bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing SARS-CoV-2 Functional Druggability Through Multi-Target Cadd Screening of Repurposable Drugs
Authors: Gupta Yash , Maciorowski Dawid , Mathur Raman , Pearce Catherine M. , Ilc David J. , Husein Hamza , Bharti Ajay , Becker Daniel , Brijesh Rathi , Bradfute Steven B , Durvasula Ravi , Kempaiah Prakasha
Published: May 2020

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.
Assessment of the Weekly Fluctuations of the Covid-19 Cases in Italy and Worldwide
Authors: Bragato Pier Luigi
Published: May 2020

The time series of daily new cases of Covid-19 infection in different zones of Italy, several European countries and New York City were analyzed in order to characterize the large fluctuations contained in them. The comparison shows that the time series share a similar evolution, although with delays of one or two weeks, with Italy that precedes the other countries. Correlation analysis indicates a strict resemblance between the time series of the first differences, which emphasize accelerations and slowdowns of the epidemic (e.g., correlation coefficient r=0.70 for Italian vs. worldwide data). According to Fourier analysis the signals have a dominant oscillatory component at a period of seven days, with minima located near the weekends. Some of the possible causes of this time modulation are discussed. In particular, it is hypothesized a delayed or missed recognition of a significant fraction of the new cases during the weekend, with possible consequences for the evolution of the epidemic.
A Proactive Energy-Awareness Based Traffic Routing in Tree Topology Wireless Sensor Networks Precluding Energy Holes Formation
Authors: Mustafa Mayada S. A. , Ali Borhanuddin M. , Rasid Fadlee F. A. , Hashim Shaiful J. B.
Published: May 2020

A single tree topology is a commonly employed topology for wireless sensor networks (WSN) to connect sensors to one or more remote gateways. However, its many-to-one traffic routing pattern imposes heavy burden on downstream nodes, as the same routes are repeatedly used for packet transfer, from one or more upstream branches. The challenge is how to choose the most optimal routing paths that minimizes energy consumption across the entire network. This paper proposes a proactive energy awareness-based many-to-one traffic routing scheme to alleviate the above said problem referred to as Energy Balance-Based Energy Hole Alleviation in tree topology (EBEHA-T). This protocol combines updated status of variations in energy consumption pattern around sink-hole zones and distribution of joint nodes among the trees. With this approach, EBEHA-T proactively prevents sink-hole formation instead of just a reactive response after they have occurred. Performance evaluation of EBEHA-T against benchmark method RaSMaLai shows increased energy saving across the entire network and a marked improvement in energy consumption balance in energy-hole zones. This precludes energy hole formation and the consequent network partitioning, leading to improved network lifetime beyond that of the RasMaLai. OMNET++ network simulation software has been used for the evaluation.
Selective Cytotoxic Effects of Annona Squamosa Leaves against Breast Cancer Cells via Apoptotic Signaling Proteins
Authors: Al-Nemari Rawan , Ben Bacha Abir , Al-Senaidy Abdulrahman , Arafah Maha , Al-Saran Hadel , Abutaha Nael , Semlali Abdelhabib
Published: May 2020

: Annona squamosa L. is an important medicinal plant used in traditional medicine for the treatment of various diseases. Different parts of A. squamosa L. have various therapeutic effects; however, the anticancer activity of the leaves has not yet been identified. In vitro, MTT, nuclear staining, and LDH assays were used to evaluate cell survival and proliferation in cells exposed to the extracts. The effect of the extracts on cell migration was investigated using a monolayer wound repair assay, and the apoptotic effects were evaluated using flow cytometry. A breast cancer model was used to study the effect of the extract on the tumor size, and the expression of different proliferative and apoptotic markers was evaluated by immunohistochemical analysis. At a concentration of 100 µg/mL, A. squamosa leaf extracts exerted strong antiproliferative and cytotoxic effects against various cell lines. The extracts reduced wound closure and strongly induced apoptosis. In vivo study, rats were sacrificed 24 h after the last injection, and tumor size, as well as the expression of proliferative and apoptotic markers, were observed to be greatly affected by treatment with the extracts. Therefore, A. squamosa leaf extract may be developed as a potential novel drug to treat breast cancer in the future
Real-world Comparison of Visual Odometry Methods
Authors: Alapetite Alexandre , Wang Zhongyu , Hansen John Paulin , Zajączkowski Marcin , Patalan Mikolaj
Published: May 2020

Positioning is an essential aspect of robot navigation, and visual odometry an important technique for continuous updating the internal information about robot position, especially indoors without GPS. Visual odometry is using one or more cameras to find visual clues and estimate robot movements in 3D relatively. Recent progress has been made, especially with fully integrated systems such as the RealSense T265 from Intel, which is the focus of this article. We compare between each other three visual odometry systems and one wheel odometry, on a ground robot. We do so in 8 scenarios, varying the speed, the number of visual features, and with or without humans walking in the field of view. We continuously measure the position error in translation and rotation thanks to a ground truth positioning system. Our result show that all odometry systems are challenged, but in different ways. In average, ORB-SLAM2 has the poorer results, while the RealSense T265 and the Zed Mini have comparable performance. In conclusion, a single odometry system might still not be sufficient, so using multiple instances and sensor fusion approaches are necessary while waiting for additional research and further improved products.
COVID-19 Vaccines:A Race Against Time in the Middle of Death and Devastation!
Authors: Khuroo Mohammad , Khuroo Mohammad , Khuroo Mehnaaz , Sofi Ahmad , Khuroo Naira
Published: May 2020

