bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mathematical Relationship Among Normal Patellar Dimensions, to Find the Pre-Diseased Patellar Thickness in Different Populations
Authors: Kerdari Mahdie , Rastegar Shima , Mustafa Yasmeen , Abbassian Mohammadreza , Aalami Harandi Armin , Staehle Mary M. , Hube Robert , Hosseinzadeh Hamid RS
Published: December 2020

Whether resurfacing or not resurfacing the patella during total knee arthroplasty (TKA) still is a challenge to orthopedic surgeons. A significant reason for this controversy is the far from perfect outcomes of both techniques, resulting from inadequate knowledge of normal patellar dimensions in a diseased one. The primary purpose of the current study is to find the pre-diseased patellar dimensions and the ethnic differences in patellar dimensions. We measured the patella's dimensions on 927 normal young adult knee MRIs from seven different ethnicities. Besides comparing the dimensions between sexes, ages, and sides, we analyzed the differences among ethnic groups. The average thickness was 25.12±2.33 mm; the average width was 44.57±4.32 mm, the average articular surface length was 32.69±3.75 mm, with significant gender, age, and ethnic differences. There were also significant differences in dimensions among ethnic groups, except for between the Indians and Far Eastern Asians and between the Arabs and North Africans. We could also find a robust mathematical relationship between the patella's width, length, and thickness. The ethnic differences in patellar dimensions found in this study can help optimize surgical technique and implant designs for patellar resurfacing. The mathematical equation will help the surgeons find the normal, pre-diseased patella thickness to prevent over-or under-stuffing during the patellar resurfacing.
Genetic Characterization of H5N8 Highly Pathogenic Avian Influenza Viruses Isolated From Falcated Ducks and Environmental Water in Japan in November 2020
Authors: Khalil Ahmed Magdy , Fujimoto Yoshikazu , Kojima Isshu , Esaki Mana , Ri Kyonha , Masatani Tatsunori , Matsui Tsutomu , Ozawa Makoto
Published: December 2020

We isolated two highly pathogenic avian influenza viruses (HPAIVs) of subtype H5N8 clade 2.3.4.4b from falcated duck (Anas falcata) feces and environmental water collected at an overwintering site in Japan. Our isolates were almost genetically identical to each other and showed high genetic similarity with H5N8 HPAIVs recently isolated in South Korea, a distant part of Japan, and European countries. These results suggest the potential role of falcated ducks in the dissemination of HPAIVs.
Prevalence of Antimicrobial Resistance (AMR) Salmonella spp. and Escherichia coli Isolated From Broilers in East Coast Malaysia
Authors: Kamaruzzaman Nor Fadhilah , Saeed Shamsaldeen
Published: December 2020

Abstract:Salmonella species (spp) and Escherichia coli (E. coli) are the most common infectious pathogens in poultry. Antimicrobials were given either for the treatment or growth promoters that can increase the possibility of emergence of bacterial resistance towards antimicrobials. The aim of this study was to determine the prevalence of antimicrobial resistant (AMR) Salmonella spp and E. coli isolated from a sample of broiler farms in East Coast Malaysia from 2018-2019. A total of 384 cloacal swabs were collected from broilers farms in Kelantan, Terengganu, and Pahang. The bacteria were isolated and confirmed by bacteriological and serological methods. Following that, confirmed isolates were subjected to antimicrobial susceptibility test. Salmonella spp and E. coli were recovered from the cloacal swabs samples with the overall prevalence of 6.5% and 51.8% respectively. In Kelantan, Terengganu and Pahang, the prevalence of Salmonella spp were 7%, 6.5% and 5.8% respectively, while the prevalence for E. coli were 50%, 48.3% and 58% respectively. Salmonella spp and E. coli displayed resistance towards the following antimicrobials: erythromycin (100% for both pathogens), chloramphenicol (76.2%, 84.5%), tetracycline (62%, 94.6%), ampicillin (47.7%, 87%), sulfamethoxazole/trimethoprim (42.9%, 83.3%), ciprofloxacin (4.8%, 23.8%), nalidixic acid (9.6%, 60.7%), streptomycin (19%,66%), and kanamycin (28.6%,57%), cephalotin (0%, 11%), gentamicin (0%, 20.2%) respectively. No resistance were recorded towards colistin for both pathogens. Multidrug resistance (MDR) was recorded in 82% of Salmonella spp and 100% of E. coli. These findings demonstrate the high prevalence of MDR Salmonella spp. and E. coli in broiler farms in East coast Malaysia. This could be attributed to the excessive use of antimicrobial agents by the poultry farm owners. Enhanced control measures and a strong monitoring system should be urgently implemented to reduce the emergence of antimicrobial resistance that is harmful to public health.
К ВОПРОСУ О ТОЧНОСТИ ЛАБОРАТОРНОЙ ДИАГНОСТИКИ COVID-2019
Authors: Куличенко Александр , Саркисян Нушик
Published: December 2020

Рассмотрены вопросы точности (чувствительности и специфичности) ПЦР-анализа в зависимости от особенностей выполнения преаналитического и аналитического этапов лабораторной диагностики COVID-19, а также сравнение результатов ПЦР и компьютерной томографии легких.

В настоящее время в основе диагностики новой коронавирусной инфекции COVID-19 молекулярно-генетический тест – полимеразная цепная реакция (ПЦР). На 1 ноября 2020 г. методом ПЦР в мире проведено более 750 млн. исследований. Накопленный к настоящему времени опыт позволяет оценить диагностическую чувствительность метода как 82-91%, специфичность – 99-100%. Имеются данные о повышении чувствительности ПЦР при повторном исследовании образцов из верхних дыхательных путей, которая составила - 82,2 % при первичном анализе и 90,6 % после двух последовательных тестов.

