bluuebunny/crossref_metadata_2025 huggingface dataset:
TÜRKİYE’DE KADININ ÖZGÜR VE EŞİTLİKÇİ TOPLUM DÜZENİ ARAYIŞININ TARİHSEL GELİŞİMİ: FEMİNİZM VE İSLAMİ FEMİNİZMİN ÇALKANTILI SERÜVENİ
Authors: ARSLAN Lütfi
Published: December 2022

Kadının toplumsal cinsiyet eşitliği ve hak arayışı meselesi 1945 tarihli Birleşmiş Milletler sözleşmesinde ilk kez yerini almıştır. BM tarafından 1975 senesi Kadın Yılı olarak kabul edilmiştir. 1975-1985 arası döneme “Kadının 10 Yılı” adı verilerek, BM tarafından kabul edilen Kadına Karşı Ayrımcılığın Engellenmesi Sözleşmesi (CEDAW) uygulamaya konulmuştur. XX. yüzyıl sonlarında İslam ülkelerinde batılılaşma/modernleşme hareketlerine bağlı olarak kadının inanca bağlı sosyal yaşamı ile kamusal alandaki statüsü tartışmaları İslami feminizm söylemini ortaya çıkarmıştır. Türkiye’de Tanzimat Dönemi’nden Cumhuriyet Dönemi’ne kadar feminizm-İslami feminizm çerçevesinde kadının eşitlikçi toplum düzeni arayışı meselesinde din-inanç ve geleneksel tutum referanslı tartışmalar kadınların ortak bir noktada birleşmelerini engellemiştir. Cumhuriyet’ten sonra hükümetler ile sivil toplum kuruluşları ve hatta ferdi çalışmalar konuyu siyasi ve sosyokültürel düzlemde başka boyutlara taşımıştır. Türkiye’de 1980’den sonra kadının hak arayışı konusunda yasal düzenlemeleri içeren uygulamalara daha fazla önem verilmiştir. Türkiye’de cinsiyet eşitliğinin sağlanmasında sivil toplum örgütleri, siyasi partiler ve hatta hükümet programlarında ortaya konan politikaların günden güne gelişmekte olması kadının toplum içindeki yerine bakış açılarının kadının lehine değişmesini sağlamıştır. Ancak Türkiye’de kadın ve onun eşitlikçi ve özgür bir toplumda yaşama konusunda ideolojik ve ön yargılı yaklaşımlar meselenin özüne inilememesine neden olmuştur. Kadının evi ve toplum içindeki aidiyetinin kapsamı ve yansımalarının tarihsel süreç içinde geçirdiği evrelerin bilinmesine ihtiyaç bulunmaktadır. Bu çalışmada, kadının tarihsel süreç içindeki özgür ve eşitlikçi toplum düzeni arayışı feminizm, İslami feminizm ve cinsiyet eşitliği kavramları çerçevesinde tarama yöntemi ile ele alınmıştır. Hükümetlerin kadın politikaları ile sivil toplum örgütleri çalışmaları kronolojik olarak işlenmiştir. Kadının aidiyeti inanç, İslami felsefe ve gelenek bağlamında irdelenmiştir.
MİKROPLARIN VE ZEHİRLERİN SAVAŞ MEYDANLARINDA KULLANILMASI: ORTAÇAĞ’DA BİYOLOJİK SAVAŞ
Authors: KARAİMAMOĞLU Tolgahan
Published: December 2022

ÖZ

İnsanlık tarihin her döneminde birçok savaş meydana gelmiştir. İrili-ufaklı ordular arasındaki bu savaşlarda ise sadece klasik silahlar kullanılmamıştır. Gündelik hayat içerisinde insan sağlığına zararlı ve genellikle de ölümcül alan ajanlarda kimi zaman savaş meydanlarında etkili birer silah haline dönüştürülmüştür. Dolayısıyla biyolojik savaşın tarihi çok eskilere dayanmakta ve hiç bitmeden de varlığını, insanlık için tehdit olma durumunu sürdürmektedir. Biyolojik unsurların ve zehirlerin kullanımına bakıldığında ise ortaçağ dünyasında dikkat çekici örnekler bulmak mümkündür. Artan nüfus nispetinde daha büyük ordularla savaşların yapılmaya başlaması ortaçağ süresince zehrin ve biyolojik unsurların harp sahalarında giderek daha yoğun ve sofistike şekilde kullanımını ortaya çıkartmıştır. Ortaçağda surlarla kaplı şehirlerin kuşatılması esnasında hastalıktan ölmüş ve hastalık saçan insan ve hayvan ölülerinin mancınıklarla attırılarak düşman kuvvetlerinin hastalıktan kırılmasının amaçlanması en belirgin biyolojik harp tekniği olmuştur. Kara Ölüm ortaçağ dünyasında biyolojik savaşın en açık ve yıkıcı örneği olmuştur. Aynı zamanda gübre ve insan sağlığına zararlı diğer ajanlarda kimi zaman mancınıklarla kalelere attırılmıştır. Hayvanlardan elde edilen veya bilinen zehirler ise özellikle su kuyularını tahrip etmek için kullanılmıştır. Avrupa periferinde ortaçağ süresinde Fransa, İtalya, İspanya ve İngiltere biyolojik unsurların savaş alanında kullanan başlıca ülkeler olmuştur. Özellikle ortaçağın son döneminde İtalyanların biyolojik savaş silahlarını kontrolsüz şekilde geliştirdikleri anlaşılmaktadır. Dolayısıyla bu kontrol ve yıkıcı etkiler ortaya çıkaran biyolojik savaşa karşı Fransa ve Almanya arasında erken devirde üstü kapalı bir anlaşma dahi yapılmıştır. Genel anlamıyla bu araştırma ortaçağ dünyasında bazı örnekler üzerinden zehir ve biyolojik unsurların savaş meydanlarında kullanılmasına odaklanmaktadır.
The multifunctional roles of autophagy in the innate immune response: Implications for regulation of transplantation rejection
Authors: Zhang Kunli , Huang Qiuyan , Peng Laru , Lin Sen , Liu Jie , Zhang Jianfeng , Li Chunling , Zhai Shaolun , Xu Zhihong , Wang Sutian
Published: December 2022

