bluuebunny/crossref_metadata_2025 huggingface dataset:
Penerapan Metode Simple Additive Weighting Dalam Sistem Pendukung Keputusan Pemilihan Smartphones
Authors: Febriyanto Ferdy , Rusi Ibnur
Published: May 2020

Abstrak -Smartphone merupakan salah satu teknologi yang sangat cepat berkembang, berbagai macam fungsi serta fitur canggih disematkan didalamnya. Para produsen Smartphone juga terus berlomba-lomba untuk memproduksi berbagai macam tipe dan jenis Smartphone setiap tahunnya. Hal ini sering membuat masyarakat kebingungan saat ingin membeli Smartphone dipasaran, karena selain banyaknya ragam Smartphone dari berbagai merk, juga disebabkan ada beberapa jenis Smartphone yang memiliki fitur dan fungsi yang sama hanya berbeda merk. Dengan dibuatnya sistem pendukung keputusan berbasis web ini, para pengguna yang khususnya ingin membeli Smartphone akan mendapatkan rekomendasi berupa perangkingan merk Smartphone berdasarkan kriteria yang diinginkan pengguna. Penerapan metode Simple Additive Weighting (SAW) dalam sistem ini menghasilkan proses perhitungan nilai akhir dengan sangat baik sehingga hasil akhir nilai dapat ditampilkan dari merk Smartphone dengan nilai tertinggi (paling sesuai dengan kriteria pengguna) sampai dengan merk Smartphone dengan nilai terendah (tidak sesuai dengan kriteria pengguna).Katakunci: peringkat, SAW, smartphone, SPKAbstract - Smartphones is one of technology that is very fast developing, various functions and sophisticated features embedded in it. The Smartphone manufacturers also continue to compete to produce various types of Smartphones every year. This makes people confused when they want to buy a Smartphone in the market, because in addition to the many kinds of Smartphones from various brands, also caused by several types of Smartphones that have the same features and functions, only different brands. With this web-based Decision Support System, users who specifically want to buy a Smartphone will get a recommendation a Smartphone brand ranking based on the criteria the user wants. The application of the Simple Additive Weighting (SAW) method in this system results in a very good final value calculation process, so that the final value can be displayed from the Smartphone brand with the highest value (most appropriate based on user criteria) up to the Smartphone brand with the lowest value (not according to user criteria).Keywords: DSS, ranking, SAW, smartphones
Morphometric and morphological analysis of Populus nigra L. leaves in flooded regions
Authors: Miljković Danijela , Čortan Dijana
Published: May 2020

Human activity induced global changes in nature, particularly the flooding regime, which is a stress factor affecting wetland ecosystems. Knowledge of plant strategies of wetland vegetation across a range of flooding gradients is therefore very important. Natural flooding events are increasing as a consequence of constant climate changes. This research was focused on the area of Special Nature Reserve “Gornje Podunavlje” which represents a complex of peculiar marshland, originating from former vast inundated parts of the Danube basin. We have selected samples located on both sides of the embankment in the defended and in the flooded area. The main aim is the assessment of Populus nigra L. riparian tree leaf morphological traits variability (centroid size, shape, developmental instability, specific leaf area and petiole lenght) between two habitats (flooded and not flooded). The geometric morphometry methods were applied to provide visual representation of differences in the leaf shape. We employed leaf composite index indices of fluctuating asymetry as a measure of developmental instability. A statistically ­significant impact of flooding was obtained only for the leaf geometric size and shape, so these traits could be an indicator of flooding as suboptimal environmental conditions.
Komasacija u funkciji poljozaštitnih šumskih pojaseva u Republici Srbiji – Kritički osvrt
Authors: Marinković Goran , Trifković Milan , Lazić Jelena , Grgić Ilija
Published: May 2020

U ovome radu prikazani su rezultati analize realizacije poljozaštitnih šumskih pojaseva u postupku komasacije. Istraživanjem su obuhvaćena tri karakteristična projekta komasacije u Autonomnoj pokrajini Vojvodini, kroz čije provođenje je trebalo realizirati i projekte poljozaštitnih šumskih pojaseva. S obzirom da se izabrani projekti nalaze u različitim dijelovima područja istraživanja, zaključci izvedeni u ovome radu mogu se smatrati reprezentativnim za teritorij Vojvodine. Studija je pokazala da nije iskorištena prilika za povećanjem šumovitosti Vojvodine, odnosno da projekti poljozaštitnih šumskih pojaseva nisu uopće razmatrani u postupku komasacije ili ako su i uzimani u obzir, zemljište odvojeno za njih nikad nije privedeno namjeni.
Histostructural organization of the cerebellum of human fetuses for 8-9 weeks of prenatal development
Authors: Zalevskiy L.L. , Shkolnikov V.S. , Prykhodko S.O.
Published: May 2020

