bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and radiological characteristics of adult hospitalized coronavirus disease-2019 patients of Dhaka, Bangladesh
Authors: Suman AHM Khairul Imam , Begum Khadija , Rahman Kaniz , Khan Saiful Bahar , Alam Mohammad Morshad
Published: March 2022

The severity of Coronavirus disease-2019 (COVID-19) varies among individuals and some influential factors leads to critical infections and death. This study aimed to assess various clinical data of hospitalized patients and identify the determinants of critical COVID-19 infection. This was a cross-sectional study among hospitalized COVID-19 patients confirmed by reverse transcription polymerase chain reaction (RT-PCR). Data was collected from a single Centre between January to April 2021 by experienced physicians of Ad-din Medical College Hospital. All of the laboratory tests were performed by technical experts and the data was analyzed by Statistical package for the social sciences software. Among the study participants 25% were Intensive care unit (ICU) patients and the mean age of them were higher (59 years) than non-ICU (55 years) patients. Our analysis has identified diabetes mellitus (AOR=2.5, 95%CI: 1.1-5.4) and ischemic heart disease (AOR=3.1, 95%CI: 1.1-8.9) as significant predictor of critical outcome (ICU admission). Anemia (AOR=3.3, 95%CI: 1.5-7.4), lymphopenia (AOR=2.9, 95%CI: 1.2-7.1), and thrombocytopenia (AOR=4.2, 95%CI: 2.7-12.9) was also associated critical outcome. Biomarkers of kidney injury (creatinine, blood urea nitrogen), liver damage (alanine transaminase, aspartate aminotransferase, fibrinogen) and electrolyte imbalance (sodium and potassium level) were also significantly associated with critical infection. A higher d-dimer level (≥2.5) was the most important predictor (AOR=11.5, 95%CI: 5.4-24.6) of critical COVID 19 infections. The study has revealed socio-demographic, comorbidity, and radiological risk factors of critical COVID-19 infections. The identified risk factors would be considered for decision making during the treatment process.
Asian J. Med. Biol. Res. 2022, 8 (1), 16-23
PENERAPAN MODEL PEMBELAJARAN INKUIRI TERBIMBING UNTUK MENINGKATKAN HASIL BELAJAR IPA PADA SISWA KELAS I SD NEGERI 2 GLANGGANG
Authors: Wibowo Andi , Suryani Sri
Published: March 2022

Penelitian ini bertujuan untuk meningkatkan hasil belajar IPA siswa kelas I SD Negeri 2 Glanggang dengan menggunakan model pembelajaran inkuiri terbimbing. Model pembelajaran inkuiri terbimbing adalah model pembelajaran terdiri dari beberapa tahapan yaitu, orientasi masalah, merumuskan masalah, membuat hipotesis, menguji hipotesis, mengumpulkan dan menganalisis data serta membuat kesimpulan. Jenis penelitian ini adalah penelitian tindakan kelas (PTK) dengan model Kemmis & Mc Taggart. Penelitian ini dalam perencanaanya menggunakan sistem spiral refleksi diri yang dimulai dengan rencana, tindakan, pengamatan, refleksi, dan perencanaan kembali. Penelitian tindakan kelas ini terdiri dari dua siklus, dimana setiap siklus terdiri atas tahapan perencanaan, pelaksanaan, observasi dan refleksi. Subjek penelitian ini adalah siswa kelas I SD Negeri Glanggang Kecamatan Pakisaji Kabupaten Malang pada tahun pelajaran 2017/2018, dengan jumlah 50 siswa. Materi IPA yang digunakan dalam penelitian ini adalah materi IPA semester 2 yaitu gerak benda.  Hasil dari penelitian ini adalah hasil belajar siswa meningkat. Hasil belajar pada kegiatan pra tindakan diperoleh nilai rata-rata siswa 62 dengan ketuntasan belajar 58%. Hasil belajar pada siklus I nilai rata-rata siswa 74,42 dengan ketuntasan belajar 72%. Hasil belajar pada iklus II nilai rata-rata siswa meningkat  menjadi 80,82 dengan ketuntasan 82%. Berdasarkan hasil penelitian tersebut dapat disimpulkan bahwa penerapan model inkuri terbimbing dapat meningkatkan hasil belajar IPA pada siswa kelas I SD Negeri 2 Glanggang Kecamatan Pakisaji Kabupaten Malang.
Pengaruh Kebijakan Dividen, Leverage, Profitabilitas dan Likuiditas Terhadap Nilai Perusahaan
Authors: Handali Wilyani , Kurniawan Kurniawan , Mulyanta Suharto
Published: March 2022

The purpose of this reseacrh was to determine the effect of dividend distribution policies that use Dividend Payout Ratio (DPR), leverage used using Debt to Equity Ratio (DER), profitability needed by using Return On Assets (ROA) and Return on Equity (ROE) and measured liquidity by using the Current Ratio hampered the value of the company collected using price to book value (PBV) in mining sector companies listed on the Indonesia Stock Exchange (IDX) in 2014-2017.This type of research is causal research. The population in this research are mining companies listed on the Indonesia Stock Exchange (IDX) in 2014-2017. The sampling technique uses purposive sampling technique. From the participation obtained by 41 sectoral companies obtained samples obtained from 10 sectoral companies listed on the Indonesia Stock Exchange (IDX) in 2014-2017, so that the research data developed must be examined 40 observations. Data analysis techniques using multiple linear regression. Based on the results of this research indicate that the dividend policy does not affect the value of the company. Leverage has a negative and significant effect on firm value. Profitability with the proxy return on assets (ROA) does not affect the value of the company. Profitability with the proxy of return on equity (ROE) does not affect the value of the company. Liquidity does not affect the value of the company.
Implementasi PSAK 16 Pasca Adopsi IFRS Dan Pemberian Insentif Perpajakan Pada Perusahaan BUMN Sektor Infrastruktur Di Indonesia
Authors: Angelia Lisa , Tresna Mochamad Farhan , Firmansyah Amrie
Published: March 2022

