bluuebunny/crossref_metadata_2025 huggingface dataset:
KADAR SERAT PANGAN DAN ORGANOLEPTIK CRACKERS BEKATUL JAGUNG DENGAN PENAMBAHAN TEPUNG KACANG BAMBARA
Authors:   Universitas Pembangunan Nasional Veteran Jakarta Indonesia, Prasetio Panji Octo
Published: January 2022

Pola makan rendah serat menjadi salah satu resiko yang dapat menyebabkan terjadinya obesitas. Menurut RISKESDAS (2018) prevalensi obesitas pada usia >18 tahun meningkat menjadi 21,8%. World Health Organization (WHO) menganjurkan konsumsi serat yang cukup berkisar 25-30 gram/hari sesuai dengan umur. Pada penerapan sebenarnya asupan serat masyarakat Indonesia rata-rata 10,5g/hari. Pangan lokal yang memiliki kadar serat yang tinggi adalah bekatul jagung dan kacang bambara. Bahan yang digunakan dalam penelitian ini adalah bekatul jagung, tepung terigu, margarin dan telur ayam. Penelitian ini menggunakan desain penelitian eksperimental dengan Rancangan Acak Lengkap (RAL) dengan dua pengulangan. Formula dibedakan menjadi 4 dengan masing-masing tingkat perbandingan bekatul jagung dengan penambahan tepung kacang bambara sebesar F0 (100%:0), F1 (80%:20&), F2 (70%:30), dan F3 (60%:40%). Hasil analisis uji organoleptik penambahan tepung kacang bambara berpengaruh nyata (p<0,05) pada tingkat kesukaan panelis pada atribut warna dan pada uji proksimat dan kadar serat pangan penambahan tepung kacang bambara berpengaruh nyata (p<0,05) terhadap kadar protein dan kadar serat pangan crackers. Formula 3 merupakan formula terpilih yang memiliki kadar air (7,99%), kadar abu (2,43%), kadar karbohidrat (51,61%), kadar lemak (26,9%), kadar protein (11,06%) dan kadar serat pangan (21,17%).
Oksidatif, Apoptotik ve İnflamatuar Sinyal Yolakları üzerinden C6 Glioblastoma Hücrelerindeki ML351'in Antiproliferatif Etkileri
Authors: HACIOĞLU Ceyhan , KAR Fatih
Published: January 2022

Amaç: Kanser tedavisindeki başarılı yaklaşımlardan biri de spesifik inhibitörlerin kullanılmasıdır. Çoklu doymamış yağ asitlerinin metabolizmasından sorumlu olan 12/15-lipoksijenaz (12/15-LOX) nöronlarda oksidatif stres kaynaklanan hücre ölümüne aracılık etmesinin yanı sıra, kanser gibi birçok önemli hastalıkta yer alan metabolitlerin üretemini de gerçekleştirir. Bu çalışmada, 12/15-LOX inhibitörü olan ML351'in C6 glioblastoma hücrelerin üzerindeki anti-proliferatif etkilerini çeşitli biyokimyasal süreçler üzerinden araştırılması amaçlanmıştır.

Gereç ve Yöntemler: Çalışmada önce C6 hücreleri için sitotoksik ML351 konsantrasyonları metil tiazolil tetrazolyum (MTT) kullanılarak tespit edilmiştir ve ardından total oksidan kapasite (TOS), sitokrom c (CYC), kaspaz 3 (CASP3), tümör nekroz faktör alfa (TNF-α) ve interlökin-6 (IL-6) seviyeleri ölçüldü.

Bulgular: Sonuç olarak, ML351 C6 hücreleri üzerinde konsantrasyon bağımlı anti-proliferatif etkilerinin olduğu görüldü. ML351 uygulamasının C6 hücrelerinde oksidatif strese neden olarak TOS seviyelerini artırdığı belirlendi. ML351 uygulanması kontrol grubu ile karşılaştırıldığında CASP3 ve CYC seviyelerini artırdı (p
Bipolar Bozukluk Hastalarında Çocukluk Çağı Travması ile Bilişsel Duygu Düzenleme ve Başa Çıkma Tutumları Arasındaki İlişki
Authors: TUMAN Taha Can , HURŞİTOĞLU Onur
Published: January 2022

Amaç: Bu çalışmada bipolar bozukluk hastalarında çocukluk çağı travması varlığı ve çocukluk çağı travmasının bilişsel duygu düzenleme ve başa çıkma tutumları ile ilişkisinin araştırılması amaçlanmıştır.

Gereç ve Yöntemler: Bu çalışmaya Temmuz 2020 ve Ocak 2021 tarihleri arasında Medipol Üniversitesi Esenler Hastanesine başvuran DSM-5 kriterlerine göre Bipolar bozukluk tanısı konmuş ve halen remisyonda olan 60 hasta dahil edilmiştir. Veriler sosyodemografik veri formu, Çocukluk çağı travma ölçeği (ÇÇTÖ), Bilişsel Duygu Düzenleme Ölçeği ve Başa Çıkma Tutumları Ölçeği (COPE) kullanılarak elde edilmiştir. Veriler Mann Whitney u testi, ki-kare testi ve Spearman korelasyon testi ile değerlendirilmiştir.

