bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting the Performance of Sub‐1 GHz IoT Wireless Networks
Authors: Yang Zebo , Ghubaish Ali , Unal Devrim , Jain Raj
Published: June 2021

Internet of Things (IoT) devices frequently utilize wireless networks operating in the Industrial, Scientific, and Medical (ISM) Sub‐1 GHz spectrum bands. Compared with higher frequency bands, the Sub‐1 GHz band provides broader coverage and lower power consumption, which are desirable properties for low‐cost IoT applications. However, low‐power and low‐cost IoT modules cause high variability in network performance. The varying influence from real‐world environments additionally undermines wireless propagation and aggravates this variability. We explore these influences and provide a checklist of potential factors affecting wireless network performance in real‐world environments. Using multiple low‐cost IoT modules, we conduct multiple experiments in five real‐world scenarios: indoor, street, open field, ground‐to‐drone (G2D), and drone‐to‐drone (D2D). Specifically, the tests are conducted inside a building, on a straight street with wooded sidewalks and aligned houses, on an open field golf course, and high up in the air between drones. To understand the difficulty of reproducibility in IoT deployments, we studied the effect of factors in four categories. This includes the effect of path (line of sight, distance, and obstruction), configuration (transmit power level), weather (precipitation, temperature, and humidity), and installation (IoT module mobility and position). We find that some of the factors in the path and weather categories have the most influence among all the factors, while the rest have moderate to low impacts. In the end, we provide a complete checklist of all the tested factors, which we believe would be constructive not only to academics but also to industrial practitioners working on wireless IoT systems.
Engaging Informal Private Health Care Providers for TB Case Detection: Experiences from RIPEND Project in India
Authors: Kelamane Santosha , Satyanarayana Srinath , Nagaraja Sharath Burugina , Panibatla Vikas , Dasari Ramesh , Rajeesham  , Khan Amera , Kamineni Vishnuvardhan
Published: June 2021

Background. Informal (unqualified) health care providers are an important source of medical care for persons with presumptive TB (PPTB) in India. A project (titled RIPEND) was implemented to engage informal providers for the identification of PPTBs and TB patients in 4 districts of Telangana State, India, during October 2018-December 2019 project period. Engagement involved sensitizing the informal providers about TB, providing them financial incentives to identify PPTBs, and linking these PPTBs to diagnostic and treatment services provided by the Government of India’s National TB Elimination Programme. Objectives. To describe (a) the characteristics of the informal providers, along with their self-reported practices on TB diagnosis, treatment, and challenges encountered by the RIPEND project staff in engaging them in the project and (b) the outputs and outcomes of this engagement. Methods. We used a combination of one-on-one interviews with informal providers, group interviews with RIPEND project staff, and secondary analysis of data available within the project’s recording and reporting systems. Results. A total of 555 informal providers were actively engaged under the project. The majority (87%) had a nonmedicine-related graduate degree and had been providing medical care for more than 10 years. Most (95%) were aware that a cough for 2 weeks or more is a symptom of pulmonary TB and that such patients should be referred for sputum-smear microscopy at a government health facility. Challenges in engaging the informal providers included motivating them to participate in the study, suboptimal mobile usage for referral services, and delays in providing financial incentives to them for referring PPTBs. During the project period (October 2018-December 2019), 8342 PPTBs were identified of which 1003 TB patients were detected and linked to TB treatment services. Conclusion. This project showed that engaging informal providers is feasible and that a large number of PPTB and TB patients can be identified through this effort. The Government of India should consider engaging informal providers for the early diagnosis of TB to reduce the missing TB cases in the country.
Reliable Reputation Review and Secure Energy Transaction of Microgrid Community Based on Hybrid Blockchain
Authors: Song Zilong , Zhang Xiaohong , Liang Miaomiao
Published: June 2021

A growing number of prosumers have entered the local power market in response to an increase in the number of residential users who can afford to install distributed energy resources. The traditional microgrid trading platform has many problems, such as low transaction efficiency, the high cost of market maintenance, opaque transactions, and the difficulty of ensuring user privacy, which are not conducive to encouraging users to participate in local electricity trading. A blockchain‐based mechanism of microgrid transactions can solve these problems, but the common single‐blockchain framework cannot manage user identity. This study thus proposes a mechanism for secure microgrid transactions based on the hybrid blockchain. A hybrid framework consisting of private blockchain and consortium blockchain is first proposed to complete market transactions. The private blockchain stores the identifying information of users and a review of their transactions, while the consortium blockchain is responsible for storing transaction information. The block digest of the private blockchain is stored in the consortium blockchain to prevent information on the private blockchain from being tampered with by the central node. A reputation evaluation algorithm based on user behavior is then developed to evaluate user reputation, which affects the results of the access audit on the private blockchain. The higher a user’s reputation score is, the more benefits he/she can obtain in the transaction process. Finally, an identity‐based proxy signcryption algorithm is proposed to help the intelligent management device with limited computing power obtain signcryption information in the transaction process to protect the transaction information. A system analysis showed that the secure transaction mechanism of the microgrid based on the hybrid blockchain boasts many security features, such as privacy, transparency, and imtamperability. The proposed reputation evaluation algorithm can objectively reflect all users’ behaviors through their reputation scores, and the identity‐based proxy signcryption algorithm is practical.
Relay Selection for Security Improvement in Cognitive Radio Networks with Energy Harvesting
Authors: Ho-Van Khuong , Do-Dac Thiem
Published: June 2021

