bluuebunny/crossref_metadata_2025 huggingface dataset:
PENDAMPING ORANG TUA SISWA DALAM PEMBELAJARAN AGAMA ISLAM TERDAPAT HIKMAH DIBALIK COVID-19
Authors: Rahmat Rosyadi Abdu , Wizman Syasya
Published: March 2021

Hikmah di balik diadakannya pembelajaran agama islam jarak jauh, para orangtua bisa dengan penuh mendampingi anak-anaknya selama proses belajar. Hubungan orang tua dan anak akan berkembang dengan baik apabila kedua belah pihak saling memupuk keterbukaan. Penelitian ini bertujuan untuk  membantu orang tua dalam menjaga terbukanya jalur komunikasi. Data penelitian dikumpulkan dengan mengunakan instrumen Wawancara, dan Survei . Hasil penelitian menunjukkan bahwa  1) Menjalin hubungan anak dengan orang tua semakin dekat , 2) Meningkatnya motivasi pembelajaran agama islam bagi manusia untuk mengembangkan kemampuan berfikir dalam mengolah potensi alam ini (Q.S.Al-Hasyr,21) , 3) Memperoleh Hikmah dibalik masa pandemi.
PELATIHAN MENULIS PUISI DENGAN MEDIA GAMBAR PADA SISWA KELAS VII SMP NEGERI KOTA BARU KEFAMENANU
Authors: Nalenan Joni Soleman
Published: March 2021

The dedication entitled “The Training of  Poetry Writing using picture to Grade Seven of  SMPN Kota Baru Kefamenanu”. This activity aimed to provide knowledge and explaination to students in SMPN Kota Baru Kefamenanu about the procedure to create a poetry using picture; improve students' creativity in writing poetry using picture; and motivate students regarding the importance of the writing, and develop literature like poetry. The targets of this dedication activity were 30 students in SMPN Kota Baru Kefamenanu. This training was  implemented through two methods, there are communicative method and action method. Communicative method was used to explain the topics like essence of poetry, and how to create poetry. Action method was used to practice writing a poetry based on observation results of the provided picture. The anthusiasm from the participants, the supports from the head masters and co-teachers, and the financial support from LPPM are helpful in accomplishing this dedication. As a result, the ability of students of grade VII in SMPN Kota Baru Kefamenanu in creating a poetry especialy using picture  is at medium category with average score 67.
Pengaruh Lama Rebusan Daun Sirih terhadap Responsifitas Mastitis Sapi Perah
Authors: Mano Serliana , Sio Stefanus , Purwantiningsih Theresia I.
Published: March 2021

Mastitis merupakan peradangan ambing yang dapat disebabkan oleh masuknya bakteri melalui lubang puting. Secara ekonomi, mastitis sangat merugikan peternak karena dapat menurunkan produksi susu. Tujuan dari penelitian ini untuk memberikan alternatif larutancelup puting yang aman, murah dan mudah ditemukan oleh masyarakat dan peternak. Penelitian ini dilaksanakan pada bulan September sampai Oktober 2019 di Peternakan Biara Claretian Benlutu, TimorTengahSelatan.Metode yang digunakan adalah Rancangan AcakLengkap (RAL) yang terdiri dari 4 perlakuan 3 ulangan sehingga terdapat 12 unit percobaan.Perlakuan yang diberikan adalah sebagai berikutR0=Air biasa, R1=Larutan antiseptik komersial, R2=Rebusandaunsirih 45 menit dan R3=Rebusandaunsirih 60 menit. Variabel yang diamatiadalahhasildeteksi mastitis dan uji derajatkeasaman susu (uji pH). Hasil penelitianmenunjukkan pemberian rebusan daun sirihmemberikan pengaruh yangtidak signifikan terhadap hasildeteksi mastitis dan tingkat keasaman (pH). Disimpulkan bahwa rebusan daun sirih mempunyai kemampuan yang sama dengan antisep komersil dalam mencegah terjadinya mastitis pada ternak sapi perah di Peternakan Claretian Benlutu.
EFFECT OF NONI FRUIT EXTRACT ON THE INTERNAL QUALITY, FOAM INDEX, AND HAUGH UNIT OF THE CHICKEN EGGS
Authors: Abi Natalius , Lisnahan Charles Venirius , Purwatiningsih Theresia Ika
Published: March 2021

This study aimed to determine the effect of noni fruit extract on the internal quality, foam index, and haugh unit of layers eggs. This research has been carried out at the Chemistry Laboratory of Widya Mandira University Kupang, and the Laboratory of the Faculty of Agriculture, University of Timor, Kefamenanu during February 12, until March 25, 2020. This study used eggs of layer chicken, each treatment using 25 eggs. The method used was a completely randomized design with a one-way pattern consisting of 5 treatments and 5 replications. The treatments given were T0 (control), T1 (2 ml noni fruit extract), T2 (4 ml noni fruit extract), T3 (6 ml noni fruit extract), and T4 (ampicillin). The variables observed were egg weight, air sac diameter, albumen height, egg yolk index, foam leakage, foam index, and Haugh unit. The results of statistical analysis showed the effect of noni fruit extract on egg weight, air sac diameter, foam leakage, foam index, and Haugh unit value. The mean value of each variable showed that the 6 ml (T3) noni extract treatment was better than the other treatments (T0, T1, T2, and T4). It was concluded that to maintain egg quality for up to 21 days, could be preserved with a concentration of 6% noni fruit extract.
PERNIKAHAN BEDA AGAMA PERSPEKTIF HUKUM ISLAM DAN HUKUM POSITIF DI INDONESIA
Authors: Fuadi Ahmad , Sy Devi Anggreni
Published: March 2021