Bulgular: Hastaların ortalama yaşları 36,97 ± 10,36 idi. Hastaların çocukluk çağı travma ölçek toplam puanı ortalama 45,82 ± 12,97 idi. Hastaların %76.6 (n=46)’ sında ÇÇTÖ puanı 35 ve üstünde saptandı. Çocukluk çağı travması olan bipolar bozukluk hastalarında, kendini suçlama belirgin olarak yüksek, duygusal odaklı başa çıkma belirgin olarak düşük saptandı. Ayrıca bipolar bozukluk hastalarında çocukluk çağı travması varlığı ile kendini suçlama ve diğerlerini suçlama arasında pozitif yönde anlamlı ilişki, olumlu yeniden değerlendirme ve pozitif yeniden yorumlama ile negatif yönde anlamlı ilişki saptandı.

Sonuç: Bipolar bozukluk hastalarında yüksek oranda çocukluk çağı travması bulunduğu ve çocukluk çağı travmasının bazı bilişsel duygu düzenleme ve başa çıkma tutumlarını etkilediği belirlenmiştir.
Akciğer Kanseri Semptom Taramasının Sigara Bıraktırmadaki Rolü
Authors: YEŞİLOĞLU Reşat , ANNAKKAYA Ali Nihat , KALKANLI Nevin , KARATAŞ Naciye , BALBAY Öner , ARBAK Peri
Published: January 2022

Amaç: Bu çalışmada Düzce ilinde 30 yaş ve üzeri sigara içenlerde akciğer kanseri semptom taramasının sigara bırakmadaki rolü araştırıldı.

Gereç ve Yöntemler: Randomize 700 hane seçilerek 30 yaş üzeri sigara anamnezi olan 500 olgu çalışmaya alındı. Olguların sigara alışkanlıkları ve akciğer kanseri semptomları bir anket formuyla yüz yüze görüşmeyle sorgulandı. Sigaranın akciğer kanseri için önemli bir risk faktörü olduğu vurgulandı. Halen aktif sigara içen 474 olgunun 353'üne 6 ay sonra telefonla sigara alışkanlıkları yeniden sorgulandı.

Bulgular: Toplam 353 sigara içen olgunun 32’si (%9,1) kadın, 321’i (%90,9) erkekti. Yaş ortalaması 46±9 olan olguların, ortalama 36±24 paket-yıl sigara anamnezi vardı. 130'u (%36,8) sigarayı bırakmayı düşünüyordu ve 65'i (%18,4) sigarayı bırakmayı denemişti. 6 ay sonraki kontrolde 17 olgu (%4,8) sigarayı bırakmış, 59 olgu (%16) sigarayı azaltmış, 2 olgu (%0,6) ise artırmıştı. Sigarayı bırakanların hiçbiri ilk görüşmede bırakmayı düşündüğünü söyleyenler veya daha önce bırakmayı deneyenlerden değildi. Sigarayı bırakanların yaş ortalaması sigara içmeye devam edenlere göre daha yüksekti (p=0,044) ve sigarayı bırakanların daha uzun süredir sigara içme öyküleri vardı (p=0,001). Hemoptizi ve çomak parmak semptomlarının varlığı sigara bırakma oranlarını anlamlı düzeyde artırmaktaydı (sırasıyla p=0,048, p=0,013). Bu çalışmada akciğer kanseri semptom sorgulamasından 6 ay sonraki sigara bırakma oranı (%4,8), kendiliğinden sigarayı bırakma oranından (%1) anlamlı düzeyde yüksekti (p=0,001).

Sonuç: Akciğer kanseri semptom taramasıyla sigara bırakma oranları artırılabilir. Sigara bırakma poliklinikleri yanında bu tip yaklaşımlar sigara mücadelesine katkıda bulunabilir.
Forensic Linguistics function in Evidentiary and Investigative Contexts
Authors: Toghuj Raed
Published: January 2022

the main aim of this paper is to provide insights into the vital role of FL in Evidentiary and Investigative Contexts. the paper contains many segments; Authorship analysis and attribution, Plagiarism Detection, Speaker identification, and voice comparison, Language as evidence in civil cases (Trademark, Brand name Law, Defamation).
Extracorporeal Cardiac Shock Wave-Induced Exosome Derived From Endothelial Colony-Forming Cells Carrying miR-140-3p Alleviate Cardiomyocyte Hypoxia/Reoxygenation Injury via the PTEN/PI3K/AKT Pathway
Authors: Yang Dan , Wang Mingqiang , Hu Zhao , Ma Yiming , Shi Yunke , Cao Xingyu , Guo Tao , Cai Hongbo , Cai Hongyan
Published: January 2022

Background: Stem cell-derived exosomes have great potential in the treatment of myocardial ischemia–reperfusion injury (IRI). Extracorporeal cardiac shock waves (ECSW) as effective therapy, in part, could activate the function of exosomes. In this study, we explored the effect of ECSW-induced exosome derived from endothelial colony-forming cells on cardiomyocyte hypoxia/reoxygenation (H/R) injury and its underlying mechanisms.

Methods: The exosomes were extracted and purified from the supernatant of endothelial colony-forming cells (ECFCs-exo). ECFCs-exo treated with shock wave (SW-exo) or without shock wave (CON-exo) were performed with high-throughput sequencing of the miRNA. H9c2 cells were incubated with SW-exo or CON-exo after H/R injury. The cell viability, cell apoptosis, oxidative stress level, and inflammatory factor were assessed. qRT-PCR was used to detect the expression levels of miRNA and mRNA in cells and exosomes. The PTEN/PI3K/AKT pathway-related proteins were detected by Western blotting, respectively.