The high incidence of anomalies in the hindbrain is due to the fact that neurulation in the cranial compartment lasts the longest time. Therefore, for more detailed study of embryogenesis and understanding of mechanisms of pathogenesis, occurrence of congenital malformations, there is a need to determine the morphometric (histometric) parameters of the cerebellum at different gestational times. The purpose of the study is to determine the morphometric parameters of the cerebellum of human embryos for 8-9 weeks of prenatal development, as well as features of cytoarchitectonics of its structures, which is inherent in the given gestation period. Anatomo-histological, immunohistochemical and morphometric examination of the cerebellum of 10 human embryos was performed. Serial sections of cerebellum preparations 8-10 microns thick were stained with hematoxylin, eosin, toluidine blue and Van Gieson, and diagnostic monoclonal antibodies of “DacoCytomation” (Denmark): Vimentin, Ki-67 and Synaptophysin were used for immunohistochemical studies. The results of measurements of the total thickness of all layers, the density of neural stem cells (NSC), as well as the area of the right and left hemispheres of the cerebellum were obtained during the study. In immunohistochemical study, we determined the direction of NSC migration and cell proliferation of all layers of the cerebellum, as well as the length of radial glia fibers. In the cerebral hemispheres of embryos of 8-9 weeks there is a clear division into ventricular, intermediate, molecular and outer granular layers. The highest density of neural stem cells was observed in the outer granular layer – 151.0±4.1 cells per 0.01 mm2. The lowest cell density was observed in the molecular layer – 22.0±0.8 cells per 0.01 mm2. The most intense cell proliferation was established in the ventricular layer and the outer granular layer of the cerebellum, and the least intense in the intermediate layer. Synaptophysin expression was only slightly expressed in the ventricular layer of the cerebellum. The radial glial fibers begin from the ventricular layer and penetrate all layers of the cerebellum, ending in the outer granular layer. The average length of radial glial fibers was: short – 120.8±5.7 μm, long – 195.3±9.4 μm. The exterior granular layer is represented by spherical undifferentiated cells with an average area size of 641.1±28.9 μm2, the molecular layer – NSC with an area of 472.9±23.7 μm2, the intermediate layer – NSC with an area of 492.2±23.1 μm2, and the ventricular layer is represented by neuroblasts with an area of 436.1±21.8 μm2. Thus, it is established that there is a clear division of the cerebellum layers into the ventricular layer, which is represented by neuroblasts, the intermediate layer – NSC, the molecular layer – NSC, and the outer granular layer is represented by undifferentiated cells; the densest neural stem cells are located in the outer granular layer and less densely in the molecular layer.
Study of Creativity as One of the Signs of Giftedness in Younger Schoolchildren From Russia and Tajikistan
Authors: Pazukhina Svetlana Vyacheslavovna , Abdurahmonov Gulruz Nurmahmadovich
Published: May 2020

An important indicator of giftedness is creativity. The authors have developed a comprehensive diagnostic system for the early detection of children with signs of giftedness. The following indicators of creativity were studied: fluency, flexibility, originality, degree of development. The model of psychological and pedagogical conditions for the successful education of gifted children was also substantiated. According to this model the actualization of giftedness is possible only with close interaction between the school and the family, as well as the activity of the most gifted child in this direction.
Conditions and Technologies of Psychological and Pedagogical Support of a Gifted Child
Authors: Dekina Elena Viktorovna
Published: May 2020

The article is devoted to the review of the types of psychological and pedagogical support of a gifted child, the features of training mentors for work with gifted children, and project technology for work with motivated pupils. The program of the optional course for teachers-psychologists "Development of giftedness in primary school age" is presented. The course program is an integration of theoretical developments and modern practices on work with gifted pupils.
Prevention of Cervical Stenosis After Cervical Conization Using a Nelaton Catheter: A Retrospective Analysis of 556 Cases
Authors: Mabuchi Seiji , Kobayashi Hiroshi , Kawahara Naoki , Kawaguchi Ryuji , Mabuchi Seiji , Matsubara Sho , Takeda Yoshinori , Yamada Yuki
Published: May 2020

Objective: This study aimed to investigate 1) the incidence of and risk factors for cervical stenosis, and 2)
the ability of prophylactic catheter insertion to prevent the cervical stenosis after cervical conization.
Methods: The clinical data of 556 females that were treated with cervical conization between August 2007
and December 2018 were collected. After excluding 65 postmenopausal women, the remaining 491 patients
were included in this study, and their data were retrospectively reviewed. Cervical stenosis was defined as
complete obstruction of the cervical canal or partial obstruction of the cervical canal accompanied by a
menstrual disorder that developed after cervical conization. The patients were divided into two groups
according to the catheter-indwelling period: the shorter group (catheter-indwelling period: <7 days) and
longer group (catheter-indwelling period: ≥7 days). Univariate and multivariate analyses were performed to
identify predictors of cervical stenosis.
Results: After a median follow-up period of 37.3 months, 80 (16.3%) patients had developed cervical
stenosis. Univariate and multivariate analyses confirmed that superficial conization (depth: <15mm) and a
long catheter-indwelling period after cervical conization were significantly associated with a reduced risk
of cervical stenosis.
Conclusion: Cervical stenosis occurred in 16.3% of patients who underwent cervical conization. It was
demonstrated that catheter insertion is safe and a longer catheter-indwelling period (≥7 days) and superficial
conization (depth: <15mm) are associated with a reduced risk of cervical stenosis after cervical conization.
Further prospective studies are needed to establish the optimal strategy for preventing cervical stenosis.
Pre-Clinical Study of Immediate Effects of Religious and Non-Religious Mindfulness Practice on Cardiovascular and Cortical Modulation
Authors: Lai Cynthia , Lai Cynthia , Y. Lai Frank H. , M. Ng Shamay S. , K. Yung Trevor W. , So Yuen-tai
Published: May 2020

