bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin Erosion and Exteriorisation of a Cardiac Implantable Electronic Device: Modified Surgical Approach
Authors: Sazzad Faizus , Ibrahim Farzana B , Khan Md Saidur Rahman
Published: June 2020

Skin erosion and exteriorization of the commonest cardiac implantable electronic device (CIED) is usually caused by localized infection as a result of “pocket” infection. But, there are other recognized factors including an advanced age with thin, fragile skin with precarious subcutaneous fat. So, exteriorisation of a generator, and/or a lead, is not always associated with bacterial contamination followed by antibiotic therapy and contra-lateral re-implantation strategy. Hence, it does not always make the removal of the material an obligation. Our notable findings in a rare case of such exteriorization stimulate us to look for and implement a modified surgical technique. This 93-year-old extremely aged wonderfully co-operative, multi-morbid woman had multiple episodes of skin erosion and fixation, re-fixation surgery till the best result achieved. We present a new technique for cardiac pacing allowing for full patient recovery via an alternative surgical way of CIED relocation.

J Bangladesh Coll Phys Surg 2020; 38(3): 155-157
5237 sayılı Türk Ceza Kanunu m. 142/2-a'daki Kişinin Ölümüne İlişkin Nitelikli Halin Değerlendirilmesi
Authors: KILIÇ Ahmet
Published: June 2020

Kişinin
ölmesinden yararlanmak, ilk defa 5237 sayılı Türk Ceza Kanunu ile hırsızlık
suçunun nitelikli hali olarak düzenlenmiştir. Ancak bu düzenlemede ölüme kimin
sebebiyet verdiği üzerinden bir sınırlamaya gidilmemiştir. Kanunun gerekçesinde
de aydınlatıcı bir açıklamaya yer verilmemesi, söz konusu nitelikli hal ile
başta yağma olmak üzere çeşitli suçlar arasındaki farkın ve ilişkinin
tespitinde farklı görüşlerin oluşmasına sebebiyet vermiştir. Çalışmamızda,
hırsızlık suçunda ölümden yararlanmaya ilişkin nitelikli hale yer verilmesinin
ceza hukuku kurumlarının uygulanması bakımından sebebiyet verdiği ayrık
durumlar tespit edilecektir. Ayrıca doktrindeki ihtilaflı hususlara ilişkin
görüşümüz bildirilerek söz konusu nitelikli halin yerindeliği değerlendirilecektir.
Kambiyo Senetlerinde Çizilmiş Cironun Hüküm ve Sonuçları
Authors: BAŞ Kadir
Published: June 2020

TTK m.686/1 ve m.790’da ciro silsilesine göre yetkili hamil belirlenirken çizilmiş ciroların yazılmamış sayılacağı düzenlenmiştir. Ancak ciro çiziminin şeklen nasıl yapılması gerektiği, kimlerin ciroyu çizebileceği ve geçerli bir ciro çiziminin şartlarının ve bu şartlara aykırılığın sonuçlarının neler olacağı konularında tam bir açıklık sağlanmamıştır. Bu hususların açıklığa kavuşturulması, özellikle bir hukuki işlem niteliğinde olan ciro çiziminin maddi hukuk alanındaki sonuçlarının belirlenmesi açısından önem taşımaktadır. Buna karşılık ciro çiziminin maddi hukuk anlamındaki geçerliliği, şekli hak sahipliğinin incelenmesinde çok sınırlı bir işleve sahiptir. Bu makale de cironun çizilmesinin geçerlilik şartlarını ve maddi hukuk ile şekli inceleme açısından hüküm ve sonuçlarını, bu konudaki belirsizlikler ve tartışmalı hususlar üzerinde durarak ele almayı amaçlamaktadır.
Mazbut Vakıflara Ait Taşınmazları Konu Edinen Kira Sözleşmelerinin Sona Ermesine İlişkin Bazı Tespitler ve Bu Konudaki Güncel Gelişmeler
Authors: AVCI Mehmet Özgür
Published: June 2020

Mazbut vakıflara ait taşınmazların kiraya verilmesinde Devlet İhale Kanunu uygulanmaktadır. Bu Kanuna göre hazırlanan tip kira sözleşmesinde kira süresinin geçmesi bir sona erme sebebi olarak gösterilmiştir. Mazbut vakıfların konut ve çatılı işyeri niteliğindeki taşınmazlarının da kira sözleşmesinin konusu olabileceği dikkate alındığında bu sebebin söz konusu taşınmazları konu edinen kira sözleşmelerini sona erdirdiği kabul edilmemelidir. Vakıflar Kanununa eklenen yeni düzenlemede, üç aylık kira bedelinin ödenmemesi sözleşmeyi sona erdiren ve taşınmazın tahliyesini gerektiren bir sebep olarak belirtilmiştir. Mazbut vakıflara ait taşınmazların onarım veya inşa karşılığı kiralanmalarını konu edinen kira sözleşmelerinin bu sebeple sona ermesi halinde tahsil edilemeyen kira alacağı ve tahliye masrafları da alınan teminattan mahsup edilir.
Seri Muhakeme ve Basit Yargılama Düzenlemelerinin Değerlendirilmesi
Authors: YILMAZ Zahit , APİŞ Özge
Published: June 2020