Results: Exosomes secreted by ECFCs could be taken up by H9c2 cells. Administration of SW-exo to H9c2 cells after H/R injury could significantly improve cell viability, inhibit cell apoptosis, and downregulate oxidative stress level (p < 0.01), with an increase in Bcl-2 protein and a decrease in Bax, cleaved caspase-3, and NF-κB protein (p < 0.05). Notably, miR-140-3p was found to be highly enriched both in ECFCs and ECFCs-exo treated with ECSW (p < 0.05) and served as a critical mediator. SW-exo increased miR-140-3p expression but decreased PTEN expression in H9c2 cells with enhanced phosphorylation of the PI3K/AKT signaling pathway. These cardioprotective effects of SW-exo on H/R injury were blunted by the miR-140-3p inhibitor. Dual-luciferase assay verified that miR-140-3p could directly target the 3′UTR of PTEN mRNA and exert a negative regulatory effect.

Conclusion: This study has shown the potential of ECSW as an effective stimulation for the exosomes derived from ECFCs in vitro. SW-exo exerted a stronger therapeutic effect on H/R injury in H9c2 cells possibly via delivering exosomal miR-140-3p, which might be a novel promising strategy for the myocardial IRI.
Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential
Authors: He Yongyu , Xie Wenqing , Li Hengzhen , Jin Hongfu , Zhang Yi , Li Yusheng
Published: January 2022

Aging promotes most degenerative pathologies in mammals, which are characterized by progressive decline of function at molecular, cellular, tissue, and organismal levels and account for a host of health care expenditures in both developing and developed nations. Sarcopenia is a prominent age-related disorder in musculoskeletal system. Defined as gradual and generalized chronic skeletal muscle disorder, sarcopenia involves accelerated loss of muscle mass, strength and function, which is associated with increased adverse functional outcomes and evolutionally refers to muscle wasting accompanied by other geriatric syndromes. More efforts have been made to clarify mechanisms underlying sarcopenia and new findings suggest that it may be feasible to delay age-related sarcopenia by modulating fundamental mechanisms such as cellular senescence. Cellular senescence refers to the essentially irreversible growth arrest mainly regulated by p53/p21CIP1 and p16INK4a/pRB pathways as organism ages, possibly detrimentally contributing to sarcopenia via muscle stem cells (MuSCs) dysfunction and the senescence-associated secretory phenotype (SASP) while cellular senescence may have beneficial functions in counteracting cancer progression, tissue regeneration and wound healing. By now diverse studies in mice and humans have established that targeting cellular senescence is a powerful strategy to alleviating sarcopenia. However, the mechanisms through which senescent cells contribute to sarcopenia progression need to be further researched. We review the possible mechanisms involved in muscle stem cells (MuSCs) dysfunction and the SASP resulting from cellular senescence, their associations with sarcopenia, current emerging therapeutic opportunities based on targeting cellular senescence relevant to sarcopenia, and potential paths to developing clinical interventions genetically or pharmacologically.
The Potential of Modified and Multimeric Antimicrobial Peptide Materials as Superbug Killers
Authors: Matthyssen Tamara , Li Wenyi , Holden James A. , Lenzo Jason C. , Hadjigol Sara , O’Brien-Simpson Neil M.
Published: January 2022

Antimicrobial peptides (AMPs) are found in nearly all living organisms, show broad spectrum antibacterial activity, and can modulate the immune system. Furthermore, they have a very low level of resistance induction in bacteria, which makes them an ideal target for drug development and for targeting multi-drug resistant bacteria ‘Superbugs’. Despite this promise, AMP therapeutic use is hampered as typically they are toxic to mammalian cells, less active under physiological conditions and are susceptible to proteolytic degradation. Research has focused on addressing these limitations by modifying natural AMP sequences by including e.g., d-amino acids and N-terminal and amino acid side chain modifications to alter structure, hydrophobicity, amphipathicity, and charge of the AMP to improve antimicrobial activity and specificity and at the same time reduce mammalian cell toxicity. Recently, multimerisation (dimers, oligomer conjugates, dendrimers, polymers and self-assembly) of natural and modified AMPs has further been used to address these limitations and has created compounds that have improved activity and biocompatibility compared to their linear counterparts. This review investigates how modifying and multimerising AMPs impacts their activity against bacteria in planktonic and biofilm states of growth.
Insights Into the Changing Landscape of Coronavirus Disease 2019
Authors: Escobedo Ruby A. , Kaushal Deepak , Singh Dhiraj K.
Published: January 2022

Coronavirus disease 2019 (COVID-19) is a highly contagious, infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2019 in Wuhan China. A year after the World Health Organization declared COVID-19 a global pandemic, over 215 million confirmed cases and approximately 5 million deaths have been reported worldwide. In this multidisciplinary review, we summarize important insights for COVID-19, ranging from its origin, pathology, epidemiology, to clinical manifestations and treatment. More importantly, we also highlight the foundational connection between genetics and the development of personalized medicine and how these aspects have an impact on disease treatment and management in the dynamic landscape of this pandemic.
Resistance to Persuasion: Examining the Influence of Political Ideology on COVID-19 Vaccine Uptake Hesitancy
Authors: Brinson Nancy H.
Published: January 2022

