bluuebunny/crossref_metadata_2025 huggingface dataset:
Manajemen Fasilitas Parkir Di Masjid Al-Falah Surabaya
Authors: Mauludi Mauludi , Wadud Abdul , Bramayudha Airlangga
Published: June 2021

ABSTRACTThe purpose of this study is to describe the management of parking facilities at places of worship. In this study using qualitative methods with a qualitative descriptive method approach. The place of worship that is the object of research is the Al-Falah Mosque. The process of collecting data is done by observation, in-depth interviews, and documentation. This study describes managerial supervision of parking facilities at Al-Falah Mosque. The Al Falah Mosque takmir committee collaborates with the Surabaya City Transportation Agency (DISHUB), residents who have vacant land and parking attendants from residents around the Al Falah Mosque. Managerial oversight of the parking area of the Al Falah Mosque is carried out with a coordinator system of permanent employees and financial reports from the security coordinator for the finance department. Suggestions for improvement, Al Falah Mosque should have a written system starting from Standard Operating Procedure (SOP) for land use, parking management and cooperation system.Â Â ABSTRAKTujuan dari penelitian ini adalah untuk mendeskripsikan tentang pengelolaan fasilitas parkir pada tempat ibadah. Dalam Penelitian ini menggunakan metode kualitatif dengan pendekatan metode kualitatif deskriptif. Tempat ibadah yang menjadi objek penelitian ialah Masjid Al-Falah. Proses pengambilan data dilakukan dengan Observasi, Wawancara mendalam, dan dokumentasi. Penelitian ini menggambarkan tentang pengawasan secara manajerial fasilitas parkir di Masjid Al-Falah. Pengurus takmir Masjid Al Falah bekerjasama dengan dinas perhubungan (DISHUB) kota Surabaya, warga yang mempunyai lahan kosong serta petugas parkir dari warga sekitar Masjid Al Falah. Pengawasan secara manajerial terhadap keparkiran Masjid Al Falah dilakukan dengan sistem satu koordinator dari karyawan tetap dan laporan keuangan dari koordinator keamanan untuk bagian keuangan. Saran untuk perbaikan, seharusnya Masjid Al Falah mempunyai sistem yang tertulis mulai dari Standar Operasional Prosedur (SOP) penggunaan lahan, pengelolaan parkir dan sistem kerjasamanya.Â
Strategi Komuikasi Dakwah Ustadz Muhammad Sholeh Drehem
Authors: Nugroho Adityo
Published: June 2021

ABSTRACTIn dakwah communication, as a communicator a preacher should have methods or ways so that the message could be delivered to the Jamaah. Ustadz Muhammad Sholeh Drehem delivers his speech throughÂ  radios andÂ  medias, he has more than other speakers who deliver their preach daily at Ar Rahmah Perak Surabaya, his strategy draws attention to researcher to conduct the research about what kind of strategy or ways implemented by Ustadz Muhammad Sholeh DrehemÂ  to deliver his preach and how he overcomes the problems he faces.The purpose of this reseach is to find out whatÂ  communication strategy implemented by Ustadz Muhammad Sholeh Drehem at Ar Rahmah mosque, how Ustadz faced his problems. This reseach is a qualitive descriptive kind of reseach which uses three techniques of data collection, through observation, interview, and documentation. The conclusion of the reseach are that Ustadzâ€™s strategy target determination, the determinstion of ways in communication, identification of the jamaahs, source credibility, the Jamaahâ€™s history and feelings, also the media election are quite well. Yet there are problems still, psychology problem, anthropological problem, semantic problem, mechanical problem, and ecological problem.ABSTRAKDalam komunikasi dakwah, seorang daâ€™i adalah sebagai komunikator dakwah diharuskan mempunyai metode atau cara supaya pesan dakwahnya dapat diterima dengan baik oleh jamaâ€™ah atau madâ€™unya. Ustadz Muhammad Sholeh Drehem berdakwah dengan menyampaikan pesan dakwahnya melalui kajian di dalam dan diluar masjid, beliau juga menyampaikan pesan dakwahnya melalui radio, dan media lainnya. Ustadz memiliki jamaâ€™ah yang lebih banyak dibandingkan dengan pengisi kajian rutin lainnya di Masjid Ar Rahmah Perak Surabaya. Hal inilah yang menarik perhatian peneliti untuk menelusuri tentang bagaimana strategi komunikasi dakwah Ustadz Muhammad Sholeh Drehem dan apa hambatan hambatannya.Penelitian ini bertujuan untuk mengetahui apa saja strategi komunikasi yang di lakukan oleh Ustadz Muhammad Sholeh Drehem di masjid Ar Rahmah dan bagaimana Ustadz Muhammad Sholeh Drehem dalam menghadapi hambatan hambatan dakwahnya. Penelitian ini merupakan penelitian diskriptif kualitatif dengan menggunkan tiga teknik pengumpulan data, melalui observasi, wawancara dan dokumentasi. Hasil penelitian memperoleh kesimpulan bahwa strategi Ustadz Muhammad Sholeh Drehem penentuan sasaran, penentuan cara berkomunikasi, kredebilitas sumber, mengidentifikasi jamaâ€™ah, latar belakang jamaâ€™ah, perasaan jamaâ€™ah, pemilihan media. Adapun hambatannya yaitu hambatan psikologis, hambatan antropologis, hambatan simantik, hambatan mikanis, hambatan ekologis
Manajemen Fasilitas Multimedia Masjid Ar-Rahmah Perak Surabaya
Authors: Qisom Shobikhul
Published: June 2021