Seri muhakeme ve basit yargılama Türk Ceza Muhakemesi Sistemi’ne 7188 sayılı Kanun ile dahil olmuşlardır. 5271 Sayılı Ceza Muhakemesi Kanunu’nun (CMK) 250 ila 252. maddeleri arasında düzenlenen kurumlar, yargı sisteminin iş yükünü azaltma temelinde şekillenmişlerdir. Hal böyle olunca, adı geçen kurumlar ceza muhakemesine hakim olan bir çok ilke ve diğer yandan şüpheli/sanık hakları bakımından eleştiriye maruz kalmıştır.
Bu kapsamda yapacağımız çalışmada, seri muhakeme ve basit yargılama usullerinin uygulanma şartları her bir madde ve fıkra kapsamında ayrı ayrı ele alınacak, bunların uygulanmasına ilişkin görüş, öneri ve eleştirilerde bulunulacaktır
İNOVASYON ODAKLI GİRİŞİMLERİN DESTEKLENDİĞİ TEKNOPARKLARIN KURULUŞ YERİ SEÇİMİNDE ETKİLİ OLAN DEĞİŞKENLERİN AHP İLE ÖNEM KATSAYILARININ BELİRLENMESİ
Authors: ÖZDEMİR Yahya
Published: June 2020

Çok hızlı küreselleşen dünyada bilgi tabanlı rekabet piyasası açısından en değerli olan unsur bilgidir. Teknoparklar bu bilginin üretildiği yenilikçi girişimlerin desteklendiği merkezler olup, bilginin üretimi ve ticarileşmesi için kümelenmede önemli enstrümanlardır. Ülkemizde kurulan ve kurulmaya devam edilen teknoparkların başarısında önem arz eden ve kuruluş yeri seçiminde hangi faktörlerin ne kadar önemli olduğunu belirlemek amacıyla bu araştırma gerçekleştirilmiştir. Bu amaçla Türkiye’de aktif olarak hizmet veren teknoparklardan rastgele örneklem seçimi yöntemiyle seçilen 19 teknoparkın yöneticileri ile görüşülmüş ve anket uygulaması gerçekleştirilmiştir.
DİJİTAL OKURYAZARLIK VE DİĞER DEĞİŞKENLERLE İNTERNET BAĞIMLILIĞI İLİŞKİSİNİN İNCELENMESİ
Authors: KUL Sinan
Published: June 2020

Bu çalışmada, üniversite öğrencilerinin dijital
okuryazarlık düzeylerine ve internet bağımlılıklarına etki eden faktörler
araştırılmıştır. Çalışma kapsamında ayrıca, Atatürk Üniversitesi Mühendislik
son sınıf öğrencilerine verilen dijital okuryazarlık dersi bağlamında
öğrencilerin internet bağımlısı olma düzeylerinde değişim olup olmadığı
araştırılmıştır. Bu çalışmada veri toplama aracı olarak Hahn ve Jerusalem
tarafından geliştirilen ve Şahin ve Korkmaz tarafından Türkçeye çevrilen
internet bağımlılığı ölçeği ve Ng tarafından geliştirilen ve Hamutoğlu ve
arkadaşları tarafından Türkçeye uyarlanan dijital okuryazarlık ölçeği kullanılmıştır.
Anket soruları, öğrencilere, dijital okuryazarlık dersi öncesi ve sonrası olmak
üzere iki defa uygulanmıştır. Çalışma sonuçlarına göre katılımcıların %5’inin
internet bağımlısı olduğu çıkarken, %70’inin bağımlı olmadığı ortaya
çıkmıştır.  İnternet bağımlısı olan
öğrencilerin günde yaklaşık 5.5 saat internet kullandığı bilgisine
ulaşılmıştır. Dijital okuryazarlık düzeyi ile internetin günde kaç saat
kullanıldığı arasında pozitif yönde bir ilişki bulunmuştur. Dijital
okuryazarlık dersinin ise gerek dijital okuryazarlık seviyesi üzerinde gerekse
internet bağımlılığı üzerinde istatistiksel olarak herhangi bir etkisinin
olmadığı tespit edilmiştir.
The Effectiveness of The Guided Discovery Learning (GDL) Method Using a Contextual Approach Reviewed from Mathematical Critical Thinking Ability of Senior High School in Muna District
Authors: Agus Imaludin , Fitriani Fitriani
Published: June 2020

Abstrak

Penelitian ini bertujuan untuk menguji efektivitas metode pembelajaran penemuan terbimbing menggunakan pendekatan kontekstual dalam hal keterampilan berpikir kritis siswa SMP. Jenis penelitian yang digunakan adalah eksperimen semu. Populasi dalam penelitian ini adalah semua siswa kelas VIII Sekolah Menengah Atas di Kecamatan Kontukowuna, Kabupaten Muna, Sulawesi Tenggara pada tahun 2016/2017. Pengumpulan data diperoleh melalui penyediaan empat item pertanyaan instrumen tes keterampilan berpikir kritis, di mana setiap pertanyaan mewakili indikator kemampuan berpikir kritis dan lembar observasi pelaksanaan pembelajaran. Hasil penelitian dianalisis menggunakan uji t satu sampel. Temuan menunjukkan bahwa nilai uji t 2,719> (t_0,05,27) = 2,0518, yang dapat disimpulkan bahwa metode pembelajaran penemuan terbimbing efektif dalam hal kemampuan berpikir kritis siswa SMP. Hasil ini didukung oleh peningkatan rata-rata pretest 27,66 ke posttest 76,00 yang lebih tinggi dari kriteria penguasaan mengajar minimum (KKM) dari 70.