Penelitian ini mengulas implementasi PSAK 16 pasca adopsi IFRS dan terbitnya PMK No. 191/PMK.010/2015 tentang Penilaian Kembali Aktiva Tetap Untuk Kepentingan Perpajakan Untuk Permohonan yang Diajukan Tahun 2015 dan 2016 sebagai insentif perpajakan untuk mendorong perusahaan menerapkan metode revaluasi. Penelitian ini menggunakan metode kualitatif dengan pendekatan analisis isi. Sampel yang digunakan adalah BUMN sektor infrastruktur yang go public. Data penelitian bersumber dari laporan keuangan perusahaan dari tahun 2015 hingga 2017 yang diperoleh dari www.idnfinancials.com dan situs resmi perusahaan. Dengan menggunakan purposive sampling, penelitian ini menggunakan sampel sebanyak 15 observasi (5 perusahaan selama 3 tahun). Penelitian ini menyimpulkan bahwa BUMN di sektor infrastruktur telah melaporkan aset tetapnya berdasarkan PSAK 16 dengan pengungkapan lengkap yang merinci dasar pengukuran aset tetap, metode penyusutan, taksiran umur ekonomis dan tingkat penyusutan, nilai tercatat bruto dan akumulasi penyusutan terkait pada awal dan akhir periode serta rekonsiliasi jumlah tercatat. Selain itu, dua dari lima perusahaan yang digunakan dalam penelitian ini, menerapkan insentif pajak pada 2015 hingga 2016 terkait revaluasi aset, yaitu PT Telekomunikasi Tbk. dan PT Garuda Indonesia Tbk.
New technologies can support data collection on endangered shark species in the Mediterranean Sea
Authors: Bargnesi F , Moro S , Leone A , Giovos I , Ferretti F
Published: March 2022

In the last 50 yr, shark populations showed steep declines in the Mediterranean Sea. The IUCN lists most Mediterranean species as threatened (55%), while considering 27.5% of them Data Deficient. Here, sharks are currently one of the rarest and more elusive groups of animals, and data from fisheries and scientific monitoring still insufficiently support robust abundance and distribution assessments. New technologies can fill this data gap by linking people and scientists through new monitoring strategies. SharkPulse, an international collaborative project, aims at creating a large world database of shark occurrence records by mining images on the web, social networks, and private archives. Here we analyzed 1186 sharkPulse records from the Mediterranean Sea. We collected records to characterize spatio-temporal patterns on 37 species, highlighting distribution changes for 5, and, by using generalized linear models, estimating trends in sighting for the most abundant species. With 273 records, Hexanchus griseus had the most sighting records since the beginning of the series. We identified pupping areas and aggregation sites for immature Prionace glauca and Isurus oxyrinchus; pinpointed strongholds of the Critically Endangered Squatina squatina to focus conservation efforts; and identified broader than previously reported regional distribution ranges for Alopias superciliosus, Dalatias licha, Heptranchias perlo, H. griseus, Oxynotus centrina, and P. glauca. We confirmed that fishing is still the major threat for Mediterranean sharks and call for a greater effort in controlling the emerging patterns with efficient conservation effort indexes. If properly standardized, opportunistic data can efficiently and cost-effectively advance our understanding of shark abundance, distribution, and conservation status.
miR-431-5p Regulates Apoptosis of Cardiomyocytes After Acute Myocardial Infarction via Targeting Selenoprotein T
Authors: GENG H , CHEN L , SU Y , XU Q , FAN M , HUANG R , LI X , LU X , PAN M
Published: March 2022

Acute myocardial infarction (AMI) represents the acute manifestation of coronary artery disease. In recent years, microRNAs (miRNAs) have been extensively studied in AMI. This study focused on the role of miR-431-5p in AMI and its effect on cardiomyocyte apoptosis after AMI. The expression of miR-431-5p was analyzed by quantitative real-time PCR (qRT-PCR). By interfering with miR-431-5p in hypoxia-reoxygenation (H/R)-induced HL-1 cardiomyocytes, the effect of miR-431-5p on cardiomyocyte apoptosis after AMI was examined. The interaction between miR-431-5p and selenoprotein T (SELT) mRNA was verified by dual-luciferase reporter assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. Cell viability was examined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. The results of qRT-PCR showed that the expression of miR-431-5p in AMI myocardial tissues and H/R-induced HL-1 cardiomyocytes was significantly increased. After interfering with miR-431-5p, the expression of SELT in HL-1 cells was up-regulated, cell apoptosis was decreased, cell viability was increased, and lactate dehydrogenase (LDH) activity was decreased. The dual-luciferase reporter assay confirmed the targeting relationship between miR-431-5p and SELT1 3’ untranslated region (UTR). In H/R-induced HL-1 cells, the simultaneous silencing of SELT and miR-431-5p resulted in a decrease of Bcl-2 expression, an increase of Bax expression, and an increase of cleaved-caspase 3 expression compared with silencing miR-431-5p alone. Also, cell viability was decreased, while LDH activity was increased by the simultaneous silencing of SELT and miR-431-5p. Interfering miR-431-5p protected cardiomyocytes from AMI injury via restoring the expression of SELT, providing new ideas for the treatment of AMI.
PEMBUATAN ALAT PENGUKUR TINGGI BADAN OTOMATIS BERBASIS ARDUINO
Authors: Bakri Muhammad Amin , Paridawati Paridawati , Sikki Ilyas , Handoyo Yopi , Sylviana Rika , Surahto Aep , Diningrum Jenny Primanita , Liliani Netta , Syahputra Novin , Asrika Sukwati Dewi , Apriliansyah Mario
Published: March 2022

