bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening, Identification and Interaction Analysis of Key MicroRNAs and Genes in Asthenozoospermia
Authors: Li Li-Man , Chen Song
Published: September 2020

Background: Asthenozoospermia, one of the most common causes of male infertility, is a complicate multifactorial pathological condition that genetic factors are involved in. However, the epigenetic signature and mechanism of asthenozoospermia still remain limited. Our study aimed to confirm the key microRNAs (miRNAs) and genes in asthenozoospermia and demonstrate the underlying epigenetic regulatory mechanisms. Methods: We screened out and pooled previous studies to extracted potential differentially expressed miRNAs (DEMs). GSE22331 and a published profile dataset were integrated to identify differentially expressed genes (DEGs). Pathway and gene ontology analysis were performed using DAVID. A protein-protein network (PPI) was constructed using STRING. The target genes of DEMs were predicted using TargetScan and then built the miRNA-mRNA network.Results: We reported 3 DEMs and 423 DEGs by pooling included dataset and published studies. Pathway analysis showed that these DEGs might participate in signaling pathways regulating pluripotency of stem cells, wnt signaling pathway and notch signaling pathway. 25 hub genes were identified, and the most significant gene was BDNF. We screened out the overlapped DEGs between the predicted target genes of 3 DEMs and the 423 DEGs. Then we constructed miRNA-mRNA network. Conclusion: This study firstly pooled several published studies and a GEO dataset to determine the significance of potential miRNAs and genes, such as miR-374b, miR-193a, miR-34b, BDNF, NTRK2, HNRNPD and EFTUD2 in regulating asthenozoospermia and underscore their interactions in the pathophysiological mechanism. Our results provided theoretical basis and new clues for potential therapeutic treatment in asthenozoospermia. Validations in vivo and in vitro are required in future studies.
A comparison between remaining and resecting the posterior longitudinal ligament in percutaneous endoscopic transforaminal discectomy for disc herniation: A retrospective cohort study
Authors: Hu Wenhao , Hu Fanqi , Liu Chao , Liu Weibo , Jiang Yi , Li Jing , Wang Yan , Li Teng , Li Li , Zhang Xuesong
Published: September 2020

Background

Nowadays, percutaneous endoscopic lumbar discectomy (PELD) has become a popular surgical option for the management of LDH, On the basis of the approach to the herniation disc materials, PELD could be classified into percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). During PETD procedure, especially in in-and-out approach, accurate determination of whether the posterior longitudinal ligament is needed resection seems particularly important.In the study, we tried assessing comparative clinical outcome, surgical duration and complications between the two different surgical methods of LDH treated by PETD via inside-and-out approach.
Methods

A total of 135 symptomatic LDH patients who were treated by PETD resecting the posterior longitudinal ligament (68 patients) or remaining the posterior longitudinal ligament (67 patients) during the surgery were included in the study. Visual analog scale (VAS) score, Oswestry disability index (ODI) and modified MacNab criteria were used to evaluate clinical outcomes. Operation time, blood loss, recurrence of LDH and other complication such as dural tear, nerve injury, intervertebral infection, etc. of these two groups were recorded. Clinical evaluation was performed preoperatively, immediately postoperatively, and at each follow-up visit (1 month, 3 months, and final follow-up).
Results

There were 38 males and 30 females in the group A that resecting the posterior longitudinal ligament (mean age = 52.40 ± 8.73 years) and 35 males and 32 females in the group B that remaining the posterior longitudinal ligament (mean age = 53.50 ± 9.24 years). The mean operation time of the group A and the group B respectively, were 82.7 ± 18.5 min and 115.6 ± 24.6 min (P < 0.01). The postoperative VAS scores and ODI were significantly higher than those before surgery in two groups (P < 0.01). The differences in the results were not significant between the two groups (P > 0.05). There was no significant difference in the complication rate, the excellent/good ratio and the recurrence rate between the two groups (P > 0.05).
Conclusion

Whether the posterior longitudinal ligament is resected do not make any difference on curative effect in PETD via inside-and-out approach, and remaining the ligament when it’s intact is preferred because of its shorter operation time.
Validation of IMU-Based Gait Event Detection During Curved Walking and Turning in Older Adults and Parkinson's Disease Patients
Authors: Romijnders Robbin , Warmerdam Elke , Hansen Clint , Welzel Julius , Schmidt Gerhard , Maetzler Walter
Published: September 2020

Background: Identication of individual gait events is essential for clinical gait analysis, because it can beused for diagnostic purposes or tracking disease progression in neurological diseases such as Parkinson'sdisease. Previous research has shown that gait events can be detected from a shank-mounted inertialmeasurement unit (IMU), however detection performance was often evaluated only from straight-line walking.For use in daily life, the detection performance needs to be evaluated in curved walking and turning as well asin single-task and dual-task conditions.Methods: Participants (older adults, people with Parkinson's disease, or people who had suered from astroke) performed three dierent walking trials: 1) straight-line walking, 2) slalom walking, 3) Stroop-and-walktrial. An optical motion capture system was used a reference system. Markers were attached to the heel andtoe regions of the shoe, and participants wore IMUs on the lateral sides of both shanks. The angular velocity ofthe shank IMUs was used to detect instances of initial foot contact (IC) and nal foot contact (FC), whichwere compared to reference values obtained from the marker trajectories.Results: The detection method showed high recall, precision and F1 scores in dierent populations for bothinitial contacts and nal contacts during straight-line walking (IC: recall = 100%, precision = 100%, F1 score= 100%; FC: recall = 100%, precision = 100%, F1 score = 100%), slalom walking (IC: recall = 100%,precision 99%, F1 score =100%; FC: recall = 100%, precision 99%, F1 score =100%), and turning (IC:recall 85%, precision 95%, F1 score 91%; FC: recall 84%, precision 95%, F1 score 89%).Conclusions: Shank-mounted IMUs can be used to detect gait events during straight-line walking, slalomwalking and turning. However, more false events were observed during turning and more events were missedduring turning. For use in daily life we recommend identifying turning before extracting temporal gaitparameters from identied gait events.
İnsan Kaynakları Departmanı için Etmen Tabanlı Sistem Tasarımı
Authors: IŞIK Melek
Published: September 2020

