bluuebunny/crossref_metadata_2025 huggingface dataset:
CONSUMER DECISION MAKING IN CHANGING DEBIT CARD FROM VISA OR MASTERCARD INTO GPN (GERBANG PEMBAYARAN NASIONAL)
Authors: Prabowo Faizal Haris Eko , Taufik Nuryanti , Rijoly Jacobus Cliff Diky
Published: October 2023

The existence of the fourth industrial revolution made the whole way of banking work a little changed. From these events, the government and the central bank took advantage of this opportunity to create a debit card that has the same function as a visa and mastercard but originated from Indonesia. The inefficiency of the velocity of money that must be paid to foreign companies makes them act and take the decision to issue a debit card with a gerbang pembayaran nasional brand. The purpose of this study is to uncover what factors are causing customers to change their cards from visa or mastercard to GPN. The method used in this study is a survey with a quantitative approach. The population in this study amounted to 978, while the sample chosen was 211. The data used in this study were primary data obtained from questionnaires. The subjects in this study were customers who had a visa or mastercard debit card which eventually changed to GPN. The research sites were conducted in East Priangan city and regency namely Tasikmalaya City, Tasikmalaya Regency and Ciamis Regency. Data analysis techniques in this study used structural equation modeling (SEM). The results revealed that there were two variables that had an influence on the customer's decision to replace their debit cards namely word of mouth and brand awareness, while the two other variables that had no influence were customer value and price. The strategy undertaken by the government and the central bank is effective enough to stimulate customers in replacing their debit cards into GPN, by making GPN a news that is always being talked about and the intensity of GPN campaigns or promotions that are spread across every bank.
PENGARUH KUALITAS BAHAN BAKU DAN PROSES PRODUKSI TERHADAP KUALITAS PRODUKSI
Authors: Sasongko Totok , Askiyanto Moh , Yovita Yovita
Published: October 2023

The motivation behind this study was to decide the impact of the nature of unrefined components and creation processes on the nature of creation at PKS Darmex Agro Bengkayang West Kalimantan to some extent and all the while. This exploration is an examination utilizing quantitative strategies. Assurance of the example of this study utilizing basic irregular inspecting technique. The information assortment procedure utilized by the scientist is a survey. The information investigation strategy utilized is numerous direct relapse utilizing the SPSS variant 21 program. The consequences of the review demonstrate that to some extent the nature of unrefined substances fundamentally affects creation quality with a worth of t_count = 3.666 and the creation cycle essentially affects creation quality with a worth of t_count = 3.522. While, at the same time (together) the nature of unrefined components and creation processes essentially affect the nature of creation at PKS Darmex Agro Bengkayang West Kalimantan with an Fcount (21.690). What should be considered by organizations to further develop creation quality is to focus on unrefined components that should meet targets and live up to assumptions so the outcomes are fitting and offset with the items delivered. As well as improving support or upkeep, review and fix regularly on creation machines so as not to hamper the creation cycle.
PENERAPAN ISAK NO. 35 TERHADAP LAPORAN KEUANGAN MASJID NURUL HAYAT LEWOLANG
Authors: Tanan Eugenia Hendrini P. , S. Bali Asriyanti
Published: October 2023

This research is aimed to collect more empirical of ISAK No. 35 related to the Presentation of Financial Statements of Non-profit Oriented Entities at the Nurul Hayat Lewolang Mosque. Data collection techniques used descriptive qualitative methods with interviews, observations and documentation. The study used secondary and primary data. The study resulted in evidence that the financial statements of the Nurul Hayat Lewolang Mosque were not in line with ISAK No. 35. The financial report of the Nurul Hayat Lewolang Mosque which has been adjusted by ISAK No. 35 by classifying transactions, compiling general journals, transferring to ledgers, compiling trial balances. Finally resulted in an accounting process flow in the form of a Statement of Financial Position, Statement of Comprehensive Income, Statement of Changes in Net Assets, and Statement of Cash Flows, as well as Notes to Financial Statements.
ANALISIS METODE ASESSMENT SALES RATIO SEBAGAI ALAT UJI AKURASI PENETAPAN NILAI JUAL OBJEK PAJAK (NJOP) BUMI TERHADAP NILAI PASAR
Authors: Novitawati Retno Ayu Dewi , Indrihastuti Poppy , Ida Walburga Jolena
Published: October 2023

Penelitian ini membandingkan nilai jual objek pajak bumi (NJOP) dengan nilai pasarnya menggunakan teknik penilaian rasio penjualan. Penelitian dilakukan di Kecamatan Borong, Kabupaten Manggarai Timur. Penelitian ini mengkaji tendensi sentral dalam pendugaan NJOP di Kabupaten Borong dalam interval IAAO (IAAO). Penelitian deskriptif dan kuantitatif. Desa Satar Peot (58,2%), Desa Nanga Labang (24,7%), dan Desa Gurung Liwut (18,9%) tidak memenuhi kriteria Ditjen Pajak (80 persen). Rata-rata/median dan rata-rata/berat 14,4% dan 11,2% tidak memenuhi standar IAAO yang berada dalam 10% dari tingkat rasio yang dapat diterima antara 90% dan 1100%, menunjukkan harga jual item pajak masih di bawah pasar.
PENGARUH HARGA DAN VARIASI PRODUK TERHADAP MINAT BELI KONSUMEN PADA ANVIBI CAFÉ MALANG
Authors: Sasongko Totok , Askiyanto Moh. , Yuniarti Yuniarti
Published: October 2023

