bluuebunny/crossref_metadata_2025 huggingface dataset:
The Syrian Refugee Crisis in Canadian Media
Authors: Tyyskä Vappu , Blower Jenna , DeBoer Samantha , Kawai Shunya , Walcott Ashley
Published: May 2021

This paper offers a critical analysis of Canadian media content (The Globe and Mail, Toronto Star, National Post, Huffington Post, CBC, and CTV), from September 2015 to April 2016, of the coverage of the Canadian resettlement effort of Syrian refugees, including representation of the refugees and the Canadian government and public. The analysis is informed by theories of orientalism, neocolonialism, neoliberalism, and feminism.
Impacts of a large and decentralized telepathology network in Canada
Authors: Paré Guy , Meyer Julien , Trudel Marie-Claude , Têtu Bernard
Published: May 2021

Background:
Telepathology is one of the fast growing segment of the telemedicine field and Canada is recognized as a world leader in this particular domain.
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Introduction:
We report a benefits evaluation study of a decentralized telepathology network deployed in Eastern Quebec. The project involves 18 hospitals, making it one of the largest telepathology networks in the world.

Materials and Methods:
We first conducted 43 semi-structured interviews with telepathology users and managers. Hard data on the impacts of the telepathology network (e.g. the number of service disruptions, the average time between initial diagnosis and surgery) was also extracted and analyzed, where available.

Results:
Users found the system to be easy to use and the quality of the virtual slides and images was also considered satisfactory by pathologists. A key objective was to provide continuous coverage of intraoperative consultations in hospitals with no pathologist. Our findings show that no service disruptions were recorded in the se sites. Surgeons agreed that the use of telepathology helped avoid second surgeries and improved accessibility to care services. Telepathology was also perceived by respondents as having positive impacts on remote hospitals’ ability to retain and recruit specialists.

Discussion:
The observed benefits should not leave the impression that implementing telepathology is a trivial matter. Indeed, many technical, human and organizational challenges may be encountered.

Conclusions:
Telepathology can be highly useful in regional hospitals that do not have a pathologist on site. More research is needed to investigate the challenges and benefits associated with this growing form of telemedicine.
Penerapan Flipped Classroom Berbasis Teknologi Informasi pada Mata Pelajaran Fiqih di MTs Al-Chusnaniyah Surabaya
Authors: Ubaidillah Muhammad
Published: May 2021

E-Learning is one of the breakthroughs in education that requires information technology. Various online learning models began to be developed. For example blended learning, distance learning (distance learning) and flipped learning. Online learning is basically trying to innovate and change the paradigm in learning. One model of online learning that is currently quite a lot of learning in educational research is reverse learning. Reverse classes are learning held in class with online learning. In turning the lassroom things that are usually done in the classroom such as explaining the material, giving assignments, exercises and homework are transferred to online learning. This research was conducted with development research design. This study aims to study the differences in student learning outcomes through pretest and posttest in students and student learning outcomes also aims to determine the level of student self-confidence. The application of Information Technology-Based Flipped Classroom learning model to classroom learning outcomes and the increase in self-confidence of class VIII students in Fiqh Subjects in MTs Al-Chusnaniyah Surabaya is relatively effective.
Kajian Amtsal dan Qasam dalam Al Qur'an
Authors: Jailani Ani , Hasbiyallah Hasbiyallah
Published: May 2021

Proses pendidikan yang menggunakan media amtsal (perumpamaan), dimaksudkan untuk membentuk berbagai premis diharapkan peserta didik mampu untuk merumuskan istimbathnya secara logis, dan melatih daya Ijtihad yang kuat. Sedangkan Qasam merupakan gaya bahasa yang dijunjung tinggi didalam kebudayaan dan kebiasaan bangsa Arab dalam rangka demi menjaga kehormatannya. Dengan bentuk gaya bahasa dengan tujuan untuk menguatkan setiap pernyataan yang disampaikan. Hakikat qasam dalam al-Tafsir al-Bayani terdiri dari dua aspek, yaitu etimologi dan terminologi. Dari segi etimologi qasam bermakna sumpah yang benar berbeda dengan kata half yang mengandung arti kebohongan sumpah dan ketidaksungguhan si pengucapnya. Secara terminologi, qasam adalah gaya bahasa dalam al-Qur’an yang menjelaskan makna sebuah ayat dengan cara penalaran indrawi yaitu pengalihan perhatian (lafitah) dari sesuatu yang dapat dirasakan (hissi) kepada sesuatu yang abstrak. Bentuknya ada dua, yaitu sumpah dengan huruf wau al-qasam dan sumpah dengan huruf la. Fungsi qasam dalam al-Tafsir al-Bayani telah beralih dari fungsi asalnya yakni untuk mengagungkan atau memuliakan objek sumpah menjadi sebuah retorika bayani yang bertujuan menganalogikan antara muqsam bih dengan jawab al-qasam.
Joseph Schacht dan Transformasi Hadis Tentang Hukum Islam dalam Konteks Dunia Timur
Authors: Munawwir A. , Lestari Ani , Prilia Fita Ratu
Published: May 2021