İşletmelerin verimli bir şekilde faaliyetlerini devam ettirebilmeleri iyi bir insan kaynakları yönetimi sayesinde gerçekleşmektedir. İnsan kaynaklarının akıllı sistemler üzerinden yönetilmesi ile işlemler daha hızlı ve bütüncül yürütülmektedir. İnsan kaynakları gibi karmaşık bir sistemin tasarım ve uygulamasında özerk akıllı etmen sistemlerinin kullanımı yaşanan problemleri çözmek açısından önemlidir. Bu bakış açısıyla, bu çalışmada, etmen tabanlı yaklaşımlardan biri olan Prometheus metodolojisi uygulanarak işletmelerdeki insan kaynakları departmanında yapılan işler için bir tasarım gerçekleştirilmiştir.
Prometheus metodolojisinin ve geliştirme ortamının sistem içerisinde uyumluluğu detaylandırılmış ve elde edilen tasarım gösterilmiştir.
Kapalı Döngü Üretim Rotalama Problemi için Bir Karar Destek Sistemi Önerisi
Authors: KUVVETLİ Yusuf , EROL Rızvan
Published: September 2020

Üretim rotalama problemi; üretim, envanter, dağıtım ve rotalama kararlarının bir arada verildiği bir tedarik zinciri problemidir. Bu problemin temel amacı, kararların entegre bir şekilde verilmesiyle birlikte maliyet açısından daha etkin kararlar almaktır. Bu çalışmada, bu problemin kapalı döngü versiyonunu ele alan bir karar destek sistemi önerilmiştir. Önerilen karar destek sisteminde kapalı döngü tedarik zincirlerindeki üretim rotalama problemi için DH algoritması uygulanmıştır. DH algoritması problemi parçalayarak alt problemleri etkileşimli bir şekilde hızla çözmeyi amaçlar. Sistemin gerçek hayat uygulamalarını gösterebilmek adına sıvı yağ üretimi yapan bir firma için bir aylık planlama dönemi için incelenen problem uygulanmış ve maliyetlerin mevcut duruma göre daha düşük olduğu görülmüştür.
İç Isı Değiştiricili Transkritik CO2 Soğutma Sisteminin Farklı Tasarım Parametreleri için Ekserji Analizi
Authors: KARAÇAYLI İbrahim , ŞİMŞEK Erdoğan
Published: September 2020

Bu çalışmada iç ısı değiştiricili karbon dioksit soğutucu akışkanla (R744) çalışan kritik nokta üstü (transkritik) soğutma çevriminin tasarım parametrelerinin enerji ve ekserji verimine olan etkileri incelenmiştir. Tasarım parametreleri olarak genleşme elemanı çıkışında soğutucu akışkanın kuruluk derecesi ile iç ısı değiştiricisiyle sağlanan kızgınlık derecesi dikkate alınmıştır. Bu amaçla, iç ısı değiştiricili CO2 soğutma çevriminin tüm bileşenlerindeki enerji transferini, ekserji yıkımını, entropi üretimini ve ekserji verimini hesaplamak amacıyla buharlaşma sıcaklığı 0 oC ve yoğuşma basıncı 10 MPa alındı. Buna ek olarak, etkinlik katsayısı ile tüm sistemin ekserji verimi hesaplandı. 5 oC ve 30 oC kızgınlık değerlerinde en uygun kuruluk derecesi sırasıyla 0,42–0,47 ve 0,31–0,36 aralığında olduğu belirlendi.
Yedek Parça Envanter Politikasının Makina Kullanılabilirliğine Etkisini Değerlendirmeye Yönelik Bir Simülasyon Algoritması
Authors: GÖLBAŞI Onur
Published: September 2020

Bu çalışmada, yedek parça envanter politikasının maden makinası kullanılabilirliğine etkisini analiz edebilecek bir simülasyon algoritmasının geliştirilmesi amaçlanmıştır. Planlı üretim ve bakım duraksamaları ve makina arızalarının neden olacağı rasgele duraksamalar algoritma içerisinde dikkate alınmıştır. Her bir makina parçasının mevcut envanter miktarları ve tedarik süreçleri, uygulanan bakım- onarım kararları ile birlikte değerlendirilmektedir. Böylelikle, uygulanan envanter politikasının makina kullanılabilirliğine olumsuz etkileri ölçülebilmektedir. Geliştirilen bu algoritma bir maden makinasına uygulanmış ve envanter politikası tanımlanmış on üç farklı parçasının bu makinanın kullanılabilirliğine muhtemel olumsuz etkileri detaylı şekilde incelemiştir. Simülasyon sonucunda, sekiz parçaya ait yedek parça stoklama ve tedarik sürecinin, bu parçaların arızalanma davranışıyla uyumlu olmadığı ve makina kullanılabilirliğini %9 oranında azalttığı tespit edilmiştir.
Evrişimli Sinir Ağları için Maksimum Ortaklama Devre Tasarımları
Authors: BÜLBÜL Büşra , GÖK Mustafa
Published: September 2020

