bluuebunny/crossref_metadata_2025 huggingface dataset:
FORMULASI DAN UJI MUTU FISIK SEDIAAN SERUM MIKROEMULSI EKSTRAK BIJI MELINJO Gnteum gnemon L
Authors: Khaira Zahratun , Monica Eva , Yoedistira Chresiani Destianita
Published: October 2022

Biji melinjo termasuk komoditas pangan yang banyak terdapat di Aceh.  Pemanfaatannya terbatas sebagai olahan sayur dan bahan baku pembuatan emping. Biji melinjo mengandung antioksidan yang tergolong dengan nilai IC50 59,52 ppm kuat bahkan setara dengan antioksidan sintetik Butylated Hydrotolune (BHT). Antioksidan adalah senyawa yang memiliki banyak manfaat untuk Kesehatan kulit yaitu sebagai antipenuaan dan perlindungan dari sinar UV. Atas dasar hal tersebut, maka biji melinjo dapat dioptimalkan penggunaanya sebagai sediaan kosmetik berupa serum mikroemulsi. Penelitian ini bertujuan untuk mengindentifikasikan formula serum ekstrak biji melinjo yang memenuhi persyaratan uji mutu fisik dan mengetahui aktivitas antioksidan yang terdapat dalam serum mikroemulsi ekstrak biji melinjo.

Jenis rancangan penelitian yang digunakan adalah eksperimental. Eksperimental ini didasarkan pada formulasi dan uji-uji yang dilakukan dalam penelitian ini. Data hasil uji yang diperoleh dalam penelitian ini dianalisa menggunakan metode ANOVA one way. Sediaan serum mikroemulsi ekstrak biji melinjo yang telah dibuat dilakukan uji mutu fisik meliputi organoleptis, homogenitas, pH, tipe emulsi, hedonik, viskositas, ukuran partikel, kelembapan, dan iritasi serta uji aktivitas antioksidan.

Hasil penelitian menunjukkan bahwa formula 3 ekstak biji melinjo 10% lebih unggul dibandingkan dua formula lainnya dalam hal pengujian organoleptis, homogenitas, pH, uji viskositas, tipe emulsi, ukuran globul, uji kelembapan, dan uji iritasi. Uji DPPH sediaan serum mikroemulsi ekstrak biji melinjo memiliki aktivitas antioksidan sedang hingga kuat dengan perolehan nilai IC50 pada F1 118,28 ppm, F2 88,03 ppm, dan F3 80,63 ppm.

Kata Kunci : biji Melinjo, antioksidan, serum mikroemulsi, mutu fisik
Uji Aktivitas Antikolesterol Kombinasi Ekstrak Daun Afrika Vernonia amygdalina dan Daun Pinus Pinus merkusii Secara In Vitro
Authors: Sianto Bella Vania , Rollando Rollando , Tambun Sabrina Handayani
Published: October 2022

Dislipidemia merupakan abnormalitas kadar lipid dan lipoprotein dalam plasma dan merupakan salah satu penyebab timbulnya berbagai penyakit kardiovaskular seperti arterosklerosis dan jantung koroner. Pencegahan dislipidemia dapat dilakukan dengan tumbuhan obat herbal yang mengandung senyawa fitokimia penurun kolesterol. Salah satu tanaman obat yang banyak dijumpai di Indonesia adalah daun afrika dan pohon pinus. Penelitian sebelumnya menunjukkan bahwa ekstrak dari tanaman tersebut bermanfaat dalam menurunkan kadar kolesterol. Oleh karena itu, dilakukan penelitian mengenai kandungan dan aktivitas ekstrak daun afrika dan daun pinus dalam menghambat kolesterol.

Pada penelitian ini, uji aktivitas antikolesterol dilakukan secara in vitro dengan metode Liebermann Burchard. Penelitian diawali dengan pengumpulan dan identifikasi bahan berupa daun afrika dan daun pinus. Daun kemudian dikeringkan dan dihaluskan sehingga diperoleh serbuk simplisia. Serbuk simplisia kemudian diekstraksi melalui proses maserasi atau perendaman dalam pelarut etanol sehingga diperoleh ekstrak daun afrika dan daun pinus. Ekstrak kemudian diidentifikasi kandungan senyawa fitokimia yang memiliki aktivitas antikolesterol, seperti flavonoid, tanin, saponin, fenolik, dan steroid. Ekstrak tersebut kemudian diuji aktivitas antikolesterolnya menggunakan spektrofotometri UV-Vis

Hasil skrining fitokimia menunjukkan bahwa dalam sampel ekstrak daun afrika mengandung senyawa fenolik, tanin, saponin, dan steroid sedangkan dalam sampel ekstrak daun pinus mengandung senyawa flavonoid, fenolik, tanin, saponin, dan steroid. Hasil uji antikolesterol dengan metode Liebermann-Burchard menunjukkan bahwa ekstrak daun afrika dan daun pinus dapat menurunkan kadar kolesterol secara in vitro dengan daya hambat EC50 sebesar 4671,91 ppm. Untuk penelitian selanjutnya disarankan agar pada proses ekstraksi digunakan jenis pelarut dan metode yang berbeda, dilakukan isolasi bahan aktif, dan dilakukan uji antikolesterol secara in vivo.
PERANCANGAN VIDEO ANIMASI 2D CERITA PUTRI MANDALIKA SEBAGAI UPAYA PELESTARIAN BUDAYA UNTUK ANAK SEKOLAH DASAR
Authors: Negara Lalu Ikhwanul Satya , Rahmadianto Sultan Arif , Nugroho Didit Prasetyo
Published: October 2022