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.
DELINEASI SUB-CEKUNGAN SORONG BERDASARKAN ANOMALI GAYA BERAT
Authors: Zaenudin Ahmad , Dani Ilham , Amalia Niar
Published: May 2020

Delineasi Sub-Cekungan Sorong ini diinterpretasi melalui pola anomali gayaberat, pola patahan, bukaan (rifting), tinggian dari anomali residual, dengan analisis Second Vertical Derivative (SVD), pemodelan 2D dan structural noses. Metode pengolahan data yang dilakukan dalam penelitian ini ialah melakukan koreksi gaya berat hingga didapatkan Anomali Bouguer Lengkap, melakukan analisis spektrum untuk mendapatkan estimasi kedalaman regional dan residual serta lebar jendela penapisan, melakukan pemisahan anomali regional dan residual dengan metode moving average, melakukan analisis SVD, melakukan interpretasi kualitatif dan kuantitatif. Hasil pengolahan menunjukkan bahwa pola Anomali Bouguer Lengkap daerah penelitian pada bagian Selatan didominasi oleh anomali rendah dengan nilai 58 hingga 76 mGal. Sedangkan anomali tinggi mendominasi bagian Utara dengan nilai 88 hingga 106 mGal. Kedalaman residual sekitar 2,7 km di bawah permukaan sedangkan kedalaman regional sekitar 10 km di bawah permukaan. Anomali residual daerah penelitian memiliki nilai anomali -9 hingga 10 mGal. Anomali regional daerah penelitian memiliki nilai anomali 60 hingga 100 mGal. Berdasarkan interpretasi kualitatif dan kuantitatif menunjukkan bahwa terdapat satu sub-cekungan pada daerah penelitian yang terletak pada Arar nose. Arah migrasi hidrokarbon berasal dari arah Barat ke Timur mengikuti struktur patahan. Berdasarkan penelitian ini, diasumsikan bahwa sesar utama Sorong tidak hanya berupa jenis sesar geser namun juga merupakan jenis sesar normal.
KARAKTERISTIK GEMPABUMI DI SESAR MATANO MENGGUNAKAN ANALISIS ENERGI KUMULATIF DAN PERIODE ULANG
Authors: Kurniawati Indah , Ratri Aldilla Damayanti Purnama , Gunawan Tomy
Published: May 2020

Aktifitas seismik Sesar Matano sangat tinggi di mana gempabumi sering dirasakan masyarakat dan mengakibatkan kerusakan di area sekitarnya. Identifikasi aktifitas gempabumi dengan mengetahui besarnya energi yang dilepaskan di 6 segmen pada Sesar Matano diperlukan untuk perencanaan mitigasi gempabumi. Dilakukan juga estimasi  periode ulang gempabumi yang akan terjadi disertai kemungkinan energi yang akan dilepaskan oleh gempabumi di masa yang akan datang. Data yang digunakan adalah katalog gempabumi EHB dan BMKG tahun 1961-2019. Energi gempabumi dihitung dengan mengkonversikan nilai momen seismik ke dalam energi fisis gempabumi. Sedangkan nilai momen seismik didapatkan dari konversi magnitudo gempabumi. Nilai periode ulang didapatkan dengan membagi nilai slip rata-rata terhadap sliprate. Berdasarkan hasil pengolahan data yang dilakukan di 6 segmen berbeda, yaitu Segmen Kuleana, Pewusai, Matano, Pamsoa, Ballawai, dan Garessa masing-masing memiliki nilai potensi magnitudo maksimum yang sedikit berbeda dengan magnitudo maksimum yang dikeluarkan PUSGEN. Semakin besar potensi magnitudo maksimumnya, maka semakin lama pula potensi gempa tersebut akan kembali berulang.
STUDI ZONA SESAR MENGGUNAKAN METODE GEOLISTRIK RESISTIVITAS DAN DATA GEOLOGI PERMUKAAN DI KECAMATAN UJUNGLOE KABUPATEN BULUKUMBA
Authors: Yusran Muhammad , Massinai Muhammad Altin , Syahruddin Muhammad Hamzah
Published: May 2020