Derin Öğrenme uygulamaları hızla gelişmekte özellikle de mobil cihazlarda yaygın olarak kullanılmaktadır. Bu platformlardaki mevcut performans, güç ve alan kısıtları, uygulamaya özgü donanım tasarımlarına ihtiyacı artırmaktadır. Görüntü işleme alanındaki en güncel yöntemlerden başlıcası Evrişimli Sinir Ağları’dır. Bu çalışmada gelişkin Evrişimli Sinir Ağı mimarilerinin önemli bir işlem bloğu olan maksimum ortaklama ünite tasarımları sunulmuştur. Maksimum-ortaklama katmanı Evrişimli Sinir Ağı tasarımlarının kritik gecikme yolunda olup, boru hatlı bir tümleşik devrenin ana çevrim hızını etki edebilecek önemdedir. Önerilen tasarımların toplam çerçeve işleme süreleri Standart Tasarıma göre çok daha kısadır. Önerilen tasarımlar farklı boru hatlı yapılara entegre edilebilecektir. Tasarımlar VHDL ile modellenmiş ve güncel bir FPGA platformu üzerinde sentezlenmiştir. Sentez sonuçları, önerilen tasarımların en hızlısının Standart Tasarımla karşılaştırıldığında 128x128’lik bir çerçeveyi yaklaşık 8,1 kat daha hızlı işlediğini göstermiştir.
Fonksiyonel Derecelenmiş Malzemeli Kirişlerin Sönümlü ve Sönümsüz Zorlanmış Titreşim Analizi
Authors: ASLAN Timuçin Alp , NOORİ Ahmad Reshad , TEMEL Beytullah
Published: September 2020

Bu çalışmada, kesit yüksekliği boyunca fonksiyonel olarak derecelendirilmiş (FD) malzemeli kirişlerin çeşitli dinamik yükler altında zorlanmış titreşim davranışı üzerine bir araştırma yapılmıştır. Farklı sınır koşulları, uzunluk-yükseklik (L/h) oranları ve malzeme değişim katsayılarının Euler-Bernoulli ve Timoshenko kirişlerinin sönümlü ve sönümsüz zorlanmış titreşimleri üzerindeki etkileri de parametrik olarak incelenmiştir. FD malzemeli çubukların davranışını idare eden hareket denklemleri, minimum toplam enerji prensibi yardımıyla elde edilmiştir. Elde edilen kanonik diferansiyel denklemler, Tamamlayıcı Fonksiyonlar Yöntemi (TFY) yardımıyla Laplace uzayında sayısal olarak çözülmüştür. Viskoelastik malzeme durumunda Kelvin tipi sönüm modeli kullanmıştır. Bu modelde elastik sabitler, elastik-viskoelastik analoji ile Laplace uzayındaki kompleks karşıtları ile değiştirilir. Önerilen yöntemin sonuçlarının doğruluğu, ANSYS sonlu elemanlar paket programının sonuçları ile karşılaştırılarak kanıtlanmıştır.
Openair® Plazma Sisteminin Polyester İçerikli Çözgülü Örme Kumaşlara Etkisinin İncelenmesi
Authors: SEZGİN BOZOK Sabiha , OĞULATA R. Tuğrul , MEZARCIÖZ Serin
Published: September 2020

Plazma, tekniği düşük enerji, su, kimyasal madde tüketimi sağlayabilmesi gibi avantajlarla konvansiyonel yaş işlemlere göre daha çevre dostu bir uygulamadır. Daha önce yapılmış çalışmalarda termal olmayan farklı plazma sistemleri tekstil yüzeylerine uygulanmış ve bazı uygulamalarda malzemenin boya alımında artış olduğu tespit edilmiştir. Bu çalışmada daha önce tekstil yüzeylerinin boyanabilirliğine etkisi denenmemiş bir teknik olan Openair® plazma sistemi üzerinde çalışılmıştır. %100 polyester içerikli çözgülü örme kumaşlara Openair® plazma sistemiyle 3 farklı sürede işlem uygulanmıştır. Ardından işlem görmemiş referans numune ve işlem görmüş numuneler dispers ve pigment boyarmaddelerle eşit boyama şartlarında renklendirilmiştir. Numunelere SEM ve FT/IR analizleri, spektrofotometre ile renk ölçümleri gerçekleştirilmiştir.
Farklı Nemde Kurutma Havası Kullanılarak Kurutulan Yerfıstığının Kuruma Kinetiklerinin Deneysel Olarak Belirlenmesi
Authors: ÇERÇİ Kamil Neyfel , HÜRDOĞAN Ertaç
Published: September 2020

Ürünlerin kurutularak saklanması eski çağlardan beri yaygın olarak kullanılan bir yöntemdir. Gıda kurutma işleminde temel amaç ürünün içerisinde bulunan suyun üründen uzaklaştırılmasıdır. Bu sayede ürün içerisindeki mikroorganizmaların gelişmesini durdurulacak ve ürünlerin raf ömrü uzatılacaktır. Bu çalışmada Osmaniye’de üretimi ve hasadı yapılan yerfıstığı ürününün kurutulması, kurutma havasının farklı mutlak nem değerleri için incelenmiştir. Yerfıstığının kuruma davranışı, tasarlanarak imal edilen deney düzeneği kullanılarak deneysel olarak belirlenmiştir. Çalışmada ayrıca deneysel olarak elde edilen alınabilir nem oranı değeri 22 farklı ince tabaka kurutma modeline fit edilmiştir. Çalışma sonucunda aynı sıcaklıkta kurutma havası için, kurutma havası nem değerinin düşmesi ile difüzyon katsayısının ve kuruma hızının arttığı gözlemlenmiştir. Hii ve arkadaşları tarafından geliştirilen ince tabaka kuruma modeli, deneysel olarak elde edilen alınabilir nem oranı değerine en iyi yakınsayan model olarak belirlenmiştir.
Gestión del conocimiento: una estrategia innovadora para el desarrollo de las universidades
Authors: Beltrán-Ríos Jaime Alberto , López-Giraldo José Antonio , Gelvez-Velásquez Claudia , Quintero-Benítez Shirley , Benítez-Cardona Viviana Katerine
Published: September 2020

