bluuebunny/crossref_metadata_2025 huggingface dataset:
Competency Based Post Graduate Residency Program at Patan Academy of Health Sciences, Nepal
Authors: Shrestha Shrijana , Shrestha Ashis , Shah Jay Narayan , Gongal Rajesh Nath
Published: April 2021

Competency-based medical education has evolved as an alternative approach in the residency training program. It shows potential to align educational programs with health system priorities through defining the competencies of graduating doctors. Designing and implementing Competency Based Post Graduate (CBPG) training in a resource-limited setting, where most of the trainings are still run in a conventional approach, is a big challenge. Patan Academy of Health Sciences, School of Medicine has taken the competency-based approach in the postgraduate residency training. Defining core competencies and connecting those to teaching methodology and assessment system are important initial steps in implementing the competency-based approach. The institution has implemented Entrustable Professional Activity (EPA), which is a unit of professional practice and helps to measure the trainees’ achievements in the form of milestones. This paper describes the process of piloting and implementing the CBPG program at this school.The school launched the CBPG training in 2018 and so far, three batches of residents have been enrolled in nine different subjects/disciplines. The first batch of trainee, having the PAHS Core competencies and the pre-defined discipline-specific EPAs certified, will be completing their training soon. The program is time and resource consuming. Continuous faculty development, commitment, supportive leadership and faculty readiness to adapt to newer approaches are the key to the program’s successful implementation.Keywords: Competency based medical education; Nepal; patan academy of health sciences; post graduate training; residency program
Dimensi Sosial dalam Tafsir Sufistik
Authors: Munshihah Aty
Published: April 2021

Faiḍ ar-Rahmān fī Tarjama Tafsīr Kalam Malik ad-Dayyān by KH. Shaleh Darat land has been read from a sufitic dimension. However, there is actually a social dimension that has escaped the previous readings. Therefore, this study provides a new perspective in reading the interpretation of KH. Soleh Darat especially in QS. al-Fatihah [1]: 1. This type of research is classified as library research . By using a contextual-sufistic approach, the results of this study are;  first , the two characteristics that are in the basmalah pronunciation not only show attributes for Allah but also humans; second , basmalah have social value in it, h al it is illustrated by their compassionate nature that also must be inculcated in ourselves humans themselves (both physical and spiritual) and then applied to the fellow beings by sharing sustenance and mutual reminded in his favor; third, the practice of social life as a symbol that there is God as the Creator.
Wakaf Uang Dalam Pandangan Fikih Muamalat Dan Undang-Undang
Authors: Sultan Antus Nasruddin Mohammad
Published: April 2021

Penelitian ini menggunakan metode kualitatif bersifat deskriptif. Pengumpulan data berasal dari wawancara kepada pihak yang terikat dengan pengelolaan wakaf uang di Bank CIMB Niaga Syariah serta mengumpulkan data dan mengkaji berbagai sumber tertulis yang terkait dengan praktik wakaf uang di Bank CIMB Niaga Syariah. Hasil penelitian ini menunjukkan bahwa: Praktik wakaf uang yang dilakukan bank CIMB Niaga Syariah adalah Wakif melakukan penyetoran dana wakaf secara langsung maupun tidak langsung melalui program atau jasa layanan di CIMB Niaga Syariah, lalu dana tersebut akan disetorkan ke rekening Giro berakad wadi’ah milik mitra Bank – yaitu Nazhir, kemudian Nazhir akan mengelola  dalam bentuk investasi di lembaga keuangan syariah dan mendapatkan bagi hasil yang akan disalurkan kepada mauquf ‘alaih. Bank CIMB Niaga Syariah Dalam tugasnya sebagai LKS PWU, Bank CIMB Niaga Syariah telah melaksanakan tugasnya sesuai dengan Hukum Islam dan Perundang-undangan yang berlaku di Indonesia.
An experimental, non-uremic rabbit model of peritoneal dialysis
Authors: Zunic-Bozinovski S , Lausevic Z , Krstic S , Jovanovic N , Trbojevic-Stankovic J , Stojimirovic B
Published: April 2021

Peritoneal dialysis (PD) is a well established method of
depuration in uremic patients. Standard dialysis solutions
currently in use are not biocompatible with the peritoneal
membrane. Studying effects of dialysate on peritoneal membrane
in humans is still a challenge. There is no consensus on the ideal
experimental model so far. We, therefore, wanted to develop a
new experimental non-uremic rabbit model of peritoneal dialysis,
which would be practical, easy to conduct, not too costly, and
convenient to investigate the long-term effect of dialysis fluids.
The study was done on 17 healthy Chinchilla male and female
rabbits, anesthetized with Thiopental in a dose of 0.5 mg/kg
body mass. A catheter, specially made from Tro-soluset (Troge
Medical GMBH, Hamburg, Germany) infusion system, was then
surgically inserted and tunneled from animals' abdomen to their
neck. The planned experimental procedure was 4 weeks of
peritoneal dialysate instillation. The presented non-uremic rabbit
model of peritoneal dialysis is relatively inexpensive, does not
require sophisticated technology and was well tolerated by the
animals. Complications such as peritonitis, dialysis fluid leakage,
constipation and catheter obstruction were negligible. This model
is reproducible and can be used to analyze the effects of different
dialysis solutions on the rabbit peritoneal membrane.
‘What's in a Name?’ Taxonomic Choices in the Field of Dance Studies
Authors: Mollenhauer Jeanette
Published: April 2021

