bluuebunny/crossref_metadata_2025 huggingface dataset:
Stone Money of Yap as an Early form of Money in the Economic Sense
Authors: Gentle Paul F.
Published: July 2021

This article examines the special case of stone money, in Yap as a store of value, medium of exchange and unit of account, which are the three traits required for something to be considered money, in the economic sense. When confidence in a system of currency with coins is present, this more conventional form of money takes precedence. A respected economic form of currency with coins has all three elements of money: medium of exchange, store of value and unit of account. Though clearly, in a certain time period, stone money was the principle type of money. To a lesser extent, beads and shell were used as money. So, for a period of time, stone money, along with some use of beads and shells, constituted the medium of exchange. The focus of this article is on the stone money of Yap. Stone was obtained by quarrying on the island of Palau, some 500 to 600 years ago. A very interesting type of money in the past, was the stone money of Yap, more formally known as Rai, or Fei. These were doughnut-shaped, carved disks of normally calcite and, up to 4 meters (12 feet) in diameter. However, there are more smaller ones, with the smallest being as little as 3.5 centimeters (1.4 inches) in diameter. The people of Yap attributed value to the Rai. After the use of Rai faded away, German Marks and then later Japanese Yen and finally the U.S. Dollar, were the monetary standard. The prior use of Rai is the main interest of this article. Today Yap is an independent country, in a “free association” with the United States. A curriculum that somewhat resembles an American one is taught in schools on Yap. Tourism to Yap is an important activity. Currently, the U.S. dollar serves as the basis for money in the nation of Yap. It has been found that this stone money met the three criteria necessary for them to be an early type of money.
Post-pandemic Scenario for University Startup Accelerators
Authors: Moskovicz Dr Abraham (Abi)
Published: July 2021

This essay focuses on the post-Covid19 environment of entrepreneurial ideas that have potentials of success and growth in the coming years, providing an insight into the prolific funding being made available for University startups, especially in their early stages of development. To achieve this objective, it seems crucial to define firstly many terms frequently used and to determinate the involved variables. Whoever is able to predict this new post-Covid reality and glimpse the later scenario, will be better prepared for the new times, which will be as changing and indefinite as in the past. It seems the right time to transform ideas into realities. Whether it is a student presenting his thesis or an entrepreneur landing his postponed projects, this new scenario more than tempting forces to undertake. Through an University startup accelerator, it is possible to anticipate your competitors, learning about new proposals, counting on the advice and mentoring of independent professional experts. Universities with a sufficiently strong entrepreneurial ecosystem can serve as an ideal launch pad for startups founded by its own students and researchers.
Characterization of Morphological and Fruit Quality Traits of Coconut (Cocos nucifera L.) Germplasm
Authors: Zhang Ruining , Cao Hongxing , Sun Chengxu , Martin Jerome Jeyakumar John
Published: July 2021

The evaluation and identification of germplasm resources is an indispensable step in the breeding processes and have important roles in the selection and improvement of new varieties. This research intended to characterize coconut germplasm to determine the quantitative, qualitative, and morphological traits of the stem, leaf, and inflorescence and the fruit characteristics. Sixteen morphological and qualitative traits of 17 coconut (Cocos nucifera L.) germplasm resources from Hainan, China, were investigated to determine the characteristics and advantages of multiple germplasm lines to create the foundation for the cultivation and breeding of coconuts. The results of the correlation analysis, principal component analysis (PCA), and cluster analysis indicate a correlation between coconut germplasm factors and their contribution to coconut traits. The results revealed that stem girth at 0.2 m was the most obvious trait, along with the fruit flavor, edible rate, fat content, hole spacing, single fruit weight, and number of female flowers, which reflect most of the information regarding coconut traits and contribute to its value. The PCA and cluster analysis indicated that two high-yield and superior-quality sweet water dwarf coconut germplasms, named ‘15-19’ and ‘15-17’, were suitable for cultivation and production in Hainan, China. The results of this study act a far-reaching influence on the collection and utilization of coconut resources and have an impact on the development and progress of the coconut industry in China.
Hydrothermal monazite trumps rutile: Applying U-Pb geochronology to evaluate complex mineralization ages of the Katbasu Au-Cu deposit, Western Tianshan, Northwest China
Authors: Zheng Jiahao , Shen Ping , Feng Wanyi
Published: July 2021

The Tianshan orogenic belt hosts several world-class gold deposits and is one of the largest gold provinces on Earth. The Katbasu Au-Cu deposit in the Chinese Western Tianshan is hosted in a granite intrusion. Previous researchers have shown that the main gold ores formed much later than the ore-hosting granite. However, the formation age of Cu mineralization and its possible link to Au mineralization remain poorly understood. This paper reports detailed mineralogical studies, combined with zircon U-Pb, in situ hydrothermal monazite as well as rutile U-Pb ages to constrain the timing of Cu mineralization and its possible link to Au mineralization. The two main ore types in the Katbasu deposit include Cu-Au ores with pyrite-chalcopyrite veins that crosscut the granite and Au ores with massive pyrite and quartz as the main minerals. The Cu-Au ores are spatially associated with diorite that intruded the granite, and they are overprinted by massive gold ores. Detailed mineralogical studies show that chalcopyrite is the main Cu-bearing mineral in the Cu-Au ores, and it is closely associated with some native gold, monazite, and rutile.