This paper selects an unlicensed relay among available self‐powered relays to not only remain but also secure information transmission from an unlicensed source to an unlicensed destination. The relays harvest energy in signals of the unlicensed source and the licensed transmitter. Then, they spend the harvested energy for their relaying operation. Conditioned on the licensed outage restriction, the peak transmission power restriction, Rayleigh fading, and the licensed interference, the current paper proposes an exact closed‐form formula of the secrecy outage probability to quickly evaluate the secrecy performance of the proposed relay selection method in cognitive radio networks with energy harvesting. The proposed formula is corroborated by computer simulations. Several results illustrate the effectiveness of the relay selection in securing information transmission. Additionally, the security capability is saturated at large peak transmission powers or large preset outage probabilities of licensed users. Furthermore, the security capability depends on many specifications among which the power splitting ratio, the relays’ positions, and the time switching ratio can be optimally selected to obtain the best security performance.
Green Communication for Sixth‐Generation Intent‐Based Networks: An Architecture Based on Hybrid Computational Intelligence Algorithm
Authors: Eldrandaly Khalid A. , Abdel-Fatah Laila , Abdel-Basset Mohamed , El-hoseny Mohamed , Abdel-Aziz Nabil M.
Published: June 2021

The sixth‐generation (6G) is envisioned as a pivotal technology that will support the ubiquitous seamless connectivity of substantial networks. The main advantage of 6G technology is leveraging Artificial Intelligence (AI) techniques for handling its interoperable functions. The pairing of 6G networks and AI creates new needs for infrastructure, data preparation, and governance. Thus, Intent‐Based Network (IBN) architecture is a key infrastructure for 6G technology. Usually, these networks are formed of several clusters for data gathering from various heterogeneities in devices. Therefore, an important problem is to find the minimum transmission power for each node in the network clusters. This paper presents hybridization between two Computational Intelligence (CI) algorithms called the Marine Predator Algorithm and the Generalized Normal Distribution Optimization (MPGND). The proposed algorithm is applied to save power consumption which is an important problem in sustainable green 6G‐IBN. MPGND is compared with several recently proposed algorithms, including Augmented Grey Wolf Optimizer (AGWO), Sine Tree‐Seed Algorithm (STSA), Archimedes Optimization Algorithm (AOA), and Student Psychology‐Based Optimization (SPBO). The experimental results with the statistical analysis demonstrate the merits and highly competitive performance of the proposed algorithm.
Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma
Authors: Besse Lenka , Besse Andrej , Stolze Sara C. , Sobh Amin , Zaal Esther A. , van der Ham Alwin J. , Ruiz Mario , Phuyal Santosh , Büchler Lorina , Sathianathan Marc , Florea Bogdan I. , Borén Jan , Ståhlman Marcus , Huber Julia , Bolomsky Arnold , Ludwig Heinz , Hannich J. Thomas , Loguinov Alex , Everts Bart , Berkers Celia R. , Pilon Marc , Farhan Hesso , Vulpe Christopher D. , Overkleeft Herman S. , Driessen Christoph
Published: June 2021

The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts. In patients with advanced, proteasome inhibitor (PI)–refractory multiple myeloma, nelfinavir-based therapy resulted in 65% partial response or better, suggesting that this may be a highly active chemotherapeutic option in this setting. The broad anticancer mechanism of action of nelfinavir implies that it interferes with fundamental aspects of cancer cell biology. We combined proteome-wide affinity-purification of nelfinavir-interacting proteins with genome-wide CRISPR/Cas9–based screening to identify protein partners that interact with nelfinavir in an activity-dependent manner alongside candidate genetic contributors affecting nelfinavir cytotoxicity. Nelfinavir had multiple activity-specific binding partners embedded in lipid bilayers of mitochondria and the endoplasmic reticulum. Nelfinavir affected the fluidity and composition of lipid-rich membranes, disrupted mitochondrial respiration, blocked vesicular transport, and affected the function of membrane-embedded drug efflux transporter ABCB1, triggering the integrated stress response. Sensitivity to nelfinavir was dependent on ADIPOR2, which maintains membrane fluidity by promoting fatty acid desaturation and incorporation into phospholipids. Supplementation with fatty acids prevented the nelfinavir-induced effect on mitochondrial metabolism, drug-efflux transporters, and stress-response activation. Conversely, depletion of fatty acids/cholesterol pools by the FDA-approved drug ezetimibe showed a synergistic anticancer activity with nelfinavir in vitro. These results identify the modification of lipid-rich membranes by nelfinavir as a novel mechanism of action to achieve broad anticancer activity, which may be suitable for the treatment of PI–refractory multiple myeloma.