На точность анализа оказывает влияние целый ряд факторов. Причинами ложноотрицательных результатов молекулярных тестов могут быть недостаточное количество генетического материала вируса в пробе, сроки и погрешности при отборе биологических образцов.

Установлено, что РНК вируса SARS-CoV-2 с максимальной диагностической чувствительностью выявляется в верхних дыхательных путях за 1–3 дня до появления симптомов и далее в течение 5-6 дней после начала болезни. В этот период наблюдается наивысший риск передачи возбудителя инфекции. На второй неделе болезни отмечается увеличение частоты детекции вирусной РНК в бронхо-легочном материале. Продолжительность детекции маркеров вируса (в том числе при отсутствии жизнеспособных форм) коррелирует с тяжестью заболевания и может достигать 1-2 мес.

Другая реальная проблема ПЦР-анализа – возможность ложноположительных ответов. Ее решение требует высокого уровня организации лабораторных исследований, особенно при их значительных объемах. При этом важно, что положительные ответы ПЦР означают присутствие в образце только фрагментов его РНК, а не жизнеспособного вируса.

Отмечено, что ПЦР-анализ имеет большую специфичность по сравнению с КТ, которая не дает возможности отличить пневмонию, вызванную SARS-CoV-2 от пневмоний другой этиологии (до 25% ложноположительных ответов). Но диагностическая чувствительность КТ составляет 97,2%, что превышает значение этого показателя для ПЦР на 10-15%. Сделано заключение, что только комплексный подход с использованием ПЦР и КТ, с учетом особенностей этих методов и факторов, влияющих на точность получаемых данных, позволяет правильно интерпретировать результаты диагностики.
ТАКТИКА ОРГАНИЗАЦИИ ЛАБОРАТОРНОЙ ДИАГНОСТИКИ COVID-19 ПРИ ПРОВЕДЕНИИ ПРОТИВОЭПИДЕМИЧЕСКИХ МЕРОПРИЯТИЙ ЗА РУБЕЖОМ
Authors: Куличенко Александр , Прислегина Дарья , Малецкая Ольга , Махова Валентина
Published: December 2020

Проведен сравнительный анализ организации лабораторной диагностики новой коронавирусной инфекции COVID-19 за рубежом на начальном этапе пандемии. Тактика сплошного лабораторного скрининга, примененная в Корее, Китае и Германии, имела более высокую эффективность по сравнению с выборочным лабораторным тестированием в США, Великобритании, Франции и Италии. Отмечена важность лабораторного мониторинга COVID-19 среди медицинского персонала. Приводятся данные об особенностях организации серологического мониторинга для изучения распространения COVID-19 среди различных групп населения в Испании, США, Великобритании, Германии и Италии. Зарубежный опыт проведения массовых лабораторных исследований в дальнейшем может быть использован как для выработки оптимальных вариантов лабораторного мониторинга COVID-19, так и формирования стратегии противоэпидемических мероприятий при эпидемиях других инфекций.
Empowerment of Urban Farming Community to Improve Food Security in Gresik
Authors: Indah Pawana Nur , Amir Indra Tjahaja , Khasan Umar
Published: December 2020

The purpose of this study is to determine the role of urban farming community empowerment to improve food security (A case study of RT 02 and RT 03 Awikoen village, Gending-Gresik Urban Village). The method of analyzing data in this study uses Structural Equation Modeling Parial Least Square (SEM-PLS) using Smart PLS 3 application. The results of this study shows that the variable empowerment of urban farming community members had a real influence to improve food security in Gending urban village, Gresik Regency.
Comparative Economic Competitiveness Analysis of Soybean Farming with and without Subsidy to Rice and Corn Farming in Bancak Sub-district, Semarang
Authors: Mbana Febyningsi Rambu Ladu , Prihtanti Tinjung Mary , Yuliawati Yuliawati
Published: December 2020

In Indonesia, soybeans are categorized as secondary crops with high demand. Indonesian government still emphasizes soybean self-sufficiency and efforts to grow soybean production, but the low yields and limited profitability of soybeans imply that Indonesian farmers will continue to grow other crops, namely rice or corn. This study aims to identify whether the Semarang district government must issue  seed subsidies to support soybean competitiveness in terms of productivity and minimum prices so that it can compete with other crops, namely rice, and corn. Primary and secondary data are used in this study. Primary data were collected in a field survey in Bancak District. The sampling method uses a purposive sampling technique, which interviewed 45 farmers. Analyzed using descriptive statistics and competitiveness matrix analysis. The results showed that the analysis of soybean competitiveness was lower than rice and corn despite the existence of subsidy assistance.
Pengaruh Kompetensi Kewirausahaan Terhadap Kinerja Usahatani Petani Kakao di Wilayah Perbatasan Indonesia-Malaysia Pulau Sebatik
Authors: Mubarak Ahmad , Sulistyo Anang , Nurlela Nurlela
Published: December 2020