Organ transplantation is the main treatment for end-stage organ failure, which has rescued tens of thousands of lives. Immune rejection is the main factor affecting the survival of transplanted organs. How to suppress immune rejection is an important goal of transplantation research. A graft first triggers innate immune responses, leading to graft inflammation, tissue injury and cell death, followed by adaptive immune activation. At present, the importance of innate immunity in graft rejection is poorly understood. Autophagy, an evolutionarily conserved intracellular degradation system, is proven to be involved in regulating innate immune response following graft transplants. Moreover, there is evidence indicating that autophagy can regulate graft dysfunction. Although the specific mechanism by which autophagy affects graft rejection remains unclear, autophagy is involved in innate immune signal transduction, inflammatory response, and various forms of cell death after organ transplantation. This review summarizes how autophagy regulates these processes and proposes potential targets for alleviating immune rejection.
Bortezomib abrogates temozolomide-induced autophagic flux through an ATG5 dependent pathway
Authors: Rahman Mohummad Aminur , Engelsen Agnete S. T. , Sarowar Shahin , Bindesbøll Christian , Birkeland Even , Goplen Dorota , Lotsberg Maria L. , Knappskog Stian , Simonsen Anne , Chekenya Martha
Published: December 2022

Introduction: Glioblastoma (GBM) is invariably resistant to temozolomide (TMZ) chemotherapy. Inhibiting the proteasomal pathway is an emerging strategy to accumulate damaged proteins and inhibit their lysosomal degradation. We hypothesized that pre-treatment of glioblastoma with bortezomib (BTZ) might sensitize glioblastoma to temozolomide by abolishing autophagy survival signals to augment DNA damage and apoptosis.

Methods: P3 patient-derived glioblastoma cells, as well as the tumour cell lines U87, HF66, A172, and T98G were investigated for clonogenic survival after single or combined treatment with temozolomide and bortezomib in vitro. We investigated the requirement of functional autophagy machinery by utilizing pharmacological inhibitors or CRISPR-Cas9 knockout (KO) of autophagy-related genes -5 and -7 (ATG5 and ATG7) in glioblastoma cells and monitored changes in autophagic flux after temozolomide and/or bortezomib treatments. P3 wild-type and P3 ATG5−/− (ATG5 KO) cells were implanted orthotopically into NOD-SCID mice to assess the efficacy of bortezomib and temozolomide combination therapy with and without functional autophagy machinery.

Results: The chemo-resistant glioblastoma cells increased autophagic flux during temozolomide treatment as indicated by increased degradation of long-lived proteins, diminished expression of autophagy markers LC3A/B-II and p62 (SQSTM1), increased co-localisation of LC3A/B-II with STX17, augmented and no induction of apoptosis. In contrast, bortezomib treatment abrogated autophagic flux indicated by the accumulation of LC3A/B-II and p62 (SQSTM1) positive autophagosomes that did not fuse with lysosomes and thus reduced the degradation of long-lived proteins. Bortezomib synergistically enhanced temozolomide efficacy by attenuating cell proliferation, increased DNA double-strand breaks, and apoptosis in an autophagy-dependent manner. Abolishing autophagy in ATG5 KOs reversed the bortezomib-induced toxicity, rescued glioblastoma cell death and reduced animal survival.

Discussion: We conclude that bortezomib abrogates temozolomide induced autophagy flux through an ATG5 dependent pathway.
Endoplasmic reticulum—Phagosome contact sites from the cradle to the grave
Authors: Ghavami Mahlegha , Fairn Gregory D.
Published: December 2022

Phagocytosis is a key component of the innate immune system used to ingest apoptotic cells and microorganisms for their destruction and recycling of macromolecules and the presentation of antigens to adaptive immune system cells. The newly formed vacuole or nascent phagosome undergoes a maturation process reminiscent of the classical endocytic maturation process, reaching a highly degradative phagolysosome stage before its tubulovesicular breakdown into lysosomes. The process is highly regulated and can be disrupted by various pathogenic organisms. The exchange of proteins, lipids, and other metabolites between organelles, including maturing phagosomes, is enabled by two processes, vesicular and non-vesicular transport at membrane contact sites (MCS). For decades the specific role(s) of the endoplasmic reticulum (ER) in phagocytosis has been the subject of much debate. In parallel, the last two decades have seen a burst in research on the numerous roles of ER contact sites and resident proteins in all aspects of organelle biology. Here, in this minireview, we describe ER-phagosome contact sites’ functions from the early stages of particle engulfment to the phagolysosome dissolution into lysosomes. We also discuss several aspects of ER–phagosome contact sites that remain to be explored.
Adeno-associated virus vector intraperitoneal injection induces colonic mucosa and submucosa transduction and alters the diversity and composition of the faecal microbiota in rats
Authors: Ma Li-Tian , Lian Jing-Xuan , Bai Yang , Shang Meng-Juan , Zhang Zhe-Zhe , Wu Fei-Fei , Chen Jing , Meng Xian-Bo , Zheng Jin , Li Tian , Li Yun-Qing , Wang Jing-Jie
Published: December 2022

Background

Viral vector technology, especially recombinant adeno-associated virus vector (rAAV) technology, has shown great promise in preclinical research for clinical applications. Several studies have confirmed that rAAV can successfully transduce the enteric nervous system (ENS), and rAAV gene therapy has been approved by the Food and Drug Administration (FDA) for the treatment of the early childhood blindness disease Leber congenital amaurosis and spinal muscular atrophy (SMA). However, until now, it has not been possible to determine the effect of AAV9 on intestinal microbiota.