Penelitian ini bertujuan untuk mengetahui pengaruh variabel harga dan variasi produk terhadap minat beli konsumen di Anvibi Cafe Malang. Dokumentasi, observasi, wawancara, dan penyebaran kuesioner menjadi teknik-teknik yang digunakan oleh peneliti guna mengumpulkan data-data penelitian, yang terbagi menjadi data primer serta data sekunder. Seluruh pengunjung Anvibi Cafe akan menjadi populasi yang ditetapkan oleh peneliti, dibarengi dengan penetapan 100 responden pengunjung yang diambil dengan metode purposive sampling sebagai sampel penelitian ini, Hasil penelitian menggambarkan tidak adanya pengaruh yang diberikan oleh variabel harga kepada variabel minat beli konsumen, yang dibuktikan dengan perolehan nilai t-hitung sejumlah 1,791 lebih kecil dari nilai t-tabel yang telah ditentukan sebesar 1,98. Sedangkan variabel variasi produk terbukti berpengaruh pada variabel minat beli konsmen, karena nilai t-hitung yang dihasilkan sejumlah 2,112 lebih besar dari nilai t-tabel dan nilai signifikansi yang berjumlah 0,000 lebih kecil dari 0,05. Nilai koefisien determinasi yang didapatkan pada penelitian ini sejumlah 0,555. Di sisi lain, variabel harga dan juga variasi produk secara simultan terbukti berpengaruh pada minat beli konsumen, didukung oleh perolehan nilai f-hitung senilai 60,588 lebih besar dari nilai f-tabel yaitu sejummlah 3,09.
PERAN GAYA KEPEMIMPINAN DALAM MENINGKATKAN KEMANDIRIAN EKONOMI MASYARAKAT DESA
Authors: Azhari Azhari , Samiani Aiti
Published: October 2023

Tujuan dari penelitian ini adalah untuk mengetahui peran gaya kepemimpinan yang dilakukan oleh kepala desa dalam melaksanakan sistem pemerintahanya untuk mewujudkan kemandirian desa. Jenis pendekatan yang dilakukan dalam penelitian ini adalah analisis kualitatif deskriptif yaitu untuk mengetahui secara mendalam tentang peran gaya kepemimpinan yang diterapkan oleh kepala desa dalam meningkatkan kemandirian ekonomi masyarakat desa. Hasil penelitian ini menjelaskan bahwa gaya kepemimpinan kepala desa yang diterapkan dalam meningkatkan kemandirian ekonomi masyarakat Desa Ngumpakdalem Kecamatan Dander Kabupaten Bojonegoro adalah gaya kepemimpinan partisipatif yang mengarah pada peningkatan ekonomi masyarakat secara mandiri, selain itu, kepala desa dan aparatur desa sangat mendukung masyarakat dan kegiatan ekonomi masyarakat. Faktor pengahambat penerapan gaya kepemimpinan kepala desa yang diterapkan dalam meningkatkan kemandirian ekonomi masyarakat adalah kurangnya dukungan masyarakat secara menyeluruh, hal ini perlu disadari bahwa tidak semua kebijakan dapat diterima masyarakat secara menyeluruh atau ada sebagian masyarakat yang masih kurang mendukung kebijakan kepala desa.
PERBANDINGAN KATEGORI KEJAHATAN EKONOMI SECARA GLOBAL DAN INDONESIA
Authors: Christian Natalis , Kelly Kelly , Venessa Jessy , Stefy Stefy
Published: October 2023

Penelitian ini bertujuan untuk menganalisis perbedaan kategori fraud yang terjadi secara global dan diakui di Indonesia. Studi ini didasarkan pada data yang dikumpulkan oleh badan-badan atau organisasi pemberantasan fraud, seperti PricewaterhouseCoopers (PwC), Association of Certified Fraud Examiners (ACFE) yang merupakan data hasil survei dari tahun 2016 sampai 2022. Hasil penelitian ini menunjukkan penyalahgunaan aset mendominasi kategori fraud di awal pandemi, namun kemudian menurun setelah pandemi dan digantikan oleh customer fraud dan cybercrime. Begitu juga kasus penipuan di Indonesia, baik sebelum maupun sesudah pandemi, kasus penipuan masih didominasi oleh korupsi.
FAKTOR-FAKTOR YANG MEMPENGARUHI NIAT BELI EMAS MELALUI MOBILE BANKING
Authors: Kurniawan Dedi , Maulana Achmad , Shihab Muchsin Saggaff
Published: October 2023

Tujuan: Tujuan dari penelitian ini adalah untuk menguji pengaruh Persepsi Kegunaan, Persepsi Kemudahan, Sikap, Pengetahuan Produk, Kepercayaan, dan Persepsi Resiko terhadap Niat nasabah pengguna BSI mobile untuk membeli emas online di Bank Syariah Indonesia. Penelitian ini secara khusus mengkaji niat beli emas online di mobile banking. Metode: jenis penelitian kuantitatif dan  data dikumpulkan dari 218 nasabah Bank Syariah Indonesia di Kota Palembang menggunakan survei online dan offline. Analisis data: Model persamaan struktural (SEM). Hasil dan diskusi: Studi ini menemukan peran pengetahuan produk dan persepsi risiko berpengaruh signifikan terhadap Niat nasabah pengguna mobile banking untuk membeli emas online di aplikasi mobile banking. Persepsi Kegunaan dan Persepsi Kemudahan berpengaruh signifikan terhadap Sikap. Kesimpulan: Penelitian ini hanya menyelidiki niat membeli emas sebagai salah satu jenis investasi emas secara online di aplikasi mobile banking. Studi ini berkontribusi pada literatur dengan memeriksa peran Persepsi Kegunaan, Persepsi Kemudahan, Sikap, Pengetahuan Produk, Kepercayaan, dan Persepsi Resiko terhadap Niat nasabah pengguna mobile banking untuk berinvestasi emas melalui aplikasi. Hasil penelitian ini menyoroti kebutuhan bank syariah untuk mengedukasi nasabah untuk meningkatkan pengetahuan produk deposan karena risiko dan persepsi nilai dan niat nasabah muslim sangat dipengaruhi oleh pengetahuan produk.
Full Day School di Madrasah Ibtidaiyah Nurul Ummah Kotagede
Authors: Prasetyo Heru
Published: October 2023