Pembangunan pertanian dengan pendekatan kewirausahaan menjadi solusi yang komprehenshif dan berkelanjutan bagi pembangunan sumber daya manusia dan ekonomi sosial di wilayah perbatasan Indonesia.  Penelitian ini bertujuan mengetahui 1) pengaruh modal sosial terhadap kompetensi kewirausahaan dan kinerja usahatani, 2) pengaruh karakteristik kewirausahaan terhadap kompetensi kewirausahaan dan kinerja usahatani, dan 3) pengaruh kompetensi kewirausahaan terhadap kinerja usahatani. Populasi dalam penelitian ini adalah petani kakao dengan sampel 250 petani yang ditentukan melalui metode purposive sampling. Pengujian model analisis data yang dikembangkan menggunakan Structural Equation Model (SEM). Hasil penelitian menunjukkan bahwa modal sosial dan karakteristik kewirausahaan berpengaruh signifikan terhadap kompetensi kewirausahaan dan kompetensi kewirausahaan berpengaruh  signifikan terhadap kinerja usahatani.
Exhumation of Metamorphic Core Complexes through Progressive Subhorizontal Shearing, Doming, and Detachment Faulting: Insights from the Cretaceous Liaonan Metamorphic Core Complex, Eastern North China Craton
Authors: Zheng Yuanyuan , Liu Junlai , Hou Chunru , Sun Yanqi , Craddock John P.
Published: December 2020

The Early Cretaceous Liaonan metamorphic core complex (MCC), eastern North China craton, provides a field setting to evaluate progressive middle-upper crustal subhorizontal shearing, doming, and detachment faulting. The MCC is bounded by a western Jinzhou detachment fault zone (JDFZ) and a southern Dongjiagou shear zone (DSZ) that were primarily suggested to be two segments of the master detachment fault zone. Integrated structural, microstructural, quartz c-axis fabrics, and fluid inclusion analysis and zircon U-Pb dating on mylonites and syn-kinematic granites along the DSZ and JDFZ reveal that the DSZ possesses deformation characteristics that are obviously different from those along the JDFZ. The DSZ is composed of a Lower Unit of sheared Archean gneisses and an Upper Unit of sheared Neoproterozoic metasedimentary rocks, between which there is an obvious tectonic discontinuity contact (TDC). Rocks from below and above the TDC possess structures and fabrics with consistent geometries and kinematics with those along the JDFZ. A metamorphic break exists between the two units that were sheared at contrasting deformation conditions. Dating of zircons from syn-kinematic granitic dikes from DSZ yields an age of ca. 134 Ma, which is similar to the ages of early shearing along the JDFZ. It is concluded that the Jinzhou and Dongjiagou faults formed parts of a detachment faulting with top-to-the WNW kinematics. Exhumation of the Liaonan MCC shearing initiation along both the JDFZ and DSZ at an early stage (ca. 133~134 Ma), subsequent progressive shearing, and doming during slow cooling and exhumation before ca. 120 Ma, followed by fast cooling and rapid exhumation of the MCC by detachment faulting along the JDFZ until ca. 107 Ma.
Developing whole-school mental health and wellbeing intervention through pragmatic formative process evaluation: A case-study of innovative local practice within the School Health Research Network
Authors: Gobat Nina H , Littlecott Hannah , Williams Andy , McEwan Kirsten , Stanton Helen , Robling Michael , Rollnick Stephen , Murphy Simon , Evans Rhiannon
Published: December 2020

Background: The evidence-base for whole school approaches aimed at improving student mental health and wellbeing remains limited. This may be due to a focus on developing and evaluating de-novo, research-led interventions, while neglecting the potential of local, contextually-relevant innovation that has demonstrated acceptability and feasibility. This study reports a novel approach to modelling and refining the programme theory of a whole-school restorative approach, alongside plans to scale up through a national educational infrastructure in order to support robust scientific evaluation. Methods: A pragmatic formative process evaluation was conducted of a routinized whole-school restorative approach aimed at improving student mental health and wellbeing in Wales. Results: The study reports the six phases of the pragmatic formative process evaluation. These are: 1) identification of innovative local practice; 2) scoping review of evidence-base to identify potential programme theory; outcomes; and contextual characteristics that influence implementation; 3) establishment of a Transdisciplinary Action Research (TDAR) group; 4) co-production and confirmation of an initial programme theory with stakeholders; 5) planning to optimise intervention delivery in local contexts; and 6) planning for feasibility and outcome evaluation. The phases of this model may be iterative and not necessarily sequential. Conclusions: Formative, pragmatic process evaluations can support researchers, policy-makers and practitioners in developing robust scientific evidence-bases for acceptable and feasible local innovations that do not already have a clear evidence base. The case of a whole-school restorative approach provides a case example of how such an evaluation may be undertaken.
Locus-specific induction of gene expression from heterochromatin loci during cellular senescence
Authors: Tomimatsu Kosuke , Bihary Dóra , Olan Ioana , Parry Aled , Schoenfelder Stefan , Chan Adelyne , Slater Guy , Ito Yoko , Rugg-Gunn Peter , Kirschner Kristina , Bermejo-Rodriguez Camino , Narita Masako , Seko Tomomi , Kugoh Hiroyuki , Shiraishi Ken , Sayama Koji , Kimura Hiroshi , Fraser Peter , Samarajiwa Shamith , Narita Masashi
Published: December 2020

Cellular senescence is a fate-determined state, accompanied by reorganization of heterochromatin. While lineage-appropriate genes can be temporarily repressed through facultative heterochromatin, stable silencing of lineage-inappropriate genes often involves the constitutive heterochromatic mark, histone H3K9me3. The fate of these heterochromatic genes during the chromatin reorganization accompanying senescence is unclear. Here we show a small number of lineage-inappropriate genes are derepressed in senescent cells from H3K9me3 regions that gain open chromatin marks. DNA FISH experiments reveal that these gene loci, which are tightly condensed at the nuclear periphery in proliferative cells, are physically decompacted during senescence. Among these gene loci, NLRP3 is predominantly expressed in immune cells, such as macrophages, where it resides within an open topologically associated domain (TAD). In contrast, NLRP3 is derepressed in senescent fibroblasts, potentially due to the local disruption of the H3K9me3-rich TAD that contains it. The role of NLRP3 has been implicated in the amplification of inflammatory cytokine signalling in senescence and aging, underscoring the functional relevance of gene induction from ‘permissive’ H3K9me3 regions in senescent cells.
Transcriptome Analysis, CmMYB1 Gene Clone From Cucumis Melo L. And Its Functional Roles Under Salt Stress  
Authors: Zhang Huijun , Zhang Yan , Dai Zuyun , Yuan Yushu , Wei Shuangqin
Published: December 2020

