bluuebunny/crossref_metadata_2025 huggingface dataset:
Cecilia Razovsky, the American Activist Who Rescued German Jewish Children (1933-1945)
Authors: Zucker Bat-Ami
Published: June 2021

This article deals with the reaction of one particular American Jewish sector – the Jewish women - and their response to Nazi persecution of European Jews in the 1930s and the 1940s. As against the widespread accusations that American Jews did not do enough to help their co-religionists during those tragic years, this paper claims that Jewish women, of all social standing – from homemakers to professionals – were actively involved in organizing rescue operations and assisting refugees. Of particular note is one extraordinary woman – Cecilia Razovsky-Davidson.
Abigail of Maon and the Wise Woman of Abel: Speaking Truth to Power
Authors: Zucker David J. , Zion Noam
Published: June 2021

In 1 Samuel Abigail of Maon and then in 2 Samuel the Wise Woman of Abel dare to Speak Truth to Power. Each woman employs the wisdom of a moral appeal to the male aggressor’s better inclinations to deescalate a situation where her community is seriously threatened with violent and immediate annihilation.
PENGARUH JUMLAH ULIR DAN KEKASARAN PERMUKAAN TERHADAP KINERJA TURBIN ULIR MIKRO HIDRO
Authors: Putra Adi , Joditiadhi Andi , Qiram Ikhwanul
Published: June 2021

Pemanfaatan energi potensial air salah satunya adalah menggunakan teknologi turbin ulir sebagai pembangkit listrik mikrohidro. Beberapa parameter yang mempengaruhi kinerja turbin ulir adalah jumlah ulir, kekasaran permukaan,sudut kemiringan poros dan debit aliran. Penelitian ini bertujuan untuk mengetahui pengaruh jumlah ulir dan kekasaran permukaan terhadap kinerja turbin ulir. Penelitian dilakukan dengan eksperimen, dimana turbin menggunakan variasi jumlah ulir 7, 9, 11. Kekasaran menggunakan variasi grid 0 (tanpa kekasaran), grid 40, grid 60. Sudut kemiringan poros menggunakan 30⁰, 33⁰, 36⁰ dan debit aliran menggunakan bukaan valve  50⁰ (502,14), 70⁰ (22,42), (90⁰) 803,52. Analisis kinerja turbin ditinjau berdasarkan kecepatan putaran (Rpm) dan tegangan (volt) yang dihasilkan. Hasil penelitian menunjukkan debit aliran, jumlah dan sudut turbin serta kekasaran permukaan sudu mempengaruhi unjuk kerja turbin ulir.  Semakin rendah jumlah ulir dan tingkat kekasaran maka putaran dan tegangan akan semakin meningkat dan sebaliknya. Jumlah sudu dan tingkat kekasaran permukaan sudu akan memicu peningkatan luas hambatan aliran fluida. Hasil pengujian menunjukkan kinerja turbin terbaik pada variasi 7 ulir, dengan sudut kemiringan 33o dengan kekasaran grid 0 (tanpa kekasaran)  menghasilkan tegangan 7,26 volt pada 2928,40 rpm.
Evaluation of Personnel Information System Performance at the Department of Population and Civil Registration of Bengkayang Regency Using COBIT 5
Authors: Linda Tania , Wijaya Agustinus Fritz
Published: June 2021

The Bengkayang Regency Population and Civil Registry Service is an institution that aims to record population administration data which includes data including birth data, marriage data and death data, identity cards, family cards, and children's identity cards. The Dukcapil Service Office is one of the services that serves the community, especially in population management. This study aims to refer to the version 5 COBIT framework for reviewing the management of Personnel SI at the Bengkayang Regency Population and Civil Registry Service. The domain used in COBIT 5 is "Monitoring, Evaluation and Assessment" (MEA). The results of the study determine the maturity of the Bengkayang Regent's Population and Civil Registry, and provide suggestions for the application of information technology to make it better in the future.
Capability Level Measurement Using COBIT 5 Framework (Case Study: PT. Jasa Cendekia Indonesia)
Authors: Harits Abdurrahman , Noer Gilang Muhamad , Widodo Aris Puji
Published: June 2021

PT. Jasa Cendekia Indonesia is a company engaged in the field of recruitment, training and consulting in the provision of human resources. Currently PT. Jasa Cendekia Indonesia has more than 500 outsourcing employees, puts hundreds of Indonesians into the job market and serves more than 30 multinational companies, of course companies need systems that are able to manage and carry out company work operations. This research study aims to conduct an assessment of Information Technology Governance at PT. Jasa Cendekia Indonesia which focuses on the DSS01 domain (manage operations) is measured using the Capability Level in the Cobit 5 Framework. The results obtained from this assessment are needed as an evaluation and input for improvements to Information Technology Governance at PT. Jasa Cendekia Indonesia in the future. The level of ability of PT. Jasa Cendekia Indonesia in the DSS01 process is at a value of 2.80 while the expected level of ability is at level 3 (established process). The recommendation to reach level 3 is expected to be implemented to improve the performance of PT. Jasa Cendekia Indonesia according to the DSS01 process.
Perencanaan Strategis Sistem Informasi Menggunakan Metode Ward and Peppard (Studi Kasus: Dinas Pariwisata Kabupaten Timor Tengah Selatan)
Authors: Tallo Dennis Christian , Papilaya Frederik Samuel
Published: June 2021