Dalam Islam Perkawinan beda agama dilarang oleh kebanyakan ulama. Hal ini merujuk pada al-Qur’an surat al-Baqarah ayat 221 dan Qur’an surat al-Mumtahanah ayat 10, Namun akibat adanya pandangan yang berbeda tentang hukum perkawinan beda agama, hal ini berdasarkan Alquran surat al-Ma‟idah ayat 5. Disamping itu juga terdapat kontradiktif tentang aturan pernikahan beda agama antara Pasal 56 Undang-Undang No. 1 Tahun 1974 Tentang Perkwainan yang membuka peluang untuk dilakukannya pernikhan beda agama dengan Kompilasi Hukum Islam Pasal 44 Kompilasi Hukum yang menutup sama sekalai pernikahan beda agama. Oleh sebab itu banyak terjadi perkawinan beda agama di kalangan umat Islam, dan menimbulkan masalah yaitu bagaimana kawin beda agama ini dipandang baik menurut hukum Islam, dan hukum positip Indonesia. Penelitian ini bersifat diskriptik analitik dengan menggunakan pendekatan yuridis normatif. Data yang sudah terkumpul dianalisa secara kualitatif dengan metode berfikir deduktif dan induktif. Pada akhirnya nanti dapat disimpulkan bahwa hakikat pernikahan adalah sebuah kontrak sosial, sehingga segala hal mengenai pernikahan sudah seyogyanya dikembalikan pada nilai-nilai subyektifitas yang akan melaksanakannya, sekalipun terdapat pelarangan seharusnya lebih bersifat sosiologis, bukan teologis dan realisasinyapun harus melalui fakta yang empirik bukan hanya prasangka-prasangka yang mengakibatkan sentimen kolektif terhadap komunitas lain
Pembuatan dan Pelatihan Website Administrasi Desa Bukit Lingkar Kecamatan Batang Cenaku Kabupaten Indragiri Hulu
Authors: Yulida Roza , Rosnita Rosnita , Kurnia Deby , Andriani Yulia , Septya Fanny
Published: March 2021

A website is a whole web page that contains enormous information contained in a domain. Information on the web is presented on a web page which is formed from a collection of text, graphics, images, sound, and video. The purpose of making a website is to facilitate an agency, organization, and so on in containing information that can be accessed by the public at large. With the development of information technology, Indragiri Hulu District, in general, Bukit Lingkar Village, can access and find out the expected information about the village. Therefore we tried to design a Village Administration Website which later on the website will contain information about the Village and Village information in Bukit Lingkar Village and provide community training on how to use the website. In the process of creating and training this website, there are several activities carried out such as training on creating websites for Kukerta students, training for village government administrators in managing the website to launching the website. This activity starts with a vulnerable time from July to August 2020.
Pembuatan Meja Bak Cuci Tangan Menggunakan Mutu Beton Sederhana dengan Memanfaatkan Limbah Olahan Rotan dan Sosialisasi Cuci Tangan 6 Langkah di Panti Asuhan Budi Mulya Kota Palangka Raya
Authors: Respati Rida , Puspasari Nirwana , Jaya Hendra Putra , Silaban Ridho Saleh , Permana Ari Widya
Published: March 2021

The development of coronavirus or Covid-19 in Central Kalimantan is currently increasingly worrying. All areas in this province are now in red zone status. This transmission is very fast spreading, so we are doing outreach to the community at Budi Mulya Orphanage, Palangka Raya City, implementing 6 recommended handwashing steps to kill the Covid 19 virus that sticks to our fingers. Washing hands with soap is one of the sanitation measures to prevent disease. Even WHO also recommends 6 steps in washing the palms of hands, the palms of backs of hands, between the fingers, the backs of hands, the thumbs, and the tips of fingers. The last method of washing hands is to clean soap with running water and dry it. To support the 6-step handwashing program, we are working with the orphanage's leadership to make a table for a water storage basin used for washing hands. The table is made permanent, made of reinforced concrete, whose composition of the reinforced concrete mixture is mixed with processed rattan waste that is no longer used as a substitute for concrete fiber. The rattan waste mixture used was 0.25% of the total volume of concrete.
Seismic Fragility Analysis of Base Isolated Structure Subjected to Near-fault Ground Motions
Authors: Liu Chengqing , Fang Dengjia , Yan Zhengxi
Published: March 2021

