bluuebunny/crossref_metadata_2025 huggingface dataset:
ASSESSMENT IN CADETS’ TECHNOLOGY COURSE
Authors:   National Defence University (NDU), Finland, Rissanen Antti , Saastamoinen Kalle ,   National Defence University (NDU), Finland
Published: September 2021

In many technology related courses in addition to the new content, previously learned knowledge about science and science related supportive tools are simultaneously studied. In the field of applied sciences, the aim is to apply technology applications derived from these scientific methods and models to the operating environment. From the point of view technical disciplines in cadets’ education are important but narrow in scope, so there is a need to look for solutions that meet the educational goals of the local community. In this research, it is considered to build a broader assessment, to support learning to be motivating, and also to guide teachers at their work. This empirical research consists of findings from three successive courses in the sensor technology education for cadets. Examination structure is analyzed according to the test scoring and student success. As a conclusion, a course of specific mix of quiz can be recommended. Moreover, the principles of the presented form-based test are transferable to electronic assessment environments. Keywords: structure of assessment, summative test, technology education.
Anlatı Oyun Pedagojisi: Erken Çocukluk Eğitiminde Oyun Temelli Bir Yaklaşım
Authors: Temel Zeynep Fulya , Temiz Çağlar Aslı
Published: September 2021

Bu çalışmada Finlandiya’da geliştirilmiş olan oyunun gücünü ve yetişkin çocuk ortaklığını savunan Anlatı Oyun Pedagojisi (Narrative Play Pedagogy) tanıtılmıştır. Çalışma kapsamında yaklaşımın teorik ve felsefi temellerine, eğitim ortamına, yetişkin rollerine, günlük eğitim akışına, planlama, uygulama ve değerlendirme sürecine ilişkin bir kavramsal çerçeve çizilmeye çalışılmıştır. Anlatı Oyun Pedagojisi, Hakkarainen ve Bredikyte tarafından 1990’lı yılların sonunda geliştirilmiştir. Teorik ve felsefi temelleri büyük oranda Kültürel Tarihsel Kurama ve Profesör Vasili Davydov ve ekibinin ileri sürdüğü görüşlere dayanmaktadır. Bu yaklaşımda çocuk oyunlarını geliştirme, genişletme ve oyun ile öğrenme hedefleri arasındaki geçişi kolaylaştırma amaçlanmıştır. Uygulamalar, çocuğu oyuna davet eden okul içi ve okul dışı çeşitli öğrenme ortamlarında yürütülür. Çocuklar anlatı oyun dünyalarında farklı yaşlardaki akran grupları ve yetişkin oyun ortakları ile hayali roller üstlenerek maceralar yaşarlar. Anlatı Oyun Pedagojisi, Türkiye’de okul öncesi eğitim kurumlarında oyun kültürünü geliştirmek için ilham verici bir örnek olarak uzmanlara ve uygulayıcılara yol gösterici olabilir.
Üniversite Öğrencilerinin Kayırmacılık Kavramına İlişkin Metaforik Algıları
Authors: Demirbilek Nesip
Published: September 2021

Araştırmanın amacı üniversite öğrencilerinin kayırmacılık kavramını nasıl kavramsallaştırdıklarını ve algıladıklarını metaforlar aracılığı ile belirlemektir. Araştırmada nitel araştırma yöntemlerinden fenomenoloji yaklaşımı benimsenmiş, katılımcıların seçilmesinde ise kolay örnekleme tekniği kullanılmıştır. Araştırmada 2020-2021 eğitim-öğretim yılında Muş Alparslan Üniversitesinde öğrenim gören toplam 159 öğrenci yer almıştır. Üniversite öğrencilerine metafor cümlesi online olarak gönderilmiştir. Verilerin analizinde “içerik analizi” tekniğinden yararlanılmıştır. Araştırma sonuçlarına göre üniversite öğrencilerinin ürettiği metaforlar ile oluşturulan kategorilerin toplam sekiz kategori başlığı altında yer aldığı görülmüştür. Sonuç olarak Muş Alparslan Üniversitesi öğrencilerinin ifadelerinden hareketle kayırmacılığın, büyük zararları olan, sosyal bir davranış bozukluğu olduğu ve toplumun çoğunu olumsuz etkilediği sonucuna varılmıştır.
C5.0 Karar Ağacı Algoritması ile Öğretmenlerin FeTeMM Farkındalıklarının İncelenmesi
Authors: Dokumacı Sütçü Neşe
Published: September 2021

Araştırmada, öğretmenlerin FeTeMM farkındalıklarını yordayan değişkenleri ve değişkenlerin önem sırasını belirlemek amaçlanmıştır. Araştırmanın katılımcıları, 2020-2021 eğitim-öğretim yılı bahar döneminde Diyarbakır’da görev yapan 267 öğretmenden oluşmaktadır. İlişkisel tarama modelinin kullanıldığı araştırmada veriler, “Kişisel Bilgi Formu” ve “FeTeMM Farkındalık Ölçeği” ile toplanmıştır. Verilerin analizinde İki Aşamalı Kümeleme Analizi ve C5.0 Karar Ağacı Algoritması kullanılmıştır. Araştırmada FeTeMM Farkındalık Ölçeği’nin her üç boyutuna ilişkin öğretmenlerin çoğunun orta düzey farkındalığa sahip oldukları ortaya çıkmıştır. Bununla birlikte ortaya çıkan bir başka bulgu ise “öğrenciye etkisi” boyutu üzerinde etki düzeyi en yüksek olan yordayıcı değişkenin öğretmenlerin görev yaptıkları okulların sosyoekonomik düzeyleri, “derse etkisi” ve “öğretmene etkisi” boyutları üzerinde etki düzeyi en yüksek olan yordayıcı değişkenin ise öğretmenlerin öğrenim durumları olduğudur.
Ebeveynlik Görevleri Kontrol Listesi’nin Türkçeye Uyarlama Çalışması
Authors: Özkan Kunduracı Hurşide Kübra , Aksoy Ayşe Belgin
Published: September 2021