Hadith studies have not only become the focus of Islamic scholars' attention, but have also become material for orientalist studies. So from this, there are many western scientists and scholars who chose the path of researching hadith. Starting from Ignaz Goldziher to leading scholars of hadith from Germany, Harald Motzki also graces the list of western scholars who are competent in the study of hadith. The long history of hadith in the west is evidence of the proliferation of hadith studies. In contrast to Muslims, western people study hadith departs from their distrust of hadith. Surely this is a different portrait of the traditions of the eastern people. Therefore, various theories and methods they used to justify that the hadith did not come from the Prophet Muhammad, but was made by people after him. This article is in the form of an attempt to explain at length the theory proposed by Joseph Schacht in order to undermine the authenticity of the hadith itself, and some of its weaknesses, which are based on the views of Islamic scholars'.
The River and the Filmmaker: A Journey towards a Meeting Place
Authors: River Dungala-Baaka , Gough-Brady Catherine
Published: May 2021

Agnès Varda’s idea of cinécriture opens up an understanding of the myriad of influences on the creation of a documentary, and its combination of malleability and certainty. For her, film is a product of exploratory walks and seemingly unconnected choices as well as the scripting, shooting and editing.
Michael Renov suggests there are four desires that influence the way a documentarian creates a film, one of them is ‘to express’. When I set out to film Rivers (2019), I was expressing anger and outrage at destruction taking place. For Donna Haraway, this ‘urgency’ arising from destruction does not create despair, rather it inspires action in response to the crisis. Thus the film became an action in response, both to the crisis the Murray-Darling river faced, and crises in my own life.
Through interviews I conducted, this article compares my own filming journey with that of two award winning filmmakers: Nicole Ma and Sabiha Sumar. I find that filmmaking involves locating a meeting place between the filmmaker, the filmed subject, and the audience.
The Positive Implications of Intentional Feedback
Authors: Ackerman Kera , Horn Channon
Published: May 2021

Positive and constructive feedback is a high leverage practice that can be learned and practiced through scaffolded and structured experiences. Teaching preservice candidates to provide effective feedback is an efficient way to increase P-12 students’ learning and behavioral outcomes. Teacher educators can craft experiences for their preservice teachers that offer rich coursework experiences, practice-based opportunities, and aligned clinical placement. Using the scaffolded approach provided in this article, teacher educators can ensure these experiences are robust and aligned with evidence-based pedagogy.
In Vitro Determination of Sun Protection Factor of Water Extract of Aerodramus fuciphagus from Central Kalimantan
Authors: Sandi Dita Ayulia Dwi , Susiani Eka Fitri , Adnyana I Ketut , Wikaningtyas Pratiwi
Published: May 2021

Sunscreen is a cosmetic substance that has the ability to reflect or absorb sunlight actively. It can prevent skin irritation due to UV rays. One of the natural ingredients with a sunscreen effect is the Edible-nest swiftlet's (Aerodramus fuciphagus) nest (ESN). This study aimed to determine the value of the sun protective factor (SPF) of the ESN water extract. The ESN water extract solution with variation concentration, this is 2000, 2500, 5000, 6000, and 7000 ppm, were measured by spectrophotometric UV-Vis at wavelength 290-375 nm with 5 nm intervals to determine the value of SPF, percentage of erythema transmission (%Te), and percentage of pigmentation transmission (%Tp) of ESN water extract. The result showed that the ESN water extract's SPF values at the concentration 2000, 2500, 5000, 6000, and 7000 ppm were 7.80; 9.68; 18.75; 20.58; and 22.24. The value of %Te of each concentration were 15.60±0.19; 10.03±0.42; 1.24±0.04; 0.81±0.01 and 0.56±0.01. While the value of %Tp of each concentration was showed the sunblock category. In conclusion, the ESN water extract from Central Kalimantan at the concentration of 6000 ppm has potential in ultraviolet protection against the skin in the ultra category with sunblock category mechanism. Further, it can be developed into sunscreen cosmetics from natural ingredients.
Formulation and Evaluation of Sustained Release Matrix Tablets of Aceclofenac
Authors: Singh Priyanka , Shrivastava Amit Kumar , Kumar Sachin , Dwivedi Manish Dhar
Published: May 2021

This study aimed to improve the dissolution rate of aceclofenac and release the drug in a controlled manner over a period of 24 hours. Matrix tablets were prepared by direct compression method, using hydrophilic polymers (HPMC/guar gum). Matrix tablets were prepared by wet granulation method using different hydrophilic polymers (HPMC/guar gum). Tablets were evaluated for in vitro drug release profile in phosphate buffer with pH 6.8 (without enzymes). The thickness and hardness of prepared tablets were 3.23 ± 0.035 to 3.28 ± 0.008 mm and 3.26 ± 0.115 to 3.60 ± 0.200 kg/cm2, respectively. The friability was within the acceptable limits of pharmacopoeial specifications (0.31 to 0.71%), which indicates the good mechanical strength of the tablets. Drug release was retarded with an increase in polymer concentration due to the gelling property of polymers. The in vitro drug release from the proposed system was best explained by Higuchi’s model, indicating that drug release from tablets displayed a diffusion-controlled mechanism. The results clearly indicate that guar gum could be a potential hydrophilic carrier in developing oral controlled drug delivery systems. Based on the study results, formulations F8 was selected as the best formulation.
Method Development and Characterization of Liposomal Formulation of Isotretinoin
Authors: Ahmad Md Iftekhar , Kumar Punet , Singh Sangam , Kumar Nitin
Published: May 2021