Dance genres sometimes require categorisation and this article addresses a collective for which no universally-accepted terminology has been located. Using the example of the author's doctoral research in Australia, four alternatives are examined in turn: ‘folk’, ‘ethnic’, ‘world’ and ‘traditional’, with analysis of the advantages and problems embedded in each term. Discussion of the Australian social and political environment exemplifies pertinent location-specific issues that need to be addressed when making taxonomic choices. The article aims to stimulate further discursive commentary and encourage epistemological and linguistic clarity among dance scholars.
The Description of Mathematics Learning for Grade IV of Muhammadiyah Islamic Elementary School of Krendetan
Authors: Meliana Wulandari Meliana Wulandari , Sapti Mujiyem , Rizkia Pangestika Rintis
Published: April 2021

This research is entitled to describe the mathematics online learning for grades IV of Muhammadiyah Islamic Elemetary School of Krendetan. This research requires some sources such as the school principal, the classroom teachers, and the student guardians. The research design uses qualitative research design. The study collects data by using direct research, data from sources, and real evidence. The instruments in this study included: observation sheets, interview guides, and documentation checklists. The results of this study indicate that (1) there is a principal's policy in mathematics online learning for grade IV of Muhammadiyah Islamic Elemetary School of Krendetan. He has an important policy in implementing Mathematics online learning. The school principal conducts some socializations to the school association, the principal and the curriculum team to arrange learning tools such as lesson plans, syllabus, annual program, and semester program. (2) There is a role of the teacher in implementing mathematics online learning. The teacher’s role is like preparing learning tools such as lesson plans, syllabus, annual program, and semester program. The teaching and learning process starts from 07.00 a.m to 12.00 a.m. the stes are first, filling out forums for student absences and the teacher provides learning videos that contain materials and assignments that students must do. After completing the assignment, the students can collect but the teacher also provides a collection limit which is until 21.00 a,m. The assignment is given by the teacher by knowing the ability of students to solve problems according to how it works. (3) There is a role of the student’s guardian in implementing mathematics online learning. The implementation of mathematics online learning for grade IV is carried out from 07.00 a.m to 12.00 a.m by filling in the student attedance list and the teacher send the subject matter in the form of a video to be listened. After listening, the students then do the assignments given by the teacher. After completing the assignmnet, the students send assignments along with photos of students while studying.
META-ANALYSIS VARIASI MINAT BIDANG PENELITIAN PADA MAHASISWA D3 MANAJEMEN INFORMATIKA JURUSAN TEKNOLOGI INFORMASI DI POLITEKNIK NEGERI MALANG
Authors: Odhitya Desta Triswidrananta  , Imam Fahrur Rozi  , Atiqah Nurul Asri  , Rudy Ariyanto
Published: April 2021

Berdasarkan pengalaman yang ada, kebaruan topik Laporan Akhir (LA) yang diangkat oleh para mahasiswa masih sangat rendah, bahkan ada beberapa topik yang sama namun tempat yang berbeda. Padahal prodi D3 Manajemen Informatika (MI) memiliki keunggulan dalam hal keterbaruan teknologi dimana saat ini bidang teknologi informasi sangat berkembang pesat. Permasalahan lain yang muncul kaitan dengan Laporan Akhir (LA) mahasiswa yaitu adanya permasalahan yang diangkat hampir sama. Tentunya hal ini sangat ironis dengan keunggulan prodi D3 MI itu sendiri. Oleh karena itu, perlu adanya pemetakan topik penelitian laporan akhir mahasiswa tersebut melalui meta analisis. Karya / laporan akhir yang dibuat oleh mahasiswa D3 MI adalah Laporan Akhir (LA). Hasil karya / laporan akhir mahasiswa berupa perancangan dan pembuatan perangkat lunak yang bersifat aplikatif dan laporannya. Hasil Laporan Akhir tersebut harus berorientasi pada penyelesaian suatu permasalahan yang ada di industri atau masyarakat pada saat ini serta dapat diterapkan dan dikembangkan untuk beberapa tahun kedepan. Adapun topik dari laporan akhir yang dibuat oleh mahasiswa dalam bentuk Laporan Akhir yang dihasilkan meliputi bidang kajian antara lain: 1) Sistem Informasi; 2) Jaringan Komputer; 3) Multimedia dan Game
PERENCANAAN DAN ANALISIS KELAYAKAN INVESTASI PROYEK PEMASANGAN KAPASITOR BANK PADA INSTALASI PEMANFAATAN ENERGI LISTRIK
Authors: Epiwardi  , Ruwahyoto  , Heri sungkowo
Published: April 2021

The low power factor in the electricity installation of Sumber Wendit 3 water pumping stations causes a bill of excess reactive energy usage or kVARh, so that the cost of using electricity becomes higher. The excess use of reactive energy can be compensated by additional investment in installing capacitor banks in the main distribution panel (MDP) Sumber Wendit 3 water pump station. Based on the data and problems, it is planned to install capacitor banks that meet the standards with a target of 0.90 and 0.95 lagging. From the results of the planning, we need 150 kVAR and 250 kVAR capacitors, with an investment value of Rp. 94,983,790 and - Rp. 120,781,210. After an investment feasibility test using the Payback Period (PP) method, it is known that for a 150 kVAR bank capacitors, the investment return is technically 2.88 months and economically is 4.01 and 3.17 months. For 250 kVAR bank capacitors, the return on investment is technically 3.66 months and economically 5.1 and 4.03 months. When compared with the economic life of the investment is 10 years, the investment of the bank capacitor installation project is very profitable and feasible to carry out
ANALISIS PEMBEBANAN BELT CONVEYOR MENGGUNAKAN MOTOR INDUKSI 3 FASE 1,5 KW DAN VSD SEBAGAI SPEED CONTROLLER
Authors: Sigi Syah Wibowo  , Abdul Manaf  , Tresna Umar
Published: April 2021