Bu araştırmanın amacını, Sanders ve Woolley (2005) tarafından geliştirilen Ebeveynlik Görevleri Kontrol Listesi’nin Türk kültürüne uyarlanması oluşturmaktadır. Araştırmanın çalışma grubuna, 24-48 aylık çocuğa olan 214 anne oluşturmuştur. Uyarlama çalışmasına ölçeğin kaynak dilden hedef dile çevrilmesiyle başlamış olup, uzman görüşü alma, dilsel eşdeğerlik ve ön pilot çalışmalarıyla esas uygulama öncesi ölçeğin Türkçe formuna son hali verilmiştir. Ölçeğin yapı geçerliğini belirlemek amacıyla yapılan doğrulayıcı faktör analizi sonuçları Türkçeye uyarlanmış ölçeğin iki alt boyuttan oluştuğunu göstermiştir. Çalışmada, faktör yük değerlerinin yanı sıra model-veri uyumuna işaret eden bir takım uyum indekslerinden de faydalanılmıştır. Ölçeğin iki alt boyutunun her biri için Cronbach Alpha katsayısı hesaplanmıştır. Araştırma sonucunda, Ebeveynlik Görevleri Kontrol Listesi’nin iki alt boyut ve 28 madde olarak Türk kültürüne uyarlandığı belirlenmiştir. Ölçeğin 24-48 ay arasındaki çocukların annelerin öz yeterliklerini ölçmede geçerli ve güvenilir bir ölçme aracı olduğu sonucuna ulaşılmıştır.
Barrows with stone lining in Belarus and Ukraine
Authors: Zajkoŭski Edvard
Published: September 2021

The range of Medieval burial structures on the territory of Belarus includes barrows with stone lining. Commonly, one layer of stones encircled a barrow, but two layers’ lining could also be met. Funeral rite can be described as inhumation at the horizon level or in a pit with western orientation of the dead. Individual burials are most characteristic though double burials were practiced too. Not every burial mound contains grave goods. The items are represented by ornaments, amulets and pots of mostly Slavic type. The finds date back to the 11th – early 12th or 12th – 13th century. The same burial ground could also contain barrows composed entirely of earth, ones including stones interspersed or in the form of thin pavement at the horizon. Barrows of this kind are spread both in central Belarus and farther to the north, covering partly the Dzvina Basin, or more often to the south-west – in the Middle Buh Basin including Polish and Belarusian parts.
In Ukraine barrows with stone construction were studied in Zhytomyr Polissya Region where almost 20 burial grounds of this type are known. Such barrows can be found in some other places too: in the Ros’ Basin, in Bukovyna (two barrows with stone lining dated back to the 12th – mid 13th century have been excavated there), in Podilia (burial sites in Zhnyborody I, Sokilets’, Hlybochok).
In archaeological studies, there’s a tendency to assign all the barrows with stone constructions to the range of so called stone barrows which are considered to be burial sites of the Jaćviahi. Though in the eastern part of Mazur Lake region and in the basin of the Chornaya Hancha river where the Jatvingians have been located according to the evidence from chronicles there’s no barrows dated back to the 10th – 13th centuries at all. At the same time, in the first millennium AD barrows with stone lining were spread in the range of the Eastern Balts tribes: on the territory of Latvia (tribal areas of Latgaly, Siely, Ziemgaly) and Lithuania (the area of the Eastern Lithuanian Barrows Culture) where they dominated between the 4th and 7th centuries and still could be met in the 7th – 10th centuries. However, we know Eastern Balts’ barrows with stone lining of the eleventh century in the south of Lithuania and bordering part of Belarus, which are chronologically close to the barrows with stone constructions in the rest part of Belarus and in the Middle Dnipro region. The emergence of these kind sites in Bukovyna and Podillia became possible in the result of the union of Volhynian and Galician principalities, i.e. after 1199.
Key words: barrows with stone lining, grave goods, Middle Buh region, Zhytomyr Polissya region, Bukovyna, Podillia, Jatvingians, the Eastern Lithuanian Barrows Culture.
Cave monastery of Galicia: the problem of interpretation, localization and protection
Authors: Berest Roman
Published: September 2021

The problem of the little-known, complex and multifaceted history of the medieval cave monasticism of Galicia is raised. In the most difficult period of national history, it defended the basic principles and principles of national dignity, social tolerance, Christian spirit and upbringing in far from difficult conditions.
Based on the results of archeological and speleological researches of a number of monuments, the existence of a significant variety of cave monuments in Galician lands (cult altars, churches, monasteries, proto-monastery houses, cells of hermits, ascetics, etc.) was noted. In the context of the presentation of the material, the peculiarities of the organizational structure of medieval monasticism, ways and reasons of development and decline of monastic communities are considered. There are also the main features and types of cave dwellings of statutory monasticism, buildings characteristic of ascetics, kinovites, keliots, idiorhythms, which are almost unknown in historical science and can be a significant addition to the treasury of national historical and cultural heritage.
The difficult problem of preserving the cave heritage of medieval monasticism is emphasized. In comparison with the information of the authors of the XIX century at present, many monuments of cave monasticism have long disappeared or suffered irreparable damage under the influence of natural, anthropogenic and other factors. Preservation of the national historical and cultural heritage should become an important and urgent task of the relevant social structures.
Key words: cave cavities, cells, localization, interpretation, historical and cultural monuments.
Increasing the Role of Work Discipline and Job Trainings on Employee Performance
Authors: Sularmi Lili , Stifanny Cherly
Published: September 2021