La actual sociedad del conocimiento responde a las crecientes demandas del entorno producto de los cambios constantes generados por el progreso del conjunto de técnicas en la información y la comunicación, la globalización y la apertura de mercados, gestionando el conocimiento como estrategia para el incremento de capacidades individuales y el desarrollo de organizaciones inteligentes. Este activo intangible gestionado eficientemente fortalece los procesos de innovación en los distintos sectores productivos donde se implemente, fomentando, incluso, el desarrollo de innovaciones con impacto social de cara al desarrollo de los países. Para una adecuada gestión del conocimiento se deben alinear las estrategias y las políticas de la organización con este proceso, además de comprender los elementos, herramientas y modelos que intervienen logrando los resultados esperados con la implementación del modelo en cuanto a la generación de valor, el desarrollo de capacidades organizacionales y la permanencia en el mercado a través de la competitividad empresarial. En consecuencia, este articulo dispone de una reflexión basada en artículos de investigaciones, que resaltan la importancia de la gestión del conocimiento, orientada al desarrollo e innovación en las instituciones de educación superior.
Evaluación de impacto del comercio electrónico en las ventas de las pymes en colombia: un análisis econométrico
Authors: Corrales-Liévano Juan David , Ruiz-Medina Cindy Johanna , Angulo-Camargo Milton Fernando
Published: September 2020

El comercio electrónico (CE) se ha convertido en un eje primordial en las diferentes sociedades. La tecnología se ha constituido como parte fundamental en el entorno empresarial y en la forma como se desarrollan y conectan las diferentes organizaciones en el mundo. Hay un número creciente de compañías que generan sistemas alternativos para incrementar sus ventas utilizando las tecnologías de información y comunicación (TIC). De aquí que el presente estudio pretenda determinar la influencia del e-commerce en las ventas de las pequeñas y medianas empresas (pymes) colombianas. Este documento comienza analizando un panel de 2 177 empresas, donde se analizan los sectores de industria, comercio y servicios entre los años 2012 a 2016. Se pretende conocer el efecto causal que tiene el comercio en línea frente a las ventas totales realizadas por las compañías, así como su impacto en las ventas desarrolladas por cada una de ellas. Mediante un análisis econométrico, aplicando el modelo de medición de impacto denominado “Diferencias en Diferencias”, se encontró que la adopción del comercio electrónico en las empresas medianas tiene mayor impacto que en las empresas pequeñas y que la actividad en el que más influye el comercio electrónico es en el sector servicios.
Monoclonal Antibodies, Small Molecule Inhibitors and Antibody-drug Conjugates as HER2 Inhibitors
Authors: Li Xiu-Fang , Liu Chen-Fu , Rao Guo-Wu
Published: September 2020

Overexpression of human epidermal growth factor receptor (HER)-2 is found in a
variety of cancers, often portending poor clinical outcomes. Therefore, HER2 is an attractive
target for treatment. This review describes the research progress of HER2 targeted inhibitors
in recent years. Excellent reviews are available, so we focus on the development, mechanisms
of action, and structure-activity relationships of different types of inhibitors, including
monoclonal antibodies, small molecule inhibitors, and antibody-drug conjugates (ADCs). In
addition, the differences among them are compared.
Repurposing of Acriflavine to Target Chronic Myeloid Leukemia Treatment
Authors: Nehme Rawan , Hallal Rawan , El Dor Maya , Kobeissy Firas , Gouilleux Fabrice , Mazurier Frédéric , Zibara Kazem
Published: September 2020

Drug repurposing has lately received increasing interest in several diseases especially in
cancers, due to its advantages in facilitating the development of new therapeutic strategies, by
adopting a cost-friendly approach and avoiding the strict Food and Drug Administration (FDA)
regulations. Acriflavine (ACF) is an FDA approved molecule that has been extensively studied
since 1912 with antiseptic, trypanocidal, anti-viral, anti-bacterial and anti-cancer effects. ACF has
been shown to block the growth of solid and hematopoietic tumor cells. Indeed, ACF acts as an
inhibitor of various proteins, including DNA-dependent protein kinases C (DNA-PKcs), topoisomerase
I and II, hypoxia-inducible factor 1α (HIF-1α), in addition to its recent discovery as an
inhibitor of the signal transducer and activator of transcription (STAT). Chronic myeloid leukemia
(CML) is a clonal myeloproliferative disorder characterized by the expression of the constitutively
active tyrosine kinase BCR-ABL. This protein allows the activation of several signaling pathways
known for their role in cell proliferation and survival, such as the JAK/STAT pathway. CML therapy,
based on tyrosine kinase inhibitors (TKIs), such as imatinib (IM), is highly effective. However,
15% of patients are refractory to IM, where in some cases, 20-30% of patients become resistant.
Thus, we suggest the repurposing of ACF in CML after IM failure or in combination with IM
to improve the anti-tumor effects of IM. In this review, we present the different pharmacological
properties of ACF along with its anti-leukemic effects in the hope of its repurposing in CML therapy.
CYP19A1 rs10046 Pharmacogenetics in Postmenopausal Breast Cancer Patients Treated with Aromatase Inhibitors: One-year Follow-up
Authors: Baatjes Karin , Peeters Armand , McCaul Micheal , Conradie Maria M. , Apffelstaedt Justus , Conradie Magda , Kotze Maritha J.
Published: September 2020

Background:

Significant individual variation in bone loss associated with aromatase inhibitors (AIs)
emphasizes the importance of identifying postmenopausal breast cancer patients at high risk for this adverse effect.
The study explores the clinical relevance of genetic variation in the Cytochrome P450 19A1 (CYP19A1)
gene in a subset of South African patients during the first year of taking AIs for estrogen receptor (ER)-positive
breast cancer.