Secondary ion mass spectrometer (SIMS) U-Pb dating of zircon grains from the ore-hosting granite and mafic enclave yielded concordant ages of 354.1 ± 1.6 and 355.8 ± 1.7 Ma, respectively. The diorite that intruded the granite has a zircon U-Pb age of 352.0 ± 3.2 Ma. The trace element compositions of the monazite suggest they were formed by hydrothermal fluids rather than inherited from the ore-hosting granite. Hydrothermal monazite coexisting with chalcopyrite and native gold yielded a concordant age of 348.7 ± 2.3 Ma, and the W-rich hydrothermal rutile grains associated with the chalcopyrite yielded a U-Pb age of 345 ± 27 Ma, indicating an early Cu-Au mineralization event prior to the major Au mineralization (ca. 323–311 Ma). The formation time of early Cu-Au mineralization is consistent with the emplacement age of the diorite and may be of magmatic-hydrothermal origin, whereas the main Au has no genetic associations with magmatic rocks in the ore district and may belong to the orogenic type. Monazite geochronology provided a more reliable age constraint than rutile in the Katbasu Au-Cu deposit, and we suggest hydrothermal monazite has advantages over rutile in dating the complex mineralization ages of gold deposits.
PENGARUH SOSIALISASI PERPAJAKAN DAN SANKSI PERPAJAKAN TERHADAP KEPATUHAN WAJIB PAJAK UMKM E-COMMERCE
Authors: Maxuel Afeni , Primastiwi Anita
Published: July 2021

ABSTRAK Penelitian ini bertujuan untuk menguji apakah sosialisasi perpajakan, kesadaran wajib pajak dan sanksi perpajakan berpengaruh terhadap kepatuhan wajib pajak UMKM e-commerce. Metode penelitian ini menggunakan metode deskriptif kuantitatif dan data primer dengan menggunakan kuesioner. Penelitian mengambil sampel pengusaha e-commerce yang ada di Indonesia. Teknik pengambilan sampel menggunakan purposive sampling. Pengumpulan data dilakukan dengan cara mengirimkan kuesioner melalui chat personal atau melalui e-mail dalam bentuk google form kepada pengusaha e-commerce. Jumlah kuesioner yang diolah adalah 100 kuesioner. Data dianalisis menggunakan analisis regresi linear berganda. Hasil penelitian ini menunjukkan bahwa sosialisasi perpajakan berpengaruh positif terhadap kepatuhan wajib pajak UMKM e-commerce sedangkan kesadaran wajib pajak dan sanksi perpajakan tidak berpengaruh signifikan terhadap kepatuhan wajib pajak UMKM e-commerce.Kata kunci: sosialisasi perpajakan, kesadaran wajib pajak, sanksi perpajakan, kepatuhan wajib pajak, umkm e-commerce. ABSTRACT This study aims to examine whether taxation socialization, awareness of taxpayers and tax sanctions affect the tax compliance of MSME e-commerce taxpayers. This research method uses quantitative descriptive methods and primary data using a questionnaire. The study took a sample of e-commerce entrepreneurs in Indonesia. The sampling technique uses purposive sampling. Data collection is done by sending questionnaires via personal chat or via e-mail in the form of Google forms to e-commerce entrepreneurs. The number of questionnaires processed was 100 questionnaires. Data were analyzed using multiple linear regression analysis. The results of this study indicate that taxation socialization has a positive effect on tax compliance of MSME e-commerce taxpayers while awareness of taxpayers and tax sanctions does not have a significant effect on tax compliance of MSME e-commerce taxpayersKeywords: taxation socialization, taxpayer awareness, tax sanction, taxpayer compliance, e-commerce SME
Entanglement, non-hermiticity, and duality
Authors: Chen Li-Mei , Chen Shuai A. , Ye Peng
Published: July 2021

Usually duality process keeps energy spectrum invariant. In this
paper, we provide a duality, which keeps entanglement spectrum
invariant, in order to diagnose quantum entanglement of non-Hermitian
non-interacting fermionic systems. We limit our attention to
non-Hermitian systems with a complete set of biorthonormal eigenvectors
and an entirely real energy spectrum. The original system has a reduced
density matrix \rho_\mathrm{o}ρo
and the real space is partitioned via a projecting operator
\mathcal{R}_{\mathrm o}ℛo.
After dualization, we obtain a new reduced density matrix
\rho_{\mathrm{d}}ρd
and a new real space projector \mathcal{R}_{\mathrm d}ℛd.
Remarkably, entanglement spectrum and entanglement entropy keep
invariant. Inspired by the duality, we defined two types of
non-Hermitian models, upon \mathcal R_{\mathrm{o}}ℛo
is given. In type-I exemplified by the "non-reciprocal model'', there exists at least one duality such that
\rho_{\mathrm{d}}ρd
is Hermitian. In other words, entanglement information of type-I
non-Hermitian models with a given \mathcal{R}_{\mathrm{o}}ℛo
is entirely controlled by Hermitian models with
\mathcal{R}_{\mathrm{d}}ℛd. As a result, we are allowed to apply known results of Hermitian systems to efficiently obtain entanglement properties of type-I models. On the other hand, the duals of type-II models, exemplified by "non-Hermitian
Su-Schrieffer-Heeger model’’, are always non-Hermitian. For the
practical purpose, the duality provides a potentially computation route
to entanglement of non-Hermitian systems. Via connecting different
models, the duality also sheds lights on either trivial or nontrivial
role of non-Hermiticity played in quantum entanglement, paving the way
to potentially systematic classification and characterization of
non-Hermitian systems from the entanglement perspective.
EFT and the SUSY index on the 2nd sheet
Authors: Cassani Davide , Komargodski Zohar
Published: July 2021