The Timor Tengah Selatan Regency Tourism Office is one of the regional apparatus organizations that has the authority to implement the regional government's authority in the tourism sector. Information Technology Systems are factors that affect the sustainability of organization's activities. The Timor Tengah Selatan Regency Tourism Office still encounters obstacles in the application of information systems that do not support the entire business process and the lack of IS implementation makes performance inefficient. One of the contributing factors is that there are not enough human resources who have the skills in managing information systems and information technology properly. The purpose of this research is to develop a strategic planning of information systems in accordance with the needs of the organization. In the preparation of information systems strategic planning research using the Ward and Peppard approach with various analyzes such as SWOT analysis, Value Chain, and Mc. Farlan Strategic Grid. Based on the results of this study resulted in several recommendations to be carried out including the creation of Contract Making Administration System, and Mobile Tourism Information System and the development of Regency Tourism Website Timor Tengah Selatan regency, SIPD (Local Government Information System), and SIMDA (Regional Management Information System) GOODS.
Perencanaan Strategis Sistem Informasi Di Sinode GKJ Menggunakan Enterprise Architecture Planning Framework
Authors: Prianti Monika , Papilaya Frederik Samuel
Published: June 2021

The GKJ Synod is one of the Church Foundations located in Salatiga which is an institution that focuses on the field of information data center and media services for the GKJ Synod. The Salatiga GKJ Synod currently has a system but still has problems with Information System problems that have not been implemented optimally, so there are often obstacles when doing work. Because it does not run quickly and well, therefore an Information System Strategic Planning is needed, this research aims to be able to help the business processes contained in the GKJ Synod implement information systems in the organization to run well. The purpose of this research is to propose and plan using the method Enterprise Architecture Planning. Enterprise Architecture Planning (EAP) is the process of defining the architecture in the use of information systems to support the architecture implementation plan. By using the approach, the Enterprise Architecture Planning (EAP)method can help the GKJ Salatiga synod to plan data quality oriented to business needs in order to achieve and support business goals for agencies and organizations, besides that, the advantages of using Enterprise Architecture Planning are a supporting method for making decisions and good planning for an organization.
Features of management of patients with seborrheic dermatitis
Authors: Markelova E. M.
Published: June 2021

Seborrheic dermatitis (SD) is a chronic recurrent inflammatory skin disease caused by changes of quantitative and qualitative sebum characteristics. SD comes out by appearing of erythematous plaques with sense of itch and peeling skin in areas with high concentration of sebaceous glands: on the scalp, face, upper part of the body and in the folds of skin. Due to the fact that the development of the SD is promoted by the colonization of the skin with a lipophilic yeast fungus Malassezia spp., in the treatment of uncomplicated simple forms of the disease can be applied external antifungal medicines, topical glucocorticosteroids and anti-inflammatory drugs of non-steroidal origin. Systemic therapy is also used in severe course of seborrheic dermatitis and in the treatment of forms, resistant to external therapy. In the treatment of persistent and long-term forms of SD, systemic antifungal agents and systemic retinoids are used, which allow for a long time to achieve regression of skin rashes and significantly improve the quality of life of the patient.
PRP application in dermatology: review of current approaches
Authors: Bondarenko V. V.
Published: June 2021

In recent years, the possibilities of a dermatologist in the treatment of patients with chronic dermatoses have significantly expanded due to the emergence of new highly effective methods, such as autologous blood plasma enriched with platelet-rich-growth factors (platelet-rich-plasma, PRP). The positive results of using this technology due to its constituent growth factors, cytokines and other biologically active substances, which have a pronounced normalizing effect on the processes of tissue repair and regeneration, expands the possibilities of its use in such skin diseases as erosive and ulcerative lichen planus, scleroatrophic lichen, acne and post-acne. The aim of this review was to analyze the literature on the mechanisms of PRP action in patients with dermatological diseases.
Modern ideas about lichen planus of vulva
Authors: Surkichin S. I. , Apolikhina I. A. , Mayorov R. Yu. , Avin M.
Published: June 2021

Lichen planus (LP) is a T-cell-mediated inflammatory dermatosis with an unclear etiology that affects the skin, nails and mucous membranes. The article outlines modern ideas about lichen planus, affecting the vulva. The issues of etiopathogenesis, clinical picture, differential diagnosis of various forms of this dermatosis are considered. The histopathological picture of vulvar LPL is described in detail. Possible complications, including anatomical abnormalities of the vulvar architectonics and the risk of malignant transformation, are considered. Various methods of treatment for this disease, local treatment regimens are presented, an overview of systemic drugs is given, as well as alternative approaches to patient management.
Issues of therapy and prevention of post-inflammatory acne pigmentation
Authors: Kruglova L. S. , Gryazeva N. V. , Bondarenko V. V.
Published: June 2021

Azelaic acid is well suited for the treatment of acne in women, where PIH occurs most often (it is not an obstacle for use during pregnancy), the drug may be combined with systemic and topical therapy, may combined with skin care and decorative cosmetics, has no restrictions when used in active sun, possesses light peeling effect.