One of the folklore in Lombok is the story of Putri Mandalika. Princess Mandalika is a princess who threw herself into the sea to avoid division between kingdoms. However, there is a lack of awareness for the younger generation in preserving folklore. For this reason, there are appropriate alternative media to introduce Putri Mandalika's story, one of them is animation video. The method used is a qualitative method. Qualitative data obtained through observation, interviews, and literature study. Animated video of Putri Mandalika story using a paper cut design style with 6 minutes 37 seconds duration.
PERANCANGAN BUKU FOTOGRAFI ARSITEKTUR KOLONIAL UNTUK MENINGKATKAN DAYA TARIK WISATA HERITAGE DI KOTA MALANG
Authors: Pratama Natasa , Rahmadianto Sultan Arif , Nugroho Didit Prasetyo
Published: October 2022

Indonesia merupakan negara yang memiliki keanekaragaman ras, suku, budaya, dan bahasa. Bahkan warisan budaya tak benda yang ada di Indonesia mencapai 819 item. Di samping keberlimpahan warisan budaya yang ada di Indonesia, arsitektur adalah bukti lain saksi bisu perjalanan Indonesia. Bahkan terdapat 175 jenis arsitektur dan 2.319 cultural heritage tersebar di berbagai wilayah Indonesia. Jawa Timur adalah pemilik cultural heritage terbanyak ke-lima di Indonesia. Kota Malang sebagai salah kota terbesar kedua di Jawa Timur juga mendapat pengaruh kuat atas budaya Belanda, terutama arsitektur kolonialnya. Bertolak belakang dengan kekayaan cultural heritage dan arsitektur milik Indonesia, keberlimpahan ini tidak didukung sepenuhnya oleh kesadaran masyarakat Indonesia untuk lebih memahami, mempelajari, dan melestarikan cultural heritage dengan baik. Oleh karena itu, perlu dibuat buku fotografi arsitektur kolonial untuk meningkatkan kesadaran masyarakat sekaligus agar menjadi daya tarik wisata heritage Kota Malang. Buku fotografi ini dibuat dengan banyak gambar dan sedikit tulisan supaya tidak membosankan dan dapat menggambarkan keseluruhan arsitektur hingga mendetail. Dalam penelitian ini metode yang digunakan adalan metode kualitatif dengan pengumpulan data secara observasi, studi pustaka, wawancara, kuisioner, dan dokumentasi. Media pendukung dalam perancangan ini adalah mug, gantungan kunci, totebag, pin, t-shirt, photosheet dan bookmark.
Kajian Resistensi Antibiotik Golongan Aminoglikosida dan Golongan Tetrasiklin
Authors: Theresylle Eunike Cynthia , Sitepu Rehmadanta , Yoedistira Chresiani Destianita
Published: October 2022

Resistance is the ability of bacteria to resist or stop antibiotics. However, according to the Centers for Disease Control and Prevention (CDC), about 23,000 people die per year from resistance. Resistance begins with exposure to antibiotics, initially there are only one or two bacteria that have a chance to live but can grow and spread. The spread through person to person, inappropriate use of antibiotics due to weak infection control.

So the purpose of this study is to find out how the process of resistance by bacteria, as well as genes that play a role in antibiotic resistance of Aminoglycosides and Tetracyclines. Thus we can wisely use antibiotics,for the medical community, the community and help in efforts to reduce the level of resistance and the impact of other resistance. The research method used is the journal review method of 40 articles which is used as material to compare the results of several research articles. The articles used using Scholar and Pubmed searches were selected based on inclusion and exclusion criteria.

From the results of a journal review that Aminoglycoside and Tetracycline antibiotics have a high level of resistance. Aminoglycoside resistance is due to enzymatic inactivation by AAC,APH and ANT. The most common resistance is the Acetyltransferase (AAC) enzyme, namely the AAC(6')-I gene. Tetracycline resistance occurs by efflux pump mechanism, ribosome protection and enzymatic inactivation. The most common gene is tetM gene on ribosome protection mechanism which is expressed to mediate resistance to several antibiotics such as Doxycycline and Minocycline.
PERANCANGAN APLIKASI BERBASIS WEB UNTUK PREDIKSI HARGA SAHAM DENGAN METODE LSTM
Authors: Simatupang Christofer Genta Kresnamurti , Swastika Windra , Suganda Tarsisius Renald
Published: October 2022

Dari data pada hari Bursa terakhir di bulan Maret 2022, jumlah investor di pasar modal meningkat mencapai 12.13% dari tahun sebelumnya dan jumlah investor reksa dana meningkat sebesar 13.12% dari tahun sebelumnya (PT Kustodian Sentral Efek Indonesia, 2022). Dengan meningkatnya investor dari tahun 2021 semakin beragam juga karakteristik investornya. Seperti dari jenis kelamin, investor laki-laki yang melakukan investasi sebanyak 62.89% sedangkan wanita adalah sisanya. Sehingga dilihat dari data yang dikumpulkan, masih banyak investor yang masih menduduki bangku SMA sehingga masih banyak pengetahuan yang belum mereka miliki mengenai saham dan akan berisiko saat melakukan investasi. Pada penelitian yang dilakukan oleh Nurjaman, Hasim, dan Zakin pada tahun 2021 mendapat nilai RMSE sebesar 0.9366032757092849 pada prediksi harga saham Pfizer Inc menggunakan LSTM. Penelitian yang dilakukan oleh Wijaksana dalam memprediksi harga saham pada PT. Telkom Indonesia mendapatkan hasil nilai MSE sebesar 0,045 dan RMSE sebesar 0,0212 untuk train score dan MSE sebesar 0,027 dan RMSE sebesar 0,165 untuk test score. Pada perancangan aplikasi ini hanya akan menggunakan dataset pada saham indeks LQ45 dengan data historis selama 5 tahun dan hanya menggunakan 15 emiten. Arsitektur LSTM yang digunakan 2 layer LSTM dengan 10 units dan menggunakan 100 dan 200 epoch dengan optimizer yang digunakan Adam dan Nadam. Aplikasi akan berbasis web dengan menggunakan framework Flask pada Python. Pengujian sistem dilakukan dengan menghitung MSE yang didapat dan juga MAPE dan trend LSTM pada model masing-masing emiten. Hasil pengujian yang didapat, dapat disimpulkan jika aplikasi berbasis website ini dapat memprediksi harga saham indeks LQ45.
DECISION SUPPORT SYSTEM USING FUCOM-MARCOS FOR AIRLINE SELECTION IN INDONESIA
Authors: Mahendra Gede Surya
Published: October 2022