Methods

We examined the efficiency of AAV9-mediated ascending colon, transverse colon and descending colon transduction through intraperitoneal (IP) injection, performed 16S rRNA gene amplicon sequencing and analysed specific faecal microbial signatures following AAV9 IP injection via bioinformatics methods in Sprague–Dawley (SD) rats.

Results

Our results showed (1) efficient transduction of the mucosa and submucosa of the ascending, transverse, and descending colon following AAV9 IP injection; (2) a decreased alpha diversity and an altered overall microbial composition following AAV9 IP injection; (3) significant enrichments in a total of 5 phyla, 10 classes, 13 orders, 15 families, 29 genera, and 230 OTUs following AAV9 IP injection; and (4) AAV9 can significantly upregulate the relative abundance of anaerobic microbiota which is one of the seven high-level phenotypes that BugBase could predict.

Conclusion

In summary, these data show that IP injection of AAV9 can successfully induce the transduction of the colonic mucosa and submucosa and alter the diversity and composition of the faecal microbiota in rats.
Feasibility, effectiveness, and safety of edoxaban administration through percutaneous endoscopic gastrostomy: 12-months follow up of the ORIGAMI study
Authors: Cappannoli Luigi , Laborante Renzo , Galli Mattia , Canonico Francesco , Ciliberti Giuseppe , Restivo Attilio , Princi Giuseppe , Arcudi Alessandra , Sabatelli Mario , De Cristofaro Raimondo , Crea Filippo , D’Amario Domenico
Published: December 2022

Background and aims

Edoxaban proved to be safe and effective also in fragile patients, but its administration through percutaneous endoscopic gastrostomy (PEG) has not been previously investigated. The purpose of this study was to evaluate the feasibility and the preliminary safety and efficacy profiles of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation.

Methods

ORIGAMI was a prospective, single-arm, observational study (NCT04271293). Patients with PEG and an indication for long-term anticoagulation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. The primary endpoint was the composite of cardio-embolic events consisting of ischemic stroke, systemic embolism, or symptomatic deep venous thrombosis/pulmonary embolism (DVT/PE). Secondary endpoints were the number of bleeding events and edoxaban plasma concentrations at steady state. We here report the 12-month results.

Results

A total of 12 patients were enrolled. The main indication for PEG implantation was amyotrophic lateral sclerosis (10/12). The primary endpoint of cardio-embolic events did not occur in any patients at 12 months. All patients were in the therapeutic range of steady-state edoxaban plasma levels. Three minor bleedings were observed, while no major bleedings occurred during the observational period. A total of five patients died. All deaths were from non-cardiovascular causes and were consistent with the natural history of the pre-existing severe disease.

Conclusion

Our study suggests that edoxaban administration via PEG is feasible and appears safe and effective in fragile, comorbid patients, resulting in therapeutic plasma concentrations of edoxaban.

Clinical trial registration

[ClinicalTrials.gov], identifier [NCT04271293].
Induced pluripotent stem cell for modeling Pompe disease
Authors: Huang Wenjun , Zhang Yanmin , Zhou Rui
Published: December 2022

Pompe disease (PD) is a rare, autosomal recessive, inherited, and progressive metabolic disorder caused by α-glucosidase defect in lysosomes, resulting in abnormal glycogen accumulation. Patients with PD characteristically have multisystem pathological disorders, particularly hypertrophic cardiomyopathy, muscle weakness, and hepatomegaly. Although the pathogenesis and clinical outcomes of PD are well-established, disease-modeling ability, mechanism elucidation, and drug development targeting PD have been substantially limited by the unavailable PD-relevant cell models. This obstacle has been overcome with the help of induced pluripotent stem cell (iPSC) reprogramming technology, thus providing a powerful tool for cell replacement therapy, disease modeling, drug screening, and drug toxicity assessment. This review focused on the exciting achievement of PD disease modeling and mechanism exploration using iPSC.
Early detection of immune checkpoint inhibitor-related subclinical cardiotoxicity: A pilot study by using speckle tracking imaging and three-dimensional echocardiography
Authors: Xu Aiqing , Yuan Ming , Zhan Xiaoping , Zhao Gangjian , Mu Guanyu , Wang Tingting , Hu Hailong , Fu Huaying
Published: December 2022

Background

Early detection of subclinical cardiotoxicity of immune checkpoint inhibitor (ICI) therapy can be challenging.

Objective

To evaluate subclinical cardiac dysfunction using two-dimensional speckle tracking imaging (2D-STI) and three-dimensional echocardiography in Chinese patients.

Methods

Fifty-five consecutive patients with malignant tumors treated by immunotherapy were included. They were examined by echocardiography before immunotherapy and after immunotherapy. Left ventricular ejection fraction (LVEF) was calculated in three-dimensional imaging. Moreover, left ventricular global longitudinal peak systolic strain (LVGLS), left ventricular global circumferential peak systolic strain (LVGCS), right ventricular global longitudinal systolic strain (RVGLS), right ventricular free wall longitudinal peak systolic strain (RVFWLS), and tricuspid annular plane systolic excursion (TAPSE) were evaluated. Clinical and laboratory parameters were recorded. Cardiac toxicity events were defined as the presence of heart failure symptoms, LVEF reduction, and increase in troponin. Subclinical cardiac toxicity was defined as cardiac dysfunction associated with ICI treatment, with absent or delayed ICI-associated cardiotoxicity clinical symptoms.