One of the roles of the mosque is to prepare for being the facilitator of the Muslim community in all aspects of life problems. Therefore, the mosques must be able to facilitate the Muslim community by adjusting their need level and enthusiasm in a particular field. One thing that is really crucial to be concerned is the rapid of technological development as the technology sector will become a very dominant sector in the future. Thus, the technology that can be used as a tool by the mosques in order to be able to facilitate Muslims community to reach more information is multimedia. In this study, there are three focuses of problem formulations, namely: 1) Multimedia planning process, 2) Procurement Process of multimedia and 3) Process of maintaining multimedia facilities. The aim that wants to be achieved in this research is to know the process of the multimedia planning at the Ar Rahmah Mosque in Surabaya and to find out how the procurement and the maintenance processes of the multimedia facilities itself. The method used in this study is a qualitative method. The type of research used is a descriptive qualitative study where the techniques of collecting the data were carried out by using interviews, observation, and documentation. The data is then processed by using data triangulation which aims to test the validity of the data obtained. Furthermore, the data will be analyzed by presenting the whole of data then the researcher will draw conclusions from the data acquired.Salah satu tugas masjid adalah menyiapkan diri sebagai fasilitator umat dalam segala aspek persoalan kehidupan. Oleh karena itu, masjid harus bisa memfasilitasi umat dengan menyesuaikan tingkat kebutuhan dan antusiasme mereka terhadap suatu bidang tertentu. Salah satu yang sangat perlu diperhatikan ialah perkembangan teknologi yang begitu pesat. Karena sektor teknologi akan menjadi sektor yang sangat dominan di masa mendatang.Maka,teknologi yang dapat digunakan masjid sebagai alat atau sarana agar mempermudah Jamaâ€™ah menjangkau informasi lebih banyak adalah multimedia.Dalam penelitian ini terdapat tiga fokus rumusan masalah, yaitu: 1) Proses perencanaan multimedia, 2) Proses pengadaan fasilitas multimedia dan 3) Proses perawatan fasilitas multimedia. Tujuan yang ingin dicapai dalam peneltian ini adalah mengetahui bagaimana proses perencanaan multimedia di Masjid Ar Rahmah Surabaya dan mengetahui bagaimana proses pengadaan serta perawatan daripada fasilitas multimedia itu sendiri.Metode yang digunakan pada penelitian ini adalah kualitatif. Jenis penelitian yang digunakan adalah deskriptif di mana teknik pengumpalan data yang dilakukan adalah dengan wawancara, observasi dan dokumentasi. Data kemudian diolah menggunakan triangulasi data dengan tujuan untuk menguji kevalidan atau keabsahan data yang diperoleh. Selanjutnya, data akan dianalisis dengan cara menyajikan data secara keseluruhan kemudian peneliti akan menarik kesimpulan dari data yang diperoleh.
Introduction: Ruminations on the “F” and “B” Words
Authors: Shannon Timothy J.
Published: June 2021

Over the past two decades, historians studying the American West have embraced the label “borderlands” as a means of distinguishing their work from the triumphalism associated with Frederick Jackson Turner’s frontier thesis. Historians of early America have made a similar transition, although the term “frontier” is still very much in use among those working in the mid-Atlantic region. The articles in this special issue of Pennsylvania History illustrate how the themes of borderlands history have found their way into studies of eighteenth-century Pennsylvania, even if the term itself has not gained wide currency there.
Hierarchical cluster analysis: A statistical tool to study sheep behavior under heat stress
Authors: Jorge Orlay Serrano  , Asiel Villares  , Francisco Dongo Manuel-Malamba  , Jorge Martínez-Melo  , Carlos Mazorra  , Ángela Borroto  , Elliosha Hajari  , Norge Fonseca-Fuentes  , José Carlos Lorenzo
Published: June 2021

Sheep farming, and the income generated from this endeavor, contributes significantly to the global economy and rural livelihoods. Therefore, it is vital to maintain the productivity of this industry in the face of changing climate patterns. In the context of sheep farming, animals are exposed to a higher heat load as global temperatures are increasing, leading to heat stress. This heat stress conditions can adversely affect animal productivity and welfare resulting in reduced feed intake, physiological (panting, higher respiration, higher heart rate, etc.) and behavioral changes (lying down, standing, seeking shade, etc.) to compensate for increased heat load ultimately leading to lowered productivity. Considering this, it is important to monitor sheep behavior in order to implement improved management practices to compensate for changes in climate. The current short study investigated sheep behavior at different times throughout the day. The data generated was analyzed using the hierarchical cluster analysis method in order to integrate all variables into a single representative dendrogram that could summarize sheep behavior. While hierarchical cluster analysis has been applied in diverse scientific fields, as far as we know, the statistical application reported here is novel in the context of sheep behavior in response to climate change. We studied sheep behavior throughout the day (9:00 – 9:50; 10:00 – 10:50; 11:00 – 11:50; 14:00 – 14:50; 15:00 – 15:50; 16:00 – 16:50). Shade was provided in the form of trees. The following indicators were recorded over a period of twelve months at two week intervals: number of animals eating grass, ruminating and resting. The statistical evaluations undertaken resulted in the generation of a dendrogram which integrated all evaluated variables to categorize the behaviors undertaken at different times during the day. The dendrogram indicated three groupings of sheep behavior that were distinctly different from each other. The analysis shown here indicates that the use of hierarchical cluster analysis culminating in the construction of a dendrogram can effectively synthesize large datasets to outline similar relationships (in this study, this was in the context of observed behaviors). This statistical method applied to sheep physiological studies may help interpret experimental data in the context of climatic change.
Immunological and molecular detection of rotavirus genotype in calves with gastroenteritis in Diyala-Iraq
Authors: Ammar Talib Nasser  , Abdulrazak Shafiq Hasan  , Amer Khazaal Saleh  , Mohammad Kassem Saleh
Published: June 2021