Abstract

This study aimed to test the effectiveness of guided discovery learning method using a contextual approach in terms of students' critical thinking skills of SMP. Type of research used was quasi experiment. Population in this research was all VIII grader students of Senior High School in sub-district Kontukowuna, Muna districts, Southeast Sulawesi in 2016/2017. Data collection was obtained through the provision of four items of question of critical thinking skills test instrumen, where each question represents an indicator of critical thinking ability and observation sheet of learning implementation. Research result was analyzed using one sample t test. The findings showed that t test value 2,719> (t_0.05,27) = 2.0518, which can be concluded that the guided discovery learning method was effective in terms of the critical thinking ability of junior high school students. This result was supported by the increase of average of pretest 27.66 to posttest 76.00 which was higher than the minimum teaching mastery criteria (KKM) of 70.
Assessing Social Support and Emotionality of Students In Problem Solving
Authors: Mubarokah Intan Laelatul
Published: June 2020

Abstrak
Penelitian ini bertujuan untuk mengetahui hubungan antara social support dengan emosionalitas siswa dalam pemecahan masalah matematika. Penelitian ini merupakan penelitian kuantitatif dengan menggunakan desain korelasional. Teknik pengambilan sampel dengan menggunakan purposive sampling dengan subyek penelitiannya siswa kelas XI IPA 2 sebanyak 39 siswa dan kelas XI IPA 3 sebanyak 40 siswa di MAN 2 Majalengka. Teknik pengumpulan data menggunakan angket pernyataan terhadap social support dan emosionalitas siswa. Hasil dari penelitian ini menunjukkan bahwa Besaran social support yang diberikan terhadap siswa sebesar 81% dalam kategori sangat kuat dan kondisi emosionalitas siswa sebesar 81% dalam kategori sangat kuat. Selain itu, Hasil pengujian hipotesis menunjukan bahwa t_hitung 5,527 dengan nilai signifikansi 5,527> 2,000. Maka Ho ditolak dan Ha diterima, sehingga dapat maknai bahwa social support berhubungan dengan emosionalitas siswa dalam pemecahan masalah matematika.

Abstract
This study aims to determine the relationship between social support and student emotionality in solving mathematical problems. This research is a quantitative study using correlational design. The sampling technique used was purposive sampling with the subjects of the XI IPA 2 class as many as 39 students and XI IPA 3 classes as many as 40 students in MAN 2 Majalengka. The data collection technique uses statement questionnaires for students' social support and emotionality. The results of this study indicate that the amount of social support given to students is 81% in the very strong category and the emotionality of students is 81% in the very strong category. In addition, the results of hypothesis testing indicate that t count is 5.527 with a significance value of 5.527> 2,000. Then HO is rejected and Ha is accepted so that it can mean that social support is related to student emotionality in mathematical problems solving.
The Development of Module to Increase Critical Thinking Skill
Authors: Ikashaum Fertilia
Published: June 2020

Penelitian ini bertujuan untuk mengetahui bagaimana mengembangkan modul matematika serta efektifitasnya ditinjau dari kemampuan berpikir kritis matematis siswa. Subjek penelitian adalah siswa kelas VII SMP IT Bina Insani Metro. Penyusunan modul dilakukan berdasarkan panduan penyusunan modul dari Depdiknas 2008. Hasil validasi menunjukkan bahwa modul telah memenuhi standar kelayakan isi, media, dan bahasa. Hasil uji coba awal menunjukkan bahwa modul termasuk dalam kategori baik. Hasil uji terbatas dalam penelitian ini berupa modul matematika pada materi segitiga dan segi empat. Data penelitian diperoleh melalui tes berpikir kritis matematis. Hasil uji efektivitas menunjukkan siswa telah memenuhi kriteria ketuntasan minimal dalam kemampuan berpikir kritis matematis.
Kata kunci: berpikir kritis, modul

Abstract
This research aimed to find out how to develop mathematics modules and its effectiveness in terms of critical thinking skills of mathematics. The subject of this research was students of VIIth grade of SMP IT Bina Insani Metro. The preparation of the module was done based on the guidelines on programming modules from Depdiknas, 2008. The result of validation indicate that the module has a standard feasibility of content, media, and languages. The results of the initial trials showed that the modules included in well category. The result of limited tests in this study was a math module on triangles and rectangles materials. The research data was obtained by the test of mathematical critical thinking. The results of effectiveness showed that students have completed a minimum standard in the ability of critical thinking of mathematics.
Dampak Sampah Plastik Bagi Ekosistem Perairan
Authors: Fahrizal Ahmad , Akib Muhaiminah
Published: June 2020

The purpose of the service to high school/vocational high school, and junior high school students in malagusa Village, Aimas Distric, Sorong Regency is to provide knowledge and understanding to students about waste and plastic waste, types of plastic waste, the solution ecosystem. The method used is a lecture and demonstration method with sxhool students in Kelurahan Malagusa about waste and its handling. The results of the implementation of this community service where students attending Malagusa Village were(1) appreciation of the local government in this case the Malagusa village Government in this case the Malagusa Government regarding the seminar activities carried out (2) the high motivation of the community service seminar participant coming from Vocational, high school and junior high school students the whole village of Malagusa with liveliness asking questions at the discussion session guided by the activity organizing committee. (3) Increaasing studentsâ€™ understanding, knowledge and ability in understanding about waste and increasing waste for the environment.
Manfaat Ekosistem Mangrove Dalam Meningkatkan Kualitas Lingkungan Masyarakat Pesisir
Authors: Nanlohy Lona Helti , Masniar Masniar
Published: June 2020

Hutan mangrove penting terhadap lingkungan dikarenakan hutan mangrove memiliki peranan atau fungsi yang penting baik fungsi fisik, fungsi kimia, fungsi biologi, fungsi ekonomi dan fungsi wisata, apabila hutan mangrove rusak atau bahkan hilang, banyak kerugian yang harus ditanggung manusia ataupun makhluk hidup lainnya serta lingkungan, seperti moluska, kepiting, ikan, udang, dan biota lainnya. Tujuan dari pengabdian masyarakat ini adalah untuk memberikan pemahaman kepada masyarakat pesisir di Kelurahan Kbalinain Distrik Aimas Kabupaten Sorong yang terlibat langsung dalam memanfaatkan ekosistem mangrove dan upaya untuk melestarikan ekosistem mangrove tersebut melalui kesadaran masyarakat pesisir. Metode yang dipergunakan dalam pengabdian masyarakat ini adalah adalah sosialisasi berupa penyuluhan kepada masyarakat pesisir. Â Hasil pengabdian yang dilakukan adalah: Peningkatan kapasitas masyarakat pesisir tentang manfaat dan pelestarian ekosistem mangrove.
Development of Heat Hyperalgesia and Changes of TRPV1 and NGF Expression in Rat Dorsal Root Ganglion Following Joint Immobilization
Authors: NISHIGAMI T. , OSAKO Y. , IKEUCHI M. , YURI K. , USHIDA T.
Published: June 2020