The COVID-19 pandemic has contributed to the death of over 625,000 Americans and it continues to have monumental consequences worldwide for economic, social and individual life. An effective vaccine program is considered vital to securing collective immunity; yet, many Americans are still hesitant to be vaccinated. This two-part study first experimentally tests two message frames (inoculation vs control) designed to counter resistance to the COVID-19 vaccine with individuals who are initially supportive, neutral or opposed to it. Based on a key finding from Study 1 (that political ideology appears to be impacting receptiveness to the messaging), Study 2 examines response to these same two messages using either a politicized (Dr. Anthony Fauci) or neutral source to test the mediating effects of political ideology. Results contribute to existing literature by examining inoculation effects in a new context (“debunking” misinformation vs “prebunking” to bolster supportive attitudes), and demonstrate how psychological reactance is working in tandem with inoculation to influence attitudes toward the COVID-19 vaccine.
How Older Adults Learn ICT—Guided and Self-Regulated Learning in Individuals With and Without Disabilities
Authors: Schlomann Anna , Even Christiane , Hammann Torsten
Published: January 2022

Learning to use information and communication technologies (ICT) may be more difficult for older people due to decreases in fluid intelligence, generational effects, and other age-related effects. Especially older people with intellectual disabilities (ID) are at a high risk of digital exclusion. To enable all older adults to use ICT, individualized technology training may be provided. However, little is known about the ICT learning preferences among older people with ID. Based on semi-structured interviews with older adults (n = 7, mean age = 76.6 years) and older adults with ID (n = 14, mean age = 62.4 years), this paper analyzes learning strategies, preferences, and learning settings. The results from content analysis show that guided learning with personal explanations in a one-to-one setting is the most preferred learning format in both groups of older adults. While many older adults without ID additionally favor self-regulated learning (i.e., learning with manuals or videos), older adults with ID mostly rely on guided learning with personal assistance. The differences can be explained by different abilities (e.g., reading skills) and social networks (e.g., living situation, having children). Not all older adults have a family or an institutional support network to help them learn ICT and community organizations may provide additional support. Researchers and practitioners should be aware of the diverse knowledge backgrounds and competencies in the group of older adults. ICT training in old age should be ideally composed in a modular way embedding self-regulated learning formats into guided learning modules.
Deep Neural Network-Aided Histopathological Analysis of Myocardial Injury
Authors: Jiao Yiping , Yuan Jie , Sodimu Oluwatofunmi Modupeoluwa , Qiang Yong , Ding Yichen
Published: January 2022

Deep neural networks have become the mainstream approach for analyzing and interpreting histology images. In this study, we established and validated an interpretable DNN model to assess endomyocardial biopsy (EMB) data of patients with myocardial injury. Deep learning models were used to extract features and classify EMB histopathological images of heart failure cases diagnosed with either ischemic cardiomyopathy or idiopathic dilated cardiomyopathy and non-failing cases (organ donors without a history of heart failure). We utilized the gradient-weighted class activation mapping (Grad-CAM) technique to emphasize injured regions, providing an entry point to assess the dominant morphology in the process of a comprehensive evaluation. To visualize clustered regions of interest (ROI), we utilized uniform manifold approximation and projection (UMAP) embedding for dimension reduction. We further implemented a multi-model ensemble mechanism to improve the quantitative metric (area under the receiver operating characteristic curve, AUC) to 0.985 and 0.992 on ROI-level and case-level, respectively, outperforming the achievement of 0.971 ± 0.017 and 0.981 ± 0.020 based on the sub-models. Collectively, this new methodology provides a robust and interpretive framework to explore local histopathological patterns, facilitating the automatic and high-throughput quantification of cardiac EMB analysis.
Prognosis and Risk Factors of Stroke After Thoracic Endovascular Aortic Repair for Stanford Type B Aortic Dissection
Authors: Zha Zhengbiao , Pan Youmin , Zheng Zhi , Wei Xiang
Published: January 2022

Background: Stroke is a severe complication of patients with type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR). Our aim is to identify predictors of stroke after TEVAR.

Methods: From February 2016 to February 2019, 445 patients with TBAD who underwent TEVAR were retrospectively analyzed. Univariate and multivariate analyses were performed to identify predictors of stroke after TEVAR.

Results: The total incidence of stroke was 11.5%, with transient neurological dysfunction (TND) of 10.6% and permanent neurological dysfunction (PND) of 0.9%. The average age of the patients was 53.0 ± 3.2 years, and the male/female ratio was 1.17. Univariate analysis suggested that age, body mass index (BMI), diabetes mellitus, chronic obstructive pulmonary disease (COPD), the urgency of repair, type of anesthesia, and left subclavian artery (LSCA) processing were potential risks factors of stroke after TEVAR. Multiple logistic regression identified that LSCA coverage (OR = 5.920, 95% CI: 2.077–16.878), diabetes mellitus (OR = 3.036, 95% CI: 1.025–8.995), and general anesthesia (OR = 2.498, 95% CI: 1.002–6.229) were independent predictors of stroke after TEVAR.

Conclusions: Left subclavian artery (LSCA) coverage, diabetes mellitus, and general anesthesia were independent risk factors of stroke after TEVAR for TBAD.
Titration of Long-Acting Insulin Using Continuous Glucose Monitoring and Smart Insulin Pens in Type 1 Diabetes: A Model-Based Carbohydrate-Free Approach
Authors: El Fathi Anas , Fabris Chiara , Breton Marc D.
Published: January 2022

Objective

Multiple daily injections (MDI) therapy is the most common treatment for type 1 diabetes (T1D), consisting of long-acting insulin to cover fasting conditions and rapid-acting insulin to cover meals. Titration of long-acting insulin is needed to achieve satisfactory glycemia but is challenging due to inter-and intra-individual metabolic variability. In this work, a novel titration algorithm for long-acting insulin leveraging continuous glucose monitoring (CGM) and smart insulin pens (SIP) data is proposed.

