bluuebunny/crossref_metadata_2025 huggingface dataset:
A nők és a cardiovascularis betegségek
Authors: Benczúr Béla
Published: November 2023

A nők és férfiak kockázati tényezői, társadalmi és környezeti faktorai, szív-ér rendszeri betegségeik megjelenési formája, felismerése és kezelése között jelentősek a különbségek. Nem véletlen, hogy a legfrissebb statisztikák szerint több nő, mint férfi veszíti életét cardiovascularis betegségekben. A klasszikus rizikófaktorokon túl a nők olyan egyedi, sajátos kockázati tényezőkkel is rendelkeznek, melyek jelentősen befolyásolják a későbbi cardiovascularis betegségeik kialakulásának kockázatát. A jelen összefoglaló áttekintést kíván adni a különböző cardiovascularis betegségek, például az érelmeszesedés, a pitvarfibrilláció, a szívelégtelenség, és a szívizominfarktus nemhez kötött jellemzőiről. Ha az egészségügyi szakemberek nagyobb figyelmet fordítanának ezekre az ismeretekre, javítható lenne a nők szív- és érrendszeri betegségeinek felismerése, kezelése és kimenetele.
Proposed Methods For Estimating Costs Of Mental Health In Canada (2007-2020)
Authors: Young Matthew M.
Published: November 2023

This report presents the results of an investigation by Greo Evidence Insights into how Canadian mental health (MH) costs could be estimated. It begins by conducting a review of studies estimating the costs of MH in Canada since 2010 and examines the various approaches employed. Based on this analysis the next section makes recommendations regarding cost types to include, the granularity of the estimates, and the approach to missing/ incomplete data. The report then recommends a phased approach to estimating the cost of mental health: Phase I describes in detail the data sources and methods to estimate public, direct health care costs associated with general and psychiatric MH-related hospitalizations and emergency room visits and non-hospital-based interventions (i.e., physician costs, pharmaceutical costs, community MH services). Phase II describes methods for estimating social and income support payments and indirect costs. Finally, Phase III describes data sources and methods for estimating private health and lost productivity costs.
BEDENSEL ENGELLİ SPORCU PERSPEKTİFİNDEN: SPORDA ÖZEL GEREKSİNİMLİ BİREYLER
Authors: ÇİL Hasibe , YILMAZ Berk Hakan , İLHAN Ekrem Levent
Published: November 2023

Öz: Kuşkusuz spor, olağan gelişim gösteren bireylerin yanı sıra özel gereksinimi bulunan bireyler için de her anlamda gelişimi destekleyen bir unsur olmuştur. Buradan hareketle çalışmada, bedensel engele sahip olan sporcuların bakış açıları ile spor yapan özel gereksinimli bireylerin spor bağlamında incelenmesi amaçlanmıştır. Nitel desende yapılan çalışma, yarı yapılandırılmış 4 sorunun katılımcılara yöneltilmesiyle gerçekleştirilmiştir. Bedensel engele sahip spor tecrübesi olan 6 katılımcı çalışmaya dâhil edilmiştir. Katılımcılar tamamen gönüllülük esasına uygun olarak çalışmaya katılım sağlamıştır. Görüşme aşamasına geçilmeden önce katılımcılara çalışma hakkında bilgi verilmiştir. Görüşmelerin kayıt altına alınması için katılımcıların izni alınmış ve görüşmeyelere geçilmiştir. Veriler, içerik analizinin kullanılmasıyla analiz edilmiştir. Çalışmanın güvenirlik hesaplaması yapılmış ve %87 olduğu tespit edilmiştir. Analiz sonucunda 3 ana tema oluşturulmuştur. Bunlar; sporda özel gereksinimli bireyler, spor çerçevesinde yaşanılan zorluklar ve spor yapan özel gereksinimli bireylerdir. Ayrıca çalışma sonucunda toplam 6 alt tema ve 30 kod oluşturulmuştur. Çalışmanın sonucunda özel gereksinimli bireylerin spor yapması, bedensel engelli sporcuların motive ve mutlu olmalarını, gurur duymalarını sağlamaktadır. Bu sayede özel gereksinimi bulunan bireylerin spor sayesinde bütün özel gereksinimli bireylere örnek olacağı ve hâlihazırda spor yapan özel gereksinimli bireylerin ise daha umutlu olarak sporda kendilerini gerçekleştirebilecekleri düşünülmektedir. Ayrıca özel gereksinimi bulunan bireylerin, spora katılım noktasında yaşadığı ulaşım, erişim ve olağan gelişim gösteren bireylerin bilinçsiz olmalarından kaynaklı zorlanmalara maruz kaldıkları ortaya koyulmuştur.
TÜRKİYE CUMHURİYETİ’NİN 100 YIL PERSPEKTİFİNDE SPOR YÖNETİMİNDEKİ GELİŞİMİ
Authors: DOĞANER Seçkin
Published: November 2023