Methods:

The study population consisted of ER-positive breast cancer patients on AIs, followed in real-life clinical
practice. Body mass index was measured and bone mineral density (BMD) was determined at baseline and at
month 12. CYP19A1 genotyping was performed using real-time polymerase chain reaction analysis of rs10046,
extended to Sanger sequencing and whole exome sequencing in 10 patients with more than 5% bone loss at
month 12 at the lumbar spine.

Results:

After 12 months of AI treatment, 72 patients had completed BMD and were successfully genotyped. Ten
patients (14%) experienced more than 5% bone loss at the lumbar spine over the study period. Genotyping for
CYP19A1 rs10046 revealed that patients with two copies of the A-allele were 10.79 times more likely to have an
ordinal category change of having an increased percentage of bone loss or no increase at the lumbar spine, compared
to patients with the GA or GG genotypes (CI of 1.771- 65.830, p=0.01). None of the 34 patients without
lumbar spine bone loss at month 12 were homozygous for the functional CYP19A1 polymorphism. At the total
hip region, patients with the AA genotype were 7. 37 times more likely to have an ordinal category change of
having an increased percentage of bone loss or no increase (CI of 1.101- 49.336, p=0.04).

Conclusions:

Homozygosity for the CYP19A1 rs10046 A-allele may provide information, in addition to clinical
and biochemical factors that may be considered in risk stratification to optimize bone health in postmenopausal
breast cancer women on AIs. Further investigation is required to place the clinical effect observed for a single
CYP19A1 gene variant in a genomic context.
Fusion Protein Targeted Antiviral Peptides: Fragment-Based Drug Design (FBDD) Guided Rational Design of Dipeptides Against SARS-CoV-2
Authors: Manna Sounik , Chowdhury Trinath , Baindara Piyush , Mandal Santi M.
Published: September 2020

:

Infectious diseases caused by viruses have become a serious public health issue in the recent
past, including the current pandemic situation of COVID-19. Enveloped viruses are most commonly
known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major
key event in the case of enveloped viruses that is required for their entry into the cell. Viral fusion
proteins play an important role in the fusion process and in infection establishment. Because of this,
the fusion process targeting antivirals become an interest to fight against viral diseases caused by the
enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial
virus (RSV), and severe acute respiratory syndrome coronavirus (SARS-CoV) are examples of such
enveloped viruses that are at the top in public health issues. Here, we summarized the viral fusion protein
targeted antiviral peptides along with their mechanism and specific design to combat the viral
fusion process. The pandemic COVID-19, severe respiratory syndrome disease is an outbreak worldwide.
There are no definitive drugs yet, but few are in on-going trials. Here, an approach of fragmentbased
drug design (FBDD) methodology is used to identify the broad spectrum agent target to the conserved
region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from
the library and designed by the systematic combination along with their possible modifications of
amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy
minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = -
62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Anyone of the active peptides from the developed
libraries may help to block the target sites competitively to successfully control COVID-19.
Novel 4-Oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors: Synthesis, Docking Studies, Molecular Dynamics Simulation and Biological Activities
Authors: Zadeh Elnaz Ebrahim , Vahabpour Rouhollah , Beirami Amirreza Dowlati , Hajimahdi Zahra , Zarghi Afshin
Published: September 2020

Background:

HIV-1 integrase (IN) has been considered as an important target for the development
of novel anti-HIV-1 drugs.

Objective:

The aim of this study was to design novel groups of HIV IN inhibitors.

Method:

In this study, we presented a novel series of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-
a]pyrimidine-3-carboxylic acid derivatives by structural modification of N-arylindole β-diketoacids
as a well-known group of IN inhibitors.

Results:

Based on in-vitro anti-HIV-1 activity in a cell-based assay, compounds 5, 6a and 6k displayed
moderate to good inhibitory activity with EC50 values of 4.14, 1.68 and 0.8 μM, respectively.
However, integrase inhibition assay showed that most of the analogues did not have significant effects
against integrase enzyme except compound 5 with an IC50 value of 45 μM. Our results indicated
that compound 6k was the best one among synthesized compounds with an EC50 of 0.8 μM and SI of
175. Docking and molecular dynamics simulation studies were also performed to provide some insights
into the probable mechanism of tested compounds.

Conclusion:

These findings suggest that 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-
carboxylic acid derivatives may consider as promising lead compounds for the development of new
anti-HIV-1 drugs.
Design, Synthesis, and Anti-Neuroinflammatory Activity of Amide- Containing Dithiolethiones
Authors: Craig Karrington , Avila Paula , Brown Dennis A.
Published: September 2020

Background:

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central
nervous system characterized by demyelination of neurons and neurodegeneration. Current MS therapies
ameliorate inflammatory damage but are unable to address the degenerative aspects of the disease.