Significance:

Nelfinavir induces lipid bilayer stress in cellular organelles that disrupts mitochondrial respiration and transmembrane protein transport, resulting in broad anticancer activity via metabolic rewiring and activation of the unfolded protein response.
MAP3K7-IKK Inflammatory Signaling Modulates AR Protein Degradation and Prostate Cancer Progression
Authors: Huang Zhenlin , Tang Bo , Yang Yinhui , Yang Zhaogang , Shi Lei , Bai Yang , Yan Binyuan , Karnes R. Jeffrey , Zhang Jun , Jimenez Rafael , Wang Liguo , Wei Qiang , Yang Jinjian , Xu Wanhai , Jia Zhankui , Huang Haojie
Published: June 2021

Androgen receptor (AR) is a major survival factor for prostate cancer. Inflammation is implicated in many cancer types, including prostate cancer. Activation of MAP3K7 (also termed TAK1) and downstream IκB kinase β (IKKβ) by proinflammatory cytokines such as TNFα stimulates NF-κB survival pathways. Paradoxically, MAP3K7 is often deleted in human prostate cancer. Here, we demonstrate that AR protein expression is lower in inflammatory tumor areas compared with non-inflammatory tissues in patients with prostate cancer. Map3k7 knockout increased AR protein levels and activity in the mouse prostate, and MAP3K7 and AR protein levels were inversely correlated in prostate cancer patient specimens. TNFα treatment increased AR protein ubiquitination and proteasomal degradation. Mechanistically, activation of IKKβ by TNFα induced phosphorylation and TRCP1/2 E3 ligase–mediated polyubiquitination and degradation of AR protein. TNFα suppressed prostate cancer proliferation, which could be rescued by blockade of AR degradation. These findings reveal a previously unrecognized tumor suppressive function of the inflammation-activated MAP3K7–IKKβ axis in degrading AR protein. Moreover, they suggest that aberrant elevation of AR protein could be a prognostic biomarker and therapeutic target for MAP3K7-deficient prostate cancer.

Significance:

This study identifies that MAP3K7–IKKβ signaling plays a tumor-suppressive role in prostate cancer by degrading AR, revealing potential prognostic and therapeutic strategies for MAP3K7-deficient tumors.
5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation–Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study
Authors: Ascierto Paolo A. , Dréno Brigitte , Larkin James , Ribas Antoni , Liszkay Gabriella , Maio Michele , Mandalà Mario , Demidov Lev , Stroyakovskiy Daniil , Thomas Luc , de la Cruz-Merino Luis , Atkinson Victoria , Dutriaux Caroline , Garbe Claus , Hsu Jessie , Jones Surai , Li Haocheng , McKenna Edward , Voulgari Athina , McArthur Grant A.
Published: June 2021

Purpose:

The randomized phase III coBRIM study (NCT01689519) demonstrated improved progression-free survival (PFS) and overall survival (OS) with addition of cobimetinib to vemurafenib compared with vemurafenib in patients with previously untreated BRAFV600 mutation–positive advanced melanoma. We report long-term follow-up of coBRIM, with at least 5 years since the last patient was randomized.

Patients and Methods:

Eligible patients were randomized 1:1 to receive either oral cobimetinib (60 mg once daily on days 1–21 in each 28-day cycle) or placebo in combination with oral vemurafenib (960 mg twice daily).

Results:

495 patients were randomized to cobimetinib plus vemurafenib (n = 247) or placebo plus vemurafenib (n = 248). Median follow-up was 21.2 months for cobimetinib plus vemurafenib and 16.6 months for placebo plus vemurafenib. Median OS was 22.5 months (95% CI, 20.3–28.8) with cobimetinib plus vemurafenib and 17.4 months (95% CI, 15.0–19.8) with placebo plus vemurafenib; 5-year OS rates were 31% and 26%, respectively. Median PFS was 12.6 months (95% CI, 9.5–14.8) with cobimetinib plus vemurafenib and 7.2 months (95% CI, 5.6–7.5) with placebo plus vemurafenib; 5-year PFS rates were 14% and 10%, respectively. OS and PFS were longest in patients with normal baseline lactate dehydrogenase levels and low tumor burden, and in those achieving complete response. The safety profile remained consistent with previously published reports.

Conclusions:

Extended follow-up of coBRIM confirms the long-term clinical benefit and safety profile of cobimetinib plus vemurafenib compared with vemurafenib monotherapy in patients with BRAFV600 mutation–positive advanced melanoma.
Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells
Authors: Lee Wen-Hsin Sandy , Ye Zhiyong , Cheung Alice M.S. , Goh Y.P. Sharon , Oh Hsueh Ling Janice , Rajarethinam Ravisankar , Yeo Siok Ping , Soh Mun Kuen , Chan Esther Hian Li , Tan Lip Kun , Tan Soo-Yong , Chuah Charles , Chng Wee Joo , Connolly John E. , Wang Cheng-I
Published: June 2021

Acute myeloid leukemia (AML) is an aggressive disease with poor outcomes, overwhelmingly due to relapse. Minimal residual disease (MRD), defined as the persistence of leukemic cells after chemotherapy treatment, is thought to be the major cause of relapse. The origins of relapse in AML have been traced to rare therapy-resistant leukemic stem cells (LSCs) that are already present at diagnosis. Effective treatment strategies for long-term remission are lacking, as it has been difficult to eliminate LSCs with conventional therapy. Here, we proposed a new approach based on the chimeric antigen receptor (CAR)-directed T lymphocytes, targeting T-cell immunoglobulin, and mucin domain 3 (TIM-3) to treat MRD in patients with AML. TIM-3 is selected as the target because it is highly expressed on AML blasts and LSCs in most subtypes regardless of the patient's genetic characteristics and treatment course. Moreover, it is absent in the normal hematopoietic stem cells, granulocytes, naïve lymphocytes, and most normal nonhematopoietic tissues. Using a naïve human Fab phage display library, we isolated an anti-human TIM-3 antibody and designed a second-generation anti–TIM-3. Our anti–TIM-3 CAR T cells exhibit potent antileukemic activity against AML cell lines and primary AML blasts, and in the mouse models. More importantly, we demonstrate efficient killing of the primary LSCs directly isolated from the patients. Hence, eradication of the LSCs present in the MRD by anti–TIM-3 CAR T-cell therapy following the first-line treatment may improve the clinical outcomes of patients with AML.
PARP and CDK4/6 Inhibitor Combination Therapy Induces Apoptosis and Suppresses Neuroendocrine Differentiation in Prostate Cancer
Authors: Wu Cheng , Peng Shan , Pilié Patrick G. , Geng Chuandong , Park Sanghee , Manyam Ganiraju C. , Lu Yungang , Yang Guang , Tang Zhe , Kondraganti Shakuntala , Wang Daoqi , Hudgens Courtney W. , Ledesma Debora A. , Marques-Piubelli Mario L. , Torres-Cabala Carlos A. , Curry Jonathan L. , Troncoso Patricia , Corn Paul G. , Broom Bradley M. , Thompson Timothy C.
Published: June 2021