Management is the science and art of regulating the process of utilizing human resources and other sources effectively and efficiently to achieve a specific goal. PD CBJ must review the increasing role of Work Discipline and Training to achieve employee performance. This study was conducted empirically and is one of the company's essential internal components to improve its general performance by facing the challenges of industrial revolution 4.0. This study applies quantitative research methods. The data collection utilizes the form of using a survey method with a questionnaire device. This study's target population was 64 (sixty-four) employees at PD CBJ as same as obtaining the saturated sample. The verification analysis takes the inferential statistics to prove the hypothesis using the multiple regression analysis techniques. This yield gives empirical evidence to show that Work Discipline plays a role in improving Employee Performance at PD CBJ. In contrast, Training does not play a role in enhancing Employee Performance at PD CBJ. As a result, Work Discipline and Training have a high position in increasing Employee Performance at PD CBJ, with a 71.3 percent determination score.
Loyalty as Affecting Mediator of Service Quality And Customer Satisfaction Towards Competitive Advantage
Authors: Sultoni Mohammad Hamim , Sudarmiatin Sudarmiatin
Published: September 2021

When preparing an effective marketing strategy, a bank must consider its competitors as well as its customers. Establishing a mutual relationship with customers requires a better means of satisfying customer needs than the competitors. Micro, Small, and Medium-sized Enterprises (MSMEs) should always analyze their competitors and develop marketing strategies that effectively give the company a good position compared to the competitors and provide a competitive advantage as strong as possible. This research was conducted using a quantitative method. The design referred to causal relationship research. The data were then analyzed using the path analysis. Findings showed that customer satisfaction, service quality, and customer loyalty affected the competitive advantage of Sentra Batik Pamekasan. The effect of customer loyalty on the competitive advantage could be viewed from the number of Sentra Batik Pamekasan's customers who decided not to move to other financial institutions (banks). When the company could give better service quality, the customer loyalty and the competitive advantage among financial institutions would get higher.

 

Abstrak

Dalam mempersiapkan strategi pemasaran yang efektif, pihak perbankan harus mempertimbangkan pesaingnya dan juga konsumennya. Membangun hubungan antara konsumen yang menguntungkan, memerlukan alat pemuasan kebutuhan konsumen sebagai sasaran yang lebih baik daripada pesaingnya. UMKM harus senantiasa menganalisis pesaing dan mengembangkan strategi pemasaran kompetitif yang secara efektif memposisikan UMKM dalam menghadapi pesaing dan memberikan keunggulan kompetitif sekuat mungkin. Penelitian ini menggunakan metode kuantitatif, jenis penelitian termasuk kategori hubungan kausal sedangkan analisis dalam penelitian ini menggunakan analisis jalur (path analysis). Hasil penelitian menunjukkan bahwa kepuasan konsumen, kualitas layanan, dan loyalitas konsumen mempengaruhi keunggulan bersaing di Sentra Batik Pamekasasan. Dampak dari loyalitas konsumen terhadap keunggulan bersaing dapat dilihat dari seberapa banyak konsumen Sentra Batik Pamekasasan yang tidak pindah ke lembaga keuangan lain. Semakin bagus kualitas layanan maka semakin tinggi tingkat loyalitas konsumen dan keunggulan bersaing antar lembaga keuangan juga akan semakin tinggi.

Kata Kunci : Loyalitas konsumen, kepuasan konsumen, kualitas layanan, keunggulan bersaing
Campomelic dysplasia: an overview of a rare genetic disorder
Authors: Antonakopoulos N. , Vrachnis D. , Loukas N. , Christodoulaki Ch. , Iliodromiti Z. , Vrachnis N.
Published: September 2021

Campomelic dysplasia is a rare and severe genetic condition that is characterized by shortening and bowing of the long bones, abnormal face, multiple congenital anomalies, and ambiguous genitalia. Having conducted a review of the existing literature on this rare genetic disorder, we herein present the most pertinent and essential data on the condition viewed from the clinical perspective. In the majority of cases when the neonate survives the condition, since the underlying cause is more often than not a de novo mutation of the SOX9 gene, there is no increased risk of recurrence. Diagnosis is tentatively made based on skeletal findings during routine prenatal ultrasound; it may subsequently be confirmed via either prenatal or postnatal molecular genetic testing or else radiologic evaluation. In general, the condition is considered to be lethal in the neonatal period, there is no prenatal treatment and pregnancy termination is an option.
Imperforate hymen: a rare cause of tenesmus
Authors: Zacharis Konstantinos , Kravvaritis Stavros , Chrysafopoulou Eleni , Charitos Theodoros , Fouka Anastasia
Published: September 2021

Imperforate hymen is an uncommon obstructive anomaly of the female reproductive tract for which early diagnosis is easy to miss. Untreated cases after menarche may cause cyclic lower abdominal pain and amenorrhea. Hymenotomy is considered proper management in order to avoid complications associated with late treatment. We report a case of an imperforate hymen in a 13-year-old adolescent girl presenting with tenesmus and acute lower abdominal pain. The patient was treated with hymenotomy and postoperative period was uneventful. Tenesmus and lower abdominal pain resolved immediately after surgery and during follow up the girl reported normal menstrual cycles. According to our case, tenesmus may be an atypical clinical presentation of imperforate hymen. Therefore, imperforate hymen should not be eliminated from differential diagnosis when it comes to adolescent females with abdominal pelvic pain and gastrointestinal symptoms and gynecological examination should be performed.
Irshad Manji on Hermeneutics: Reconsidering Her Method of Interpretation of LGBT-Q Verses in Al-Qur’an
Authors: Maulana Abdullah Muslich Rizal
Published: September 2021

