bluuebunny/crossref_metadata_2025 huggingface dataset:
Türk Devletleri Teşkilatı Ülkelerinin Yurtdışında Yerleşik Yaşayan Vatandaşlarına Yönelik Uygulamalarının Analizi
Authors: TOKMAK Ahmet , KARA İlyas
Published: April 2023

Tarih boyunca çeşitli sebeplerle yaşadıkları coğrafyalardan ayrılarak farklı ülkelerde diaspora oluşturan Türkler bugün 20 milyon kişilik potansiyeli ile siyasi, toplumsal ve ekonomik olarak önemli bir güç haline gelmişlerdir. Günümüzde ise var olan siyasi sınırlar ve ulus devletlerin inşa sürecinin tamamlanması göç gerçeğini farklı bir boyuta taşımıştır. Yaşanan savaşlar, ülke içinde gerçekleşen karmaşa ortamı, salgın hastalıklar, ekonomik faktörler vb. sebeplerle gerçekleşmeye devam eden göçler diasporalara yönelik yürütülecek faaliyetlerin önemini her geçen gün daha da arttırmaktadır. Bu kapsamda Türk Devletleri Teşkilatı Türk dünyası ülkelerinin potansiyellerini ortaya çıkarması açısından stratejik bir kurum olarak varlığını sürdürmektedir. Tarihsel arka planlarına bakıldığında Türk Devletleri Teşkilatı üye ülkelerinin bağımsızlık süreçlerinin acılı ve sancılı süreci bağımsızlıklarıyla birlikte vatandaşlık bilincinin geliştirilmesi konusunda özel bir farkındalık ortaya çıkarmıştır. Bu farkındalık günümüzde üye ülkelerin soydaşlarına yönelik politikalarına ve faaliyetlerine etki etmektedir. Bu çalışmada Türk Devletleri Teşkilatı üye ülkeleri olan Türkiye, Azerbaycan, Kırgızistan, Kazakistan ve Özbekistan devletlerinin diasporalarına ilişkin politikaları genel yapı ve işleyiş açısından ele alınmaya çalışılmıştır. Nitel bir araştırma olarak yürütülen bu çalışmanın verileri ilgili ülkelerin resmi iletişim ağlarında servis edilen haberlerden seçilmiştir. Çalışma sonuçlarına göre Türk dünyasında tek milletin birden fazla diasporası olmaz anlayışının her geçen gün güç kazandığı ve bu durumun ülkelerin diaspora politikalarına yön verdiği belirlenmiştir.
Kırgızistan’da Din Eğitimi ve Din(i) Eğitim Modelleri
Authors: AĞGÜN Kadri
Published: April 2023

Bağımsızlıkla birlikte Kırgızistan Cumhuriyeti’nde Yüksek Konsey tarafından 16 Aralık 1991 tarihinde yasal anlamda düzenleme adına “Vicdan Özgürlüğü ve Dini Kuruluşlar Kanunu” kabul edilerek Kırgızistan vatandaşlarının hangi dini inançtan olursa olsun din alanındaki hak ve özgürlükleri devlet güvencesi altına alındı. Bu durum 1993 yılında kabul edilen Anayasa ile ve bunun 2007 yılındaki referandumla değiştirilmiş olan yeni şekli, din-devlet ilişkilerinde laiklik anlayışını getirmiştir. Dini özgürlükler yasal güvence altına alınmıştır. Din alanındaki yasal çerçeveye insan hakları ile ilgili “İnsan Hakları Evrensel Beyannamesi’’ başta olmak üzere, Avrupa parlamentosunun insan haklarıyla ilgili kararları, Sivil ve Siyasi Haklarla İlgili Uluslararası Paktı ve Avrupa Güvenlik ve İşbirliği Teşkilatı gibi çok sayıda uluslararası kurumlarla yapılan anlaşmalar da katkı sağlamıştır. Kırgızistan dini eğitiminin ve din eğitimi meselelerinin kapsamlı iyileştirme çabaları göze çarpmaktadır. Bu çalışmada nitel araştırma yöntemleri kullanılarak Kırgızistan’da din eğitim ve öğretiminin tarihi süreci, gelişimi ve güncel durumu incelenmiştir
Aneurisma de aorta abdominal: fisiopatologia, farmacoterapia e atenção farmacêutica
Authors: Cardoso Felipe Lima , Toledo Carlos Augusto Barbosa , Fróes Yuri Nascimento
Published: April 2023