We analyzed the efficacy and mechanistic interactions of PARP inhibition (PARPi; olaparib) and CDK4/6 inhibition (CDK4/6i; palbociclib or abemaciclib) combination therapy in castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) models. We demonstrated that combined olaparib and palbociblib or abemaciclib treatment resulted in synergistic suppression of the p-Rb1–E2F1 signaling axis at the transcriptional and posttranslational levels, leading to disruption of cell-cycle progression and inhibition of E2F1 gene targets, including genes involved in DDR signaling/damage repair, antiapoptotic BCL-2 family members (BCL-2 and MCL-1), CDK1, and neuroendocrine differentiation (NED) markers in vitro and in vivo. In addition, olaparib + palbociclib or olaparib + abemaciclib combination treatment resulted in significantly greater growth inhibition and apoptosis than either single agent alone. We further showed that PARPi and CDK4/6i combination treatment–induced CDK1 inhibition suppressed p-S70-BCL-2 and increased caspase cleavage, while CDK1 overexpression effectively prevented the downregulation of p-S70-BCL-2 and largely rescued the combination treatment–induced cytotoxicity. Our study defines a novel combination treatment strategy for CRPC and NEPC and demonstrates that combination PARPi and CDK4/6i synergistically promotes suppression of the p-Rb1-E2F1 axis and E2F1 target genes, including CDK1 and NED proteins, leading to growth inhibition and increased apoptosis in vitro and in vivo. Taken together, our results provide a molecular rationale for PARPi and CDK4/6i combination therapy and reveal mechanism-based clinical trial opportunities for men with NEPC.
SHP2 Inhibition Enhances the Effects of Tyrosine Kinase Inhibitors in Preclinical Models of Treatment-naïve ALK-, ROS1-, or EGFR-altered Non–small Cell Lung Cancer
Authors: Kano Hirohisa , Ichihara Eiki , Watanabe Hiromi , Nishii Kazuya , Ando Chihiro , Nakasuka Takamasa , Ninomiya Kiichiro , Kato Yuka , Kubo Toshio , Rai Kammei , Ohashi Kadoaki , Hotta Katsuyuki , Tabata Masahiro , Maeda Yoshinobu , Kiura Katsuyuki
Published: June 2021

After molecular-targeted therapy, some cancer cells may remain that are resistant to therapies targeting oncogene alterations, such as those in the genes encoding the EGFR and anaplastic lymphoma kinase (ALK) as well as c-ros oncogene 1 (ROS1). The mechanisms underlying this type of resistance are unknown. In this article, we report the potential role of Src homology 2 domain–containing phosphatase 2 (SHP2) in the residual cells of ALK/ROS1/EGFR-altered non–small cell lung cancer (NSCLC). Molecular-targeted therapies failed to inhibit the ERK signaling pathway in the residual cells, whereas the SHP2 inhibitor SHP099 abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo. Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising therapeutic strategy for oncogene-driven NSCLC.
Targeting TfR1 with the ch128.1/IgG1 Antibody Inhibits EBV-driven Lymphomagenesis in Immunosuppressed Mice Bearing EBV+ Human Primary B-cells
Authors: Martínez Laura E. , Daniels-Wells Tracy R. , Guo Yu , Magpantay Larry I. , Candelaria Pierre V. , Penichet Manuel L. , Martínez-Maza Otoniel , Epeldegui Marta
Published: June 2021

Epstein–Barr virus (EBV) is a human gammaherpesvirus associated with the development of hematopoietic cancers of B-lymphocyte origin, including AIDS-related non-Hodgkin lymphoma (AIDS-NHL). Primary infection of B-cells with EBV results in their polyclonal activation and immortalization. The transferrin receptor 1 (TfR1), also known as CD71, is important for iron uptake and regulation of cellular proliferation. TfR1 is highly expressed in proliferating cells, including activated lymphocytes and malignant cells. We developed a mouse/human chimeric antibody targeting TfR1 (ch128.1/IgG1) that has previously shown significant antitumor activity in immunosuppressed mouse models bearing human malignant B-cells, including multiple myeloma and AIDS-NHL cells. In this article, we examined the effect of targeting TfR1 to inhibit EBV-driven activation and growth of human B-cells in vivo using an immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ [NOD/SCID gamma (NSG)] mouse model. Mice were implanted with T-cell–depleted, human peripheral blood mononuclear cells (PBMCs), either without EBV (EBV−), or exposed to EBV in vitro (EBV+), intravenously via the tail vein. Mice implanted with EBV+ cells and treated with an IgG1 control antibody (400 μg/mouse) developed lymphoma-like growths of human B-cell origin that were EBV+, whereas mice implanted with EBV+ cells and treated with ch128.1/IgG1 (400 μg/mouse) showed increased survival and significantly reduced inflammation and B-cell activation. These results indicate that ch128.1/IgG1 is effective at preventing the growth of EBV+ human B-cell tumors in vivo, thus, indicating that there is significant potential for agents targeting TfR1 as therapeutic strategies to prevent the development of EBV-associated B-cell malignancies.