Results

Compared with baseline, the LVGLS, TAPSE, and RVGLS significantly deteriorated after ICI treatment [(–18.63 ± 2.53)% vs. (–17.35 ± 2.58)%, P = 0.000; 18.29 ± 6.23 vs. 14.57 ± 3.81, P = 0.0001; and (–18.45 ± 4.65)% vs. (–14.98 ± 3.85)%, P = 0.0001, respectively]. LVGLS (–17.35 ± 2.58, P = 0.000), TAPSE (14.57 ± 3.81, P = 0.0001), and RVGLS [(–14.98 ± 3.85)%, P = 0.0001] were decreased after ICI immunotherapy. Kaplan-Meier curve analysis showed that LVGLS was more sensitive than the cardiac toxicity events to assess ICI-related subclinical cardiac dysfunction (log-rank P = 0.205). The ROC curve showed that the cutoff value of ΔLVGLS was -13%.

Conclusion

Subclinical cardiac dysfunction can be detected using two-dimensional speckle-tracking imaging. LVGLS, RVGLS, and TAPSE are more sensitive indices for detection.

Clinical trial registration

[https://www.chictr.org.cn/showprojen.aspx?proj=27498], identifier [ChiCTR1800016216].
Radiomic analysis of enhanced CMR cine images predicts left ventricular remodeling after TAVR in patients with symptomatic severe aortic stenosis
Authors: He Wenzhang , Huang He , Chen Xiaoyi , Yu Jianqun , Liu Jing , Li Xue , Yin Hongkun , Zhang Kai , Peng Liqing
Published: December 2022

Objective

This study aimed to develop enhanced cine image-based radiomic models for non-invasive prediction of left ventricular adverse remodeling following transcatheter aortic valve replacement (TAVR) in symptomatic severe aortic stenosis.

Methods

A total of 69 patients (male:female = 37:32, median age: 66 years, range: 47–83 years) were retrospectively recruited, and severe aortic stenosis was confirmed via transthoracic echocardiography detection. The enhanced cine images and clinical variables were collected, and three types of regions of interest (ROIs) containing the left ventricular (LV) myocardium from the short-axis view at the basal, middle, and apical LV levels were manually labeled, respectively. The radiomic features were extracted and further selected by using the least absolute shrinkage and selection operator (LASSO) regression analysis. Clinical variables were also selected through univariate regression analysis. The predictive models using logistic regression classifier were developed and validated through leave-one-out cross-validation. The model performance was evaluated with respect to discrimination, calibration, and clinical usefulness.

Results

Five basal levels, seven middle levels, eight apical level radiomic features, and three clinical factors were finally selected for model development. The radiomic models using features from basal level (Rad I), middle level (Rad II), and apical level (Rad III) had achieved areas under the curve (AUCs) of 0.761, 0.909, and 0.913 in the training dataset and 0.718, 0.836, and 0.845 in the validation dataset, respectively. The performance of these radiomic models was improved after integrating clinical factors, with AUCs of the Combined I, Combined II, and Combined III models increasing to 0.906, 0.956, and 0.959 in the training dataset and 0.784, 0.873, and 0.891 in the validation dataset, respectively. All models showed good calibration, and the decision curve analysis indicated that the Combined III model had a higher net benefit than other models across the majority of threshold probabilities.

Conclusion

Radiomic models and combined models at the mid and apical slices showed outstanding and comparable predictive effectiveness of adverse remodeling for patients with symptomatic severe aortic stenosis after TAVR, and both models were significantly better than the models of basal slice. The cardiac magnetic resonance radiomic analysis might serve as an effective tool for accurately predicting left ventricular adverse remodeling following TAVR in patients with symptomatic severe aortic stenosis.
School dropouts in Spain: A systematic review
Authors: Berral-Ortiz Blanca , Ramos-Navas-Parejo Magdalena , Lara-Lara Fernando , Moreno-Palma Natalia
Published: December 2022

Dropout is a phenomenon that is unfortunately occurring worldwide and is of increasing concern to authorities. It is a reality that quality indicators in many models are affected by the number of students who drop out of school at higher levels. However, this is not only reflected at the educational level, but also affects the social and personal development of young people. The analysis of school dropout among young Spaniards is a topic of interest due to the repercussions it generates in social, personal, and institutional spheres. The objectives of this study were to analyse how many studies have been published on the subject since 2010, locating the selected articles in areas of knowledge and studying the institutions where the research has been carried out. On the other hand, it has been observed how many studies have been focused on the search for the reasons that lead to high dropout rates and the main factors. Finally, an attempt has been made to analyse how many of them are aimed at solving the problem and preventing early school leaving in primary education in order to avoid drop-out at higher levels, by examining the proposals established to reduce the problem. In order to achieve the proposed objectives, a systematic review was carried out with the aim of carrying out a rigorous analysis of the existing and relevant scientific literature on the subject. After applying various exclusion and inclusion criteria, eliminating duplicate records and analysing the works in depth, 28 articles were selected. The results suggest that, currently, despite the problems caused by early school leaving, it is not a subject that has been widely studied and that the main causes are due to educational and social reasons. In the same context, of the articles selected, only 12 present different proposals for the prevention of early school leaving. In the light of the above, it is necessary to look more deeply into the nature of early school leaving in Spanish institutions.
Learners’ satisfaction of courses on Coursera as a massive open online course platform: A case study
Authors: Nguyen Long Quoc
Published: December 2022