MYB TFs plays an important role in plant adaptation to abiotic stress, especially in response to salt stress. Preliminary research found that the stress resistance of the two melon varieties ‘M15’ and ‘baogua’ are quite different. To this end, we compared the transcriptomes of ‘M15’ and ‘baogua’. Transcriptome analysis found that the expression levels of 12 MYB transcription factors were significantly different between the two varieties.CmMYB1 gene was cloned from muskmelon (Cucumis melo L.), and the subcellular localization results showed that CmMYB1 was expressed in the cytoplasm and nucleus. Transform CmMYB1 gene into Arabidopsis thaliana, observe T3 phenotypes during the vegetative and reproductive growth periods.The results showed that the transgenic A. thaliana phenotype did not change significantly compared with the wild type . After treatment with 200 mM sodium chloride solution for 1 h and 3 h, the CmMYB1 expression increased significantly and began to decline after 6 h of salt stress, indicating that it functions in the early response to salt stress. These results provide a theoretical basis for the further study of the biological function of CmMYB1.
The structural dynamics of macropinosome formation and PI3-kinase-mediated sealing revealed by lattice lightsheet microscopy
Authors: Quinn Shayne , Huang Lu , Kerkvliet Jason , Swanson Joel , Smith Steve , Hoppe Adam , Anderson Robert , Thiex Natalie , Scott Brandon
Published: December 2020

Macropinosomes are formed by shaping actin-rich plasma membrane ruffles into large intracellular organelles in a phosphatidylinositol 3-kinase (PI3K)-coordinated manner. Here, we utilize lattice lightsheet microscopy and image visualization methods to map the three-dimensional structure and dynamics of macropinosome formation relative to PI3K activity. We show that multiple ruffling morphologies produce macropinosomes and that the majority form through non-specific collisions of adjacent PI3K-rich ruffles. By combining multiple volumetric representations of the plasma membrane structure and PI3K products, we show that PI3K activity begins early throughout the entire ruffle volume and continues to increase until peak activity concentrates at the base of the ruffle after the macropinosome closes. Additionally, areas of the plasma membrane rich in ruffling had increased PI3K activity and produced many macropinosomes of various sizes. Pharmacologic inhibition of PI3K activity had little effect on the rate and morphology of membrane ruffling, demonstrating that early production of 3'-phosphoinositides within ruffles plays a minor in regulating their morphology. However, 3'-phosphoinositides are critical for the fusogenic activity that seals ruffles into macropinosomes. Taken together these data indicate that local PI3K activity is amplified in ruffles and serves as a priming mechanism for closure and sealing of ruffles into macropinosomes.
Germline Determinants of Humoral Immune Response To HPV-16 Protect Against Oropharyngeal Cancer
Authors: Ferreiro-Iglesias Aida , McKay James , Brenner Nicole , Virani Shama , Lesseur Corina , Gaborieau Valérie , Ness Andrew , Hung Rayjean , Liu Geoffrey , Diergaarde Brenda , Olshan Andrew , Hayes D , Weissler Mark , Schroeder Lea , Bender Noemi , Pawlita Michael , Thomas Steven , Pring Miranda , Dudding Tom , Kanterewicz Beatriz , Ferris Robert , Thomas Sera , Brhane Yonathan , Díez-Obrero Virginia , Milojevic Maja , Smith-Byrne Karl , Mariosa Daniela , Johansson Mattias , Herrero Rolando , Boccia Stefania , Cadoni Gabriella , Lacko Martin , Holcátová Ivana , Ahrens Wolfgang , Lagiou Pagona , Lagiou Areti , Polesel Jerry , Simonato Lorenzo , Merletti Franco , Healy Claire , Hansen Bo , Nygård Mari , Conway David , Wright Sylvia , Macfarlane Tatiana , Robinson Max , Alemany Laia , Agudo Antonio , Znaor Ariana , Amos Christopher , Waterboer Tim , Brennan Paul
Published: December 2020

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conducted a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer(OCC)) and 5,256 controls. Four novel susceptibility loci were detected pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, revealed two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.
Weaning from Mechanical Ventilation: On the Improvement of the Prediction of Patients' Readiness with Cardiopulmonary Coupling Indices
Authors: Armañac-Julián Pablo , Hernando David , Lázaro Jesús , de Haro Candelaria , Magrans Rudys , Morales John , Moeyersons Jonathan , Sarlabous Leonardo , López-Aguilar Josefina , Subirà Carles , Fernández Rafael , Orini Michele , Laguna Pablo , Varon Carolina , Gil Eduardo , Bailón Raquel , Blanch Lluís
Published: December 2020