Since deregulation in 1999, the development of the Indonesian aviation industry has continued to develop. However, many airlines still face various problems before and during flights. Problems in the plane, ranging from engine problems, technical problems, tire damage, cockpit problems to air pressure problems. Airlines customers have personal considerations and preferences when choosing an airline. The many choices and many considerations of airlines often confuse customers. To solve this problem, a decision support system (DSS) can be used to provide advice in selecting airlines based on customer preferences. This study uses the FUCOM-MARCOS method, using 8 criteria and 6 testing alternatives. When using FUCOM to calculate criterion weights, it appears that the factor price (C5) is the factor that counts most. Calculations using FUCOM-MARCOS show that Garuda Indonesia is the favorite airline in Indonesia with a preference value of 0.7390, followed by Citilink in second place, and Batik Air in third. Testing using consistency analysis shows that Garuda Indonesia remains stable and is the first choice by being ranked first 15 times out of 17 tests, with an average ranking distribution reaching 1.23466.
IMPLEMENTATION OF ARAS ALGORITHM ON DECISION SUPPORT SYSTEM TO DETERMINE THE BEST LECTURER
Authors: Supriatin Supriatin , Saputra Alex Rizky , Satria Budy
Published: October 2022

In the world of higher education, lecturers are one of the main components in building quality and quantity. Good quality will give good results as well, to improve the quality of each lecturer, it is necessary to have an award given to lecturers from the campus so that it becomes a motivation for lecturers to improve the quality given to students and the community. Amik Mitra Gama is a private campus located in the Duri Riau area, in this case to improve the quality of education one of the steps taken is to give awards and appreciation to the best lecturers who will be selected every year. To realize this, we need an easy calculation system that is carried out in the form of ranking according to the final value, therefore a decision support system using the ARAS method is chosen because it is very appropriate for the selection process and provides convenience in the calculations which are determined based on ranking. The decision support system using the ARAS method uses 8 criteria that are set as a reference in determining the best lecturers, namely Recent Education, Lecturer Functional Position, Lecturer Certification, Number of Journal Publications, Roles in Research, Journal Publication History, Research Grants, and Community Service. There are 10 lecturers in the field of computers who will be used as alternative data with lecturer codes D01, D02, D03, D04, D05, D06, D07, D08, D09, D10. The results obtained from this study are the lecturer code D04 = 0.0974, D06 = 0.0965, D09 = 0.0932, D07 = 0.0903, D03 = 0.0901 was selected as the best lecturer in 2021/2022. So that the results of this study can help the campus to determine the best lecturers every year fairly and be selected based on rankings.
IDENTIFY CHOLESTEROL DISEASE RISK LEVELS USING MULTIPLE LINEAR REGRESSION ALGORITHMS
Authors: Haryadi Deny , Umi Atmaja Dewi Marini
Published: October 2022

Cholesterol is one of the fat compounds found in the bloodstream that are necessary for the formation of several hormones and new cell walls in the liver. Normal cholesterol levels in the human body are in the range of < 200 mg / dL. If cholesterol levels in the blood are abnormal or excessive, it can result in dangerous diseases such as heart disease or stroke. In this study, cholesterol disease prediction will be carried out using models formed from linear regression methods, so that the results of this study can be used as a reference for early prevention of cholesterol disease and become a means of decision making. Linear regression is one of the prediction methods in data mining that can be used to find out how dependent variables/criteria can be predicted through independent variables or predictor variables individually. In this study by utilizing some data of patients with cholesterol disease that has been stored in the database using several attributes, namely age, BMI, glucose, and cholesterol. So by applying a linear regression algorithm can be done a prediction in the identification of cholesterol diseases based on functional relationships on the attributes in the data. The results of this study showed an RMSE value of 0.347 with a standard deviation of /- 0.000. This shows that the model resulting from linear regression algorithms with the above cases is quite accurate.
HEMŞİRELER İÇİN BASINÇ YARALANMASI YÖNETİMİ ÖZ YETERLİLİK ÖLÇEĞİ’NİN TÜRKÇE GEÇERLİLİK VE GÜVENİRLİLİK ÇALIŞMASI
Authors: UTLİ Hediye , DİNÇ Mahmut
Published: October 2022