Online education has become more prevalent in the 21st century, especially after the COVID-19 pandemic. One of the major trends is the learning via Massive Open Online Courses (MOOCs), which is increasingly present at many universities around the world these days. In these courses, learners interact with the pre-designed materials and study everything mostly by themselves. Therefore, gaining insights into their satisfaction of such courses is vitally important to improve their learning experiences and performances. However, previous studies primarily focused on factors that affected learners’ satisfaction, not on how and what the satisfaction was. Moreover, past research mainly employed the narrative reviews posted on MOOC platforms; very few utilized survey and interview data obtained directly from MOOC users. The present study aims to fill in such gaps by employing a mixed-methods approach including a survey design and semi-structured interviews with the participation of 120 students, who were taking academic writing courses on Coursera (one of the world-leading MOOC platforms), at a private university in Vietnam. Results from both quantitative and qualitative data showed that the overall satisfaction of courses on Coursera was relatively low. Furthermore, most learners were not satisfied with their learning experience on the platform, primarily due to inappropriate assessment, lack of support, and interaction with teachers as well as improper plagiarism check. In addition, there were moderate correlations between students’ satisfaction and their perceived usefulness of Coursera courses. Pedagogically, teachers’ feedback and grading, faster support from course designers as well as easier-to-use plagiarism checking tools are needed to secure learners’ satisfaction of MOOCs.
Osteopontin - The stirring multifunctional regulatory factor in multisystem aging
Authors: Du Yuxiang , Mao Liwei , Wang Zhikun , Yan Kai , Zhang Lingli , Zou Jun
Published: December 2022

Osteopontin (OPN) is a multifunctional noncollagenous matrix phosphoprotein that is expressed both intracellularly and extracellularly in various tissues. As a growth regulatory protein and proinflammatory immunochemokine, OPN is involved in the pathological processes of many diseases. Recent studies have found that OPN is widely involved in the aging processes of multiple organs and tissues, such as T-cell senescence, atherosclerosis, skeletal muscle regeneration, osteoporosis, neurodegenerative changes, hematopoietic stem cell reconstruction, and retinal aging. However, the regulatory roles and mechanisms of OPN in the aging process of different tissues are not uniform, and OPN even has diverse roles in different developmental stages of the same tissue, generating uncertainty for the future study and utilization of OPN. In this review, we will summarize the regulatory role and molecular mechanism of OPN in different tissues and cells, such as the musculoskeletal system, central nervous system, cardiovascular system, liver, and eye, during senescence. We believe that a better understanding of the mechanism of OPN in the aging process will help us develop targeted and comprehensive therapeutic strategies to fight the spread of age-related diseases.
Could VGF and/or its derived peptide act as biomarkers for the diagnosis of neurodegenerative diseases: A systematic review
Authors: Alqarni Saleha , Alsebai Mashael
Published: December 2022

Background

The increasing ageing population has led to an increase in the prevalence of neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). However, as yet, there are no simple biomarkers to predict the onset of such diseases. Recently, VGF and its peptides have been highlighted in neurodegenerative diseases. VGF (non-acronymic) is a polypeptide induced in PC12 cells by neurotrophic factors.

Objective

This systematic review aimed to determine whether VGF and/or its derived peptides can be used as biomarkers for the diagnosis of ALS, PD, and AD with specific attention to (1) the levels of VGF and/or its derived peptides, (2) amyloid-beta, (3) dopamine, and (4) cognitive score.

Methodology

A search was undertaken in the Ovid EMBASE, Cochrane Library, PubMed, Scopus, and Web of Science for observational studies. Publications that assessed the level of VGF and/or its derived peptides among people with neurodegenerative diseases and compared them with healthy people were included. The quality of the included studies was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool.

Result

A search of the databases yielded 834 studies, of which, eight observational studies met the inclusion criteria with a total of 673 participants (51.7% males) aged >18 years. Seven studies showed significant decreases in VGF and its derived peptides in adults with AD, PD, and ALS compared to healthy controls (p<0.05). However, one study showed that there was no significant difference in VGF in AD compared to healthy control(p>0.05). Furthermore, only one study reported that VGF levels were positively correlated with those of tissue dopamine but not with Aβ1-42, and low levels of VGF were associated to cognitive deficits.

Conclusion

The use of VGF and its derivatives for the diagnosis of PD, ALS, AD remains unclear, so further investigation of the role of VGF in neurodegenerative diseases and pathophysiology is needed to provide new insights.
Yield, cell composition, and function of islets isolated from different ages of neonatal pigs
Authors: Arefanian Hossein , Ramji Qahir , Gupta Nancy , Spigelman Aliya F. , Grynoch Donald , MacDonald Patrick E. , Mueller Thomas F. , Gazda Lawrence S. , Rajotte Ray V. , Rayat Gina R.
Published: December 2022