Significance:

An anti-TfR1 antibody, ch128.1/IgG1, effectively inhibits the activation, growth, and immortalization of EBV+ human B-cells in vivo, as well as the development of these cells into lymphoma-like tumors in immunodeficient mice.
Development of a High-throughput NanoBRET Screening Platform to Identify Modulators of the RAS/RAF Interaction
Authors: Durrant David E. , Smith Emily A. , Goncharova Ekaterina I. , Sharma Nirmala , Alexander Patrick A. , Stephen Andrew G. , Henrich Curtis J. , Morrison Deborah K.
Published: June 2021

Activating mutations in RAS are found in approximately 30% of human cancers, resulting in the delivery of a persistent signal to critical downstream effectors that drive tumorigenesis. RAS-driven malignancies respond poorly to conventional cancer treatments and inhibitors that target RAS directly are limited; therefore, the identification of new strategies and/or drugs to disrupt RAS signaling in tumor cells remains a pressing therapeutic need. Taking advantage of the live-cell bioluminescence resonance energy transfer (BRET) methodology, we describe the development of a NanoBRET screening platform to identify compounds that modulate binding between activated KRAS and the CRAF kinase, an essential effector of RAS that initiates ERK cascade signaling. Using this strategy, libraries containing synthetic compounds, targeted inhibitors, purified natural products, and natural product extracts were evaluated. These efforts resulted in the identification of compounds that inhibit RAS/RAF binding and in turn suppress RAS-driven ERK activation, but also compounds that have the deleterious effect of enhancing the interaction to upregulate pathway signaling. Among the inhibitor hits identified, the majority were compounds derived from natural products, including ones reported to alter KRAS nanoclustering (ophiobolin A), to impact RAF function (HSP90 inhibitors and ROS inducers) as well as some with unknown targets and activities. These findings demonstrate the potential for this screening platform in natural product drug discovery and in the development of new therapeutic agents to target dysregulated RAS signaling in human disease states such as cancer.
Parosteal Osteosarcoma with Pancreatic Metastasis and Multiple Relapses: A Case Report and Review of the Literature
Authors: Cirotski Daniel , Panicker Jyoti
Published: June 2021

Osteosarcoma is the most common primary bone cancer in all age groups. Metastasis mostly occurs with high-grade tumors disseminating to the lungs and other bones. Spread to the pancreas is rare and undocumented in the low-grade subtypes. Additionally, it is uncommon for the disease course of low-grade subtypes to involve multiple relapses. We present a 35-year-old woman with parosteal osteosarcoma who has experienced an atypical metastasis to the pancreas as well as multiple local and pulmonary relapses. The lesion was identified incidentally on routine imaging, and the patient underwent resection. We compare our case to the other reports of pancreatic metastasis in the literature. Despite being especially rare, clinicians ought to be aware of pancreatic metastasis of osteosarcoma. Furthermore, despite parosteal osteosarcoma’s less aggressive disease course, it can uncommonly lead to multiple relapses. We present a rare case exemplifying these phenomena in the prognostically favorable histologic subtype of parosteal osteosarcoma.
Atemwegsallergien: Schimmelpilz-Sensibilisierungen bei Asthma-Patienten in Betracht ziehen
Authors: Joest Marcus
Published: June 2021

Background: Fungal spores are ubiquitous allergens. Severe forms of asthma are particularly highly associated with fungal sensitization. National and international asthma guidelines recommend the implementation of allergen immunotherapy if indicated. Thus, detection and treatment of relevant allergies are key components of primary care of these patients. Objectives: The aims of the study were (i) to investigate trends in the prevalence of sensitization to twelve fungi in central Germany over the last 20 years and (ii) to dissect specific sensitization patterns among the 3 most important fungi: Aspergillus, Alternaria, and Cladosporium. Methods: This single-center study evaluated skin prick test (SPT) results of 3,358 patients with suspected airway allergies over a period of 20 years (1998–2017). Results: While 19.2% of all study patients had positive test results to at least 1 of the 3 fungi (Alternaria, Aspergillus, or Cladosporium) in the first study decade, this rate increased to 22.5% in the second decade. Slight increases in sensitization rates to almost all fungi were observed over the 20-year period. In the last decade, polysensitization to Alternaria, Aspergillus, and Cladosporiumincreased significantly. Sensitization to fungi is age-dependent and peaks in the age-group of 21–40 years during the second decade. Conclusion: Fungi are relevant allergens for perennial and seasonal allergy symptoms. We currently recommend including Aspergillus, Alternaria, and Cladosporiumin the standard series of SPTs for airway allergies.
Obras de arte da Companhia Paulista no século XIX: pequeno estudo sobre suas pontes ferroviárias
Authors: Silva Tainá Maria , Oliveira Eduardo Romero de
Published: June 2021