Aim: To explore the prevalence of rotavirus infection along with the molecular detection and genotyping of group A rotavirus (RVA) among bovine calves up to 5 months old in Diyala province-Iraq. Methods: This is a cross sectional study conducted in Diyala province-Iraq during the period of 2019-2020. One hundred bovine calves with age range of 1-5 months were included in the study. All were suffering acute gastroenteritis. Serum anti-rotavirus IgM and IgG plus fecal rotavirus Ag were tested for using ELISA techniques. Stool samples positive for rotavirus Ag were submitted for reverse transcription PCR (RT-PCR) for G and P genes, followed by sequencing and genotyping thereafter. Statistical analysis was done using SPSS version 25 and P values ≤ 0.05 were considered significant. Results: The positivity rate of anti-rotavirus IgM was 80% (P = 0.0001), and that of anti-rotavirus IgG was 79% (P = 0.0001). The rotavirus stool antigen was detected in 68% of calves (P = 0.01). A total of 45 stool samples which were positive for rotavirus Ag were submitted for RT-PCR; 13 (28.9%) were positive and 32 (71.1%) were negative (P = 0.084). 10 PCR positive samples were used for sequencing and genotyping and indicated that all investigated strains belonged to G1P[8] genotype. Conclusion: The current strains analyzed belonged to the G1P[8] RVA genotypes, affirming that employment of VP7 gene polymorphism accurately yielded uniform phylogenetic distances amongst investigated rotavirus strains and that there were no noticeable assortment events between human and animal rotavirus strains in Diyala province.
Die zeitliche Wirkung von Urteilen des EuGH
Authors: Riegger Stephan
Published: June 2021

Against the background of the interconnection between the Union legal order and the legal orders of the Member States, the temporal effect of ECJ judgments is one of the central elements of Union law. Following a careful analysis of the parameters of Union law that shape it, the book deals with the possibilities of courts of Member States to react to an interpretation of Union law by the ECJ whose effects have not been limited in time. By focusing in particular on the "enforcement dimension" of Union law, it contributes to determining the status of the primacy of Union law and makes the hybrid nature of interpretation in conformity with directives more visible.
Construção de um novo instrumento orientador para o exame físico respiratório de equinos
Authors: Santi Thasla De Freitas , Mendes Barussi Fernanda Cristina , Zettel Bastos Fernanda , Deitos Joan Emilio , Weber Saulo Henrique , Ribeiro Carvalho Deborah , Vicente Michelotto Júnior Pedro
Published: June 2021

O diagnóstico de doenças respiratórias é desafiador aos médicos veterinários, pois os mesmos sinais clínicos são encontrados em diferentes doenças. O presente estudo objetivou o aprimoramento de um instrumento orientador ao exame clínico respiratório de equinos, com a hipótese de que auxiliará no trabalho médico veterinário. Neste estudo de coorte, 19 médicos veterinários (MV) atuantes em medicina equina aceitaram participar do estudo, sendo divididos em dois grupos: MV generalistas (GMVG, n = 16), com profissionais graduados a menos de 10 anos e MV especialistas (GMVE, n = 3), com mais de 10 anos de experiência profissional. Um instrumento de avaliação inicial (instrumento 1) foi disponibilizado a todos os avaliadores para ser empregado no exame físico de um equino qualquer, para em seguida responderem a um questionário a respeito da complexidade geral, preenchimento, compreensão, praticidade e tempo para preenchimento, com espaço para comentários. Com base nas respostas, um novo instrumento (2) foi construído para nova avaliação pelos MV. Foi realizada a comparação das respostas obtidas pelos avaliadores para os dois instrumentos. Como resultado inicial, a avaliação dos instrumentos foi concordante entre os dois grupos, evidenciando que a utilização dos instrumentos na prática clínica independe de experiência profissional. O instrumento de avaliação 2 foi considerado menos complexo (p = 0,046), de fácil preenchimento (p = 0,005) e maior compreensão (p = 0,003). Assim, mesmo em se tratando de um processo a ser continuado, conseguiu-se obter um instrumento de avaliação respiratória de equinos de melhor qualidade, e que visa auxiliar o MV de campo.
Industrialização do ensino e política de educação a distância
Authors: Costa Antonio Roberto Faustino da
Published: June 2021

O livro Industrialização do ensino e política de educação a distância coloca-se como um trabalho sério e rigoroso ao aceitar o desafio de afirmar que “o discurso da industrialização do ensino governa a prática discursiva que norteia a política nacional de educação a distância”. O autor recorre a três ideologias que deram origem a diferentes teorias, concepções, abordagens e modelos de educação a distância: a “teoria da interdependência e autonomia”, a “teoria da comunicação e interação” e a “teoria da industrialização do ensino”. A partir desta última, faz um exame da política nacional de EAD, para mostrar que a “abordagem parte da premissa de que, enquanto a educação face a face compreende formas pré-industriais, a educação a distância pressupõe essencialmente condições industriais de ensino”, as quais teriam “como base o princípio da racionalização” que afeta o espírito, a letra e a política do processo de ensino-aprendizagem.
Anterior Mitral Leaflet Tear during Balloon Mitral Valvotomy in a Case of Juvenile Mitral Restenosis
Authors: Rai Rohit , Gawande Gajanan D. , Shaikh Shakil S. , Bansal Narender O.
Published: June 2021

Recurrent attacks of rheumatic fever can lead to mitral stenosis. In a country like India mitral stenosis can develop in the first decade of life. Our patient presented with recurrent mitral stenosis at twelve years of age. He had undergone balloon mitral valvotomy at the age of seven. However this time he developed anterior mitral valve leaflet tear after balloon mitral valvotomy and had to be taken for mitral valve repair. Due to severe fibrosis of mitral valve the patient underwent mitral valve replacement. He was started on warfarin and dose titrated according to PT / INR. Patient was discharged but has to be on lifelong anticoagulation from the age of twelve.
Antibiotic Resistant Profile of Lactic Acid Bacteria Isolated from Swine and Poultry Faeces in Umuahia Metropolis
Authors: Osaro-Matthew R. C. , Nweke O. G.
Published: June 2021

Aim: This study’s aim was to determine the antibiotics resistant profile of lactic acid bacteria isolated from poultry and swine faeces.