The counting of BPS states in four-dimensional
\mathcal{N}=1𝒩=1
theories has attracted a lot of attention in recent years. For
superconformal theories, these states are in one-to-one correspondence
with local operators in various short representations. The generating
function for this counting problem has branch cuts and hence several
Cardy-like limits, which are analogous to high-temperature limits.
Particularly interesting is the second sheet, which has been shown to
capture the microstates and phases of supersymmetric black holes in
AdS_55.
Here we present a 3d Effective Field Theory (EFT) approach to the
high-temperature limit on the second sheet. We use the EFT to derive the
behavior of the index at orders \beta^{-2},\beta^{-1},\beta^0β−2,β−1,β0.
We also make a conjecture for O(\beta)O(β),
where we argue that the expansion truncates up to exponentially small
corrections. An important point is the existence of vector multiplet
zero modes, unaccompanied by massless matter fields. The runaway of
Affleck-Harvey-Witten is however avoided by a non-perturbative
confinement mechanism. This confinement mechanism guarantees that our
results are robust.
Perbandingan Aktivitas Reaksi Fotodegradasi Remazol Red dengan TiO2 Anatas 50%-Rutil 50% dan TiO2 Anatas Tersupport AgI
Authors: Astuti Sri Rejeki Dwi , Sari Anggi Ristiyana Puspita , Karlinda Karlinda
Published: July 2021

Kandungan ikatan azo dalam zat pewarna tekstil remazol red mengakibatkan zat warna lebih mudah larut dalam air dan memiliki stabilitas yang tinggi. Hal ini menyebabkan limbah tekstil memerlukan penanganan khusus agar aman dan tidak memberikan dampak negatif ketika dilepas ke perairan. Salah satu cara alternatif untuk menangani limbah non-degradable adalah dengan menggunakan metode fotodegradasi dengan bantuan fotokatalis. Penelitian ini bertujuan untuk membandingkan aktivitas reaksi fotodegradasi remazol red dengan fotokatalis TiO2 anatas 50%-rutil 50% dan TiO2 anatas tersupport AgI. Proses fotodegradasi Remazol red dilakukan dengan memvariasi fotokatalis yang digunakan yaitu fotokatalisis TiO2 anatas 50%-rutil 50% dan TiO2 anatas tersupport AgI dan lama waktu penyinaran yaitu 15 menit, 30 menit, 45 menit, 60 menit, 75 menit, dan 90 menit. Untuk mengetahui pengaruh lama penyinaran terhadap fotodegradasi Remazol red, maka dilakukan pengukuran absorbansi larutan menggunakan spectronic 200 pada panjang gelombang 558nm setiap selang waktu 15 menit. Hasil aktivitas fotokatalitis menunjukkan persentase degradasi remazol red pada sistem TiO2 anatas tersupport AgI, TiO2 anatas 50%-rutil 50% dan tanpa katalis berturut-turut sebesar 32%, 16%, dan 7%. Oleh karena itu fotokatalis TiO2 anatas tersupport AgI memiliki aktivitas fotokatalisis yang lebih baik daripada fotokatalis TiO2 anatas 50% - rutil 50%
Produksi Biofuel Berbantuan Ultrasonik dari Minyak Kelapa Terkatalisis Ca/gamma-Al2O3 dan K/gamma-Al2O3: Suatu Studi Perbandingan
Authors: Supriadi Eko , Basuki Rahmat , Prajitno Danawati Hadi , Mahfud Mahfud
Published: July 2021

Penelitian ini bertujuan untuk membandingkan doping Kalium (K) dan Kalsium (Ca) pada support γ-Al2O3 dalam produksi biofuel yang berbentuk fatty acid methyl ester (FAME) melalui reaksi transesterifikasi minyak kelapa berbantuan ultrasonik. Reaksi dilakukan dalam tipe reaktor batch dengan perbandingan mol minyak kelapa:etanol = 1:9, dan variasi konsentrasi berat katalis untuk masing-masing katalis K/γ-Al2O­3 dan Ca/γ-Al2O3 terhadap minyak kelapa (0,5%; 1,0%; 1,5%; 2% dan 2,5%), waktu reaksi (30, 60, 90, 120 dan 150 detik), dan frekuensi ultrasonik (20 dan 40 KHz). Keberhasilan doping ditunjukkan pada hasil karakterisasi K/g-Al2O3 ­dan Ca/g-Al2O3 menggunakan X-Ray Diffraction (XRD) yang menghasilkan puncak 2θ karakteristik K (29,70° dan 32,65°) dan Ca (25,35°, 26,77°, dan 27,17°) pada support g-Al2O3 (37,66°, 45,82° dan 67,22°). Karakterisasi menggunakan Surface Area Analyzer (SAA) menunjukkan bahwa katalis K/g-Al2O3 memiliki luas permukaan yang lebih kecil (34,03 m2/g) dibanding Ca/g-Al2O3 (83,77 m2/g), namun diameter pori yang lebih besar (66,12 Å) dibanding Ca/g-Al2O3 (35,22 Å). Katalis K/g-Al2O3 menghasilkan yield FAME yang lebih besar (93,19%) dibanding Ca/γ-Al2O3 (29,76%) pada konsentrasi katalis 2,5%, waktu reaksi 150 detik dan frekuensi ultrasonik 40 kHz. Kualitas FAME terkatalisis K/g-Al2O3 yang dihasilkan memenuhi empat parameter uji: densitas, viskositas kinematic, titik nyala, dan titik tuang sesuai dengan standar SNI 04-7182-2006.
Ultrasonido y accesos venosos periféricos difíciles: de las barreras al éxito, un reporte de casos
Authors: Garcia Uribe John Camilo
Published: July 2021