The ideal moment to withdraw respiratory supply of patients under Mechanical Ventilation (MV) at Intensive Care Units (ICU), is not easy to be determined for clinicians. Although the Spontaneous Breathing Trial (SBT) provides a measure of the patients’ readiness, there is still around 15-20% of predictive failure rate. This work explores both Heart Rate Variability (HRV) and Cardiopulmonary Coupling (CPC) estimates as complementary information for readiness prediction. The CPC is related to how the mechanisms regulating respiration and cardiac pumping are working simultaneously, and it is defined from HRV in combination with respiratory information. Three different techniques are used to measure CPC, including Orthogonal Subspace Projections, Dynamic Mutual Information and Time-Frequency Coherence. 22 patients undergoing SBT in pressure support ventilation are analysed in the 24 hours previous to the SBT. 13 had a successful weaning and 9 failed the SBT or needed reintubation –being both considered as failed weaning. Results illustrate that traditional variables such as heart rate, respiratory frequency, and the parameters derived from HRV do not differ in patients with successful or failed weaning. However, significant statistical differences are found for the novel CPC parameters, throughout the whole recordings, comparing the values of the two groups. In addition, the night prior to SBT is the moment where differences are higher, probably because patients with failed weaning might be experiencing more respiratory episodes, e.g. apneas during the night, which is directly related to a reduced RSA. Therefore, results suggest that the traditional measures could be used in combination with these novel CPC biomarkers to help clinicians better predict if patients are ready to be weaned.
Transcriptome signatures reveal candidate key genes in the peripheral blood mononuclear cells of patients with coronary artery disease and prediction of small drug molecules
Authors: Kolur Vijayakrishna , Vastrad Basavaraj , Tengli Anandkumar , Vastrad Chanabasayya , Kotturshetti Iranna
Published: December 2020

Coronary artery disease (CAD) is one of the most common disorders in the cardiovascular system. This study aims to explore potential signaling pathways and important biomarkers that drive CAD development. The CAD GEO Dataset GSE113079 was featured to screen differentially expressed genes (DEGs). The pathway and Gene Ontology (GO) enrichment analysis of DEGs were analyzed using the ToppGene. We screened hub and target genes from protein-protein interaction (PPI) networks, target gene - miRNA regulatory network and target gene - TF regulatory network, and Cytoscape software. Validations of hub genes were performed to evaluate their potential prognostic and diagnostic value for CAD. A final, molecular docking study was performed. 1,036 DEGs were captured according to screening criteria (525upregulated genes and 511downregulated genes). Pathway and Gene Ontology (GO) enrichment analysis of DEGs revealed that these up and down regulated genes are mainly enriched in thyronamine and iodothyronamine metabolism, cytokine-cytokine receptor interaction, nervous system process, cell cycle and nuclear membrane. Hub genes were validated to find out potential prognostic biomarkers, diagnostic biomarkers and novel therapeutic target for CAD. A small drug molecule was predicted. In summary, our findings discovered pivotal gene expression signatures and signaling pathways in the progression of CAD. CAPN13, ACTBL2, ERBB3, GATA4, GNB4, NOTCH2, EXOSC10, RNF2, PSMA1 and PRKAA1 might contribute to the progression of CAD, which could have potential as biomarkers or therapeutic targets for CAD.
Efficacy of S-1 after Pemetrexed in Patients with Non-small Cell Carcinoma: A Retrospective Multi-institutional Analysis
Authors: Takemoto Shinnosuke , Akagi Kazumasa , Ono Sawana , Tomono Hiromi , Honda Noritaka , Suyama Takayuki , Umeyama Yasuhiro , Dotsu Yosuke , Taniguchi Hirokazu , Ogawara Daiki , Senju Hiroaki , Gyotoku Hiroshi , Sugasaki Nanae , Yamaguchi Hiroyuki , Nakatomi Katsumi , Fukuda Minoru , Mukae Hiroshi
Published: December 2020

Back ground: This study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. Methods: This retrospective study included patients with advanced (c-stage III or IV, UICC 7th) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at 6 hospitals in Japan. Primary endpoint: Overall response rate (ORR). Secondary endpoint: Disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). Results: A total of 53 NSCLC patients met the criteria. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidential interval (CI): 0.00-10.1%). Median TTF, PFS, and OS were 65 days, 84 days, and 385 days, respectively. Conclusion: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with non-SQ NSCLC was low compared to the historical control. It might be one of the choices to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.
Identification of Mutation Resistance Coldspots for Targeting the SARS-CoV2 Main Protease
Authors: Krishnamoorthy Navaneethakrishnan , Fakhro Khalid
Published: December 2020

Most attempts to target the novel coronavirus SARS-CoV2 are focusing on the main protease (Mpro) 1-9. However, >19,000 mutations in the Mpro have already been reported 10. The mutations encompassing 282 amino acid positions and these “hotspots” might change the Mpro structure and activity, potentially rendering novel antivirals and vaccines ineffective. Here we identified 24 mutational “coldspots” that have resisted mutation since the virus was first detected. We compared the structure-function relationship of these coldspots with several SARS-CoV2 Mpro X-ray crystal structures. We found that three coldspot residues (Leu141, Phe185 and Gln192) help to form the active site, while six (Gly2, Arg4, Tyr126, Lys137, Leu141 and Leu286) contribute to dimer formation that is required for Mpro activity. The surface of the dimer interface is more resistant to mutations compared to the active site. Interestingly, 16 coldspots are found in conserved patterns when compared with other coronaviruses. Importantly, several conserved coldpots are available on the surface of the active site and at the dimer interface for targeting. The identification and short list of these coldspots offers a new perspective to target the SARS-CoV2 Mpro while avoiding mutation-based drug resistance.
Selenomethionine Alleviates Intestinal Ischemia Reperfusion Injury by Inhibiting Mitochondrion-mediated Apoptosis in Mice 
Authors: Liu Zhe , Mou Guangze , Li Yang , Zhong Yangsheng , Zhao Rui , Zhang Hua , Wu Rui , Jin Chenghao
Published: December 2020