Ο presente trabalho aborda sobre o diagnóstico e terapias medicamentosas para o Aneurisma de Aorta Abdominal (AAA) cοmο fοrma de levantar discussões sοbre a segurança de pacientes acometidos pela doença ou ao diagnóstico precoce de AAA. É observado que a morbidade de AAA está relacionada a falta de cuidados ou a negligência no rastreamento de saúde (exames de imagem) e complicações farmacológicas. Para rastrear métodos diagnóstico e tratamento mais atuais contra o AAA, realizamos uma revisão de literatura integrativa. Selecionamos аrtigοs publicаdοs nο períοdο entre 2017 e 2021 nas bаses de dаdοs Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), MEDLINE, PUBMED e Scientific Electronic Library Online (SciELΟ). Foram encontrados 11 аrtigοs, οs quais, após utilizadοs οs critériοs de inclusão e exclusãο, restaram 09 artigοs seleciοnаdοs pаrа аnálise dοs resultаdοs. Foi pοssível observar que ο diagnósticο precοce e ο acοmpanhamentο ultrassοnοgráficο dο crescimentο dο sacο aneurismáticο de pacientes cοm AAA é importante para redução da mortalidade, principalmente em idosos, onde o rompimento pode acontecer ao acaso. O AAA é mais prevalente do que o Aneurisma de Aorta Torácica e a descoberta destas doenças cardiovasculares está relacionada com o desenvolvimento de tecnologias de observação por imagem (imagenologia). Intervenções cirúrgicas podem ser realizadas, como a introdução de Stent ou correção endovascular. As terapias medicamentosas mais utilizadas para profilaxia de complicações de AAA, mas não para redução do tamanho do aneurisma. Entre os medicamentos utilizados, pode-se citar as estatinas para redução da inflamação arterial e hipolipidêmica, os Antiagregante plaquetários para melhoria da fluidez do sangue e manutenção de Stent, corticoides (proteção inflamatória), betabloqueadores para redução da contratilidade cardíaca e redução do risco de hemorragia interna. Ratificamos que não há evidências científicas que terapias medicamentosas auxiliem na redução do tamanho do AAA. O rastreamento precoce, utilização de medidas corretivas, adesão ao tratamento farmacológico e monitoramento do aneurisma reduzem a mortalidade e promovem segurança ao paciente.
Survival of an Indian Ocean humpback dolphin Sousa plumbea in the wild despite chronic osteologic pathologies
Authors: Lingham-Soliar T , Bloodgood J , Rothschild B , Bouveroux T
Published: April 2023

Skeletal examination of a female adult Indian Ocean humpback dolphin Sousa plumbea from South Africa suggested a chronic disease process. It manifested as erosions and pitting of the atlanto-occipital articulation as well as circumferential hyperostosis and ankylosis of some of the caudal vertebrae, findings rarely recorded together in the same animal. The character of the erosive process and vertebral fusion appeared chronic, and further findings of underdevelopment of the fluke, sternum and left humerus with remodeling of the periarticular region of the left scapula may support initiation of the process early in life. Because such chronic pathology would have affected the individual’s locomotion and foraging abilities, we also postulate how this individual survived until its demise in a human-derived environmental hazard. Ecological and socio-behavioral aspects observed in S. plumbea, including habitat preference for inshore and shallow waters, small social group aggregations and feeding cooperation, may have contributed to its ability to survive.
The laws and effects of terahertz wave interactions with neurons
Authors: Shaoqing Ma , Zhiwei Li , Shixiang Gong , Chengbiao Lu , Xiaoli Li , Yingwei Li
Published: April 2023

Introduction: Terahertz waves lie within the energy range of hydrogen bonding and van der Waals forces. They can couple directly with proteins to excite non-linear resonance effects in proteins, and thus affect the structure of neurons. However, it remains unclear which terahertz radiation protocols modulate the structure of neurons. Furthermore, guidelines and methods for selecting terahertz radiation parameters are lacking.

Methods: In this study, the propagation and thermal effects of 0.3–3 THz wave interactions with neurons were modelled, and the field strength and temperature variations were used as evaluation criteria. On this basis, we experimentally investigated the effects of cumulative radiation from terahertz waves on neuron structure.

Results: The results show that the frequency and power of terahertz waves are the main factors influencing field strength and temperature in neurons, and that there is a positive correlation between them. Appropriate reductions in radiation power can mitigate the rise in temperature in the neurons, and can also be used in the form of pulsed waves, limiting the duration of a single radiation to the millisecond level. Short bursts of cumulative radiation can also be used. Broadband trace terahertz (0.1–2 THz, maximum radiated power 100 μW) with short duration cumulative radiation (3 min/day, 3 days) does not cause neuronal death. This radiation protocol can also promote the growth of neuronal cytosomes and protrusions.

Discussion: This paper provides guidelines and methods for terahertz radiation parameter selection in the study of terahertz neurobiological effects. Additionally, it verifies that the short-duration cumulative radiation can modulate the structure of neurons.
Adipose tissue expansion in obesity, health, and disease
Authors: White Ursula
Published: April 2023

White adipose tissue (WAT) expands under physiological conditions via an increase in adipocyte size (hypertrophy) and/or number (hyperplasia; adipogenesis), and the ability of WAT to expand to accommodate energy demands is a significant determinant of metabolic health status. Obesity is associated with impaired WAT expansion and remodeling, which results in the deposition of lipids to other non-adipose organs, leading to metabolic derangements. Although increased hyperplasia has been implicated as a cornerstone in promoting healthy WAT expansion, recent developments suggest that the role of adipogenesis as a contributing factor in the transition from impaired subcutaneous WAT expansion to impaired metabolic health remains up for debate. This mini-review will summarize recent developments and highlight emerging concepts on the features of WAT expansion and turnover, and the significance in obesity, health, and disease.
Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques
Authors: Ali Sadaqat , Noreen Asifa , Qamar Adeem , Zafar Imran , Ain Quratul , Nafidi Hiba-Allah , Bin Jardan Yousef A. , Bourhia Mohammed , Rashid Summya , Sharma Rohit
Published: April 2023