Pendistribusian bahan baku maupun hasil produksi pada dunia industri dilakukan oleh alat pemindah bahan, seperti conveyor. Conveyor memiliki beberapa jenis, yaitu belt conveyor, screw conveyor, apron conveyor, dan pneumatic conveyor. Belt conveyor merupakan peralatan angkut material secara horizontal dengan cara mentransport muatan berupa unit maupun curah di atas sabuk yang digerakkan oleh drive / head pulley yang terhubung dengan puli transmisi, gear box, dan motor induksi 3 fasa 1,5 kW. Pengaturan kecepatan pada belt conveyor dilakukan oleh VSD dengan mode pengoperasian nLd melalui perubahan frekuensi yang dibutuhkan. Perencanaan dan pembuatan modul pembebanan belt conveyor memiliki kapasitas 6 ton/jam (100 kg/menit) dengan kecepatan 0,05 m/s dan diharapkan dapat digunakan untuk kegiatan praktikum mahasiswa di Laboratorium Gedung AL 1.01 Politeknik Negeri Malang. Rancang bangun modul pembebanan belt conveyor ini bertujuan untuk mengetahui perancangan, pembuatan, dan pengujian belt conveyor menggunakan motor induksi 3 phasa 1,5kW dan VSD sebagai speed controller. Selain itu juga mengetahui pengaruh variasi beban dan frekuensi terhadap kecepatan laju belt conveyor. Sehingga dengan model pembebanan tersebut dapat diketahui karakteristik modul berupa arus input motor, daya input, kecepatan motor, slip, efisiensi, dan kecepatan belt conveyor
PENGARUH PENDIDIKAN DAN KOMPETENSI DOSEN TERHADAP KUALITAS PENGAJARAN DI PROGRAM STUDI TEKNIK LISTRIK POLITEKNIK NEGERI MALANG
Authors: Hari Sucipto  , Sigit Setya Wiwaha  , Khrisna Hadiwinata
Published: April 2021

Penelitian ini bertujuan untuk mengetahui Pengaruh Pendidikan Dan Kompetensi Dosen Terhadap Kualitas Pengajaran Di Program Studi Teknik Listrik Politeknik Negeri Malang. Analisis data yang digunakan dalam penelitian ini adalah metode analisis data deskriptif kualitatif, yaitu analisis data yang mendeskripsikan serta menganalisis data yang diperoleh, kemudian dijabarkan dalam bentuk penjelasan yang sebenarnya, yang diawali dengan proses pengumpulan data, penyederhanaan data (data reduction), penyajian data (data display) dan penarikan kesimpulan (conclution drawing). Manfaat dari penelitian diharapkan dapat menjadi masukan bagi institusi dalam pengembangan dan peningkatan kemampuan dosen.
ANALISA CLOCK GENERATOR PADA RANGKAIAN POWER SUPPLY UNTUK APLIKASI TRIGER IC TTL DILABORATORIUM DIGITAL PROGRAM STUDI TEKNIK ELEKTRONIKA DI POLITEKNIK NEGERI MALANG
Authors: Hariyanto  , Rosita Ferdiyana
Published: April 2021

The good performance of a clock generator circuit in the power supply for triger TTL IC is very influential on the success of the lab. A series. Therefore, the effectiveness of use must be adapted to its use in the practicum. To create a clock generator circuit as a source of pulses from a digital counter IC, a timer IC can be used. This pulse generator or clock generator can be used for clock sources in making counters up and down. Clock generators are often referred to as clock generators. The pulse generator in making the circuit is often used linear integrated circuit (IC: Integrated Circuit). A linear IC that is commonly used in general is usually the NE555 which is a timer IC. As a timer it can also be used analogically as a Clock Generator or pulse generator which can generally generate the frequency or time as needed.
METODE INPUTING DATA SISTEM INFORMASI PEMINJAMAN LABORATORIUM TEKNIK ELEKTRONIKA POLITEKNIK NEGERI MALANG
Authors: Imam Saukani  , Eko Pamuji
Published: April 2021

This research report is a response to address the deficiencies in the lending system in laboratory instrumentation that is, the lending system is still done manually. The definition of a student loan to manually write the name, code and the number of tools that will be borrowed and submit the Student Identity Card (KTM) as collateral. Such borrowing procedure causes the system to become less effective ministry. In this Research Report, applications are made to the database in the laboratory identification using barcode technology. This application is created using ms access 2003 software for the database. The main function of this application is to simulate the process of borrowing and repayment instrumentation. The process was carried out through scanning the barcode on the card members (KTM) and instrumentation devices using barcode scanner. After the whole simulation process is complete, the data is stored in a database and can be printed to be used as evidence of borrowing. Other functions include, process data search've borrowed, instrumentation load, as well as lending report.
VALIDASI METODE ANALISA TOTAL FLAVONOID CONTENT MENGGUNAKAN SPECTROFOTOMETER UV/VIS JURUSAN TEKNIK KIMIA DI POLITEKNIK NEGERI MALANG
Authors: Rilla Agustina  , Lia Agustin  , Slamet Priyadi
Published: April 2021