Material and methods.The study evaluated the effectiveness of the combined method, including systemic isotretinoin and Skinaren®cream 20 %, in patients with moderate acne – group 1A (n = 24) in comparison with isotretinoin monotherapy – group 1B (n = 25). The efficacy of Skinoren®20 % cream was also studied in patients with post-inflammatory hyperpigmentation – the group 2 (n = 37).

Research results.The combination of 20 % azelaic acid cream (Skinoren®) with oral isotretinoin (from 4th months of admission) in patients with adult acne allows to influence the formation of post-inflammatory hyperpigmentation, which ultimately leads to a more significant aesthetic result (88 % with the achievement of IGA0) and contributes to an improvement in the quality of life (reduction of APSEA by 87 %) The safety of the 20 % azelaic acid cream (Skinoren®) is assessed as very high, which is confirmed by the absence of adverse events in most patients. The use of 20 % azelaic acid cream (Skinoren®) as a monotherapy for post-inflammatory hyperpigmentation causes a pronounced positive effect in stopping PIH in all patients, while achieving clear skin is noted in 78.4 %.
Chlamydial etiology balanoposthitis therapy experience with combined topic steroid
Authors: Nefedyeva Yu. V. , Ziganshin O. R. , Kosavchinskaya N. A. , Brik V. V.
Published: June 2021

The widespread spread of balanoposthitis necessitates the development of highly effective treatment methods. The experience of using combined topic steroid in a patient with balanoposthitis complicated by reactive arthritis and keratoderma is described. The high efficiency of treatment of balanoposthitis and keratoderma with a combined topical steroid with anti-inflammatory, antimicrobial, fungicidal and wound healing effects has been shown.
The Effect of Different Processing Methods on Fishmeal Element Quality: Evaporator System
Authors: BAYRAKLI Barış , DUYAR Hünkar Avni
Published: June 2021

Anchovy (Engraulis encrasicolus L., 1758) is the main source of fishmeal in Turkey. The research was carried out in 3 fishmeal factories where anchovy is processed in the Black Sea during the 2007-2008 fishing season. Factories A and B have an evaporator system, while factory C does not have an evaporator system. In the study, it was aimed to reveal the effect of the evaporator system on the mineral substance quality of the fishmeal produced in fishmeal oil factories. As a result of this study, the elements in fishmeal are listed in descending order as Ca>P>K>Na>Mg>Fe>Zn>Mn>Cu. According to the results of the research, it was determined that the phosphorus, sodium, potassium, calcium and zinc values of fish fishmeal produced in A and B factories using evaporator system were higher than the C factory without an evaporator system, and the difference between factories was statistically significant (P<0.05). It is recommended that all factories have an evaporator system in order to produce fishmeal of higher quality (protein and mineral substances) in fishmeal-oil factories.
Balıkesir Üniversitesi’nden Balıkesir Tıp Fakültesine: Kısa Bir Öykü
Authors: YILDIRIM CAN Hümeyra , USTA Akın , CAN Muhammet
Published: June 2021

Tıp fakülteleri, sağlık hizmetlerinin yapılandırılması ve uygulanmasında, toplumun sağlık gereksinimlerine uygun kalitede hekim yetiştirilmesinde önemli bir rolü olan akademik bilimsel kurumlardır. Aynı zamanda, ülkede uygulanan sağlık politikalarından etkilenen (tıp eğitimi, öğrenci kontenjanı, Ar-Ge araştırmaları ve üniversite bütçeleri vb.) kurumlardır. Ülkemizde tıp fakültesi sayısı 1945 yılına kadar 1 iken, günümüzde Yüksek Öğrenim Kurumu, 2019-2020 eğitim-öğretim döneminde 5’i yurt dışında olmak üzere, 122 tıp fakültesi için 15 bin 500 öğrenci kadrosu ilân etmiştir. Balıkesir Üniversitesi Tıp Fakültesi, bir yandan Güney Marmara Bölgesinin diğer yanda Kuzey Ege Bölgesinin Tıp Fakültesi olarak, 2006 yılında kurulmuştur. Makalede, Balıkesir Üniversitesi Tıp Fakültesinin kuruluşunu hazırlayan etkenler, dönemin sağlık politikaları ve kuruluşu anlatılmaktadır.
Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo
Authors: Walle Matthias , Marques Francisco C. , Ohs Nicholas , Blauth Michael , Müller Ralph , Collins Caitlyn J.
Published: June 2021