Although low levels of stress can be motivating, high levels of stress – especially when it is sustained
– can be detrimental to mental and physical health. Mindfulness practice has been widely applied in
health care worldwide as an effective stress management approach. This study compared the
immediate effects of two types (religious: Serenity Prayer; and non-religious: Body Scan) of
mindfulness practice with a control condition (resting: sitting) in six adults. This study found no
statistically significant difference between the conditions, but data visualization showed a trend of
cardiovascular modulation (increased high frequency of heart rate variability) and cortical
modulation (increased alpha to beta ratio and theta to beta ratio of quantitative encephalogram) with
a greater level of perceived stress-relieved by both types of mindfulness practice. In addition,
religious belief may be a moderator of the effects of intervention. The results of this study offered
insight into the effect of prayer on cardiovascular and cortical modulation for promoting the wellbeing of a person.
First record of Sinodiaptomus sarsi (Copepoda: Calanoida) from the East European Plain
Authors: Podshivalina V.N. , Sheveleva N.G.
Published: May 2020

The calanoid copepod species Sinodiaptomus sarsi (Rylov, 1923) is recorded from the East European Plain (the Sura River floodplain, Middle Volga Region, Russia) for the first time. A brief description and illustrations of the species are provided, and some differences between its European and Asian populations are revealed. The studied population of S. sarsi from the Sura River basin is mostly similar in morphological characters to populations from China and Japan.
Rola Inspekcji Ochrony Środowiska w zakresie ścigania karnego
Authors: Jasińska Marta
Published: May 2020

According to legal regulation of the criminal proceedings code, non-judicial bodies bear responsibility for conducting preparatory proceedings. Prosecutor as the main body conducts or supervises proceedings. In regard to scope of the regulation, proceedings are conducted by Police or a body with the same eligibility as Police. Aforementioned powers result directly from the criminal code, and also from the Minister for Justice’s ordinance of September 22nd, 2015 regarding bodies that are, along with Police, approved to conduct proceedings. The regulation also regards bodies approved to bring and support accusation to trial in frst instance courts in cases which the proceedings were conducted in, as well as the scope of cases delegable to this bodies. Aforementioned powers result also from special statutes. This deliberation is based on revised statute of Inspection of Environmental Protection which expanses the range of bodies entitled to conduct preparatory proceedings in cases directly determined in the criminal code against environment.
Grundsätze der Strafprozessordnung der Schweiz (Band 2)
Authors: Trefilov Aleksandr
Published: May 2020

W drugiej części artykułu Autor kontynuuje analizę zasad procesu karnego, zdefiniowanych w szwajcarskim Kodeksie postępowania karnego. W tej części zostaną omówione zasady swobodnej oceny dowodów, zakaz podwójnego egzekwowania prawa, zasada ustnej formy postępowania, zasada ograniczenia dostępu do informacji, zasada języka procedury, zasada faworyzowania obrony, zasada podziału funkcji oskarżenia i rozpatrzenia sprawy oraz domniemania niewinności. Autor dochodzi do wniosku, że opisane zasady odzwierciedlają wyraźnie kontynentalny charakter szwajcarskiego systemu wymiaru sprawiedliwości.
Swoboda wypowiedzi podczas czynności przesłuchania (zagadnienia wybrane na tle udziału świadka)
Authors: Jagiełło Dariusz
Published: May 2020

The article aims to indicate doubts as to the interpretation of freedom of expression as the stage of the interview. Guaranteeing the interrogated freedom of expression, other than being a legal requirement, guarantees the proper performance of the interrogation activity. This action can also be used for: psychological observation, assessment of truthfulness (with knowledge of the course of the event), confrontation with evidence gathered in the proceedings, etc. It will also allow the adoption of appropriate tactics, methods or interrogation strategies, or give rise to modify the one already used. The work focuses exclusively on the participation of the witness and the procedural activities carried out with him.
Jezioro jako nieruchomość?
Authors: Klimach Anna , Bagan-Kurluta Katarzyna
Published: May 2020

The surface of the earth is very diverse, there are various elements on it that shape it: mountains, forests, and water. Not all elements of its shape are relevant to the concept of real estate or the scope of ownership rights. The regulations state that the majority of real estate may be owned by any civil law entities, without differentiating them and limiting the possibility of acquiring ownership rights. Some properties are in principle owned by the State Treasury (or municipalities, as a rule). Whether a property may be owned by any entity may depend on its type, location or what is on it. The following article discusses whether a lake can be treated as a property within the meaning of civil law. In addition, it was examined whether two land and mortgage registers could be kept for one lake.
Sistem Pendukung Keputusan Penentuan Matakuliah Pilihan Menggunakan Metode TOPSIS (Studi Kasus : Prodi S1 Sistem Informasi FMIPA Universitas Riau)
Authors: Sukamto Sukamto , Fitriansyah Aidil , Putra Pratama Rangga
Published: May 2020