Suatu pengembangan metode analisis diperlukan untuk mengurangi oksidan atau radikal bebas. Oksidan dapat menimbulkan kerusakan sel, menjadi penyebab atau mendasari berbagai keadaan patologik, dan ikut berperan dalam proses penuaan (aging). Flavonoid serupa dengan antioksidan, yang memiliki beragam manfaat untuk tubuh Anda, seperti dapat memperbaiki sel yang rusak akibat radikal bebas. Suplemen flavonoid juga diduga bisa mengurangi risiko kanker, hipertensi, dan diabetes. Pengujian terhadap kandungan Flavonoid Total metode AlCl3 menggunakan Spectrofotometer UV/Vis sangatlah perlu untuk di validasi. Perlunya validasi metode tersebut adalah untuk menentukan apakah seluruh tahap pengujian telah memenuhi standar yang ditetapkan. Hasil uji yang akurat adalah pencerminan dari pelaksanaan yang baik dari seluruh tahapan pengujian, maka: validasi metode dilakukan dengan cara menguji linieritas, presisi, akurasi, sampai LOD dan LOQ. Hasil penelitian menunjukkan linierisasi baik dengan nilai koefisien kolerasi (r) 0,9955, persen perolehan kembali sebesar 99,89%, batas deteksi sebesar 1,37 ppm dan batas kuantitas sebesar 0,516 ppm. Berdasarkan hasil penelitian tersebut, metode Total Flavonoid Content metode AlCl3 menggunakan spektrofotometri UV/Vis telah memenuhi standar validasi dan dikatakan valid.
Liquid Crystal Based Binding Assay for Detecting HIV-1 Surface Glycoprotein
Authors: Abbasi Amna Didar , Hussain Zakir , Liaqat Usman , Arif Dooa , Yang Kun-Lin
Published: April 2021

Surface protein gp-120 of HIV-1 virus plays an important role in the infection of HIV-1, but detection of gp-120 during the early stage of infection is very difficult. Herein, we report a binding bioassay based on an RNA aptamer B40t77, which binds specifically to gp-120. The bioassay is built upon a hydrophobic glass slide with surface immobilized gp-120. When the glass surface is incubated in a solution containing B40t77, the aptamer is able to bind to gp-120 specifically and remove it from the surface after a short incubation time of 30 min. The result of the binding event can be amplified by using liquid crystal (LC) into optical signals in the final step. By using this bioassay, we are able to detect as low as 1 μg/ml of gp-120 with high specificity within 30 min. No response is obtained when gp-120 is replaced by other protein such as bovine serum albumin (BSA). This is the first qualitative bioassay which provides a simple way for the detection of gp-120 with the naked eye. The assay is robust, low-cost and does not require additional labeling. Thus, the bioassay is potentially useful for the early detection of HIV-1 in resources-limited regions.
A Perovskite-Based Paper Microfluidic Sensor for Haloalkane Assays
Authors: Xie Lili , Zan Jie , Yang Zhijian , Wu Qinxia , Chen Xiaofeng , Ou Xiangyu , Lin Caihou , Chen Qiushui , Yang Huanghao
Published: April 2021

Detection of haloalkanes is of great industrial and scientific importance because some haloalkanes are found serious biological and atmospheric issues. The development of a flexible, wearable sensing device for haloalkane assays is highly desired. Here, we develop a paper-based microfluidic sensor to achieve low-cost, high-throughput, and convenient detection of haloalkanes using perovskite nanocrystals as a nanoprobe through anion exchanging. We demonstrate that the CsPbX3 (X = Cl, Br, or I) nanocrystals are selectively and sensitively in response to haloalkanes (CH2Cl2, CH2Br2), and their concentrations can be determined as a function of photoluminescence spectral shifts of perovskite nanocrystals. In particular, an addition of nucleophilic trialkyl phosphines (TOP) or a UV-photon-induced electron transfer from CsPbX3 nanocrystals is responsible for achieving fast sensing of haloalkanes. We further fabricate a paper-based multichannel microfluidic sensor to implement fast colorimetric assays of CH2Cl2 and CH2Br2. We also demonstrate a direct experimental observation on chemical kinetics of anion exchanging in lead-halide perovskite nanocrystals using a slow solvent diffusion strategy. Our studies may offer an opportunity to develop flexible, wearable microfluidic sensors for haloalkane sensing, and advance the in-depth fundamental understanding of the physical origin of anion-exchanged nanocrystals.
Salmonella Typhimurium Triggers Extracellular Traps Release in Murine Macrophages
Authors: Mónaco Amy , Canales-Huerta Nicole , Jara-Wilde Jorge , Härtel Steffen , Chabalgoity Jose Alejandro , Moreno María , Scavone Paola
Published: April 2021

