernandes Sujatha
Published: November 2021

In recent decades, there have been major changes in the organisation of social reproduction. As middle-class women have entered the workforce in large numbers, and state provision of childcare and other welfare services has been scaled back under neo-liberalism, there has been an unprecedented outsourcing of household labour to the market. The resulting commodification of social reproduction has not liberated women from the demands of housework but has largely shifted this work away from women in the Global North towards migrant women workers from poor and heavily indebted countries of the Global South. At the same time, there has also been a huge increase in internal migration within Global South countries, as newly wealthy middle classes in the cities are being serviced by poor rural women. Commodified domestic labour relies on the existence of gendered and racialised migrant workers. This article examines the domestic workers’ strike as an effective and urgent mode of political action given the massive and growing concentration of migrant women in domestic work. This requires a reassessment of earlier feminist strategies based on a nuclear family model and current advocacy strategies that, influenced by foundations, have rejected the strike tactic in favour of limited legal strategies. This article draws on my empirical research on domestic workers’ movements in the USA and India in order to highlight emerging strategies of labour movements.