Patients at high risk of fracture due to metabolic diseases frequently undergo long-term antiresorptive therapy. However, in some patients, treatment is unsuccessful in preventing fractures or causes severe adverse health outcomes. Understanding load-driven bone remodelling, i.e., mechanoregulation, is critical to understand which patients are at risk for progressive bone degeneration and may enable better patient selection or adaptive therapeutic intervention strategies. Bone microarchitecture assessment using high-resolution peripheral quantitative computed tomography (HR-pQCT) combined with computed mechanical loads has successfully been used to investigate bone mechanoregulation at the trabecular level. To obtain the required mechanical loads that induce local variances in mechanical strain and cause bone remodelling, estimation of physiological loading is essential. Current models homogenise strain patterns throughout the bone to estimate load distribution in vivo, assuming that the bone structure is in biomechanical homoeostasis. Yet, this assumption may be flawed for investigating alterations in bone mechanoregulation. By further utilising available spatiotemporal information of time-lapsed bone imaging studies, we developed a mechanoregulation-based load estimation (MR) algorithm. MR calculates organ-scale loads by scaling and superimposing a set of predefined independent unit loads to optimise measured bone formation in high-, quiescence in medium-, and resorption in low-strain regions. We benchmarked our algorithm against a previously published load history (LH) algorithm using synthetic data, micro-CT images of murine vertebrae under defined experimental in vivo loadings, and HR-pQCT images from seven patients. Our algorithm consistently outperformed LH in all three datasets. In silico-generated time evolutions of distal radius geometries (n = 5) indicated significantly higher sensitivity, specificity, and accuracy for MR than LH (p < 0.01). This increased performance led to substantially better discrimination between physiological and extra-physiological loading in mice (n = 8). Moreover, a significantly (p < 0.01) higher association between remodelling events and computed local mechanical signals was found using MR [correct classification rate (CCR) = 0.42] than LH (CCR = 0.38) to estimate human distal radius loading. Future applications of MR may enable clinicians to link subtle changes in bone strength to changes in day-to-day loading, identifying weak spots in the bone microstructure for local intervention and personalised treatment approaches.
The Use of Zwitterionic Methylmethacrylat Coated Silicone Inhibits Bacterial Adhesion and Biofilm Formation of Staphylococcus aureus
Authors: Woitschach Franziska , Kloss Marlen , Schlodder Karsten , Rabes Anne , Mörke Caroline , Oschatz Stefan , Senz Volkmar , Borck Alexander , Grabow Niels , Reisinger Emil Christian , Sombetzki Martina
Published: June 2021

In recent decades, biofilm-associated infections have become a major problem in many medical fields, leading to a high burden on patients and enormous costs for the healthcare system. Microbial infestations are caused by opportunistic pathogens which often enter the incision already during implantation. In the subsequently formed biofilm bacteria are protected from the hosts immune system and antibiotic action. Therefore, the development of modified, anti-microbial implant materials displays an indispensable task. Thermoplastic polyurethane (TPU) represents the state-of-the-art material in implant manufacturing. Due to the constantly growing areas of application and the associated necessary adjustments, the optimization of these materials is essential. In the present study, modified liquid silicone rubber (LSR) surfaces were compared with two of the most commonly used TPUs in terms of bacterial colonization and biofilm formation. The tests were conducted with the clinically relevant bacterial strainsStaphylococcus aureusandStaphylococcus epidermidis. Crystal violet staining and scanning electron microscopy showed reduced adhesion of bacteria and thus biofilm formation on these new materials, suggesting that the investigated materials are promising candidates for implant manufacturing.
SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer
Authors: Xiao Zhao-Ming , Lv Dao-Jun , Yu Yu-zhong , Wang Chong , Xie Tao , Wang Tao , Song Xian-Lu , Zhao Shan-Chao
Published: June 2021

Background

SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms.

Methods

The expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.

Results

Our finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells.

Conclusion

SMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.
Biological Properties of Milk-Derived Extracellular Vesicles and Their Physiological Functions in Infant
Authors: Jiang Xue , You Lianghui , Zhang Zhenxing , Cui Xianwei , Zhong Hong , Sun Xingzhen , Ji Chenbo , Chi Xia
Published: June 2021

Extracellular vesicles (EVs) are released by all cells under pathological and physiological conditions. EVs harbor various biomolecules, including protein, lipid, non-coding RNA, messenger RNA, and DNA. In 2007, mRNA and microRNA (miRNA) carried by EVs were found to have regulatory functions in recipient cells. The biological function of EVs has since then increasingly drawn interest. Breast milk, as the most important nutritional source for infants, contains EVs in large quantities. An increasing number of studies have provided the basis for the hypothesis associated with information transmission between mothers and infants via breast milk-derived EVs. Most studies on milk-derived EVs currently focus on miRNAs. Milk-derived EVs contain diverse miRNAs, which remain stable both in vivo and in vitro; as such, they can be absorbed across different species. Further studies have confirmed that miRNAs derived from milk-derived EVs can resist the acidic environment and enzymatic hydrolysis of the digestive tract; moreover, they can be absorbed by intestinal cells in infants to perform physiological functions. miRNAs derived from milk EVs have been reported in the maturation of immune cells, regulation of immune response, formation of neuronal synapses, and development of metabolic diseases such as obesity and diabetes. This article reviews current status and advances in milk-derived EVs, including their history, biogenesis, molecular contents, and biological functions. The effects of milk-derived EVs on growth and development in both infants and adults were emphasized. Finally, the potential application and future challenges of milk-derived EVs were discussed, providing comprehensive understanding and new insight into milk-derived EVs.
Combining Hyperbranched and Linear Structures in Solid Polymer Electrolytes to Enhance Mechanical Properties and Room-Temperature Ion Transport
Authors: Jing Benxin , Wang Xiaofeng , Shi Yi , Zhu Yingxi , Gao Haifeng , Fullerton-Shirey Susan K.
Published: June 2021