Bu araştırmanın amacı, Hemşireler için Basınç Yaralanması Yönetimi Öz Yeterlilik Ölçeği’nin Türkçe geçerlilik ve güvenilirliğini yapmaktır. Bu metodolojik tipteki çalışmaya, 149 hemşire katıldı. Araştırma verilerin toplanmasında “Hemşire Bilgi Formu” ve “Hemşireler için Basınç Yaralanması Yönetimi Öz Yeterlilik Ölçeği (BYY-ÖYÖ)” kullanıldı. Ölçek toplam 10 maddeden oluşmaktadır. Her bir madde 1 (hiç yetkin değil)’den 5 (tamamıyla yetkin)’e kadar puanlandırılıp geçerlik analizi sonucunda, Hemşireler için Basınç Yaralanması Yönetimi Öz Yeterlilik Ölçeğinin dört alt boyuttan oluştuğu belirlendi. Ölçeğin hiçbir maddesi çıkarılmamış olup çalışmanın kapsam geçerlik indeksi 0.83-1.00 arasında bulundu. Ölçeğin yapı geçerliliği için korelasyon analizi yapılıp ve yapılan analiz sonucunda; 10 maddelik ölçeğin toplam varyansı en çok %74.41’ini açıkladığı bulundu. Ölçeğin güvenirliliği için maddelerin toplam puan korelasyon değerlerinin 0.404 ile 0.661 arasında olup Cronbach Alpha değerinin 0.838 olduğu saptandı. Ölçeğin, hemşireler için basınç yaralanması yönetimi öz yeterlilik düzeyini ölçmek için kullanılabileceği sonucuna varıldı.
Leadership Transitions and Rebel Group Violence: Evidence from Syria
Authors: Fawcett Weiner Joshua
Published: October 2022

I propose a novel theoretical framework and examine whether leadership change can affect the behavior of rebel groups using updated original data on assassination attempts of rebel leaders during the Syrian civil war. The relationship between rebel leaders and insurgent group violence is tested on 15 of the largest rebel groups in Syria’s civil war using a quantitative design that leverages variation in insurgent group violence, as well as leadership transitions within insurgent groups. I exploit the inherent randomness of the success or failure of assassination attempts to identify the causal effect of rebel leadership removal on insurgent group violence. I find that successful assassination attempts reduce rebel group violence, but only when senior leaders are targeted, not mid-level officials. Importantly, successful attempts degrade groups, but do not reduce overall levels of violence in the conflict. This points to defection as an understudied mechanism in conflict with multiple armed groups.
THE CONCEPT OF DARK TOURISM, VISITORS’ MOTIVATION AND THE ENTAILED DISSONANCE IN SITES REPRESENTATION
Authors: Mavragani Eleni , Mandrinou Evangelia
Published: October 2022

The purpose of this research is to explore the concept of dark tourism, focusing on the conceptual approach of dark tourism, the different terms stated for its nature, the review of its historical background as well as its main categories. Emphasis is placed on the identification of the tourists’ general beliefs regarding the concept of dark tourism, their emotions related to visits to specific dark tourism monuments and the internal motives that serve as driving forces for visits to dark tourism spots of interest. The study investigates whether the contemporary representation of dark tourism monuments in Greece accurately reflects the historical background and the horrific events that took place in the past. The research aims to investigate whether there is a statistically significant correlation between the variables of dissonance in the representation of the sites, the motives and emotions of the tourists, and whether there is a statistical difference in the dissonance, emotions and motives based on the demographic results. The type of the research implemented is the primary quantitative research and the outcomes reveal that the overall picture of emotions is at an average level, with dark tourism eliciting both positive and negative emotions from the tourism audience.
Yield of sainfoin depending on the method of soil treatment and the background of fertilizers on the slope
Authors: Il'inskaya Izida , Gaevaya Emma
Published: October 2022

The article presents the results of field studies to establish the influence of the main tillage method and the level of mineral nutrition on the yield of perennial grasses (sainfoin) on the erosion-dangerous slope of ordinary chernozems in the Rostov region. The variability of the yield value depending on the agrotechnical and hydrothermal conditions of cultivation has been studied. It has been established that an increase in the stability of the sainfoin crop on an erosion-prone slope is provided by chisel tillage against the background of P60K40 kg/ha active substance with 40% of perennial grasses in a five-field crop rotation.
Optimization of productive potential of mountain forage land in the Central Caucasus
Authors: Soldatova Irina , KOZYREV Soslan , SOLDATOV Eduard
Published: October 2022

The unregulated use of mountain fodder lands has led to the degradation of soil and vegetation. The use of the biologically active drug "Extrasol", zeolite-containing agro-ore and humus of sheep manure on the natural forage land of the mountain zone contributed to a change in the composition of soil nutrients by reducing the acidity of the soil solution. The germination of fallow seeds of cereals increased from 30.4 to 55.3%, legumes from 5.2 to 17.1-26.8%, which had an impact on the reduction of weed forbs from 64 to 27.6-19.5 %. The change in the structure of the herbage contributed to an increase in yield from 9.9 to 69.4 c/ha of dry weight, the concentration of feed units from 0.9 to 6.1 thousand feed units and MA to 73.9 GJ/ha, allowing to increase the load livestock on pasture and its productivity, while maintaining the ecological stability of mountain agricultural landscapes.
General consensus on multimodal functions and validation analysis of perinatal derivatives for regenerative medicine applications
Authors: Pozzobon Michela , D’Agostino Stefania , Roubelakis Maria G. , Cargnoni Anna , Gramignoli Roberto , Wolbank Susanne , Gindraux Florelle , Bollini Sveva , Kerdjoudj Halima , Fenelon Mathilde , Di Pietro Roberta , Basile Mariangela , Borutinskaitė Veronika , Piva Roberta , Schoeberlein Andreina , Eissner Guenther , Giebel Bernd , Ponsaerts Peter
Published: October 2022