In order to better evaluate the performance of the base isolated structure under the near-fault earthquakes, this paper takes into consideration an existing engineering case study in China as the prototype, and uses OpenSEES platform to establish the nonlinear finite element model of the base isolated structure. The nonlinear response of the isolated structure under the near-fault earthquake is analyzed. The incremental dynamic analysis (IDA) method is used to calculate the damage probability of the structure under the near-fault earthquake, and the fragility curve of the base isolated structure is established. The fragility equation is obtained by nonlinear regression, and the error of fragility equation is analyzed. The results show that the maximum value of the inter-story drift of the upper structure under the action of near-fault earthquake is significantly greater than that under the action of far-fault earthquake. With the increase of seismic intensity, the damage probability of base isolated structure increases nonlinearly, and the maximum response value of horizontal displacement of bearing and inter-story drift of superstructure increases generally. In addition, the exceeding probability of the fragility curve based on PSDA is greater than that based on EDP criterion. When the sample points of the two methods are the same, the exceeding probability points calculated based on PSDA can be regarded as accurate values. The fragility curve based on PSDA may overestimate the exceeding probability to some extent, and the overestimation may be enlarged with the increase of failure stage.
Optimal Plastic Analysis and Design of Pile Foundations Under Reliable Conditions
Authors: Movahedi Rad Majid , Khaleel Ibrahim Sarah
Published: March 2021

In this research, in order to evaluate the plastic limit load and also plastic design parameters of the long pile foundations subjected to horizontal loads, shakedown method is applied. In carrying out shakedown analysis and design methods, large plastic deformations and residual displacements could develop in the pile foundation which might lead to the failure of the structure. For this reason, complementary strain energy of residual forces proposed as a limit condition to control the plastic deformation of the pile structure. Furthermore, considering the uncertainties (strength, manufacturing, geometry) the limit conditions on the complementary strain energy of residual forces are assumed randomly and the reliability condition was formed by the use of the strict reliability index. The influence of the limit conditions on the plastic limit load and design parameters of the long pile in cohesionless soil subjected to lateral load were investigated and limit curves for shakedown load factors are presented. The numerical results show that the probabilistic given limit conditions on the complementary strain energy of residual forces have significant influence on the load bearing limit and the design parameters of pile foundations. The formulations of the reliability based problems lead to mathematical programming which were carried out by the use of non-linear algorithm.
Method for optimization of switching frequency in frequency converters
Authors: Nerubatskyi V. P. , Plakhtii O. A. , Tugay D. V. , Hordiienko D. A.
Published: March 2021

Purpose. To present a methodology for determining the optimal switching frequency in frequency converters and autonomous voltage inverters, the load of which is an asynchronous electric motor. The methodology is based on determining the dependences of static and dynamic power losses in the power switches of the inverter on the switching frequency and the dependence of power losses in the windings of an induction motor on the higher harmonics of currents, which also depend on the switching frequency. Methodology. Polynomial approximation of the energy characteristics of power transistors. General provisions of the theory of electrical circuits. The determination of additional power losses in the windings of an induction motor from higher harmonics is based on analytical calculation and simulation in the Matlab/Simulink software environment and a specialized program from the manufacturer of power switches Mitsubishi MelcoSim5.1. Findings. A method for optimizing the frequency of pulse-width modulation in frequency converters, the load of which is an asynchronous motor, is presented according to the criterion of the minimum total power losses in the power transistors of the inverter and the resistance of the motor windings. The proposed calculation technique allows determining the dependence of static and dynamic losses in power IGBT-transistors with a sufficiently high accuracy while being in the MelcoSim software environment. To calculate the losses in the motor, it is shown that the switching frequency of the power switches affects the harmonic distortion factor and the average value of the phase current of the induction motor. Provided that only the first harmonic of the current performs the useful action in an asynchronous motor, the dependence of additional power losses on the switching frequency is given. Originality. A method for optimizing the frequency of pulse-width modulation by the criterion of minimum additional power losses in the resistance of the motor windings from higher harmonics of the current and static and dynamic losses in the power transistors of the inverter is presented. An analytical dependence of additional power losses in the active resistance of the windings of induction motors as a function of the harmonic distortion factor of the phase current of an autonomous voltage inverter is presented. Practical value. The presented technique makes it possible to determine the optimal modulation frequency in frequency converters with asynchronous motors and to ensure the minimum total power losses and the maximum value of efficiency in the autonomous voltage inverter asynchronous motor system.
Company business process optimization as an imperative of its economic security
Authors: Zelisko I. , Sosnovska O. , Oliinyk L. , Stefkivskyy V. , Manaienko I.
Published: March 2021