Salmonella comprises two species and more than 2500 serovars with marked differences in host specificity, and is responsible for a wide spectrum of diseases, ranging from localized gastroenteritis to severe life-threatening invasive disease. The initiation of the host inflammatory response, triggered by many Pathogen-Associated Molecular Patterns (PAMPs) that Salmonella possesses, recruits innate immune cells in order to restrain the infection at the local site. Neutrophils are known for killing bacteria through oxidative burst, amid other mechanisms. Amongst those mechanisms for controlling bacteria, the release of Extracellular Traps (ETs) represents a newly described pathway of programmed cell death known as ETosis. Particularly, Neutrophil Extracellular Traps (NETs) were first described in 2004 and since then, a number of reports have demonstrated their role as a novel defense mechanism against different pathogens. This released net-like material is composed of cellular DNA decorated with histones and cellular proteins. These structures have shown ability to trap, neutralize and kill different kinds of microorganisms, ranging from viruses and bacteria to fungi and parasites. Salmonella was one of the first microorganisms that were reported to be killed by NETs and several studies have confirmed the observation and deepened into its variants. Nevertheless, much less is known about their counterparts in other immune cells, e.g. Macrophage Extracellular Traps (METs) and Salmonella-induced MET release has never been reported so far. In this work, we observed the production of METs induced by Salmonella enterica serovar Typhimurium and recorded their effect on bacteria, showing for the first time that macrophages can also release extracellular DNA traps upon encounter with Salmonella Typhimurium. Additionally we show that METs effectively immobilize and reduce Salmonella survival in a few minutes, suggesting METs as a novel immune-mediated defense mechanism against Salmonella infection. Of note, this phenomenon was confirmed in primary macrophages, since MET release was also observed in bone marrow-derived macrophages infected with Salmonella. The evidence of this peculiar mechanism provides new incipient insights into macrophages´ role against Salmonella infection and can help to design new strategies for the clinical control of this transcendental pathogen.
Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort—Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation
Authors: Hulshof Anne-Marije , Brüggemann Renée A. G. , Mulder Mark M. G. , van de Berg Tom W. , Sels Jan-Willem E. M. , Olie Renske H. , Spaetgens Bart , Streng Alexander S. , Verhezen Paul , van der Horst Iwan C. C. , Ten Cate Hugo , Spronk Henri M. H. , van Bussel Bas C. T , Henskens Yvonne M. C.
Published: April 2021

Background: Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy.

Objective: To unravel underlying coagulopathy and fibrinolysis over time as measured by serial assessment heparin-independent (FIBTEM and EXTEM) and fibrinolysis illustrating (tissue plasminogen activator; tPA) ROTEM assays.

Patients/Methods: Between April 23 and June 12, consecutive adult patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included, and a comprehensive set of clinical, physiological, pharmaceutical, and laboratory variables were collected daily. Twice per week, EXTEM, FIBTEM, and tPA ROTEM were performed. Clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT) were determined to assess clot development and breakdown and were compared to routine hemostatic assays.

Results: In 36 patients, 96 EXTEM/FIBTEM and 87 tPA ROTEM tests were performed during a 6-week follow-up. CT prolongation was present in 54% of EXTEM measurements, which were not matched by prothrombin time (PT) in 37%. Respectively, 81 and 99% of all EXTEM and FIBTEM MCF values were above the reference range, and median MCF remained elevated during follow-up. The ROTEM fibrinolysis parameters remained prolonged with median LOT consequently >49 min and unmeasurable LT in 56% of measurements, suggesting a severe hypofibrinolytic phenotype.

Conclusion: ROTEM tests in COVID-19 ICU patients show hypercoagulability and severe hypofibrinolysis persisting over at least 6 weeks.
Promoting Well-Being of Children at School: Parental Agency in the Context of Negotiating for Support
Authors: Koskela Teija
Published: April 2021

This study describes how parents experience their role in enhancing the well-being of their children and what this reveals about parental agency in the context of collaborations between home and school. In Finland, schools are among the most important environments for delivering services to children. The goal of this study is to bring into focus the parental dispositions in multi-agency interactions based on their experiences and to make sense of both their successes and the barriers they face. The Finnish education system aims to develop itself according to the inclusive principles. However, the inclusive school culture is still a work in progress. The parental agency and positions in collaboration with school personnel are ambivalent, and there are several assets and barriers that affect their ability to participate fully in discussions about the well-being of their children at school. In this article, the parental positions are connected to situations where they negotiate the process of collaborative planning of support for the learning and well-being of their children in the school environment. Participants are 13 mothers and one couple, mother and father. Their experiences are analyzed qualitatively via interviews and the concept of agency, a sociological concept that refers to the mutual relation between a culture or structure and the opportunities of human agents to interact within the given contexts. The results reveal qualitative differences in the experienced parental agency. The parental agency is connected to the given opportunities, and the key role in making the agency possible in the schools is given for the teachers. Behind everyday practices, there are deeper questions about the parental positions and their value in collaboration.
Recovering Spatially-Varying Cell-Specific Gene Co-expression Networks for Single-Cell Spatial Expression Data
Authors: Yu Jinge , Luo Xiangyu
Published: April 2021

Recent advances in single-cell technologies enable spatial expression profiling at the cell level, making it possible to elucidate spatial changes of cell-specific genomic features. The gene co-expression network is an important feature that encodes the gene-gene marginal dependence structure and allows for the functional annotation of highly connected genes. In this paper, we design a simple and computationally efficient two-step algorithm to recover spatially-varying cell-specific gene co-expression networks for single-cell spatial expression data. The algorithm first estimates the gene expression covariance matrix for each cell type and then leverages the spatial locations of cells to construct cell-specific networks. The second step uses expression covariance matrices estimated in step one and label information from neighboring cells as an empirical prior to obtain thresholded Bayesian posterior estimates. After completing estimates for each cell, this algorithm can further predict or interpolate gene co-expression networks on tissue positions where cells are not captured. In the simulation study, the comparison against the traditional cell-type-specific network algorithms and the cell-specific network method but without incorporating spatial information highlights the advantages of the proposed algorithm in estimation accuracy. We also applied our algorithm to real-world datasets and found some meaningful biological results. The accompanied software is available on https://github.com/jingeyu/CSSN.
Nucleic Acid Immunity and DNA Damage Response: New Friends and Old Foes
Authors: Taffoni Clara , Steer Alizée , Marines Johanna , Chamma Hanane , Vila Isabelle K. , Laguette Nadine
Published: April 2021