The mechanism of supplement selenomethionine (SeMet) mitigates ischemia reperfusion (I/R)- damage remains to be elucidated in the intestinal tissues of mice. In this study, a model of intestinal I/R injury was established. The levels of redox factors, such as the activities of glutathione peroxidase-1(Gpx1), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) content, were detected using ELISA assays in the intestinal tissues of mice. Several apoptosis-related markers (cytochrome c (Cyt-c), Bcl-2, Bax, and caspase-3) were detected using qPCR and Western blot. The results showed that SeMet alleviated I/R damage by increasing the activities of Gpx1, CAT, SOD and reducing MDA content. Our data demonstrated that SeMet reduced I/R induced mitochondrial damage and inhibited the expression of Cyt-c. SeMet also increased the Bcl-2 /Bax ratio and reduced the expression of Bax and caspase-3 in the mice intestinal tissues. Thus our data reveals that I/R could lead to increased apoptosis, and SeMet alleviated I/ R-induced apoptosis via maintaining REDOX homeostasis and attenuating mitochondrial pathway in the mice intestinal tissues.
Geographical Distribution and Regional Differences in 532 Clinical Isolates of Rapidly Growing Mycobacterial Species in Japan
Authors: Kamada Keisuke , Yoshida Atsushi , Iguchi Shigekazu , Arai Yuko , Uzawa Yutaka , Konno Satoshi , Shimojima Masahiro , Kikuchi Ken
Published: December 2020

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly becoming a major global problem. Additionally, Mycobacteroides abscessus subsp. abscessus (MAB) infections are refractory to macrolides. This study was conducted to investigate the epidemiology of rapidly growing mycobacteria (RGM) species isolated from clinical specimens in Japan and assess differences in the regional distribution of lower respiratory specimens (LRS)- and non-lower respiratory specimens (NLRS)-derived species. 532 strains (427 LRS, 92 NLRS and 15 unknown specimens) were isolated in nine areas of Japan. Their epidemiological differences were examined according to the specimen type, region and climate. Fifteen species were identified. The top three RGM species from LRS and NLRS were identical. The proportion of M. abscessus group (MAG) strains was significantly lower in NLRS than in LRS (35.9% vs. 68.4%). The proportion of MAG strains was higher in northern Japan than in other regions (83.7% vs. 60.5%). Variations in strain abundance among RGM species was evident in regions with a mean annual temperature below 15 °C. We conclude that the proportions of MAG strains differed between NLRS and LRS in Japan. In addition, the mean annual temperature likely influenced the distribution of RGM species.
Estimation of Years of Life Lost by Sweden's Relaxed COVID-19 Mitigation Strategy
Authors: Rypdal Martin , Rypdal Kristoffer , Løvsletten Ola , Sørbye Sigrunn , Ytterstad Elinor , Bianchi Filippo Maria
Published: December 2020

Objective: To estimate the weekly excess all-cause mortality in Norway and Sweden, and to estimate the years of life lost (YLL) attributed to COVID-19 in Sweden and the significance of mortality displacement. Methods: We found expected mortality by taking the declining trend and the seasonality in mortality into account. From the excess mortality in Sweden in 2019/20, we estimated the YLL attributed to COVID-19 using the life expectancy in different age groups. We adjusted this estimate for possible displacement using an auto-regressive model for the year-to-year variations in excess mortality. Results: We found that excess all-cause mortality over the epidemic year (July to July) 2019/20 was 517 (95%CI -12, 1074) in Norway and 4329 (3331, 5325) in Sweden. There were reported 255 COVID-19 related deaths in Norway, and 5741 in Sweden, that year. During the epidemic period March 11 – November 11, there were 6247 reported COVID-19 deaths and 5517 (4701, 6330) excess deaths in Sweden. The estimated number of life-years lost attributed to the more relaxed Swedish strategy was 45850 (13915, 80276) without adjusting for mortality displacement and 43073 (12160, 85451) after adjusting for possible displacement.
Does Generative Adversarial Network Ensure Diversity in Data? Morphologic Evaluation of Synthetic Isocitrate Dehydrogenase-Mutant Glioblastomas in A Clinical Diagnostic Model
Authors: Park Ji Eun , Eun Dain , Kim Ho Sung , Lee Da Hyun , Jang Ryoung Woo , Kim Namkug
Published: December 2020

Generative adversarial network (GAN) creates synthetic images to increase data quantity, but whether GAN ensures diversity is still unknown. We investigated whether GAN-based synthetic images provide sufficient morphologic variability to improve molecular-based prediction, as a rare disease of isocitrate dehydrogenase (IDH)-mutant glioblastomas. GAN was initially trained on 500 normal brains and 110 IDH-mutant high-grade astocytomas, and paired contrast-enhanced T1-weighted and FLAIR MRI data were generated. Diagnostic models were developed from real IDH-wild type (n = 80) with real IDH-mutant glioblastomas (n = 38), or with synthetic IDH-mutant glioblastomas, or augmented by adding both real and synthetic IDH-mutant glioblastomas. Turing tests showed synthetic data showed reality (classification rate of 55%). Both the real and synthetic data showed that a more frontal or insular location (odds ratio [OR], 1.34 vs. 1.52; P = .04) and distinct non-enhancing tumor margins (OR, 2.68 vs. 3.88; P <.001), which become significant predictors of IDH-mutation. In an independent validation set, diagnostic accuracy was higher for the augmented model (90.9% [40/44] and 93.2% [41/44] for each reader, respectively) than for the real model (84.1% [37/44] and 86.4% [38/44] for each reader, respectively). The GAN-based synthetic images yield morphologically variable, realistic-seeming IDH-mutant glioblastomas. GAN will be useful to create a realistic training set in terms of diversity and quality, thereby improving diagnostic performance in a clinical model.
Key Features of the Anatomy and Topography of the Sphenoid Sinus in Different Age Periods
Authors: Aliyeva Merey , Bathalla Mahmoud Farid Mahrous , Balmagambetova Aru , Zhurabekova Gulmira
Published: December 2020