Currently, the madrasah has an important role in fostering students by holding positive and beneficial activities for the future, then the full-day school system emerged which was finally widely applied in Indonesia. This full-day school aims to foster attitudes or morals and form better character in students amid the rampant moral decadence of the nation's children, this program is also accompanied by the provision of religious values because students have a lot of time in the madrasah, so coaching will be easily done by the madrasah. This study aims to determine the implementation of a full-day school that has been implemented by MI Nurul Ummah Kotagede. The type of research used is qualitative research with descriptive methods. Data collection was done by observation and interviews. Data processing and analysis techniques used are data reduction techniques, presentation, and conclusions. The results showed that the implementation of a full-day school at MI Nurul Ummah in the learning process lasted for 9 hours per day. Covering religious activities and other public lessons then complemented by extracurriculars to support the interests and talents of students

[Saat ini madrasah memiliki peran penting dalam membina peserta didik dengan mengadakan kegiatan-kegiatan yang positif dan bermanfaat untuk masa depan, kemudian muncul sistem full day school yang akhirnya diterapkan secara luas di Indonesia. Sekolah sehari penuh ini bertujuan untuk membina sikap atau akhlak dan membentuk karakter yang lebih baik pada siswa di tengah maraknya dekadensi moral anak bangsa, program ini juga dibarengi dengan pemberian nilai-nilai religi karena peserta didik memiliki banyak waktu di madrasah , sehingga pembinaan akan mudah dilakukan oleh pihak madrasah. Penelitian ini bertujuan untuk mengetahui implementasi full day school yang telah dilaksanakan oleh MI Nurul Ummah Kotagede. Jenis penelitian yang digunakan adalah penelitian kualitatif dengan metode deskriptif. Pengumpulan data dilakukan dengan observasi dan wawancara. Teknik pengolahan dan analisis data yang digunakan adalah teknik reduksi data, penyajian dan penarikan kesimpulan. Hasil penelitian menunjukkan bahwa pelaksanaan full day school di MI Nurul Ummah dalam proses pembelajaran berlangsung selama 9 jam per hari. Meliput kegiatan keagamaan dan pelajaran umum lainnya kemudian dilengkapi dengan ekstrakurikuler untuk menunjang minat dan bakat siswa]
Reconstruction of the face with botox and filler injections
Authors: TUNÇER Fatma
Published: October 2023

This article deals with the women’s narratives of “natural” and “unnatural” appearance and the possible meanings in which these narratives indicate regarding the use of botox and filler technologies and applications, which are among the today’s “youth” work interventions. This study, which was based on a field research and the participant observation technique, was carried out at the X Aesthetic Center in Ankara/Turkey between the years of 2021-2022. The data were obtained from in-depth interviews with the doctor who performed the botox and filler procedure and from the female participants in different range of ages who have these applications. In this study, which is based on the meanings attributed by the participants to the “natural” and “unnatural” appearance, and which takes the concept of “natural” as problematic, the discourse of “naturalness” is discussed in connection with the literature on nature, culture, body and technology. In the light of these discussions, we will focus on where and how we should position the bodily regimes of the participants involved in botox and filler procedures, and on the boundaries between the “natural” and “unnatural” body which will be tried to be blurred. In oder to do so, it will be argued that Donna J. Haraway’s cyborg figure, i.e. “machine-organism hybrids”, can be adapted to the field of botox and filler applications.
Cebirli Omurgalı Fosil Lokalitesi kazı çalışmaları
Authors: SAĞIR Mehmet
Published: October 2023

Anadolu coğrafyası Miyosen Dönem fosil faunasının zenginliği açısından dünya üzerinde önemli bir yere sahiptir. Bu dönemde, Afrika, Avrupa ve Asya kıtaları arasında uygun koşullar, faunal göçlere olanak sağlamıştır. Cebirli Lokalitesi, bu göçlerin etkilerini gözlemlemek için Anadolu’daki diğer fosil buluntu alanları gibi önemli bir lokalitedir. Geç Miyosen dönem fosil faunası içeren Cebirli lokalitesi Ankara ili, Evren ilçesi, Cebirli mahallesi sınırları içerisinde, Darlık mevkiinde Hirfanlı baraj gölünün hemen kıyısında, deniz seviyesinden yaklaşık 850 metre yüksekliktedir. Cebirli Geç Miyosen Dönem fosil lokalitesi 2009 yılında Raif Şanlı ve birkaç kişinin tekne gezintisi sırasında Hirfanlı Barajı’nın kıyısında tespit edilmiştir. Maden Tetkik ve Arama Genel Müdürlüğü tarafında bu alanda 2009 yılında bir kazı gerçekleştirilmiştir. 2019 yılında Prof.Dr. Mehmet Sağır başkanlığında yürütülen “Ankara İli ve İlçeleri Yüzey Araştırması Projesi” kapsamında bu alanda yapılan incelemelerde, alanda açığa çıkmış olan fosil kalıntıların fazlasıyla tahrip olduğu görülerek 2020 yılında Anadolu Medeniyetleri Müzesi Müdürlüğü başkanlığında kurtarma kazısı, 2021 yılında ise yine Anadolu Medeniyetleri Müzesi Müdürlüğü başkanlığı altında kazı çalışmaları yürütülmüştür. 2022 yılı itibari ile Cumhurbaşkanı Kararlı Kazı statüsüne dönüşen Cebirli Kazısı çalışmaları devam etmektedir. 2020-2022 yılları arasında 3 sezonda gerçekleştirilen kazı çalışmalarında 143, yüzey temizlik çalışmalarında ise tanımlanabilir nitelikte 154 adet fosil elde edilmiştir. Ön çalışmalar sonucunda lokaliteye ait fauna içerisinde atlar (Equidae), gergedanlar (Rhinocerotidae), hortumlular (Proboscidae), zürafalar (Giraffidae), domuzlar (Suidae), boynuzlugiller (Bovidae), geyikler (Cervidae) ve etçillerin (Carnivora) birden fazla türle temsil edildikleri ve fosil kalıntıların oldukça yoğun olduğu görülmüştür.
Kitap incelemesi: Bir Japon antropoloğun kırsaldaki kadınların gündelik yaşantısı bağlamında modernleşmeye dair düşündürdükleri. Noriko Nakayama (2021). Köy kadını, modernite ve İslam: Bir antropoloğun gözünden 1990’ların Türkiye’si (T. Özşen, Çev.). Tarih Vakfı Yurt Yayınları, 190 S. ISBN: 978-975-333-392-4
Authors: AKSOY SUGIYAMA Ceren
Published: October 2023