The yield, cell composition, and function of islets isolated from various ages of neonatal pigs were characterized using in vitro and in vivo experimental models. Islets from 7- and 10-day-old pigs showed significantly better function both in vitro and in vivo compared to islets from 3- and 5-day-old pigs however, the islet yield from 10-day-old pigs were significantly less than those obtained from the other pigs. Since islets from 3-day-old pigs were used in our previous studies and islets from 7-day-old pigs reversed diabetes more efficiently than islets from other groups, we further evaluated the function of these islets post-transplantation. B6 rag-/- mouse recipients of various numbers of islets from 7-day-old pigs achieved normoglycemia faster and showed significantly improved response to glucose challenge compared to the recipients of the same numbers of islets from 3-day-old pigs. These results are in line with the findings that islets from 7-day-old pigs showed reduced voltage-dependent K+ (Kv) channel activity and their ability to recover from post-hypoxia/reoxygenation stress. Despite more resident immune cells and immunogenic characteristics detected in islets from 7-day-old pigs compared to islets from 3-day-old pigs, the combination of anti-LFA-1 and anti-CD154 monoclonal antibodies are equally effective at preventing the rejection of islets from both age groups of pigs. Collectively, these results suggest that islets from various ages of neonatal pigs vary in yield, cellular composition, and function. Such parameters may be considered when defining the optimal pancreas donor for islet xenotransplantation studies.
Untargeted metabolomics reveals gender- and age- independent metabolic changes of type 1 diabetes in Chinese children
Authors: Zhang Jianwei , Wu Wei , Huang Ke , Dong Guanping , Chen Xuefeng , Xu Cuifang , Ni Yan , Fu Junfen
Published: December 2022

Introduction

Type 1 diabetes (T1D) is a chronic condition associated with multiple complications that substantially affect both the quality of life and the life-span of children. Untargeted Metabolomics has provided new insights into disease pathogenesis and risk assessment.

Methods

In this study, we characterized the serum metabolic profiles of 76 children with T1D and 65 gender- and age- matched healthy controls using gas chromatography coupled with timeof-flight mass spectrometry. In parallel, we comprehensively evaluated the clinical phenome of T1D patients, including routine blood and urine tests, and concentrations of cytokines, hormones, proteins, and trace elements.

Results

A total of 70 differential metabolites covering 11 metabolic pathways associated with T1D were identified, which were mainly carbohydrates, indoles, unsaturated fatty acids, amino acids, and organic acids. Subgroup analysis revealed that the metabolic changes were consistent among pediatric patients at different ages or gender but were closely associated with the duration of the disease.

Discussion

Carbohydrate metabolism, unsaturated fatty acid biosynthesis, and gut microbial metabolism were identified as distinct metabolic features of pediatric T1D. These metabolic changes were also associated with T1D, which may provide important insights into the pathogenesis of the complications associated with diabetes.
Tele-education model for primary care providers to advance diabetes equity: Findings from Project ECHO Diabetes
Authors: Addala Ananta , Filipp Stephanie L. , Figg Lauren E. , Anez-Zabala Claudia , Lal Rayhan A. , Gurka Matthew J. , Haller Michael J. , Maahs David M. , Walker Ashby F. ,   for the Project ECHO Diabetes Research Team
Published: December 2022

Introduction

In the US, many individuals with diabetes do not have consistent access to endocrinologists and therefore rely on primary care providers (PCPs) for their diabetes management. Project ECHO (Extension for Community Healthcare Outcomes) Diabetes, a tele-education model, was developed to empower PCPs to independently manage diabetes, including education on diabetes technology initiation and use, to bridge disparities in diabetes.

Methods

PCPs (n=116) who participated in Project ECHO Diabetes and completed pre- and post-intervention surveys were included in this analysis. The survey was administered in California and Florida to participating PCPs via REDCap and paper surveys. This survey aimed to evaluate practice demographics, protocols with adult and pediatric T1D management, challenges, resources, and provider knowledge and confidence in diabetes management. Differences and statistical significance in pre- and post-intervention responses were evaluated via McNemar’s tests.

Results

PCPs reported improvement in all domains of diabetes education and management. From baseline, PCPs reported improvement in their confidence to serve as the T1D provider for their community (pre vs post: 43.8% vs 68.8%, p=0.005), manage insulin therapy (pre vs post: 62.8% vs 84.3%, p=0.002), and identify symptoms of diabetes distress (pre vs post: 62.8% vs 84.3%, p=0.002) post-intervention. Compared to pre-intervention, providers reported significant improvement in their confidence in all aspects of diabetes technology including prescribing technology (41.2% vs 68.6%, p=0.001), managing insulin pumps (41.2% vs 68.6%, p=0.001) and hybrid closed loop (10.2% vs 26.5%, p=0.033), and interpreting sensor data (41.2% vs 68.6%, p=0.001) post-intervention.

Discussion

PCPs who participated in Project ECHO Diabetes reported increased confidence in diabetes management, with notable improvement in their ability to prescribe, manage, and troubleshoot diabetes technology. These data support the use of tele-education of PCPs to increase confidence in diabetes technology management as a feasible strategy to advance equity in diabetes management and outcomes.
Association of paternal MTHFR polymorphisms (C677T) with clinical outcomes in ICSI treatment
Authors: Wan Yangyang , Liu Wenjing , Xu Bo , Jiang Xiaohua , Hua Juan
Published: December 2022

Purpose

This study aims to investigate the association between paternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T) and embryonic development, pregnancy, and neonatal outcomes in intracytoplasmic sperm injection (ICSI) treatment.

Methods

A total of 191 infertile men undergoing ICSI treatment at the Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, were recruited between January 2020 and June 2021. The MTHFR C677T polymorphism genotyping was evaluated in these male patients, and they were stratified into three groups according to genotyping results: Control (CC), heterozygote mutated (CT), and mutated homozygote (TT). In addition, we conducted a comparative analysis of embryonic development, pregnancy, and neonatal outcomes among these three groups.