The facilities used by Posyandu cadres in weighing and measuring the height of children under five are not sufficient, because apart from that, they are not feasible nor are they calibrated accurately. Especially for measuring the height of toddlers, so far the posyandu generally still use the manual method, Based on this background, a digital height measuring device was designed in order to refer to the mission of the Unisma Bekasi Faculty of Engineering in an effort to increase the quantity and quality of community service (PPM) in the field of applied technology (appropriate technology), so this program was implemented. The PPM partners targeted for this program are Posyandu Kemuning cadres, Jatirasa Village, Jatiasih District, Bekasi City. The results of the design of this tool complete the automatic height measurement which is quite satisfactory at the Kemuning Posyandu, Jatirasa Village, Jatiasih District, Bekasi City. Development of a baby height and body mass measurement tool based on the ATmega 8535 microcontroller by utilizing a phototransistor sensor.
AKSI MASYARAKAT MENJAGA IMUNITAS TUBUH DAN BERBAGI JAHE DI KECAMATAN TAMBUN SELATAN
Authors: Nusantara Dimas Taruna , Ridlo Azi Fais , Iskandar Tatang
Published: March 2022

The body's immune system is the most important thing to maintain a person's health to avoid Covid-19. Many people ignore their immunity in Tambun Selatan sub-district. In this activity, the author uses the method of conducting online webinar with descriptive analysis techniques. he activity plan is carried out by creating a whatsapp group first, then participants fill out the pre-test, and participate in webinar activities, followed by filling out the post-test, and ending with evaluation and follow-up activities. From the results of the webinar activity, 9 people felt very satisfied (45%), 10 people felt satisfied (50%), 1 person felt dissatisfied (5%) so that revalance can help people's knowledge.
SOSIALISASI PROTOKOL KESEHATAN DAN VAKSINASI SERTA PELATIHAN MANAJEMEN KEUANGAN BAGI RUMAH TANGGA
Authors: Pratiwi Fahrunisa , Risa Nurma , Putra Purnama
Published: March 2022

Since its appearance in 2019, the Covid-19 virus has quickly spread to various countries in the world. Indonesia is one of the countries with a fairly high number of positive COVID-19 cases. The high number of positive COVID-19 cases has prompted the Indonesian government to implement various policies to prevent the spread and transmission of Covid-19, starting with the imposition of Large-Scale Social Restrictions, the 5M Health Protocol Policy to the Covid-19 Vaccination Program. The purpose of this Real Work Lecture activity is to help prevent the spread and transmission of Covid-19 in the Griya Alam Sentosa Housing Block P19 RT 01 neighborhood through online socialization. Based on the results of the pre-test and post-test, there was an increase in the understanding and behavior of community prevention before and after the socialization. Other problems that have arisen due to the Covid-19 pandemic are the weakening of the economy, some people have difficulty in financial management because people have not planned well. The household financial management socialization and training program with the Money Lover application is carried out with the aim of helping the community in carrying out good financial management so that expenses are not greater than their income so as to avoid being dependent on debt with someone or a money lending institution.
Surface Characteristics of Dental Implant Doped with Si, Mg, Ca, and P Ions via Plasma Electrolytic Oxidation
Authors: Paek Seon-Yeong , Choe Han-Cheol
Published: March 2022

The surface characteristics of a dental implant doped with Si, Mg, Ca, and P ions via plasma electrolytic oxidation (PEO) were investigated using various experimental instruments. Plasma electrolytic oxidation of the alloy was performed in a solution containing Ca, P, Si, and Mg ions at 280 V for 3 min. The potentiodynamic polarization test of the porous surface was conducted in a 0.9% NaCl solution. The Si and Mg ion-doped HA films exhibited small and large micro-pores with uniform distributions after the PEO treatment. The micro-pores formed on the 5~20Mg/5Si coated samples were smaller than those on the Si and Mg ion-free CaP coated surfaces, as the Mg ion concentration increased. The XRD peaks of Si, Mg, Ca, and P appeared and the Si, Mg, Ca, and P were well distributed on the PEO-treated surface, especially on the top, valley and crest of the screw. The Ca/P ratio decreased as Mg content increased in the electrolyte. The diffraction peak of anatase TiO2 was observed on the Si and Mg ion HA film formed on the Ti-6Al-4V alloy. The adhesion force of the Si and Mg doped HA films increased with increasing Mg and Si ion concentrations. A passive region due to passive film formation was observed. The HA film surface with Si and Mg ions showed lower Ecorr and higher Icorr compared to the HA film surface without Si and Mg ions. And the Ipp and I300 for 5~20Mg/5Si formed on the Ti-6Al-4V alloy were lower than those of the surface coated with HA without Si and Mg ions.
Evaluation of the Genital Hygiene Behavior and Related Factors of Women Aged 15-49
Authors: Uzun Asiye , Ozturk Guzin Zeren , Aksu Saliha Busra
Published: March 2022

Aim: Approximately one million people in the world are exposed to urogenital tract infections every year and at least 75% of women have a history of genital infection. The frequency of vaginal infections in women aged 15-49 in Turkey is known to be 35-68%. Genital infections can be asymptomatic and can cause negativity in sexual and family life. Therefore, it is important to take preventive measures. Mentioning correct genital hygiene behaviors in the training and consultancy services provided by healthcare professionals helps people to increase their awareness. In our study, we aimed to evaluate women's genital hygiene behaviors and related factors.