Methods

The algorithm is based on a glucoregulatory model that describes insulin and meal effects on blood glucose fluctuations. The model is individualized on patient’s data and used to extract the theoretical glucose curve in fasting conditions; the individualization step does not require any carbohydrate records. A cost function is employed to search for the optimal long-acting insulin dose to achieve the desired glycemic target in the fasting state. The algorithm was tested in two virtual studies performed within a validated T1D simulation platform, deploying different levels of metabolic variability (nominal and variance). The performance of the method was compared to that achieved with two published titration algorithms based on self-measured blood glucose (SMBG) records. The sensitivity of the algorithm to carbohydrate records was also analyzed.

Results

The proposed method outperformed SMBG-based methods in terms of reduction of exposure to hypoglycemia, especially during the night period (0 am–6 am). In the variance scenario, during the night, an improvement in the time in the target glycemic range (70–180 mg/dL) from 69.0% to 86.4% and a decrease in the time in hypoglycemia (<70 mg/dL) from 10.7% to 2.6% was observed. Robustness analysis showed that the method performance is non-sensitive to carbohydrate records.

Conclusion

The use of CGM and SIP in people with T1D using MDI therapy has the potential to inform smart insulin titration algorithms that improve glycemic control. Clinical studies in real-world settings are warranted to further test the proposed titration algorithm.

Significance

This algorithm is a step towards a decision support system that improves glycemic control and potentially the quality of life, in a population of individuals with T1D who cannot benefit from the artificial pancreas system.
A Bibliometric Analysis of Fintech Trends and Digital Finance
Authors: Brika Said Khalfa Mokhtar
Published: January 2022

Digital finance has piqued the curiosity of academics, students, and institutions all around the globe for more than a decade. Innovative financial services companies are offering a wide range of new financial products and new ways of interacting with customers via digital finance (Fintech). Research on finance and information systems has thus examined these shifts as well as the implications of technological advancements on the financial industry. Through presenting a bibliometric analysis, the article summarizes how scientific research has developed on the connections between financial technology developments and digital finance during the previous years. According to the ScienceDirect database, we base this literature review on journals and articles that have been published. We conducted a content analysis of 343 articles based on the discovered clusters, finding research gaps and suggesting actionable areas for further study. The results offer a solid path for future research in this area. We discuss the significance of the aforementioned publications and articles as well as potential areas of future study. The next step is to analyze the citation linkages between the most important articles to identify how they are related to one another. For financial technology research, the study looks at the way they are organized. The research is concerned with the roles of Fintech and the limits of research in digital financing. We point out potential routes for researchers to take to expand on current knowledge while also seeking possibilities for new, interesting, and creative research that adds to the expansion of the topic of research.
HLA-G in Allergy: Does It Play an Immunoregulatory Role?
Authors: Negrini Simone , Contini Paola , Murdaca Giuseppe , Puppo Francesco
Published: January 2022

Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, are known to play a key immunoregulatory role and their involvement in allergic diseases is supported by increasing literature data. HLA-G expression and secretion is specifically induced in peripheral blood mononuclear cells of allergic patients afterin vitroincubation with the causal allergen. Elevated levels of soluble HLA-G molecules are detected in serum of patients with allergic rhinitis correlating with allergen-specific IgE levels, clinical severity, drug consumption and response to allergen-specific immunotherapy. HLA-G genetic polymorphisms confer susceptibility to allergic asthma development and high levels of soluble HLA-G molecules are found in plasma and bronchoalveolar lavage fluid of patients with allergic asthma correlating with allergen-specific IgE levels. Interestingly, allergic pregnant women have lower plasma sHLA-G levels than non-allergic women during the 3rdtrimester of pregnancy and at delivery. Finally, in allergic patients with atopic dermatitis HLA-G molecules are expressed by T cells, monocytes-macrophages and Langerhans cells infiltrating the dermis. Although at present is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are specifically expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.
The Role of Microglial Phagocytosis in Ischemic Stroke
Authors: Jia Junqiu , Yang Lixuan , Chen Yan , Zheng Lili , Chen Yanting , Xu Yun , Zhang Meijuan
Published: January 2022

Microglia are the resident immune cells of the central nervous system that exert diverse roles in the pathogenesis of ischemic stroke. During the past decades, microglial polarization and chemotactic properties have been well-studied, whereas less attention has been paid to phagocytic phenotypes of microglia in stroke. Generally, whether phagocytosis mediated by microglia plays a beneficial or detrimental role in stroke remains controversial, which calls for further investigations. Most researchers are in favor of the former proposal currently since efficient clearance of tissue debris promotes tissue reconstruction and neuronal network reorganization in part. Other scholars propose that excessively activated microglia engulf live or stressed neuronal cells, which results in neurological deficits and brain atrophy. Upon ischemia challenge, the microglia infiltrate injured brain tissue and engulf live/dead neurons, myelin debris, apoptotic cell debris, endothelial cells, and leukocytes. Cell phagocytosis is provoked by the exposure of “eat-me” signals or the loss of “don’t eat-me” signals. We supposed that microglial phagocytosis could be initiated by the specific “eat-me” signal and its corresponding receptor on the specific cell type under pathological circumstances. In this review, we will summarize phagocytic characterizations of microglia after stroke and the potential receptors responsible for this programmed biological progress. Understanding these questions precisely may help to develop appropriate phagocytic regulatory molecules, which are promoting self-limiting inflammation without damaging functional cells.
Evidence of Microglial Immune Response Following Coronavirus PHEV Infection of CNS
Authors: Zhang Jing , Li Zi , Lu Huijun , Shi Junchao , Gao Rui , Ma Ying , Lan Yungang , Guan Jiyu , Zhao Kui , Gao Feng , He Wenqi
Published: January 2022