Polyethylene oxide (PEO)-based polymers are commonly studied for use as a solid polymer electrolyte for rechargeable Li-ion batteries; however, simultaneously achieving sufficient mechanical integrity and ionic conductivity has been a challenge. To address this problem, a customized polymer architecture is demonstrated wherein PEO bottle-brush arms are hyperbranched into a star architecture and then functionalized with end-grafted, linear PEO chains. The hierarchical architecture is designed to minimize crystallinity and therefore enhance ion transport via hyperbranching, while simultaneously addressing the need for mechanical integrity via the grafting of long, PEO chains (Mn = 10,000). The polymers are doped with lithium bis(trifluoromethane) sulfonimide (LiTFSI), creating hierarchically hyperbranched (HB) solid polymer electrolytes. Compared to electrolytes prepared with linear PEO of equivalent molecular weight, the HB PEO electrolytes increase the room temperature ionic conductivity from ∼2.5 × 10–6 to 2.5 × 10−5 S/cm. The conductivity increases by an additional 50% by increasing the block length of the linear PEO in the bottle brush arms from Mn = 1,000 to 2,000. The mechanical properties are improved by end-grafting linear PEO (Mn = 10,000) onto the terminal groups of the HB PEO bottle-brush. Specifically, the Young’s modulus increases by two orders of magnitude to a level comparable to commercial PEO films, while only reducing the conductivity by 50% below the HB electrolyte without grafted PEO. This study addresses the trade-off between ion conductivity and mechanical properties, and shows that while significant improvements can be made to the mechanical properties with hierarchical grafting of long, linear chains, only modest gains are made in the room temperature conductivity.
Chemistry-Assisted Proteomic Profiling of O-GlcNAcylation
Authors: Zhu Qiang , Yi Wen
Published: June 2021

The modification on proteins with O-linked N-acetyl-β-D-glucosamine (O-GlcNAcylation) is essential for normal cell physiology. Dysregulation of O-GlcNAcylation leads to many human diseases, such as cancer, diabetes and neurodegenerative diseases. Recently, the functional role of O-GlcNAcylation in different physiological states has been elucidated due to the booming detection technologies. Chemical approaches for the enrichment of O-GlcNAcylated proteins combined with mass spectrometry-based proteomics enable the profiling of protein O-GlcNAcylation in a system-wide level. In this review, we summarize recent progresses on the enrichment and proteomic profiling of protein O-GlcNAcylation.
Recapitulating Zika Virus Infection in Vagina of Tree Shrew (Tupaia belangeri)
Authors: Baloch Zulqarnain , Shen Zhili , Zhang Li , Feng Yue , Li Daoqun , Zhang Na-Na , Deng Yong-Qiang , Yang Chunguang , Sun Xiaomei , Dai Jiejie , Yang Zifeng , Qin Cheng-Feng , Xia Xueshan
Published: June 2021

Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01viathe intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetusin vivo.
Development and Evaluation of Technology Enhanced Interaction Framework Method for Designing Accessible Technologies for Visually Impaired People
Authors: Angkananon Kewalin , Wald Mike , Phetkeaw Thimaporn
Published: June 2021

This research developed and evaluated a software development support method to help non-expert developers evaluating or gathering requirements and designing or evaluating digital technology solutions to accessibility barriers people with visual impairment encounter. The Technology Enhanced Interaction Framework (TEIF) Visual Impairment (VI) Method was developed through literature review and interviews with 20 students with visual impairment, 10 adults with visual impairment and five accessibility experts. It is an extension of the Technology Enhanced Interaction Framework (TEIF) and its “HI-Method” that had been developed and validated and evaluated for hearing impairment and supports other methods by providing multiple-choice questions to help identify requirements, the answers to which help provide technology suggestions that support the design stage. Four accessibility experts and three developer experts reviewed and validated the TEIF VI-Method. It was experimentally evaluated by 18 developers using the TEIF VI-Method and another 18 developers using their preferred “Other Methods” to identify the requirements and solution to a scenario involving barriers for people with visual impairment. The “Other Methods” group were then shown the TEIF VI-Method and both groups were asked their opinions of its ease of use. The mean number of correctly selected requirements was significantly higher (p < 0.001) for developers using the TEIF VI-Method (X̄ = 8.83) than the Other Method (X̄ = 6.22). Developers using the TEIF VI-Method ranked technology solutions closer to the expert rankings than developers using Other Methods (p < 0.05). All developers found the TEIF VI-Method easy to follow. Developers could evaluate requirements and technology solutions to interaction problems involving people with visual impairment using the TEIF VI-Method better than existing Other Methods. Developers could benefit from using the TEIF VI-Method when developing technology solutions to interaction problems faced by people with visual impairment.
Marketing Products With Wildlife: How to Make It Benefit Conservation
Authors: Braczkowski Alexander , Allan James R. , Jones Kendall R. , Natali Meganne , Biggs Duan , Maron Martine
Published: June 2021