Matakuliah pilihan juga merupakan matakuliah yang penting, karena pengetahuan dari matakuliah pilihan dapat membantu mahasiswa dalam matakuliah lainnya, skripsi bahkan dalam pekerjaan kedepannya. Maka dari itu, penentuan matakuliah pilihan tidak boleh sembarangan. Tujuan penelitian ini adalah untuk membuat suatu sistem pendukung keputusan berbasis Web untuk membantu mahasiswa Sistem Informasi FMIPA Universitas Riau dalam menentukan matakuliah pilihan yang akan dipilih menggunakan metode Technique for Order Performance of Similarity to Ideal Solution (TOPSIS). TOPSIS mempunyai prinsip bahwa alternatif yang terpilih harus mempunyai jarak terdekat dari solusi ideal positif dan mempunyai jarak terjauh dari solusi ideal negatif. Sistem yang dihasilkan dapat membantu mahasiswa dalam memilih matakuliah pilihan dengan menggunakan kriteria seperti tingkat kesulitan, referensi, lapangan pekerjaan, minat dan bakat. Hasil akhir dari sistem ini adalah lembar hasil perhitungan yang nilai preferensinya telah diurutkan dari yang tertinggi ke terendah. Alternatif dengan nilai tertinggi adalah matakuliah yang direkomendasikan untuk dipilih. Untuk kasus mahasiswa semester IV matakuliah pilihan berdasarkan rangking adalah  Data Mining, Perancangan Sumber Daya Perusahaan, dan  Pengolahan Citra Digital
Implementasi SCRUM dalam Perancangan Aplikasi Emergency Button PMI Kota Malang
Authors: Lia Farokhah  , Fadhli Almu'iini Ahda  , Lukman Hakim
Published: May 2020

Abstrak

Palang Merah Indonesia (PMI) Malang merupakan salah satu organisasi kemasyarakatan yang bergerak dalam bidang sosial kemanusiaan. PMI membutuhkan media komunikasi yang efektif kepada masyarakat. PMI bertugas menanggulangi kecelakaan, kedaruratan medis dan mengevakuasi korban. PMI memiliki beberapa kendala dalam menjalankan tugasnya yaitu kurangnya peran serta pelapor atau masyarakat dalam melaporkan kejadian. PMI menerima laporan kejadian melalui media sosial atau komunitas sehingga penanganannya kurang cepat dan tanggap. Perancangan Aplikasi emergency button dirancang untuk memenuhi kebutuhan para stakeholder yaitu PMI dan masyarakat. Pengembangan rancangan sistem menggunakan metode SCRUM. Metode ini membuat timeline pekerjaan menjadi lebih tertata dan detail Penelitian ini mengukur tingkat prioritas produk backlogs. Prioritas produk backlog admin PMI, driver dan masyarakat atau pelapor cukup tinggi dengan prosentase sekitar 70-100%. Adapun satu fasilitas pelapor memiliki prioritas terendah sekitar 44% tentang pemberian feedback kepada PMI tentang kecepatan layanan yang diberikan kepada pelapor.

 

 

Kata kunci: Kecelakaan, Darurat, Medis, PMI, SCRUM

 

Abstract

            Palang Merah Indonesia (PMI) Malang is one of the social organizations engaged in social humanity. PMI requires effective communication media to the public. PMI has a duty to deal with accidents, medical emergencies and evacuate victims to health facilities. PMI has several obstacles in carrying out of their duties, namely the lack participation of the society. PMI receives incident reports through social media so that the handling is less fast and responsive. Emergency button application is designed to meet the needs of the stakeholders namely PMI and the community. Development of system design using SCRUM. This method makes the work timeline more organized and detailed. This research measures the priority level of backlog products. The backlog product priority of PMI administrator, driver and society are quite high with a percentage of around 70-100%. One report facility has the lowest priority of about 44% regarding providing feedback to PMI about the speed of service provided to the society.

Keywords: Accident, Emergency, Medical, PMI, SCRUM
Incorporating Communicative Competence in Assessment and English Language Teaching in Multilingual Settings
Authors: Yuzar Ella
Published: May 2020

There has been a high level of agreement among scholars that communicative competence should be integrated within language learning and assessments. The study attempts to unravel the issues of how communicative competence can be assessed and measured in multilingual environments and how communicative language testing can be promoted. Using the content analysis approach as the qualitative method, it begins with the historical review of communicative competence that started at the beginning of 1970s to the most current concept involving intercultural communicative competence. Then, some practical models of communicative competence that can be used to propose a measurement of communicative competence are presented. Later, this article argues that there is an upsurge need to shift the paradigm of language testing and language assessment towards communicative competence. Moreover, the nature of language testing should not only concern linguistic or knowledge competence but also recognize the different varieties of English. This study implies that, in the field of language testing, language test designers should encompass the concept of communicative competence in the test construct to include real-life language use, and by extension, to increase test validity. As for teachers, a reform integrating communicative competence in classroom language assessment has become essential within the scope of language teaching.
Caracterización de Sífilis en embarazadas controladas en la unidad de Atención y Control en Salud Sexual del Hospital San José, Santiago de Chile (2010-2016)
Authors: Moya Nicolás , Gubelin Hans Walter , Santander Ester , Correa Claudia , Arévalo Paola , Zemelman Viviana
Published: May 2020