The aim of this study was to examine whether threshold to heat stimuli, and expression of transient receptor potential vanilloid1 (TRPV1) and nerve growth factor (NGF) in dorsal root ganglion (DRG) altered under conditions of long-term limb immobilization. A plastic cast was wrapped around the right limb from the forearm to the forepaw to keep wrist joint at 90° of flexion for 5 weeks. Heat hyperalgesia was tested using the plantar test at 6 h after removing cast. The rats were perfused transcardially with 4 % paraformaldehyde and DRGs were excised at 24 h after removing cast. For size distributions of the TRPV1-IR and NGF-IR neuronal profile, the DRG area measurements over 1000 DRG neurons per animal were measured in each side, on both the immobilized (ipsilateral) and contralateral sides. Ipsilateral withdrawal latency was significantly shorter than contralateral sides. Ipsilateral percentage of immunoreactive neurons in the total DRG neurons was significantly higher than contralateral sides in TRPV1-IR and NGF-IR. Long-term casting induced heat hyperalgesia, and up-regulation and phenotypic change of TRPV1-IR and NGF-IR in DRGs on the immobilized side. These DRG alterations may involve heat hyperalgesia after long-term limb immobilization.
Anti-Obesity Effect of n-3 Polyunsaturated Fatty Acids in Mice Fed High-Fat Diet Is Independent of Cold-Induced Thermogenesis
Authors: JANOVSKÁ P. , FLACHS P. , KAZDOVÁ L. , KOPECKÝ J.
Published: June 2020

Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) exert beneficial effects on health and they could help to prevent development of obesity and associated metabolic disorders. In our previous studies in mice fed high-fat (cHF; ~60 % calories as fat) diet and maintained at 20 °C, dietary LC n-3 PUFA could counteract accretion of body fat, without inducing mitochondrial uncoupling protein 1 (UCP1) in adipose tissue, suggesting that the anti-obesity effect was not linked to adaptive (UCP1-mediated) thermogenesis. To exclude a possible dependence of the anti-obesity effect on any mechanism inducible by cold, experiments were repeated in mice maintained at thermoneutrality (30 °C). Male C57BL/6J mice were fed either cHF diet, or cHF diet supplemented with LC n-3 PUFA, or standard diet for 7 months. Similarly as at 20 °C, the LC n-3 PUFA supplementation reduced accumulation of body fat, preserved lipid and glucose homeostasis, and induced fatty acid re-esterification in epididymal white adipose tissue. Food consumption was not affected by LC n-3 PUFA intake. Our results demonstrated anti-obesity metabolic effect of LC n-3 PUFA, independent of cold-induced thermogenesis and they suggested that induction of fatty acid re-esterification creating a substrate cycle in white fat, which results in energy expenditure, could contribute to the anti-obesity effect.
Refinement concept of the moment of force in mechanics
Authors: Pozhidaev Serhii
Published: June 2020

A refined definition of the concept at the moment of force is obtained. Its application eliminates the contradiction existing in the Іnternational System of Units (SI). It is established that the unit of the force moment is N·m/rad, and the unit of the coefficient, which connects of force and torque, is m/rad. It is shown that the concept of “shoulder strength“ has no relation to the determination of the moment of force.
Keywords: Іnternational System of Units (SI), energy, work, force moment, dimensional formula.
The unimpeded movement of persons with disabilities by highways in the world
Authors: Voloshyna I. V. , Dokukina V. I. , Mykolaienko Olha , Stoianovych Natalia
Published: June 2020

Over the last decade social policies of many European countries for persons with disabilities has undergone significant changes. Addicted to this social group of people as patients who need care only and can not engage in active social life has changed the attitude towards them as full members of society. They have equal rights with other citizens of the country. The basic principles and requirements for living environment and its most important elements for physically weak people control by the relevant regulations. Keywords: handicapped, rampant, escalator, hoist, elevator.
The level of saturation by automobile equipment of regional and urban settlements and the number of accidents
Authors: Fornalchik Yevgenii , Gilevich V. V.
Published: June 2020

In order to determine the impact of motorization growth on the number of accidents, it is proposed to assess the level of motorization of the population not because of the number of cars, but because of the total number of all automobile equipment per 1000 inhabitants. The results of studies, such as the Lviv region and the city Lviv, do not support previous assumptions about such an impact.
Keywords: motorization, cars, automobile equipment, level of saturation, road accident, city, region.
Analysis of research on the quality of cycling service
Authors: Boykiv M. V. , Zhytenko Oleksandr , Matseh R. Z.
Published: June 2020

The existing research methods and criteria for assessing the efficiency and quality of cycling services are analyzed.
Keywords: cycling, bicycle path, quality of transport service, efficiency.
The Role of Mitochondria in Cardiovascular Diseases
Authors: Poznyak Anastasia V. , Ivanova Ekaterina A. , Sobenin Igor A. , Yet Shaw-Fang , Orekhov Alexander N.
Published: June 2020