O presente artigo tem por finalidade investigar questões sumárias sobre as obras de arte ferroviárias, especificamente as pontes do século XIX da Companhia Paulista, estudando seus materiais, sistemas construtivos e profissionais envolvidos na construção. A investigação se justifica pelo fato das obras de arte se mostrarem semelhantes às demais estruturas ferroviárias, se tornando passíveis de maiores investigações no que compete ao campo da arquitetura e da engenharia. Foram consultados os relatórios administrativos da companhia, plantas, fotografias e bibliografias específicas. Efetuado um levantamento inicial de pontes da Companhia Paulista, compreendeu-se o motivo da utilização de determinados materiais bem como sua relação com questões econômicas e profissionais disponíveis.
A construção do Estatuto da Cidade e da ideia de Plano Diretor numa perspectiva histórica: discutindo a adequação destes instrumentos aos municípios de pequeno porte populacional
Authors: Lage Selena Duarte Lage e , Francisco Filho Lauro Luís
Published: June 2021

O conteúdo que compõe o Estatuto da Cidade é resultado de um longo processo de construção que tem influências de matrizes discursivas diversas. Nesta trajetória, observa-se um processo de ressignificação da ideia de Plano Diretor. Este artigo busca refazer o caminho de construção do Estatuto da Cidade e da conotação atual do Plano Diretor. Objetiva-se compreender as ambiguidades e contradições do Estatuto da Cidade, em especial no que se refere ao Plano Diretor, e verificar a adequação destes instrumentos aos municípios de pequeno porte populacional. A metodologia utilizada foi a revisão e análise crítica da bibliografia pertinente. Como resultado, o artigo põe em foco entraves importantes à adequação dos planos diretores pós-Estatuto da Cidade aos municípios de pequeno porte populacional.
Being Theological in a Comparative Manner in Today’s Indonesia
Authors: Laksana Albertus Bagus
Published: June 2021

In today’s Indonesia, public theological discourse is messy, sectarian, superficial, and highly apologetic. While the state philosophy of Pancasila offers an inclusive theological vision of citizenship and nationhood, its inclusiveness and dialogical character suffer from the exclusive use of the combination of the modern world-religion paradigm, European Christian theology, and Islamic parameters. This essay argues that the new comparative theology can serve as a dialogical theological reasoning that is particularly helpful to foster theologically constructive encounters among different religions, and thus able to address public concern, especially identity politics. This essay presents some concrete examples of comparative theological works in the Indonesian context, drawn from the author’s experiments. These highlight the dialogical, confessional, spiritual, and constructive characters of this theological reasoning, and pay attention to the hybrid identity and local cultures that form the richness of the Indonesian reality.
Identification of Specific Modules and Hub microRNAs Related to Osteosarcoma by Weighted microRNA Co-Expression Network Analysis
Authors: Hanying Mei , Zhao Yueling , Suo Na
Published: June 2021

Osteosarcoma (OS) is a malignant tumor with high morbidity and poor prognosis, especially for patients with metastasis. New therapeutic approaches are extremely needed. MicroRNAs can affect manykey biological processes, including the development and progression of complex diseases,
such as OS. Here we identified specific modules and hub microRNAs related to OS through weighted gene co-expression network analysis (WGCNA). A module consisting of 72 microRNAs were found to be highly related to OS and 22 of them have been reported as deregulatedmicroRNAs in OS patients which
play a role in OS tumorigenesis, development or prognosis. Then the target genes of the microRNAs were predicted and the functional enrichment analysis was performed on these genes. This study will provide a more clear understanding for facilitating the characterization and identification
of new biomarkers and treatment for patients with OS by targeted miRNA.
Effect of microRNA-4268 on Proliferation and Apoptosis of Non-Small Cell Lung Cancer Cells Through Regulating Signal Transducer and Activator of Transcription 3 Level
Authors: Han Lei , Yu Renzhi , Ni Xin , Zhang Zenglei
Published: June 2021

STAT3 is closely related to non-small cell lung cancer (NSCLC). miR-4268 is predicted to regulate STAT3 level by MiRDB analysis. Therefore, our study investigated whether miR-4268 affects NSCLC cells by regulating STAT3. The control group (NC group), miR-4268 Mimics group, and miR-4268
Mimics +pFBD-STAT3 group were set up followed by analysis of miR-4268 and STAT3 mRNA level by QRT-PCR, relationship between miR-4268 and STAT3 by dual fluorescein reporter assay, STAT3 and Tubulin protein level by Western blot, cell proliferation by MTT assay and apoptosis by Annexin V-FITC/PI
staining. Compared with normal tissue, miR-4268 expression in cancer tissue was significantly reduced (P <0.01), while STAT3 level was elevated (P <0.01). STAT3 was a target gene of miR-4268. Compared with NC group, STAT3 level was significantly reduced in miR-4268 Mimics
group (P <0.01) and increased in miR-4268 Mimics+pFBD-STAT3 group compared with miR-4268 Mimics group (P <0.05). Compared to NC group, miR-4268 Mimics group had reduced cell proliferation and increased cell apoptosis and opposite changes were observed in miR-4268 Mimics+pFBD-STAT3
group which had increased cell proliferation and decreased apoptosis (P < 0.05). miR-4268 regulates STAT3 mRNA level and inhibits NSCLC cell proliferation and promotes apoptosis. However, over-expression of STAT3 can inhibit the effect of miR-4268.
Accounting for skew when post-processing MOGREPS-UK temperature forecast fields
Authors: Allen Sam , Evans Gavin R , Buchanan Piers , Kwasniok Frank
Published: June 2021