For the period of 2019, magnetic resonance imaging of the head of patients aged 20–71 years was performed. The majority of males have mezocran the shape of the skull, in contrast to females. There was no universal type of pneumatization for both sexes. In young men, the sellar type prevails, but at the age of 60, this type is 2 times less common and there are no protrusions of the channels of the optic nerves and internal carotid arteries. However, only the protrusion of the internal carotid artery channel is more common in women over 60 years of age than in men. In men, there were no cases of canal protrusion, and 49% of young women had a depression in the wall of the sphenoid sinus. In men under the age of 60, the protrusion of the optic nerve channels and internal carotid arteries occurs in approximately the same way as in women over 80 years of age. Due to the variability of the anatomical configuration of the sphenoid sinuses, the impact on access to the cell through the nose can be serious. The surgeon must be aware of these results before surgery in order to reach the cell safely and effectively.
Percutaneous Nephrostomy Versus Retrograde Ureteral Stenting for Acute Obstructive Uropathy: A Systematic Review and Meta-Analysis
Authors: ISMAIL ZUL KHAIRUL AZWADI , NOOR NORHAYATI MOHD , ABDULLAH MOHD SHAFIE
Published: December 2020

Acute obstructive uropathy is associated with significant morbidity among patients with any condition that leads to urinary tract obstruction. Immediate urinary diversion is necessary to prevent further damage to the kidneys. In many centres, the two main treatment options include percutaneous nephrostomy (PCN) and retrograde ureteral stenting (RUS). The purpose of this study if to compare the efficacy and safety of PCN and RUS for the treatment of acute obstructive uropathy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE, the World Health Organisation International Clinical Trials Registry Platform and ClinicalTrials.gov. We also searched the reference lists of included studies to identify any additional trials. We included randomised controlled trials and controlled clinical trials comparing the outcomes of clinical improvement (septic parameters and hospitalisation duration), quality of life, urinary-related symptoms, failure rates, post-procedural pain [measured using a visual analogue scale (VAS)] and analgesics use. We conducted statistical analyses using random effects models and expressed the results as risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). Seven trials were identified that included 667 patients. Meta-analysis of the data revealed no difference in the two methods in improvement of septic parameters, quality of life, failure rates, post-procedural pain (VAS), or analgesics use. Patients receiving PCN had lower rates of haematuria and dysuria post-operatively and longer hospitalisation duration than those receiving RUS. PCN and RUS are effective for the decompression of an obstructed urinary system, with no significant difference in most outcomes. However, PCN is preferable to RUS because of its reduced impact on the patient’s post-operative quality of life due to haematuria and dysuria, although it is associated with slightly longer hospitalisation duration.
Genetic Variants Modifying the Risk of Lung Cancer and Its Subtypes: A Comprehensive Meta-analysis and a Case-control Study
Authors: Sengupta Debmalya , Banerjee Souradeep , Mitra Ritabrata , Chaudhuri Tamohan , Sarkar Abhijit , Bhattacharjee Gautam , Nath Somsubhra , Roychoudhury Susanta , Bhattacharjee Samsiddhi , Sengupta Mainak
Published: December 2020

Association studies on lung cancer have often yielded conflicting and inconclusive results. We performed a comprehensive meta-analysis to dissect the precise effects of the candidate variants. We searched for association studies on lung cancer from the Indian subcontinent. Cochran’s Q-test assessed heterogeneity. Both overall and histotype-stratified meta-analysis was done using fixed-effect and random-effects models. Smoking status stratified subgroup analysis and effect modification tests were done. An associated variant with significant heterogeneity was genotyped in an eastern Indian population to investigate the contribution of potential confounders followed by a comprehensive meta-analysis across world populations. Significant heterogeneity was observed for the 8 variants. Both fixed-effect and random-effects meta-analysis of 24 variants showed FDR-corrected associations of rs3547/XRCC1 and rs1048943/CYP1A1 with lung cancer along with 5 nominal associations. del1/GSTT1, rs4646903/CYP1A1, and rs10488943/CYP1A1 were associated with adenocarcinoma, squamous cell carcinoma, and both, respectively. rs4646903/CYP1A1 was associated with lung cancer among smokers with significant effect modification by smoking. rs10488943/CYP1A1 was associated with lung adenocarcinoma in the East Indian case-control study. rs1048943/CYP1A1 was associated with lung cancer across world populations. Our work confirms the risk loci for lung cancer and its subtypes in the context of smoking and other aetiological factors, which could aid in personalised treatment.
Serum Epidermal Growth Factor-like domain 7 Serves as a Novel Diagnostic Marker for Early Hepatocellular Carcinoma
Authors: Yang Meng-Yuan , Wu Fan , Fang Feng , Yang Hao , Zhang Jing-Fan , Chen Guo-Dong , Yang Lian-Yue
Published: December 2020