Results

The embryonic development (including normal fertilization rate (80.14% vs. 83.06% vs. 85.10%; p = 0.37), high-quality embryo rate (45.26% vs. 43.69% vs. 46.04%; p = 0.72), blastocyst formation rate (42.47% vs. 43.18% vs. 39.38%; p = 0.62), implantation rate (42.47% vs. 36.25% vs. 41.22%; p = 0.62), and clinical pregnancy rate (64.71% vs. 58.75% vs. 66.67%; p = 0.59) were not comparable among these three groups. Moreover, no significant difference was observed in terms of pregnancy outcomes (including miscarriage rate (24.24% vs. 12.77% vs. 22.5%; p = 0.35) and live birth rate (49.02% vs. 51.25% vs. 51.66%; p = 0.96)). Additionally, no marked difference was observed in terms of neonatal outcome (including, preterm delivery rate (24% vs. 14.63% vs. 9.67%; p = 0.35), birth height (p = 0.75), birth weight (p = 0.35), neonatal sex (p = 0.48), gestational age at delivery (p = 0.24), Apgar score (p = 0.34), and birth defects (0% vs. 2% vs. 9%; p = 0.23) among the study groups.

Conclusion

The paternal MTHFR C677T polymorphism is not associated with embryo quality, pregnancy, or neonatal outcomes in ICSI treatment. Therefore, in our population, MTHFR polymorphisms do not provide helpful information in explaining ICSI failure.
The evolution of monogamy in cichlids and marine reef fishes
Authors: Stanbrook Emily , Fitzpatrick John L. , Balshine Sigal , Shultz Susanne
Published: December 2022

Although several hypotheses have been proposed to explain the emergence of social monogamy, its origin is still intensely debated. Monogamy has many potential drivers, but evolutionary causality among them remains unclear. Using phylogenetic comparative methods within a Bayesian framework we explored the evolution of monogamy in cichlids and in marine reef fishes because, while both groups are characterised by unusually high incidence of social monogamy, they face very different ecological challenges. For each group, we examined four classic hypotheses that explain the evolution of monogamy: female dispersal, male mate guarding, female–female intolerance, and the biparental care hypotheses. We also explored whether the ecological traits of diet and shelter use are evolutionarily coupled with these hypotheses or with monogamy. First, we found that the evolution of monogamy was predicted by male territoriality in cichlids and simultaneous male and female territoriality in marine reef fishes. We suggest that these results provide support for the male mate guarding hypothesis in cichlids and female–female intolerance hypothesis in marine reef fishes. Second, we demonstrate clear evidence against the biparental care hypothesis, as biparental care was a consequence, not a cause, of monogamy in our analyses. Third, as female dispersal drove the loss of monogamy in both cichlids and marine reef fishes, this suggests the female dispersal hypothesis is not driving the evolution of monogamy in either group. These findings in two highly-monogamous fish taxa largely support prior findings from primate and bird comparative studies and provide novel large-scale evidence for a link between mate guarding and the evolution of monogamy.
Evolutionary history of Nasutitermes kemneri (Termitidae, Nasutitermitinae), a termite from the South American diagonal of open formations
Authors: Kohari Karolina S. , Palma-Onetto Valeria , Scheffrahn Rudolf H. , Vasconcellos Alexandre , Cancello Eliana M. , Santos Rafaella G. , Carrijo Tiago F.
Published: December 2022

Little is known about the phylogeography of termites in the Neotropical region. Here, we explored the genetic patterns and phylogeographical processes in the evolutionary history ofNasutitermes kemneri,an endemic termite of the South American diagonal of open formations (DOF) formed by the Chaco, Cerrado, and Caatinga phytogeographic domains. We sampled 60 individuals across the three domains of the DOF, and using the mitochondrial genes 16S, COI, and COII, as well as the nuclear gene ITS, evaluated the genetic diversity and divergence time of the populations, along with their genetic structure. The results show a strong genetic and spatial structure within the samples, evidencing the existence of two well-differentiated genetic groups: the Northeastern and the Southwestern populations, which diverged about 2.5 Mya, during the Pliocene-Pleistocene boundary. The Northeastern population, which encompasses Caatinga and northern portions of Cerrado, has an intricate structure and seems to have suffered repetitive retraction-expansion events due to climactic fluctuations during the Quaternary. The Southwestern population, which ranges from central-south Cerrado to the northeast peripherical portions of the Chaco, displays a star-shaped haplotype structure, indicating that this region may have acted as a refugia during interglacial periods.
GSC-MIM: Global semantic integrated self-distilled complementary masked image model for remote sensing images scene classification
Authors: Wang Xuying , Zhang Yunsheng , Zhang Zhaoyang , Luo Qinyao , Yang Jingfan
Published: December 2022

Masked image modeling (MIM) is a learning method in which the unmasked components of the input are utilized to learn and predict the masked signal, enabling learning from large amounts of unannotated data. However, due to the scale diversity and complexity of features in remote sensing images (RSIs), existing MIMs face two challenges in the RSI scene classification task: (1) If the critical local patches of small-scale objects are randomly masked out, the model will be unable to learn its representation. (2) The reconstruction of MIM relies on the visible local contextual information surrounding the masked regions and overemphasizing this local information will potentially lead the model to disregard the global semantic information of the input RSI. Regarding the above considerations, we proposed a global semantic integrated self-distilled complementary masked image model (GSC-MIM) for RSI scene classification. To prevent information loss, we proposed an information-preserved complementary masking strategy (IPC-Masking), which generates two complementary masked views for the same image to resolve the problem of masking critical areas of small-scale objects. To incorporate global information into the MIM pre-training process, we proposed the global semantic distillation strategy (GSD). Specifically, we introduced an auxiliary network pipeline to extract the global semantic information from the full input RSI and transfer the knowledge to the MIM by self-distillation. The proposed GSC-MIM is validated on three publicly available datasets of AID, NWPU-RESISC45, and UC-Merced Land Use, and the results show that the proposed method's Top-1 accuracy surpasses the baseline approaches in three datasets by up to 4.01, 3.87, and 5.26%, respectively.
Evaluating drivers of female dominance in the spotted hyena
Authors: McCormick S. Kevin , Laubach Zachary M. , Strauss Eli D. , Montgomery Tracy M. , Holekamp Kay E.
Published: December 2022

Introduction

Dominance relationships in which females dominate males are rare among mammals. Mechanistic hypotheses explaining the occurrence of female dominance suggest that females dominate males because (1) they are intrinsically more aggressive or less submissive than males, and/or (2) they have access to more social support than males.