Methods: Our study was carried out with 457 women between the ages of 15-49 in the Gynecology Outpatient Clinic of Nisa Hospital. The socio-demographic characteristics and gynecological characteristics of the subjects were collected by face-to-face interviews using the questionnaire form that consisted of 20 questions and the “Genital Hygiene Behavior Inventory”. The IBM SPSS version 22 program was used for statistical analysis.

Results: This study was conducted with 457 women. A significant negative correlation was found between the Genital Hygiene Behavior Inventory score and the number of pregnancies and number of children (p=0.028, r=-0.128, p=0.037, r=-0.128, respectively), and a significant positive correlation was found between education status, income status, and having children (p=0.010, p=0.000, p=0.007, respectively). Participants who stated that they had the knowledge and received this information from doctors and/or nurses had higher Genital Hygiene Behavior Inventory scores.

Conclusion: Questioning genital complaints of women by all healthcare professionals, determining hygiene behaviors, and correcting erroneous practices will positively affect urogenital health.

Keywords: hygiene, education, genital infection, reproductive health, family practice
Pulmonary Visceral Pleura Biomaterial: Elastin- and Collagen-Based Extracellular Matrix
Authors: Lu Xiao , Han Ling , Kassab Ghassan S.
Published: March 2022

Objective: The goal of the study is to determine the structural characteristics, mechanical properties, cytotoxicity, and biocompatibility of the pulmonary visceral pleura (PVP).

Background: Collagen and elastin are the major components of the extracellular matrix. The PVP has an abundance of elastin and collagen that can serve as a potential biomaterial for clinical repair and reconstructions.

Methods: The PVP was processed from swine and bovine lungs. Chemical analyses were used to determine collagen and elastin contents in the PVPs. Immunofluorescence microscopy was used to analyze the structure of the PVP. The stress–strain relationships and stress relaxation were determined by using the planar uniaxial test. The cytotoxicity of the PVP was tested in cultured cells. In in vivo evaluations, the PVP was implanted in the sciatic nerve and skin of rats.

Results: Collagen and elastin contents are abundant in the PVP with larger proportions of elastin than in the bovine pericardium and porcine small intestinal submucosa. A microstructural analysis revealed that the elastin fibers were distributed throughout the PVP and the collagen was distributed mainly in the mesothelial basal lamina. The incremental moduli in stress–strain curves and relaxation moduli in the Maxwell–Wiechert model of PVP were approximately one-tenth of the bovine pericardium and small intestinal submucosa. The minimal cytotoxicity of the PVP was demonstrated. The axons proliferated in the PVP conduit guidance from proximal to distal sciatic nerves of rats. The neo-skin regenerated under the PVP skin substitute within 4 weeks.

Conclusions: The PVP is composed of abundant collagen and elastin. The structural characteristics and mechanical compliance of the PVP render a suitable biological material for repair/reconstruction.
A Minireview on Brain Models Simulating Geometrical, Physical, and Biochemical Properties of the Human Brain
Authors: Bouattour Yassine , Sautou Valérie , Hmede Rodayna , El Ouadhi Youssef , Gouot Dimitri , Chennell Philip , Lapusta Yuri , Chapelle Frédéric , Lemaire Jean-Jacques
Published: March 2022

There is a growing body of evidences that brain surrogates will be of great interest for researchers and physicians in the medical field. They are currently mainly used for education and training purposes or to verify the appropriate functionality of medical devices. Depending on the purpose, a variety of materials have been used with specific and accurate mechanical and biophysical properties, More recently they have been used to assess the biocompatibility of implantable devices, but they are still not validated to study the migration of leaching components from devices. This minireview shows the large diversity of approaches and uses of brain phantoms, which converge punctually. All these phantoms are complementary to numeric models, which benefit, reciprocally, of their respective advances. It also suggests avenues of research for the analysis of leaching components from implantable devices.
The Shape of Corneal Deformation Alters Air Puff–Induced Loading
Authors: Yousefi Atieh , Roberts Cynthia J. , Reilly Matthew A.
Published: March 2022

Purpose: To determine the dynamic modification of the load exerted on the eye during air-puff testing by accounting for the deformation of the cornea.

Methods: The effect of corneal load alteration with surface shape (CLASS) was characterized as an additional component of the load produced during the concave phase where the fluid outflow tangential to the corneal surface creates backward pressure. Concave phase duration (tCD), maximum CLASS value (CLASSmax), and the area under CLASS-time curve (CLASSint) are calculated for 26 keratoconic (KCN), 102 normal (NRL), and 29 ocular hypertensive (OHT) subjects. Tukey’s HSD tests were performed to compare the three subject groups. A p-value less than 0.05 was considered statistically significant.

Results: Accounting for CLASS increased the load by 34.6% ± 7.7% at maximum concavity; these differences were greater in KCN subjects (p < 0.0001) and lower in OHT subjects (p = 0.0028) than in NRL subjects. tCD and CLASSint were significantly longer and larger, respectively, for KCN subjects than those in the NRL and OHT groups (p < 0.0001).