Este es un reporte de serie de casos sobre accesos venosos difíciles guiados por técnica de ultrasonido, en el servicio de cirugía de la Fundación Clínica Norte en Bello, Colombia. El objetivo principal fue describir la efectivi¬dad, seguridad de la técnica ecográfica y las características clínicas de los pacientes con difícil acceso venoso. El muestreo fue consecutivo. En el muestreo final se incluyeron 14 pacientes para realizar el procedimiento ecoguiado; previamente se excluyeron 8 posibles participantes debido a venas profundas y falta de líneas medias; la principal patología en los pa¬cientes fue la obesidad (50%) y en segundo lugar la diabetes (28%); en los pacientes sanos el principal factor de riesgo fue cirugías de extremidades superiores. Adicionalmente, se revisaron historias clínicas de pacientes multipuncionados, durante el tiempo estudiado (específicamente los días en que se realizaron procedimientos) encontrándose un total de 13 casos, en los cuales, se realizaron dos punciones más para canalizar un acceso venoso y no se recurrió a la valoración ecográfica. La efectividad al primer intento estuvo alrededor del 80% y las principales barreras fueron barre¬ras humanas y técnicas, no se presentaron complicaciones asociadas. En conclusión, la ecografía es una necesidad para la canalización de accesos venosos difíciles y las enfermeras deben estar preparadas para una técnica desafiante que permite brindar atención con calidad y seguridad, conocer la técnica y familiarizarse con ella son los pasos necesarios para que integrar el ultrasonido al cuidado de enfermería.
Micobioma: diversidad fúngica en el cuerpo humano
Authors: Restrepo-Rivera Lina Marcela , Cardona-Castro Nora
Published: July 2021

Introducción: los hongos hacen parte de los microorganismos que se encuentran en el ser humano y que interactúan con bacterias, virus y archaeas. El equilibrio inter e intra-especies es importante para mantener la salud en los seres humanos. La mayoría de los estudios sobre la micobioma se han relacionado con estados de enfermedad causados por hongos, siendo de relevancia la exploración de las comunidades comensales en individuos sanos. Métodos: se realizó una búsqueda bibliográfica en PubMed, ScienceDirect, Scopus y Google Scholar, usando los términos mycobiome, intestinal fungi, skin mycobiome, vaginal mycobiome, fungal microbiome. Se incluyeron artículos desde 1996 hasta 2020, de revisión y de resultados de investigación en todos los idiomas. Resultados y discusión: existe variabilidad en las comunidades fúngicas en los sitios corporales según sus características intrínsecas y la relación con el medio ambiente. El estado de salud en los seres humanos puede estar influenciado por la densidad y diversidad fúngica, a diferencia de los individuos enfermos en quienes se evidencia una disminución en la diversidad y que se asocia con el oportunismo de agentes patógenos.
El reto del diagnóstico en síndrome de embolia grasa
Authors: Sierra Elsy Cristina , Gómez-Rosero Jaime Alberto
Published: July 2021

El síndrome de embolia grasa es una complicación inusual del trauma ortopédico. Las manifestaciones clínicas son inespecíficas y no hay una prueba diagnóstica de oro, por lo que se debe tener un alto índice de sospecha. Se describen cuatro pacientes quienes luego de presentar fractura de huesos largos se complicaron con síndrome de embolia grasa. La manifestación común en todos ellos fue la hipoxemia. Los hallazgos más frecuentes en la tomografía de tórax fueron opacidades en vidrio esmerilado, compromiso del pulmón derecho y de los lóbulos inferiores, y derrame pleural laminar. La evolución clínica fue satisfactoria en tres pacientes; el cuarto presentó extenso compromiso pulmonar, requirió ventilación mecánica invasiva y tuvo una hospitalización prolongada. Ningún paciente falleció ni quedó con secuelas. Esta es la primera serie de casos en Colombia que muestra el comportamiento clínico e imagenológico de pacientes con síndrome de embolia grasa.
Bazo accesorio secundario en púrpura trombocitopénica refractaria – Un reto diagnóstico: Reporte de caso
Authors: Cabrera Rivera Paulo Andrés , Kadamani Abiyomaa Akram , Diagama Restrepo Sebastián , Corso Ramirez Julian Miguel
Published: July 2021

En la trombocitopenia autoinmune primaria hay formación de autoanticuerpos contra las membranas plaquetarias causando destrucción plaquetaria esplénica y compromiso clínico consistente en petequias, hemorragias y trombocitopenia. Cuando falla el manejo médico con corticoides e inmunoglobulinas está indicada la realización de esplenectomía, que funciona para remisión parcial de la enfermedad persistente. Realizar la esplenectomía hace necesario el estudio de un bazo accesorio o material esplénico recurrente, que comúnmente se asocia con la pobre respuesta a tratamiento y recaídas de la enfermedad. Se presenta el caso de una paciente de 27 años y antecedentes de trombocitopenia autoinmune primaria quien requirió esplenectomía, con adecuada evolución postoperatoria y remisión de los síntomas por dos años. Posteriormente, presentó recaída clínica y paraclínica, con plaquetas en 11 000 cel/uL, en contexto de trombocitopenia severa sintomática, presencia de gingivorragia, petequias en los miembros inferiores y el abdomen. Se realizó búsqueda activa de bazo supernumerario por medio de estudios complementarios, los cuales evidenciaron bazo accesorio localizado en el ligamento gastro cólico, que fue resecado por vía laparoscópica, con adecuada respuesta y remisión sintomática de la trombocitopenia autoinmune primaria refractaria. En pacientes esplenectomizados con púrpura trombocitopénica idiopática que tengan recaída de su enfermedad se requiere búsqueda activa de bazos supernumerarios, puesto que es una causa frecuente de su reaparición.
Using a grey multivariate model to predict impacts on the water quality of the Zhanghe River in China
Authors: Fan Feifei , Qiao Zhengran , Wu Lifeng
Published: July 2021