Perinatal tissues, such as placenta and umbilical cord contain a variety of somatic stem cell types, spanning from the largely used hematopoietic stem and progenitor cells to the most recently described broadly multipotent epithelial and stromal cells. As perinatal derivatives (PnD), several of these cell types and related products provide an interesting regenerative potential for a variety of diseases. Within COST SPRINT Action, we continue our review series, revising and summarizing the modalities of action and proposed medical approaches using PnD products: cells, secretome, extracellular vesicles, and decellularized tissues. Focusing on the brain, bone, skeletal muscle, heart, intestinal, liver, and lung pathologies, we discuss the importance of potency testing in validating PnD therapeutics, and critically evaluate the concept of PnD application in the field of tissue regeneration. Hereby we aim to shed light on the actual therapeutic properties of PnD, with an open eye for future clinical application. This review is part of a quadrinomial series on functional/potency assays for validation of PnD, spanning biological functions, such as immunomodulation, anti-microbial/anti-cancer, anti-inflammation, wound healing, angiogenesis, and regeneration.
Aspalathin-rich green rooibos tea in combination with glyburide and atorvastatin enhances lipid metabolism in a db/db mouse model
Authors: Patel Oelfah , Muller Christo J. F. , Joubert Elizabeth , Rosenkranz Bernd , Louw Johan , Awortwe Charles
Published: October 2022

Rooibos (Aspalathus linearis), an indigenous South African plant and its major flavonoid, aspalathin, exhibited positive effects on glycemia and dyslipidemia in animal studies. Limited evidence exists on the effects of rooibos extract taken in combination with oral hypoglycemic and lipid-lowering medications. This study investigated the combined effects of a pharmaceutical grade aspalathin-rich green rooibos extract (GRT) with the sulfonylurea, glyburide, and atorvastatin in a type 2 diabetic (db/db) mouse model. Six-week-old male db/db mice and their nondiabetic lean db+ littermates were divided into 8 experimental groups (n=6/group). Db/db mice were treated orally with glyburide (5 mg/kg bodyweight), atorvastatin (80 mg/kg bodyweight) and GRT (100 mg/kg bodyweight) as mono- and combination therapies respectively, for 5 weeks. An intraperitoneal glucose tolerance test was conducted at 3 weeks of treatment. Serum was collected for lipid analyses and liver tissues for histological examination and gene expression. A significant increase in the fasting plasma glucose (FPG) of the db/db mice compared to their lean counterparts (from 7.98 ± 0.83 to 26.44 ± 1.84, p < 0.0001) was observed. Atorvastatin reduced cholesterol (from 4.00 ± 0.12 to 2.93 ± 0.13, p < 0.05) and triglyceride levels (from 2.77 ± 0.50 to 1.48 ± 0.23, p < 0.05). In db/db mice, the hypotriglyceridemic effect of atorvastatin was enhanced when combined with both GRT and glyburide (from 2.77 ± 0.50 to 1.73 ± 0.35, p = 0.0002). Glyburide reduced the severity and pattern of steatotic lipid droplet accumulation from a mediovesicular type across all lobular areas, whilst combining GRT with glyburide reduced the abundance and severity of lipid droplet accumulation in the centri- and mediolobular areas. The combination of GRT, glyburide and atorvastatin reduced the abundance and severity of lipid accumulation and the intensity score compared to the administered drugs alone. The addition of either GRT or glyburide in combination with atorvastatin had no effect on blood glucose or lipid profiles, but significantly reduced lipid droplet accumulation.
Ena/VASP proteins at the crossroads of actin nucleation pathways in dendritic cell migration
Authors: Visweshwaran Sai Prasanna , Nayab Hafiza , Hoffmann Lennart , Gil Marine , Liu Fan , Kühne Ronald , Maritzen Tanja
Published: October 2022

As sentinels of our immune system dendritic cells (DCs) rely on efficient cell migration for patrolling peripheral tissues and delivering sampled antigens to secondary lymphoid organs for the activation of T-cells. Dynamic actin polymerization is key to their macropinocytic and migratory properties. Both major actin nucleation machineries, formins and the Arp2/3 complex, are critical for different aspects of DC functionality, by driving the generation of linear and branched actin filaments, respectively. However, the importance of a third group of actin nucleators, the Ena/VASP family, has not been addressed yet. Here, we show that the two family members Evl and VASP are expressed in murine DCs and that their loss negatively affects DC macropinocytosis, spreading, and migration. Our interactome analysis reveals Ena/VASP proteins to be ideally positioned for orchestrating the different actin nucleation pathways by binding to the formin mDia1 as well as to the WAVE regulatory complex, a stimulator of Arp2/3. In fact, Evl/VASP deficient murine DCs are more vulnerable to inhibition of Arp2/3 demonstrating that Ena/VASP proteins contribute to the robustness and efficiency of DC migration.
The high toxicity of DSB-clusters modelling high-LET-DNA damage derives from inhibition of c-NHEJ and promotion of alt-EJ and SSA despite increases in HR
Authors: Mladenova Veronika , Mladenov Emil , Chaudhary Shipra , Stuschke Martin , Iliakis George
Published: October 2022