La sífilis gestacional continúa siendo un problema de salud pública en el mundo. Produce severos efectos adversos en la madre y en el feto de no ser tratada. En Chile, el Ministerio de Salud ha establecido un tamizaje para esta infección cada 3 meses en el embarazo y al momento del parto. Un tratamiento adecuado y oportuno es capaz de prevenir todos los efectos adversos de la sífilis en el embarazo.Este fue un estudio transversal retrospectivo que incluyó a 406 embarazadas controladas en la Unidad de Atención y Control en Salud Sexual (UNACESS) del Hospital San José (HSJ) entre los años 2010-2016. Los resultados del estudio fueron que un 87,7% de las embarazadas eran chilenas y un 12,3% de otras nacionalidades. Las nacionalidades más frecuentes para el grupo de extranjeras fueron: 54% peruanas y 18% haitianas. Al ingreso al estudio, 47,5% de las embarazadas se encontraban en el segundo trimestre de embarazo. De todas las participantes, un 38,7% se encontraba en riesgo de sífilis congénita.  En total, un 23% de las participantes presentó un falso positivo biológico, cifra similar a la reportada en otros estudios. En este estudio encontramos que, en gestantes extranjeras, había mayor proporción de diagnóstico tardío en que chilenas.  Esto podría deberse a dificultades para ingresar a la atención en salud.Pese a que en Chile contamos con buenas tasas de diagnóstico, el manejo de la sífilis gestacional ser mejorado con una detección y tratamiento temprano.  Las extranjeras buscaron atención en salud más tarde que las chilenas, por lo tanto, recibieron tratamiento más tardío y con mayor riesgo de sífilis congénita. Esto se puede explicar por dificultades para ingresar al sistema de salud.
INVESTIGATION OF HEAVY METAL CONCENTRATIONS IN SOIL CAUSED BY WILD STORAGE DUMPSITE IN KASTAMONU CITY
Authors: SAVACI Gamze , ÖKSÜZ Çağatay
Published: May 2020

The aim of this study was to reveal the effects of domestic dumpsite on the some soil chemical properties in the surface soils in Kastamonu city. The soil samples were collected from the 5 different distances namely; Very adjacent (VA), Adjacent (A), Middle (M), Far (F) and Very far (VF). The results showed that the accumulation of heavy metal in the soil varied significantly with the distances. Among the heavy metals, the concentrations of Co, Cr, Cu (only A and VA), Zn (only A and VA), Ni (except for M) exceeded the Maximum Allowable Limit (MAL) for Turkey values. However, the concentrations of Mo, Pb and Cd were below the MAL limit values. When all results are considered, it can be stated that the waste dumpsites can negatively affect the environment. Therefore, we make sure that the dumped materials should be concentrated and recycled in order to decrease the amount of heavy metals in the dumpsites and in the soils around the dumpsites. In addition, phytoremediation, which is all the remediation technique available for metal contaminated soils, is the most costly, environmentally friendly and easy to apply. Phytoremediation can be used to remove, displace or reduce contaminants from soil by using plants that hyperaccumulate these contaminants.
The effect of hematocrit, fibrinogen concentration and temperature on the kinetics of clot formation of whole blood
Authors: Windberger U. , Dibiasi Ch. , Lotz E.M. , Scharbert G. , Reinbacher-Koestinger A. , Ivanov I. , Ploszczanski L. , Antonova N. , Lichtenegger H.
Published: May 2020

BACKGROUND: Dynamic mechanical analysis of blood clots can be used to detect the coagulability of blood. OBJECTIVE: We investigated the kinetics of clot formation by changing several blood components, and we looked into the clot “signature” at its equilibrium state by using viscoelastic and dielectric protocols. METHODS: Oscillating shear rheometry, ROTEM, and a dielectro-rheological device was used. RESULTS: In fibrinogen- spiked samples we found the classical high clotting ability: shortened onset, faster rate of clotting, and higher plateau stiffness. Electron microscopy explained the gain of stiffness. Incorporated RBCs weakened the clots. Reduction of temperature during the clotting process supported the development of high moduli by providing more time for fiber assembly. But at low HCT, clot firmness could be increased by elevating the temperature from 32 to 37°C. In contrast, when the fibrinogen concentration was modified, acceleration of clotting via temperature always reduced clot stiffness, whatever the initial fibrinogen concentration. Electrical resistance increased continuously during clotting; loss tangent (D) (relaxation frequency 249 kHz) decreased when clots became denser: fewer dipoles contributed to the relaxation process. The relaxation peak (Dmax) shifted to lower frequencies at higher platelet count. CONCLUSION: Increasing temperature accelerates clot formation but weakens clots. Rheometry and ROTEM correlate well.
A computational model of bidirectional axonal growth in micro-tissue engineered neuronal networks (micro-TENNs)
Authors: Marinov Toma , López Sánchez Haven A. , Yuchi Liang , Adewole Dayo O. , Cullen D. Kacy , Kraft Reuben H.
Published: May 2020

Micro-Tissue Engineered Neural Networks (Micro-TENNs) are living three-dimensional constructs designed to replicate the neuroanatomy of white matter pathways in the brain and are being developed as implantable micro-tissue for axon tract reconstruction, or as anatomically-relevant in vitro experimental platforms. Micro-TENNs are composed of discrete neuronal aggregates connected by bundles of long-projecting axonal tracts within miniature tubular hydrogels. In order to help design and optimize micro-TENN performance, we have created a new computational model including geometric and functional properties. The model is built upon the three-dimensional diffusion equation and incorporates large-scale uni- and bi-directional growth that simulates realistic neuron morphologies. The model captures unique features of 3D axonal tract development that are not apparent in planar outgrowth and may be insightful for how white matter pathways form during brain development. The processes of axonal outgrowth, branching, turning and aggregation/bundling from each neuron are described through functions built on concentration equations and growth time distributed across the growth segments. Once developed we conducted multiple parametric studies to explore the applicability of the method and conducted preliminary validation via comparisons to experimentally grown micro-TENNs for a range of growth conditions. Using this framework, the model can be applied to study micro-TENN growth processes and functional characteristics using spiking network or compartmental network modeling. This model may be applied to improve our understanding of axonal tract development and functionality, as well as to optimize the fabrication of implantable tissue engineered brain pathways for nervous system reconstruction and/or modulation.
Quantifying and Describing the Natural History and Costs of Alzheimer’s Disease and Effects of Hypothetical Interventions
Authors: Wimo Anders , Handels Ron , Winblad Bengt , Black Christopher M. , Johansson Gunilla , Salomonsson Stina , Eriksdotter Maria , Khandker Rezaul K.
Published: May 2020

Background:

A long-term horizon is necessary when the socioeconomic consequences and the potential effects of interventions in Alzheimer’s disease (AD) are estimated.