The role of mitochondria in cardiovascular diseases is receiving ever growing attention. As a central player in the regulation of cellular metabolism and a powerful controller of cellular fate, mitochondria appear to comprise an interesting potential therapeutic target. With the development of DNA sequencing methods, mutations in mitochondrial DNA (mtDNA) became a subject of intensive study, since many directly lead to mitochondrial dysfunction, oxidative stress, deficient energy production and, as a result, cell dysfunction and death. Many mtDNA mutations were found to be associated with chronic human diseases, including cardiovascular disorders. In particular, 17 mtDNA mutations were reported to be associated with ischemic heart disease in humans. In this review, we discuss the involvement of mitochondrial dysfunction in the pathogenesis of atherosclerosis and describe the mtDNA mutations identified so far that are associated with atherosclerosis and its risk factors.
Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors
Authors: Oh Felix , Modiano Jaime F. , Bachanova Veronika , Vallera Daniel A.
Published: June 2020

Ligand-targeted toxins (LTTs) are bioengineered molecules which are composed of a targeting component linked to a toxin that induces cell death once the LTT binds its target. Bispecific targeting allows for the simultaneous targeting of two receptors. In this review, we mostly focus on the epidermal growth factor receptor (EGFR) as a target. We discuss the development and testing of a bispecific LTT targeting EGFR and urokinase-type plasminogen activator receptor (uPAR) as two attractive targets implicated in tumor growth and in the regulation of the tumor microvasculature in solid tumors. In vitro and mouse xenograft studies have shown that EGFR-targeted bispecific angiotoxin (eBAT) is effective against human solid tumors. Canine studies have shown that eBAT is both safe and effective against canine hemangiosarcoma, which is physiologically similar to human angiosarcoma. Finding the appropriate dosing strategy and sequencing of eBAT administration, in combination with other therapeutics, are among important factors for future directions. Together, the data indicate that eBAT targets cancer stem cells, it may have a role in inhibiting human tumor vasculature, and its bispecific conformation may have a role in reducing toxicity in comparative oncologic trials in dogs.
Immunoglobulin M Paraproteinaemias
Authors: Girard Louis-Pierre , Soekojo Cinnie Yentia , Ooi Melissa , Poon Li Mei , Chng Wee-Joo , de Mel Sanjay
Published: June 2020

Monoclonal paraproteinaemia is an increasingly common reason for referral to haematology services. Paraproteinaemias may be associated with life-threatening haematologic malignancies but can also be an incidental finding requiring only observation. Immunoglobulin M (IgM) paraproteinaemias comprise 15–20% of monoclonal proteins but pose unique clinical challenges. IgM paraproteins are more commonly associated with lymphoplasmacytic lymphoma than multiple myeloma and can occur in a variety of other mature B-cell neoplasms. The large molecular weight of the IgM multimer leads to a spectrum of clinical manifestations more commonly seen with IgM paraproteins than others. The differential diagnosis of B-cell and plasma cell dyscrasias associated with IgM gammopathies can be challenging. Although the discovery of MYD88 L265P and other mutations has shed light on the molecular biology of IgM paraproteinaemias, clinical and histopathologic findings still play a vital role in the diagnostic process. IgM secreting clones are also associated with a number of “monoclonal gammopathy of clinical significance” entities. These disorders pose a novel challenge from both a diagnostic and therapeutic perspective. In this review we provide a clinical overview of IgM paraproteinaemias while discussing the key advances which may affect how we manage these patients in the future.
Impact of Tumor Localization and Molecular Subtypes on the Prognostic and Predictive Significance of p53 Expression in Gastric Cancer
Authors: Grosser Bianca , Kohlruss Meike , Slotta-Huspenina Julia , Jesinghaus Moritz , Pfarr Nicole , Steiger Katja , Novotny Alexander , Gaida Matthias M. , Schmidt Thomas , Hapfelmeier Alexander , Ott Katja , Weichert Wilko , Keller Gisela
Published: June 2020

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact.
Integrated Assessment of Circulating Cell-Free MicroRNA Signatures in Plasma of Patients with Melanoma Brain Metastasis
Authors: Bustos Matias A. , Tran Kevin D. , Rahimzadeh Negin , Gross Rebecca , Lin Selena Y. , Shoji Yoshiaki , Murakami Tomohiro , Boley Christine L. , Tran Linh T. , Cole Hunter , Kelly Daniel F. , O’Day Steven , Hoon Dave S. B.
Published: June 2020

Primary cutaneous melanoma frequently metastasizes to distant organs including the brain. Identification of cell-free microRNAs (cfmiRs) found in the blood can be used as potential body fluid biomarkers for detecting and monitoring patients with melanoma brain metastasis (MBM). In this pilot study, we initially aimed to identify cfmiRs in the blood of MBM patients. Normal donors plasma (healthy, n = 48) and pre-operative MBM patients’ plasma samples (n = 36) were compared for differences in >2000 microRNAs (miRs) using a next generation sequencing (NGS) probe-based assay. A 74 cfmiR signature was identified in an initial cohort of MBM plasma samples and then verified in a second cohort of MBM plasma samples (n = 24). Of these, only 58 cfmiRs were also detected in MBM tissues (n = 24). CfmiR signatures were also found in patients who have lung and breast cancer brain metastasis (n = 13) and glioblastomas (n = 36) compared to MBM plasma samples. The 74 cfmiR signature and the latter cfmiR signatures were then compared. We found a 6 cfmiR signature that was commonly upregulated in MBM plasma samples in all of the comparisons, and a 29 cfmiR signature that distinguishes MBM patients from normal donors’ samples. In addition, we assessed for cfmiRs in plasma (n = 20) and urine (n = 14) samples collected from metastatic melanoma patients receiving checkpoint inhibitor immunotherapy (CII). Pre- and post-treatment samples showed consistent changes in cfmiRs. Analysis of pre- and post-treatment plasma samples showed 8 differentially expressed (DE) cfmiRs that overlapped with the 35 cfmiR signature found in MBM patients. In paired pre-treatment plasma and urine samples receiving CII 8 cfmiRs overlapped. This study identified specific cfmiRs in MBM plasma samples that may potentially allow for assessment of melanoma patients developing MBM. The cfmiR signatures identified in both blood and urine may have potential utility to assess CII responses after further validation.
Hierarchical Multi-Blockchain Architecture for Scalable Internet of Things Environment
Authors: Oktian Yustus Eko , Lee Sang-Gon , Lee Hoon Jae
Published: June 2020