Heavy-ion radiotherapy utilizing high linear energy transfer (high-LET) ionizing radiation (IR) is a promising cancer treatment modality owing to advantageous physical properties of energy deposition and associated toxicity over X-rays. Therapies utilizing high-LET radiation will benefit from a better understanding of the molecular mechanisms underpinning their increased biological efficacy. Towards this goal, we investigate here the biological consequences of well-defined clusters of DNA double-strand breaks (DSBs), a form of DNA damage, which on theoretical counts, has often been considered central to the enhanced toxicity of high-LET IR. We test clonal cell lines harboring in their genomes constructs with appropriately engineered I-SceI recognition sites that convert upon I-SceI expression to individual DSBs, or DSB-clusters comprising known numbers of DSBs with defined DNA-ends. We find that, similarly to high-LET IR, DSB-clusters of increasing complexity, i.e. increasing numbers of DSBs, with compatible or incompatible ends, compromise classical non-homologous end-joining, favor DNA end-resection and promote resection-dependent DSB-processing. Analysis of RAD51 foci shows increased engagement of error-free homologous recombination on DSB-clusters. Multicolor fluorescence in situ hybridization analysis shows that complex DSB-clusters markedly increase the incidence of structural chromosomal abnormalities (SCAs). Since RAD51-knockdown further increases SCAs-incidence, we conclude that homologous recombination suppresses SCAs-formation. Strikingly, CtIP-depletion inhibits SCAs-formation, suggesting that it relies on alternative end-joining or single-strand annealing. Indeed, ablation of RAD52 causes a marked reduction in SCAs, as does also inhibition of PARP1. We conclude that increased DSB-cluster formation that accompanies LET-increases, enhances IR-effectiveness by promoting DNA end-resection, which suppresses c-NHEJ and enhances utilization of alt-EJ or SSA. Although increased resection also favors HR, on balance, error-prone processing dominates, causing the generally observed increased toxicity of high-LET radiation. These findings offer new mechanistic insights into high-LET IR-toxicity and have translational potential in the clinical setting that may be harnessed by combining high-LET IR with inhibitors of PARP1 or RAD52.
The proneural transcription factor ASCL1 regulates cell proliferation and primes for differentiation in neuroblastoma
Authors: Parkinson Lydia M. , Gillen Sarah L. , Woods Laura M. , Chaytor Lewis , Marcos Daniel , Ali Fahad R. , Carroll Jason S. , Philpott Anna
Published: October 2022

Neuroblastoma is believed to arise from sympathetic neuroblast precursors that fail to engage the neuronal differentiation programme, but instead become locked in a pro-proliferative developmental state. Achaete-scute homolog 1 (ASCL1) is a proneural master regulator of transcription which modulates both proliferation and differentiation of sympathetic neuroblast precursor cells during development, while its expression has been implicated in the maintenance of an oncogenic programme in MYCN-amplified neuroblastoma. However, the role of ASCL1 expression in neuroblastoma is not clear, especially as its levels vary considerably in different neuroblastoma cell lines. Here, we have investigated the role of ASCL1 in maintaining proliferation and controlling differentiation in both MYCN amplified and Anaplastic Lymphoma Kinase (ALK)-driven neuroblastoma cells. Using CRISPR deletion, we generated neuroblastoma cell lines lacking ASCL1 expression, and these grew more slowly than parental cells, indicating that ASCL1 contributes to rapid proliferation of MYCN amplified and non-amplified neuroblastoma cells. Genome-wide analysis after ASCL1 deletion revealed reduced expression of genes associated with neuronal differentiation, while chromatin accessibility at regulatory regions associated with differentiation genes was also attenuated by ASCL1 knock-out. In neuroblastoma, ASCL1 has been described as part of a core regulatory circuit of developmental regulators whose high expression is maintained by mutual cross-activation of a network of super enhancers and is further augmented by the activity of MYC/MYCN. Surprisingly, ASCL1 deletion had little effect on the transcription of CRC gene transcripts in these neuroblastoma cell lines, but the ability of MYC/MYCN and CRC component proteins, PHOX2B and GATA3, to bind to chromatin was compromised. Taken together, our results demonstrate several roles for endogenous ASCL1 in neuroblastoma cells: maintaining a highly proliferative phenotype, regulating DNA binding of the core regulatory circuit genes to chromatin, while also controlling accessibility and transcription of differentiation targets. Thus, we propose a model where ASCL1, a key developmental regulator of sympathetic neurogenesis, plays a pivotal role in maintaining proliferation while simultaneously priming cells for differentiation in neuroblastoma.
Alpha-lipoic acid supplementation restores the meiotic competency and fertilization capacity of porcine oocytes induced by arsenite
Authors: Zhang Mianqun , Sun Lei , Zhang Zihao , Shentu Luyan , Zhang Yiwen , Li Ziyi , Zhang Yongteng , Zhang Yunhai
Published: October 2022

Arsenite is known as a well-known endocrine disrupting chemicals, and reported to be associated with an increased incidence of negative health effects, including reproductive disorders and dysfunction of the endocrine system. However, it still lacks of the research regarding the beneficial effects of ALA on arsenite exposed oocytes, and the underlying mechanisms have not been determined. Here, we report that supplementation of alpha-lipoic acid (ALA), a strong antioxidant naturally present in all cells of the humans, is able to restore the declined meiotic competency and fertilization capacity of porcine oocytes induced by arsenite. Notably, ALA recovers the defective nuclear and cytoplasmic maturation of porcine oocytes caused by arsenite exposure, including the impaired spindle formation and actin polymerization, the defective mitochondrion integrity and cortical granules distribution. Also, ALA recovers the compromised sperm binding ability to maintain the fertilization potential of arsenite-exposed oocytes. Importantly, ALA suppresses the oxidative stress by reducing the levels of ROS and inhibits the occurrence of DNA damage along with apoptosis. Above all, we provide a new perspective for the application of ALA in effectively preventing the declined oocyte quality induced by environmental EDCs.
Comprehensive analysis of histone methylation modification regulators for predicting prognosis and drug sensitivity in lung adenocarcinoma
Authors: Ye Ying , Li Li , Dai Qinjin , Liu Yan , Shen Lin
Published: October 2022