A Canadian Muslim Reformist, Irshad Manji, has strived to introduce her thoughts concerning the emancipation of LGBT-Q rights around the world. Accordingly, She offered a ‘reformed interpretation’ of The Qur’an to reveal alternatives of theological understanding regarding some verses about LGBT-Q. This paper will enquire Manji’s fundamental idea and the method in commenting and interpreting LGBT-Q verses in the Qur’an, as her endeavor was considered closely similar to Hermeneutics, a method of interpretation developed in the Catholic-Christian World. This paper found the domination of Hermeneutics on Manji’s attempt in understanding the Qur’an constructing her argumentation about LGBT-Q. In the perspective of Science of Qur’an and Tafsir, Manji has manipulated Qur’anic verses to support her campaign emancipating LGBT-Q rights in the whole domains, especially in their sexual expression.
MANAGEMENT SYSTEM OF PESANTREN SAFETY OFFICER FOR LEARNING ORDER
Authors: Hakim Luqmanul
Published: September 2021

The purpose of this study was to determine the implementation of the learning control system in Pondok Pesantren Darussalam Sumbersari Kediri. The orderliness of students' learning can be improved through the boarding school's security management system. This control system relies on the maximum role of Islamic boarding school security staff in the activities and activities that exist in Islamic boarding schools. This study uses a qualitative field method. This research is intended to understand the phenomenon of what is experienced by research subjects, for example behavior, perception, motivation, action, and others related to orderliness of learning in Darussalam Islamic Boarding School and security management systems and security strategies in improving learning order. This study concludes that the system for controlling learning activities at Pondok Pesantren Darussalam Sumbersari Kediri uses a punishment strategy that has value in learning. This punishment is termed takzir.

 Keywords: safety officer, pesantren, learning order, ta'zir.

 SISTEM PENGELOLAAN PETUGAS KEAMANAN PESANTREN DALAM KETERTIBAN PEMBELAJARAN

Abstrak

Tujuan penelitian ini adalah untuk mengetahui implementasi sistem penertiban pembelajaran di Pondok Pesantren Darussalam Sumbersari Kediri. Ketertiban pembelajaran santri dapat ditingkatkan melalui sistem pengelolaan keamanan pondok pesantren. Sistem penertiban ini bertumpu pada peran maksimal staf keamanan pondok pesantren dalam kegiatan dan aktifitas yang ada dipondok pesantren. Penelitian ini menggunakan metode kualitatif lapangan. Penelitian ini dimaksudkan untuk memahami fenomena tentang apa yang dialami oleh subjek penelitian misalnnya perilaku, persepsi, motivasi, tindakan, dan lain-lain berkaitan dengan ketertiban pembelajaran di Pondok Pesantren Darussalam dan sistem pengelolaan keamanan dan strategi keamanan dalam meningkatkan ketertiban pembelajaran. Penelitian ini menyimpulkan bahwa system penertiban kegiatan pembelajaran di Pondok Pesantren Darussalam Sumbersari Kediri menggunakan strategi punishment (hukuman) yang bernilai pembelajaran. Hukuman ini diistilahkan dengan takzir.

Kata kunci: petugas keamanan,  pondok pesantren, ketertiban pembelaran, takzir.
HepParser: An Intelligent Software Program for Deciphering Low-Molecular-Weight Heparin Based on Mass Spectrometry
Authors: Wang Hui , Wang Yu , Hou Meijie , Zhang Chunming , Wang Yaojun , Guo Zhendong , Bu Dongbo , Li Yan , Huang Chuncui , Sun Shiwei
Published: September 2021

Low-molecular-weight heparins (LMWHs) are considered to be the most successful carbohydrate-based drugs because of their wide use as anticoagulants in clinics. The efficacy of anticoagulants made by LMWHs mainly depends on the components and structures of LMWHs. Therefore, deciphering the components and identifying the structures of LMWHs are critical to developing high-efficiency anticoagulants. However, most LMWHs are mixtures of linear polysaccharides which are comprised of several disaccharide repeating units with high similarity, making it extremely challenging to separate and decipher each component in LMWHs. Here, we present a new algorithm named hepParser to decipher the main components of LMWHs automatically and precisely based on the liquid chromatography/mass spectrometry (LC/MS) data. When tested on the general LMWH using hepParser, profiling of the oligosaccharides with different degrees of polymerization (dp’s) was completed with high accuracy within 1 minute. When compared with the results of GlycReSoft on heparan sulfate samples, hepParser achieved more comprehensive and reasonable results automatically.
Protected Area Rangers as Cultural Brokers? Implications for Wildlife Crime Prevention in Viet Nam
Authors: Rizzolo Jessica B. , Gore Meredith L. , Long Barney , Trung Cao T. , Kempinski Josh , Rawson Benjamin , Huyẽn Hoàng T. , Viollaz Julie
Published: September 2021