Methods

Here, we examine the determinants of female dominance across ontogenetic development in spotted hyenas (Crocuta crocuta) using 30 years of detailed behavioral observations from the Mara Hyena Project to evaluate these two hypotheses.

Results

Among adult hyenas, we find that females spontaneously aggress at higher rates than males, whereas males spontaneously submit at higher rates than females. Once an aggressive interaction has been initiated, adult females are more likely than immigrant males to elicit submission from members of the opposite sex, and both adult natal and immigrant males are more likely than adult females to offer submission in response to an aggressive act. We also find that adult male aggressors are more likely to receive social support than are adult female aggressors, and that both adult natal and immigrant males are 2–3 times more likely to receive support when attacking a female than when attacking another male. Across all age classes, females are more likely than males to be targets of aggressive acts that occur with support. Further, receiving social support does slightly help immigrant males elicit submission from adult females compared to immigrant males acting alone, and it also helps females elicit submission from other females. However, adult females can dominate immigrant males with or without support far more often than immigrant males can dominate females, even when the immigrants are supported against females.

Discussion

Overall, we find evidence for both mechanisms hypothesized to mediate female dominance in this species: (1) male and female hyenas clearly differ in their aggressive and submissive tendencies, and (2) realized social support plays an important role in shaping dominance relationships within a clan. Nevertheless, our results suggest that social support alone cannot explain sex-biased dominance in spotted hyenas. Although realized social support can certainly influence fight outcomes among females, adult females can easily dominate immigrant males without any support at all.
CHI3L1 enhances melanoma lung metastasis via regulation of T cell co-stimulators and CTLA-4/B7 axis
Authors: Ma Bing , Kamle Suchitra , Akosman Bedia , Khan Hina , Lee Chang-Min , Lee Chun Geun , Elias Jack A.
Published: December 2022

ICOS/ICOSL and CD28/B7-1/B7-2 are T cell co-stimulators and CTLA-4 is an immune checkpoint inhibitor that play critical roles in the pathogenesis of neoplasia. Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it portends a poor prognosis and contributes to tumor metastasis. Here we demonstrate that CHI3L1 inhibits the expression of ICOS, ICOSL and CD28 while stimulating CTLA-4 and the B7 moieties in melanoma lung metastasis. We also demonstrate that RIG-like helicase innate immune activation augments T cell co-stimulation, inhibits CTLA-4 and suppresses pulmonary metastasis. At least additive antitumor responses were seen in melanoma lung metastasis treated with anti-CTLA-4 and anti-CHI3L1 antibodies in combination. Synergistic cytotoxic T cell-induced tumor cell death and the heightened induction of the tumor suppressor PTEN were seen in co-cultures of T and tumor cells treated with bispecific antibodies that target both CHI3L1 and CTLA-4. Thus, CHI3L1 contributes to pulmonary metastasis by inhibiting T cell co-stimulation and stimulating CTLA-4. The simultaneous targeting of CHI3L1 and the CTLA-4 axis with individual and, more powerfully with bispecific antibodies, represent promising therapeutic strategies for pulmonary metastasis.
CCR7/dendritic cell axis mediates early bacterial dissemination in Orientia tsutsugamushi-infected mice
Authors: Liang Yuejin , Wang Hui , Gonzales Casey , Thiriot Joseph , Sunyakumthorn Piyanate , Melby Peter C. , Sun Jiaren , Soong Lynn
Published: December 2022

Scrub typhus is a life-threatening zoonosis caused by the obligate intracellular bacterium Orientia tsutsugamushi (Ot) that is transmitted by the infected larvae of trombiculid mites. However, the mechanism by which Ot disseminates from the bite site to visceral organs remains unclear; host innate immunity against bacterial dissemination and replication during early infection is poorly understood. In this study, by using an intradermal infection mouse model and fluorescent probe-labeled Ot, we assessed the dynamic pattern of innate immune cell responses at the inoculation site. We found that neutrophils were the first responders to Ot infection and migrated into the skin for bacterial uptake. Ot infection greatly induced neutrophil activation, and Ot-neutrophil interaction remarkably promoted cell death both in vitro and in vivo. Depletion of neutrophils did not alter bacterial dissemination in mice, as evidenced by similar bacterial burdens in the skin and draining lymph nodes (dLN) at day 3, as well as in the lungs and brains at day 14, as compared to the control mice. Instead, dendritic cells (DCs) and macrophages played a role as a Trojan horse and transmitted Ot from the skin into dLN. Importantly, the absence of homing receptor CCR7 or neutralization of its ligand, CCL21, significantly impaired DC migration, resulting in reduced bacterial burdens in dLN. Taken together, our study sheds light on a CCR7/dendritic cell-mediated mechanism of early Ot dissemination and provides new insights into therapeutic and vaccine development strategies for scrub typhus.