This study aims to develop a liposomal drug delivery system of isotretinoin, an acne drug-using spray drying, as a cost-effective and time-effective technique. The liposomal formulation was prepared by using spray drying; three different strategies were adopted: suspension spray drying (SSD), thin-film hydration and spray drying (TFHSD), and emulsion spray drying (ESD). Isotretinoin was 99% bound with lipid, so lipids hydrogenated soy phosphatidylcholine (HSPC), distearoyl phosphatidylglycerol (DSPG), and cholesterol were selected for the formulation development. The HSPC, DSPG, cholesterol, and isotretinoin were taken in the ratio 4 : 1 : 0.16 : 3.1 mmol. In vitro drug release studies, microscopy, drug content, and related substance characterizations were done to formulate each strategy of spray drying prepared dry liposomes of isotretinoin. Results were compared with the USP monograph of isotretinoin. It was revealed that isotretinoin's liposomal formulation using ESD was having drug release according to the USP limits. Drug content was also according to the USP requirement; no free drug crystals were found in microscopy, multivesicular vesicles were found in shape, a particle size of up 60 µ was found. The ESD technique was a successful, time-effective, and cost-effective technique for preparing a liposomal drug delivery system for isotretinoin.
Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Oral Delivery of Cod Liver Oil
Authors: Priani Sani Ega , Rahayu Desti Puspa , Maulana Indra Topik
Published: May 2021

Cod liver oil (CLO) has long been used as medicine or as a functional food. The CLO is a potential source of vitamin D, vitamin A, and omega fatty acids (eicosapentaenoic acid/EPA and docosahexaenoic acid/DHA). Self-nanoemulsifying drug delivery system (SNEDDS) can enhance dissolution, absorption, and bioavailability of hydrophilic and lipophilic substances for oral administration. The objective of this study was to develop a SNEDDS of CLO with good physical characteristics and stability. The optimization formula was carried out using various ratios of oil, surfactant, and cosurfactant. The physical properties of SNEDDS were determined by transmittance percentage, dispersibility, robustness, thermodynamics stability (heating-cooling cycle, centrifugation, and freeze-thaw cycle), and globule size distribution. The optimum formula of CLO-SNEDDS was obtained at a ratio of surfactant and cosurfactant 2 : 1  and a comparison of oil and surfactant mixtures 1 : 6. The CLO-SNEDDS meets the requirement of percent transmittance (97.90±0.85), dispersibility (grade A), and stability based on robustness and thermodynamic stability tests. Diluted SNEDDS has an average globule size of 125 nm with a polydispersity index (PDI) of 0.515. CLO-SNEDDS preparation has good physical characteristics and stability.
ГЕНПРОКУРОРИ НЕЗАЛЕЖНОЇ УКРАЇНИ: 30 РОКІВ ПОЛІТИКО-ПРАВОВОГО ДОСВІДУ З ПЕРЕДУМОВ ПРИЗНАЧЕННЯ НА ПОСАДУ, СТРОКУ ПОВНОВАЖЕНЬ ТА ПІДСТАВ ЗВІЛЬНЕННЯ
Authors: Руденко М. В.
Published: May 2021

У статті досліджено питання конституційної моделі посади "Генерального прокурора". Стисло розглянуто історичний шлях щодо передумов призначення на посаду кожного Генерального прокурора України, строку їх повноважень та підстав звільнення з посади у контексті 30-річного політико-правового досвіду. Значну увагу акцентовано на конституційної процедурі призначення (звільнення) Генерального прокурора, яка передбачає задіяння у цьому процесі двох вищих центрів влади: Верховної Ради та Президента України. Така законодавча конструкція піддана авторської критиці, адже за неї політично незаангажованим Генпрокурор бути не може, бо де-факто стає виконавцем політичної волі або Президента або Верховної Ради України, що, звичайно, не правильно. Тому подальша діяльність Генерального прокурора потребує нових гарантій незалежності та відсутності побічних факторів, які б її підривали, тобто запровадження в Україні нової конституційної моделі посади Генерального прокурора.

Ключові слова: Генеральний прокурор, призначення Генерального прокурора, строк повноважень, підстави звільнення Генерального прокурора, модель посади Генерального прокурора.
УКРАЇНСЬКЕ ЗАКОНОДАВСТВО І ПОТРЕБИ СУСПІЛЬСТВА
Authors: Попов А. А. , Рязанцев О. Є. , Рязанцева Н. О.
Published: May 2021

У статті розглянуті проблеми відповідності ряду норм українського законодавства потребам українського суспільства, охарактеризовані головні форми та моделі взаємодії громадських організацій з державою, що визначені законодавчо та мають чітке нормативно-правове регулювання. Автори висувають і обґрунтовують пропозицію щодо розробки більш ефективних норм законодавства України, порівняно із зарубіжних країнах в деяких сферах (податкове, сімейне, міжнародне приватне право і т.д.).

У дослідженні критично проаналізовані положення Угоди про асоціацію Україна – ЄС, а також запропоновано запозичення досвіду у таких західних країн, як: Німеччина, Франція, США та інших, у побудові громадянського суспільства.