Cancer is a primary global health concern, and researchers seek innovative approaches to combat the disease. Clinical bioinformatics and high-throughput proteomics technologies provide powerful tools to explore cancer biology. Medicinal plants are considered effective therapeutic agents, and computer-aided drug design (CAAD) is used to identify novel drug candidates from plant extracts. The tumour suppressor protein TP53 is an attractive target for drug development, given its crucial role in cancer pathogenesis. This study used a dried extract of Amomum subulatum seeds to identify phytocompounds targeting TP53 in cancer. We apply qualitative tests to determine its phytochemicals (Alkaloid, Tannin, Saponin, Phlobatinin, and Cardic glycoside), and found that alkaloid composed of 9.4% ± 0.04% and Saponin 1.9% ± 0.05% crude chemical constituent. In the results of DPPH Analysis Amomum subulatum Seeds founded antioxidant activity, and then we verified via observing methanol extract (79.82%), BHT (81.73%), and n-hexane extract (51.31%) found to be positive. For Inhibition of oxidation, we observe BHT is 90.25%, and Methanol (83.42%) has the most significant proportion of linoleic acid oxidation suppression. We used diverse bioinformatics approaches to evaluate the effect of A. subulatum seeds and their natural components on TP53. Compound-1 had the best pharmacophore match value (53.92), with others ranging from 50.75 to 53.92. Our docking result shows the top three natural compounds had the highest binding energies (−11.10 to −10.3 kcal/mol). The highest binding energies (−10.9 to −9.2 kcal/mol) compound bonded to significant sections in the target protein’s active domains with TP53. Based on virtual screening, we select top phytocompounds for targets which highly fit based on pharmacophore score and observe these compounds exhibited potent antioxidant activity and inhibited cancer cell inflammation in the TP53 pathway. Molecular Dynamics (MD) simulations indicated that the ligand was bound to the protein with some significant conformational changes in the protein structure. This study provides novel insights into the development of innovative drugs for the treatment of cancer disorders.
Lactobacillus rhamnosus GG ameliorates noise-induced cognitive deficits and systemic inflammation in rats by modulating the gut-brain axis
Authors: Li Xiaofang , Zheng Pengfang , Cao Wa , Cao Yang , She Xiaojun , Yang Honglian , Ma Kefeng , Wu Fangshan , Gao Xiujie , Fu Yu , Yin Jiayi , Wei Fei , Jiang Shoufang , Cui Bo
Published: April 2023

Background

Environmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats.

Methods

Learning and memory were assessed using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms.

Results

The results indicated that Lactobacillus rhamnosus GG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited the growth of harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFA levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by Lactobacillus rhamnosus GG intervention.

Conclusion

Taken together, Lactobacillus rhamnosus GG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.
The buzz in the field: the interaction between viruses, mosquitoes, and metabolism
Authors: Ratnayake Oshani C. , Chotiwan Nunya , Saavedra-Rodriguez Karla , Perera Rushika
Published: April 2023

Among many medically important pathogens, arboviruses like dengue, Zika and chikungunya cause severe health and economic burdens especially in developing countries. These viruses are primarily vectored by mosquitoes. Having surmounted geographical barriers and threat of control strategies, these vectors continue to conquer many areas of the globe exposing more than half of the world’s population to these viruses. Unfortunately, no medical interventions have been capable so far to produce successful vaccines or antivirals against many of these viruses. Thus, vector control remains the fundamental strategy to prevent disease transmission. The long-established understanding regarding the replication of these viruses is that they reshape both human and mosquito host cellular membranes upon infection for their replicative benefit. This leads to or is a result of significant alterations in lipid metabolism. Metabolism involves complex chemical reactions in the body that are essential for general physiological functions and survival of an organism. Finely tuned metabolic homeostases are maintained in healthy organisms. However, a simple stimulus like a viral infection can alter this homeostatic landscape driving considerable phenotypic change. Better comprehension of these mechanisms can serve as innovative control strategies against these vectors and viruses. Here, we review the metabolic basis of fundamental mosquito biology and virus-vector interactions. The cited work provides compelling evidence that targeting metabolism can be a paradigm shift and provide potent tools for vector control as well as tools to answer many unresolved questions and gaps in the field of arbovirology.
Emblematics and metaphor: theoretical facets and hermeneutic issues
Authors: Borgogni Daniele
Published: April 2023