Study design: Faecal samples from swine and birds were randomly collected from livestock and poultry farms located in Umuahia metropolis, Abia State.

Place and duration of study: Department of microbiology, Michael Okpara University of Agriculture Umudike, between January 2019 to August 2019.

Methodology: A total of 12 faecal samples, 6 each from swines and birds were examined for the presence of lactic acid bacteria using  Deman Rogosa Sharpe agar supplemented with 0.3% CaCO3 (w/v). Isolates were identified based on their physiological and biochemical characteristics. Antibiotic susceptibility was carried out using disk diffusion method.

Results: Of the 12 faecal samples examined, all were positive for lactic acid bacteria, with counts ranging from 1.74 – 2.36 x 106 in swine and 1.52 – 2.08 x 106 in birds. Total of 14 strains that belong to three genera; Lactobacillus, Lactococcus and Streptococcus were isolated, genus Lactobacillus occurred highest 8(57.1%). The isolates showed multidrug resistance and exhibited high rate of resistance to Augmentin (100%), Ceftazidime (100%), Cefotaxime (92.9%), Erythromycin (85.7%), Ceftriaxone (71.4%) and Azithromycin (71.4%).

Conclusion: The antibiotic resistance pattern of the isolated lactic acid bacteria is a clear indication that most animal farmers are misusing antibiotics. Therefore, animal farmers should be advised on antibiotic application safety measures.
Role of Endoscopic Ultrasound in the Diagnosis of Solid Pancreatic Lesions: A Prospective Study
Authors: Elgawish Mahmoud Abdelhamid , Elnady Mohamed Ali Ahmed , Elbedewy Tamer Abd Elhamid , Elbedewy Mohamed Mohamed
Published: June 2021

Background: Endoscopic ultrasonography (EUS) provides high-resolution images of the pancreas, and it is considered one of the most accurate methods for the diagnosis and staging of solid pancreatic lesions (SPL), EUS guided fine-needle aspiration (EUS–FNA) can obtain cytological samples of pancreatic lesions, making a pathologic diagnosis possible, however, it is associated with small, but not insignificant, morbidity. The aim of this work is to determine in a prospective study, the role of EUS in the diagnosis of SPL in comparison with different radiological studies and to determine the diagnostic value of EUS guided FNA and elastography in differentiation between benign and malignant pancreatic lesions.

Patients and methods: A total of 50 patients with SPL identified by EUS after imaging studies were enrolled in the study. The qualitative elastography score was done, also the semi quantitative score of elastography was represented by the strain ratio (SR) method where two areas were selected, area (A) representing the region of interest and area (B) representing the normal area. Area (B) was then divided by area (A). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated by comparing diagnosis made by elastography, SR with the final diagnosis (by EUS-FNA, surgery, and/or follow up for 6 months).

Results: SPL were found to be malignant in 38 patients and benign in 12 patients. SPL was diagnosed by different imaging modalities in 39 patients with a percentage of (78%), while it was diagnosed by EUS in all 50 patients with a percentage of (100%). Elastography score alone had a sensitivity of 89.4%, a specificity of 75%, a PPV of 91.8% and an NPV of 69.2% and an accuracy of 86%. The best cut-off level of SR to obtain the maximal area under the curve was 8.42 with a sensitivity of 92.1%, specificity of 83.3%, PPV of 94.6%, NPV of 76.9% and an accuracy of 93.1%. Adding both elastography score to SR resulted in a sensitivity of 94.7%, specificity of 83.3%, PPV of 94.7%, NPV of 83.3% and accuracy of 94.3% for the diagnosis of SPL.

Conclusion: EUS has a role in diagnosis of SPL which may be superior to different radiological studies; also, EUS-elastography and SR can be a valuable complementary supplement for EUS-FNA.
Study of Antiemetic Potential of Ruta graveolens Extracts by Copper Sulphate and Brassica campestris Induced Emesis in Chicks
Authors: Nazir Sara , Malik Javeria Arshad , Malik Mahrukh , Gondal Muhammad Usman , Akhtar Muhammad Shoaib Muhammad Shoaib , Erum Alia
Published: June 2021

The antiemetic effect of aqueous and methanolic extracts of R. graveolens in young chicks was investigated. In addition, the phytochemical screening of the test plant and its acute toxicity studies were also conducted. Different doses of the extracts were tested for their antiemetic properties and were compared with the positive control antiemetic drug Chlorpromazine (150 mg/kg), Metoclopramide (50 mg/kg) and an untreated control (normal saline) against copper sulphate and Brassica-induced emesis. The phytochemical screening of R. graveolens showed that it contains certain alkaloids and flavonoids. It was found to be safe up to the dose of 2000 mg/kg body weight. The aqueous extracts in 50 and 150 mg/kg doses produced 41.49% and 66.49% inhibition of emesis, respectively by copper sulphate-induced emesis, while 34.66% and 57.95% inhibition of emesis, respectively by B. campestris-induced emesis. The methanolic extracts of Ruta graveolens in 50 and 150 mg/kg doses produced 46.80% and 70.20% inhibition of emesis, respectively by copper sulphate-induced emesis while 31.95% and 61.94%, respectively in Brassica campestris-induced chick emesis model. These results have suggested R. graveolens possess significant antiemetic properties that implicate its use as traditional medicine to treat emesis. However, further studies are needed to isolate the active principle(s) i.e. flavonoids contained in the plant drug tested and its real safety and efficacy as antiemetic agent.
Quantum Memory
Authors: Bashkansky Mark , Black Adam T. , Kwolek Jonathan M. , Kuzmich Alex
Published: June 2021

Quantum Memory (QM) commonly refers to a system that reversibly transfers quantum states between a material storage system and a propagating electromagnetic field. It represents a key component in quantum information science and technology.