Many researchers challenge the possibility of using blockchain and smart contracts to disrupt the Internet of Things (IoT) architecture because of their security and decentralization guarantees. However, the state-of-the-art blockchain architecture is not scalable enough to satisfy the requirements of massive data traffics in the IoT environment. The main reason for this issue is one needs to choose the consensus trade-off between either coping with a high throughput or a high number of nodes. Consequently, this issue prevents the applicability of blockchain for IoT use cases. In this paper, we propose a scalable two-tiered hierarchical blockchain architecture for IoT. The first tier is a Core Engine, which is based on a Practical Byzantine Fault Tolerance (PBFT) consensus to cope with a high throughput, that supervises the underlying subordinate engines (sub-engines) as its second tier. This second tier comprises of the Payment, Compute, and Storage Engine, respectively. We can deploy multiple instances of these sub-engines as many as we need and as local as possible near to the IoT domains, where IoT devices reside, to cope with a high number of nodes. Furthermore, to further extend the scalability of the proposed architecture, we also provide additional scalability features on the Core Engine such as request aggregation, request prioritization, as well as sub-engine parallelism. We implement all of our engines and expose them to IoT applications through the Engine APIs. With these APIs, developers can build and run IoT applications in our architecture. Our evaluation results show that our proposed features on the Core Engine can indeed enhance the overall performance of our architecture. Moreover, based on our proof-of-concept IoT car rental application, we also show that the interoperability between sub-engines through the Core Engine is possible, even when the particular sub-engine is under sub-engine parallelism.
Anti-Thermal Shock Binding of Liquid-State Food Waste to Non-Wood Pellets
Authors: Moreira Bruno Rafael de Almeida , Silva Viana Ronaldo da , Cruz Victor Hugo , Matos Lopes Paulo Renato , Miasaki Celso Tadao , Magalhães Anderson Chagas , Figueiredo Paulo Alexandre Monteiro de , Lisboa Lucas Aparecido Manzani , Ramos Sérgio Bispo , May André , Caraschi José Claudio
Published: June 2020

The development and implementation of strategies to assist safe and effective transport and storage of pellets in containers and indoor facilities without heating systems are challenging. This study primarily aimed to reshape the organic fraction of municipal solid waste into a liquid-state binder in order to develop freezing–defrosting-proof non-wood pellets. The introduction of the standard solution of food waste into the process of pelleting consisted of stirring it together with the residual biomass from distillation of cellulosic bioethanol or alternatively spraying very fine droplets on the layer of the starting material before it entered the pilot-scale automatic machine at 200 MPa and 125 °C. The addition by spraying of carbohydrate-rich supplement boiled for five minutes caused the pellets to show increases in apparent density (1250.8500 kg·m−3), durability (99.7665%), and hydrophobicity (93.9785%), and consistently prevented them from suffering severe mechanical fracture by thermal shock. The fractal dimension of breakpoints, cracks, and delamination on the finished surface for these products was the smallest at 1.7500–1.7505. Sprayed pellets would fall into the strictest grid of products for residential heat-and-power units, even after freezing and defrosting. The conclusion is therefore that spraying can spectacularly ensure the reliability of liquid-state food waste as an anti-thermal shock binder for non-wood pellets.
Molecular Cytogenetic Characterization of the Sicilian Endemic Pond Turtle Emys trinacris and the Yellow-Bellied Slider Trachemys scripta scripta (Testudines, Emydidae)
Authors: Scardino Rita , Mazzoleni Sofia , Rovatsos Michail , Vecchioni Luca , Dumas Francesca
Published: June 2020

Turtles, a speciose group consisting of more than 300 species, demonstrate karyotypes with diploid chromosome numbers ranging from 2n = 26 to 2n = 68. However, cytogenetic analyses have been conducted only to 1/3rd of the turtle species, often limited to conventional staining methods. In order to expand our knowledge of the karyotype evolution in turtles, we examined the topology of the (TTAGGG)n telomeric repeats and the rDNA loci by fluorescence in situ hybridization (FISH) on the karyotypes of two emydids: the Sicilian pond turtle, Emys trinacris, and the yellow-bellied slider, Trachemys scripta scripta (family Emydidae). Furthermore, AT-rich and GC-rich chromosome regions were detected by DAPI and CMA3 stains, respectively. The cytogenetic analysis revealed that telomeric sequences are restricted to the terminal ends of all chromosomes and the rDNA loci are localized in one pair of microchromosomes in both species. The karyotype of the Sicilian endemic E. trinacris with diploid number 2n = 50, consisting of 13 pairs of macrochromosomes and 12 pairs of microchromosomes, is presented here for first time. Our comparative examination revealed similar cytogenetic features in Emys trinacris and the closely related E. orbicularis, as well as to other previously studied emydid species, demonstrating a low rate of karyotype evolution, as chromosomal rearrangements are rather infrequent in this group of turtles.
Economic Burden of Road Traffic Injuries in Nepal
Authors: Banstola Amrit , Kigozi Jesse , Barton Pelham , Mytton Julie
Published: June 2020