Conclusion: Load characterization is an essential step in assessing the cornea’s biomechanical response to air-puff–induced deformation. The dynamic changes in the corneal surface shape significantly alter the load experienced by the corneal apex. This implies a subject-specific loading dynamic even if the air puff itself is identical. This is important when comparing the same eye after a surgical procedure or topical medication that alters corneal properties. Stiffer corneas are least sensitive to a change in load, while more compliant corneas show higher sensitivity.
The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives
Authors: Verkuijl Sebald A. N. , Ang Joshua X. D. , Alphey Luke , Bonsall Michael B. , Anderson Michelle A. E.
Published: March 2022

Making discrete and precise genetic changes to wild populations has been proposed as a means of addressing some of the world’s most pressing ecological and public health challenges caused by insect pests. Technologies that would allow this, such as synthetic gene drives, have been under development for many decades. Recently, a new generation of programmable nucleases has dramatically accelerated technological development. CRISPR-Cas9 has improved the efficiency of genetic engineering and has been used as the principal effector nuclease in different gene drive inheritance biasing mechanisms. Of these nuclease-based gene drives, homing endonuclease gene drives have been the subject of the bulk of research efforts (particularly in insects), with many different iterations having been developed upon similar core designs. We chart the history of homing gene drive development, highlighting the emergence of challenges such as unintended repair outcomes, “leaky” expression, and parental deposition. We conclude by discussing the progress made in developing strategies to increase the efficiency of homing endonuclease gene drives and mitigate or prevent unintended outcomes.
Branched PCL-Based Thermogelling Copolymers: Controlling Polymer Architecture to Tune Drug Release Profiles
Authors: Lin Qianyu , Ow Valerie , Boo Yi Jian , Teo Vincent T. A. , Wong Joey H. M. , Tan Rebekah P. T. , Xue Kun , Lim Jason Y. C. , Loh Xian Jun
Published: March 2022

Temperature-responsive hydrogels, or thermogels, are a unique class of biomaterials that show facile and spontaneous transition from solution to gel when warmed. Their high biocompatibility, and ease of formulation with both small molecule drugs and biologics have made these materials prime candidates as injectable gel depots for sustained local drug delivery. At present, controlling the kinetics and profile of drug release from thermogels is achieved mainly by varying the ratio of hydrophobic: hydrophilic composition and the polymer molecular weight. Herein, we introduce polymer branching as a hitherto-overlooked polymer design parameter that exhibits profound influences on the rate and profile of drug release. Through a family of amphiphilic thermogelling polymers with systematic variations in degree of branching, we demonstrate that more highly-branched polymers are able to pack less efficiently with each other during thermogel formation, with implications on their physical properties and stability towards gel erosion. This in turn resulted in faster rates of release for both encapsulated small molecule hydrophobic drug and protein. Our results demonstrate the possibility of exploiting polymer branching as a hitherto-overlooked design parameter for tailoring the kinetics and profile of drug release in injectable thermogel depots.
Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer
Authors: Wang Dan , Ao Jiangen , Xiong Youwen , Zhang Xinyi , Zhang Weifang
Published: March 2022

Lung cancer has the world’s second highest cancer incidence and second highest cancer-related mortality rate. However, the mechanism underlying non-small cell lung cancer (NSCLC) remained to be unclear. Overall, this study for the first time revealed Stress Granule Regulators were mutated and dysregulated in NSCLC samples by analyzing TCGA database. Moreover, three subtypes of NSCLC were identified based on the expression levels of Stress Granule Regulators. Patients in cluster 2 showed a higher survival rate than those in clusters 1 and 3. Bioinformatics analysis indicated the cell cycle, mTOR signaling pathway, EGFR signaling, PI3K/Akt signaling and DNA damage repair signaling were significantly related to molecular subtypes. Moreover, we performed a prediction analysis of the response to the inhibitors against the aforementioned signaling. Our results showed patients in C2 NSCLC had the highest sensitivity to MK.2206 (AKT.inhibitor) and Rapamycin (mTOR inhibitor). Patients in C3 NSCLC had the highest sensitivity for Temsirolimus (PI3K/mTOR signaling), BIBW2992 (EGFR signaling), Erlotinib (EGFR signaling), PD.0332991 (CDK4/6 inhibitor), CGP.60474 (CDK inhibitor), and Gefitinib (EGFR signaling). Moreover, our results showed patients in C1 NSCLC had the highest sensitivity to AKT.inhibitor, AZD6482 (PI3K inhibitor). To evaluate the response to immune therapy of different subtypes, we analyzed the tumor immune inflation, immune regulators expression, and TIDE score in different SG related subtypes. These results showed that C2 and C3 may be more sensitive to immune therapy. To better predict the prognosis of NSCLC, we analyzed the correlation between stress granule regulator expression and overall survival time in NSCLC and constructed a Stress Granule Score including EIF2S1, CTSG, EIF4G1, IGF2BP1, PABPC1 to predict the prognosis of NSCLC. Overall, this study for the first time uncovers the effect of stress particles on drug response, immune response, and prognosis, laying a new theoretical foundation for the NSCLC prognosis and treatment.
Microfluidic Chip for the Electrochemical Detection of MicroRNAs: Methylene Blue Increasing the Specificity of the Biosensor
Authors: Poujouly Claire , Le Gall Jérémy , Freisa Martina , Kechkeche Djamila , Bouville David , Khemir Jihed , Gonzalez-Losada Pedro , Gamby Jean
Published: March 2022

MicroRNAs (miRNAs) are biomarkers involved in biological processes that are released by cells and found in biological fluids such as blood. The development of nucleic acid-based biosensors has significantly increased in the past 10 years because the detection of such nucleic acids can easily be applied in the field of early diagnosis. These biosensors need to be sensitive, specific, and fast in order to be effective. This work introduces a newly-built electrochemical biosensor that enables a fast detection in 30 min and, as a result of its integration in microfluidics, presents a limit of detection as low as 1 aM. The litterature concerning the specificity of electrochemical biosensors includes several studies that report one base-mismatch, with the base-mismatch located in the middle of the strand. We report an electrochemical nucleic acid biosensor integrated into a microfluidic chip, allowing for a one-base-mismatch specificity independently from the location of the mismatch in the strand. This specificity was improved using a solution of methylene blue, making it possible to discriminate a partial hybridization from a complete and complementary hybridization.
Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors
Authors: Hui Qian , Li Xueming , Fan Wenli , Gao Congying , Zhang Lin , Qin Hongyu , Wei Liuya , Zhang Lei
Published: March 2022