The maintenance of genomic stability in multicellular organisms relies on the DNA damage response (DDR). The DDR encompasses several interconnected pathways that cooperate to ensure the repair of genomic lesions. Besides their repair functions, several DDR proteins have emerged as involved in the onset of inflammatory responses. In particular, several actors of the DDR have been reported to elicit innate immune activation upon detection of cytosolic pathological nucleic acids. Conversely, pattern recognition receptors (PRRs), initially described as dedicated to the detection of cytosolic immune-stimulatory nucleic acids, have been found to regulate DDR. Thus, although initially described as operating in specific subcellular localizations, actors of the DDR and nucleic acid immune sensors may be involved in interconnected pathways, likely influencing the efficiency of one another. Within this mini review, we discuss evidences for the crosstalk between PRRs and actors of the DDR. For this purpose, we mainly focus on cyclic GMP-AMP (cGAMP) synthetase (cGAS) and Interferon Gamma Inducible Protein 16 (IFI16), as major PRRs involved in the detection of aberrant nucleic acid species, and components of the DNA-dependent protein kinase (DNA-PK) complex, involved in the repair of double strand breaks that were recently described to qualify as potential PRRs. Finally, we discuss how the crosstalk between DDR and nucleic acid-associated Interferon responses cooperate for the fine-tuning of innate immune activation, and therefore dictate pathological outcomes. Understanding the molecular determinants of such cooperation will be paramount to the design of future therapeutic approaches.
Contribution of T Cell Receptor Alpha and Beta CDR3, MHC Typing, V and J Genes to Peptide Binding Prediction
Authors: Springer Ido , Tickotsky Nili , Louzoun Yoram
Published: April 2021

Introduction

Predicting the binding specificity of T Cell Receptors (TCR) to MHC-peptide complexes (pMHCs) is essential for the development of repertoire-based biomarkers. This affinity may be affected by different components of the TCR, the peptide, and the MHC allele. Historically, the main element used in TCR-peptide binding prediction was the Complementarity Determining Region 3 (CDR3) of the beta chain. However, recently the contribution of other components, such as the alpha chain and the other V gene CDRs has been suggested. We use a highly accurate novel deep learning-based TCR-peptide binding predictor to assess the contribution of each component to the binding.

Methods

We have previously developed ERGO-I (pEptide tcR matchinG predictiOn), a sequence-based T-cell receptor (TCR)-peptide binding predictor that employs natural language processing (NLP) -based methods. We improved it to create ERGO-II by adding the CDR3 alpha segment, the MHC typing, V and J genes, and T cell type (CD4+ or CD8+) as to the predictor. We then estimate the contribution of each component to the prediction.

Results and Discussion

ERGO-II provides for the first time high accuracy prediction of TCR-peptide for previously unseen peptides. For most tested peptides and all measures of binding prediction accuracy, the main contribution was from the beta chain CDR3 sequence, followed by the beta chain V and J and the alpha chain, in that order. The MHC allele was the least contributing component. ERGO-II is accessible as a webserver athttp://tcr2.cs.biu.ac.il/and as a standalone code athttps://github.com/IdoSpringer/ERGO-II.
Neurological Symptoms of COVID-19: The Zonulin Hypothesis
Authors: Llorens Sílvia , Nava Eduardo , Muñoz-López Mónica , Sánchez-Larsen Álvaro , Segura Tomás
Published: April 2021

The irruption of SARS-CoV-2 during 2020 has been of pandemic proportions due to its rapid spread and virulence. COVID-19 patients experience respiratory, digestive and neurological symptoms. Distinctive symptom as anosmia, suggests a potential neurotropism of this virus. Amongst the several pathways of entry to the nervous system, we propose an alternative pathway from the infection of the gut, involving Toll-like receptor 4 (TLR4), zonulin, protease-activated receptor 2 (PAR2) and zonulin brain receptor. Possible use of zonulin antagonists could be investigated to attenuate neurological manifestations caused by SARS-CoV-19 infection.
Cholinergic and Noradrenergic Modulation of Corticothalamic Synaptic Input From Layer 6 to the Posteromedial Thalamic Nucleus in the Rat
Authors: Nersisyan Syune , Bekisz Marek , Kublik Ewa , Granseth Björn , Wróbel Andrzej
Published: April 2021

Cholinergic and noradrenergic neuromodulation of the synaptic transmission from cortical layer 6 of the primary somatosensory cortex to neurons in the posteromedial thalamic nucleus (PoM) was studied using anin vitroslice preparation from young rats. Cholinergic agonist carbachol substantially decreased the amplitudes of consecutive excitatory postsynaptic potentials (EPSPs) evoked by a 20 Hz five pulse train. The decreased amplitude effect was counteracted by a parallel increase of synaptic frequency-dependent facilitation. We found this modulation to be mediated by muscarinic acetylcholine receptors. In the presence of carbachol the amplitudes of the postsynaptic potentials showed a higher trial-to-trial coefficient of variation (CV), which suggested a presynaptic site of action for the modulation. To substantiate this finding, we measured the failure rate of the excitatory postsynaptic currents in PoM cells evoked by “pseudominimal” stimulation of corticothalamic input. A higher failure-rate in the presence of carbachol indicated decreased probability of transmitter release at the synapse. Activation of the noradrenergic modulatory system that was mimicked by application of norepinephrine did not affect the amplitude of the first EPSP evoked in the five-pulse train, but later EPSPs were diminished. This indicated a decrease of the synaptic frequency-dependent facilitation. Treatment with noradrenergic α-2 agonist clonidine, α-1 agonist phenylephrine, or β-receptor agonist isoproterenol showed that the modulation may partly rely on α-2 adrenergic receptors. CV analysis did not suggest a presynaptic action of norepinephrine. We conclude that cholinergic and noradrenergic modulation act as different variable dynamic controls for the corticothalamic mechanism of the frequency-dependent facilitation in PoM.
Synaptic Effect of Aδ-Fibers by Pulse-Train Electrical Stimulation
Authors: Tanaka Shota , Gomez-Tames Jose , Inui Koji , Ueno Shoogo , Hirata Akimasa , Wasaka Toshiaki
Published: April 2021