Türkiye Cumhuriyeti, 100.yılında tüm alanlarda olduğu gibi spor alanında da gelişme göstermiş ve uluslararası rekabet düzeyine erişmiştir. Bu durum, genç Türkiye Cumhuriyeti içerisinde görev almış olan spor elemanlarının çeşitli özverili çalışmaları neticesinde gerçekleşmiştir. Spor yönetimi alanında önce ulusal, daha sonraları ise uluslararası başarı kazanabilmek ve küresel dünyada Türkiye’nin yükselen sesini duyurmak amacıyla birçok örgütlenme yapısı kurulmuştur. Bu yapılar, her zaman bir öncekinin devamı niteliğinde olup, spor alanında gelişmiş bir perspektif sunmaya çalışmıştır. Kurulan tüm spor örgütleri, uluslararası alanda sportif başarısı olan ülkelerin çalışmalarını model almış ve ulusal anlamda uygulamaya çalışmıştır. Ulu Önder Mustafa Kemal Atatürk ile başlamış olan bu politika; zaman içerisinde yurt dışından gelen veya oraya gönderilen spor elamanlarının doğrudan katkıları sayesinde hızlı bir ivme göstermiştir. Zaman içerisinde spor yönetimi açısından ülkemizin eksikleri belirlenerek, kurulan örgütlenme yapısı genişletilmeye çalışılmış ve yıllar ilerledikçe yerini daha profesyonel spor örgütlenmesine bırakmıştır. Bu doğrultuda alanında uzman ekiplerin görevlendirilmesi, antrenörlerin yurt dışı eğitimleri ile yetiştirilmesi, sosyal ve ekonomik katkıların genişletilmesi gibi politikalar uygulanmış ve neticesinde büyüyen spor örgütlenmesi Bakanlık düzeyine erişmiştir. Bakanlık düzeyine gelmiş spor politikaları, başta Olimpiyatlar olmak üzere birçok ulusal ve uluslararası başarılar getirmiş ve gerekli olan ihtiyaçların ilerleyen dönemlerde daha doğru belirlenerek, giderilmesi sağlanmıştır. Spor yönetimi ve örgüt yapısı ülkemizde halen gelişen ve kendisine asıl istenen rolü bulmaya çalışan bir yapıdır. Dolayısıyla 100.yılda ortaya konulan bu başarı, gelecek spor politikaları için bir başlangıç noktası olacak ve daha rasyonel adımların atılması adına yapılan girişimlerin ilk halkası olacaktır. Türk gençliği ve spor elemanları, bu geçen 100 yıllık perspektiften öğrenecekleri ile spor alanındaki başarılarını katlayacaktır.
A Negative Sociology of the State: Thinking the State with Pierre Bourdieu
Authors: ÖZPOLAT Gürhan
Published: November 2023