Kabupaten Bulukumba merupakan daerah yang berpotensi mengalami bencana gempa bumi karena adanya aktivitas sesar walanae di dataran Bulukumba. Penelitian ini bertujuan mengetahui (1) gambaran struktur geologi pada daerah penelitian dan (2) keberadaan zona sesar dan gambaran struktur bawah permukaan berdasarkan metode geolistrik pada daerah penelitian. Identifikasi awal kenampakan sesar di daerah penelitian dimulai dengan analisis citra dari Google Earth, pengamatan lapangan terhadap pencirian sesar, kemudian dilakukan pengukuran menggunakan metode geolistrik resistivitas konfigurasi Wenner-Schlumberger untuk mendapatkan nilai tahanan jenis untuk setiap perlapisan batuan di bawah permukaan. Pengukuran dilakukan pada dua lintasan yang berbeda dengan panjang lintasan masing-masing 300 m dan jarak antar elektroda sebesar 5 m. Data-data yang diperoleh kemudian diolah dan diinterpretasikan untuk menarik kesimpulan hasil penelitian. Hasil penelitian menunjukkan bahwa terdapat aktivitas sesar di daerah penelitian yang ditandai dengan terbentuknya lembah Sungai Bijawang, penurunan bidang daratan yang membentuk bidang horst dan graben serta adanya pembelokan yang cukup tajam pada alur sungai dan gawir sesar yang terdapat di sepanjang lembah pada jalur sungai tersebut. Selain itu, berdasarkan hasil pengolahan data geolistrik resistivitas disimpulan bahwa terdapat zona sesar di daerah penelitian berdasarkan interpretasi penampang 2D dari data hasil inversi nilai resistivitas, dimana struktur perlapisan batuan antara lintasan 1 dan lintasan 2 memiliki karakteristik yang identik sehingga mengindikasikan keterdapatan aktivitas sesar mendatar yang telah memisahkan kedua bidang tersebut. Struktur perlapisan tanah di daerah penelitian di dominasi oleh lapisan lempung berpasir dengan nilai tahanan jenis berkisar antara 100 - 400 Ωm dan 10 – 200 Ωm.Kata Kunci: zona sesar; geolistrik; struktur geologi.
PENENTUAN NILAI RESISTIVITAS UNCONSOLIDATE SAND PADA LOW MOISTURE CONTENT MENGGUNAKAN MIKROAMPERMETER PADA ALIRAN SUNGAI KRASAK, SLEMAN, DAERAH ISTIMEWA YOGYAKARTA
Authors: Setiahadiwibowo Ajimas Pascaning , Nugroho Ocky Bayu , Pratama Yudha Agung
Published: May 2020

Uji resistivitas unconsolidated sand pada low moisture content menggunakan peralatan dengan resolusi mikroampermeter. Nilai resistivitas pada penelitian ini dipengaruhi oleh banyaknya air yang terdapat pada endapan pasir. Penelitian ini dilakukan dengan mengambil 3 conto yang tersebar pada endapan Sungai Krasak, Kabupaten Sleman. Nilai resistivitas pada penelitian ini diperoleh dari conto yang dikeringkan kemudian ditambahkan air secara bertahap (3 ml). Berdasarkan hasil penelitian ini maka nilai resistivitas endapan pasir lepas di Sungai Krasak berkisar antara 23,31 Ωm – 1086,302 Ωm, semakin jauh dari batuan sumber maka sebaran variasi nilai resistivitas lebih bervariasi dan semakin tinggi moisture content maka nilai resistivitas semakin rendah.
Early-stage clinical outcomes and rotational stability of TECNIS toric intraocular lens implantation in cataract cases with long axial length
Authors: He Suhong , Chen Xiang , Wu Xingdi , Ma Yajuan , Yu Xuewen , Xu Wen
Published: May 2020

Background: A major focus of toric intraocular lens (IOL) implantation is the rotational stability, especially in the patients with long axial length (AL). In this study, we aimed to evaluate the clinical outcomes after implantation of TECNIS toric IOL in eyes with long AL and identify factors influencing their early-stage stability with preoperative corneal astigmatism.Methods: The study population consisted of 64 eyes from 52 cataract patients, and these patients had preoperative corneal astigmatism between 1.0 and 3.7 diopters (D) and underwent phacoemulsification and TECNIS toric IOL implantation. Ophthalmic biological measurements were carried out preoperatively, including AL, anterior chamber depth (ACD), lens thickness (LT), vitreous length (VL), anterior chamber volume (ACV), sulcus-to-sulcus (STS) and keratometric value (K). Clinical examinations, including visual acuity, manifest refraction, keratometry, digital anterior segment photographs with pupillary dilation, were performed at 1 and 3 months after surgery. Results: The mean best corrected distance visual acuity (BCDVA) was improved from 0.93±0.35 logarithms of the minimal angle of resolution (logMAR) preoperatively to 0.07±0.10 logMAR postoperatively at 3 months after surgery. The mean residual astigmatism (RAS) was 0.91±0.74D at 3 months, which was significantly decreased compared with the preoperative corneal astigmatism of 1.71±0.55 D. The mean absolute rotation of TECNIS toric IOL at 1 and 3 months was 7.42±11.32 degree (°) (0-79°) and 7.48±11.19°(0-79°), respectively. The mean area of capsulorhexis and the overlapped area between capsulorhexis and optic intraoperatively was 21.04±3.30 mm2 and 7.40±2.87 mm2.A positive correlation was found between IOL rotation and the area of capsulorhexis (p=0.017) at 3 months after surgery. No correlation was found between IOL rotation and AL (p=0.876), ACD (p=0.387), LT (p=0.523), VL (p=0.546), ACV (p=0.480), STS (p=0.884), K1 (p=0.429)，K2 (p=0.644), average of K1 and K2 (p=0.520), intraoperative IOL axial direction (p=0.396), preoperative corneal astigmatism (p=0.269) or the overlapped area between capsulorhexis and optic intraoperatively (p=0.131) .Conclusions: The large CCC was a risk factor for toric IOL rotation. An appropriately smaller sized CCC was conducive to increase the rotational stability of TECNIS toric IOL implantation in cataract cases with long AL.
WITHDRAWN: Transconjunctival Cryo-Assisted Extraction of Intraconal Cavernous Hemangioma
Authors: ghafar ayman el sayed abd el sayed , Saleh Sameh M , Elwehidy Ahmed S , awara amr mahmoud
Published: May 2020