Electrical stimulation of specific small fibers (Aδ- and C-fibers) is used in basic studies on nociception and neuropathic pain and to diagnose neuropathies. For selective stimulation of small fibers, the optimal stimulation waveform parameters are an important aspect together with the study of electrode design. However, determining an optimal stimulation condition is challenging, as it requires the characterization of the response of the small fibers to electrical stimulation. The perception thresholds are generally characterized using single-pulse stimulation based on the strength-duration curve. However, this does not account for the temporal effects of the different waveforms used in practical applications. In this study, we designed an experiment to characterize the effects of multiple pulse stimulation and proposed a computational model that considers electrostimulation of fibers and synaptic effects in a multiscale model. The measurements of perception thresholds showed that the pulse dependency of the threshold was an exponential decay with a maximum reduction of 55%. In addition, the frequency dependence of the threshold showed a U-shaped response with a reduction of 25% at 30 Hz. Moreover, the computational model explained the synaptic effects, which were also confirmed by evoked potential recordings. This study further characterized the activation of small fibers and clarified the synaptic effects, demonstrating the importance of waveform selection.
Velocity and Pulsatility Measures in the Perforating Arteries of the Basal Ganglia at 3T MRI in Reference to 7T MRI
Authors: Arts Tine , Meijs Timion A. , Grotenhuis Heynric , Voskuil Michiel , Siero Jeroen , Biessels Geert Jan , Zwanenburg Jaco
Published: April 2021

Cerebral perforating artery flow velocity and pulsatility can be measured using 7 tesla (T) MRI. Enabling these flow metrics on more widely available 3T systems would make them more employable. It is currently unknown whether these measurements can be performed at 3T MRI due to the lower signal-to-noise ratio (SNR). Therefore, the aim of this study is to investigate if flow velocity and pulsatility in the perforating arteries of the basal ganglia (BG) can be measured at 3T MRI and assess the agreement with 7T MRI measurements as reference. Twenty-nine subjects were included, of which 14 patients with aortic coarctation [median age 29 years (21–72)] and 15 controls [median age 27 years (22–64)]. Using a cardiac-gated 2D phase-contrast MRI sequence BG perforating arteries were imaged at 3T and 7T MRI and perforating artery density (Ndensity, #/cm2), flow velocity (Vmean, cm/s) and pulsatility index (PI) were determined. Agreement between scanner modalities was assessed using correlation and difference plots with linear regression. A p-value ≤ 0.05 indicated statistical significance. It was shown that perforating artery flow velocity and pulsatility can be measured at 3T MRI (Ndensity = 0.21 ± 0.11; Vmean = 6.04 ± 1.27; PI = 0.49 ± 0.19), although values differed from 7T MRI measurements (Ndensity = 0.95 ± 0.21; Vmean = 3.89 ± 0.56; PI = 0.28 ± 0.08). The number of detected arteries was lower at 3T (5 ± 3) than 7T MRI (24 ± 6), indicating that 3T MRI is on average a factor 4.8 less sensitive to detect cerebral perforating arteries. Comparison with 7T MRI as reference showed some agreement in Ndensity, but little to no agreement for Vmean and PI. Equalizing the modalities’ sensitivity by comparing the detected arteries on 7T MRI with the highest velocity with all vessels detected on 3T MRI, showed some improvement in agreement for PI, but not for Vmean. This study shows that it is possible to measure cerebral perforating artery flow velocity and pulsatility at 3T MRI, although an approximately fivefold sample size is needed at 3T relative to 7T MRI for a given effect size, and the measurements should be performed with equal scanner field strength and protocol.
Association of Malnutrition, as Defined by the PG-SGA, ESPEN 2015, and GLIM Criteria, With Complications in Esophageal Cancer Patients After Esophagectomy
Authors: Yin Liangyu , Cheng Nian , Chen Ping , Zhang Mengyuan , Li Na , Lin Xin , He Xiumei , Wang Yingjian , Xu Hongxia , Guo Wei , Liu Jie
Published: April 2021

Background:There are several approaches that can be used for the pre-treatment identification of malnutrition in oncology populations including the Patient-Generated Subjective Global Assessment (PG-SGA), the 2015 consensus statement by the European Society for Clinical Nutrition and Metabolism (ESPEN 2015) and the Global Leadership Initiative on Malnutrition (GLIM).

Aims:This study aimed to evaluate whether malnutrition, as defined by these three methods, can be used to predict complications in esophageal cancer (EC) patients after esophagectomy.

Methods:We performed a single center, observational cohort study that included 360 EC patients undergoing esophagectomy from December 2014 to November 2019 at Daping Hospital in China. The prevalence of malnutrition in the study population was prospectively defined using the PG-SGA (≥9 defined malnutrition), and retrospectively defined using the ESPEN 2015 and the GLIM. The prevalence of malnutrition and association with postoperative complications were compared in parallel for the three methods.