The article focuses on Renaissance emblematics and its privileged relationship with metaphor, considered in the light of contemporary theories as an inherently tensional form, steeped in interchange and transition and heavily relying on a basically conflictual dynamic. Though often dismissed as an academic, antiquarian form of figurality or as a pleasing symbolical form steeped in monologic stability, emblematics was in fact conceived as a brand-new hybrid textual mode whose complex interplay of signs favored multiplied discursive models and the constant relay between visual and textual elements, between abstract conceptualization and thoughts-made-visible. The paper, in other words, will try to reassess and re-evaluate emblematics as a profoundly plural form of communication whose connections with metaphor were much deeper and qualitatively different than it is usually thought. This slant approach to what is conventionally considered a tame example of early modern textuality highlights, on the contrary, its idiosyncratic meaning procedures: the metaphorical conceptualizations of emblematic compositions were not necessarily based on similarity and testify to their cognitive potential which ushered in an idea of communication as projective and dislocating, as a dialogic space allowing for the paradoxical copresence of ideological consistency and its deconstruction.
Mammalian dental diversity: an evolutionary template for regenerative dentistry
Authors: Popowics Tracy , Mulimani Priti
Published: April 2023

The discovery of odontogenic mechanisms essential for regenerating dental tissues and eventually developing a biomimetic artificial whole tooth for replacement is an ongoing aspiration for dental clinicians and researchers. Studying the diversity, development and evolutionary changes of mammalian dentitions can provide key insights into the mechanisms of odontogenesis that can be harnessed for regenerative dental medicine. A myriad of influences is expected to have shaped the dentitions of mammals and our objective is to highlight the contributions of phylogeny, functional adaptation, and development to tooth shape. Innovations in tooth shape analysis will be discussed, such as in imaging methodologies and quantitative comparisons, molecular biology approaches to phylogeny and the ontogenetic basis of tooth form. Study of the inter- and intra-species differences in tooth form as well as dental anomalies has provided clues toward the mechanisms of evolutionary change in dental form. Thus, phenotypic variation in tooth shape will also be discussed, including the role of development in creating tooth shape differences that evolutionary selection pressures may act upon. Functional adaptations have occurred in the context of the phylogenetic signal of primitive mammals, and predecessors to each phylogenetic branch, and examples will be discussed within members of the Order Carnivora, the Superfamily Suoidea and the Order Primates. The comparative study of mammalian tooth shape holds the potential to inform dental research areas, such as etiopathogeneses of dental variation and tooth shape anomalies, molecular mechanisms of tooth development and functional issues. Ultimately, insights from these research areas can be potentially translated for futuristic clinical applications like regeneration of various tooth tissue layers and eventually full tooth replacement.
Effect of adipokine and ghrelin levels on BMD and fracture risk: an updated systematic review and meta-analysis
Authors: Lee Seoyul , Kim Jeong Hun , Jeon Yun Kyung , Lee Jung Sub , Kim Keunyoung , Hwang Sun-Kyung , Kim Jae Ho , Goh Tae Sik , Kim Yun Hak
Published: April 2023

Context

Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed.

Objective

This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis.

Data sources

Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed.

Study selection

We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status.

Data extraction

We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies.

Data synthesis

A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18).

Conclusions

Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
Case report: A novel mutation of RecQ-like helicase 5 in a Chinese family with early myocardial infarction, coronary artery disease, and stroke hemiplegia
Authors: Tang Yi , Wang Qian , Zhang Wei-Kai , Liu Yu-Xing , Zheng Zhao-Fen , Fan Liang-Liang , Liu Lv , He Jin
Published: April 2023

Background: Myocardial infarction (MI) is a type of severe coronary artery disease (CAD) that can lead to heart failure and sudden cardiac death. The prevalence of heart failure globally is estimated at 1%–2%, of which ∼60% of cases are the consequence of MI as the primary cause. At present, several disease-causing genes have been identified that may be responsible for MI, such as autophagy-related 16-like 1 (ATG16L1) and RecQ-like helicase 5 (RECQL5).

Methods: In this study, we enrolled a Chinese family with MI, CAD, and stroke hemiplegia. Whole-exome sequencing was applied to analyze the genetic lesion of the proband. Sanger sequencing was used to validate the candidate mutation in five family members and 200 local control cohorts.

Results: After data filtering, we detected a novel mutation (NM_004259: c.1247T>C/p.I416T) of RECQL5 in the proband. Sanger sequencing further validated that the novel mutation was existent in the affected individuals, including the proband’s younger sister and her mother, and absent in the other healthy family members and 200 local control cohorts. Furthermore, bioinformatics analysis confirmed that the novel mutation, located in a highly evolutionarily conserved site, was predicted to be deleterious and may change the hydrophobic surface area and aliphatic index of RECQL5.

Conclusion: Here, we report the second mutation (NM_004259: c.1247T>C/p.I416T) of RECQL5 underlying MI and CAD by whole-exome sequencing. Our study expanded the spectrum of RECQL5 mutations and contributed to genetic diagnosis and counseling of MI and CAD.
Compound heterozygous FAM20C gene variants in a patient with severe Raine syndrome: a case report
Authors: Chirteș Camelia , Bogliș Alina , Toth Andrea , Rac Corina , Bănescu Claudia
Published: April 2023