Background: The aim of this study is to evaluate the safety and efficacy of cryo-assisted transconjunctival orbitotomy for the extraction of intraconal cavernous hemangiomas.Methods: The study was performed at the Mansoura Ophthalmic Center, Mansoura University, Egypt from May 2017 to August 2018 and included 18 patients with orbital intraconal cavernous hemangiomas. In all the cases, preoperative orbital magnetic resonance imaging (MRI) with contrast was performed, the transconjunctival approach was used and cryo-assisted lesion extraction was performed. Cases were followed for six months after the surgery.Results: This study included 18 patients with intraconal cavernous hemangiomas, ten females (55.6%) and eight males (44.4%) with a mean age of 35.6 years. .The hemangiomas were lateral to the optic nerve in eight(44.5%), above the optic nerve in four cases(22.2%), and below the optic nerve in six cases(33.3%). Eight cases had postoperative complications: three cases (16.7%) had postoperative diplopia due to lateral rectus paresis that improved in all three cases within six months, one case (5.6%) had postoperative retrobulbar hemorrhage and proptosis that resolved within two weeks without sequelae, and four cases (22.2%) showed subconjunctival hemorrhages which resolved within two weeks. Of the two cases with preoperative decreases in visual acuity preoperative, one case (5.6%) showed improvement and one case (5.6%) did not improve. Conclusions: Cryoprobe-assisted transconjunctival orbitotomy for the excision of intraconal cavernous hemangiomas is a good approach with minor resolvable complications.Ethics approval : Mansoura institutional review board (IRB)Registration number: R/17.05.26Registration date: 10/5/2017Trial Registration:Name of registry: ISRCTN RegisterTrial registration number: ISRCTN45970569Retrospectively registered on 24/4/2020
Effect of grape seed proanthocyanidin extract in peripheral blood mononuclear cells of severe asthmatic patients
Authors: Sun Yun , Gu Bin , Qian Yan , Chen Yi , Mao Zheng-dao , Shi Yu-jia , Cao Qi , Wu Di , Zhang Qian
Published: May 2020

Backgroud To explore the Effect of grape seed proanthocyanidin extract（GSPE） in peripheral blood mononuclear cells of severe asthmatic patients. Methods 40 severe asthmatic patients were randomly and averagely divided into 2 groups: DXM group (n=20) and GSPE+DXM group (n=20), and 20 healthy volunteers as control gorup. Heparinized peripheral venous blood from each subject was collected in a sterile vacuum tube. The levels of interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 were detected by ELISA. The protein and mRNA expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2), glutamatecysteine ligase modifier subunit (GCLM) inducible nitric oxide synthase (iNOS) and inactivation of histone deacetylase-2 (HDAC2) were detected by Western blot and qRT-PCR respectively. Glutathion(GSH) was measured by using Glutathione Fluorometric Detection Kit, and Nrf2-ARE binding ability was measured by using TransAM Nrf2 Transcription Factor ELISA Kit. Results The results showed that the levels of IL-8 and MCP-1 in normal control group were lower than those in severe asthma group (P <0.05). Treatment with GSPE+DXM reduced the levels of IL-8 and MCP-1 significantly when compared with DXM only ( P <0.05).The mRNA expression of iNOS in DXM group was significantly higher than that in control group. However, after adding GSPE treatment, the expression dramatically decreased ( P <0.001). On the contrary, lower mRNA expressions of Nrf2, GCLM and HDAC2 were found in DXM group than in control group ( P <0.001). Accordingly, when treated with GSPE, these expressions elevated and reached a statistical significance ( P <0.05). Consistently, the results from western blot analysis confirmed the role of GSPE on the protein expressions of iNOS, Nrf2, GCLM and HDAC2 in PBMCs of patients with severe asthma ( P <0.001). The PBMCs from patients with severe asthma exhibited lower Nrf2-ARE binding ability and produced less GSH than normal controls. GSPE treatment effectively augmented the Nrf2-ARE binding ability and the expression of GSH, which demonstrated the biological antioxidant potential of GSPE ( P <0.001). Conclusion GSPE can alleviate glucocorticoid resistance by regulating Nrf2-iNOS-HDAC2 signaling pathway in severe asthma, suggesting that GSPE have potential clinical application prospects in the treatment of severe asthma.
Reinvestigation of the origins of pineal meningiomas based on its related veins and arachnoid membranes
Authors: Yu Lei , Orazmyradov Berdimyrat , Qi Songtao , Song Ye , Fang Luxiong
Published: May 2020