Histone methylation is an epigenetic modification regulated by histone methyltransferases, histone demethylases, and histone methylation reader proteins that play important roles in the pathogenic mechanism of cancers. However, the prognostic value of histone methylation in lung adenocarcinoma (LUAD) remains unknown. Here, we found that LUAD cases could be divided into 2 subtypes by the 144 histone methylation modification regulators (HMMRs), with a significant difference in OS time. Ninety-five of the HMMRs were identified as differentially expressed genes (DEGs) between normal and tumor samples, and 13 of them were further discovered to be survival-related genes (SRGs). By applying the least absolute shrinkage and selector operator (LASSO) Cox regression, we constructed an 8-gene-based risk signature according to the TCGA (training) cohort, and the risk score calculated by the signature was proven to be an independent factor in both the training and validation cohorts. We then discovered that the immune functions were generally impaired in the high-risk groups defined by the HMMR signature (especially for the DCs and immune check-point pathway). Functional analyses showed that the DEGs between the low- and high-risk groups were related to the cell cycle. The drug sensitivity analysis indicated that our risk model could predict the sensitivity of commonly used drugs. Moreover, according to the DEGs between the low- and high-risk groups, we discovered several new compounds that showed potential therapeutic value for high-risk LUAD patients. In conclusion, our study demonstrated that HMMRs were promising predictors for the prognoses and drug therapeutic effects for LUAD patients.
Native valve, prosthetic valve, and cardiac device-related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies
Authors: Kouijzer Joop J. P. , Noordermeer Daniëlle J. , van Leeuwen Wouter J. , Verkaik Nelianne J. , Lattwein Kirby R.
Published: October 2022

Infective endocarditis (IE) is a life-threatening microbial infection of native and prosthetic heart valves, endocardial surface, and/or indwelling cardiac device. Prevalence of IE is increasing and mortality has not significantly improved despite technological advances. This review provides an updated overview using recent literature on the clinical presentation, diagnosis, imaging, causative pathogens, treatment, and outcomes in native valve, prosthetic valve, and cardiac device-related IE. In addition, the experimental approaches used in IE research to improve the understanding of disease mechanisms and the current diagnostic pipelines are discussed, as well as potential innovative diagnostic and therapeutic strategies. This will ultimately help towards deriving better diagnostic tools and treatments to improve IE patient outcomes.
Synthesis, thermal behaviors, and energetic properties of asymmetrically substituted tetrazine-based energetic materials
Authors: Wang Shenghui , Chen Xiang , Chen Yuankai , Nan Hai , Li Yuanyuan , Ma Haixia
Published: October 2022

1,2,4,5-tetrazine ring is a common structure for the construction of energy-containing compounds, and its high nitrogen content and large conjugation effect give it the advantage of a good balance between energy and mechanical stability as a high-nitrogen energy-containing material. However, most of the reported works about tetrazine energetic materials (EMs) are symmetrically substituted tetrazines due to their easy accessibility. A small number of reports show that asymmetrically substituted tetrazines also have good properties, such as high density and generation of enthalpy and energy. Herein, two asymmetrically substituted tetrazines and their five energetic salts were prepared and fully characterized by IR spectroscopy, NMR spectra, elemental analysis, and differential scanning calorimetry (DSC). The structure of the two compounds was further confirmed by single-crystal X-ray diffraction studies. The thermal behaviors and thermodynamic parameters were determined and calculated. In addition, the energetic properties and impact sensitivities of all the compounds were obtained to assess their application potential. The results show that compounds 2–4 and 7–9 show higher detonation velocities than TNT, and the hydrazinium salt 9 possesses the best detonation properties (D = 8,232 m s−1 and p = 23.6 GPa). Except for 4 and 3, all the other compounds are insensitive, which may be applied as insensitive explosives. Noncovalent interaction analysis was further carried out, and the result shows that the strong and high proportion of hydrogen bonds may contribute to the low-impact sensitivity.
Current status of pulmonary artery denervation
Authors: Davies Mark G. , Miserlis Dimitrios , Hart Joseph P.
Published: October 2022

Pulmonary hypertension is a progressive disease with a poor long-term prognosis and high mortality. Pulmonary artery denervation (PADN) is emerging as a potential novel therapy for this condition. The basis of pursuing a sympathetic denervation strategy has its origins in a body of experimental translation work that has demonstrated that denervation can reduce sympathetic nerve activity in various animal models. This reduction in pulmonary sympathetic nerve activity is associated with a reduction in pathological pulmonary hemodynamics in response to mechanical, pharmacological, and toxicologically induced pulmonary hypertension. The most common method of PADN is catheter-directed thermal ablation. Since 2014, there have been 12 reports on the role of PADN in 490 humans with pulmonary hypertension (311:179; treated: control). Of these, six are case series, three are randomized trials, and three are case reports. Ten studies used percutaneous PADN techniques, and two combined PADN with mitral and/or left atrial surgery. PADN treatment has low mortality and morbidity and is associated with an improved 6-minute walking distance, a reduction in both mean pulmonary artery pressure and pulmonary vascular resistance, and an improvement in cardiac output. These improved outcomes were seen over a median follow-up of 12 months (range 2–46 months). A recent meta-analysis of human trials also supports the effectiveness of PADN in carefully selected patients. Based on the current literature, PADN can be effective in select patients with pulmonary hypertension. Additional randomized clinical trials against best medical therapy are required.
Experimental constraints on the stability and oscillation of water vapor film—a precursor for phreatomagmatic and explosive submarine eruptions
Authors: Sonder Ingo , Moitra Pranabendu
Published: October 2022