Raine syndrome is a congenital disorder caused by biallelic mutations in the FAM20C gene. While most diagnosed cases of the syndrome are lethal in the first few months of life, there are also reports of non-lethal cases with Raine syndrome. The characteristic of this syndrome is typical facial dysmorphism and generalized osteosclerosis, as well as possible intracranial calcification, hearing loss, and seizures. We report a case of a 4-day-old patient at the time of examination, born with a distinct facial dysmorphism, short neck, narrow chest, and curved tibia. The parents, affirmative gypsy and non-consanguineous, had a previous male child born with the same phenotype who died at 4 months old. The computed tomography scan revealed choanal atresia, while transfontanelar ultrasound showed hypoplasia of the frontal and temporal lobes, corpus callosum dysgenesis, and multiple areas of intracranial hyperechogenicity. The chest X-Ray revealed generalized increased bone density. A skeletal disorders gene panel was performed which identified two variants in the FAM20C gene: a pathogenic variant c.1291C>T (p.Gln431*) and a likely pathogenic variant (c.1135G>A) (p.Gly379Arg), confirming the clinical diagnosis. The parents were also tested, and each was found to carry one of the variants. The particularity of this case is the severe phenotype in a compound heterozygous case that consists of FAM20C c.1291C>T (p.Gln431*) variant that has recently been reported in the literature. Also, our case is one of the few compound-heterozygous mutations in the FAM20C gene that has been described in a non-consanguineous marriage.
Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse
Authors: Zhao Meng , Zhou Jingxin , Tang Yihu , Liu Mingzhu , Dai Yawei , Xie Hui , Wang Zihao , Chen Liang , Wu Yanhu
Published: April 2023

Objectives

We investigated the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of mitral valve prolapse (MVP).

Methods

For RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from five patients with MVP, with or without chordae tendineae rupture, and five healthy individuals. High-throughput sequencing was used for RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) analysis, alternative splicing (AS) analysis, functional enrichment analysis, co-expression of RBPs, and alternative splicing events (ASEs) analysis were conducted.

Results

The MVP patients exhibited 306 up-regulated genes and 198 down-regulated genes. All down- and up-regulated genes were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested. We identified 13 RNA-binding proteins (RBPs) from the DEGs and screened out four RBPs (ZFP36, HSPA1A, TRIM21, and P2RX7). We selected four RASEs based on the co-expression analyses of RBPs and RASEs, including exon skipping (ES) of DEDD2, alternative 3′ splice site (A3SS) of ETV6, mutually exclusive 3′UTRs (3pMXE) of TNFAIP8L2, and A3SS of HLA-B. Furthermore, the selected four RBPs and four RASEs were validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and showed high consistency with RNA sequencing (RNA-seq).

Conclusion

Dysregulated RBPs and their associated RASEs may play regulatory roles in MVP development and may therefore be used as therapeutic targets in the future.
Mesenchymal stem cell-derived exosomes for treatment of sepsis
Authors: Homma Kento , Bazhanov Nikolay , Hashimoto Kazuki , Shimizu Masaru , Heathman Thomas , Hao Qi , Nawgiri Ranjana , Muthukumarana Vidarshi , Lee Jae Woo , Prough Donald S. , Enkhbaatar Perenlei
Published: April 2023

Introduction

The pathogenesis of sepsis is an imbalance between pro-inflammatory and anti-inflammatory responses. At the onset of sepsis, the lungs are severely affected, and the injury progresses to acute respiratory distress syndrome (ARDS), with a mortality rate of up to 40%. Currently, there is no effective treatment for sepsis. Cellular therapies using mesenchymal stem cells (MSCs) have been initiated in clinical trials for both ARDS and sepsis based on a wealth of pre-clinical data. However, there remains concern that MSCs may pose a tumor risk when administered to patients. Recent pre-clinical studies have demonstrated the beneficial effects of MSC-derived extracellular vesicles (EVs) for the treatment of acute lung injury (ALI) and sepsis.

Methods

After recovery of initial surgical preparation, pneumonia/sepsis was induced in 14 adult female sheep by the instillation of Pseudomonas aeruginosa (~1.0×1011 CFU) into the lungs by bronchoscope under anesthesia and analgesia. After the injury, sheep were mechanically ventilated and continuously monitored for 24 h in a conscious state in an ICU setting. After the injury, sheep were randomly allocated into two groups: Control, septic sheep treated with vehicle, n=7; and Treatment, septic sheep treated with MSC-EVs, n=7. MSC-EVs infusions (4ml) were given intravenously one hour after the injury.

Results

The infusion of MSCs-EVs was well tolerated without adverse events. PaO2/FiO2 ratio in the treatment group tended to be higher than the control from 6 to 21 h after the lung injury, with no significant differences between the groups. No significant differences were found between the two groups in other pulmonary functions. Although vasopressor requirement in the treatment group tended to be lower than in the control, the net fluid balance was similarly increased in both groups as the severity of sepsis progressed. The variables reflecting microvascular hyperpermeability were comparable in both groups.