Over the past 25 years, a wide range of theoretical protocols and experimental approaches to QM has been studied. These include optical delays, mechanical resonators, topological approaches, solid state spins, trapped single atoms and ions, and atomic ensembles.

New applications of QM are being investigated and discovered all the time, including quantum computation, long‐distance entanglement distribution, quantum teleportation, and long‐distance quantum key distribution.

Challenges to the implementation of QM include inefficiencies in storing and recovering the quantum state, and decoherence, which usually manifests by environment‐induced dephasing.

In this monograph we describe, in general terms, methods and protocols that are used in many forms of QM. We also discuss the various experimental systems in which QM has been demonstrated or proposed. Additionally, we discuss the applications of QM that have been identified and progress made in implementing those applications.
Biological Function of Solanaceous Withanolides and Their Effects on Herbivorous Insects
Authors: Sell Marie Pauline , Amezian Dries , Heckel David G. , Pauchet Yannick
Published: June 2021

Naturally occurring withanolides are secondary metabolites with interesting biological activities in vivo and in vitro. The role of withanolide production in plants is still conjectural though numerous studies strongly indicate a potent feeding deterrent effect against insects and other herbivores. In contrast to the potential medical applications of withanolides, the ecological effects on herbivores have not been studied intensively. In this article, we collect and summarise present studies on herbivore–plant interactions in the light of potential insecticidal functions of withanolides. Moreover, taking the case of the specialist noctuid moth
Chloridea
(
Heliothis
)
subflexa
, we not only illustrate the known negative effects of these compounds seem to have on herbivorous insect species but also discuss how
C. subflexa
larvae might benefit from adaptation to their host plants in the genus
Physalis
. Further, we describe potential activation and detoxification mechanisms based on the current state of knowledge.
Correlating Nanocrystalline Structure with Electronic Properties in 2D Platinum Diselenide
Authors: Lukas Sebastian , Hartwig Oliver , Prechtl Maximilian , Capraro Giovanna , Bolten Jens , Meledin Alexander , Mayer Joachim , Neumaier Daniel , Kataria Satender , Duesberg Georg S. , Lemme Max C.
Published: June 2021

Platinum diselenide (PtSe2) is a 2D material with outstanding electronic and piezoresistive properties. The material can be grown at low temperatures in a scalable manner, which makes it extremely appealing for many potential electronics, photonics, and sensing applications. Here, the nanocrystalline structure of different PtSe2 thin films grown by thermally assisted conversion (TAC) is investigated and is correlated with their electronic and piezoresistive properties. Scanning transmission electron microscopy for structural analysis, X‐ray photoelectron spectroscopy (XPS) for chemical analysis, and Raman spectroscopy for phase identification are used. Electronic devices are fabricated using transferred PtSe2 films for electrical characterization and piezoresistive gauge factor measurements. The variations of crystallite size and their orientations are found to have a strong correlation with the electronic and piezoresistive properties of the films, especially the sheet resistivity and the effective charge carrier mobility. The findings may pave the way for tuning and optimizing the properties of TAC‐grown PtSe2 toward numerous applications.
Sphere‐on‐Tube Biomimetic Hierarchical Nanostructures Coupled with Engineered Surfaces for Enhanced Photoelectrochemical Biosensing of Cancer Cells Expressing Folate Receptors
Authors: Gao Ning , Wang Xueying , Feng Jinhui , Li Xiaojian , Wang Huan , Fan Dawei , Zhang Yong , Ma Hongmin , Wei Qin , Ju Huangxian
Published: June 2021

The quantitative detection of cancer cells and the evaluation of folate receptor (FR) expression on cell membranes are of great significance for tumor‐related research. In this work, a photoelectrochemical (PEC) biosensing interface is proposed for detection of cancer cells based on the construction of nanostructured platforms coupled with surface engineering. A “sphere‐on‐tube” hierarchical nanostructure is fabricated by depositing biomimetic polydopamine nanospheres on TiO2 nanotube arrays. Enhanced PEC responses are achieved with the formation of polyethylene glycol antifouling layers and the immobilization of folic acid as a recognition ligand. Based on the ligand–receptor interaction, the antifouling PEC biosensor exhibits a wide linear range for the detection of the breast cancer cell line MDA‐MB‐231 from 20 to 2.0 × 106 cells mL−1 with a low detection limit of 15 cells mL−1 (S/N = 3). The expressing differentiation of FR on several cancer cells is well discriminated. The proposed PEC cytosensing method shows great potential in detection of cancer cells expressing folate receptors.
Engineering Gene Therapy: Advances and Barriers
Authors: Shahryari Alireza , Burtscher Ingo , Nazari Zahra , Lickert Heiko
Published: June 2021