Background: A series of patients harboring pineal region meningiomas were respectively analyzed to explore the origin of these tumors and the true meaning of the term "velum interpositum (VI) meningiomas".Methods: 21 patients with pineal meningiomas underwent operation in Nanfang Hospital of Southern Medical University from January 2005 to December 2016 were retrospectively included to analyze the clinical features, imaging findings and surgical video data of these patients. According to the method of literature, the data of this group were also divided into falcotentorial (FT) meningiomas and VI meningiomas, and the differences between the two types of tumors were compared.Results: Among the 21 cases of tumor, there were 12 cases of FT meningiomas, including 4 cases originating from cerebral falx, 4 cases from tentorium of cerebellum and 4 cases from straight sinus; there were 9 cases of VI meningiomas, 7 of which originated from the arachnoid sleeve of the Galen vein, 1 from the posterior part of the internal cerebral vein and 1 from the posterior surface of the pineal gland. Postoperative pathological examination showed meningiomas in all the 21 patients, including 16 cases of total resection and 5 cases of subtotal resection. Postoperatively limitation of binocular vertical motion was found in 3 cases, homotropic hemianopia in 7 cases, hemiplegia in 1 case and death in 1 case.Conclusions: This study suggests that pineal meningiomas are more suitable to be described by FT meningioma and meningiomas of the arachnoid of the pineal region by analyzing the origin of tumors. The term "VI meningiomas" can only reflect a part of meningiomas of the arachnoid of the pineal region. Before the removal of pineal meningiomas, more attention should be paid to the effects of the two types of tumors on the Galen vein and the straight sinus, and the establishment of venous collateral circulation.
Glycinin-induced porcine IPEC-J2 cells damage via the NF-κB/MAPK signaling pathway
Authors: Peng Chenglu , Sun Zhifeng , Wang Lei , Shu Yingshuang , He Mengchu , Ding Hongyan , Li Yu , Wang Xichun , Feng Shibin , Li Jinchun , Wu Jinjie
Published: May 2020

Background: Glycinin, a protein found in soybean, is a human and animal allergen that causes damage to the intestinal barrier. However, its mechanisms of action remain unclear. Therefore, in this study, the intestinal porcine epithelial cell line IPEC-J2 was used to evaluate the effect of glycinin concentration on the intestinal epithelium and identify the related signaling pathways. Results: IPEC-J2 cells were divided into seven treatment groups and a control group; the cells were treated for 24 h with 1, 5, or 10 mg/mL glycinin or with 5 mg/mL glycinin after 30 min of pre-treatment with 1 μmol/L nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), inducible nitric oxide synthase inhibitor ( N -ω-nitro-l-arginine methyl ester), Jun N-terminal kinase (JNK) inhibitor (SP600125), or p38 inhibitor (SB202190). A series of molecular and biochemical experiments revealed that the levels of NF-κB, p38, and JNK, as well as their downstream proteins, were increased after treatment compared to those in the control group. Conclusion: Glycinin damaged IPEC-J2 cells in a concentration-dependent manner via the NF-κB/MAPK signaling pathway.
Closed-loop target-controlled infusion system for propofol guided by bispectral index applied in patients undergoing shoulder arthroscopy in the beach chair position- a randomized controlled trial
Authors: Zhao Zhao , Li Junjie , Fang Yang , Nanbo Luo , Han Yang , Xinping Yang , Liangquan Peng , Wei Lu , Fang Guangguang , Daping Wang , Liu Zhiheng
Published: May 2020

Background To compare the efficacy of anesthetic depth control using closed-loop and open-loop target controlled infusion (TCI) system of propofol guided by BIS in patients undergoing shoulder arthroscopy in the beach chair position (BCP). Methods 120 patients underwent shoulder arthroscopy surgery in the BCP were randomized into two groups, the open-loop (O) group and the closed-loop (C) group. During the maintenance phase, BIS value was used as the feedback variable for TCI system of propofol in both groups. The Global score (GS) and the percentage of adequate anesthesia, the frequency of propofol regulation, and consumption of propofol were calculated. The MMSE scores of the day before and 1 day after surgery, serum GFAP and S100B proteins before anesthesia, after extubation and 1 day after surgery were compared. Results The GS and the proportion of appropriate anesthesia time were better in the group C. The percentage of overshoot time was lower in the group C. The frequency of propofol regulation was observed higher in the group C. Propofol consumption in the group C was significantly lower than that in the group O. The MMSE scores, the GFAP and S100B protein concentrations had no significant difference between the two groups. Conclusion Propofol administration using close-loop TCI system guided by BIS may increase the percentage of adequate anesthesia and shorten the percentage of overshoot time compared with open-loop TCI model in anesthesia maintenance phase in patients undergoing shoulder arthroscopy in the BCP, and do not increase the risk of POCD.
Trial staff views on barriers recruitment in a digital intervention for psychosis and how to work around them: A qualitative study within a trial
Authors: Allan Stephanie , Mcloed Hamish , Bradstreet Simon , Morton Emma , Bell Imogen , Wilson-Kay Alison , Whitehill Helen , Clark Andrea , Matrunola Claire , Farhall John , Gleeson John , Gumley Andrew
Published: May 2020