Objective:

In this report, we evaluate the ability of amide-based dithiolethiones (DTTs) to suppress
neuroinflammation in microglia and increase anti-oxidant capacity in neuron-like cells.

Methods:

A series of amide-containing DTTs were designed, synthesized, and assayed for the ability
to suppress pro-neuroinflammatory cytokines IL-12p40 and IL-23p19 induced by LPS in the BV2
microglial cell line. Lead analog 2c was identified and further characterized.

Results:

Structure-activity data revealed tolerance towards a variety of amides. Morpholine analog 2c
dose-dependently reduced various other inflammatory cytokines and mediators, including TNF, IL-6,
IL-1β, NOS2, and COX2. Additionally, 2c elevated cellular levels of glutathione in SH-SH5Y neuronal
cell line. Furthermore, mechanistic studies showed that 2c increased the expression of antiinflammatory
Nrf2 and HMOX proteins.

Conclusion:

The combination of anti-neuroinflammatory and anti-oxidant activities of amide-based
DTTs suggests that they are promising agents for the treatment of both demyelination and neurodegeneration
in MS.
RNA Splicing: Basic Aspects Underlie Antitumor Targeting
Authors: Fergany Alzahraa A.M. , Tatarskiy Victor V.
Published: September 2020

Background:

RNA splicing, a fundamental step in gene expression, is aimed at intron removal
and ordering of exons to form the protein’s reading frame.

Objective:

This review is focused on the role of RNA splicing in cancer biology; the splicing abnormalities
that lead to tumor progression emerge as targets for therapeutic intervention.

Methods:

We discuss the role of aberrant mRNA splicing in carcinogenesis and drug response.

Results and Conclusion:

Pharmacological modulation of RNA splicing sets the stage for treatment
approaches in situations where mRNA splicing is a clinically meaningful mechanism of the disease.
Transcriptionomic Study on Apoptosis of SKOV-3 Cells Induced by Phycoerythrin from Gracilaria lemaneiformis
Authors: Ying Jun , Tang Zhouhao , Zhao Guanan , Li Xia , Pan Ruowang , Lin Shuangxiang , Lou Yang , Wang Wanping , Li Peizhen , Bao Qiyu , Yan Chunxia
Published: September 2020

Objective:

To investigate the effects of phycoerythrin (PE) on the human ovarian cancer cell line SKOV-3 and
its antitumor mechanisms from a transcriptional point of view.

Methods:

SKOV-3 cells were exposed to different concentrations of phycoerythrin. The efficiency of this treatment was
evaluated through cell growth inhibition, changes in cell morphology, apoptosis and intracellular ROS levels. High
throughput sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs), which was verified
using RT-PCR and Western blotting.

Results:

PE showed a significant inhibitory effect on the growth of SKOV-3 cells in a time- and dose-dependent manner.
H&E staining, electron microscopy and flow cytometry revealed that PE induced apoptosis in SKOV-3 cells.
Transcriptome analysis showed that 2963 genes were differentially expressed between untreated or PE-treated cells. GO
and KEGG pathway analyses identified 16 classical pathways that were enriched. We verified 8 DEGs including, JNK,
GADD45A, EDEM2, RAD23, UBQLN, CAPN1, XBP1, and OS9. These results were consistent with results from
transcriptional sequences.

Conclusion:

The inhibitory effect of PE on SKOV-3 cells was a result of interaction with multiple pathways and signaling
molecules. Among these, the ROS/JNK/Bcl-2 signaling pathway, upregulation of JNK, GADD45A and RAD23 as well as
downregulation of XBP1 and OS9 played a critical role in the PE -induced apoptosis in human ovarian cancer cells.
Fabrication, In vitro and In vivo Characterization of Solid Dispersion- Microsphere Controlled Release System for Lornoxicam
Authors: Nupane Suraj , Srivastava Dipti , Chaurasia Mohini , Awasthi Himani
Published: September 2020

Background:

Lornoxicam is widely used for its anti-inflammatory, analgesic and antipyretic
properties. However, it suffers from the limitations of possessing a relatively short elimination half-life
ranging from 3 to 5 h, thereby; leading to repeated dosing which in turn may cause local irritation and
ulceration. In addition, LXM also exhibits pH-dependent solubility. Effective management of inflammation
in diseases such as arthritis requires the formulation of delivery systems that may be able to
provide immediate release of drug for instant relief which shall be maintained for a prolonged period.

Objective:

The present research work was aimed to modify the release pattern of poorly water-soluble
drug Lornoxicam by designing a biphasic tablet comprising of solid dispersion (immediate release
form) and microspheres (controlled release form) for the effective management of inflammation.

Methods:

The solid dispersion (SD) was prepared by melting method using PEG 4000 and tween 80
and formation was confirmed by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction
(PXRD) studies. Polymeric microspheres loaded with Lornoxicam were prepared by ‘Emulsion
Solvent-Evaporation’ method using Eudragit S-100 and Eudragit L-100. Microspheres (MS) were evaluated
for drug entrapment efficiency, drug loading, drug content, particle size and in vitro release
behaviour. Optimized microspheres (polymer concentration 0.5% w/v and drug concentration
0.1% w/v and solid dispersion (drug: PEG 4000: 4:6) were compressed in the ratio of 1:3 to produce
biphasic tablet. The prepared tablets were evaluated for various pre-compression and post-compression
parameters. Anti-inflammatory activity of the F4, M6 and the combination of SD and Microspheres in a
ratio of 1:3 was carried out by Carrageenan induced paw edema method in Wistar rats.