Currently, 33 gene‐therapy drugs/products have been approved in the clinic. Over 3000 completed and ongoing clinical gene therapy trials have been reported worldwide. The development/maturation of tools for gene manipulation and gene delivery, as well as molecular advances in the diagnosis of genetic diseases, have played a central role in gene therapy, which have greatly revolutionized the field. Versatile and diverse genetic tools for gene manipulations and deliveries, with the possibility of short and long‐term effects, are vital advantages of gene therapy tools, paving the road for the development of new therapies. However, efficacy and safety concerns, immune system responses, laborious approaches for developing and manufacturing, unknown gene‐therapy drug interactions with the host and the high cost of drugs/products, are significant barriers in gene therapy. Here, the authors review the attempts for engineering of the gene manipulations that have been undertaken in the last three decades and used in clinical trials focusing on 1) gene‐editing platforms, 2) viral gene delivery systems, and 3) nonviral gene tools. In this comprehensive review, the principles of these gene manipulation tools as well as advances and barriers for their application in modern therapies are discussed. Furthermore, trends and future directions in gene therapy are discussed.
Engineering the Immune Adaptor Protein STING as a Functional Carrier
Authors: Sun Xin , Ni Yun , He Yanpu , Yang Mengdi , Tani Tetsuo , Kitajima Shunsuke , Barbie David A. , Li Jiahe
Published: June 2021

Activation of the stimulator of interferon genes (STING) pathway through cyclic dinucleotides (CDNs) is being explored as potent vaccine adjuvants against infectious diseases and to increase tumor immunogenicity toward cancer immunotherapy. To date, a myriad of synthetic vehicles, including liposomes, polymers, and other nanoparticle platforms, have been developed to improve the bioavailability and therapeutic efficacy of STING agonists in preclinical mouse models. Compared to synthetic materials, protein‐based carriers represent an attractive delivery platform owing to their biocompatibility, amenability to genetic engineering, and intrinsic capacity to form well‐defined structures. Here, the immune adaptor STING is engineered as aprotein‐based delivery system for efficient encapsulation and intracellular delivery of CDNs. Through genetic fusion with a protein transduction domain, the recombinant STING can spontaneously penetrate cells to markedly enhance the delivery of CDNs in a mouse vaccination model and a syngeneic melanoma model. As certain tumor cells can evade immune surveillance via loss of STING expression, authors further unveiled that the STING platform can serve as a functional vehicle to restore the STING signaling in cell lines with impaired STING expression. Altogether, their delivery platform may offer a unique direction toward targeting STING‐silenced tumors and augmenting the efficacy of STING‐based vaccine adjuvants.
Association of mitochondrial variants and haplogroups identified by whole exome sequencing with Alzheimer's disease
Authors: Zhang Xiaoling , Farrell John J. , Tong Tong , Hu Junming , Zhu Congcong ,   Alzheimer's Disease Sequencing Project, Wang Li‐San , Mayeux Richard , Haines Jonathan L. , Pericak‐Vance Margaret A. , Schellenberg Gerard D. , Lunetta Kathryn L. , Farrer Lindsay A.
Published: June 2021

Introduction

Findings regarding the association between mitochondrial DNA (mtDNA) variants and Alzheimer's disease (AD) are inconsistent.

Methods

We developed a pipeline for accurate assembly and variant calling in mitochondrial genomes embedded within whole exome sequences (WES) from 10,831 participants from the Alzheimer's Disease Sequencing Project (ADSP). Association of AD risk was evaluated with each mtDNA variant and variants located in 1158 nuclear genes related to mitochondrial function using the SCORE test. Gene‐based tests were performed using SKAT‐O.

Results

Analysis of 4220 mtDNA variants revealed study‐wide significant association of AD with a rare MT‐ND4L variant (rs28709356 C>T; minor allele frequency = 0.002; P = 7.3 × 10−5) as well as with MT‐ND4L in a gene‐based test (P = 6.71 × 10−5). Significant association was also observed with a MT‐related nuclear gene, TAMM41, in a gene‐based test (P = 2.7 × 10−5). The expression of TAMM41 was lower in AD cases than controls (P = .00046) or mild cognitive impairment cases (P = .03).

Discussion

Significant findings in MT‐ND4L and TAMM41 provide evidence for a role of mitochondria in AD.
Fluoreszenz‐detektierte Pump‐Probe‐Spektroskopie
Authors: Malý Pavel , Brixner Tobias
Published: June 2021

Fluoreszenzdetektierte Pump‐Probe‐(F‐PP‐)Spektroskopie überwindet einige Einschränkungen der traditionellen PP‐Spektroskopie. F‐PP unterdrückt die Absorption angeregter Zustände, bietet eine untergrundfreie Detektion, entfernt Artefakte, die aus der Anregepuls‐Streuung, aus nicht‐resonanter Lösungsmittelantwort oder aus kohärenter Pulsüberlappung resultieren, und erlaubt eine Extrahierung der Dynamik angeregter Zustände unter bestimmten Bedingungen. Trotz inkohärenter Detektion ist die zeitliche Auflösung von F‐PP durch die Dauer der Laserpulse gegeben und unabhängig von der Fluoreszenzlebensdauer. Wir beschreiben das Funktionsprinzip von F‐PP und liefern eine theoretische Beschreibung. Zudem veranschaulichen wir spezifische Eigenschaften von F‐PP im direkten Vergleich mit PP. Zu diesem Zweck untersuchen wir mittels beider Techniken ein molekulares Squarain‐Heterodimer, Kern‐Schale‐CdSe/ZnS‐Quantenpunkte sowie das fluoreszierende Protein mCherry. F‐PP ist umfassend anwendbar auf chemische Systeme in verschiedensten Umgebungen und in unterschiedlichen Spektralbereichen.
Synergetic Metal Defect and Surface Chemical Reconstruction into NiCo2S4/ZnS Heterojunction to Achieve Outstanding Oxygen Evolution Performance
Authors: Sun Jing , Xue Hui , Guo Niankun , Song Tianshan , Hao Yi‐ru , Sun Jiawen , Zhang Jiangwei , Wang Qin
Published: June 2021