In discovery of novel SIRT3 inhibitors for the treatment of cancer, a series of 2-(4-acrylamidophenyl)-quinoline-4-carboxylic acid derivatives were designed and synthesized. Among the derived compounds, molecule P6 exhibited SIRT3 inhibitory selectivity with IC50 value of 7.2 µM over SIRT1 (32.6 µM) and SIRT2 (33.5 µM). molecular docking analysis revealed a specific binding pattern of P6 in the active site of SIRT3 compared with the bindings in the active site of SIRT1 and SIRT2. In the antiproliferative and colony forming assay, molecule P6 showed potent inhibitory activity against a group of MLLr leukemic cell lines. Further analysis revealed that induction of G0/G1 phase cell cycle arrest and cell differentiation, but not apoptosis, makes contributions to the anticancer effects of P6. Collectively, a potent SIRT3 inhibitor (P6) was discovered as a lead compound for the leukemic differentiation therapy.
Effects of Exogenous Hydrogen Sulfide on Diabetic Metabolic Disorders in db/db Mice Are Associated With Gut Bacterial and Fungal Microbiota
Authors: Liu Jian , Zhao Wei , Gao Zi-Wei , Liu Ning , Zhang Wei-Hua , Ling Hong
Published: March 2022

The effects of hydrogen sulfide (H2S) on diabetic metabolic disorders are still controversial, and the mechanisms underlying these effects remain largely unknown. This study was conducted to investigate the potential relationship between the gut microbiota and the improvement of diabetic metabolic disorders by exogenous H2S in obese db/db mice. The db/db mice were treated with sodium hydrosulfide (NaHS) (80 μmol/kg), or vehicle for 16 weeks, respectively. We measured the serum H2S, obesity parameters, glucose homeostasis, and triglyceride. The sequencing of bacterial 16S rRNA gene and fungal internal transcribed spacer (ITS) in the cecal contents of NaHS-treated mice was performed to evaluate the gut microbial communities. We found that supplying exogenous H2S for 16 weeks significantly inhibited the increase of serum triglyceride, blood glucose, and insulin levels and altered specifically the gut bacterial microbiota structure in db/db mice. The relative abundance of some bacterial genera was correlated with the H2S or blood glucose level. Indeed, exogenous H2S increased Firmicutes and decreased Bacteroidetes at the phylum level along with changes of abundance of multifarious genera. Among them, Unclassified_Enterobacteriaceae, Prevotella, and Lactobacillus decreased and Unclassified_Ruminococcaceae, Oscillospira, Ruminococcus, Sutterella, and Desulfovibrio increased. For fungi, exogenous H2S decreased the abundance of Candida and Aspergillus. Here we demonstrated that, in diabetes, microbial dysbiosis may not be just limited to bacteria due to the inter-linked metabolic interactions among bacteria and fungi in the gut. The beneficial effects of exogenous H2S on diabetic metabolic disorders are likely associated with the alterations of specific microbiota.
Lacticaseibacillus rhamnosus GG Counteracts Rotavirus-Induced Ion Secretion and Enterocyte Damage by Inhibiting Oxidative Stress and Apoptosis Through Specific Effects of Living and Postbiotic Preparations
Authors: Buccigrossi Vittoria , Poeta Marco , Cioffi Valentina , Terranova Sara , Nunziata Francesco , Lo Vecchio Andrea , Guarino Alfredo
Published: March 2022

Background

Administration of Lacticaseibacillus rhamnosus GG (LGG) to children with gastroenteritis is recommended by universal guidelines. Rotavirus (RV) causes diarrhea through combined cytotoxic and enterotoxic effects. Aim of this study was to evaluate the mechanisms of efficacy of LGG in an in-vitro model of RV diarrhea in its viable form (LGG) and conditioned medium (mLGG).

Methods

Ion secretion corresponding to the NSP4 enterotoxic effect, was evaluated by short circuit current (Isc) and the cytotoxic effect by transepithelial electrical resistance (TEER) in Ussing chambers, upon exposure to RV in Caco-2 enterocyte monolayers treated or not with living probiotic or its culture supernatant. Mechanisms of enterotoxic and cytotoxic damage were evaluated including oxidative stress measured by reactive oxygen species, apoptosis evaluated by DAPI and nuclear staining, NFkβ immunofluorescence.

Results

RV induced Isc increase and TEER decrease, respectively indicating ion secretion and epithelial damage, the two established pathways of diarrhea. Both probiotic preparations reduced both diarrheal effects, but their potency was different. Live LGG was equally effective on both enterotoxic and cytotoxic effect whereas mLGG was highly effective on ion secretion and showed minimal protective effects on cytoskeleton, apoptosis and NFkβ.

Conclusions

LGG counteracts RV-induced diarrhea by inhibiting both cytotoxic and enterotoxic pathogenic mechanisms. Namely, LGG inhibits chloride secretion by specific moieties secreted in the medium with a direct pharmacologic-like action. This is considered a postbiotic effect. Subsequently, live bacteria exert a probiotic effect protecting the enterocyte structure.
Cost Utility Analysis of Multidisciplinary Postacute Care for Stroke: A Prospective Six-Hospital Cohort Study
Authors: Chen Yu-Ching , Yeh Yu-Jo , Wang Chung-Yuan , Lin Hsiu-Fen , Lin Ching-Huang , Hsien Hong-Hsi , Hung Kuo-Wei , Wang Jung-Der , Shi Hon-Yi
Published: March 2022

Background

Few studies have compared the optimal duration and intensity of organized multidisciplinary neurological/rehabilitative care delivered in a regional/district hospital with the standard rehabilitative care delivered in the general neurology/rehabilitation ward of a medical center. This study measured functional outcomes and conducted cost-utility analysis of an organized multidisciplinary postacute care (PAC) project in secondary care compared with standard rehabilitative care delivered in tertiary care.