A key obstacle to wildlife conservation is a scarcity of funding. A recent paper [Courchamp, F., Jaric, I., Albert, C., Meinard, Y., Ripple, W. J., and Chapron, G. (2018). The paradoxical extinction of the most charismatic animals. PLoS Biol. 16:e2003997. doi: 10.1371/journal.pbio.2003997] illustrates how for-profit businesses' widespread use of threatened wildlife imagery could create complacency in the public about their conservation. A wildlife imagery royalty, whereby businesses that use threatened wildlife in their marketing pay a small percentage of their sales to the conservation of those species could be revolutionary for conservation funding. However, businesses are not currently compelled to support the protection of the species espoused in their products. We build upon the arguments presented by recent publications [Good, C., Burnham, D., and Macdonald, D. W. (2017). A cultural conscience for conservation. Animals 7:52. doi: 10.3390/ani7070052; Courchamp, F., Jaric, I., Albert, C., Meinard, Y., Ripple, W. J., and Chapron, G. (2018). The paradoxical extinction of the most charismatic animals. PLoS Biol. 16:e2003997. doi: 10.1371/journal.pbio.2003997] to explore limitations and a number of key pathways that may help bring a wildlife imagery royalty to fruition.
Machine Learning With GA Optimization to Model the Agricultural Soil-Landscape of Germany: An Approach Involving Soil Functional Types With Their Multivariate Parameter Distributions Along the Depth Profile
Authors: Ließ Mareike , Gebauer Anika , Don Axel
Published: June 2021

Societal demands on soil functionality in agricultural soil-landscapes are confronted with yield losses and environmental impact. Soil functional information at national scale is required to address these challenges. On behalf of the well-known theory that soils and their site-specific characteristics are the product of the interaction of the soil-forming factors, pedometricians seek to model the soil-landscape relationship using machine learning. Following the rationale that similarity in soils is reflected by similarity in landscape characteristics, we defined soil functional types (SFTs) which were projected into space by machine learning. Each SFT is described by a multivariate soil parameter distribution along its depth profile. SFTs were derived by employing multivariate similarity analysis on the dataset of the Agricultural Soil Inventory. Soil profiles were compared on behalf of differing sets of soil properties considering the top 100 and 200 cm, respectively. Various depth weighting coefficients were tested to attribute topsoil properties higher importance. Support vector machine (SVM) models were then trained employing optimization with a distributed multiple-population hybrid Genetic algorithm for parameter tuning. Model training, tuning, and evaluation were implemented in a nested k-fold cross-validation approach to avoid overfitting. With regards to the SFTs, organic soils were differentiated from mineral soils of various particle size distributions being partly influenced by waterlogging and groundwater. Further SFTs reflect soils with a depth limitation within the top 100 cm and high stone content. Altogether, with SVM predictive model accuracies between 0.7 and 0.9, the agricultural soil-landscape of Germany was represented with eight SFTs. Soil functionality with regards to the soil’s capacity to store plant-available water and soil organic carbon is well characterized. Four additional soil functions are described to a certain extent. An extension of the approach to fully cover soil functions such as nutrient cycling, agricultural biomass production, filtering of contaminants, and soil as a habitat for soil biota is possible with the inclusion of additional soil properties. Altogether, the developed data product represents the 3D multivariate soil parameter space. Its agglomerated simplicity into a limited number of spatially allocated process units provides the basis to run agricultural process models at national scale (Germany).
Honey Bees Can Taste Amino and Fatty Acids in Pollen, but Not Sterols
Authors: Ruedenauer Fabian A. , Biewer Niklas W. , Nebauer Carmen A. , Scheiner Maximilian , Spaethe Johannes , Leonhardt Sara D.
Published: June 2021

The nutritional composition of food is often complex as resources contain a plethora of different chemical compounds, some of them more, some less meaningful to consumers. Plant pollen, a major food source for bees, is of particular importance as it comprises nearly all macro- and micronutrients required by bees for successful development and reproduction. However, perceiving and evaluating all nutrients may be tedious and impair quick foraging decisions. It is therefore likely that nutrient perception is restricted to specific nutrients or nutrient groups. To better understand the role of taste in pollen quality assessment by bees we investigated nutrient perception in the Western honey bee, Apis mellifera. We tested if the bees were able to perceive concentration differences in amino acids, fatty acids, and sterols, three highly important nutrient groups in pollen, via antennal reception. By means of proboscis extension response (PER) experiments with chemotactile stimulation, we could show that honey bees can distinguish between pollen differing in amino and fatty acid concentration, but not in sterol concentration. Bees were also not able to perceive sterols when presented alone. Our finding suggests that assessment of pollen protein and lipid content is prioritized over sterol content.
South African Buffalo-Derived Theileria parva Is Distinct From Other Buffalo and Cattle-Derived T. parva
Authors: Maboko Boitumelo B. , Sibeko-Matjila Kgomotso P. , Pierneef Rian , Chan Wai Y. , Josemans Antoinette , Marumo Ratselane D. , Mbizeni Sikhumbuzo , Latif Abdalla A. , Mans Ben J.
Published: June 2021