The scope, scale, and socio-environmental impacts of wildlife crime pose diverse risks to people, animals, and environments. With direct knowledge of the persistence and dynamics of wildlife crime, protected area rangers can be both an essential source of information on, and front-line authority for, preventing wildlife crime. Beyond patrol and crime scene data collected by rangers, solutions to wildlife crime could be better built off the knowledge and situational awareness of rangers, in particular rangers' relationships with local communities and their unique ability to engage them. Rangers are often embedded in the communities surrounding the conserved areas which they are charged with protecting, which presents both challenges and opportunities for their work on wildlife crime prevention. Cultural brokerage refers to the process by which intermediaries, like rangers, facilitate interactions between other relevant stakeholders that are separate yet proximate to one another, or that lack access to, or trust in, one another. Cultural brokers can function as gatekeepers, representatives, liaisons, coordinators, or iterant brokers; these forms vary by how information flows and how closely aligned the broker is to particular stakeholders. The objectives of this paper are to use the example of protected area rangers in Viet Nam to (a) characterize rangers' cultural brokerage of resources, information, and relationships and (b) discuss ranger-identified obstacles to the prevention of wildlife crime as an example of brokered knowledge. Using in-depth face-to-face interviews with rangers and other protected area staff (N = 31, 71% rangers) in Pu Mat National Park, 2018, we found that rangers regularly shift between forms of cultural brokerage. We offer a typology of the diverse forms of cultural brokerage that characterize rangers' relationships with communities and other stakeholders. We then discuss ranger-identified obstacles to wildlife protection as an example of brokered knowledge. These results have implications for designing interventions to address wildlife crime that both improve community-ranger interactions and increase the efficiency of wildlife crime prevention.
Case Report: Lymphohistiocytic Myocarditis With Severe Cardiogenic Shock Requiring Mechanical Cardiocirculatory Support in Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection
Authors: Bemtgen Xavier , Klingel Karin , Hufnagel Markus , Janda Ales , Bode Christoph , Staudacher Dawid L. , Supady Alexander , Jandova Ilona
Published: September 2021

Multisystem Inflammatory Syndrome (MIS) is a novel hyperinflammatory syndrome associated with SARS-CoV-2 infection. It predominantly affects children (MIS-C) a few weeks after a usually asymptomatic SARS-CoV-2 infection and is only rarely seen in adults above 21 years (MIS-A). Only scarce data on histological findings in both pediatric and adult patients has been published so far. An 18-year-old male patient was admitted to hospital in a febrile state, which progressed to severe cardiogenic shock and multi-organ failure requiring extracorporeal life support. Myocardial biopsy revealed small vessel-associated immune cell infiltrates. Diagnosis of MIS-C was made after ruling out all potential differential diagnosis. Use of immunosuppressive treatment with steroids, interleukin-1 blockade and high-dose intravenous immunoglobulins resulted in the patient's full recovery. Multisystem Inflammatory Syndrome (MIS) is a new differential diagnosis of cardiac dysfunction in pediatric and adult patients. The lack of myocardial necrosis differentiates the disease from other viral myocarditis and offers an explanation for the fast response to immunomodulatory therapy and the favorable prognosis. The preceding SARS-CoV-2 infection might only have been mildly symptomatic or even asymptomatic.
Hydrogeochemistry and Acidic Property of Submarine Groundwater Discharge Around Two Coral Islands in the Northern South China Sea
Authors: Lui Hon-Kit , Liu Min-Yun , Lin Hsiu-Chin , Tseng Hsiao-Chun , Liu Li-Lian , Wang Feng-Yu , Hou Wei-Ping , Chang Rae , Chen Chen-Tung Arthur
Published: September 2021

Submarine groundwater discharge (SGD) is an important source of nutrients in many coastal regions, yet little information is available on its carbonate chemistry and controlling factors. This study examined the processes and factors controlling the hydrogeochemistry and acidic property of the groundwaters and SGD waters of two isolated coral islands, Liuqiu Island (13 km off southwestern Taiwan) and Dongsha Island (located in the northern South China Sea, 420 km away from Liuqiu Island). Our results showed that the total alkalinity and dissolved inorganic carbon (DIC) of the fresh SGD waters were controlled mainly by the chemical weathering of carbonate minerals. Part of the DIC came from the organic matter decomposition or soil CO2, reducing the pH and CO32− concentration. Distributions of the carbonate chemistry and nutrients of the SGD waters were controlled mainly by physical mixing between the groundwater and the ambient seawater under the seabed, the so-called subterranean estuary. The Ca2+ released through weathering significantly increased the saturation state of aragonite or calcite, reducing the corrosiveness of the SGD waters on the carbonate rocks. This study is likely the first to examine the effects of the acidic property of SGD waters on the biogenic carbonate spine of a sea urchin and a pteropod shell. The spring water with similar carbonate chemistry to that of the freshwater SGD endmember from Liuqiu Island with a saturation state of aragonite of 0.96 caused observable dissolution on the spine of a sea urchin and a pteropod shell, but the spine dissolved more readily. This was because the spine is made of high-Mg calcite, which has higher solubility than that of aragonite or calcite. Such a result implies that some marine organisms with carbonate skeletons or shells containing high Mg:Ca ratios may suffer the impact of ocean acidification earlier. Although the SGD may contribute less than 10% of freshwater discharge by rivers to the coastal area, its impact on coastal biogeochemical cycles and ecosystems due to its acidic property and continual effect on the coast all year round deserves further investigation.
Molecular Genetics, Clinical Characteristics, and Treatment Outcomes of KATP-Channel Neonatal Diabetes Mellitus in Vietnam National Children’s Hospital
Authors: Ngoc Can Thi Bich , Dien Tran Minh , De Franco Elisa , Ellard Sian , Houghton Jayne A. L. , Lan Nguyen Ngoc , Thao Bui Phuong , Khanh Nguyen Ngoc , Flanagan Sarah E. , Craig Maria E. , Dung Vu Chi
Published: September 2021

Background

Neonatal diabetes mellitus (NDM) is defined as insulin-requiring persistent hyperglycemia occurring within the first 6 months of life, which can result from mutations in at least 25 different genes. Activating heterozygous mutations in genes encoding either of the subunits of the ATP-sensitive K+ channel (KATP channel; KCNJ11 or ABCC8) of the pancreatic beta cell are the most common cause of permanent NDM and the second most common cause of transient NDM. Patients with NDM caused by KATP channel mutations are sensitive to sulfonylurea (SU) treatment; therefore, their clinical management can be improved by replacing insulin with oral agents.