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus that invades the host central nervous system (CNS) and causes neurological dysfunction. Microglia are key immune cells in the CNS, however, whether and how they response to PHEV infection remains unclear. Herein, microglial activation and proliferation were detected in the CNS of PHEV-infected mice, as along with the proinflammatory response. Moreover, the production of proinflammatory cytokines induced by moderately activated microglia limited viral replication in the early stage of infection. Microglial depletion assays showed that during late infection, excess activation of microglia aggravated neurological symptoms, BBB destruction, and peripheral monocyte/macrophage infiltration into the CNS. Using an in vitro brain slice model, PHEV was identified to specifically and moderately induce microglial activation in the absence of peripheral immune cells infiltration. Consistently, macrophage clearance from circulating blood indicated that peripheral monocytes/macrophages crossing the BBB of mice were responsible for excess activation of microglia and CNS damage in late PHEV infection. Overall, our findings provide evidence supporting a dual role for microglia in the host CNS in response to coronavirus PHEV invasion.
Structural Biology Illuminates Molecular Determinants of Broad Ebolavirus Neutralization by Human Antibodies for Pan-Ebolavirus Therapeutic Development
Authors: Murin Charles D. , Gilchuk Pavlo , Crowe James E. , Ward Andrew B.
Published: January 2022

Monoclonal antibodies (mAbs) have proven effective for the treatment of ebolavirus infection in humans, with two mAb-based drugs Inmazeb™ and Ebanga™ receiving FDA approval in 2020. While these drugs represent a major advance in the field of filoviral therapeutics, they are composed of antibodies with single-species specificity for Zaire ebolavirus. The Ebolavirus genus includes five additional species, two of which, Bundibugyo ebolavirus and Sudan ebolavirus, have caused severe disease and significant outbreaks in the past. There are several recently identified broadly neutralizing ebolavirus antibodies, including some in the clinical development pipeline, that have demonstrated broad protection in preclinical studies. In this review, we describe how structural biology has illuminated the molecular basis of broad ebolavirus neutralization, including details of common antigenic sites of vulnerability on the glycoprotein surface. We begin with a discussion outlining the history of monoclonal antibody therapeutics for ebolaviruses, with an emphasis on how structural biology has contributed to these efforts. Next, we highlight key structural studies that have advanced our understanding of ebolavirus glycoprotein structures and mechanisms of antibody-mediated neutralization. Finally, we offer examples of how structural biology has contributed to advances in anti-viral medicines and discuss what opportunities the future holds, including rationally designed next-generation therapeutics with increased potency, breadth, and specificity against ebolaviruses.
Dynamic Regulation of the Nexus Between Stress Granules, Roquin, and Regnase-1 Underlies the Molecular Pathogenesis of Warfare Vesicants
Authors: Srivastava Ritesh Kumar , Mishra Bharat , Muzaffar Suhail , Gorbatyuk Marina S. , Agarwal Anupam , Mukhtar M. Shahid , Athar Mohammad
Published: January 2022

The use of chemical warfare agents is prohibited but they have been used in recent Middle Eastern conflicts. Their accidental exposure (e.g. arsenical lewisite) is also known and causes extensive painful cutaneous injury. However, their molecular pathogenesis is not understood. Here, we demonstrate that a nexus of stress granules (SGs), integrated stress, and RNA binding proteins (RBPs) Roquin and Reganse-1 play a key role. Lewisite and its prototype phenylarsine oxide (PAO) induce SG assembly in skin keratinocytes soon after exposure, which associate with various RBPs and translation-related proteins. SG disassembly was detected several hours after exposure. The dynamics of SG assembly-disassembly associates with the chemical insult and cell damage. Enhanced Roquin and Regnase-1 expression occurs when Roquin was recruited to SGs and Regnase-1 to the ribosome while in the disassembling SGs their expression is decreased with consequent induction of inflammatory mediators. SG-targeted protein translational control is regulated by the phosphorylation-dependent activation of eukaryotic initiation factors 2α (eIF2α). Treatment with integrated stress response inhibitor (ISRIB), which blocks eIF2α phosphorylation, impacted SG assembly dynamics. Topical application of ISRIB attenuated the inflammation and tissue disruption in PAO-challenged mice. Thus, the dynamic regulation of these pathways provides underpinning to cutaneous injury and identify translational therapeutic approach for these and similar debilitating chemicals.
The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves’ Disease Patients Through Regulating the Intestinal Microbiome
Authors: Han Zhe , Cen Chaoping , Ou Qianying , Pan Yonggui , Zhang Jiachao , Huo Dongxue , Chen Kaining
Published: January 2022