Results:The prevalence of malnutrition before surgery was 23.1% (83/360), 12.2% (44/360), and 33.3% (120/360) in the study population, as determined by the PG-SGA, the ESPEN 2015 and the GLIM, respectively. The PG-SGA and GLIM had higher diagnostic concordance (Kappa = 0.519,P< 0.001) compared to the ESPEN 2015 vs. GLIM (Kappa = 0.361,P< 0.001) and PG-SGA vs. ESPEN 2015 (Kappa = 0.297,P< 0.001). The overall incidence of postoperative complications for the study population was 58.1% (209/360). GLIM- and ESPEN 2015-defined malnutrition were both associated with the total number of postoperative complications in multivariable analyses. Moreover, GLIM-defined malnutrition exhibited the highest power to identify the incidence of complications among all independent predictors in a pooled analysis.

Conclusion:Among the PG-SGA, the ESPEN 2015 and the GLIM, the GLIM framework defines the highest prevalence rate of malnutrition and appears to be the optimal method for predicting postoperative complications in EC patients undergoing esophagectomy. These results support the importance of preoperatively identifying malnutrition using appropriate assessment tools, because it can facilitate the selection of management strategies that will optimize the clinical outcomes of EC patients.
Identification of Resectable N2 in NSCLC: A Single Center Experience and Review of the SEER Database
Authors: Wang Yan-qing , Liu Xu-dong , Bai Wen-liang , Li Shan-qing
Published: April 2021

Background

Non-small cell lung carcinoma (NSCLC) with ipsilateral and/or subcarinal mediastinal lymphatic spread (N2) is a heterogeneous disease. The role of surgical resection in patients with N2 NSCLC remains controversial and no survival-based definition of “resectable N2” exists. The purpose of this study is to evaluate the factors that potentially affect the survival of N2 NSCLC patients who receive surgical resection and to define “resectable N2” based on the survival benefits.

Methods

Data from the open Surveillance, Epidemiology, and End Results (SEER) database from the National Cancer Institute in the United States were used to construct a nomogram. Patients who received surgery between 2010 and 2015 for N2 NSCLC were included. Independent prognostic factors for survival identified through Cox regression analysis were used to create the nomogram. The C-index, receiver operating characteristics (ROC) analyses, calibration curves, and risk stratification were used to evaluate the nomogram. The nomogram was also validated using data from 222 patients from Peking Union Medical College Hospital (PUMCH). Furthermore, lung cancer–related deaths were compared using competitive risk analysis.

Results

In total, 4267 patients were included in the SEER cohort. Male gender, old age, high T stage and grade, adenosquamous and squamous cell carcinoma, lower lobe and overlapping lesions, extended lobe or bilobectomy and pneumonectomy, no chemotherapy, radiation before and after surgery, positive number of lymph nodes, and lymph node ratio (LNR) were identified as independent risk factors for higher mortality. The nomogram was created using these parameters. The C-index was 0.665 (95% confidence interval (CI), 0.651-0.679) and 0.722 (95% CI, 0.620-0.824) in the SEER and PUMCH cohorts, respectively. The calibration curves showed satisfactory consistency between the predicted and actual survival status in both the SEER and PUMCH cohorts. Competitive risk analysis confirmed that the variables in the nomogram, except radiation, are risk factors for prognosis.

Conclusions

“Resectable N2” should be assessed by a multidisciplinary team. The novel nomogram developed in this study may help with clinical decision-making for this patient population.
Performance of 18F-DCFPyL PET/CT Imaging in Early Detection of Biochemically Recurrent Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Sun Jiale , Lin Yuxin , Wei Xuedong , Ouyang Jun , Huang Yuhua , Ling Zhixin
Published: April 2021

Background: Prostate-specific membrane antigen (PSMA)-targeted 2-(3-{1-carboxy-5-[(6-[18F] fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) positron emission tomography/computed tomography (PET/CT) has shown advantages in primary staging, restaging, and metastasis detection of prostate cancer (PCa). However, little is known about the role of 18F-DCFPyL PET/CT in biochemically recurrent prostate cancer (BRPCa). Hence, we performed a systematic review and meta-analysis to evaluate 18F-DCFPyL PET/CT as first-line imaging modality in early detection of BRPCa.

Methods: A comprehensive literature search of PubMed, Web of Science, Embase, and Cochrane Library was conducted until December 2020. The pooled detection rate on a per-person basis and together with 95% confidence interval (CI) was calculated. Furthermore, a prostate-specific antigen (PSA)-stratified performance of detection positivity was obtained to assess the sensitivity of 18F-DCFPyL PET/CT in BRPCa with different PSA levels.

Results: A total of nine eligible studies (844 patients) were included in this meta-analysis. The pooled detection rate (DR) of 18F-DCFPyL PET/CT in BRPCa was 81% (95% CI: 76.9–85.1%). The pooled DR was 88.8% for PSA ≥ 0.5 ng/ml (95% CI: 86.2–91.3%) and 47.2% for PSA < 0.5 ng/ml (95% CI: 32.6–61.8%). We also noticed that the regional lymph node was the most common site with local recurrence compared with other sites (45.8%, 95% CI: 42.1–49.6%). Statistical heterogeneity and publication bias were found.

Conclusion: The results suggest that 18F-DCFPyL PET/CT has a relatively high detection rate in BRPCa. The results also indicate that imaging with 18F-DCFPyL may exhibit improved sensitivity in BRPCa with increased PSA levels. Considering the publication bias, further large-scale multicenter studies are warranted for validation.