In order to assess the social factors affecting the water quality of the Zhanghe River and predict the potential impact of growth in primary, secondary, tertiary industries and population on water quality of the Zhanghe River in the next few years, a deformation derivative cumulative grey multiple convolution model (DGMC(1,N)) was applied. In order to improve the accuracy of the model, the accumulation of deformation derivatives is introduced, and the particle swarm optimization algorithm is used to solve the optimal order. The DGMC(1,N) model was compared with GM(1,2) and GM(1,1) models. The results show that the DGMC(1,N) model has the highest prediction accuracy. Finally, DGMC(1,N) model is used to predict the potential impact of growth in primary, secondary, tertiary industries and population on water quality in the Zhanghe River (using chemical oxygen demand (COD) as the water quality indicator).
Removal of psychoactive pharmaceuticals from wastewaters using microbial electrolysis cells producing hydrogen
Authors: Akagunduz Dilan , Cebecioglu Rumeysa , Ozdemir Murat , Catal Tunc
Published: July 2021

In this study, hydrogen production was analyzed along with methane and carbon dioxide generation using paroxetine, venlafaxine, and o-desmethylvenlafaxine (ODV) as substrates in single-chamber microbial electrolysis cells (MECs). Combinations of all three drugs were examined at concentrations of 750 ng/mL and 170 ng/mL. At the beginning of MEC operations using a 750 ng/mL mixture of drugs, there was no hydrogen or methane, but carbon dioxide was detected. When the concentration of the drug mixture was reduced to 170 ng/mL, MECs produced hydrogen and methane gas. Removal of the drugs during MEC operations was also analyzed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Paroxetine, venlafaxine and ODV drugs were removed up to 99% by MECs. In conclusion, MECs could offer an alternative treatment method for wastewaters containing psychoactive pharmaceuticals with the added benefit of fuel hydrogen generation.
PCSK 9: A Link Between Inflammation and Atherosclerosis
Authors: Patriki Dimitri , Saravi Seyed Soheil Saeedi , Camici Giovanni G. , Liberale Luca , Beer Jürg H.
Published: July 2021

:

Proprotein convertase subtilisin/Kexin 9 (PCSK 9) is revealed to be a key player in
lipid metabolism and, therefore, in the development and progression of atherosclerosis. PCSK
9 binds to the low-density lipoprotein (LDL) receptor, induces its degradation, and increases
circulating blood LDL. As a result, PCSK 9 inhibitors represent an essential pillar in cardiovascular
risk reduction therapies due to their highly sufficient LDL decreasing properties.
While the influence of PCSK 9 on lipid metabolism has been widely investigated, the full
pathophysiological spectrum of PCSK 9 is yet to be determined. Statins have already been
demonstrated to have beneficial anti-inflammatory effects. In this context, evidence suggests
that PCSK 9 also interferes with inflammatory processes, thereby contributing to the development
of atherosclerosis. As lipid metabolism on its own affects inflammatory processes, it
is difficult to distinguish between lipid-dependent and -independent inflammatory properties
of PCSK 9. A body of evidence has revealed that PCSK9 LDL-independently regulates the
secretion of pro-inflammatory cytokines and inflammation-underlying pathways in vascular
walls, whereas recent observations suggest that PCSK9 also interacts with lectin-like oxidized
LDL receptor-1 (LOX-1) and dampens inflammatory responses through LDL reduction. In
conclusion, this review provides mounting evidence indicating how PCSK9 promotes vascular
inflammation and subsequent atherosclerosis to shed light on the anti-inflammatory effects
of PCSK9 inhibitors in the prevention of atherosclerosis.
Recent Advances in Computer-aided Antiviral Drug Design Targeting HIV-1 Integrase and Reverse Transcriptase Associated Ribonuclease H
Authors: Xue Weiwei , Zhu Feng , Yang Fengyuan , Yang Jingyi , Zhang Zhao , Tu Gao , Yao Xiaojun
Published: July 2021

:

Acquired immunodeficiency syndrome (AIDS) has been a chronic, life-threatening
disease for a long time. Though, a broad range of antiretroviral drug regimens is applicable
for the successful suppression of virus replication in human immunodeficiency virus type 1
(HIV-1) infected people. The mutation-induced drug resistance problems during the treatment
of AIDS forced people to continuously look for new antiviral agents. HIV-1 integrase (IN)
and reverse transcriptase associated ribonuclease (RT-RNase H), two pivotal enzymes in
HIV-1 replication progress, have gained popularity as druggable targets for designing novel
HIV-1 antiviral drugs. During the development of HIV-1 IN and/or RT-RNase H inhibitors,
computer-aided drug design (CADD), including homology modeling, pharmacophore, docking,
molecular dynamics (MD) simulation and binding free energy calculation, represent a
significant tool to accelerate the discovery of new drug candidates and reduce costs in antiviral
drug development. In this review, we summarized the recent advances in the design of single-
and dual-target inhibitors against HIV-1 IN or/and RT-RNase H as well as the prediction
of mutation-induced drug resistance based on computational methods. We highlighted the results
of the reported literatures and proposed some perspectives on the design of novel and
more effective antiviral drugs in the future.
Synthesis and Development of Indole Based 5-HT3 Receptor Antagonists
as Anti-Emetic Drugs in Oncology: An Update
Authors: Rivera-Fonseca Johana L. , González-Rivas Nelly , Unnamatla M. V. Basavanag , García-Eleno Marco A. , Reyes Horacio , López-Valdez L. Germán , Corona-Becerril David , Cuevas-Yañez Erick
Published: July 2021

:

An important group of antiemetic drugs used in the treatment of nausea and vomiting
after chemotherapy containing an indole moiety in their structures, working as 5-
hydroxytryptamine type 3 serotonin receptor antagonist (5-HT3). This study focuses on compounds
bearing an indole core that present a 5-HT3 receptor antagonist activity, which have
been successfully used as antiemetic drugs for reducing chemotherapy adverse secondary effects
during cancer treatment. Their synthesis, biological activities, and some outstanding
characteristics are discussed, providing a general outlook towards the development of more
efficient antiemetic drugs.
Prediction Mechanism of Nevadensin as Antibacterial Agent against S.
sanguinis: In vitro and In silico Studies
Authors: Kurnia Dikdik , Shadrina Aldina Amalia Nur , Herdiyati Yetty , Wiani Ika , Satari Mieke Hemiawati
Published: July 2021

Background:

Streptococcus sanguinis can contribute to tooth demineralization, which
can lead to dental caries. Antibiotics used indefinitely to treat dental caries can lead to bacterial
resistance. Discovering new antibacterial agents from natural products, like Ocimum basilicum,
will help combat antibiotic resistance. In silico analysis (molecular docking) can help determine
the lead compound by studying the molecular interaction between the drug and the target receptor
(MurA enzyme and DNA gyrase). It is a potential candidate for antibacterial drug development.

Objective:

The research objective is to isolate the secondary metabolite of O. basilicum extract that
exhibits activity against S. sanguinis through in vitro and in silico analysis.

Methods:

n-Hexane extract of O. basilicum was purified by combining column chromatography
with bioactivity-guided fractionation. The in vitro antibacterial activity against S. sanguinis was
determined using the disc diffusion and microdilution method, while molecular docking simulation
of nevadensin (1) with MurA enzyme and DNA gyrase was performed by using PyRx 0.8 program.

Results:

Nevadensin from O. basilicum was successfully isolated and characterized by
spectroscopic methods. This compound showed antibacterial activity against S. sanguinis with
MIC and MBC values of 3750 and 15000 μg/mL, respectively. In silico analysis showed that the
binding affinity to MurA was -8.5 Kcal/mol, and the binding affinity to DNA gyrase was -6.7
Kcal/mol. The binding of nevadensin-MurA is greater than fosfomycin-MurA. Otherwise,
Nevadensin-DNA gyrase has a weaker binding affinity than fluoroquinolone-DNA gyrase and
chlorhexidine-DNA gyrase.

Conclusion:

Nevadensin showed potential as a new natural antibacterial agent by inhibiting the
MurA enzyme rather than DNA gyrase.
KIAA0101 in Malignant Pleural Mesothelioma: A Potential Diagnostic
and Prognostic Marker
Authors: Liang Zongan , Lin Ping , Zhao Yuean , Li Xiaoqian
Published: July 2021

Background:

Currently, there are no reliable diagnostic and prognostic markers for
Malignant Pleural Mesothelioma (MPM). The objective of this study was to identify hub genes that
could be helpful for diagnosis and prognosis in MPM by using bioinformatics analysis.

Materials and Methods:

The gene expression profiles were downloaded from the Gene Expression
Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Weighted Gene Co-expression
Network Analysis (WGCNA), LASSO regression analysis, Cox regression analysis, and Gene Set
Enrichment Analysis (GSEA) were performed to identify hub genes and their functions.

Results:

A total of 430 upregulated and 867 downregulated genes in MPM were identified based
on the GSE51024 dataset. According to the WGCNA analysis, differentially expressed genes were
classified into 8 modules. Among them, the pink module was most closely associated with MPM.
According to genes with GS > 0.8 and MM > 0.8, six genes were selected as candidate hub genes
(NUSAP1, TOP2A, PLOD2, BUB1B, UHRF1, KIAA0101) in the pink module. In the LASSO
model, three genes (NUSAP1, PLOD2, and KIAA0101) were identified with non-zero regression
coefficients and were considered as hub genes among the 6 candidates. The hub gene-based
LASSO model can accurately distinguish MPM from controls (AUC=0.98). Moreover, the high
expression level of KIAA0101, PLOD2, and NUSAP1 was associated with poor prognosis
compared to the low level in Kaplan–Meier survival analyses. After further multivariate Cox
analysis, only KIAA0101 (HR = 1.55, 95% CI = 1.05-2.29) was identified as an independent
prognostic factor among these hub genes. Finally, GSEA revealed that high expression of
KIAA0101 was closely associated with 10 signaling pathways.

Conclusion:

Our study identified several hub genes relevant to MPM, including NUSAP1,
PLOD2, and KIAA0101. Among these genes, KIAA0101 appears to be a useful diagnostic and
prognostic biomarker for MPM, which may provide new clues for MPM diagnosis and therapy.
Learning, Neurogenesis and Effects of Flavonoids on Learning
Authors: Almulla Asan Yalmaz Hasan , Mogulkoc Rasim , Baltaci Abdulkerim Kasim , Dasdelen Dervis
Published: July 2021

Learning and memory are two of our mind's most magical abilities. Different brain regions
have roles to process and store different types of memories. The hippocampus is the part of the brain
responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics
of the hippocampus is its capacity for neurogenesis which is a process, new neurons are
produced and then transformed into mature neurons and integrated into neural circuits. The neurogenesis
process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid
hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus
and integrated into the pre-existing neuronal network, this allows old memories already stored
in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting
neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The
flavonoids can exert particularly powerful actions in mammalian cognition and improve hippocampaldependent
learning and memory by positively affecting hippocampal neurogenesis.
Cubosomes: Versatile Nanosized Formulation for Efficient Delivery of
Therapeutics
Authors: Kumar Amrish , Singhal Keshav , Kaushik Niranjan
Published: July 2021