Background: Recruitment processes for clinical trials of digital interventions for psychosis are seldom described in detail within the literature. While trial staff have expertise in describing barriers and facilitators to recruitment a specific focus on understanding recruitment from the point of view of trial staff is rare.Methods: We applied pluralistic ethnographic methods including analysis of trial documents, observation and focus groups explored the recruitment processes of the EMPOWER feasibility trial (ISRCTN: 99559262).Results: Recruitment barriers fell into two main themes; service characteristics (lack of time available to mental health staff to support recruitment, staff turnover, patient turnover (within Australia only), management styles of community mental health teams, physical environment) and clinician expectations (filtering effects and resistance to research participation). Trial staff negotiated these barriers through strategies such as emotional labour (trial staff managing feelings and expressions in order to successfully recruit participants) and trying to build relationships with clinical staff working within community mental health teams.Conclusions: Researchers in clinical trials for digital psychosis interventions face numerous recruitment barriers and do their best to work flexibly negotiate these barriers and meet recruitment targets. The recruitment process appeared to be enhanced by trial staff supporting each other throughout the recruitment stage of the trial.Trial Registration: (ISRCTN: 99559262 registered 21/12/2015)
MiR-199b-3p prevent the epithelial-mesenchymal transition (EMT) and fibrosis of renal tubule by regulating E-cadherin through targeting KDM6A in Diabetic nephropathy (DN)
Authors: Tang Bo , Li Weiliang , Ji Tingting , Li Xiaoying , Qu Xiaolei , Bai Shoujun
Published: May 2020

Background

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Although dysfunction of renal tubule, also exhibited as epithelial-mesenchymal transition (EMT) and fibrosis, is closely associated with DN, the mechanism underlying renal tubule dysfunction still remains obscure.
Methods

Here, we identify that miR-199b-3p protect renal tubule from diabetic- induced injury by repressing KDM6A, a histone lysine demethylase reinforcing diabetic renal tubule dysfunction through regulating E-cadherin expression. We investigated the relationship between KDM6A, E-cadherin and miR-199b-3p with a series of gain- and loss- function assay in different cell models and animal models. The expression of KDM6A, E-cadherin and miR-199b-3p was tested by qPCR, western bolt or IHC. The EMT was measured by wound healing assay. The dysfunction of renal tubule were observed through HE and PAS stain and the kidney functions were monitored through several pathological signs detection assay, such as albumin to creatinine ratio (ACR), blood urea nitrogen (BUN), creatinine (Cr), proteinuria.
Results

Lower expression of E-cadherin was related to a higher level of KDM6A, while E-cadherin was increased with KDM6A-inhibitor GSK-J4 treatment both in HG-induced HK-2 cells and STZ-induced kidney. However, the variable expression of E-cadherin caused by overexpression or silence RNA was failed to alter the KDM6A expression. The target prediction and dual-luciferase assay results showed miR-199b-3p is a new miRNA targeting KDM6A. Overexpression of miR-199b-3p increased E-cadherin expression and prevented EMT through repressing KDM6A expression in HG-induced HK-2 cells, whereas miR-199b-3p knockdown by inhibitor displayed opposite results with lower E-cadherin and worse EMT accompanying with higher level of KDM6A. In addition, the miR-199b-3p knockout mice exhibited more dysfunctional renal tubule and more serious damage in kidney tissue treated with STZ.
Conclusions

These results demonstrate that miR-199b-3p improve E-cadherin expression and prevent the progression of DN through targeting KDM6A. MiR-199b-3p could be a potential biomarker or target for the diagnosis and treatment of diabetic nephropathy in the future.
LINC01255 combined with BMI1 to regulate Human Mesenchymal Stromal Senescence and Acute myeloid leukemia cell proliferation through repress the transcription of MCP-1
Authors: Liu Qinghua , Dong Jing , Li Jie , Duan Yanchao , Wang Keqiang , Kong Qiuhong , Zhang Hong
Published: May 2020

Background: Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular biology processes, for example, participate in chromatin remodeling, imprinting, splicing, transcriptional regulation and translation. Dysregulation of lncRNA expression is act as a feature of various diseases and cancers, including hematopoietic malignancies. However, the clinical relevance of myelodysplastic syndrome (MDS) and acute myeloid leukemia preceded by MDS (MDS-AML) requires further research. Recently, lncRNAs have been demonstrated plays an important role in hematopoiesis, thus, to further finding more functional lncRNA seemed particularly important.Methods: Western blotting, real-time PCR, RNA-pulldown, RIP, Chromatin immunoprecipitation (ChIP), cellular compartments extraction assays, SA-β-gal staining, lentivirus transfection, cell viability assay and cell proliferation assays were used to examine the relationship between lncRNA LINC01255 and its regulation of p53-p21 pathway in human mesenchymal stromal and acute myeloid leukemia cells.Results: LncRNA LINC01255 is highly expressed in bone marrow cells of AML patients, CD34+ cells of MDS-AML patients and AML cell lines and the higher expression of LINC01255 is assocoated with poor survival rate of AML patients. LINC01255 can interact with BMI1 and repress the transcription of MCP-1 to active p53-p21 pathway, thus inhibiting the senescence of human mesenchymal stromal and proliferation of acute myeloid leukemia cell.Conclusions: We discovered a novel functional lncRNA LINC01255, which can regulate the senescence of human mesenchymal stromal and the proliferation of acute myeloid leukemia cell through inhibiting the transcription of MCP-1.
Age associated level of estradiol (E2) and progesterone (4) influence IL-8 response to Mycobacterium tuberculosis (Mtb) antigens in women.
Authors: MENSAH Priscillia Virginie Liesse MBOUROU , LEBOUENY Marielle , ESSONE Paulin NDONG , SIAWAYA Anicet Christel MALOUPAZOA , ALAME-EMANE Amel Kévin , BIYOGO Oriane Cordelia ABOUMEGONE , TADATSIN Patrice Hemery DAPNET , NZOGHE Amandine MVEANG , ESSAMAZOKOU Dimitri Ulrich , NDJINDJI Ofilia MVOUNDZA , PADZYS Guy-Stéphane , ONDO Joseph Privat , TAKIFF Howard , GICQUEL Brigitte , Siawaya Joel Fleury Djoba
Published: May 2020