Conclusion

We have previously demonstrated the beneficial effects of bone marrow-derived MSCs (10×106 cells/kg) in the same model of sepsis. However, despite some improvement in pulmonary gas exchange, the present study demonstrated that EVs isolated from the same amount of bone marrow-derived MSCs failed to attenuate the severity of multiorgan dysfunctions.
The role of tumor metabolism in modulating T-Cell activity and in optimizing immunotherapy
Authors: Ganjoo Shonik , Gupta Priti , Corbali Halil Ibrahim , Nanez Selene , Riad Thomas S. , Duong Lisa K. , Barsoumian Hampartsoum B. , Masrorpour Fatemeh , Jiang Hong , Welsh James W. , Cortez Maria Angelica
Published: April 2023

Immunotherapy has revolutionized cancer treatment and revitalized efforts to harness the power of the immune system to combat a variety of cancer types more effectively. However, low clinical response rates and differences in outcomes due to variations in the immune landscape among patients with cancer continue to be major limitations to immunotherapy. Recent efforts to improve responses to immunotherapy have focused on targeting cellular metabolism, as the metabolic characteristics of cancer cells can directly influence the activity and metabolism of immune cells, particularly T cells. Although the metabolic pathways of various cancer cells and T cells have been extensively reviewed, the intersections among these pathways, and their potential use as targets for improving responses to immune-checkpoint blockade therapies, are not completely understood. This review focuses on the interplay between tumor metabolites and T-cell dysfunction as well as the relationship between several T-cell metabolic patterns and T-cell activity/function in tumor immunology. Understanding these relationships could offer new avenues for improving responses to immunotherapy on a metabolic basis.
A spinning method for low-torsion composite yarn with basalt fibers and staple cotton fibers
Authors: Li Wei , Peng Zhiyong , Zhang Ruicheng , Wang Xin , Li Juan , Sun Yue , Xu Weilin , Xu Duo , Liu Keshuai
Published: April 2023

Basalt fibers play an indispensable role in aerospace as well as fireproof suits in specialty fields. However, basalt fibers usually have properties such as high temperature and corrosion resistance, severely lack comfort, and are prone to brittle fracture or splitting when subjected to bending or impact forces because of their high modulus. Although considerable efforts have been made to solve the above problems by wrapping soft staple fibers with basalt, but the problem of difficult stress balance exists in the composite process. Herein, we demonstrate that a stress balance spinning method to control the composite conformation between high stiffness basalt fibers and soft cotton fibers, possess significant modulus differences, for high spinnability and comfort composite yarns production on ring spinning. Geometric analysis demonstrated that the stress during retwisting adjusts the internal structure of the basalt fiber and changes the arrangement of exposed cotton fiber bundles, causing the fiber motion track to change from concentric helix to deformed non-concentric helix. The mechanical aspects show that over-twisted composite yarns lead to fiber exposure as well as detachment due to irregular fiber twisting, while low-twisted composite yarns can overcome residual torque and modulus differences. Afterwards, a systematic comparison of composite yarns with different parameters reveals that low-twisted composite yarns have a better helicoid structure, strength and uniformity than raw and over-twisted composite yarns.
Metatranscriptomic analysis of the gut microbiome of black soldier fly larvae reared on lignocellulose-rich fiber diets unveils key lignocellulolytic enzymes
Authors: Kariuki Eric G. , Kibet Caleb , Paredes Juan C. , Mboowa Gerald , Mwaura Oscar , Njogu John , Masiga Daniel , Bugg Timothy D. H. , Tanga Chrysantus M.
Published: April 2023

Recently, interest in the black soldier fly larvae (BSFL) gut microbiome has received increased attention primarily due to their role in waste bioconversion. However, there is a lack of information on the positive effect on the activities of the gut microbiomes and enzymes (CAZyme families) acting on lignocellulose. In this study, BSFL were subjected to lignocellulose-rich diets: chicken feed (CF), chicken manure (CM), brewers’ spent grain (BSG), and water hyacinth (WH). The mRNA libraries were prepared, and RNA-Sequencing was conducted using the PCR-cDNA approach through the MinION sequencing platform. Our results demonstrated that BSFL reared on BSG and WH had the highest abundance of Bacteroides and Dysgonomonas. The presence of GH51 and GH43_16 enzyme families in the gut of BSFL with both α-L-arabinofuranosidases and exo-alpha-L-arabinofuranosidase 2 were common in the BSFL reared on the highly lignocellulosic WH and BSG diets. Gene clusters that encode hemicellulolytic arabinofuranosidases in the CAZy family GH51 were also identified. These findings provide novel insight into the shift of gut microbiomes and the potential role of BSFL in the bioconversion of various highly lignocellulosic diets to fermentable sugars for subsequent value-added products (bioethanol). Further research on the role of these enzymes to improve existing technologies and their biotechnological applications is crucial.
Optimizing the scale-up production of fermented astragalus and its benefits to the performance and egg quality of laying hens
Authors: Dong Weiwei , Fan Zhanlei , Li Panxian , Liu Jun , Sun Guoping , Peng Nan , Liang Yunxiang , Zhao Shumiao
Published: April 2023