Purpose. To work out an algorithm of an entrepreneur business process optimization in order to systemize and ensure the quality of implementation of key business processes of an insurer as the condition of increasing his/her level of economic security in a turbulent business environment. Methodology. In the study there were used general scientific and specific methods of cognition, in particular: logical colligation, analysis, dialectic synthesis and grouping, induction and deduction, process approach, factor analysis, graphical visualization, economic-mathematical modelling. Findings. The necessity of business process optimization for an insurer was established as a strategically important subject of market relationship development. A logical-structural scheme of interconnection of the main business processes of an insurer is formed; the processes are gradually implemented by stages of insurance services progress, risks underwriting, reinsurance, effecting of an insurance agreement, forming and placing insurance funds and settlement of losses. The main structural elements of the insurers business process optimization were systemized. The methodical approach to the insurers business processes reengineering was proposed on the basis of the games theory just to form a new model of business processes and to increase its optimization process effectiveness. Originality. An algorithm of the insurers business process optimization was worked out, which includes the process of their planning, diagnostics, implementation of changes and monitoring just to increase the quality of key business process realization as the condition for ensuring economically safe functioning of the business entity. Practical value. The practical value is in the possibility to use them in insurance companies activities, which will ensure their sustainable functioning and development in the strategic perspective.
Relación entre calidad de servicio y retención del cliente del servicio móvil en operadora telefónica
Authors: Aguirre John , Pillaca Caleb , Quispe Rocío
Published: March 2021

Hoy en día el servicio telefónico en el mundo ha pasado a ser indispensable, no solo en el ámbito comercial, sino también en el social. Por lo que, la falta de optimización en la presentación de este servicio público en Anco Huallo, Chincheros, llevó a establecer una investigación en donde su principal objetivo es conocer la relación que existe entre la calidad de servicio y la retención del cliente, para ello fue necesario recoger y analizar datos cuantitativos, que aportaron a la creación de una base teórica sobre la relación de las variables de estudio. Siendo utilizado como fundamento teórico el Reglamento General de la Calidad de los Servicios Públicos de Telecomunicaciones emitido por el ente regulador, mientras que para la recolección de datos se estructuro un cuestionario con 10 preguntas para la variable calidad de servicio y 11 preguntas para la variable retención del cliente, la misma que fue aplicado en formato de encuesta. Dando como resultado en el análisis de confiabilidad de Alfa de Cronbach de cada instrumento un 0,61 y 0,65, ello muestra una alta confiabilidad. Por otra parte, se usó del coeficiente Rho de Spearman para conocer la relación entre la calidad de servicio y la retención de los clientes, se obtuvo como resultado un valor 0,691; concluyéndose que existe una relación significativamente moderada entre las variables de estudio.
A Reforma Trabalhista e os Honorários Advocatícios Sucumbenciais: A mitigação das garantias constitucionais do amplo acesso à jurisdição e da assistência judiciária integral gratuita
Authors: Salomão Pedro Emílio Amador , Vieira Rodrigo Gomes de Castro , Leonarde Geovana Silveira Soares
Published: March 2021

A presente obra evidencia, a priori, um enfoque amplo acerca dos aspectos básicos inerentes à lei 13.467/2017, conhecida como a Reforma Trabalhista, objetivando a exposição de questões essenciais da desta, e, ainda, nesta temática, demonstra-se a contradição legislativa existente entre as sucintas mudanças legislativas objetivadas pelo projeto de lei que deu origem à lei 13.467/2017 e as reais e inúmeras alterações efetuadas pela Reforma Trabalhista, culminando em variados impactos no direito material e processual trabalhista. De maneira contextual, esta obra expõe, ademais, a colossal incidência dos direitos constitucionais na seara justrabalhista, salientando, mormente, a devida definição e valorosa aplicação dos princípios constitucionais fundamentais do amplo acesso à justiça e da assistência gratuita e integral neste ramo jurídico. Inserindo-se em temática específica, este artigo apresenta o novo artigo 791-A, da CLT, e explicita as graves consequências provocadas por este dispositivo legal sobre o paradigma processual trabalhista, culminando na indevida e nociva mitigação de garantias constitucionais que eram sinal de segurança e proteção jurídica ao jurisdicionado.
Female philopatry in smalltooth sawfish Pristis pectinata: conservation and management implications
Authors: Smith KL , Feldheim K , Carlson JK , Wiley TR , Taylor SS
Published: March 2021

Populations are more effectively managed with information on breeding and dispersal behavior, making the evaluation of these characteristics essential for effective conservation of a species. In the USA, 2 critical habitat units were designated in 2009 for the federally endangered smalltooth sawfish Pristis pectinata. Previous research in the Charlotte Harbor Estuary Unit (CHEU) of critical habitat shows that female smalltooth sawfish are polyandrous and highly philopatric to nursery grounds. However, these characteristics have not yet been examined in a larger area of designated critical habitat: the Ten Thousand Islands/Everglades Unit (TTIEU). We used microsatellite genotypes from 214 juvenile smalltooth sawfish to examine mating and dispersal behavior via sibship analyses and reconstruction of parental genotypes with the program COLONY. Parental reconstruction yielded 71 female and 117 male genotypes. Many females returned to the same region within TTIEU for parturition on a biennial cycle; however, at least 1 female switched parturition sites within TTIEU and at least 2 females produced litters in both TTIEU and CHEU over the study period. The maximum number of pups genetically assigned to 1 female was 12, a number that is consistent with that found for CHEU (8 pups), and within the litter size range reported (7 to 14) for the species. Confirmation of these mating behaviors and reproductive characteristics is important for understanding how the present population uses these protected habitats at different life stages, and for determining future habitat protection and population expansion strategies to restore smalltooth sawfish to previously occupied areas of their range.
INTERAKSI SOSIAL ONLINE DAN KECEMASAN SOSIAL SEBAGAI PREDIKTOR KECANDUAN INTERNET PADA REMAJA
Authors: Hidayat Putra
Published: March 2021