Defect and interface engineering are recognized as effective strategies to regulate electronic structure and improve activity of metal sulfide. However, the practical application of sulfide is restricted by their low conductivity and rapid decline in activity derived from large volume fluctuation during electrocatalysis process. More importantly, the determination of exact active site of sulfide is complicated due to the inevitable electrochemical reconstruction. Herein, ZnS nanoparticles with Zn defect are anchored onto the surface of NiCo2S4 nanosheet to construct NiCo2S4/ZnS hybrids, which exhibit outstanding oxygen evolution performance with an ultralow overpotential of 140 mV. The anchoring of defective ZnS nanoparticles inhibit the volume expansion of NiCo2S4 nanosheet during the cycling process. Density‐functional theory reveals that the build‐in interfacial potential and Zn defect can facilitate the thermodynamic formation of *O to *OOH, thus improve their intrinsic activity.
Preparation, characterization and antioxidant activity of acetylated garlic polysaccharide, and garlic polysaccharide‐Zn (II) complex
Authors: Chen Xin , Huang Gangliang
Published: June 2021

Garlic polysaccharide (PS) was extracted from garlic by hot‐water extraction. Acetylated garlic polysaccharide (AcPS) and garlic polysaccharide‐zinc complex (ZnPS) were synthesized. The results of Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy analysis showed that the modifications were successful. The antioxidant activities of PS, AcPS, and ZnPS were further investigated in vitro, including scavenging superoxide anion and hydroxyl radicals, antilipid peroxidation capacity, and reducing power. The results showed that the scavenging abilities of AcPS and ZnPS on hydroxyl radical (The IC50 of PS, AcPS, and ZnPS were 2.86, 1.62 and, 1.49 mg/ml, respectively,) and superoxide anion radical (The scavenging rate of PS, AcPS, and ZnPS were 1.5% and 1.8%, and 2.3%, respectively, when concentration was at 1.0 mg/ml.) were stronger than that of PS, and the inhibitory effect of AcPS on lipid peroxidation was significantly stronger than that of PS (The IC50 of PS and AcPS were 1.05 and 0.53 mg/ml, respectively.). It indicated that the acetylation was a favorable way to enhance the antioxidant activity of garlic PS; ZnPS complex could be applied as potential candidate for antioxidant and Zn supplement.
Screening and clinical significance of lymph node metastasis‐related genes within esophagogastric junction adenocarcinoma
Authors: Han Rui , Chen Gang , Li Meng , Peng Zhong‐Min , Xu Lin
Published: June 2021

Background

Despite recent improvements in treatment technologies, such as surgical resection and chemoradiotherapy, the prognosis of patients with esophagogastric junction adenocarcinoma (EJA) remains poor due to early lymph node metastasis. Since few studies have investigated genes associated with lymph node metastasis in EJA, we aimed to screen lymph node metastasis‐associated genes and clarify their expression status and prognostic significance in EJA.

Methods

The differential frequency of mutations between carcinoma and para‐carcinoma tissues from 199 cases with EJA was detected using targeted next‐generation sequencing (tNGS). Following a stratified analysis to determine that gender has no effect on the frequency of gene mutations, lymph node metastasis‐related genes, including CDK6, MET, NOTCH1, and LRP1B, were screened, and CDK6 and LRP1B were selected for further study as they displayed significant differences in mutation rates. Differences in their expression status were verified using immunohistochemical (IHC) staining in 18 CDK6‐ and 17 LRP1B‐mutated samples and a randomly matched control group.

Results

tNGS revealed that CDK6 and LRP1B mutation frequencies were significantly different between EJA cases with (N ≥ 1) or without (N = 0) lymph node metastasis. In particular, CDK6 mutation frequency was expected less, whereas that of LRP1B was remarkably higher in cases with stage N0 than in those with stage N ≥ 1. IHC staining confirmed significant differences in CDK6 and LRP1B expression status between the study and control cohorts. Chi‐square tests revealed that a high CDK6 expression status correlated significantly with smoking history (p = 0.044), T stage (p = 0.035), N stage (p = 0.000), and advanced TNM stage (p = 0.001) in EJA, whereas a high LRP1B expression status only correlated with BMI (p = 0.013) and N stage (p = 0.000). Furthermore, as confirmed by survival status investigation, a high LRP1B expression status predicted good prognosis, and a high CDK6 expression status was an independent predictor of poor prognosis in patients with EJA.

Conclusions

Taken together, the findings of this study demonstrate that a high CDK6 and LRP1B expression status promotes and inhibits lymph node metastasis in patients with EJA, respectively, suggesting that both CDK6 and LRP1B are significantly potential predictors of lymph node metastasis and prognosis in EJA.
Redevelopment of the Predict: Breast Cancer website and recommendations for developing interfaces to support decision‐making
Authors: Farmer George D. , Pearson Mike , Skylark William J. , Freeman Alexandra L. J. , Spiegelhalter David J.
Published: June 2021

Objectives

To develop a new interface for the widely used prognostic breast cancer tool: Predict: Breast Cancer. To facilitate decision‐making around post‐surgery breast cancer treatments. To derive recommendations for communicating the outputs of prognostic models to patients and their clinicians.

Method

We employed a user‐centred design process comprised of background research and iterative testing of prototypes with clinicians and patients. Methods included surveys, focus groups and usability testing.

Results

The updated interface now caters to the needs of a wider audience through the addition of new visualisations, instantaneous updating of results, enhanced explanatory information and the addition of new predictors and outputs. A programme of future research was identified and is now underway, including the provision of quantitative data on the adverse effects of adjuvant breast cancer treatments.