Patients and Methods

Seventy patients were diagnosed with NDM between May 2008 and May 2021 at Vietnam National Children’s Hospital, and molecular genetic testing for all genes known to cause NDM was performed at the Exeter Genomic Laboratory, UK. Patients with ABCC8 or KCNJ11 mutations were transferred from insulin to oral SU. Clinical characteristics, molecular genetics, and annual data relating to glycemic control, SU dose, severe hypoglycemia, and side effects were collected. The main outcomes of interest were SU dose, SU failure (defined as permanent reintroduction of daily insulin), and glycemic control (HbA1c).

Results

Fifty-four of 70 patients (77%) with NDM harbored a genetic mutation and of these; 27 (50%) had activating heterozygous mutations in ABCC8 or KCNJ11. A total of 21 pathogenic mutations were identified in the 27 patients, including 13 mutations in ABCC8 and 8 mutations in KCNJ11. Overall, 51% had low birth weight (below 3rd percentile), 23 (85%) were diagnosed before 3 months of age, and 23 (85%) presented with diabetic ketoacidosis. At diagnosis, clinical and biochemical findings (mean ± SD) were pH 7.16 ± 0.16; HCO3−, 7.9 ± 7.4 mmol/L; BE, −17.9 ± 9.1 mmol/L; HbA1C, 7.98% ± 2.93%; blood glucose, 36.2 ± 12.3 mmol/L; and C-peptide median, 0.09 (range, 0–1.61 nmol/l). Twenty-six patients were successfully transferred from insulin to SU therapy. In the remaining case, remission of diabetes occurred prior to transfer. Glycemic control on SU treatment was better than on insulin treatment: HbA1c and blood glucose level decreased from 7.58% ± 4.63% and 19.04 ± 14.09 mmol/L when treated with insulin to 5.8 ± 0.94% and 6.87 ± 3.46 mmol/L when treated with SU, respectively.

Conclusions

This is the first case series of NDM patients with ABCC8/KCNJ11 mutations reported in Vietnam. SU is safe in the short term for these patients and more effective than insulin therapy, consistent with all studies to date. This is relevant for populations where access to and cost of insulin are problematic, reinforcing the importance of genetic testing for NDM.
Implementing and Interpreting Refugee Resettlement Through a Veil of Secrecy: A Case of LGBT Resettlement From Africa
Authors: Menetrier Agathe
Published: September 2021

In the last decade the number of countries aiming to resettle refugees increased and complementary pathways aiming to relocate humanitarian migrants expanded. Stakeholders in charge of the selection process of candidates and logistical organization of these programs multiplied as a consequence. Because refugee resettlement and complementary pathways are not entrenched in international law, selection processes and logistical organization are at the discretion of stakeholders in charge, sometimes hardly identifiable themselves, and can vary greatly from one scheme to another. For displaced candidates to resettlement and complementary pathways, this opacity can have dramatic consequences in regions of origin. This article will present the case of a group of African lesbian and gay asylum seekers who first sought asylum in a neighboring country, hoping for resettlement to the global North. Because their first country of asylum criminalizes homosexuality, the responsible regional office of the United Nations High Commissioner for Refugees (UNHCR) must circumvent the said country’s sovereignty on asylum matters and recognize LGBT asylum seekers as refugees under UN mandate before submitting their cases to resettlement countries. UNHCR agents thus conduct refugee status determination (RSD) and resettlement procedures behind a veil of secrecy, at the risk of antagonizing their local partners and confusing aspiring refugees. Meanwhile, INGOs from the global North cooperate with local LGBT associations to relocate LGBT Africans out of the same African countries. This paper will show African asylum asylum seekers’ efforts to qualify for all these programs simultaneously, unaware of the mutually exclusive aspects of some; to become visible to institutions and “sponsors” they deem more powerful, at the expense of solidarity within their group.
HLA-G1+ Expression in GGTA1KO Pigs Suppresses Human and Monkey Anti-Pig T, B and NK Cell Responses
Authors: Rao Joseph Sushil , Hosny Nora , Kumbha Ramesh , Naqvi Raza Ali , Singh Amar , Swanson Zachary , Levy Heather , Matson Anders W. , Steinhoff Magie , Forneris Nicole , Walters Eric , Hering Bernhard J. , Burlak Christopher
Published: September 2021

The human leukocyte antigen G1 (HLA-G1), a non-classical class I major histocompatibility complex (MHC-I) protein, is a potent immunomodulatory molecule at the maternal/fetal interface and other environments to regulate the cellular immune response. We created GGTA1-/HLAG1+pigs to explore their use as organ and cell donors that may extend xenograft survival and function in both preclinical nonhuman primate (NHP) models and future clinical trials. In the present study, HLA-G1 was expressed from the porcine ROSA26 locus by homology directed repair (HDR) mediated knock-in (KI) with simultaneous deletion of α-1-3-galactotransferase gene (GGTA1; GTKO) using the clustered regularly interspersed palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) (CRISPR/Cas9) gene-editing system. GTKO/HLAG1+pigs showing immune inhibitory functions were generated through somatic cell nuclear transfer (SCNT). The presence of HLA-G1 at the ROSA26 locus and the deletion of GGTA1 were confirmed by next generation sequencing (NGS) and Sanger’s sequencing. Fibroblasts from piglets, biopsies from transplantable organs, and islets were positive for HLA-G1 expression by confocal microscopy, flow cytometry, or q-PCR. The expression of cell surface HLA-G1 molecule associated with endogenous β2-microglobulin (β2m) was confirmed by staining genetically engineered cells with fluorescently labeled recombinant ILT2 protein. Fibroblasts obtained from GTKO/HLAG1+pigs were shown to modulate the immune response by lowering IFN-γ production by T cells and proliferation of CD4+and CD8+T cells, B cells and natural killer (NK) cells, as well as by augmenting phosphorylation of Src homology region 2 domain-containing phosphatase-2 (SHP-2), which plays a central role in immune suppression. Islets isolated from GTKO/HLA-G1+genetically engineered pigs and transplanted into streptozotocin-diabetic nude mice restored normoglycemia, suggesting that the expression of HLA-G1 did not interfere with their ability to reverse diabetes. The findings presented here suggest that the HLA-G1+transgene can be stably expressed from the ROSA26 locus of non-fetal maternal tissue at the cell surface. By providing an immunomodulatory signal, expression of HLA-G1+may extend survival of porcine pancreatic islet and organ xenografts.
Genetic Connectivity of Seamount Populations of Bluenose Warehou (Hyperoglyphe antarctica)
Authors: Heyworth Stephanie M. , Bell James B. , Wade Christopher M. , Cavalcante Geórgenes , Robinson Nicholas , Young Emma , Glass James , Feary David A.
Published: September 2021