This study aims to examine the effect of online social interaction and social anxiety  on internet addiction in adolescents. Employing an ex-post facto design, this research was conducted in the regency of Purbalingga involving 366 teenagers as sample which was determined using a multistage random sampling techniques. Data were collected through questionnaires consisting of internet addiction questionnaires, online social interaction questionnaires, and social anxiety questionnaires. These instruments were validation through content validity and reliability based on Cronbach’s Alpha coefficient. The data where then analysed by means of a multiple regression analysis.The results showed that there was a significant effect of online social interaction and social anxiety  on internet addiction in adolescents (p=0,000). Therefore, it can be concluded that there is a effect between online social interaction and social anxiety towards the adolescents internet addiction. Online social interaction and social anxiety can be strong predictors of internet addiction among adolescents.
A Parallel Perifusion Slide From Glass for the Functional and Morphological Analysis of Pancreatic Islets
Authors: Schulze Torben , Mattern Kai , Erfle Per , Brüning Dennis , Scherneck Stephan , Dietzel Andreas , Rustenbeck Ingo
Published: March 2021

An islet-on-chip system in the form of a completely transparent microscope slide optically accessible from both sides was developed. It is made from laser-structured borosilicate glass and enables the parallel perifusion of five microchannels, each containing one islet precisely immobilized in a pyramidal well. The islets can be in inserted via separate loading windows above each pyramidal well. This design enables a gentle, fast and targeted insertion of the islets and a reliable retention in the well while at the same time permitting a sufficiently fast exchange of the media. In addition to the measurement of the hormone content in the fractionated efflux, parallel live cell imaging of the islet is possible. By programmable movement of the microscopic stage imaging of five wells can be performed. The current chip design ensures sufficient time resolution to characterize typical parameters of stimulus-secretion coupling. This was demonstrated by measuring the reaction of the islets to stimulation by glucose and potassium depolarization. After the perifusion experiment islets can be removed for further analysis. The live-dead assay of the removed islets confirmed that the process of insertion and removal was not detrimental to islet structure and viability. In conclusion, the present islet-on-chip design permits the practical implementation of parallel perifusion experiments on a single and easy to load glass slide. For each immobilized islet the correlation between secretion, signal transduction and morphology is possible. The slide concept allows the scale-up to even higher degrees of parallelization.
Longtime Vision Function Prediction in Childhood Cataract Patients Based on Optical Coherence Tomography Images
Authors: Xiang Yifan , Chen Jingjing , Xu Fabao , Lin Zhuoling , Xiao Jun , Lin Zhenzhe , Lin Haotian
Published: March 2021

The results of visual prediction reflect the tendency and speed of visual development during a future period, based on which ophthalmologists and guardians can know the potential visual prognosis in advance, decide on an intervention plan, and contribute to visual development. In our study, we developed an intelligent system based on the features of optical coherence tomography images for long-term prediction of best corrected visual acuity (BCVA) 3 and 5 years in advance. Two hundred eyes of 132 patients were included. Six machine learning algorithms were applied. In the BCVA predictions, small errors within two lines of the visual chart were achieved. The mean absolute errors (MAEs) between the prediction results and ground truth were 0.1482–0.2117 logMAR for 3-year predictions and 0.1198–0.1845 logMAR for 5-year predictions; the root mean square errors (RMSEs) were 0.1916–0.2942 logMAR for 3-year predictions and 0.1692–0.2537 logMAR for 5-year predictions. This is the first study to predict post-therapeutic BCVAs in young children. This work establishes a reliable method to predict prognosis 5 years in advance. The application of our research contributes to the design of visual intervention plans and visual prognosis.
On the Wrong Track: Alterations of Ciliary Transport in Inherited Retinal Dystrophies
Authors: Sánchez-Bellver Laura , Toulis Vasileios , Marfany Gemma
Published: March 2021

Ciliopathies are a group of heterogeneous inherited disorders associated with dysfunction of the cilium, a ubiquitous microtubule-based organelle involved in a broad range of cellular functions. Most ciliopathies are syndromic, since several organs whose cells produce a cilium, such as the retina, cochlea or kidney, are affected by mutations in ciliary-related genes. In the retina, photoreceptor cells present a highly specialized neurosensory cilium, the outer segment, stacked with membranous disks where photoreception and phototransduction occurs. The daily renewal of the more distal disks is a unique characteristic of photoreceptor outer segments, resulting in an elevated protein demand. All components necessary for outer segment formation, maintenance and function have to be transported from the photoreceptor inner segment, where synthesis occurs, to the cilium. Therefore, efficient transport of selected proteins is critical for photoreceptor ciliogenesis and function, and any alteration in either cargo delivery to the cilium or intraciliary trafficking compromises photoreceptor survival and leads to retinal degeneration. To date, mutations in more than 100 ciliary genes have been associated with retinal dystrophies, accounting for almost 25% of these inherited rare diseases. Interestingly, not all mutations in ciliary genes that cause retinal degeneration are also involved in pleiotropic pathologies in other ciliated organs. Depending on the mutation, the same gene can cause syndromic or non-syndromic retinopathies, thus emphasizing the highly refined specialization of the photoreceptor neurosensory cilia, and raising the possibility of photoreceptor-specific molecular mechanisms underlying common ciliary functions such as ciliary transport. In this review, we will focus on ciliary transport in photoreceptor cells and discuss the molecular complexity underpinning retinal ciliopathies, with a special emphasis on ciliary genes that, when mutated, cause either syndromic or non-syndromic retinal ciliopathies.
All Roads Lead to Cytosol: Trypanosoma cruzi Multi-Strategic Approach to Invasion
Authors: Ferri Gabriel , Edreira Martin M.
Published: March 2021