Bu değerlendirmenin konusu olan eser, Japonya’nın Aichi İli’nde yer alan Chubu Üniversitesi, Uluslararası İlişkiler Bölümü’nde öğretim üyesi olan Noriko Nakayama’nın, Haziran 1992 - Haziran 1993 arasında Zonguldak-Ereğli’de gerçekleştirmiş olduğu alan çalışmasına dayanmaktadır. Bu yazı her ne kadar bu eserin bir değerlendirmesi olsa da bir yandan da antropolojinin kendine has-en azından bir zamanlar- yönelimlerinden biri olan dışarıdan bakışın bir toplumun kendine has durumlarını ortaya koymada yaratabileceği farkı ve sosyal bilimler literatüründe var olan her kavramın her coğrafyaya uygun genel bir reçete sunamayacağını göstermeye çalışacaktır.
Three-dimensional vector ECG analysis in the diagnosis of the left anterior fascicular block
Authors: Teregulov Yu. E. , Atsel E. A. , Ganieva S. F. , Teregulova E. T. , Maksimova M. S. , Teregulov A.  Yu. , Kamaletdinova Z. A.
Published: October 2023

The relevance of the study is due to the complexity of the differential diagnosis of left anterior fascicular block (LAFB) with myocardial infarction and left ventricular hypertrophy based on a standard ECG.

Aim. Determination of the criteria for LAFB according to the data of three- dimensional vectorcardiography with an analysis of the rate of formation of the vector loop.

Material and research methods. The study included 85 patients who underwent a 12-lead ECG study. 2 groups of patients were selected. The main group of 56 patients with LAFB, mean age was 63.3±16.6 (M±δ) years, 34 men and 22 women. The control group included 29 healthy individuals, the mean age was 21.4±2.5 (M± δ) years, 12 men and 17 women. All patients underwent synchronous recording of 12 standard ECG leads in the IS «Unified Cardiologist of the Republic of Tatarstan» and reconstruction of a three-d imensional vectorcardiogram using the McFee-Parungao system with an analysis of the vector loop formation  rate using EasyECG Rest ATES Medica software (Russia).

Results and conclusions. It is shown that for LAFB the movement of the vector loop counterclockwise is typical in the frontal plane; the presence of 2 extrema, the second is directed upwards, to the right and back. On the graph of the rate of formation of a spatial vector loop, 2 peaks are recorded with a decrease in the rate in the final part of the QRS loop by 2–2.5 times relative to the first peak, which reflects a slowdown in myocardial excitation in the output section of the left ventricle.
Method of dynamic one-stage Dopplerography of coronary and cerebral blood flow with analysis of efficiency of antler balneotherapy in patients with arterial hypertension
Authors: Avkhimenko V. A. , Trivozhenko A. B. , Grebenyuk O. V.
Published: October 2023

Integration of highly sensitive Doppler methods of assessment of coronary and cerebral blood circulation into process of functional and diagnostic audit of results of recovery treatment of patients with an arterial hypertension allows to estimate positive tendencies at normalization of processes regional perfusion. Use of the designated technologies showed reliable decrease in peak velocity in middle cerebra artery without increase in vascular resistance at the persons which passed a therapeutic course of antler reindeer breeding.

Peak velocity in an middle cerebra artery before the designated treatment was within 92–115 cm/ c (Me 105 [96,3–104,5]), after the therapeutic procedures was registered in a big way 78–98 cm / c (Me 90 [82,4–94,3]). The designated phenomenon indicated improvement of regional cerebral oxygenation and natural reduction of volume of brain perfusion. At the same time, Doppler parameters in coronary arteries at the patients who completed the analyzed course of recovery treatment were transformed minimum, without reliable distinctions that presumably.
Advance Thermography diagnostics: automatic algorithm to find out acute sinusitis
Authors: Dolgov I. M. , Karamyshev Yu. V. , Zheleznyak I. S. , Karamysheva A. A. , Makhnovsky A. I. , Khriupkovskiy D. N.
Published: October 2023

Development of medical imaging techniques (including medical thermography) provided an opportunity to mine data that can be explored for the development of clinical decision support systems.

Aim.Find out quantitative thermography criteria for acute rhinosinusitis and implement these criteria into automated analysis protocols to create a diagnostic complex suitable for use by professionals of any medical speciality.