Ключові слова: національні інтереси, податкові пільги, громадські організації, законодавча ініціатива, громадськість.
Study on respiratory problems and respiratory function amongst females exposed to biomass fuel and gas/ electricity fuel in a district of Bangladesh
Authors: Alim Md Abdul , Nurunnabi Abu Sadat Mohammad , Ahmad Salahuddin , Khan Mohammad Adnan , Ahmad SK Akhter
Published: May 2021

Indoor air pollution from biomass smoke is now regarded as public health hazard in the developing world causing different respiratory diseases. A cross-sectional study was conducted to see the prevalence of respiratory disease and status of respiratory function among female biomass fuel users and gas/electricity fuel users in a selective area of Bangladesh. A total of 103 females from Madla, a rural area under Bogra District of Bangladesh, which having good communication facilities, meeting the defined enrollment criteria for biomass fuel group were selected purposively as cases, while 101 females from the urban households from Thanthania in the same district, meeting the defined eligibility criteria for controls were included in gas/electricity fuel group. The participants were interviewed on a semi-structured questionnaire from March to June 2007. Moreover, peak expiratory flow rate (PEFR) of 98 participants from each group was measured as a lung function parameter. In the biomass group, majority (61.6%) used open type of kitchen, 21.2% partially closed kitchen, 11.1% closed and 6.1% closed non-ventilated kitchen. Nearly three-quarter (73%) of the gas/electricity group used closed ventilated type of kitchen, 26% used partially closed kitchen and only 1 case used open kitchen. Nearly one-quarter (24%) of the biomass group had habit of taking beetle-nut compared to only 3% of the gas/electricity group and chewing tobacco was also revealed to be proportionately higher in the former group (22.8%) than that in the latter group (4%) (p<0.001). The biomass group exhibited a significantly higher frequency of respiratory problem (16.5%) compared to their gas/electricity counterpart (5%). 30.4% of the participants of biomass group suffered from allergic rhinitis as opposed to 13% of the gas/electricity group. Coughing was also significantly higher in the biomass group (13.7%) than that in the gas/electricity group (1%). Coughing in the early morning and cough with productive sputum also demonstrated their significant presence in the former group than that in the latter group. Peak expiratory flow rate (PEFR) shows that it was significantly lower in the biomass fuel user group (225.0±38.6 L/min.) than that of the gas/electricity user group (247.5±34.4 L/min.) (p<0.001). It was found that smoke generated from biomass fuel combustion is a significant risk factor for respiratory problems among the female household members who, by tradition, are associated with cooking activities.

CBMJ 2014 January: Vol. 03 No. 01 P: 08-12
Hermite-Hadamard Type Inequalities for the Functions Whose Absolute Values of First Derivatives are $p$-Convex
Authors: SEZER Sevda
Published: May 2021

In this paper, we extend some estimates of a Hermite-Hadamard type inequality for functions whose absolute values of the first derivatives are $p$-convex. By means of the obtained inequalities, some bound functions involving beta functions and hypergeometric functions are derived as applications. Also, we suggest an upper bound for error in numerical integration of $p$-convex functions via composite trapezoid rule.
Modified high-flow nasal cannula for children with respiratory distress
Authors: Itdhiamornkulchai Sarocha , Preutthipan Aroonwan , Vaewpanich Jarin , Anantasit Nattachai
Published: May 2021

Background: High-flow nasal cannula (HFNC) is a noninvasive respiratory support that provides the optimum flow of an air-oxygen mixture. Several studies demonstrated its usefulness and good safety profile for treating pediatric respiratory distress patients. However, the cost of the commercial HFNC is high; therefore, the modified high-flow nasal cannula was developed.Purpose: This study aimed to compare the effectiveness, safety, and nurses’ satisfaction of the modified system versus the standard commercial HFNC.Methods: This prospective comparative study was performed in a tertiary care hospital. We recruited children aged 1 month to 5 years who developed acute respiratory distress and were admitted to the pediatric intensive care unit. Patients were assigned to 2 groups (modified vs. commercial). The effectiveness and safety assessments included vital signs, respiratory scores, intubation rate, adverse events, and nurses’ satisfaction.Results: A total of 74 patients were treated with HFNC. Thirty- nine patients were assigned to the modified group, while the remaining 35 patients were in the commercial group. Intubation rate and adverse events did not differ significantly between the 2 groups. However, the commercial group had higher nurses’ satisfaction scores than the modified group.Conclusion: Our findings suggest that our low-cost modified HFNC could be a useful respiratory support option for younger children with acute respiratory distress, especially in hospital settings with financial constraints.
CONTEXTUALIZATION AND CONNECTIVITY OF DIGITAL LITERACY IN PRIMARY SCHOOL SOCIAL STUDIES DURING THE COVID-19 PANDEMIC
Authors: Kowiyah Siti , Riyanto Yatim , Harmanto Harmanto
Published: May 2021

This research identifies and explores Social Science (IPS) learning at the Elementary School level (SD) delivered by utilizing digital technology during the Covid-19 pandemic in Indonesia. This study explores the use of the internet and how social knowledge learning is in dialogue with digital literacy that occurs in it. This research is a qualitative study of digital literacy in social studies learning in elementary schools. The data sources were elementary school teachers using random sampling, with spatial boundaries in Surabaya and Sidoarjo, East Java. The temporal limitation of this research is data taken from April 2020 to January 2021. The collected data is then analyzed with Kathleen Tyner's perspective regarding literacy in the digital world and June Chapin about social studies learning in primary education. The results showed that contextuality and connectivity through digital literacy in elementary social studies raise constructive aspects through collective memory about experiencing something and using previous knowledge through digital literacy. The constructive and cognitive aspects present two essential dimensions that explain the occurrence of elementary social knowledge learning. First, relating to information processing; in terms of receiving, storing, and then remembering information when it has needed. Second, related to meaningful learning about social life in society, how children shape and organize existing and new information that comes to mind. Therefore, this model can teach and study any subject matter related to social studies at the elementary school level.
Automatic Voter Registration as a Housewarming Gift: Quantifying Causal Effects on Turnout Using Movers
Authors: Kim Seo-young Silvia
Published: May 2021