Tuberculosis (TB) is an intracellular infection controlled the effective recruitment of effectors immune cells at infection site. In aged premenopausal or menopausal women, there is an increased pro-inflammatory cytokines secretion suggesting an underlying link between cytokines response and estrogen (E2) and progesterone (P4) levels. In this study we compared women aged 40 years old and above (premenopausal) and women aged below 40 years old with and without latent TB infection to determine the link between E2, P4 and cytokines response to Mycobacterium tuberculosis (M. tuberculosis) stimuli. E2 and P4 levels were significantly higher in women under 40 years old than in women above 40 years old irrespective their LTB status (p < [0.0001–0.05]). In women under 40 years old, E2 and P4 were found to correlate negatively and significantly with IL-8 response to M. tuberculosis antigens stimulation ((p < [0.001–0.01]). Furthermore, M. tuberculosis IL-8 specific response was significantly higher in women above 40 years old than women under 40 years old. This study demonstrates that women aging and the linked hormonal changes are associated with hence IL-8 response to M. tuberculosis antigen, which may have implications for the age-related susceptibility or resistance to active tuberculosis.
Trends in the outpatient-visits and allergens of allergic rhinitis in Chongqing, China from 2008 to 2017
Authors: shen yang , Zou Qi-Yuan , Li Jia , Ke Xia , Kang Hou-Yong , Hong Su-Ling
Published: May 2020

Background The prevalence of allergic rhinitis (AR) has increased globally. This study was conducted to investigate the changing trends of AR’ s outpatient visits and inhaled allergens, also the possible association between air pollution and AR visits in Chongqing, China.Methods We analyzed all the skin prick test results from patients diagnosed as AR in Departments of Otolaryngology of the first affiliated hospital of Chongqing Medical University during 2008 to 2017. The trend of AR visit rate and inhaled allergens was observed. Then, air quality data were acquired from the Chongqing Municipal Environmental Protection Monitoring Center. We explored the effects of air pollutants (SO2, NO2, PM2.5, PM10, CO and O3) on outpatient visits for AR.Results From 2008 to 2017, the ratio of AR outpatient visits increased. The number of polysensitization was more than that of monosensitization. However, the rate of mono-specific sensitization to dust mite allergen was on the increase, especially in patients of 20–39 y. No correlations were found between AR visits and pollutants, while mono-mite-sensitized AR visits were significantly correlated with the concentrations of atmospheric SO2, PM10 and PM2.5.Conclusions the rising trends in AR visits reflect both a real increase in the occurrence and a more effective diagnosis of cases. Increment in mono-mite sensitization implies the rising trends of new AR cases. The significant correlation between mono-mite-sensitized AR visits and concentration of SO2, PM10 and PM2.5 supports opinion about an influence of atmospheric pollutants on mite induced immune response in AR.
Short bouts of gait data and inertial sensors can provide reliable measures of spatiotemporal gait parameters from bilateral gait data of participants with multiple sclerosis
Authors: Ader Lilian Genaro Motti , Greene Barry R. , McManus Killian , Tubridy Niall , Caulfield Brian
Published: May 2020