T. cruzihas a complex life cycle involving four developmental stages namely, epimastigotes, metacyclic trypomastigotes, amastigotes and bloodstream trypomastigotes. Although trypomastigotes are the infective forms, extracellular amastigotes have also shown the ability to invade host cells. Both stages can invade a broad spectrum of host tissues, in fact, almost any nucleated cell can be the target of infection. To add complexity, the parasite presents high genetic variability with differential characteristics such as infectivity. In this review, we address the several strategiesT. cruzihas developed to subvert the host cell signaling machinery in order to gain access to the host cell cytoplasm. Special attention is made to the numerous parasite/host protein interactions and to the set of signaling cascades activated during the formation of a parasite-containing vesicle, the parasitophorous vacuole, from which the parasite escapes to the cytosol, where differentiation and replication take place.
A Refined Method to Analyze Insoluble Particulate Matter in Ice Cores, and Its Application to Diatom Sampling in the Antarctic Peninsula
Authors: Tetzner Dieter , Thomas Elizabeth R. , Allen Claire S. , Wolff Eric W.
Published: March 2021

The insoluble particulate matter deposited on ice sheets provide key information to reconstruct past climate. The low concentration of some insoluble particulate matter, such as terrigenous particles and microfossils, challenges the efficiency of the recovery and the representativeness of the results. Here we present a new optimized method to extract, quantify and classify targeted low concentration insoluble particulate matter. Particle recovery rates and particle distribution were investigated using polystyrene particle standards filtered through Polycarbonate membrane filters and subsequently scanned in a scanning electron microscope. Experimental results in continuous and discrete sampling systems reveal consistent trends in the transport and removal of particulate material inside a filtration system. Statistical simulations are used to optimize the sample analyses required to achieve representative results. The analysis of diatoms in ice cores using this new method uncovered their potential to hold valuable climate records from the Antarctic Peninsula region. The data presented here evidence the presence of a measurable amount of marine diatoms with sub-annual variations, highlighting the potential of this record as a seasonal indicator. The new method presented provides an optimized and statistically representative approach for extracting, recovering and analyzing micrometre-sized, low-concentration insoluble particulate matter in ice.
Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice
Authors: Ramirez-Hernandez Gabriela , Adan-Castro Elva , Diaz-Lezama Nundehui , Ruiz-Herrera Xarubet , Martinez de la Escalera Gonzalo , Macotela Yazmin , Clapp Carmen
Published: March 2021

Prolactin (PRL) levels are reduced in the circulation of rats with diabetes or obesity, and lower circulating levels of PRL correlate with increased prevalence of diabetes and a higher risk of metabolic alterations in the clinic. Furthermore, PRL stimulates β-cell proliferation, survival, and insulin production and pregnant mice lacking PRL receptors in β-cells develop gestational diabetes. To investigate the protective effect of endogenous PRL against diabetes outside pregnancy, we compared the number of cases and severity of streptozotocin (STZ)-induced hyperglycemia between C57BL/6 mice null for the PRL receptor gene (Prlr-/-) and wild-type mice (Prlr+/+). STZ-treated diabetic Prlr-/- mice showed a higher number of cases and later recovery from hyperglycemia, exacerbated glucose levels, and glucose intolerance compared to the Prlr+/+ mice counterparts. Consistent with the worsening of hyperglycemia, pancreatic islet density, β-cell number, proliferation, and survival, as well as circulating insulin levels were reduced, whereas α-cell number and pancreatic inflammation were increased in the absence of PRL signaling. Deletion of the PRL receptor did not alter the metabolic parameters in vehicle-treated animals. We conclude that PRL protects whole body glucose homeostasis by reducing β-cell loss and pancreatic inflammation in STZ-induced diabetes. Medications elevating PRL circulating levels may prove to be beneficial in diabetes.
Association of Other Autoimmune Diseases With Thyroid Eye Disease
Authors: Kelada Mary , Avari Parizad , Farag Soma , Akishar Rashmi , Jain Rajni , Aziz Ahmad , Feeney Claire , Bravis Vassiliki , Meeran Karim , Lee Vickie
Published: March 2021

Background

Thyroid eye disease (TED) is a potentially disfiguring and sight-threatening autoimmune (AI) orbitopathy, affecting up to 400,000 people in the UK. There are no accurate early predictors of TED severity. Although polyautoimmunity has been shown to affect AI disease severity, its influence on TED severity has never been investigated. The prevalence of polyautoimmunity among TED patients is also unclear, with discordant results reported in the literature. This study evaluates the prevalence of non-thyroid/“other” AI (OAI) conditions in an ethnically diverse TED cohort and assesses how polyautoimmunity affects TED severity and activity.