Theileria parvais a protozoan parasite transmitted by the brown-eared ticks,Rhipicephalus appendiculatusandRhipicephalus zambeziensis. Buffaloes are the parasite’s ancestral host, with cattle being the most recent host. The parasite has two transmission modes namely, cattle–cattle and buffalo–cattle transmission. Cattle–cattleT. parvatransmission causes East Coast fever (ECF) and January disease syndromes. Buffalo to cattle transmission causes Corridor disease. Knowledge on the genetic diversity of South AfricanT. parvapopulations will assist in determining its origin, evolution and identify any cattle–cattle transmitted strains. To achieve this, genomic DNA of blood andin vitroculture material infected with South African isolates (8160, 8301, 8200, 9620, 9656, 9679, Johnston, KNP2, HL3, KNP102, 9574, and 9581) were extracted and paired-end whole genome sequencing using Illumina HiSeq 2500 was performed. East and southern African sample data (Chitongo Z2, Katete B2, Kiambu Z464/C12, Mandali Z22H10, Entebbe, Nyakizu, Katumba, Buffalo LAWR, and Buffalo Z5E5) was also added for comparative purposes. Data was analyzed using BWA and SAMtools variant calling with theT. parvaMuguga genome sequence used as a reference. Buffalo-derived strains had higher genetic diversity, with twice the number of variants compared to cattle-derived strains, confirming that buffaloes are ancestral reservoir hosts ofT. parva. Host specific SNPs, however, could not be identified among the selected 74 gene sequences. Phylogenetically, strains tended to cluster by host with South African buffalo-derived strains clustering with buffalo-derived strains. Among the buffalo-derived strains, South African strains were genetically divergent from other buffalo-derived strains indicating possible geographic sub-structuring. Geographic sub- structuring was also observed within South Africa strains. The knowledge generated from this study indicates that to date, ECF is not circulating in buffalo from South Africa. It also shows thatT. parvahas historically been present in buffalo from South Africa before the introduction of ECF and was not introduced into buffalo during the ECF epidemic.
Challenging Disease Ontology by Instances of Atypical PKHD1 and PKD1 Genetics
Authors: de Fallois Jonathan , Schönauer Ria , Münch Johannes , Nagel Mato , Popp Bernt , Halbritter Jan
Published: June 2021

Background

Autosomal polycystic kidney disease is distinguished into dominant (ADPKD) and recessive (ARPKD) inheritance usually caused by either monoallelic (PKD1/PKD2) or biallelic (PKHD1) germline variation. Clinical presentations are genotype-dependent ranging from fetal demise to mild chronic kidney disease (CKD) in adults. Additionally, exemptions from dominant and recessive inheritance have been reported in both disorders resulting in respective phenocopies. Here, we comparatively report three young adults with microcystic-hyperechogenic kidney morphology based on unexpected genetic alterations beyond typical inheritance.

Methods

Next-generation sequencing (NGS)-based gene panel analysis and multiplex ligation-dependent probe amplification (MLPA) of PKD-associated genes, familial segregation analysis, and reverse phenotyping.

Results

Three unrelated individuals presented in late adolescence for differential diagnosis of incidental microcystic-hyperechogenic kidneys with preserved kidney and liver function. Upon genetic analysis, we identified a homozygous hypomorphic PKHD1 missense variant causing pseudodominant inheritance in a family, a large monoallelic PKDH1-deletion with atypical transmission, and biallelic PKD1 missense hypomorphs with recessive inheritance.

Conclusion

By this report, we illustrate clinical presentations associated with atypical PKD-gene alterations beyond traditional modes of inheritance. Large monoallelic PKHD1-alterations as well as biallelic hypomorphs of both PKD1 and PKHD1 may lead to mild CKD in the absence of prominent macrocyst formation and functional liver impairment. The long-term renal prognosis throughout life, however, remains undetermined. Increased detection of atypical inheritance challenges our current thinking of disease ontology not only in PKD but also in Mendelian disorders in general.
Efficacy and Safety of Bone Marrow-Derived Mesenchymal Stem Cells for Chronic Antibody-Mediated Rejection After Kidney Transplantation- A Single-Arm, Two-Dosing-Regimen, Phase I/II Study
Authors: Wei Yongcheng , Chen Xiaoyong , Zhang Huanxi , Su Qun , Peng Yanwen , Fu Qian , Li Jun , Gao Yifang , Li Xirui , Yang Shicong , Ye Qianyu , Huang Huiting , Deng Ronghai , Li Gang , Xu Bowen , Wu Chenglin , Wang Jiali , Zhang Xiaoran , Su Xiaojun , Liu Longshan , Xiang Andy Peng , Wang Changxi
Published: June 2021

Objective

To investigate the efficacy and safety of bone marrow-derived mesenchymal stem cells (BM-MSCs) on chronic active antibody-mediated rejection (cABMR) in the kidney allograft.

Methods

Kidney recipients with biopsy-proven cABMR were treated with allogeneic third-party BM-MSCs in this open-label, single-arm, single-center, two-dosing-regimen phase I/II clinical trial. In Regimen 1 (n=8), BM-MSCs were administered intravenously at a dose of 1.0×106 cells/kg monthly for four consecutive months, while in Regimen 2 (n=15), the BM-MSCs dose was 1.0×106 cells/kg weekly during four consecutive weeks. The primary endpoints were the absolute change of estimated glomerular filtration rate (eGFR) from baseline (delta eGFR) and the incidence of adverse events associated with BM-MSCs administration 24 months after the treatment. Contemporaneous cABMR patients who did not receive BM-MSCs were retrospectively analyzed as the control group (n =30).