Astragalus is a homologous medicine and food that benefits human beings and poultry rearing. Fermented astragalus (FA) is a valuable product obtained by fermentation, but its scale-up production requires optimization and expansion of solid-state fermentation (SSF). In this study, Lactobacillus pentosus Stm was screened as the most suitable LAB strain for fermenting astragalus due to its excellent capacity. After optimization and expansion of SSF, LAB count and lactic acid content reached 206 × 108 cfu/g and 15.0%, respectively. Meanwhile, the content of bioactive compounds in FA was significantly enhanced. Feeding experiments with laying hens indicated that supplementing FA in the diet significantly improved the performance and egg quality, as evidenced by reduced feed-to-egg ratio and egg cholesterol. This was due to the promotion of intestinal health by shifting intestinal microbiota. Therefore, this is a systematical endeavor of producing scaled-up FA with promising potential as a feed additive in the poultry breeding industry.
Brain region dependent molecular signatures and myelin repair following chronic demyelination
Authors: Samtani Grace , Kim Sunja , Michaud Danielle , Hillhouse Andrew E. , Szule Joseph A. , Konganti Kranti , Li Jianrong
Published: April 2023

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system, characterized by myelin destruction, axonal degeneration, and progressive loss of neurological functions. Remyelination is considered an axonal protection strategy and may enable functional recovery, but the mechanisms of myelin repair, especially after chronic demyelination, remain poorly understood. Here, we used the cuprizone demyelination mouse model to investigate spatiotemporal characteristics of acute and chronic de- and remyelination and motor functional recovery following chronic demyelination. Extensive remyelination occurred after both the acute and chronic insults, but with less robust glial responses and slower myelin recovery in the chronic phase. Axonal damage was found at the ultrastructural level in the chronically demyelinated corpus callosum and in remyelinated axons in the somatosensory cortex. Unexpectedly, we observed the development of functional motor deficits after chronic remyelination. RNA sequencing of isolated brain regions revealed significantly altered transcripts across the corpus callosum, cortex and hippocampus. Pathway analysis identified selective upregulation of extracellular matrix/collagen pathways and synaptic signaling in the chronically de/remyelinating white matter. Our study demonstrates regional differences of intrinsic reparative mechanisms after a chronic demyelinating insult and suggests a potential link between long-term motor function alterations and continued axonal damage during chronic remyelination. Moreover, the transcriptome dataset of three brain regions and over an extended de/remyelination period provides a valuable platform for a better understanding of the mechanisms of myelin repair as well as the identification of potential targets for effective remyelination and neuroprotection for progressive MS.
Stability of mental motor-imagery classification in EEG depends on the choice of classifier model and experiment design, but not on signal preprocessing
Authors: Rosenfelder Martin Justinus , Spiliopoulou Myra , Hoppenstedt Burkhard , Pryss Rüdiger , Fissler Patrick , della Piedra Walter Mario , Kolassa Iris-Tatjana , Bender Andreas
Published: April 2023

Introduction

Modern consciousness research has developed diagnostic tests to improve the diagnostic accuracy of different states of consciousness via electroencephalography (EEG)-based mental motor imagery (MI), which is still challenging and lacks a consensus on how to best analyse MI EEG-data. An optimally designed and analyzed paradigm must detect command-following in all healthy individuals, before it can be applied in patients, e.g., for the diagnosis of disorders of consciousness (DOC).

Methods

We investigated the effects of two important steps in the raw signal preprocessing on predicting participant performance (F1) and machine-learning classifier performance (area-under-curve, AUC) in eight healthy individuals, that are based solely on MI using high-density EEG (HD-EEG): artifact correction (manual correction with vs. without Independent Component Analysis [ICA]), region of interest (ROI; motor area vs. whole brain), and machine-learning algorithm (support-vector machine [SVM] vs. k-nearest neighbor [KNN]).

Results

Results revealed no significant effects of artifact correction and ROI on predicting participant performance (F1) and classifier performance (AUC) scores (allps > 0.05) in the SVM classification model. In the KNN model, ROI had a significant influence on the classifier performance [F(1,8.939)= 7.585,p= 0.023]. There was no evidence for artifact correction and ROI selection changing the prediction of participants performance and classifier performance in EEG-based mental MI if using SVM-based classification (71–100% correct classifications across different signal preprocessing methods). The variance in the prediction of participant performance was significantly higher when the experiment started with a resting-state compared to a mental MI task block [X2(1)= 5.849,p= 0.016].

Discussion

Overall, we could show that classification is stable across different modes of EEG signal preprocessing when using SVM models. Exploratory analysis gave a hint toward potential effects of the sequence of task execution on the prediction of participant performance, which should be taken into account in future studies.
Virtual simulation with AneuShape™ software for microcatheter shaping in intracranial aneurysm coiling: a validation study
Authors: Wu Zeng-Bao , Zeng Ying , Zhang Hua-Qiu , Shu Kai , Li Gao-Hui , Xiang Jian-Ping , Lei Ting , Zhu Ming-Xin
Published: April 2023

Background

The shaping of an accurate and stable microcatheter plays a vital role in the successful embolization of intracranial aneurysms. Our study aimed to investigate the application and the role of AneuShape™ software in microcatheter shaping for intracranial aneurysm embolization.

Methods

From January 2021 to June 2022, 105 patients with single unruptured intracranial aneurysms were retrospectively analyzed with or without AneuShape™ software to assist in microcatheter shaping. The rates of microcatheter accessibility, accurate positioning, and stability for shaping were analyzed. During the operation, fluoroscopy duration, radiation dose, immediate postoperative angiography, and procedure-related complications were evaluated.