Methods

This prospective cohort study enrolled 1,476 patients who had a stroke between March 2014 and March 2018 and had a modified Rankin scale score of 2–4. After exact matching for age ± 1 year, sex, year of stroke diagnosis, nasogastric tube, and Foley catheter and propensity score matching for the other covariates, we obtained 120 patients receiving PAC (the PAC group) from four regional/district hospitals and 120 patients not receiving PAC (the non-PAC group) from two medical centers.

Results

At baseline, the non-PAC group showed significantly better functional outcomes than the PAC group, including EuroQol-5 dimensions (EQ-5D), Mini-Mental State Examination (MMSE) and Barthel index (BI). During weeks 7–12 of rehabilitation, improvements in all functional outcomes were significantly larger in the PAC group (P < 0.001) except for Functional Oral Intake Scale (FOIS). Cost-utility analysis revealed that the PAC group had a significantly lower mean (± standard deviation) of direct medical costs (US$3,480 ± $1,758 vs. US$3,785 ± $3,840, P < 0.001) and a significantly higher average gain of quality-adjusted life years (0.1993 vs. 0.1233, P < 0.001). The PAC project was an economically “dominant” strategy.

Conclusions

The PAC project saved costs and significantly improved the functional outcomes of patients with stroke with slight to moderately severe disabilities. Randomized control trials are required to corroborate these results.
Effects of Excessive Activation of N-methyl-D-aspartic Acid Receptors in Neonatal Cardiac Mitochondrial Dysfunction Induced by Intrauterine Hypoxia
Authors: Liu Yang , Luo Ziqiang , Liao Zhengchang , Wang Mingjie , Zhou Yan , Luo Siwei , Ding Ying , Liu Teng , Cao Chuangding , Yue Shaojie
Published: March 2022

Intrauterine hypoxia is a common complication during pregnancy and could increase the risk of cardiovascular disease in offspring. However, the underlying mechanism is controversial. Memantine, an NMDA receptor antagonist, is reported to be a potential cardio-protective agent. We hypothesized that antenatal memantine treatment could prevent heart injury in neonatal offspring exposed to intrauterine hypoxia. Pregnant rats were exposed to gestational hypoxia or antenatal memantine treatment during late pregnancy. Newborns were then sacrificed to assess multiple parameters. The results revealed that Intrauterine hypoxia resulted in declining birth weight, heart weight, and an abnormally high heart weight/birth weight ratio. Furthermore, intrauterine hypoxia caused mitochondrial structural, functional abnormalities and decreased expression of DRP1, and upregulation of NMDAR1 in vivo. Antenatal memantine treatment,an NMDARs antagonist, improved these changes. In vitro, hypoxia increased the glutamate concentration and expression of NMDAR1. NMDAR activation may lead to similar changes in mitochondrial function, structure, and downregulation of DRP1 in vitro. Pharmacological blockade of NMDARs by the non-competitive NMDA antagonist MK-801 or knockdown of the glutamate receptor NR1 significantly attenuated the increased mitochondrial reactive oxygen species and calcium overload-induced by hypoxia exposure. These facts suggest that memantine could provide a novel and promising treatment for clinical use in intrauterine hypoxia during pregnancy to protect the cardiac mitochondrial function in the offspring. To our best knowledge, our research is the first study that shows intrauterine hypoxia can excessively activate cardiac NMDARs and thus cause mitochondrial dysfunction.
The Effects of Exercise on Plaque Volume and Composition in a Mouse Model of Early and Late Life Atherosclerosis
Authors: Stanton Kelly M. , Liu Hongjuan , Kienzle Vivian , Bursill Christina , Bao Shisan , Celermajer David S.
Published: March 2022

Background

Exercise is associated with a less atherogenic lipid profile; however, there is limited research on the effect of exercise on atherosclerotic plaque composition and markers of plaque stability.

Methods

A total of 110 apolipoprotein (apo)E−/− mice were placed on a chow diet and randomly assigned to control or exercise for a period of 10 weeks, commencing either at 12 weeks of age (the early-stage atherosclerosis, EA group) or at 40 weeks of age (the late-stage atherosclerosis, LA group). At the end of the exercise period, blood was assayed for lipids. Histologic analysis of the aortic sinus was undertaken to assess plaque size and composition that includes macrophage content, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase-2 (MMP-2), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and 2).

Results

A total of 103 mice (38 EA, 65 LA) completed the protocol. In the EA group, exercise reduced plasma total cholesterol (TC) (−16%), free cholesterol (−13%), triglyceride (TG) (−35%), and phospholipid (−27%) levels, when compared to sedentary control mice (p < 0.01). In the EA group, exercise also significantly reduced plaque stenosis (−25%, p < 0.01), and there were higher levels of elastin (3-fold increase, p < 0.0001) and collagen (11-fold increase, p < 0.0001) in plaques, compared to control mice. There was an increase in plaque MMP-2 content in the exercise group (13% increase, p < 0.05) but no significant difference in macrophage or MCP-1 content. In the LA group, exercise reduced plaque stenosis (−18%, p < 0.05), but there was no significant difference in plaque composition. There was no difference in macrophage, MCP-1, or MMP-2 content in the LA groups. TIMP-1 was lower with exercise in both the EA and LA groups (−59%, p < 0.01 and −51%, p < 0.01 respectively); however, there was no difference in TIMP-2 levels.