Material, methods.After necessary adaptation, facial thermography by mean of thermography camera ТВС300-меd LLC “СТК СИЛАР” Russia, (384x288 pixel, 30 mK) was performed in 100 healthy volunteers and 305 patients with suspected acute rhinosinusitis (in 173 of them diagnosis was supported). Resulted thermograms were processed in “cloud service” TVision (LLC “Dignosys”, Russia). Point and regions of interest (ROI), namely, point in the middle of the line, connected inner edge of eyebrows (Тср) and ROI, covered the projections of maxillary sinuses were marked automatically. Difference between temperature in Тср point and mean temperature in each ROI (ΔТr/ΔТl), as well as mean temperature between ROI were calculated (ΔTпаз).

Result.The best results ( sensitivity 82%, specificity 74%, accuracy 78%) were received when complex of ΔТr/ΔТl ≤0 and module |ΔTпаз| ≥0,5°C (both or at least one criterion) was applied. Based on these data, automatic algorithm of thermography acute rhinosinusitis diagnostics was created to use in primary medical care routine as clinical decision support systems.
In vitro compositional and phytochemical analysis of green and black tea
Authors: Aslam Iram , Ahmad Asif , Raja Muhammad Usman , Ahmed Saleha
Published: October 2023

The traditional beverage that people consume more after water is a tea. The ethanolic extract of green and black tea have antioxidant and antimicrobial activity and these activities may differ in their processing methods. In this study, physiochemical analysis of green and black tea was carried out.  The physiochemical analysis showed that green tea has higher moisture content, crude fat and crude fiber except for crude protein and ash content which is found higher in black tea. The maceration process was used for extraction purposes. This extract was used to analyze the total phenolic and flavonoid content, antioxidant potential, and antimicrobial activity. A significant difference was found in the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity of green and black tea. The flavonoids and phenolic content in T1 (ethanol 100%) acquired average and significant in the extract of green and black tea. The maximum value of TPC was observed in green tea extract 152.17a ± 0.28 mg GAE/g in treatment T1, and the value of TFC in green tea was found 40.26±11.387mg QE/g and the minimum value was found in black tea at 36.85±13.68 mg QE/g of extract. Antioxidant activity of green tea extract ranged from 90.64% to 69.07%, and black tea extract ranged from 89.05% to 50.93% in each extract. The parallel determination of the inhibitory effect of gram-negative and positive bacterial strains (Streptococcus pyogenes, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) was found sensitivity and resistivity towards extract of tea. The positive and negative effect was found in antimicrobial activity by using antibiotics against these bacterial strains.
Recent advances in epicutaneous immunotherapy and potential applications in food allergy
Authors: Hervé Pierre-Louis , Dioszeghy Vincent , Matthews Katie , Bee Katharine J. , Campbell Dianne E. , Sampson Hugh A.
Published: October 2023

Given the potent immunological properties of the skin, epicutaneous immunotherapy (EPIT) emerges as a promising treatment approach for inducing immune tolerance, particularly for food allergies. Targeting the highly immunocompetent, non-vascularized epidermis allows for the application of microgram amounts of allergen while significantly reducing the risk of allergen passage into the bloodstream, thus limiting systemic allergen exposure and distribution. This makes EPIT highly suitable for the treatment of potentially life-threatening allergies such as food allergies. Multiple approaches to EPIT are currently under investigation for the treatment of food allergy, and these include the use of allergen-coated microneedles, application of allergen on the skin pretreated by tape stripping, abrasion or laser-mediated microperforation, or the application of allergen on the intact skin using an occlusive epicutaneous system. To date, the most clinically advanced approach to EPIT is the Viaskin technology platform. Viaskin is an occlusive epicutaneous system (patch) containing dried native allergen extracts, without adjuvants, which relies on frequent application for the progressive passage of small amounts of allergen to the epidermis through occlusion of the intact skin. Numerous preclinical studies of Viaskin have demonstrated that this particular approach to EPIT can induce potent and long-lasting T-regulatory cells with broad homing capabilities, which can exert their suppressive effects in multiple organs and ameliorate immune responses from different routes of allergen exposure. Clinical trials of the Viaskin patch have studied the efficacy and safety for the treatment of life-threatening allergies in younger patients, at an age when allergic diseases start to occur. Moreover, this treatment approach is designed to provide a non-invasive therapy with no restrictions on daily activities. Taken together, the preclinical and clinical data on the use of EPIT support the continued investigation of this therapeutic approach to provide improved treatment options for patients with allergic disorders in the near future.
N-acetylcysteine prevents catheter occlusion and inflammation in catheter associated-urinary tract infections by suppressing urease activity
Authors: Manoharan Arthika , Farrell Jessica , Aldilla Vina R. , Whiteley Greg , Kriel Erik , Glasbey Trevor , Kumar Naresh , Moore Kate H. , Manos Jim , Das Theerthankar
Published: October 2023

Introduction

Proteus mirabilis is a key pathobiont in catheter-associated urinary tract infections (CA-UTIs), which is well known to form crystalline biofilms that occlude catheters. Urease activity alkylates urine through the release of ammonia, consequentially resulting in higher levels of Mg2+ and Ca2+ and formation of crystals. In this study, we showed that N-acetyl cysteine (NAC), a thiol antioxidant, is a potent urease inhibitor that prevents crystalline biofilm formation.

Methods

To quantify urease activity, Berthelot’s method was done on bacterial extracts treated with NAC. We also used an in vitro catheterised glass bladder model to study the effect of NAC treatment on catheter occlusion and biofilm encrustation in P. mirabilis infections. Inductively-coupled plasma mass spectrometry (ICP-MS) was performed on catheter samples to decipher elemental profiles.