Quantifying the level of population connectivity within and between geographically separated single-species deep-water fisheries stocks will be vital for designing effective management plans to preserve such populations. Despite this, stock structure in many fisheries is still poorly described and, at best, subject to precautionary management. Here we use rapidly evolving mitochondrial genes and microsatellite markers to investigate population connectivity patterns in commercially targeted Hyperoglyphe antarctica populations between four seamounts within the Tristan da Cunha Exclusive Economic Zone (EEZ). We find little evidence of population genetic structure between fished populations, with both mtDNA and microsatellite markers showing that there is low genetic population diversity (reflecting substantial gene flow) across the four seamounts. We also find little genetic differentiation between H. antarctica across the wider Southern Hemisphere. Such results support the role for coordinated management of all four populations across the seamounts, and potentially including stocks associated with Australia and New Zealand, with expansion of the fishery clearly having the potential to substantially impact the source of recruits and therefore wider population sustainability.
Current Regulatory Requirements for Biosimilars in Six Member Countries of BRICS-TM: Challenges and Opportunities
Authors: Rahalkar Hasumati , Sheppard Alan , Santos Gustavo Mendes Lima , Dasgupta Chitralekha , Perez-Tapia Sonia Mayra , Lopez-Morales Carlos A. , Salek Sam
Published: September 2021

Background: The aim of the study was to identify, interpret, and compare the current perspectives of regulatory agencies in six member countries of BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, and Mexico) on the different criteria used for biosimilar development and marketing authorisation process.

Methods: A semi-quantitative questionnaire was developed covering the organisation of agency, biosimilar development criteria and marketing authorisation process and sent to seven regulatory agencies covering the BRICS-TM countries. All data was kept anonymous and confidential. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data.

Results: Out of the seven regulatory agencies included in the study, six representatives provided the responses. The perspectives of these six regulatory agencies varied on a number of aspects relating to the review criteria for biosimilar development and licencing process. The most prevalent model for data assessment is the “full review” of a marketing authorisation application. There is lack of a standard approach across the agencies on sourcing of the reference biological product, in vivo toxicity studies and confirmatory clinical studies. Most agencies restrict interaction with biosimilar developers and any scientific advice is non-binding. The marketing authorisation approval depends on scientific assessment of the dossier, sample analysis and GMP certification. The agencies do not issue any public assessment report specifying the summary basis of biosimilar approval.

Conclusion: Regulatory agencies across the six emerging economies are steadily improving the regulatory mechanism in the area of biosimilars. However, there remains scope for increasing the effectiveness and efficiency of the processes by encouraging open and transparent interaction with developers, adopting a flexible approach toward accepting advanced analytical data in lieu of clinical studies and enhancing regulatory reliance amongst agencies. This will help to simplify the new biosimilar development programmes and make them more cost-effective.
T-Lymphocyte Subsets Alteration, Infection and Renal Outcome in Advanced Chronic Kidney Disease
Authors: Xiong Jiachuan , Qiao Yu , Yu Zhikai , Huang Yinghui , Yang Ke , He Ting , Zhao Jinghong
Published: September 2021

Background:T-lymphocyte subsets reflect patients' immune status and are associated with adverse outcomes in various diseases. However, the association between T-lymphocyte subsets and major infection and renal outcome in chronic kidney disease (CKD) patients has not been well-addressed.

Methods:Patients diagnosed with stage 3–5 of non-dialysis CKD were recruited, and healthy subjects were selected as the controls. T-lymphocyte subsets (CD3+, CD4+, CD8+) were detected by flow cytometry, and the CD4+/CD8+T cell ratio was then calculated. Patients were divided into the normal-level group and the low-level group according to the clinical reference value. The primary outcomes were the major infection and renal outcome.

Results:A total of 410 CKD patients were enrolled; the average age was 47.25 years. Compared to the healthy controls, the level of CD3+, CD4+, CD8+T cells, and the CD4+/CD8+T cell ratio were significantly decreased in CKD patients (p< 0.05). During the median follow-up of 2.56 (quartile interval 1.24–3.46) years, major infections occurred in 15.10% of the CKD patients. The incidence of infection was significantly higher in the low-level group of CD3+, CD4+T cells, and CD4+/CD8+T cell ratio compared with the normal level groups. Kaplan-Meier analysis showed that the lower level of CD3+, CD4+T cells, and CD4+/CD8+T cell ratio is associated with a greater risk of infection. Cox regression analysis further confirmed that low CD3+, CD4+T cells, and CD4+/CD8+T cell ratio were independent risk factors of infection in CKD patients. Moreover, during the follow-up, renal events occurred in 37.50% of patients. Kaplan-Meier analysis indicated that low levels of CD3+, CD4+, and CD8+T cells are significantly associated with renal outcome in CKD patients. Cox regression analysis showed that low level of CD3+T cells (HR = 2.407, 95% CI: 1.664–3.482,p< 0.001), CD4+T cells (HR = 2.397, 95% CI: 1.633–3.518,p< 0.001) and CD8+T cells (HR = 2.416, 95% CI: 1.476–3.955,p< 0.001) were independent risk factors for renal outcome after multivariable-adjusted.