Conclusion

A 10-week exercise period reduces atherosclerotic plaque stenosis when commenced at both early- and late-stage atherosclerosis. Intervening earlier with exercise had a greater beneficial effect on lipids and plaque composition than when starting exercise at a later disease stage.
Genetically Predicted Atrial Fibrillation and Valvular Heart Disease: A Two-Sample Mendelian Randomization Study
Authors: Gao Jie , Bai Yulin , Ji Hongwen
Published: March 2022

Background

Previous studies have found atrial fibrillation (AF) is associated with valvular heart disease (VHD). However, whether there is a causal relationship between these two diseases or it is just a result of bias caused by confounding factors is uncertain. This study aims to examine the potential causal association between AF and VHD by using Mendelian randomization.

Methods

In order to examine the causal relationship between AF and VHD, we performed a two-sample Mendelian randomization study by collecting exposure and outcome data from genome-wide association study (GWAS) datasets. We utilized data from FinnGen project (FinnGen, 11,258 cases for VHD including rheumatic fever, 3,108 cases for non-rheumatic VHD, and 75,137 cases for participants) and European Bio-informatics Institute database (EBI, 55,114 cases for AF and 482,295 cases for participants). Inverse-variance weighted (IVW), MR-Egger, and weighted median approaches were performed to estimate the causal effect.

Results

The Mendelian randomization analysis indicated that AF increased the risk of VHD by all three MR methods [For VHD including rheumatic fever: IVW, odds ratio (OR) = 1.255; 95% confidence interval (CI), 1.191~1.322; p = 1.23 × 10−17; Weighted median, OR = 1.305, 95% CI, 1.216~1.400, p = 1.57 × 10−13; MR-Egger, OR = 1.250, 95% CI, 1.137~1.375, p = 1.69 × 10−5; For non-rheumatic VHD: IVW, OR = 1.267; 95% CI, 1.169~1.372; p = 6.73 × 10−9; Weighted median, OR = 1.400; 95% CI, 1.232~1.591; p = 2.40 × 10−7; MR-Egger, OR = 1.308; 95% CI, 1.131~1.513; p = 5.34 × 10−4]. After the one outlier SNP was removed by heterogeneity test, the results remained the same. No horizontal pleiotropic effects were observed between AF and VHD.

Conclusions

Our study provides strong evidence of a causal relationship between AF and VHD. Early intervention for AF patients may reduce the risk of developing into VHD.
Establishment of Reference Interval and Aging Model of Homocysteine Using Real-World Data
Authors: Ma Chaochao , Li Lei , Wang Xinlu , Hou Li’an , Xia Liangyu , Yin Yicong , Cheng Xinqi , Qiu Ling
Published: March 2022

Objective

The level of Homocysteine (Hcy) in males is generally higher than that of females, but the same reference interval (RI) is often used in clinical practice. This study aims to establish a sex-specific RI of Hcy using five data mining algorithms and compare these results. Furthermore, age-related continuous RI was established in order to show the relationship between Hcy concentration distribution and age.

Methods

A total of 20,801 individuals were included in the study and Tukey method was used to identify outliers in subgroups by sex and age. Multiple linear regression and standard deviation ratio (SDR) was used to determine whether the RI for Hcy needs to be divided by sex and age. Five algorithms including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR were utilized to establish the RI of Hcy. Generalized Additive Models for Location Scale and Shape (GAMLSS) algorithm was used to determine the aging model of Hcy and calculate the age-related continuous RI.

Results

RI of Hcy needed to be partitioned by sex (SDR = 0.735 > 0.375). RIs established by Hoffmann, Bhattacharya, EM (for females) and kosmic are all within the 95% CI of reference limits established by refine R. The Sex-specific aging model of Hcy showed that the upper limits of the RI of Hcy declined with age beginning at age of 18 and began to rise approximately after age of 40 for females and increased with age for males.

Conclusion

The RI of Hcy needs to be partitioned by sex. The RIs established by the five data mining algorithms showed good consistency. The dynamic sex and age-specific model of Hcy showed the pattern of Hcy concentration with age and provide more personalized tools for clinical decisions.
The Histone Deacetylase 9 Stroke-Risk Variant Promotes Apoptosis and Inflammation in a Human iPSC-Derived Smooth Muscle Cells Model
Authors: Granata Alessandra , Kasioulis Ioannis , Serrano Felipe , Cooper James D. , Traylor Matthew , Sinha Sanjay , Markus Hugh S.
Published: March 2022

A common variant in the Histone Deacetylase 9 (HDAC9) gene is the strongest genetic risk for large-vessel stroke, and HDAC9 offers a novel target for therapeutic modulation. However, the mechanisms linking the HDAC9 variant with increased stroke risk is still unclear due to the lack of relevant models to study the underlying molecular mechanisms. We generated vascular smooth muscle cells using human induced pluripotent stem cells with the HDAC9 stroke risk variant to assess HDAC9-mediated phenotypic changes in a relevant cells model and test the efficacy of HDAC inhibitors for potential therapeutic strategies. Our human induced pluripotent stem cells derived vascular smooth muscle cells show enhanced HDAC9 expression and allow us to assess HDAC9-mediated effects on promoting smooth muscle cell dysfunction, including proliferation, migration, apoptosis and response to inflammation. These phenotypes could be reverted by treatment with HDAC inhibitors, including sodium valproate and small molecules inhibitors. By demonstrating the relevance of the model and the efficacy of HDAC inhibitors, our model provides a robust phenotypic screening platform, which could be applied to other stroke-associated genetic variants.