Cubosomes are bicontinuous cubic phase nanoparticles with a size range from 10-500
nm. They offer various advantages with some limitations at the production level, e.g., cubosomes
have the feature to encapsulate a large amount of the drug due to its large internal area owing to
cuboidal shape but limited in large scale production due to its high viscosity which is associated
with the problem in homogenization. This nanoparticulate formulation is compatible for administration
by various routes like oral, transdermal, topical, buccal, etc. The drug release mechanism from
cubosomes was reported to be dependent on the partition coefficient and diffusion process. Compared
with liposomes, cubosomes show many differences in various aspects like shape, size, ingredients,
and mode of action. The main ingredients for the preparation of cubosomes include lipids,
stabilizers, aqueous phase and therapeutic agents. Several methods have been reported for cubosomes,
including the top-down method, the bottom-up method and the adopted coarse method. For
the optimization of cubosomes, the key factors to be considered, which will affect the cubosomes
characteristics include the concentration of lipid, temperature and pH. At present, many research
groups are exploring the potential of cubosomes as biosensors and nanocarriers. Based on the latest
reports and research, this review illuminates the structure of the cubosomes, mechanism of the drug
release, different methods of preparation with factors affecting the cubosomes, application of cubosomes
in different sectors, differences from the liposomes, and their advantages.
Cervical Cancer Metastasis and Recurrence Risk Prediction Based on Deep Convolutional Neural Network
Authors: Ye Zixuan , Zhang Yunxiang , Liang Yuebin , Lang Jidong , Zhang Xiaoli , Zang Guoliang , Yuan Dawei , Tian Geng , Xiao Mansheng , Yang Jialiang
Published: July 2021

Background:

Evaluating the risk of metastasis and recurrence of a cervical cancer patient is
critical for appropriate adjuvant therapy. However, current risk assessment models usually involve the
testing of tens to thousands of genes from patients’ tissue samples, which is expensive and timeconsuming.
Therefore, computer-aided diagnosis and prognosis prediction based on Hematoxylin and Eosin
(H&E) pathological images have received much attention recently.

Objective:

The prognosis of whether patients will have metastasis and recurrence can support accurate
treatment for patients in advance and help reduce patient loss. It is also important for guiding treatment
after surgery to be able to quickly and accurately predict the risk of metastasis and recurrence of a cervical
cancer patient.

Method:

To address this problem, we propose a hybrid method. Transfer learning is used to extract features,
and it is combined with traditional machine learning in order to analyze and determine whether
patients have the risks of metastasis and recurrence. First, the proposed model retrieved relevant patches
using a color-based method from H&E pathological images, which were then subjected to image preprocessing
steps such as image normalization and color homogenization. Based on the labeled patched
images, the Xception model with good classification performance was selected, and deep features of
patched pathological images were automatically extracted with transfer learning. After that, the extracted
features were combined to train a random forest model to predict the label of a new patched image.
Finally, a majority voting method was developed to predict the metastasis and recurrence risk of a patient
based on the predictions of patched images from the whole-slide H&E image.

Results:

In our experiment, the proposed model yielded an area under the receiver operating characteristic
curve of 0.82 for the whole-slide image. The experimental results showed that the high-level features
extracted by the deep convolutional neural network from the whole-slide image can be used to predict
the risk of recurrence and metastasis after surgical resection and help identify patients who might receive
additional benefit from adjuvant therapy.

Conclusion:

This paper explored the feasibility of predicting the risk of metastasis and recurrence from
cervical cancer whole slide H&E images through deep learning and random forest methods.
Withdrawal Notice: Identifying Genetic Related Neuroimaging Biomarkers of Alzheimer's Disease via Diagnosis-Guided Group Sparse Multitask Learning Method
Authors: Lin Anshi , Kong Wei , Wang Shuaiqun
Published: July 2021

The article has been withdrawn at the request of the editor of the journal Current Bioinformatics CBIO due to
incoherent content:

Bentham Science apologizes to the readers of the journal for any inconvenience this may caused.

The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php

BENTHAM SCIENCE DISCLAIMER:

It is a condition of publication that manuscripts submitted to this journal have not been published and will not be
simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been
published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is
strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal
right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By
submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and
when the article is accepted for publication.
CRISPR/ Cas9 Off-targets: Computational Analysis of Causes, Prediction,
Detection, and Overcoming Strategies
Authors: Roy Roshan Kumar , Debashree Ipsita , Srivastava Sonal , Rishi Narayan , Srivastava Ashish
Published: July 2021

:

CRISPR/Cas9 technology is a highly flexible RNA-guided endonuclease (RGEN)
based gene-editing tool that has transformed the field of genomics, gene therapy, and genome/
epigenome imaging. Its wide range of applications provides immense scope for understanding
as well as manipulating genetic/epigenetic elements. However, the RGEN is prone to
off-target mutagenesis that leads to deleterious effects. This review details the molecular and cellular
mechanisms underlying the off-target activity, various available detection tools and prediction
methodology ranging from sequencing to machine learning approaches, and the strategies to
overcome/minimise off-targets. A coherent and concise method increasing target precision would
prove indispensable to concrete manipulation and interpretation of genome editing results that
can revolutionise therapeutics, including clarity in genome regulatory mechanisms during development.
Retracted: miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in
Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway
Authors: Guo Lin , Bao Chen-hui
Published: July 2021

The article entitled “miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway”, by Chen-Hui Bao and Lin Guo, has been retracted on the request of the Author in light of the changes to the University’s promotion policy, due to which the article needs further content.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

Kindly see Bentham Science Policy on Article retraction at the link https://benthamscience.com/journals/anti-canceragents-in-medicinal-chemistry/editorial-policies/

Bentham Science Disclaimer:

It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
Apoptotic Effect of Novel Benzimidazole Derivatives Bearing Pyridyl/Pyrimidinyl Piperazine Moiety
Authors: Çiftçi Gulsen A. , Temel Halide E. , Yurttaş Leyla
Published: July 2021

Background:

Benzimidazole derivatives bearing pyridyl/pyrimidinyl piperazine moiety has attracted attention
in medicinal chemistry and modern drug discovery since it exhibited a variety of biological activities, including
anticancer activity.