This article explores Pierre Bourdieu’s theory on the state’s pivotal role in producing and perpetuating social order, symbolic power, and domination. Bourdieu challenges the traditional view of the state as a monolithic entity and emphasizes its function as a generator of symbolic capital. According to Bourdieu, the state is the central bank of symbolic capital, confers privileges and authorizations upon social actors, thereby cements its position as the monopoly of legitimate symbolic violence. He contends that the state operates within a universe of belief, much like a sorcerer, and its power lies in its capacity to make itself invisible while maintaining social order. By examining the state as a meta-field, Bourdieu challenges conventional state theories, uncovering the underlying power dynamics and interests within the bureaucratic sphere. In conclusion, Bourdieu’s multifaceted perspective on the state provides a robust framework for understanding the intricate interplay of symbolic power, domination, and social order. This article highlights the importance of critically analysing the state’s role in shaping collective beliefs and underscores the necessity of comprehensively understanding state power, encompassing both its symbolic and material dimensions.
The actin-bundling protein, PLS3, is part of the mechanoresponsive machinery that regulates osteoblast mineralization
Authors: Chin Samantha M. , Unnold-Cofre Carmela , Naismith Teri , Jansen Silvia
Published: November 2023

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During this phase, osteoblasts heavily rely on mechanosensitive signaling pathways to sustain mineral deposition in response to increasing stiffness of the extracellular matrix (ECM). PLS3 prominently localizes to focal adhesions (FAs), which are intricately linked to mechanosensation. In line with this, we observed that depletion of PLS3 rendered osteoblasts unresponsive to changes in ECM stiffness and showed the same cell size, FA lengths and number of FAs when plated on soft (6 kPa) versus stiff (100 kPa) substrates in contrast to control cells, which showed an increased in each of these parameters when plated on 100 kPa substrates. Defective cell spreading of PLS3 KD cells on stiff substrates could be rescued by expression of wildtype PLS3, but not by expression of three PLS3 mutations that were identified in patients with early onset osteoporosis and that have aberrant actin-bundling activity. Altogether, our results show that actin-bundling by PLS3 is part of the mechanosensitive mechanism that promotes osteoblast mineralization and thus begins to elucidate how PLS3 contributes to the development of bone defects such as osteoporosis.
The role of extended synaptotagmin at membrane contact sites in cancer research
Authors: Pan Yuetian , Strohmer Dorothee , Feng Shikai , Zhang Guibin , Cui Hongshang , Song Yongbin
Published: November 2023

Membrane contact sites (MCSs) are adjacent locations between the membranes of two different organelles and play important roles in various physiological processes, including cellular calcium and lipid signaling. In cancer research, MCSs have been proposed to regulate tumor metabolism and fate, contributing to tumor progression, and this function could be exploited for tumor therapy. However, there is little evidence on how MCSs are involved in cancer progression. In this review, we use extended synaptotagmins (E-Syts) as an entry point to describe how MCSs affect cancer progression and may be used as new diagnostic biomarkers. We then introduced the role of E-Syt and its related pathways in calcium and lipid signaling, aiming to explain how MCSs affect tumor proliferation, progression, metastasis, apoptosis, drug resistance, and treatment through calcium and lipid signaling. Generally, this review will facilitate the understanding of the complex contact biology of cancer cells.
Mechanochemistry and oleochemistry: a green combination for the production of high-value small chemicals
Authors: Len Christophe , Duhan Vaishaly , Ouyang Weiyi , Nguyen Remi , Lochab Bimlesh
Published: November 2023

Mechanochemistry and oleochemistry and their combination have been known for centuries. Nevertheless, bioeconomy and circular economy concepts is much more recent and has motivated a regain of interest of dedicated research to improve alternative technologies for the valorization of biomass feedstocks. Accordingly, this review paper aims essentially at outlining recent breakthroughs obtained in the field of mechanochemistry and oleochemicals such as triglycerides, fatty acids, and glycerol derivatives. The review discusses advances obtained in the production of small chemicals derived from oils with a brief overview of vegetable oils, mechanochemistry and the use of mechanochemistry for the synthesis of biodiesel, lipidyl-cyclodextrine, dimeric and labelled fatty acids, calcium diglyceroxide, acylglycerols, benzoxazine and solketal. The paper also briefly overviews advances and limits for an industrial application.
Primary architecture and energy requirements of Type III and Type IV secretion systems
Authors: Cabezón Elena , Valenzuela-Gómez Fernando , Arechaga Ignacio
Published: November 2023