How much does automatic voter registration (AVR) increase turnout? Unlike many democracies, American voters in many states face additional costs of registration, resulting in potential disenfranchisement. AVR is expected to promote turnout by alleviating registration costs, but its causal effects have rarely been quantified due to violations of crucial assumptions. I show that automatic voter (re)registration increases turnout by 5.8 percentage points by exploiting a discontinuity in a novel dataset of voters who moved. Election officials in Orange County, California, notified existing registrants who moved that their residential addresses were automatically updated. The treatment alleviated registrants of re-registration burdens--but only for those who moved before the legal cutoff date. Contrary to the popular narrative, AVR had no significant effect on the turnout of registered Democratic voters, but Republicans' and nonpartisans' turnout increased by 8.1 and 7.4 percentage points.
Hard to Boil Massecuite
Authors: Fowkes Neville , Hennessy M.G. , Moyles I. , Thompson S. , Fareo G. , Atherfold J.
Published: May 2021

Evaporators are used to remove most of the water from sugar cane juice leaving a syrup which is fed into the pan boiler. Seed crystals are then added to the syrup and the mixture (referred to as massecuite) is further heated to remove moisture so that sugar crystals grow. The pan boiling process normally works smoothly. However, in the South African harvesting season (the wet season) the syrup does not appear to boil and crystallisation is significantly slowed. The problem is thought to be due to the presence of impurities (specifically polysaccharides) which change the rheological properties of the massecuite. A range of models were produced to examine the effects of changes in massecuite properties on the operation on the boiler and the boiling process itself. The results suggest that the primary cause of hard to boil massecuite is bubble suppression although other mechanisms may also be involved.
Pelatihan Peningkatan Pendidikan Kesehatan tentang Persiapan Menjelang Menopause di Puskesmas Mojo
Authors: Rijanto Rijanto , Alfiah Siti , Jeniawaty Sherly
Published: May 2021

In general, menopause occurs at the age of 48-50 years, including in the climacteric period, which is a syndrome of endocrine, somatic, and psychological changes at the end of the fertile / reproductive period. The aim of this study was to evaluate the success of cadre training in optimizing preparation for menopause. The intervention was given in the working area of Puskesmas Mojo, Surabaya. The intervention targets of health cadres and elderly women were selected using a quota sampling technique. The results of the evaluation show that there had been a 70% increase in the knowledge of elderly cadres about preparation for menopause.

Keywords: menopause; health education; elderly women; health cadres

ABSTRAK

Pada umumnya menopause terjadi pada usia 48-50 tahun, termasuk dalam masa klimakterium yang merupakan sindrom perubahan endokrin, somatik, dan psikik pada akhir masa subur/reproduktif. Tujuan studi ini adalah mengevaluasi keberhasilan pelatihan kader dalam optimalisasi persiapan menjelang menopause. Intervensi diberikan di wilayah kerja Puskesmas Mojo, Surabaya. Sasaran intervensi kader kesehatan dan wanita usia lanjut, yang dipilih dengan teknik quota sampling. Hasil evaluasi menunjukkan bahwa telah terjadi peningkatan sebesar 70% tentang pengetahuan ibu kader lansia mengenai persiapan menjelang menopause.

Kata kunci: menopause; pendidikan kesehatan; wanita usia lanjut; kader kesehatan
Social Integrating Robots Suggest Mitigation Strategies for Ecosystem Decay
Authors: Schmickl Thomas , Szopek Martina , Mondada Francesco , Mills Rob , Stefanec Martin , Hofstadler Daniel N. , Lazic Dajana , Barmak Rafael , Bonnet Frank , Zahadat Payam
Published: May 2021

We develop here a novel hypothesis that may generate a general research framework of how autonomous robots may act as a future contingency to counteract the ongoing ecological mass extinction process. We showcase several research projects that have undertaken first steps to generate the required prerequisites for such a technology-based conservation biology approach. Our main idea is to stabilise and support broken ecosystems by introducing artificial members, robots, that are able to blend into the ecosystem’s regulatory feedback loops and can modulate natural organisms’ local densities through participation in those feedback loops. These robots are able to inject information that can be gathered using technology and to help the system in processing available information with technology. In order to understand the key principles of how these robots are capable of modulating the behaviour of large populations of living organisms based on interacting with just a few individuals, we develop novel mathematical models that focus on important behavioural feedback loops. These loops produce relevant group-level effects, allowing for robotic modulation of collective decision making in social organisms. A general understanding of such systems through mathematical models is necessary for designing future organism-interacting robots in an informed and structured way, which maximises the desired output from a minimum of intervention. Such models also help to unveil the commonalities and specificities of the individual implementations and allow predicting the outcomes of microscopic behavioural mechanisms on the ultimate macroscopic-level effects. We found that very similar models of interaction can be successfully used in multiple very different organism groups and behaviour types (honeybee aggregation, fish shoaling, and plant growth). Here we also report experimental data from biohybrid systems of robots and living organisms. Our mathematical models serve as building blocks for a deep understanding of these biohybrid systems. Only if the effects of autonomous robots onto the environment can be sufficiently well predicted can such robotic systems leave the safe space of the lab and can be applied in the wild to be able to unfold their ecosystem-stabilising potential.
Microcarrier Screening and Evaluation for Dynamic Expansion of Human Periosteum-Derived Progenitor Cells in a Xenogeneic Free Medium
Authors: Van Beylen Kathleen , Papantoniou Ioannis , Aerts Jean-Marie
Published: May 2021