Objectives:

To illustrate the potential societal costs of AD across the disease continuum and to illustrate the potential cost-effectiveness of a hypothetical intervention with disease modifying treatment (DMT).

Methods:

Based on the Swedish dementia registry, a Markov model was used to simulate a virtual cohort of 100,000 people with mild cognitive impairment (MCI) due to AD (AD-MCI) in Sweden for 40 years starting at the age of 60. A simulated hypothetical intervention assumed a 25% reduction in progression rate during AD-MCI and mild AD-dementia. A comprehensive set of sensitivity analyses was included.

Results:

The cumulative risk to develop dementia was 96%. The mean simulated survival was 19.0 years. The net present value for a person year with dementia was 252,843 SEK (about 29,500 US$). The cost effectiveness model illustrated how the hypothetical scenario of a 25% reduction in progression to AD-dementia would require 41 AD-MCI patients to be treated to prevent one case of AD-dementia (2,447 avoided AD-dementia cases of 100,000 with AD-MCI). Most scenarios illustrated hypothetical cost effectiveness (based on a willingness to pay level of 600,000 SEK (70,000 US$) per gained QALY), but not cost savings.

Discussion:

Lifetime societal costs of AD are substantial. A future DMT may be potentially cost-effective given assumed treatment effects and costs, but cost savings are unlikely.
Hospitalizations and Mortality of Individuals with Dementia: Evidence from Czech National Registers
Authors: Broulikova Hana Marie , Arltova Marketa , Kuklova Marie , Formanek Tomas , Cermakova Pavla
Published: May 2020

Background:

Facing an increasing prevalence of dementia, the Czech Republic is developing a new nationwide strategy for the management and prevention of dementia. Lack of evidence about characteristics of individuals with dementia in the country is a major obstacle.

Objective:

The study aimed to 1) characterize individuals with dementia, 2) compare their mortality with the general population, and 3) analyze differences in survival between different dementia disorders.

Methods:

The study capitalizes on two nationwide registers in the Czech Republic, from which information about individuals who were hospitalized with dementia or died from it between 1994 and 2014 was retrieved. Standardized intensity of hospitalizations was calculated for each year, mortality was studied using standardized mortality ratio, life-tables, Kaplan-Mayer curves, and Cox proportional hazard models.

Results:

Standardized intensity of hospitalizations for dementia increased more than 3 times from 1994 to 2014. Standardized mortality ratio was 3.03 (95% confidence interval 2.97–3.08). One-year survival rate was 45% and five-year survival rate 16%. Vascular dementia was the most common type of dementia disorders and was associated with higher hazard of death than Alzheimer’s disease, even after adjusting for sociodemographic and clinical covariates (hazard ratio 1.04; 95% confidence interval 1.02–1.05).

Conclusion:

The study provides estimates on demographic characteristics and mortality of the Czech hospitalized dementia population, which have not been so far available and which are unique also in the context of the entire region of Central and Eastern Europe.
Memory and Executive Dysfunction Predict Complex Activities of Daily Living Impairment in Amnestic Multi-Domain Mild Cognitive Impairment
Authors: García-García-Patino Rosalía , Benito-León Julián , Mitchell Alex J. , Pastorino-Mellado Damián , García García Ricardo , Ladera-Fernández Valentina , Vicente-Villardón Jose Luis , Perea-Bartolomé María Victoria , Cacho Jesús
Published: May 2020

Background:

Specific cognitive alterations could be one of the predictors that lead to the complex activities of daily living (CADL) impairment in mild cognitive impairment (MCI) and, hence, help to explain the continuum between MCI and dementia.

Objective:

We aimed to reevaluate the existing uncertainty regarding the impact of memory and executive functions on CADL in patients with MCI.

Methods:

Caregivers of 161 patients with amnestic multi-domain MCI and of 150 patients with incipient Alzheimer’s disease as well as 100 age-, sex-, and education-matched controls, completed the Interview for Deterioration in Daily Living Activities in Dementia, a suitable instrument for the description and discrimination of CADL. In addition, all patients and controls were assessed with a neuropsychological battery to measure explicit memory and executive functions performance.

Results:

Multiple regression analyses showed that in the group of patients with amnestic multi-domain MCI, 67.4% of the variability of the CADL impairment was explained by worse performance on executive functions tests ( p < 0.0001) and 41.8% by different explicit memory components impairment ( p < 0.0001). Further, in patients with incipient AD, 44.0% of the variability of CADL impairment was explained by worse performance on executive functions tests ( p < 0.0001) and 39.9% by different explicit memory components worsening ( p < 0.0001).