Objective:

In this study, we designed and synthesized novel 1-[2-oxo-2-(4-substituted phenyl)ethyl]benzimidazol-2-
yl)methyl 4-(2-pyridyl/pyrimidin-2-yl)piperazine-1-carbodithioate derivatives (2a-m). We also investigated their anticancer
activities against A549 lung adenocarcinoma and C6 rat glioma cell lines. We further studied the selectivity of
the compounds against the NIH/3T3 mouse embryonic fibroblast cell line. Cholinesterase inhibition effects of these
compounds were also investigated to measure the relationship between anticancer activity and cholinesterases.

Method:

The cytotoxic activities of these acquired thirteen final compounds were screened using MTT assay on
A549, C6, and NIH/3T3 cell lines. Cell proliferation ELISA, BRDU (colorimetric) assay was used to measure the
proliferation in replicative cells in which DNA synthesis occurs. Flow cytometric analysis was used to measure apoptotic
cell percentages, caspase 3 activity, and mitochondrial membrane depolarised cell percentages.

Results:

Compounds 2e, 2f, and 2k were shown to be the most active antitumor agents with selective cytotoxicities
(the results for A549 were 76.58±6.43, 55.13±5.75, and 32.94±3.02 μM, respectively; and for C6 they were
86.48±3.60, 97.12±30.21, and 59.29±3.95 μM, respectively), high DNA synthesis inhibition rates and high apoptotic
cell percentages on both cell lines.

Conclusion:

The results showed that compounds 2e, 2f, and 2k have potential anticancer activity against A549 and C6
cell lines
Ternary Copper (II) Complex Induced Apoptosis and Cell Cycle Arrest in Colorectal
Cancer Cells
Authors: Arikrishnan Sathiavani , Loh Jian Sheng , Tor Yin Sim , Teo Xian Wei , bin Norizan Faris , Low May Lee , Lee Sau Har , Foo Jhi Biau
Published: July 2021

Background:

The lack of specificity, severe side effects, and development of drug resistance have largely
limited the use of platinum-based compounds in cancer treatment. Therefore, copper complexes have emerged as potential
alternatives to platinum-based compounds.

Objective:

Ternary copper (II) complex incorporated with 1-10-phenanthroline and L-tyrosine was investigated for its
anti-cancer effects in HT-29 colorectal cancer cells.

Methods:

Cytotoxic effects of ternary copper (II) complex in HT-29 cells was evaluated using MTT assay, Real-Time
Cell Analysis (RTCA) and lactate dehydrogenase (LDH) assay. Cell cycle analysis was performed using flow cytometry.
Apoptosis induction was studied by Annexin V-FITC/Propidium Iodide (PI) staining and mitochondrial membrane
potential analysis (JC-10 staining) using flow cytometry. Intracellular Reactive Oxygen Species (ROS) were detected
by DCFH-DA assay. The expression of proteins involved in the apoptotic signalling pathway (p53, caspases, and
PARP-1) was evaluated by western blot analysis.

Results:

Ternary copper (II) complex reduced the cell viability of HT-29 cells in a time- and dose-dependent manner,
with IC50 of 2.4 ± 0.4 and 0.8 ± 0.04 μM at 24 and 48 hours, respectively. Cell cycle analysis demonstrated induction of
S-phase cell cycle arrest. Morphological evaluation and Annexin V-FITC/PI flow cytometry analysis confirmed induction
of apoptosis that was further supported by cleavage and activation of caspase-8, caspase-9, caspase-3, and PARP-
1. Mutant p53 was also downregulated in a dose-dependent manner. No LDH release, mitochondrial membrane potential
disruption, and ROS production were observed.

Conclusion:

Ternary copper (II) complex holds great potential to be developed for colorectal cancer treatment.
Synergistic Cytotoxicity Effect of 5-Fluorouracil and SHP2 Inhibitor Demethylincisterol A3 on Cervical Cancer Cell
Authors: Liu Yang , Fu Hua , Zuo Li
Published: July 2021

Background:

Demethylincisterol A3 (DTA3) has been identified as an SHP2 inhibitor and suppresses the
growth of many cancer cells. 5-Fluorouracil (5-FU) is widely used for the clinical treatment of various cancers. However,
the combination effects of 5-FU and DTA3 on cervical cancer cells remain unknown.

Objective:

This study evaluates the mechanism of the combination effects of 5-FU and DTA3 in cervical cancer cells.

Methods:

The synergistic cytotoxic effects of 5-FU and DTA3 in cervical cancer cells were calculated. Apoptosis was
analysed by flow cytometry. Western blot analyses were used to examine the related signalling pathways.

Results:

DTA3 and 5-FU synergized to induce apoptosis and repress proliferation of cervical cancer cells by downregulating
the activation of PI3K/AKT and NF-κB signalling pathways. We provided evidence that the upregulation of
SHP2 expression by transfection significantly inhibited the cytotoxicity of 5-FU and DTA3. SHP2 knockdown enhanced
the anti-proliferation activity of 5-FU, indicating targeting SHP2 sensitized cervical cancer cells to 5-FU.

Conclusion:

Our study demonstrates that SHP2 inhibitor DTA3 and 5-FU have a synergistic cytotoxic effect on cervical
cancer cells. The synergistic combination of SHP2 inhibitor and 5-FU may present a promising strategy for the
treatment of cervical cancer.