Results:

The solid dispersions prepared by melting technique showed an enhanced dissolution rate as
compared to the pure drug. LXM microspheres exhibited a sustained drug release. In vitro release of
lornoxicam from biphasic tablets showed that 20% of the drug released at the end of first one hour, followed
by 33% release at the end of 4th h and maximum release of 94.1% at the end of 10 h. The prolonged
effect continued till the end of 12 h. Results showed that the mixture of MS + SD exhibited 48%
inhibition in 30 min which is increased to 88.63% at the end of 4 h which can be explained by initial
burst release from the soluble layer of SD (which gave initial required effective concentration of Lornoxicam)
followed by sustained release from matrix of microspheres (which maintained required level
of Lornoxicam in blood).

Conclusion:

A successful modification of the release pattern of LXM was achieved by designing a biphasic
tablet comprising of solid dispersion for the effective management of inflammation.
Applications of Selectfluor for the Oxidation of Sulfides, Urazoles and Alcohols Under the Solvent-free Conditions
Authors: Chehardoli Gholamabbas , Zolfigol Mohammad A. , Mallakpour Shadpour
Published: September 2020

Aims:

Using Selectorfluor® for the oxidation of urazoles and sulfides as well as the oxidation
of alcohols under mild conditions.

Background:

[1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane-bis(tetrafluoroborate)]
so-called Selectorfluor®, is a reagent/catalyst that is donor of the electrophilic fluorine atom. Selectorfluor
® is a colorless salt which was first introduced in 1992. This year, Banks et al. prepared a
salt from the reaction of dichloromethane with dabco and sodium tetrafluoroborate, and then reacted
it with fluorine gas to prepare the Selectorfluor®.

Objective:

Unlike the highly hazardous F2, the Selectorfluor® is a stable, non-hygroscopic, easy to
handle and commercially available reagent that has many applications in organic reactions.

Methods:

Substrate [alcohols, urazoles or sulfides (1 mmol)] was added to the mixture of Selectorfluor
® (0.708 g, 2 mmol), KBr (0.236 g, 2 mmol), and 0.2 g wet SiO2 (50%). The mixture was
ground with a mortar and pestle for 10-15 minutes. Then, the product was extracted with CH2Cl2
(2×10 mL). The solution was dried with anhydrous sodium sulfate and filtered again. Simple distillation
of the CH2Cl2 gave the crude product. Aldehyde/ketones and sulfoxides were purified by
short column chromatography on silica gel with EtOAc/n-hexane (1:3 to 1:5). Urazoles were purified
by the sublimation method.

Results:

Some advantages of these oxidation reactions using the Selectorfluor®/KBr system are: a)
both reagent and catalyst are safe and easy to handle; b) the procedure is solvent-free; c) the reaction
is carried out at room temperature; d) yields are good to excellent; e) work-up is convenient
since the reagent/catalyst residue is ionic and insoluble in the organic solvents.

Conclusion:

Selectorfluor® is a safe and stable reagent that is easy to work with, although it is slow
and lazy in reaction, and it cannot react well at room temperature. The literature survey shows that
the best conditions for a reaction are acetonitrile reflux and that the solvent-free is not very desirable
conditions.
Comparative analysis of the effectiveness of existing methods of networks security from DDoS attacks
Authors: Evglevskaya N. V. , Zuev A. Yu. , Karasenko A. O. , Lauta O. S.
Published: September 2020

At present, issues related to information security are highly relevant. DoS and DDoS attacks are carried out by cybercriminals quite often, because cyberattacks can bring almost any system to failure, leaving no legally significant evidence. At the same time, the failure of the attacked subsystem can be an intermediate stage towards the target system. The most vulnerable to DDoS attacks are online stores, online payment systems, news resources and companies, whose activities depend on the frequency of user access to the resource. The main methods of protection against cyberattacks and DDoS attacks, in particular, are currently antivirus programs and firewalls. The article presents a description of some types of DDoS attacks as well as the results of a comparative analysis of several existing methods of networks security from DDoS attacks, which will simplify the choice of the optimal solution to ensure reliable protection of a telecommunication facility. Considering all the advantages and disadvantages, the method of organizing a network protection system against DDoS attacks based on the technology of artificial neural networks is the most suitable solution for ensuring the information security of networks of various purpose.
Intervention Enhancement Strategies Among Adults With Type 2 Diabetes in a Very Low–Carbohydrate Web-Based Program: Evaluating the Impact With a Randomized Trial
Authors: Saslow Laura R , Moskowitz Judith Tedlie , Mason Ashley E , Daubenmier Jennifer , Liestenfeltz Bradley , Missel Amanda L , Bayandorian Hovig , Aikens James E , Kim Sarah , Hecht Frederick M
Published: September 2020

Background

Adults with type 2 diabetes may experience health benefits, including glycemic control and weight loss, from following a very low–carbohydrate, ketogenic (VLC) diet. However, it is unclear which ancillary strategies may enhance these effects.

Objective

This pilot study aims to estimate the effect sizes of 3 intervention enhancement strategies (text messages, gifts, and breath vs urine ketone self-monitoring) that may improve outcomes of a 12-month web-based ad libitum VLC diet and lifestyle intervention for adults with type 2 diabetes. The primary intervention also included other components to improve adherence and well-being, including positive affect and mindfulness as well as coaching.