Conclusions:

Memory and executive functions alterations impact similarly on the CADL in both amnestic multi-domain MCI and incipient Alzheimer’s disease. Given the continuum that exists between both conditions, we conclude that CADL impairment may be an important early step in the evolution towards Alzheimer’s disease from amnestic multi-domain MCI.
Comparison of Two Analytical Platforms in Cerebrospinal Fluid Biomarkers for the Classification of Alzheimer’s Disease Spectrum with Amyloid PET Imaging
Authors: Lim Ho Jae , Park Jung Eun , Kim Byeong C. , Choi Seong-Min , Song Min-Kyung , Cho Soo Hyun , Seo Hyeon Jeong , Kim Jahae , Song Ho-Chun , Choi Kyu Yeong , Lee Jang Jae , Kim Hoo-Won , Ha Jung-Min , Song Woo Keun , Park Sung-Gyoo , Lee Jung Sup , Lee Kun Ho
Published: May 2020

Background:

Cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ1-42), total tau protein (t-Tau), and phosphorylated Tau (p-Tau) are ATN biomarkers for Alzheimer’s disease (AD) and reflect pathogenic changes in the brain. CSF biomarkers of AD are considered for inclusion in the diagnostic criteria for research and clinical purposes to reduce the uncertainty of clinical diagnosis and to distinguish among AD stages.

Objective:

This study aims to compare two commercially available analytical platforms with respect to accuracy and the potential for early diagnosis of AD.

Methods:

A total of 211 CSF samples from healthy control (HC) and AD subjects were analyzed using two analytical platforms, INNOTEST ELISA and INNOBIA AlzBio3 xMAP kits. The accuracy of diagnosis and AUC values distinguishing study groups were compared between the two analytical platforms.

Results:

The absolute values for Aβ1-42, t-Tau, and p-Tau181 levels differed between the two platforms. The Aβ1-42 levels decreased, while t-Tau and p-Tau levels increased according to the AD stages. The AUC of Aβ1-42 and t-Tau, which distinguish the early stages of AD (preclinical and prodromal AD), were similar between the two platforms, whereas there were significant differences in p-Tau AUC values. CSF p-Tau using the INNOBIA was highly accurate for distinguishing both preclinical AD (AUC = 0.826, cut-off score≥38.89) and prodromal AD (AUC = 0.862, cut-off score≥41.88) from HC.

Conclusion:

The accuracy of CSF p-Tau levels in the preclinical and prodromal AD is higher for the INNOBIA than the INNOTEST, and the early stage AD can be accurately distinguished from HC.
Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease
Authors: Manniche Christina , Simonsen Anja Hviid , Hasselbalch Steen Gregers , Andreasson Ulf , Zetterberg Henrik , Blennow Kaj , Høgh Peter , Juhler Marianne , Hejl Anne-Mette
Published: May 2020

Background:

Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail.

Objective:

To determine if novel CSF biomarkers, neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40), and the core Alzheimer’s disease (AD) biomarkers, amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes.

Methods:

Patients with iNPH ( n = 28), SIVD ( n = 30), AD ( n = 57), and HC ( n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays.

Results:

Lower levels of NFL, NG, Aβ42, and t-tau were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and Aβ42 were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with Aβ42, t-tau, and p-tau resulted in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined.

Conclusion:

An addition of NFL to the CSF panel of Aβ42, t-tau, and p-tau may improve the differentiation of iNPH from SIVD.
IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer’s Disease Pathology
Authors: Babić Leko Mirjana , Nikolac Perković Matea , Klepac Nataša , Štrac Dubravka Švob , Borovečki Fran , Pivac Nela , Hof Patrick R. , Šimić Goran
Published: May 2020

Background:

Neuroinflammation plays an important role in Alzheimer’s disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1 α, IL-1β, IL-6, and tumor necrosis factor α (TNF α) that participate in neuron damage, but also anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response. Previous studies showed the association of IL-1 α –889C/T (rs1800587), IL-1β–1473G/C (rs1143623), IL-6 –174C/G (rs1800795), IL-10 –1082G/A (rs1800896), and TNF α –308A/G (rs1800629) polymorphisms with AD.

Objective:

We aimed to investigate whether people with certain IL-1 α, IL-1β, IL-6, IL-10, and TNF α genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid-β1-42, total tau (t-tau), tau phosphorylated at Thr 181 (p-tau181), Ser 199 (p-tau199), and Thr 231 (p-tau231), and visinin-like protein 1 (VILIP-1).

Methods:

The study included 115 AD patients, 53 patients with mild cognitive impairment, and 11 healthy controls. The polymorphisms were determined using real-time polymerase chain reaction. Levels of CSF biomarkers were determined by enzyme-linked immunosorbent assay.

Results:

A significant increase in p-tau CSF levels was found in patients with the AA IL-10 –1082G/A and GG TNF α –308A/G genotypes, and in carriers of a G allele in IL-1β –1473C/G and IL-6 –174C/G polymorphisms. t-tau levels were increased in carriers of a G allele in IL-1β –1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1β –1473C/G, GC IL-6 –174C/G, and GG TNF α –308A/G genotype.

Conclusion:

These results suggest that persons carrying certain genotypes in IL10 (–1082G/A), IL1β (1473C/G), IL6 (–174C/G), and TNFI α (–308A/G) could be more vulnerable to development of neuroinflammation, and consequently of AD.
Aberrant Hippocampal Functional Connectivity Is Associated with Fornix White Matter Integrity in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Wang Pan , Zhou Bo , Yao Hongxiang , Xie Sangma , Feng Feng , Zhang Zengqiang , Guo Yan’e , An Ningyu , Zhou Yuying , Zhang Xi , Liu Yong
Published: May 2020

Background:

Alzheimer’s disease (AD) is the most common cause of dementia in older individuals, and amnestic mild cognitive impairment (aMCI) is currently considered the prodromal stage of AD. The hippocampus and fornix interact functionally and structurally, with the fornix being the major efferent white matter tract from the hippocampus.