Results

Twenty-three recipients with cABMR received BM-MSCs. The median delta eGFR of the total BM-MSCs treated patients was -4.3 ml/min per 1.73m2 (interquartile range, IQR -11.2 to 1.2) 2 years after BM-MSCs treatment (P=0.0233). The median delta maximum donor-specific antibody (maxDSA) was -4310 (IQR -9187 to 1129) at 2 years (P=0.0040). The median delta eGFR of the control group was -12.7 ml/min per 1.73 m2 (IQR -22.2 to -3.5) 2 years after the diagnosis, which was greater than that of the BM-MSCs treated group (P=0.0342). The incidence of hepatic enzyme elevation, BK polyomaviruses (BKV) infection, cytomegalovirus (CMV) infection was 17.4%, 17.4%, 8.7%, respectively. There was no fever, anaphylaxis, phlebitis or venous thrombosis, cardiovascular complications, or malignancy after BM-MSCs administration. Flow cytometry analysis showed a significant decreasing trend of CD27-IgD- double negative B cells subsets and trend towards the increase of CD3+CD4+PD-1+/lymphocyte population after MSCs therapy. Multiplex analysis found TNF-α, CXCL10, CCL4, CCL11 and RANTES decreased after MSCs treatment.

Conclusion

Kidney allograft recipients with cABMR are tolerable to BM-MSCs. Immunosuppressive drugs combined with intravenous BM-MSCs can delay the deterioration of allograft function, probably by decreasing DSA level and reducing DSA-induced injury. The underlying mechanism may involve immunomodulatory effect of MSCs on peripheral B and T cells subsets.
Mapping T Cell Responses to Native and Neo-Islet Antigen Epitopes in at Risk and Type 1 Diabetes Subjects
Authors: Arif Sefina , Pujol-Autonell Irma , Kamra Yogesh , Williams Evangelia , Yusuf Norkhairin , Domingo-Vila Clara , Shahrabi Yasaman , Pollock Emily , Khatri Leena , Peakman Mark , Tree Timothy , Lorenc Anna
Published: June 2021

Aims

Recent studies highlight the potentially important role of neoepitopes in breaking immune tolerance in type 1 diabetes. T cell reactivity to these neoepitopes has been reported, but how this response compares quantitatively and phenotypically with previous reports on native epitopes is not known. Thus, an understanding of the relationship between native and neoepitopes and their role as tolerance breakers or disease drivers in type 1 diabetes is required. We set out to compare T cell reactivity and phenotype against a panel of neo- and native islet autoantigenic epitopes to examine how this relates to stages of type 1 diabetes development.

Methods

Fifty-four subjects comprising patients with T1D, and autoantibody-positive unaffected family members were tested against a panel of neo- and native epitopes by ELISPOT (IFN-γ, IL-10, and IL-17). A further subset of two patients was analyzed by Single Cell Immune Profiling (RNAseq and TCR α/β) after stimulation with pools of native and neoepitope peptides.

Results

T cell responses to native and neoepitopes were present in patients with type 1 diabetes and at-risk subjects, and overall, there were no significant differences in the frequency, magnitude, or phenotype between the two sets of peptide stimuli. Single cell RNAseq on responder T cells revealed a similar profile in T1D patients stimulated with either neo- or native epitopes. A pro-inflammatory gene expression profile (TNF-α, IFN-γ) was dominant in both native and neoepitope stimulated T cells. TCRs with identical clonotypes were found in T cell responding to both native and neoepitopes.

Conclusion/Interpretation

These data suggest that in peripheral blood, T cell responses to both native and neoepitopes are similar in terms of frequency and phenotype in patients with type 1 diabetes and high-risk unaffected family members. Furthermore, using a combination of transcriptomic and clonotypic analyses, albeit using a limited panel of peptides, we show that neoepitopes are comparable to native epitopes currently in use for immune-monitoring studies.
Screening and Validation of the Hypoxia-Related Signature of Evaluating Tumor Immune Microenvironment and Predicting Prognosis in Gastric Cancer
Authors: Pei Jun-Peng , Zhang Chun-Dong , Yusupu Maimaititusun , Zhang Cheng , Dai Dong-Qiu
Published: June 2021

Background

Hypoxia is one driving factor of gastric cancer. It causes a series of immunosuppressive processes and malignant cell responses, leading to a poor prognosis. It is clinically important to identify the molecular markers related to hypoxia.

Methods

We screened the prognostic markers related to hypoxia in The Cancer Genome Atlas database, and a risk score model was developed based on these markers. The relationships between the risk score and tumor immune microenvironment were investigated. An independent validation cohort from Gene Expression Omnibus was applied to validate the results. A nomogram of risk score model and clinicopathological factor was developed to individually predict the prognosis.

Results

We developed a hypoxia risk score model based on SERPINE1 and EFNA3. Quantified real-time PCR was further applied to verified gene expressions of SERPINE1 and EFNA3 in gastric cancer patients and cell lines. A high-risk score is associated with a poor prognosis through the immunosuppressive microenvironment and immune escape mechanisms, including infiltration of immunosuppressive cells, expression of immune checkpoint molecules, and enrichment of signal pathways related to cancer and immunosuppression. The nomogram basing on the hypoxia-related risk score model showed a good ability to predict prognosis and high clinical net benefits.

Conclusions

The hypoxia risk score model revealed a close relationship between hypoxia and tumor immune microenvironment. The current study potentially provides new insights of how hypoxia affects the prognosis, and may provide a new therapeutic target for patients with gastric cancer.