The evidence of the economic burden of road traffic injuries (RTIs) in Nepal is limited. The most recent study, conducted in 2008, is now considered outdated because there has been a rapid increase in vehicle numbers and extensive road building over the last decade. This study estimated the current economic costs of RTIs in Nepal, including the direct costs, productivity costs, and valuation of pain, grief, and suffering. An incidence-based cost-of-illness analysis was conducted from a societal perspective, employing a bottom-up approach using secondary data. All costs incurred by the patients, their family members, and costs to society were estimated, with sensitivity analyses to consider uncertainty around the data estimates available. Productivity loss was valued using the human capital approach. The total costs of RTIs in 2017 were estimated at USD 122.88 million. Of these, the costs of productivity loss were USD 91.57 million (74.52%) and the pain, grief, and suffering costs were USD 18.31 million (14.90%). The direct non-medical costs were USD 11.50 million (9.36%) whereas the direct medical costs were USD 1.50 million (1.22%). The economic costs of RTIs increased by threefold since 2007 and are equivalent to 1.52% of the gross national product, indicating the growing national financial burden associated with preventable RTIs.
Hyperosmolar Treatment for Patients at Risk for Increased Intracranial Pressure: A Single-Center Cohort Study
Authors: Wiórek Agnieszka , Jaworski Tomasz , Krzych Łukasz J.
Published: June 2020

Treatment with osmoactive agents such as mannitol or hypertonic saline (HTS) solutions is widely used to manage or prevent the increase of intracranial pressure (ICP) in central nervous system (CNS) disorders. We sought to evaluate the variability and mean plasma concentrations of the water and electrolyte balance parameters in critically ill patients treated with osmotic therapy and their influence on mortality. This cohort study covered patients hospitalized in an intensive care unit (ICU) from January 2017 to June 2019 with presumed increased ICP or considered to be at risk of it, treated with 15% mannitol (G1, n = 27), a combination of 15% mannitol and 10% hypertonic saline (HTS) (G2, n = 33) or 10% HTS only (G3, n = 13). Coefficients of variation (Cv) and arithmetic means (mean) were calculated for the parameters reflecting the water and electrolyte balance, i.e., sodium (NaCv/NaMean), chloride (ClCv/ClMean) and osmolality (mOsmCv/mOsmMean). In-hospital mortality was also analyzed. The study group comprised 73 individuals (36 men, 49%). Mortality was 67% (n = 49). Median NaCv (G1: p = 0.002, G3: p = 0.03), ClCv (G1: p = 0.02, G3: p = 0.04) and mOsmCv (G1: p = 0.001, G3: p = 0.02) were higher in deceased patients. NaMean (p = 0.004), ClMean (p = 0.04), mOsmMean (p = 0.003) were higher in deceased patients in G3. In G1: NaCv (AUC = 0.929, p < 0.0001), ClCv (AUC = 0.817, p = 0.0005), mOsmCv (AUC = 0.937, p < 0.0001) and in G3: NaMean (AUC = 0.976, p < 0.001), mOsmCv (AUC = 0.881, p = 0.002), mOsmMean (AUC = 1.00, p < 0.001) were the best predictors of mortality. The overall mortality prediction for combined G1+G2+G3 was very good, with AUC = 0.886 (p = 0.0002). The mortality of critically ill patients treated with osmotic agents is high. Electrolyte disequilibrium is the independent predictor of mortality regardless of the treatment method used. Variations of plasma sodium, chloride and osmolality are the most deleterious factors regardless of the absolute values of these parameters
Bed Bugs (Hemiptera, Cimicidae): Overview of Classification, Evolution and Dispersion
Authors: Akhoundi Mohammad , Sereno Denis , Durand Remy , Mirzaei Asad , Bruel Christiane , Delaunay Pascal , Marty Pierre , Izri Arezki
Published: June 2020

The bed bugs (Cimex lectularius and C. hemipterus) have undergone a significant resurgence worldwide since the 1990s. A compilation of findings from a database, including 2650 scientific publications from seven major medical databases, allowed us to document main evolutionary events, from fossil evidence, dating from 11,000 years ago, until the present that has led to the current worldwide expansion of Cimicid species. We present the hypotheses on the possible dispersion pathways of bed bugs in light of the major historical and evolutionary events. A detailed classification of the Cimicidae family and finally, an illustrative map displaying the current distribution of known Cimex species in each geographical ecozone of Asia, Europe, Africa, the Americas, and Australia are presented.
The Impact of Regeneration and Climate Adaptations of Urban Green–Blue Assets on All-Cause Mortality: A 17-Year Longitudinal Study
Authors: Tieges Zoë , McGregor Duncan , Georgiou Michail , Smith Niamh , Saunders Josie , Millar Richard , Morison Gordon , Chastin Sebastien
Published: June 2020

Urban waterways are underutilised assets, which can provide benefits ranging from climate-change mitigation and adaptation (e.g., reducing flood risks) to promoting health and well-being in urban settings. Indeed, urban waterways provide green and blue spaces, which have increasingly been associated with health benefits. The present observational study used a unique 17-year longitudinal natural experiment of canal regeneration from complete closure and dereliction in North Glasgow in Scotland, U.K. to explore the impact of green and blue canal assets on all-cause mortality as a widely used indicator of general health and health inequalities. Official data on deaths and socioeconomic deprivation for small areas (data zones) for the period 2001–2017 were analysed. Distances between data zone population-weighted centroids to the canal were calculated to create three 500 m distance buffers. Spatiotemporal associations between proximity to the canal and mortality were estimated using linear mixed models, unadjusted and adjusted for small-area measures of deprivation. The results showed an overall decrease in mortality over time (β = −0.032, 95% confidence interval (CI) [−0.046, −0.017]) with a closing of the gap in mortality between less and more affluent areas. The annual rate of decrease in mortality rates was largest in the 0–500 m buffer zone closest to the canal (−3.12%, 95% CI [−4.50, −1.73]), with smaller decreases found in buffer zones further removed from the canal (500–1000 m: −3.01%, 95% CI [−6.52, 0.62]), and 1000–1500 m: −1.23%, 95% CI [−5.01, 2.71]). A similar pattern of results was found following adjustment for deprivation. The findings support the notion that regeneration of disused blue and green assets and climate adaptions can have a positive impact on health and health inequalities. Future studies are now needed using larger samples of individual-level data, including environmental, socioeconomic, and health variables to ascertain which specific elements of regeneration are the most effective in promoting health and health equity.
When a Head Is about to Burst: Attachment Mediates the Relationship Between Childhood Trauma and Migraine
Authors: Kascakova Natalia , Furstova Jana , Hasto Jozef , Madarasova-Geckova Andrea , Tavel Peter
Published: June 2020