Background:Wearable devices equipped with inertial sensors enable objective gait assessment for persons with multiple sclerosis (MS), with potential use in ambulatory care or home and community-based assessments. However, gait data collected in non-controlled settings is often fragmented and may not provide enough information for reliable measures. We evaluate a novel approach, extracting pre-defined numbers of gait cycles from the full length of a walking task, and their effects on the reliability of spatiotemporal gait parameters.Methods:The present study evaluates intra-session reliability of spatiotemporal gait parameters for short bouts of gait data extracted from the full length of the walking tasks to 1) determine the effects of the length of the walking task on the reliability of calculated measures and 2) identify spatiotemporal gait parameters that can provide reliable measures for gait assessments and reference data in different settings.Thirty-seven participants (37) diagnosed with relapsing-remitting MS (EDSS rage 0 to 4.5) executed two trials, walking 20m each, with inertial sensors attached to their right and left shanks. Previously published algorithms were applied to identify gait events from the medio-lateral angular velocity. Short bouts of gait data were extracted from each trial, with lengths varying from 3 to 9 gait cycles. Twenty-one measures of spatiotemporal gait parameters were calculated. Intraclass correlation coefficients (ICCs) were calculated to evaluate how the degree of agreement between the two trials of each participant varied with the number of gait cycles included in the analysis.Results:Spatiotemporal gait parameters calculated as the mean across included gait cycles reach excellent reliability from three gait cycles. Stride time variability and asymmetry, as well as stride velocity variability and asymmetry, reach good reliability from six gait cycles and should be further explored for persons with MS, while stride time asymmetry and step time asymmetry do not seem to provide reliable measures and should be reported carefully.Conclusion:Short bouts of gait data, including at least six gait cycles of bilateral data, can provide reliable gait measurements for persons with MS, opening new perspectives for gait assessment using wearable devices in non-controlled environments, to support monitoring of symptoms of persons with neurological diseases.Trial registrationNot applicable.
A Cohort Study Evaluating the Association Between Concurrent Mental Disorders, Mortality, Morbidity, and Continuous Treatment Retention for Patients in Opioid Agonist Treatment (OAT) Across Ontario, Canada Using Administrative Health Data
Authors: Morin Kristen , Eibl Joseph K , Gauthier Graham , Rush Brian , Mushquash Christopher , Lightfoot Nancy E , Marsh David
Published: May 2020

Background: Due to the high prevalence of mental disorders among people with opioid use disorder, the objective of this study was to determine the association between concurrent mental disorders, mortality, morbidity and continuous treatment retention for patients in opioid agonist treatment in Ontario, Canada. Methods: We conducted a retrospective cohort study of patients enrolled in opioid agonist treatment between January 1, 2011, and December 31, 2015. Patients were stratified into two groups: those diagnosed with concurrent mental disorders and opioid use disorder and those with opioid use disorder only, using data from the Ontario Health Insurance Plan Database, Ontario Drug Benefit Plan Database. The primary outcome studied was all-cause mortality using data from the Registered Persons Database. Emergency Department visits from the National Ambulatory Care Database, hospitalizations Discharge Abstract Database, and continuous retention in treatment, defined as one year of uninterrupted opioid agonist treatment using data from the Ontario Drug Benefit Plan Database, were measured as secondary outcomes. Encrypted patient identifiers were used to link information across databases.Results: We identified 55,924 individuals enrolled in opioid agonist treatment, and 87% had a concurrent mental disorder diagnosis during this period. We observed that having a mental disorder was associated with an increased likelihood of all-cause mortality (Odds Ratio (OR) 1.4; 95% Confidence Interval (CI) 1.2-1.5, frequent emergency department visits (OR 3.69; 95% CI 3.7-4.1) and hospitalizations (OR 2.6; 95%CI 2.5-2.7). However,there was no association between having a diagnosis of a mental disorderand one-year treatment retention in OAT OR 1.0; 95%CI 0.9-1.1). Conclusion: Our findings highlight the consequences of the high prevalence of mental disorders for individuals with opioid use disorder in Ontario, Canada
Inhibition Mechanism of Caffeine in Tea Pathogenic Fungi Botryosphaeria Dothidea and Colletotrichum Gloeosporioides
Authors: Thangaraj Kuberan , Deng Cheng , Cheng Lin-Lin , Deng Wei-Wei , Zhang Zheng-Zhu
Published: May 2020

Background Caffeine acts as an antifungal agent; however, its underlying inhibition mechanism remains unclear. To investigate variations in caffeine antifungal activity, this study was evaluate the inhibition mechanisms of caffeine on phytopathogens Botryosphaeria dothidea and Colletotrichum gloeosporioides through transcriptomic analysis, which causes leaf necrosis and anthracnose on tea leaves, respectively.Results Our in vitro results shows that the antifungal activity of caffeine quite different between B. dothidea and C. gloeosporioides. Furthermore, microscopic observation and bioactivity assay results proved that caffeine destroyed the fungal protective layers (cell wall and cell membrane) and subcellular organelles. The transcriptomes of these two fungi exposed to different caffeine concentrations were analyzed by high-throughput sequencing and the results showed that caffeine repressed gene expression involved in the pathways of mRNA surveillance, ribosome biogenesis in eukaryotes, aminoacyl-tRNA biosynthesis, etc. Particularly, caffeine affected gene expression in melanin biosynthesis in C. gloeosporioides, resulting in the disturbances of melanin production and fungal pathogenicity. Manually infected tea leaves showed melanin pigment was important to appressorium development and fungal infection by histopathological observation and fungal biomass quantification. Besides, C. gloeosporioides successfully enters into the host tissue even plant could build multilayer defenses against the fungus, this might be due to the variation in pathogen targets and quantities of secondary metabolites by the host cells.Conclusions Overall, our findings indicate that caffeine in the environment can reduce the fungal growth and physiological activities. However, the genome-wide expression showed different transcriptional profiles between these fungal isolates. Thus, we believe that target of the caffeine varied among isolates and melanin may play a major role in fungus caffeine tolerance. Further in-depth research required to conclude this hypothesis.