Methods

Overweight or obese adults (n=44; BMI 25-45 kg/m2) with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.5%), who had been prescribed either no glucose-lowering medications or metformin alone, participated in a 12-month web-based intervention. Using a 2×2×2 randomized factorial design, we compared 3 enhancement strategies: (1) near-daily text messages about the intervention’s recommended behaviors (texts n=22 vs no texts n=22), (2) mailed gifts of diet-relevant foods and cookbooks (6 rounds of mailed gifts n=21 vs no gifts n=23), and (3) urine- or breath-based ketone self-monitoring (urine n=21 vs breath n=23). We assessed HbA1c and weight at baseline and at 4, 8, and 12 months. We evaluated whether each strategy exerted a differential impact on HbA1c and weight at 12 months against an a priori threshold of Cohen d of 0.5 or greater.

Results

We retained 73% (32/44) of the participants at 12 months. The intervention, across all conditions, led to improvements in glucose control and reductions in body weight at the 12-month follow-up. In intent-to-treat (ITT) analyses, the mean HbA1c reduction was 1.0% (SD 1.6) and the mean weight reduction was 5.3% (SD 6.0), whereas among study completers, these reductions were 1.2% (SD 1.7) and 6.3% (SD 6.4), respectively, all with a P value of less than .001. In ITT analyses, no enhancement strategy met the effect size threshold. Considering only study completers, 2 strategies showed a differential effect size of at least a d value of 0.5 or greater

Conclusions

Text messages, gifts of food and cookbooks, and urine-based ketone self-monitoring may potentially enhance the glycemic or weight loss benefits of a web-based VLC diet and lifestyle intervention for individuals with type 2 diabetes. Future research could investigate other enhancement strategies to help create even more effective solutions for the treatment of type 2 diabetes.

Trial Registration

ClinicalTrials.gov NCT02676648; http://clinicaltrials.gov/ct2/show/NCT02676648
Evaluation of ReachOut.com, an Unstructured Digital Youth Mental Health Intervention: Prospective Cohort Study
Authors: Kahl Bianca Lorraine , Miller Hilary May , Cairns Kathryn , Giniunas Hayley , Nicholas Mariesa
Published: September 2020

Background

Young people experience a disproportionate burden associated with mental illness that Australia’s mental health care system is ill-equipped to handle. Despite improvements in the provision of mental health services, the rates of service utilization among young people remain suboptimal, and there are still considerable barriers to seeking help. Digital mental health services can overcome a number of barriers and connect young people requiring support; however, the evidence base of digital interventions is limited.

Objective

The aim of this study is to examine the effectiveness of a brief, self-directed, unstructured digital intervention, ReachOut.com (hereafter ReachOut), in reducing depression, anxiety, stress, and risk of suicide.

Methods

A cohort of 1982 ReachOut users participated in a 12-week longitudinal study, with a retention rate of 81.18% (1609/1982) across the duration of the study. Participants completed web-based surveys, with outcome measures of mental health status and suicide risk assessed at 3 time points across the study period.

Results

The results demonstrated that over the 12-week study period, young people using ReachOut experienced modest yet significant reductions in symptoms of depression, anxiety, and stress. Significant, albeit modest, reductions in the proportion of participants at high risk of suicide were also observed.

Conclusions

The findings of this research provide preliminary evidence of the promise of an unstructured digital mental health intervention, ReachOut, in alleviating symptoms of mental ill-health and promoting well-being in young people. These findings are particularly important given that digital services are not only acceptable and accessible but also have the potential to cater to the diverse mental health needs of young people at scale, in a way that other services cannot.
Problematic internet use in Chinese rural adolescents and its association with adverse life experiences and resilience: A nationwide cross-sectional study (Preprint)
Authors: Kang Chun , Chang Hongjuan , Yuan Shanshan , Xiang Jingjing , Yu Yizhen
Published: September 2020

BACKGROUND

Problematic internet use (PIU) is a growing public health and social issue among adolescents, however, its prevalence in rural adolescents remains to be investigated. Adverse life experiences (ALEs) and resilience have been reported to be important influence factors of PIU, but little is known about the interaction effects of ALEs and resilience on PIU, or gender differences in these effects.

OBJECTIVE

This study aimed to provide the first prevalence report of PIU in Chinese rural adolescents based on a nationwide sample, and to examine the association among ALEs, resilience and PIU, as well as the gender difference within these relationships.

METHODS

A school-based survey was conducted in rural areas from five provinces in China in 2014-2015. A total of 15950 students aged 11-22 years finished a complete self-report questionnaire, including demographic characteristics, measurements of PIU, stressful life events, child neglect and maltreatment, and resilience. ALEs were defined as having experienced stressful life events and/or child neglect and maltreatment. Univariate and multivariable logistic regression analyses were used.

RESULTS

There were 2734 adolescents assessed with PIU in our sample, with a prevalence rate of 17.1%. Multiple adjusted odds ratios for PIU was significantly increased with higher ALEs scores (5-6: OR=1.28, 95% CI=1.11-1.48; 7-8: OR=1.66, 95% CI=1.43-1.92) and significantly decreased with higher resilience level (Mild: OR=0.83, 95% CI=0.74-0.93; Moderate: OR=0.68, 95% CI=0.60-0.77; High: OR=0.59; 95% CI=0.52-0.67). Moderate resilience had significantly protective effect on PIU in adolescents with high ALEs scores (OR=0.63, 95% CI=0.41-0.97). A significant interaction effect was found between ALEs and resilience on PIU only in girls (P=0.021) but not in boys (P=0.081), however, this gender difference showed no significance (P=0.305).

CONCLUSIONS

This study suggests a relative high prevalence of PIU among Chinese rural adolescents. More ALEs and lower resilience are associated with higher risk for PIU, and resilience can moderate the association between ALEs and PIU. Strategies combining ALEs prevention and resilience promotion both in girls and boys would yield better to decrease PIU problems in adolescents.