Graves’ disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients’ TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.
Suppression of the Cycloidal Spin Arrangement in BiFeO3 Caused by the Mechanically Induced Structural Distortion and Its Effect on Magnetism
Authors: Da Silva Klebson Lucenildo , Trautwein Rafael Santiago , Da Silva Rodolfo Bezerra , Fabián Martin , Čižmár Erik , Holub Mariia , Skurikhina Olha , Harničárová Marta , Girman Vladimír , Menzel Dirk , Becker Klaus Dieter , Hahn Horst , Šepelák Vladimír
Published: January 2022

Bismuth ferrite (BiFeO3) particles are prepared by a combined mechanochemical−thermal processing of a Bi2O3 + α-Fe2O3 mixture. Structural, magnetic, hyperfine, morphological and chemical properties of the as-prepared BiFeO3 are studied using X-ray diffraction (Rietveld refinement), 57Fe Mössbauer spectroscopy, SQUID magnetometry, electron microscopy and energy dispersive X-ray spectroscopy. It is revealed that the structure of the ferrite exhibits the long-range distortion (significantly tilted FeO6 octahedra) and the short-range disorder (deformed FeO6 octahedra). Consequently, these structural features result in the suppression of a space modulated cycloidal spin arrangement in the material. The latter manifests itself by the appearance of only single spectral component in the 57Fe Mössbauer spectrum of BiFeO3. The macroscopic magnetic behavior of the material is interpreted as a superposition of ferromagnetic and antiferromagnetic contributions with a large coercive field and remanent magnetization. Taking into account the average particle size of the as-prepared BiFeO3 particles (∼98 nm), exceeding the typical period length of cycloid (∼62 nm), both the suppression of the spiral spin structure in the material and its partly ferromagnetic behavior are attributed to the crystal lattice distortion caused by mechanical stress during the preparation procedure.
Preparing a Bioactive (Chitosan/Sodium Hyaluronate)/SrHA Coating on Mg–Zn–Ca Alloy for Orthopedic Implant Applications
Authors: Feng Yashan , Chang Lei , Zhu Shijie , Yang Yongxin , Wei Baoli , Lv Meng , Wang Jun , Guan Shaokang
Published: January 2022

The uncontrollable rapid degradation rate of the Mg alloy substrate limited its clinical application, and implant-associated infections have been reported to be the main reason for the secondary surgery of orthopedic implantation. The aim of this study was to produce a multifunctional coating on magnesium-based alloys that have improved corrosion resistance, bioactivity, and antibacterial properties through the preparation of polyelectrolytic multilayers (PEMs) consisting of chitosan (CS) and sodium hyaluronate (HA) on silane-modified strontium-substituted hydroxyapatite (hereafter referred to as Bil (SH + CS)/SrHA). The multifunctional coatings were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS). The results showed the polyelectrolyte complex SH/CS layer to be uniformly and tightly attached on to the surface of silane-treated SrHA. At the same time, a potentiodynamic polarization test and hydrogen evolution test showed the Bil (SH + CS)/SrHA coatings to exhibit superior corrosion resistance than bulk Mg-based alloys. The results of the cell–surface interactions revealed Bil (SH + CS)/SrHA coatings to be in favor of cell initial adhesion and more beneficial to the proliferation and growth of cells with the processing of co-culture. In addition, antibacterial tests demonstrated the strong bactericidal effect of Bil (SH + CS)/SrHA coatings against both Escherichia coli (E. coli) and Staphylococcus (S. aureus), suggesting that Bil (SH + CS)/SrHA coatings can successfully achieve multifunctionality with enhanced corrosion resistance, biocompatibility, and antibacterial properties.
The Optimization of an Anti-VEGF Therapeutic Regimen for Neovascular Glaucoma
Authors: Bai Ling , Wang Yanfen , Liu Xindi , Zheng Yuping , Wang Wenjing , He Na , Tariq Farheen , Wang Feng , Zhang Shu
Published: January 2022

This study investigates the safety and efficacy of conbercept injection through different routes for neovascular glaucoma (NVG) treatment, in which seventy-four patients (81 eyes) with NVG caused by ischemia retinopathy had participated. Patients were divided into three stages according to the progression of NVG and were randomly assigned to receive intracameral or intravitreal conbercept injection. After conbercept injection, patients experienced improved best-corrected visual acuity (BCVA), good intraocular pressure (IOP) control, and neovascularization of Iris (NVI) regression. In stage III, patients required trabeculectomy with mitomycin C plus pan-retinal photocoagulation (PRP) to achieve complete NVI regression. Compared to the intravitreal group, the intracameral group had significantly lower IOP in 2 days in stage III and 1 day in stages I and II after injection, complete NVI regression before PRP in stages I and II, and better NVI regression in stage III. The rates of hyphema after trabeculectomy and malfunction filtering bleb suffering needle bleb revision were lower in the intracameral group, but only the hyphema rate was significantly different. Injections through different routes are all safe. We recommend intravitreal injections for patients in stages I and II, but for stage III, intracameral injection is better, and trabeculectomy with mitomycin C should be conducted within 2 days after injection to maximally reduce the risk of perioperative hyphema.

Trial Registration:ClinicalTrials.gov, identifier NCT03154892.
Optical Coherence Tomographic Features and Prognostic Values of Macular Edema in Vogt-Koyanagi-Harada Disease
Authors: Qin Peng , Ye Zi , Su Guannan , Kijlstra Aize , Yang Peizeng
Published: January 2022

Purpose: To determine optical coherence tomographic (OCT) features of macular edema (ME) and identify potential prognostic values for ME and visual outcomes in Vogt-Koyanagi-Harada disease (VKH).