When statistically post-processing temperature forecasts, it is almost always assumed that the future temperature follows a Gaussian distribution conditional on the output of an ensemble prediction system. Recent studies, however, have demonstrated that it can at times be beneficial to employ alternative parametric families when post-processing temperature forecasts, that are either asymmetric or heavier-tailed than the normal distribution. In this article, we compare choices of the parametric distribution used within the Ensemble Model Output Statistics (EMOS) framework to statistically post-process 2m temperature forecast fields generated by the Met Office’s regional, convection-permitting ensemble prediction system, MOGREPS-UK. Specifically, we study the normal, logistic and skew-logistic distributions. A flexible alternative is also introduced that first applies a Yeo-Johnson transformation to the temperature forecasts prior to post-processing, so that they more readily conform to the assumptions made by established post-processing methods. It is found that accounting for the skewness of temperature when post-processing can enhance the performance of the resulting forecast field, particularly during summer and winter and in mountainous regions.
Veteran Teachers’ Understanding of “Balanced Literacy”
Authors: Fisher Douglas , Frey Nancy , Lapp Diane
Published: June 2021

The term balanced literacy was popularized in the mid-1990s to describe a middle ground in terms of text selection, instruction, skills, and strategies. The intention was to merge the promising elements of whole language and phonics. Interactions with educators and literacy leaders across the country currently suggest that a term that had been seemingly well defined 20 years ago had become more vague. This descriptive study polled 25 veteran teachers to identify commonalities among their definitions and instructional applications.
Differences between Young Children’s Actual, Self-perceived and Parent-perceived Aquatic Skills
Authors: D’Hondt Eva , Buelens Lise , Barnett Lisa M. , Howells Kristy , Sääkslahti Arja , Costa Aldo M. , Jidovtseff Boris , Mertens Lisa , Martelaer Kristine De
Published: June 2021

As drowning is a leading cause of unintentional injury/death in children worldwide, perceptions of their actual aquatic skills are of critical importance. Children’s self-perceptions may influence the risks they take, and parental perceptions may influence the degree of supervision deemed to be necessary for children in and around water. Accordingly, we examined the differences between young children’s actual, self-perceived and parent-perceived aquatic skills. Using a three-way repeated measures ANCOVA, we analyzed data from 134 child-parent dyads (56.0% boys; M age = 7.1, SD = 1.1 years; and 71.6% mothers). We measured self and parental perceptions of the child’s aquatic skills with the ‘Pictorial Scale of Perceived Water Competence’ (PSPWC), and we applied the exact same 17 test items of the PSPWC to assess the child’s actual aquatic skill level in the water. Controlling for years of swimming school experience, within-subject differences between the total scores on the ‘Actual Aquatic Skills Test’ (AAST) and both the child- and parent-completed PSPWC indicated lower than actual estimates of the children’s aquatic skill level. The degree of disagreement against the AAST was more pronounced in parents than in 6-7 year-old children but was similar between parents and 8-9 year-old children, with these patterns being evident regardless of the children’s sex. Our study contributes to an ongoing validation of the PSPWC and represents a key advance in assessing and comparing children’s actual and perceived aquatic skill competence, using perfectly aligned instruments. Future research and practice might explore children’s actual aquatic skills in different contexts (e.g., open water), include perspectives of non-parent caregivers and assess perceived and actual water competence across development.
Effectiveness of Parenting Training on Emotional and Behavioral Problems in First through Fourth Grade Thai Children with ADHD: A Randomized Controlled Study
Authors: Tiwawatpakorn Nichanan , Worachotekamjorn Juthamas , Tassanakijpanich Nattaporn
Published: June 2021

Objective

To evaluate the effectiveness of parenting training on emotional and behavioral problems of first through fourth grade Thai children with ADHD compared with routine clinical care in a university hospital in southern Thailand.

Material and methods

Caregivers of the children were invited and assessed for eligibility. Eighty children with ADHD were randomly assigned to either a parenting training group or a routine clinical care group. The primary caregivers of the parenting training group participated in 6 120-minute weekly sessions in addition to routine clinical care. Caregiver and teacher ADHD ratings and oppositional-defiant disorder ratings were collected at the time of enrollment and after the 6 weeks of training in both groups. The differences in scores in both groups were analyzed using a mixed model ANOVA.

Results

Each arm had 40 participants. The mean (SD) age of the children was 8.3 (1.1) years and their mean (SD) age at the first diagnosis of ADHD was 6.8 (1.3) years. Most of them were receiving methylphenidate for treatment of their ADHD. The mother was the primary caregiver for 83.5% of the children. The ADHD symptoms and oppositional-defiant symptoms showed significant improvement after receiving the treatment in both groups; however, no significant differences were found between groups.