Conclusion:CKD patients had a defect in T-lymphocyte subpopulation. T-lymphocyte subsets were closely associated with infection and renal outcome in CKD patients. Suggesting T-lymphocyte subsets are independent predictors of infection and renal outcome in CKD patients.
Extremophilic Prokaryotic Endoxylanases: Diversity, Applicability, and Molecular Insights
Authors: Verma Digvijay
Published: September 2021

Extremophilic endoxylanases grabbed attention in recent years due to their applicability under harsh conditions of several industrial processes. Thermophilic, alkaliphilic, and acidophilic endoxylanases found their employability in bio-bleaching of paper pulp, bioconversion of lignocellulosic biomass into xylooligosaccharides, bioethanol production, and improving the nutritious value of bread and other bakery products. Xylanases obtained from extremophilic bacteria and archaea are considered better than fungal sources for several reasons. For example, enzymatic activity under broad pH and temperature range, low molecular weight, cellulase-free activity, and longer stability under extreme conditions of prokaryotic derived xylanases make them a good choice. In addition, a short life span, easy cultivation/harvesting methods, higher yield, and rapid DNA manipulations of bacterial and archaeal cells further reduces the overall cost of the product. This review focuses on the diversity of prokaryotic endoxylanases, their characteristics, and their functional attributes. Besides, the molecular mechanisms of their extreme behavior have also been presented here.
A Critical Review of Alien Limb-Related Phenomena and Implications for Functional Magnetic Resonance Imaging Studies
Authors: Di Pietro Martina , Russo Mirella , Dono Fedele , Carrarini Claudia , Thomas Astrid , Di Stefano Vincenzo , Telese Roberta , Bonanni Laura , Sensi Stefano L. , Onofrj Marco , Franciotti Raffaella
Published: September 2021

Consensus criteria on corticobasal degeneration (CBD) include alien limb (AL) phenomena. However, the gist of the behavioral features of AL is still “a matter of debate.” CBD-related AL has so far included the description of involuntary movements, frontal release phenomena (frontal AL), or asomatognosia (posterior or “real” AL). In this context, the most frequent symptoms are language and praxis deficits and cortical sensory misperception. However, asomatognosia requires, by definition, intact perception and cognition. Thus, to make a proper diagnosis of AL in the context of CBD, cognitive and language dysfunctions must be carefully verified and objectively assessed. We reviewed the current literature on AL in CBD and now propose that the generic use of the term AL should be avoided. This catchall AL term should instead be deconstructed. We propose that the term AL is appropriate to describe clinical features associated with specific brain lesions. More discrete sets of regionally bound clinical signs that depend on dysfunctions of specific brain areas need to be assessed and presented when posing the diagnosis. Thus, in our opinion, the AL term should be employed in association with precise descriptions of the accompanying involuntary movements, sensory misperceptions, agnosia-asomatognosia contents, and the presence of utilization behavior. The review also offers an overview of functional magnetic resonance imaging-based studies evaluating AL-related phenomena. In addition, we provide a complementary set of video clips depicting CBD-related involuntary movements that should not mistakenly be interpreted as signs of AL.
Ornidazole-Induced Recurrent Encephalopathy in a Chinese Man: A Rare Case Report and Literature Review
Authors: Tang Rong , Liang Jia , Li Yuanfang , Wu Tingting , Zhang Yuhao , Ma Yu , Liu Xu
Published: September 2021

Ornidazole-induced encephalopathy (OIE) is seldom seen in the clinic. In this study, we report a new case of a patient who had taken 1,000 mg ornidazole daily for nearly 4 years because of suspected diarrhea and proctitis and presented with subacute symptoms such as unsteady gait, slurred speech, and psychiatric disorder. These symptoms were significantly relieved 3 days after the patient stopped taking ornidazole. When he took this medicine again, however, similar symptoms occurred 4 months later, which were again reduced after 4 days of drug discontinuation. After the second onset, abnormal signals were identified around the aqueduct of the midbrain, around the fourth ventricle, and in the dentate nuclei of the cerebellum bilaterally. After 9 days of drug discontinuation, lesions disappeared in the magnetic resonance imaging (MRI) results. According to the clinical manifestations, imaging features, and the reduced symptoms after drug withdrawal, we clinically diagnosed the patient with OIE. This paper also reviews the literature on OIE. Only five cases (including our case) have been reported, all of whom presented with cerebellar ataxia and dysarthria and three with additional mental symptoms such as agitation and irritability. All five patients had abnormal lesions in the dentate nucleus of the cerebellum bilaterally, among whom four also had lesions in the corpus callosum and three around the periaqueduct of the midbrain. After withdrawal of ornidazole, the symptoms in all patients vanished or were alleviated, and three of them showed reduced or disappeared lesions in a head MRI reexamination. Overall, OIE has rarely been reported. Our case report and literature review show that the lesions in the cerebellum, corpus callosum, and brainstem can be reversed. The main manifestations of the lesions—cerebellar ataxia, dysarthria, and mental symptoms—quickly weaken or disappear after drug withdrawal, with good prognosis. Nevertheless, clear pathogenesis has yet to be further investigated.