Background: People exposed to childhood trauma show insecure attachment patterns and are more prone to chronic and pain-related conditions, including migraine. The aim of this study was to explore the mediating role of attachment in the association between childhood trauma and adulthood chronic health conditions, with a focus on migraine. Methods: Respondents from a representative sample of citizens of the Czech Republic (n = 1800, mean age: 46.6 years, 48.7% male) were asked to report various chronic and pain-related conditions, childhood trauma (The Childhood Trauma Questionnaire, CTQ), and attachment anxiety and avoidance (The Experience in Close Relationships Revised, ECR-R) in a cross-sectional, questionnaire-based survey conducted in 2016. Structural equation models (SEM) adjusted for sociodemographic variables were used to assess the relationship between childhood trauma, adulthood attachment, and adulthood chronic health conditions (migraine, other pain-related conditions, chronic health conditions other than pain, no chronic health complaints). Results: After adjusting for sociodemographic variables, SEM confirmed a significant mediation of the relationship between childhood trauma and migraine through adulthood attachment. There was no mediation effect of adulthood attachment found in other health complaints. Conclusion: This study highlights the mediation effect of attachment in the link between childhood trauma and migraine. Attachment-based therapeutic interventions can be useful in the treatment of patients with migraine.
Molecular Decolonization: An Indigenous Microcosm Perspective of Planetary Health
Authors: Redvers Nicole , Yellow Bird Michael , Quinn Diana , Yunkaporta Tyson , Arabena Kerry
Published: June 2020

Indigenous peoples are resilient peoples with deep traditional knowledge and scientific thought spanning millennia. Global discourse on climate change however has identified Indigenous populations as being a highly vulnerable group due to the habitation in regions undergoing rapid change, and the disproportionate burden of morbidity and mortality already faced by this population. Therefore, the need for Indigenous self-determination and the formal recognition of Indigenous knowledges, including micro-level molecular and microbial knowledges, as a critical foundation for planetary health is in urgent need. Through the process of Indigenous decolonization, even at the smallest molecular scale, we define a method back to our original selves and therefore to our planetary origin story. Our health and well-being is directly reflected at the planetary scale, and we suggest, can be rooted through the concept of molecular decolonization, which through the English language emerged from the ‘First 1000 Days Australia’ and otherwise collectively synthesized globally. It is through our evolving understanding of decolonization at a molecular level, which many of our Indigenous cultural and healing practices subtly embody, that we are better able to translate the intricacies within the current Indigenous scientific worldview through Western forms of discourse.
Chemical Modification of Aptamers for Increased Binding Affinity in Diagnostic Applications: Current Status and Future Prospects
Authors: Elskens Jan P. , Elskens Joke M. , Madder Annemieke
Published: June 2020

Aptamers are short single stranded DNA or RNA oligonucleotides that can recognize analytes with extraordinary target selectivity and affinity. Despite their promising properties and diagnostic potential, the number of commercial applications remains scarce. In order to endow them with novel recognition motifs and enhanced properties, chemical modification of aptamers has been pursued. This review focuses on chemical modifications, aimed at increasing the binding affinity for the aptamer’s target either in a non-covalent or covalent fashion, hereby improving their application potential in a diagnostic context. An overview of current methodologies will be given, thereby distinguishing between pre- and post-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) modifications.
Full Rescue of F508del-CFTR Processing and Function by CFTR Modulators Can Be Achieved by Removal of Two Regulatory Regions
Authors: Uliyakina Inna , Botelho Hugo M. , da Paula Ana C. , Afonso Sara , Lobo Miguel J. , Felício Verónica , Farinha Carlos M. , Amaral Margarida D.
Published: June 2020

Cystic Fibrosis (CF) is caused by mutations in the CF Transmembrane conductance Regulator (CFTR), the only ATP-binding cassette (ABC) transporter functioning as a channel. Unique to CFTR is a regulatory domain which includes a highly conformationally dynamic region—the regulatory extension (RE). The first nucleotide-binding domain of CFTR contains another dynamic region—regulatory insertion (RI). Removal of RI rescues the trafficking defect of CFTR with F508del, the most common CF-causing mutation. Here we aimed to assess the impact of RE removal (with/without RI or genetic revertants) on F508del-CFTR trafficking and how CFTR modulator drugs VX-809/lumacaftor and VX-770/ivacaftor rescue these variants. We generated cell lines expressing ΔRE and ΔRI CFTR (with/without genetic revertants) and assessed CFTR expression, stability, plasma membrane levels, and channel activity. Our data demonstrated that ΔRI significantly enhanced rescue of F508del-CFTR by VX-809. While the presence of the RI seems to be precluding full rescue of F508del-CFTR processing by VX-809, this region appears essential to rescue its function by VX-770, suggesting some contradictory role in rescue of F508del-CFTR by these two modulators. This negative impact of RI removal on VX-770-stimulated currents on F508del-CFTR can be compensated by deletion of the RE which also leads to the stabilization of this mutant. Despite both regions being conformationally dynamic, RI precludes F508del-CFTR processing while RE affects mostly its stability and channel opening.