Conclusion

Adding parenting training to the routine clinical care for children with uncomplicated ADHD who are being medicated was not more effective than the routine clinical care alone. However, the power of this study is limited, and follow-up is needed to evaluate the long-term effectiveness.
The Biden Administration: An Opportunity to Affirm a Flexible and Adaptive American World Leadership
Authors: Struye de Swielande Tanguy
Published: June 2021

The article develops a strategic framework to redefine American international leadership under the Biden administration. While the decline of the American‐led order is not a new trend, it has been accelerated under the Trump administration, which focused on domestic policies and left the global stage in disarray. The challenges are many for the new president, and many pressures can already be felt. Biden's administration is under high expectations to stabilize the international system and deal with the many issues that the world faces: economic recovery, COVID‐19, climate change, cybersecurity, and relations with China, Russia, Iran, and North Korea, to name but a few. Yet, while the Biden presidency is—wrongly—understood as “U.S. back to normal,” the international stage has evolved. The article thus argues that restoring American world leadership means modifying that leadership and adapting it to the new reality. Building on management theories and the English School of international relations theories, the research presents a theoretical framework for reinventing and reconstructing a new form of leadership. It then applies the resulting strategic design to the Biden administration's objectives and policies in the form of seven strategic recommendations. Ultimately, the article explains how the United States can remain world leader by acknowledging the current global situation and adopting a pragmatic vision of international affairs.
Imputation of Missing Covariate Data Prior to Propensity Score Analysis: A Tutorial and Evaluation of the Robustness of Practical Approaches
Authors: Leite Walter L. , Aydin Burak , Cetin-Berber Dee D.
Published: June 2021

Background:

Propensity score analysis (PSA) is a popular method to remove selection bias due to covariates in quasi-experimental designs, but it requires handling of missing data on covariates before propensity scores are estimated. Multiple imputation (MI) and single imputation (SI) are approaches to handle missing data in PSA.

Objectives:

The objectives of this study are to review MI-within, MI-across, and SI approaches to handle missing data on covariates prior to PSA, investigate the robustness of MI-across and SI with a Monte Carlo simulation study, and demonstrate the analysis of missing data and PSA with a step-by-step illustrative example.

Research design:

The Monte Carlo simulation study compared strategies to impute missing data in continuous and categorical covariates for estimation of propensity scores. Manipulated conditions included sample size, the number of covariates, the size of the treatment effect, missing data mechanism, and percentage of missing data. Imputation strategies included MI-across and SI by joint modeling or multivariate imputation by chained equations (MICE).

Results:

The results indicated that the MI-across method performed well, and SI also performed adequately with smaller percentages of missing data. The illustrative example demonstrated MI and SI, propensity score estimation, calculation of propensity score weights, covariate balance evaluation, estimation of the average treatment effect on the treated, and sensitivity analysis using data from the National Longitudinal Survey of Youth.
COVID‐19 in the Clinic: Aerosol Containment Mask for Endoscopic Otolaryngologic Clinic Procedures
Authors: Ference Elisabeth H. , Kim Wihan , Oghalai John S. , Kim Jee‐Hong , Applegate Brian E.
Published: June 2021

Objective

To create an aerosol containment mask (ACM) that contains aerosols during common otolaryngologic endoscopic procedures while protecting patients from environmental aerosols.

Study Design

Bench testing.

Setting

Mannequin testing.

Methods

The mask was designed in SolidWorks and 3‐dimensional printed. Mannequins were fitted with a nebulizer to generate aerosols. Commercial particle counters were used to measure mask performance.

Results

The ACM has 2 ports on either side for instruments and endoscopes, a port for a filter, and a port that can evacuate aerosols contained within the mask via a standard suction pump. The mask contained aerosols on a mannequin with and without facial hair when the suction was set to 18.5 L/min. Other types of masks demonstrated substantial aerosol leakage under similar conditions. In a subsequent experiment, the ACM contained aerosols generated by a nebulizer up to the saturation of the particle detector without measurable leakage with or without suction.

Conclusion

The ACM will accommodate rigid and flexible endoscopes plus instruments and prevent leakage of patient‐generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions.

Level of evidence

2.
Physical activity, emotional state and socialization in the elderly: study protocol for a clinical multicentre randomized trial
Authors: Ruiz-Comellas Anna , Sauch Valmaña Glòria , Mendioroz Peña Jacobo , Roura Poch Pere , Sabata Carrera Anna , Cornet Pujol Irene , Gómez Baena Isabel , Casaldàliga Solà Àngels , Saldaña Vila Carme , Fusté Gamisans Montserrat , Boix De la Casa Carme , Rodoreda Pallàs Berta , Ramirez-Morros Anna , Vazquez Abanades Lorena , Vidal-Alaball Josep
Published: June 2021

Objective

To evaluate whether a 4-month physical activity (PA) group program and visits to sociocultural organizations improve emotional state, social support levels and health-related quality of life in elderly individuals with depression and/or anxiety and/or loneliness.

Methods

This will be a multicentre, randomized, two-group clinical trial with a 1-year follow-up. Participants will be 150 primary care patients aged >64 years allocated equally to a control group and an intervention group. Inclusion criteria are Beck Depression Inventory (BDI-II) score ≥14 and/or General Anxiety Disorder (GAD-7) scale score ≥10 and/or Duke-UNC-11 scale score ≥32. The intervention group will participate in a 4-month group PA program. The program will comprise two walks per week and a monthly visit to a sociocultural facility.

Results

Measured outcomes are clinical remission of depression (BDI-II score <14) and anxiety (GAD-7 scale score <10), improved social support (reduction in DUKE-UNC-11 score), improved quality of life and/or response to the intervention at 4 and 12 months post-intervention. Intervention satisfaction and adherence and post-intervention links with sociocultural organizations will also be assessed.

Conclusion

The findings could encourage the provision of activity-based community interventions for older individuals.