Methods

A retrospective study of patients presenting to multidisciplinary TED clinics across three North-West London hospitals between 2011 and 2019. Data collected included: 1) demographics; 2) OAI conditions and management; 3) endocrine management of thyroid dysfunction; 4) details of TED and clinical activity score at presentation.

Results

Two hundred and sixty-seven patients with a median age of 46 (35–54) years were included, 79.4% were female and 55% were Black, Asian and minority ethnic (BAME). Thirty-seven patients (13.9%) had OAI conditions, with rheumatoid arthritis (3.7%), vitiligo (3.0%) and psoriasis (3.0%) among the most prevalent. Of patients with OAI conditions, 43.2% (16/37) required immunosuppression prior to TED onset. Non-immunosuppressed patients with OAI conditions had a significantly higher clinical activity score at presentation than TED-only and previously immunosuppressed patients (p=0.02). No significant differences were observed in thyroid receptor antibody titers between these groups.

Conclusions

This study finds a 13.9% prevalence of OAI conditions among TED patients. Patients with OAI conditions overall have a tendency for more severe and significantly more clinically active TED than those without OAI conditions. Larger, prospective studies are warranted to further evaluate polyautoimmunity as an early predictor of TED severity.
Bovine Holo-Beta-Lactoglobulin Cross-Protects Against Pollen Allergies in an Innate Manner in BALB/c Mice: Potential Model for the Farm Effect
Authors: Afify Sheriene Moussa , Pali-Schöll Isabella , Hufnagl Karin , Hofstetter Gerlinde , El-Bassuoni Maha Abdel-Rafea , Roth-Walter Franziska , Jensen-Jarolim Erika
Published: March 2021

The lipocalin beta-lactoglobulin (BLG) is a major protein compound in cow’s milk, and we detected it in cattle stable dust. BLG may be a novel player in the farm protective effect against atopic sensitization and hayfever. In previous studies, we demonstrated that only the ligand-filled holo-form of BLG prevented sensitization to itself. Here, we investigated whether holo-BLG could, in an innate manner, also protect against allergic sensitization to unrelated birch pollen allergens using a murine model. BALB/c mice were nasally pretreated four times in biweekly intervals with holo-BLG containing quercetin–iron complexes as ligands, with empty apo-BLG, or were sham-treated. Subsequently, mice were intraperitoneally sensitized two times with apo-BLG or with the unrelated birch pollen allergen apo-Bet v 1, adjuvanted with aluminum hydroxide. After subsequent systemic challenge with BLG or Bet v 1, body temperature drop was monitored by anaphylaxis imaging. Specific antibodies in serum and cytokines of BLG- and Bet v 1-stimulated splenocytes were analyzed by ELISA. Additionally, human peripheral blood mononuclear cells of pollen allergic subjects were stimulated with apo- versus holo-BLG before assessment by FACS. Prophylactic treatment with the holo-BLG resulted in protection against allergic sensitization and clinical reactivity also to Bet v 1 in an unspecific manner. Pretreatment with holo-BLG resulted in significantly lower BLG-as well as Bet v 1-specific antibodies and impaired antigen-presentation with significantly lower numbers of CD11c+MHCII+ cells expressing CD86. Pretreatment with holo-BLG also reduced the release of Th2-associated cytokines from Splenocytes in BLG-sensitized mice. Similarly,in vitrostimulation of PBMCs from birch pollen allergic subjects with holo-BLG resulted in a relative decrease of CD3+CD4+ and CD4+CRTh2 cells, but not of CD4+CD25+CD127− Treg cells, compared to apo-BLG stimulation. In conclusion, prophylactic treatment with holo-BLG protected against allergy in an antigen-specific and -unspecific manner by decreasing antigen presentation, specific antibody production and abrogating a Th2-response. Holo-BLG therefore promotes immune resilience against pollen allergens in an innate manner and may thereby contribute to the farm protective effect against atopic sensitization.
The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India
Authors: Shabrish Snehal , Kelkar Madhura , Yadav Reetika Malik , Bargir Umair Ahmed , Gupta Maya , Dalvi Aparna , Aluri Jahnavi , Kulkarni Manasi , Shinde Shweta , Sawant-Desai Sneha , Kambli Priyanka , Hule Gouri , Setia Priyanka , Jodhawat Neha , Gaikwad Pallavi , Dhawale Amruta , Nambiar Nayana , Gowri Vijaya , Pandrowala Ambreen , Taur Prasad , Raj Revathi , Uppuluri Ramya , Sharma Ratna , Kini Pranoti , Sivasankaran Meena , Munirathnam Deenadayalan , Vedam Ramprasad , Vignesh Pandiarajan , Banday Aaqib , Rawat Amit , Aggarwal Amita , Poddar Ujjal , Girish Meenakshi , Chaudhary Abhijit , Sampagar Abhilasha , Jayaraman Dharani , Chaudhary Narendra , Shah Nitin , Jijina Farah , Chandrakla S. , Kanakia Swati , Arora Brijesh , Sen Santanu , Lokeshwar Madhukar , Desai Mukesh , Madkaikar Manisha
Published: March 2021