An increasing need toward a more efficient expansion of adherent progenitor cell types arises with the advancements of cell therapy. The use of a dynamic expansion instead of a static planar expansion could be one way to tackle the challenges of expanding adherent cells at a large scale. Microcarriers are often reported as a biomaterial for culturing cells in suspension. However, the type of microcarrier has an effect on the cell expansion. In order to find an efficient expansion process for a specific adherent progenitor cell type, it is important to investigate the effect of the type of microcarrier on the cell expansion. Human periosteum-derived progenitor cells are extensively used in skeletal tissue engineering for the regeneration of bone defects. Therefore, we evaluated the use of different microcarriers on human periosteum-derived progenitor cells. In order to assess the potency, identity and viability of these cells after being cultured in the spinner flasks, this study performed several in vitro and in vivo analyses. The novelty of this work lies in the combination of screening different microcarriers for human periosteum-derived progenitor cells with in vivo assessments of the cells’ potency using the microcarrier that was selected as the most promising one. The results showed that expanding human periosteum-derived progenitor cells in spinner flasks using xeno-free medium and Star-Plus microcarriers, does not affect the potency, identity or viability of the cells. The potency of the cells was assured with an in vivo evaluation, where bone formation was achieved. In summary, this expansion method has the potential to be used for large scale cell expansion with clinical relevance.
Plasma HSP90AA1 Predicts the Risk of Breast Cancer Onset and Distant Metastasis
Authors: Liu Haizhou , Zhang Zihan , Huang Yi , Wei Wene , Ning Shufang , Li Jilin , Liang Xinqiang , Liu Kaisheng , Zhang Litu
Published: May 2021

Aim

We aimed to develop and validate a comprehensive nomogram containing pre-treatment plasma HSP90AA1 to predict the risk of breast cancer onset and metastasis.

Methods

We assessed the expression of HSP90s in breast cancer patients using an online database. To verify the results, 677 patients diagnosed with breast cancer and 146 patients with benign breast disease between 2014 and 2019 were selected from our hospital and were divided into cancer risk and metastasis risk cohorts. We focused on HSP90AA1 to elucidate the risks of onset and metastasis in the cohorts.

Results

Expression levels of HSP90AA1, HSP90AA2, HSP90AB1, HSP90B1, and TRAP1 were linked to disease progression. Survival analysis using the GEPIA and OncoLnc databases indicated that the upregulation of HSP90AA1 and HSP90AB1 was related to poor overall survival. In the cancer risk cohort, carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), HSP90AA1, T cells%, natural killer cells%, B cells%, neutrophil count, monocyte count, and d-dimer were incorporated into the nomogram. A high Harrell’s concordance index (C-index) value of 0.771 [95% confidence interval (CI), 0.725–0.817] could still be reached in the interval validation. In the metastasis risk cohort, predictors contained in the prediction nomogram included the use of CEA, CA153, HSP90AA1, carbohydrate antigen 125 (CA125), natural killer cells%, B cells%, platelet count, monocyte count, and d-dimer. The C-index was 0.844 (95% CI, 0.801–0.887) and it was well-calibrated. HSP90AA1 raised net clinical benefit of breast cancer onset and metastasis risk prediction nomogram in a range of risk thresholds (5–92%) and (1–90%).

Conclusion

Our study revealed that pretreatment plasma HSP90AA1 combined with other markers could conveniently predict the risk of breast cancer onset and metastasis.
Spatiotemporal Developmental Upregulation of Prestin Correlates With the Severity and Location of Cyclodextrin-Induced Outer Hair Cell Loss and Hearing Loss
Authors: Ding Dalian , Jiang Haiyan , Manohar Senthilvelan , Liu Xiaopeng , Li Li , Chen Guang-Di , Salvi Richard
Published: May 2021

2-Hyroxypropyl-beta-cyclodextrin (HPβCD) is being used to treat Niemann-Pick C1, a fatal neurodegenerative disease caused by abnormal cholesterol metabolism. HPβCD slows disease progression, but unfortunately causes severe, rapid onset hearing loss by destroying the outer hair cells (OHC). HPβCD-induced damage is believed to be related to the expression of prestin in OHCs. Because prestin is postnatally upregulated from the cochlear base toward the apex, we hypothesized that HPβCD ototoxicity would spread from the high-frequency base toward the low-frequency apex of the cochlea. Consistent with this hypothesis, cochlear hearing impairments and OHC loss rapidly spread from the high-frequency base toward the low-frequency apex of the cochlea when HPβCD administration shifted from postnatal day 3 (P3) to P28. HPβCD-induced histopathologies were initially confined to the OHCs, but between 4- and 6-weeks post-treatment, there was an unexpected, rapid and massive expansion of the lesion to include most inner hair cells (IHC), pillar cells (PC), peripheral auditory nerve fibers, and spiral ganglion neurons at location where OHCs were missing. The magnitude and spatial extent of HPβCD-induced OHC death was tightly correlated with the postnatal day when HPβCD was administered which coincided with the spatiotemporal upregulation of prestin in OHCs. A second, massive wave of degeneration involving IHCs, PC, auditory nerve fibers and spiral ganglion neurons abruptly emerged 4–6 weeks post-HPβCD treatment. This secondary wave of degeneration combined with the initial OHC loss results in a profound, irreversible hearing loss.
Inhibition of Col6a5 Improve Lipid Metabolism Disorder in Dihydrotestosterone-Induced Hyperandrogenic Mice
Authors: Sun Li-Feng , Yang Ya-Li , Wang Mei-Yue , Zhao Hua-Shan , Xiao Tian-xia , Li Meng-Xia , Wang Bao-Bei , Huang Chen , Ren Pei-Gen , Zhang Jian V.
Published: May 2021