Methods: In the retrospective case series, a total of 1,377 VKH patients who were seen in a tertiary uveitis center between September 2011 and January 2018 were reviewed on their demographics, visual acuity, ocular and extraocular manifestations, modes of treatment, and OCT examinations. Of these patients, 79 (5.7%) having ME were included for analysis of OCT features. Four patients were missed without ME resolution, and the remaining 75 patients who either had ME resolved or were followed up for 2 years were included for analysis of disease outcomes.

Results: Of the 115 affected eyes in these 79 patients, 100 (87.0%) had cystoid ME (CME), accounting for the most common OCT feature of VKH-related ME. Disruption of the inner-segment/outer-segment junction (IS/OS) band seen in 33 (28.7%) affected eyes of 24 (30.4%) patients was found as a risk factor for the development of persistent ME [10 of 62 (16.1%) vs. 13 of 13 (100%); P < 0.001] and a poor visual outcome (1.16 ± 0.42 vs. 1.17 ± 0.46 in logMAR unit; P = 0.89). CME patients with a concurrent choroidal neovascular membrane often had a disrupted IS/OS band, thus becoming refractory cases. A 6-month well-controlled intraocular inflammation following standard treatment regimens was found to associate with complete resolution of the refractory edema [4 of 5 (80%) vs. 2 of 13 (15%); P = 0.02].

Conclusions: Intraretinal cystoid changes are most commonly seen in the edematous macula of VKH patients. Disruption of the IS/OS band is a useful risk sign for poor ME and visual outcomes in VKH-related ME, and a long-term well-controlled intraocular inflammation may be critical for the resolution of refractory cases.
Quality Management in Polish Biobanking Network—Current Status Before the Implementation of Unified and Harmonized Integrated Quality Management System
Authors: Matera-Witkiewicz Agnieszka , Krupińska Magdalena , Sitek Patrycja , Laskowski Michał , Zagórska Karolina , Gleńska-Olender Joanna
Published: January 2022

In 2017, Polish Biobanking Network was established in Poland, within BBMRI.pl project titled “Organization of Polish Biobanking Network within the Biobanking and Biomolecular Resources Research Infrastructure BBMRI-ERIC” as a strategic scientific infrastructure concept. One of the key elements of the project was the verification of the current status of QMS in the Polish biobanking institutions and the implementation of common solutions. The main goal was to indicate the current QMS level and determine the starting points for QMS development for each biobank of the Polish Biobanking Network (PBN). Within 3 years, 35 audit visits were performed. The current status and the level of QMS implementation in each biobank were assessed. Five hundred and seventy recommendations were prepared. The data was analyzed using Fischer Exact test to determine whether or not a significant association was observed. Three areas of analysis were covered: (1) BBMRI.pl status, (2) QMS implementation level and (3) private/public party, respectively. The results were discussed within 15 areas. Concluding remarks showed that some differences were observed in the case of subgroups analysis. There is convergence in QMS within the biobanks where Tissue Banks are located. Moreover, some discrepancies between the QMS implementation level in BBMRI.pl Consortium biobanks and PBN biobanks are observed. Nevertheless, the consortium members are obliged to prepare other biobanks willing to enter the PBN as Members/Observers or which already are in the PBN, so that they can meet the requirements of the quality management system that will enable efficient management of biobanking processes in these units. That is why some actions within BBMRI.pl projects are organized to help the whole biobanking community in Poland implement the harmonized solution.
Awareness and Use of Post-exposure Prophylaxis for HIV Prevention Among Men Who Have Sex With Men: A Systematic Review and Meta-Analysis
Authors: Jin Junyan , Sun Runsong , Mu Tingting , Jiang Taiyi , Dai Lili , Lu Hongyan , Ren Xianlong , Chen Jing , Ye Jingrong , Sun Lijun , Wu Hao , Zhang Tong , Zou Huachun , Su Bin
Published: January 2022

Background: The use of post-exposure prophylaxis (PEP) is effective in reducing HIV risk, but it is underused by men who have sex with men (MSM) due to certain psychological and sociostructural factors. This article assessed the awareness and use of PEP among MSM in an effort to increase the visibility and uptake of PEP among at-risk populations.

Methods: We conducted a systematic literature search of the PubMed, Web of Science, PsycINFO, and Google Scholar electronic databases. Studies were screened for inclusion, and relevant data were abstracted, assessed for bias, and synthesized. Pooled effect estimates were calculated using random effects meta-analysis, meta-regression and subgroup analysis, and a qualitative review and risk of bias assessment were performed (PROSPERO, CRD42019123815).

Results: Twenty eligible studies involving 12,579 MSM were included in the meta-analysis. The pooled estimate of the proportions of MSM who were aware of PEP was modest at 59.9% (95% CI: 50.5~68.7) and that of MSM who previously used PEP was very low at 4.9% (95% CI: 2.4~9.8). PEP awareness showed no clear change over time, while PEP use significantly changed over time. Multiple factors affected awareness, including educational attainment, race/ethnicity, levels of HIV stigma, access to condoms, and so on. Many factors could potentially impede or facilitate the use of PEP, such as income, lack of PEP information, and partnership.

Conclusion: We observed that PEP is an underused HIV prevention strategy among MSM and that once MSM become aware of PEP, the majority are willing to use it if they are supported appropriately in terms of a range of individual, social, and structural barriers.

Systematic Review Registration: http://www.cdr.york.ac.uk/prospero, PROSPERO [CRD42019123815].