Results

NAC inhibits urease activity of clinical P. mirabilis isolates at concentrations as low as 1 mM, independent of bacterial killing. The study also showed that NAC is bacteriostatic on P. mirabilis, and inhibited biofilm formation and catheter occlusion in an in vitro. A significant 4-8log10 reduction in viable bacteria was observed in catheters infected in this model. Additionally, biofilms in NAC treated catheters displayed a depletion of calcium, magnesium, or phosphates (>10 fold reduction), thus confirming the absence of any urease activity in the presence of NAC. Interestingly, we also showed that not only is NAC anti-inflammatory in bladder epithelial cells (BECs), but that it mutes its inflammatory response to urease and P. mirabilis infection by reducing the production of IL-6, IL-8 and IL-1b.

Discussion

Using biochemical, microbiological and immunological techniques, this study displays the functionality of NAC in preventing catheter occlusion by inhibiting urease activity. The study also highlights NAC as a strong anti-inflammatory antibiofilm agent that can target both bacterial and host factors in the treatment of CA-UTIs.
Cryptosporidiosis diagnosed using metagenomic next-generation sequencing in a healthy child admitted to pediatric intensive care unit: a case report
Authors: Liu Xiaoyi , Wang Jing , Liu Jun , Li Xuming , Guan Yuanlin , Qian Suyun , Jia Xinlei
Published: October 2023

Background

Cryptosporidium infections in humans typically result in symptoms such as abdominal pain and diarrhea. When the diarrhea is severe, it can cause serious complications and even be life-threatening, especially in patients with compromised immune systems.

Case presentation

Here, we reported the use of metagenomic next-generation sequencing (mNGS) to assist in the diagnosis and treatment of a 10-year-old boy with severe Cryptosporidium infection. Despite the absence of any history of immunocompromise, the infection still resulted in severe symptoms, including shock, as well as damage to his pancreas and kidneys. The mNGS tests detected the presence of Cryptosporidium parvum when conventional methods failed. The patient received anti-parasite treatment along with supportive care to manage the condition. With disease surveillance based on regular clinical tests and sequential mNGS tests, the child recovered from the severe conditions.

Conclusion

Our study emphasized the importance of recognizing the potential severity of Cryptosporidium infection, even among individuals with normal immune systems. Timely diagnosis and ongoing monitoring are essential for patient prognosis.
“A hard-won capability”: the experiences of parents managing their babies' medicines after discharge from a neonatal unit
Authors: Bracken Louise , Clark Janet , Gill Andrea , O'Brien Fiona , Dewey Rachael , Barker Catrin , Carter Bernie
Published: October 2023

Introduction

Parents of babies who required neonatal care are responsible for managing their medicines after they are discharged home. There is wide variation in the information and amount of preparation given to parents prior to assuming this challenging task. The aim of the Parent co-Designed Drug Information for parents and Guardians Taking Neonates home (PADDINGToN) study was to explore parents' experiences of managing their babies' medicines post discharge from a neonatal unit and to use this information to develop suitable resources for future families.

Methods

A qualitative participatory interpretative approach using a mixture of remote and face-to-face small group interviews or one-to-one interviews was used. Parents were recruited using social media advertisements and convenience sampling from five study sites (four neonatal units in England and one in Ireland). Parents from other neonatal units were invited to take part through social media advertisement. The interviews were audio-recorded and inductive reflexive thematic analysis was used to analyze the data.

Results

17 parents (14 mothers, 3 fathers) participated. One over-arching theme, 'A hard won capability', and four major interpretive themes were generated from the analysis of the data: Being in NICU and the prospect of going home: emotional and practical challenges; Living the reality of being at home: the uncertainty associated with giving medicines; Being at home: battling the system and a lack of support/knowledge; and Suggesting ways forward: parents' lived insights into improving information and resources.

Conclusion

Despite the challenges they faced, parents developed strategies for safely and reliably managing medicines administration and they assimilated knowledge, built their confidence and achieved a capability in medicines administration. Their experiences have been used to build a suite of medicines administration resources to support future parents.
Interdisciplinary students’ reflections on the development of their epistemic fluency
Authors: van Goch Merel Margot
Published: October 2023

Introduction

How can higher education institutions foster students’ epistemic fluency, that is, their ability to identify, reflect upon, and connect different knowledges and different ways of knowing? As higher education institutions put interdisciplinary research and education prominently on their strategic agendas, there is a call for knowledge on how to teach students to identify and integrate insights from different disciplines. This study approached this topic from the viewpoint of the student: what are the drivers and barriers to the development of epistemic fluency, according to interdisciplinary students?

Methods

Participants were undergraduate students enrolled in a course on the interdisciplinary research process with a specific emphasis on integration. In the first and last lectures of the course, students were asked to reflect on their openness to alternative perspectives and their connective thinking. They also reflected on their development in general and specifically in this interdisciplinary course.