Objective:

The main aim of this study was to examine the impairments present in subjects with AD or aMCI and the relationship of these impairments with the microstructure of the fornix and the functional connectivity (FC) and gray matter volume of the hippocampus.

Methods:

Forty-four AD, 34 aMCI, and 41 age- and gender-matched normal controls (NCs) underwent neuropsychological assessments and multimode MRI. We chose the bilateral hippocampi as the region of interest in which gray matter alterations and FC with the whole brain were assessed and the fornix body as the region of interest in which the microstructural integrity of the white matter was observed. We also evaluated the relationship among gray matter alterations, the abnormal FC of the hippocampus and the integrity of the fornix in AD/aMCI

Results:

Compared to the NC group, the AD and aMCI groups demonstrated decreased gray matter volume, reduced FC between the bilateral hippocampi and several brain regions in the default mode network and control network, and damaged integrity of the fornix body (decreased fractional anisotropy and increased diffusivity). We also found that left hippocampal FC with some regions, the integrity of the fornix body, and cognition ability were significantly correlated. Therefore, our findings suggest that damage to white matter integrity may partially explain the reduced resting-state FC of the hippocampus in AD and aMCI.

Conclusion:

AD and aMCI are diseases of disconnectivity including not only functional but also structural disconnectivity. Damage to white matter integrity may partially explain the reduced resting-state FC in AD and aMCI. These findings have significant implications for diagnostics and modeling and provide insights for understanding the disconnection syndrome in AD.
Amyloid Metabolism and Amyloid-Targeting Blood-Based Biomarkers of Alzheimer’s Disease
Authors: Pyun Jung-Min , Kang Min Ju , Ryoo Nayoung , Suh Jeewon , Youn Young Chul , Park Young Ho , Kim SangYun
Published: May 2020

Amyloid-β (Aβ) is a key protein in Alzheimer’s disease (AD) in that its accumulation induces complex pathological changes. Although there has been extensive research on the metabolism of Aβ in AD, new compelling results have recently emerged. Historically, the production and clearance of Aβ have been thought to originate in the central nervous system (CNS). However, recent evidence suggests that the production and clearance of Aβ can also occur in the peripheral system, and that the peripherally driven Aβ migrates to the CNS and induces amyloidopathy with subsequent AD pathologic changes in the brain. This concept implies that AD is not restricted to the CNS but is a systemic disease instead. As such, the development of blood-based biomarkers targeting Aβ is of great interest. Central and peripheral Aβ are both active contributors to the pathology of AD and interact bidirectionally. Measuring peripheral Aβ is not just observing the reflection of the residual Aβ removed from the CNS but also tracking the ongoing process of AD pathology. Additionally, blood-based biomarkers could be a more accessible tool in clinical and research settings. Through arduous research, several blood-based biomarker assays have demonstrated notable results. In this review, we describe the metabolism of Aβ and the amyloid-targeting blood-based biomarkers of AD.
Omega-3 Fatty Acids Increase Amyloid-β Immunity, Energy, and Circadian Rhythm for Cognitive Protection of Alzheimer’s Disease Patients Beyond Cholinesterase Inhibitors
Authors: Fiala Milan , Lau Yik Chai Charles , Aghajani Anthony , Bhargava Sneha , Aminpour Eli , Kaczor-Urbanowicz Karolina Elżbieta , Mirzoyan Hayk , Nichols India , Ko Meng-Wei , Morselli Marco , Santana Joslyn , Dang Johnny , Sayre James , Paul Ketema , Pellegrini Matteo
Published: May 2020

Background:

The cholinesterase inhibitor therapeutics (CI) approved for use in Alzheimer’s disease (AD) are palliative for a limited time.

Objective:

To examine the outcome of AD patients with add-on therapy of the omega-3 fatty acid drink Smartfish.

Methods:

We performed a prospective study using Mini-Mental State Examination, amyloid-β (Aβ) phagocytosis blood assay, and RNA-seq of peripheral blood mononuclear cells in 28 neurodegenerative patients who had failed their therapies, including 8 subjective cognitive impairment (SCI), 8 mild cognitive impairment (MCI), 2 AD dementia, 1 frontotemporal dementia (FTD), 2 vascular cognitive impairment, and 3 dementia with Lewy bodies (DLB) patients.

Results:

MCI, FTD, and DLB patients patients volunteered for the addition of a ω-3 fatty acid drink Smartfish protected by anti-oxidants to failing CI therapy. On this therapy, all MCI patients improved in the first year energy transcripts, Aβ phagocytosis, cognition, and activities of daily living; in the long term, they remained in MCI status two to 4.5 years. All FTD and DLB patients rapidly progressed to dementia. On in vivo or in vitro ω-3 treatments, peripheral blood mononuclear cells of MCI patients upregulated energy enzymes for glycolysis and citric acid cycle, as well as the anti-inflammatory circadian genes CLOCK and ARNTL2.

Conclusion:

Add-on ω-3 therapy to CI may delay dementia in certain patients who had failed single CI therapy.