Pre-mixing of magma and external water plays a key role in driving explosive phreatomagmatic and submarine volcanic eruptions. A thin film of water vapor forms at the magma–water interface as soon as hot magma comes in direct contact with the cold water (Leidenfrost effect). The presence of a stable vapor film drives efficient mixing and mingling between magma and water, as well as magma and wet and water-saturated sediments. Such mixing occurs before explosive molten fuel–coolant type interactions. Using high-temperature laboratory experiments, we investigate the effect of magma and water temperatures on the stability of vapor film, which has not been performed systematically for a magmatic heat source. The experiments were performed with re-melted volcanic rock material, from which spherically-shaped rock samples were produced. These samples were heated to 1,110°C and then submerged in a water pool with a constant temperature (3–93°C). The experiments were recorded on video, and, synchronously, sample and water temperatures were measured using thermocouples. The time-dependent thickness of the vapor film was measured from the video material. The vapor film tends to oscillate with time on the order of 102 Hz. We find that the vertical collapse rates of vapor films along the sample–water interfaces are 13.7 mm s−1 and 4.2 mm s−1 for water temperatures of 3.0°C and 65°C, respectively. For a given initial sample temperature, the thickness and stability time scales decrease with decreasing water temperature, which has implications for the efficiency of pre-mixing required for explosive eruptions. Using thermodynamics and previously measured material parameters, it is shown that a sudden collapse of the vapor film can start brittle fragmentation of the melt and thus serves as the starting point of thermohydraulic explosions.
Hydrodynamics of a tidal inlet under gray to green coastal protection interventions
Authors: Velasquez-Montoya Liliana , Wargula Anna , Nangle Jessica , Sciaudone Elizabeth , Smyre Elizabeth , Tomiczek Tori
Published: October 2022

Structural coastal protection interventions have been implemented worldwide to stabilize channels and shorelines in tidal inlets. Although these conventional “gray” interventions typically attain their goals, there is an increasing interest and need to consider nature-based or “green” interventions that also address system resilience and environmental impacts. For a better implementation of gray to green interventions in tidal inlets, their effectiveness and their effects on the velocity of these dynamic coastal systems need to be understood. The effects on flow velocity of gray to green coastal protection interventions for tidal inlets are assessed here by exploring six interventions intended to protect against erosion on the estuarine-side shoreline near the inlet. A field-calibrated numerical model with Willmott Skill scores rated as excellent for Oregon Inlet located in North Carolina, United States, is used to simulate tidal currents under present conditions and after implementing a seawall, a set of bendway weirs, a terminal groin extension, a dual-jetty system, a flood channel relocation, and an island restoration project. Comparisons of time series of flow velocities in the flood channel along an eroding, estuarine shoreline are used to identify the effectiveness of each coastal protection alternative at reducing erosive velocities. Geospatial difference maps are used to determine velocity changes caused by each alternative throughout the inlet system. With no coastal protection interventions, the velocities along the eroding shoreline exceeded an erosive threshold velocity (defined as 0.2 m/s) during 50% of the simulated period. Alternatives closer to the green side of the coastal protection intervention spectrum, such as channel relocation and island restoration, tend to display the most effectiveness at reducing flow velocities at the eroding shoreline while resulting in minimal inlet-wide hydrodynamic changes. On the other hand, gray alternatives either cause minimal (seawall and bendway weirs) or extreme (jetties) changes in velocities throughout the inlet system. This comparison of gray and green coastal protection interventions in tidal inlets serves as an example to contrast the effectiveness of different coastal protection alternatives at reducing erosive flow velocities and to inform alternative selection at other inlet systems.
Enhanced anti-cancer effects of oestrogen and progesterone co-therapy against colorectal cancer in males
Authors: Mahbub Amani A. , Aslam Akhmed , Elzubier Mohamed E. , El-Boshy Mohamed , Abdelghany Abdelghany H. , Ahmad Jawwad , Idris Shakir , Almaimani Riyad , Alsaegh Aiman , El-Readi Mahmoud Zaki , Baghdadi Mohammed A. , Refaat Bassem
Published: October 2022

Although ovarian sex steroids could have protective roles against colorectal cancer (CRC) in women, little is currently known about their potential anti-tumorigenic effects in men. Hence, this study measured the therapeutic effects of 17β-oestradiol (E2) and/or progesterone (P4) against azoxymethane-induced CRC in male mice that were divided into (n = 10 mice/group): negative (NC) and positive (PC) controls, E2 (580 µg/Kg/day; five times/week) and P4 (2.9 mg/Kg/day; five times/week) monotherapies, and concurrent (EP) and sequential (E/P) co-therapy groups. Both hormones were injected intraperitoneally to the designated groups for four consecutive weeks. Similar treatment protocols with E2 (10 nM) and/or P4 (20 nM) were also used in the SW480 and SW620 human male CRC cell lines. The PC group showed abundant colonic tumours alongside increased colonic tissue testosterone levels and androgen (AR) and oestrogen (ERα) receptors, whereas E2 and P4 levels with ERβ and progesterone receptor (PGR) decreased significantly compared with the NC group. E2 and P4 monotherapies equally increased ERβ/PGR with p21/Cytochrome-C/Caspase-3, reduced testosterone levels, inhibited ERα/AR and CCND1/survivin and promoted apoptosis relative to the PC group. Both co-therapy protocols also revealed better anti-cancer effects with enhanced modulation of colonic sex steroid hormones and their receptors, with E/P the most prominent protocol. In vitro, E/P regimen showed the highest increases in the numbers of SW480 (2.1-fold) and SW620 (3.5-fold) cells in Sub-G1 phase of cell cycle. The E/P co-therapy also disclosed the lowest percentages of viable SW480 cells (2.8-fold), whilst both co-therapy protocols equally showed the greatest SW620 apoptotic cell numbers (5.2-fold) relative to untreated cells. Moreover, both co-therapy regimens revealed maximal inhibitions of cell cycle inducers, cell survival markers, and AR/ERα alongside the highest expression of cell cycle suppressors, pro-apoptotic molecules, and ERβ/PGR in both cell lines. In conclusion, CRC was associated with abnormal levels of colonic sex steroid hormones alongside aberrant protein expression of their receptors. While the anti-cancer effects of E2 and P4 monotherapies were equal, their combination protocols showed boosted tumoricidal actions against CRC in males, possibly by promoting ERβ and PGR-mediated androgen deprivation together with inhibition of ERα-regulated oncogenic pathways.