Hyperandrogenism is a key pathological feature of polycystic ovarian syndrome (PCOS). Excess androgen can lead to PCOS-like cell hypertrophy in the ovaries and adipose tissue of rodents. Here, we established a dihydrotestosterone (DHT)-induced hyperandrogenic mouse model to analyze the differences in gene expression and signaling pathways of the ovaries and gonad fat pads of mice treated with or without DHT by RNA microarray analysis. From the results, we focused on the overlapping differentially expressed gene—Col6a5—and the major differentially enriched signaling pathway—lipid metabolism. We employed DHT-induced mouse ovarian stromal cell, adipogenic 3T3-L1 cell and hepatic cell line NCTC1469 models to investigate whether androgens directly mediate lipid accumulation and hypertrophy. We found that DHT increased lipid droplet accumulation in ovarian stromal cells and adipogenic 3T3-L1 cells but not NCTC1469 cells. DHT significantly altered stromal cell cholesterol metabolism and steroidogenesis, as indicated by changes in cholesterol levels and the expression of related genes, but these effects were not observed in 3T3-L1 cells. Moreover, Col6a5 expression was significantly increased in ovaries and gonadal fat pads of DHT-treated mice, and Col6a5 inhibition alleviated DHT-induced excess lipid accumulation and hypertrophy of ovarian stromal cells and adipogenic 3T3-L1 cells, even improved lipid metabolism in overnourished NCTC1469 cells. Our results indicate that Col6a5 plays important roles in the pathogenesis of DHT-induced lipid metabolism disorder and the hypertrophy of ovarian stromal cells and adipocytes.
Priming With Toll-Like Receptor 3 Agonist Poly(I:C) Enhances Content of Innate Immune Defense Proteins but Not MicroRNAs in Human Mesenchymal Stem Cell-Derived Extracellular Vesicles
Authors: Pierce Lisa M. , Kurata Wendy E.
Published: May 2021

Mesenchymal stem cells (MSCs) help fight infection by promoting direct bacterial killing or indirectly by modulating the acute phase response, thereby decreasing tissue injury. Recent evidence suggests that extracellular vesicles (EVs) released from MSCs retain antimicrobial characteristics that may be enhanced by pretreatment of parent MSCs with the toll-like receptor 3 (TLR3) agonist poly(I:C). Our aim was to determine whether poly(I:C) priming can modify EV content of miRNAs and/or proteins to gain insight into the molecular mechanisms of their enhanced antimicrobial function. Human bone marrow-derived MSCs were cultured with or without 1 μg/ml poly(I:C) for 1 h and then conditioned media was collected after 64 h of culture in EV-depleted media. Mass spectrometry and small RNA next-generation sequencing were performed to compare proteomic and miRNA profiles. Poly(I:C) priming resulted in 49 upregulated EV proteins, with 21 known to be important in host defense and innate immunity. In contrast, EV miRNA content was not significantly altered. Functional annotation clustering analysis revealed enrichment in biological processes and pathways including negative regulation of endopeptidase activity, acute phase, complement and coagulation cascades, innate immunity, immune response, and Staphylococcus aureus infection. Several antimicrobial peptides identified in EVs remained unaltered by poly(I:C) priming, including dermcidin, lactoferrin, lipocalin 1, lysozyme C, neutrophil defensin 1, S100A7 (psoriasin), S100A8/A9 (calprotectin), and histone H4. Although TLR3 activation of MSCs improves the proteomic profile of EVs, further investigation is needed to determine the relative importance of particular functional EV proteins and their activated signaling pathways following EV interaction with immune cells.
Intricate Regulatory Mechanisms of the Anaphase-Promoting Complex/Cyclosome and Its Role in Chromatin Regulation
Authors: Bodrug Tatyana , Welsh Kaeli A. , Hinkle Megan , Emanuele Michael J. , Brown Nicholas G.
Published: May 2021

The ubiquitin (Ub)-proteasome system is vital to nearly every biological process in eukaryotes. Specifically, the conjugation of Ub to target proteins by Ub ligases, such as the Anaphase-Promoting Complex/Cyclosome (APC/C), is paramount for cell cycle transitions as it leads to the irreversible destruction of cell cycle regulators by the proteasome. Through this activity, the RING Ub ligase APC/C governs mitosis, G1, and numerous aspects of neurobiology. Pioneering cryo-EM, biochemical reconstitution, and cell-based studies have illuminated many aspects of the conformational dynamics of this large, multi-subunit complex and the sophisticated regulation of APC/C function. More recent studies have revealed new mechanisms that selectively dictate APC/C activity and explore additional pathways that are controlled by APC/C-mediated ubiquitination, including an intimate relationship with chromatin regulation. These tasks go beyond the traditional cell cycle role historically ascribed to the APC/C. Here, we review these novel findings, examine the mechanistic implications of APC/C regulation, and discuss the role of the APC/C in previously unappreciated signaling pathways.
Diagnostic Performance of Various Methodologies for Group B Streptococcus Screening in Pregnant Woman in China
Authors: Gao Kankan , Deng Qiulian , Huang Lianfen , Chang Chien-Yi , Zhong Huamin , Xie Yongqiang , Guan Xiaoshan , Liu Haiying
Published: May 2021