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.
The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity
Authors: Torti Maria Florencia , Giovannoni Federico , Quintana Francisco Javier , García Cybele Carina
Published: March 2021

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which interacts with a wide range of organic molecules of endogenous and exogenous origin, including environmental pollutants, tryptophan metabolites, and microbial metabolites. The activation of AHR by these agonists drives its translocation into the nucleus where it controls the expression of a large number of target genes that include the AHR repressor (AHRR), detoxifying monooxygenases (CYP1A1 and CYP1B1), and cytokines. Recent advances reveal that AHR signaling modulates aspects of the intrinsic, innate and adaptive immune response to diverse microorganisms. This review will focus on the increasing evidence supporting a role for AHR as a modulator of the host response to viral infection.
Lacunar Stroke Lesion Extent and Location and White Matter Hyperintensities Evolution 1 Year Post-lacunar Stroke
Authors: Valdés Hernández Maria del C. , Grimsley-Moore Tara , Sakka Eleni , Thrippleton Michael J. , Chappell Francesca M. , Armitage Paul A. , Makin Stephen , Wardlaw Joanna M.
Published: March 2021

Lacunar strokes are a common type of ischemic stroke. They are associated with long-term disability, but the factors affecting the dynamic of the infarcted lesion and the brain imaging features associated with them, reflective of small vessel disease (SVD) severity, are still largely unknown. We investigated whether the distribution, volume and 1-year evolution of white matter hyperintensities (WMH), one of these SVD features, relate to the extent and location of these infarcts, accounting for vascular risk factors. We used imaging and clinical data from all patients [n = 118, mean age 64.9 (SD 11.75) years old] who presented to a regional hospital with a lacunar stroke syndrome within the years 2010 and 2013 and consented to participate in a study of stroke mechanisms. All patients had a brain MRI scan at presentation, and 88 had another scan 12 months after. Acute lesions (i.e., recent small subcortical infarcts, RSSI) were identified in 79 patients and lacunes in 77. Number of lacunes was associated with baseline WMH volume (B = 0.370, SE = 0.0939, P = 0.000174). RSSI volume was not associated with baseline WMH volume (B = 3.250, SE = 2.117, P = 0.129), but predicted WMH volume change (B = 2.944, SE = 0.913, P = 0.00184). RSSI location was associated with the spatial distribution of WMH and the pattern of 1-year WMH evolution. Patients with the RSSI in the centrum semiovale (n = 33) had significantly higher baseline volumes of WMH, recent and old infarcts, than patients with the RSSI located elsewhere [median 33.69, IQR (14.37 50.87) ml, 0.001 ≤ P ≤ 0.044]. But patients with the RSSI in the internal/external capsule/lentiform nucleus experienced higher increase of WMH volume after a year [n = 21, median (IQR) from 18 (11.70 31.54) ml to 27.41 (15.84 40.45) ml]. Voxel-wise analyses of WMH distribution in patients grouped per RSSI location revealed group differences increased in the presence of vascular risk factors, especially hypertension and recent or current smoking habit. In our sample of patients presenting to the clinic with lacunar strokes, lacunar strokes extent influenced WMH volume fate; and RSSI location and WMH spatial distribution and dynamics were intertwined, with differential patterns emerging in the presence of vascular risk factors. These results, if confirmed in wider samples, open potential avenues in stroke rehabilitation to be explored further.
The Relationship Between the Healthy Diet Index, Chronic Diseases, Obesity and Lifestyle Risk Factors Among Adults in Kaunas City, Lithuania
Authors: Dėdelė Audrius , Bartkutė Žydrūnė , Chebotarova Yevheniia , Miškinytė Auksė
Published: March 2021

A healthy and balanced diet is an important factor contributing to overall health and wellness. The aim of this study was to develop a Healthy Diet Index (HDI) score and assess its association with various chronic diseases and lifestyle risk factors. A cross-sectional survey included 1,111 adults aged 18 years and older. Information on dietary habits was collected using a questionnaire. Additional demographic, socioeconomic and lifestyle risk factors data were also collected. Sixteen food groups were used to develop the HDI score for the residents of Kaunas city, Lithuania based on the national recommendations, World Health Organization (WHO) and other guidance on a healthy diet. We used logistic regression models to assess the association of the HDI score with chronic diseases, obesity and lifestyle risk factors. We found that both males and females were lacking the optimal consumption of the base components of a healthy diet–fruits and vegetables, starchy carbohydrates, and proteins. We also observed significant associations between the HDI score and several outcomes such as hypertension, arrhythmia, physical activity, and obesity. The suggested HDI score could serve as a valuable tool in assessing and improving dietary habits beneficial for promoting health and preventing many diseases.