Results

Students were able to meaningfully reflect on their development and the results showed a varied picture of students’ epistemic fluency.
A cognitive task analysis of the teacher skills and knowledge required for differentiated instruction in secondary education
Authors: Meutstege Kyra , Vrielink Marlijn , van Geel Marieke , Visscher Adrie J.
Published: October 2023

Providing differentiated instruction (DI) is a complex teacher task that many secondary school teachers do not master well. In the current study, a cognitive task analysis of this teacher task was conducted by analyzing how expert teachers do this and why, resulting in an inventory of the necessary teacher skills and knowledge for providing DI, and a description of the factors that influence the complexity of DI. The results of this analysis show what providing DI in secondary education entails, which is valuable for designing teacher professional development programs for DI at that level.
Exploring the predictive influence of licensure examination results for beginning teachers’ performance: the case of the Philippines
Authors: Cadosales Maria Nancy Q. , Sanchez Joje Mar P. , Cordova Monique E. , Merin Jewish A. , Augusto William S.
Published: October 2023

Passing the Board Licensure Examination for Professional Teachers (BLEPT) is a major requirement for graduates to be accepted to teach in the Department of Education (DepEd). The holistic preparation of these teachers determines how well they perform in the field. This study investigated the relationship between the beginning teachers’ performance in the licensure examination and their results-based performance management system rating. The descriptive-correlational research design was used in this study. The data were systematically obtained from 2,680 teachers representing the 17 regions in the Philippines through a researcher-made survey instrument administered online from May to July 2022. Means and standard deviations described the BLET and RPMS performances. At the same time, hierarchical regression, path, and effect analyses were used to determine the impact of BLET performance, teaching experience, and college preparation on teaching performance. The beginning teachers with BEEd, BSEd, and DPE degrees received satisfactory BLEPT performance and a very satisfactory RPMS performance. Furthermore, the performance in General Education, Professional Education, and Specialization components predicted the RPMS performance of teachers who graduated from the BSEd degree program. College preparation impacted RPMS performance, while teaching experience in private and public schools showed different impacts in their teaching. Finally, the findings of this study show that the BLET performance of teachers impacts the RPMS ratings; hence, licensure exam results can predict teachers’ performance in public schools. The quality of teacher preparation influences the preservice teachers’ performance in the board licensure examination for professional teachers. Hence, it is recommended that teacher education institutions intensify their measures in preparing preservice teachers to pass the board licensure examination for professional teachers.
Perirenal fat thickness as a superior obesity-related marker of subclinical carotid atherosclerosis in type 2 diabetes mellitus
Authors: Guo Xiu Li , Wang Jian Wen , Tu Mei , Wang Wei
Published: October 2023

Objective

Emerging evidence highlighted that perirenal adipose tissue might regulate the cardiovascular and metabolism system through several pathways. This study aimed to assess the association between perirenal fat thickness (PrFT) and subclinical carotid atherosclerosis (SCCA) in type 2 diabetes mellitus (T2DM).

Method

A total of 670 participants with complete data were included in this study. The trained reviewer collected demographic and anthropometric information. Laboratory assessments were determined by standard methods. PrFT and SCCA were evaluated by computed tomography and ultrasound. Binomial logistic regression analysis was conducted to assess the association between PrFT and SCCA. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the identifying value of PrFT for SCCA.

Results

Overall, the prevalence of SCCA was 61.8% in T2DM. PrFT was significantly increased in the SCCA group. Growing trends were observed in the prevalence of hypertension, carotid intima-media thickness (cIMT) > 1, plaque, and SCCA across the PrFT quartiles. Spearman correlation analysis revealed that PrFT was positively associated with cIMT (r = 0.401, p < 0.001). This correlation remained significant after adjustment for visceral fat area (VFA), subcutaneous fat area (SFA), and traditional metabolic risk factors (β = 0.184, p < 0.001). Meanwhile, PrFT was independently correlated with plaque, cIMT > 1 mm, and SCCA. The ORs (95% CI) were 1.072 (1.014–1.135), 1.319 (1.195–1.455), and 1.216 (1.119–1.322). Furthermore, PrFT remained correlated considerably with SCCA in subgroup analysis after stratification for age, sex, smoking, hypertension, and body mass index. From the ROC curve analysis, the AUCs (95% CI) of PrFT, VFA, and SFA identifying SCCA were 0.794 (0.760–0.828), 0.760 (0.724–0.796), and 0.697 (0.656–0.737), respectively. The AUC of PrFT was significantly higher than VFA (p = 0.028) and SFA (p < 0.001). The optimal cutoff values of PrFT were 14.0 mm, with a sensitivity of 66.7% and a specificity of 76.2%.

Conclusion

PrFT was independently associated with cIMT, plaque, cIMT > 1 mm, and SCCA as a superior obesity-related marker of SCCA in T2DM.

Clinical trial registration

Clinical Trials.Gov, identifier ChiCTR2100052032.
Borealin/CDCA8 deficiency alters thyroid development and results in papillary tumor-like structures
Authors: Didier-Mathon Hortense , Stoupa Athanasia , Kariyawasam Dulanjalee , Yde Sonny , Cochant-Priollet Beatrix , Groussin Lionel , Sébag Frédéric , Cagnard Nicolas , Nitschke Patrick , Luton Dominique , Polak Michel , Carré Aurore
Published: October 2023

Background

BOREALIN/CDCA8 mutations are associated with congenital hypothyroidism and thyroid dysgenesis. Borealin is involved in mitosis as part of the Chromosomal Passenger Complex. Although BOREALIN mutations decrease thyrocyte adhesion and migration, little is known about the specific role of Borealin in the thyroid.

Methods

We characterized thyroid development and function in Borealin-deficient (Borealin+/−) mice using histology, transcriptomic analysis, and quantitative PCR.

Results

Thyroid development was impaired with a hyperplastic anlage on embryonic day E9.5 followed by thyroid hypoplasia from E11.5 onward. Adult Borealin+/− mice exhibited euthyroid goiter and defect in thyroid hormone synthesis. Borealin+/− aged mice had disorganized follicles and papillary-like structures in thyroids due to ERK pathway activation and a strong increase of Braf-like genes described by The Cancer Genome Atlas (TCGA) network of papillary thyroid carcinoma. Moreover, Borealin+/− thyroids exhibited structural and transcriptomic similarities with papillary thyroid carcinoma tissue from a human patient harboring a BOREALIN mutation, suggesting a role in thyroid tumor susceptibility.