Based on our user‐centred design process, we identify six recommendations for communicating the outputs of prognostic models including the need to contextualise statistics, identify and address gaps in knowledge, and the critical importance of engaging with prospective users when designing communications.

Conclusions

For prognostic algorithms to fulfil their potential to assist with decision‐making they need carefully designed interfaces. User‐centred design puts patients and clinicians needs at the forefront, allowing them to derive the maximum benefit from prognostic models.
Clinical and cost outcomes following genomics‐informed treatment for advanced cancers
Authors: Weymann Deirdre , Pollard Samantha , Chan Brandon , Titmuss Emma , Bohm Alexandra , Laskin Janessa , Jones Steven J. M. , Pleasance Erin , Nelson Jessica , Fok Alexandra , Lim Howard , Karsan Aly , Renouf Daniel J. , Schrader Kasmintan A. , Sun Sophie , Yip Stephen , Schaeffer David F. , Marra Marco A. , Regier Dean A.
Published: June 2021

Background

Single‐arm trials are common in precision oncology. Owing to the lack of randomized counterfactual, resultant data are not amenable to comparative outcomes analyses. Difference‐in‐difference (DID) methods present an opportunity to generate causal estimates of time‐varying treatment outcomes. Using DID, our study estimates within‐cohort effects of genomics‐informed treatment versus standard care on clinical and cost outcomes.

Methods

We focus on adults with advanced cancers enrolled in the single‐arm BC Cancer Personalized OncoGenomics program between 2012 and 2017. All individuals had a minimum of 1‐year follow up. Logistic regression explored baseline differences across patients who received a genomics‐informed treatment versus a standard care treatment after genomic sequencing. DID estimated the incremental effects of genomics‐informed treatment on time to treatment discontinuation (TTD), time to next treatment (TTNT), and costs. TTD and TTNT correlate with improved response and survival.

Results

Our study cohort included 346 patients, of whom 140 (40%) received genomics‐informed treatment after sequencing and 206 (60%) received standard care treatment. No significant differences in baseline characteristics were detected across treatment groups. DID estimated that the incremental effect of genomics‐informed versus standard care treatment was 102 days (95% CI: 35, 167) on TTD, 91 days (95% CI: −9, 175) on TTNT, and CAD$91,098 (95% CI: $46,848, $176,598) on costs. Effects were most pronounced in gastrointestinal cancer patients.

Conclusions

Genomics‐informed treatment had a statistically significant effect on TTD compared to standard care treatment, but at increased treatment costs. Within‐cohort evidence generated through this single‐arm study informs the early‐stage comparative effectiveness of precision oncology.
Synthesis and Surface Behaviour of NDI Chromophores Mounted on a Tripodal Scaffold: Towards Self‐Decoupled Chromophores for Single‐Molecule Electroluminescence
Authors: Balzer Nico , Lukášek Jan , Valášek Michal , Rai Vibhuti , Sun Qing , Gerhard Lukas , Wulfhekel Wulf , Mayor Marcel
Published: June 2021

This paper reports the efficient synthesis, absorption and emission spectra, and the electrochemical properties of a series of 2,6‐disubstituted naphthalene‐1,4,5,8‐tetracarboxdiimide (NDI) tripodal molecules with thioacetate anchors for their surface investigations. Our studies showed that, in particular, the pyrrolidinyl group with its strong electron‐donating properties enhanced the fluorescence of such core‐substituted NDI chromophores and caused a significant bathochromic shift in the absorption spectrum with a correspondingly narrowed bandgap of 1.94 eV. Cyclic voltammetry showed the redox properties of NDIs to be influenced by core substituents. The strong electron‐donating character of pyrrolidine substituents results in rather high HOMO and LUMO levels of ‐5.31 and ‐3.37 eV when compared with the parental unsubstituted NDI. UHV‐STM measurements of a sub‐monolayer of the rigid tripodal NDI chromophores spray deposited on Au(111) show that these molecules mainly tend to adsorb flat in a pairwise fashion on the surface and form unordered films. However, the STML experiments also revealed a few molecular clusters, which might consist of upright oriented molecules protruding from the molecular island and show electroluminescence photon spectra with high electroluminescence yields of up to 6×10−3. These results demonstrate the promising potential of the NDI tripodal chromophores for the fabrication of molecular devices profiting from optical features of the molecular layer.
The Binding Pocket at the Interface of Multimeric Telomere G‐quadruplexes: Myth or Reality?
Authors: Manoli Francesco , Doria Filippo , Colombo Giorgio , Zambelli Barbara , Freccero Mauro , Manet Ilse
Published: June 2021

Human telomeric DNA with hundreds of repeats of the 5’‐TTAGGG‐3’ motif plays a crucial role in several biological processes. It folds into G‐quadruplex (G4) structures and features a pocket at the interface of two contiguous G4 blocks. Up to now no structural NMR and crystallographic data are available for ligands interacting with contiguous G4s. Naphthalene diimide monomers and dyads were investigated as ligands of a dimeric G4 of human telomeric DNA comparing the results with those of the model monomeric G4. Time‐resolved fluorescence, circular dichroism, isothermal titration calorimetry and molecular modeling were used to elucidate binding features. Ligand fluorescence lifetime and induced circular dichroism unveiled occupancy of the binding site at the interface. Thermodynamic parameters confirmed the hypothesis as they remarkably change for the dyad complexes of the monomeric and dimeric telomeric G4. The bi‐functional ligand structure of the dyads is a fundamental requisite for binding at the G4 interface as only the dyads engage in complexes with 1 : 1 stoichiometry, lodging in the pocket at the interface and establishing multiple interactions with the DNA skeleton. In the absence of NMR and crystallographic data, our study affords important proofs of binding at the interface pocket and clues on the role played by the ligand structure.