Maternal vaginal/rectal colonization of group B streptococcus (GBS) is a main risk for neonatal invasive infection. Efficient determination of GBS colonization in pregnant women is crucial. This study aimed to investigate the prevalence of GBS carriage and evaluate the diagnostic performance of six methodologies for GBS screening conducted in China, including blood agar plate, liquid chromogenic medium, and loop-mediated isothermal amplification (LAMP) without pre-enrichment, chromogenic agar plate with pre-enrichment, and GBS antigen detection without and with pre-enrichment in comparison with the standard reference method (Lim broth-enriched subculture with plating on 5% sheep blood agar). Vaginal/rectal swabs were collected from 1,281 pregnant women at 35–37 weeks of gestation. Of them, 309 were taken in triplicate, one for Lim broth-enriched subculture, one for blood agar plate, and the third for GBS antigen detection (Reagent W); 177 were acquired in duplicate, one for Lim broth-enriched subculture and the other for GBS antigen detection (Reagent H); 502 were obtained in duplicate, one for Lim broth-enriched subculture and the other for liquid chromogenic medium; 158 were collected in duplicate, one for Lim broth-enriched subculture and the other for LAMP; and 135 were inoculated in Lim broth-enriched for GBS antigen detection (Reagent W) and subculture with chromogenic agar plate and 5% blood agar plate. The overall prevalence of GBS carriage was 10.1% (130/1,281, 95% CI: 8.5–12.1%) according to the standard reference method. Compared with the standard reference method, the LAMP had excellent performance of sensitivity (100%, 95%CI: 83.4–100%), specificity (94%, 95%CI: 88.1–97.1%), and Yoden index (0.940); as well as the blood agar plate with sensitivity (81.5%, 95%CI: 61.3–93.0%), specificity (100%, 95%CI: 98.3–100.0%), and Yoden index (0.815). The other four methods were not sufficient to reach the threshold in terms of sensitivity or specificity compared to the standard reference method. Furthermore, for LAMP, results can be obtained within 0.5–1 h, while for blood agar plate, which needed 24–48 h, and further identification was required. Our data suggested that the performance of LAMP was highly comparable to the standard Lim broth-enriched subculture and LAMP is considered as an alternative for fast and accurate GBS screening.
Rational and Design of the SIMULATOR Study: A Multicentre Randomized Study to Assess the Impact of SIMULation-bAsed Training on Transoesophageal echocardiOgraphy leaRning for Cardiology Residents
Authors: Pezel Théo , Bernard Anne , Lavie Badie Yoan , Dreyfus Julien , Audureau Etienne , Bohbot Yohann , Fard Damien , Hubert Arnaud , Nguyen Lee S. , Monteil Cécile , Bière Loïc , Le Ven Florent , Canu Marjorie , Ribeyrolles Sophie , Mion Baptiste , Mouhat Basile , Bazire Baptiste , Fauvel Charles , Ternacle Julien , Cautela Jennifer , Cambet Théo , Le Tourneau Thierry , Donal Erwan , Lafitte Stéphane , Mansencal Nicolas , Coisne Augustin
Published: May 2021

Introduction: Simulation-based training in transesophageal echocardiography (TEE) seems promising. However, data are limited to non-randomized or single-center studies. To assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology.

Materials and Methods: Nationwide prospective randomized multicenter study involving 43 centers throughout France allowing for the inclusion of >70% of all French cardiology residents. All cardiology residents naive from TEE will be included. Randomization with stratification by center will allocate residents to either a control group receiving theoretical knowledge by e-learning only, or to an intervention group receiving two simulation-based training sessions on a TEE simulator in addition.

Results: All residents will undergo both a theoretical test (0–100 points) and a practical test on a TEE simulator (0–100 points) before and 3 months after the training. Satisfaction will be assessed by a 5-points Likert scale. The primary outcomes will be to compare the scores in the final theoretical and practical tests between the two groups, 3 months after the completion of the training.

Conclusion: Data regarding simulation-based learning in TEE are limited to non-randomized or single-center studies. The randomized multicenter SIMULATOR study will assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology, and whether such an educational program should be proposed in first line for TEE teaching.
What Makes for a Successful Digital Health Integrated Program of Work? Lessons Learnt and Recommendations From the Melbourne Children's Campus
Authors: Hourani Danah , Darling Simone , Cameron Eloise , Dromey James , Crossley Louise , Kanagalingam Sanji , Muscara Frank , Gwee Amanda , Gell Grace , Hiscock Harriet , Anderson Vicki
Published: May 2021

Embedding digital technologies in healthcare has the potential to streamline and personalize medical care. However, healthcare systems are often fragmented, and therefore achieving a truly integrated digital health program can be challenging. To promote a streamlined, evidence-based approach to implementing digital health solutions in a healthcare system, the Murdoch Children's Research Institute (MCRI) established the Digital Health Translation and Implementation Program (DHTI) bringing together clinicians, researchers and digital health experts. From the program commencement, frontline clinical innovators have collaborated with DHTI team members to develop and implement digital solutions to address pain-points in the healthcare system. Throughout this program, important lessons have been learnt relating to the development, evaluation and implementation of digital solutions in the healthcare system. This paper explores these lessons and makes recommendations for the successful implementation of digital health solutions in healthcare systems under five main categories: (1) design and usability, (2) stakeholder engagement and uptake, (3) project management and resourcing, (4) process and implementation, and (5) evaluation. Recommendations suggested here are designed to support future healthcare-based digital health programs to maximize the impact digital solutions can have on the healthcare system and patients.