Conclusion

These findings demonstrate Borealin involvement in critical steps of thyroid structural development and function throughout life. They support a role for Borealin in thyroid dysgenesis with congenital hypothyroidism. Close monitoring for thyroid cancer seems warranted in patients carrying BOREALIN mutations.
Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus
Authors: Baxter Ryan M. , Wang Christine S. , Garcia-Perez Josselyn E. , Kong Daniel S. , Coleman Brianne M. , Larchenko Valentyna , Schuyler Ronald P. , Jackson Conner , Ghosh Tusharkanti , Rudra Pratyaydipta , Paul Debdas , Claassen Manfred , Rochford Rosemary , Cambier John C. , Ghosh Debashis , Cooper Jennifer C. , Smith Mia J. , Hsieh Elena W. Y.
Published: October 2023

Introduction

Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN. While many studies have linked dysregulation of germinal center formation to SLE pathogenesis, other work supports a role for extrafollicular B cell activation in generation of pathogenic antibody secreting cells. However, whether extrafollicular B cell subsets and their T cell collaborators play a role in specific organ involvement in cLN and/or track with disease activity remains unknown.

Methods

We analyzed high-dimensional mass cytometry and gene expression data from 24 treatment naïve cSLE patients at the time of diagnosis and longitudinally, applying novel computational tools to identify abnormalities associated with clinical manifestations (cLN) and disease activity (SLEDAI).

Results

cSLE patients have an extrafollicular B cell expansion signature, with increased frequency of i) DN2, ii) Bnd2, iii) plasmablasts, and iv) peripheral T helper cells. Most importantly, we discovered that this extrafollicular signature correlates with disease activity in cLN, supporting extrafollicular T/B interactions as a mechanism underlying pediatric renal pathogenesis.

Discussion

This study integrates established and emerging themes of extrafollicular B cell involvement in SLE by providing evidence for extrafollicular B and peripheral T helper cell expansion, along with elevated type 1 IFN activation, in a homogeneous cohort of treatment-naïve cSLE patients, a point at which they should display the most extreme state of their immune dysregulation.
Myeloid Vamp3 deletion attenuates CFA-induced inflammation and pain in mice via ameliorating macrophage infiltration and inflammatory cytokine production
Authors: Dai Xiaolong , Li Lianlian , Yan Xinrong , Fan Qianqian , Wang Ruizhen , Zhang Wenhao , Chen Weiwei , Liu Yang , Meng Jianghui , Wang Jiafu
Published: October 2023

Persistent inflammation and associated pain significantly impact individuals’ quality of life, posing substantial healthcare challenges. Proinflammatory cytokines, released by activated macrophages, play crucial roles in the development of chronic inflammatory conditions such as rheumatoid arthritis. To identify and evaluate potential therapeutic interventions targeting this process for mitigating inflammation and pain, we created myeloid cell-specific knockout of Vamp3 (vesicle-associated membrane protein 3) mice (Vamp3Δmyel) by crossing LysM-Cre mice with newly engineered Vamp3flox/flox mice. Bone marrow-derived macrophages and peritoneal resident macrophages from Vamp3Δmyel mice exhibited a significant reduction in TNF-α and IL-6 release compared to control mice. Moreover, Vamp3 deficiency led to decreased paw edema and ankle joint swelling induced by intraplantar injection of complete Freund’s adjuvant (CFA). Furthermore, Vamp3 depletion also mitigated CFA-induced mechanical allodynia and thermal hyperalgesia. Mechanistically, Vamp3 loss ameliorated the infiltration of macrophages in peripheral sites of the hind paw and resulted in reduced levels of TNF-α and IL-6 in the CFA-injected paw and serum. RT-qPCR analysis demonstrated downregulation of various inflammation-associated genes, including TNF-α, IL-6, IL-1β, CXCL11, TIMP-1, COX-2, CD68, and CD54 in the injected paw at the test day 14 following CFA administration. These findings highlight the novel role of Vamp3 in regulating inflammatory responses and suggest it as a potential therapeutic target for the development of novel Vamp-inactivating therapeutics, with potential applications in the management of inflammatory diseases.
Lesion-aware attention network for diabetic nephropathy diagnosis with optical coherence tomography images
Authors: Liu Yuliang , Zhang Fenghang , Gao Xizhan , Liu Tingting , Dong Jiwen
Published: October 2023

Purpose

For early screening of diabetic nephropathy patients, we propose a deep learning algorithm to screen high-risk patients with diabetic nephropathy from retinal images of diabetic patients.

Methods

We propose the use of attentional mechanisms to improve the model’s focus on lesion-prone regions of retinal OCT images. First, the data is trained using the base network and the Grad-CAM algorithm locates image regions that have a large impact on the model output and generates a rough mask localization map. The mask is used as a auxiliary region to realize the auxiliary attention module. We then inserted the region-guided attention module into the baseline model and trained the CNN model to guide the model to better focus on relevant lesion features. The proposed model improves the recognition of the lesion region.

Results

To evaluate the lesion-aware attention network, we trained and tested it using OCT volumetric data collected from 66 patients with diabetic retinal microangiopathy (89 eyes, male = 43, female = 23). There were 45 patients (60 eyes, male=27, female = 18) in DR group and 21 patients (29 eyes, male = 16, female = 5) in DN group. Our proposed model performs even better in disease classification, specifically, the accuracy of the proposed model was 91.68%, the sensitivity was 89.99%, and the specificity was 92.18%.

Conclusion

The proposed lesion-aware attention model can provide reliable screening of high-risk patients with diabetic nephropathy.