Background: Epidermal growth factor-like domain 7 (Egfl7), a recently identified secreted protein, was significantly increased in patients with HCC by our previous studies. However, its efficacy in diagnosis of early HCC remains unknown. In this study we evaluate the efficacy of serum Egfl7 for early HCC diagnosis and compare it with alpha-fetoprotein (AFP).Methods: Serum Egfl7 levels in testing cohort (1065 participants) and validation cohort (464 participants) were measured by a sandwich enzyme-linked immunoassay (ELISA). The efficacies of Egfl7 and AFP in diagnosing early HCC were estimated by receiver operating characteristic (ROC).Results: Serum Egfl7 was significantly elevated in patients with early HCC than all non-HCC controls. At the cut-off value of 2610 ng/mL, the area under ROC, sensitivity, specificity and accuracy of Egfl7 were 0.800, 75.2 %, 71.7% and 73.5% in discriminating early HCC from chronic liver disease (CLD), compared with 0.675, 61.8%, 62.0% and 61.9% for AFP using 20 ng/mL as a cut-off value. Egfl7 also exhibited a significant higher sensitivity and accuracy than AFP in differentiating early HCC patients from non-HCC individuals including healthy individuals and patients with CLD (76.6% vs. 64.0%, 79.9% vs. 66.1%). Additionally, 70.8% of early HCC patients with negative AFP could be diagnosed by Egfl7 and the combined use of Egfl7 and AFP increased the sensitivity to 91.0%. These results were confirmed by a validation cohort.Conclusion: Egfl7 is a valuable serum marker in early diagnosis of HCC with a better sensitivity and accuracy than AFP.
Comparative Finite Element Analysis of Osseointegration System in Trans-Radial Amputation: A Proposal of New Design
Authors: Lee Seung Gun , Jeoung Heaseong , Kim Dong-Hong , Lee Chang-Hun
Published: December 2020

Introduction: Conventional osseointegration systems have been applied in patients requiring trans-humeral and trans-femoral amputations. However, the application of these systems to trans-radial amputations is limited by the small diameter of the radius and ulna. Our study aimed to compare the biomechanical stability of a novel osseointegration system with that of a conventional system used in trans-radial amputations using a finite element(FE) models.Methods: We established three-dimensional FE models of trans-radial amputations, which were osseointegrated with both the novel and conventional systems. External loads were applied to the FE models with compressive force and tensile force along the long axis, horizontal shear force, and vertical shear force. The maximum equivalent stress(MES) and the distribution of stress through the radius and ulna was evaluated.Results : The MES of the radius and ulna was higher in the conventional system when compressive, tensile, and vertical shear forces were applied. However, when the horizontal shear force was applied, the opposite result was found. The distribution of stress was more effective in the novel system.Conclusion : Three-dimensional FE modeling showed that the novel system enables to have a lower stress level and a more even distribution of stress for osseointegration in trans-radial amputations.
A Pictorial Account of Heart Development: Spatial and Temporal Aspects of The Human Embryonic Heart Between 3.5 and 8 Weeks of Development
Authors: Hikspoors Jill , Kruepunga Nuthmethee , Mommen Greet , Koehler Eleonore , Anderson Robert , Lamers Wouter
Published: December 2020

Heart development is topographically complex and requires visualization to understand its progression. No comprehensive 3-dimensional primer of human cardiac development is currently available. We prepared detailed reconstructions of 12 hearts between 3.5 and 8 weeks post fertilization, using Amira® 3D-reconstruction and Cinema4D®-remodeling software. The models were visualized as calibrated interactive 3D-PDFs. We describe the developmental appearance and subsequent remodeling of 70 different structures incrementally, using sequential segmental analysis. Pictorial timelines of structures highlight age-dependent events, while graphs visualize growth and spiraling of the wall of the heart tube. The basic cardiac layout is established between 3.5 and 4.5 weeks. Septation at the venous pole is completed at 6 weeks. Between 5.5 and 6.5 weeks, as the outflow tract becomes incorporated in the ventricles, the spiraling course of its subaortic and subpulmonary channels is transferred to the intrapericardial arterial trunks. The remodeling of the interventricular foramen is complete at 7 weeks.
Phase Shift MRI in Assessement of Vertebral Compression Fracture: Trial for a New Scoring System
Authors: Matrawy Khaled , Fattah Nadia Abdel , ElNekidy Abdel Aziz , Gawad Mohamed Abdel , Elnaggar Alaa , Shehata Gihan , Reda Ihab , Shalabi Adel
Published: December 2020

PurposeTo assess the value of in /opposed-phase quantitative chemical shift MRI in differentiating malignant from benign vertebral compression fractures (VCF).Patients and methodsTwenty patients (8 men), mean age 56 years, with low back and radiological proof of VCF were included in the study. MRI of spine with standard conventional sequences and special chemical shift sequence (in/opposed phase) as well as diffusion weighted imaging were performed (at 1.5 Tesla). Quantitative image analysis of regions of interest (ROI) on the abnormal marrow in the compressed (study group) and related normal vertebra in same patient (control group) was done in each patient. The signal intensity ratio (SIR) of the marrow was determined by dividing the mean signal intensity on the opposed-phase and in-phase images was performed.ResultsMean SIR of benign VCF [0.6 ± 0.27 (range 0.23–1.1)] was significantly lower than malignant VCF values [1.115 ± 0.14 (range 0.87–1.45)] (p < 0.0001, ROC 0.97). The optimal SIR cutoff value for separating benign and malignant VCF was found to be 0.9 with a calculated sensitivity of 91.5%, specificity of 87.5% and accuracy of 90%. We also found a cut-off value of 0.9, to be a statistically significant in differentiating benign from malignant causes of VCF. If SIR of 0.91 as a cutoff is applied, with >0.91 indicating malignant result and <0.91 defined as a benign result.ConclusionQuantitative chemical shift MR imaging could be a valuable addition to standard MR imaging techniques in differentiating benign from malignant vertebral compression fracture. We designed a new scoring system based on conventional MRI, in/opposed phase chemical shift and diffusion weighted imaging. The new scoring system may be a useful tool and add value in the diagnosis of compression vertebral fractures.