Results

Compared to the manual group, aneurysm-coiling procedures involving the AneuShape™ software exhibited superior results. The use of the software resulted in a lower rate of reshaping microcatheters (21.82 vs. 44.00%, p = 0.015) and higher rates of accessibility (81.82 vs. 58.00%, p = 0.008), better positioning (85.45 vs. 64.00%, p = 0.011), and higher stability (83.64 vs. 62.00%, p = 0.012). The software group also required more coils for both small (<7 mm) and large (≥7 mm) aneurysms compared to the manual group (3.50 ± 0.19 vs. 2.78 ± 0.11, p = 0.008 and 8.22 ± 0.36 vs. 6.00 ± 1.00, p = 0.081, respectively). In addition, the software group achieved better complete or approximately complete aneurysm obliteration (87.27 vs. 66.00%, p = 0.010) and had a lower procedure-related complication rate (3.60 vs. 12.00%, p = 0.107). Without this software, the operation had a longer intervention duration (34.31 ± 6.51 vs. 23.87 ± 6.98 min, p < 0.001) and a higher radiation dose (750.50 ± 177.81 vs. 563.53 ± 195.46 mGy, p < 0.001).

Conclusions

Software-based microcatheter shaping techniques can assist in the precise shaping of microcatheters, reduce operating time and radiation dose, improve embolization density, and facilitate more stable and efficient intracranial aneurysm embolization.
Noise and vestibular perception of passive self-motion
Authors: Lacquaniti Francesco , La Scaleia Barbara , Zago Myrka
Published: April 2023

Noise defined as random disturbances is ubiquitous in both the external environment and the nervous system. Depending on the context, noise can degrade or improve information processing and performance. In all cases, it contributes to neural systems dynamics. We review some effects of various sources of noise on the neural processing of self-motion signals at different stages of the vestibular pathways and the resulting perceptual responses. Hair cells in the inner ear reduce the impact of noise by means of mechanical and neural filtering. Hair cells synapse on regular and irregular afferents. Variability of discharge (noise) is low in regular afferents and high in irregular units. The high variability of irregular units provides information about the envelope of naturalistic head motion stimuli. A subset of neurons in the vestibular nuclei and thalamus are optimally tuned to noisy motion stimuli that reproduce the statistics of naturalistic head movements. In the thalamus, variability of neural discharge increases with increasing motion amplitude but saturates at high amplitudes, accounting for behavioral violation of Weber’s law. In general, the precision of individual vestibular neurons in encoding head motion is worse than the perceptual precision measured behaviorally. However, the global precision predicted by neural population codes matches the high behavioral precision. The latter is estimated by means of psychometric functions for detection or discrimination of whole-body displacements. Vestibular motion thresholds (inverse of precision) reflect the contribution of intrinsic and extrinsic noise to perception. Vestibular motion thresholds tend to deteriorate progressively after the age of 40 years, possibly due to oxidative stress resulting from high discharge rates and metabolic loads of vestibular afferents. In the elderly, vestibular thresholds correlate with postural stability: the higher the threshold, the greater is the postural imbalance and risk of falling. Experimental application of optimal levels of either galvanic noise or whole-body oscillations can ameliorate vestibular function with a mechanism reminiscent of stochastic resonance. Assessment of vestibular thresholds is diagnostic in several types of vestibulopathies, and vestibular stimulation might be useful in vestibular rehabilitation.
Endovascular thrombectomy is cost-effective in acute basilar artery occlusion stroke
Authors: Schwarting Julian , Rühling Sebastian , Bodden Jannis , Schwarting Stéphanie K. , Zimmer Claus , Mehrens Dirk , Kirschke Jan S. , Kunz Wolfgang G. , Boeckh-Behrens Tobias , Froelich Matthias F.
Published: April 2023

Objective

Endovascular thrombectomy is a long-established therapy for acute basilar artery occlusion (aBAO). Unlike for anterior circulation stroke, cost-effectiveness of endovascular treatment has not been evaluated and is urgently needed to calculate expected health benefits and financial rewards. The aim of this study was therefore to simulate patient-level costs, analyze the economic potential of endovascular thrombectomy in patients with acute basilar artery occlusion (aBAO), and identify major determinants of cost-effectiveness.

Methods

A Markov model was developed to compare outcome and cost parameters between patients treated by endovascular thrombectomy and patients treated by best medical care, based on four recent prospective clinical trials (ATTENTION, BAOCHE, BASICS, and BEST). Treatment outcomes were derived from the most recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. Willingness to pay per QALY thresholds were set at 1x gross domestic product per capita, as recommended by the World Health Organization.

Results

Endovascular treatment of acute aBAO stroke yielded an incremental gain of 1.71 quality-adjusted life-years per procedure with an incremental cost-effectiveness ratio of $7,596 per QALY. This was substantially lower than the Willingness to pay of $63,593 per QALY. Lifetime costs were most sensitive to costs of the endovascular procedure.

Conclusion

Endovascular treatment is cost-effective in patients with aBAO stroke.