Many pathogens use Type III and Type IV protein secretion systems to secrete virulence factors from the bacterial cytosol into host cells. These systems operate through a one-step mechanism. The secreted substrates (protein or nucleo-protein complexes in the case of Type IV conjugative systems) are guided to the base of the secretion channel, where they are directly delivered into the host cell in an ATP-dependent unfolded state. Despite the numerous disparities between these secretion systems, here we have focused on the structural and functional similarities between both systems. In particular, on the structural similarity shared by one of the main ATPases (EscN and VirD4 in Type III and Type IV secretion systems, respectively). Interestingly, these ATPases also exhibit a structural resemblance to F1-ATPases, which suggests a common mechanism for substrate secretion. The correlation between structure and function of essential components in both systems can provide significant insights into the molecular mechanisms involved. This approach is of great interest in the pursuit of identifying inhibitors that can effectively target these systems.
Staphylococcus aureus activates NRLP3-dependent IL-1β secretion from human conjunctival goblet cells using α toxin and toll-like receptors 2 and 1
Authors: Li Dayu , Hodges Robin , AukrustNaqvi Maria , Bair Jeffrey , Bispo Paulo J. M. , Gilmore Michael S. , Gregory-Ksander Meredith , Dartt Darlene A.
Published: November 2023

We used cultured human conjunctival goblet cells to determine (i) whether the toxigenic S. aureus- induced activation of the epithelial goblet cells requires two signals to activate the NLRP3 inflammasome, (ii) if one signal is mediated by TLR1, TLR2, or TLR6, and (iii) if the S. aureus toxin α toxin is another signal for the activation of the inflammasome and secretion of mature IL-1β. Cultured cells were incubated with siRNA to knock down the different TLRs. After stimulation with toxigenic S. aureus RN6390, pro-IL-1β synthesis, caspase-1 activity, and mature IL-1β secretion were measured. In a separate set of experiments, the cells were incubated with toxigenic S. aureus RN6390 or mutant S. aureus ALC837 that does not express α toxin with or without exogenous α toxin. A gentamicin protection assay was used to determine if intracellular bacteria were active. We conclude that α toxin from toxigenic S. aureus triggers two separate mechanisms required for the activation of the NLRP3 inflammasome and secretion of mature IL-1β. In the first mechanism, α toxin secreted from internalized S. aureus produces a pore, allowing the internalized bacteria and associated pathogen-associated molecular patterns to interact with intracellular TLR2 and, to a lesser extent, TLR1. In the second mechanism, α toxin forms a pore in the plasma membrane, leading to an efflux of cytosolic K+ and influx of Ca2+. We conclude that α toxin by these two different mechanisms triggers the synthesis of pro-IL-1β and NLRP3 components, activation of capase-1, and secretion of mature IL-1β to defend against bacterial infection.
White capitalism within communities of craftivism: mask making and health maintenance disparities during COVID-19
Authors: Anderson Wendy K. Z. , Davis LaShara A.
Published: November 2023

When lockdown started, my anxiety kept me on a tight string—I (author 1) remember drowning in intense, omnipresent agitation as I used every “extra” moment I could to research mask styles, adapt patterns published online or distributed by different organizations to increase access to masks for better functionality, and distribute masks to those who needed them via an old ice cream bucket on my front bench. Yet, I recognized that the time I used, my ability to quarantine and so much more contributed to my privilege in doing so. I (author 2) had no masks on hand, so after watching a few tutorials online, I concocted my own makeshift mask. Not only did my MacGyvered creation not fit properly, it was superhot and lacked sufficient air flow due to the thickness of the fabric. Although this initial mask-making strategy wasn't very practical, I recognized the importance of having not only a mask but one that would fit such that it properly served its purpose: to preserve my health. By fashioning a collaborative, autoethnographic approach to understanding craftivism during the 2020 coronavirus crisis, from a Black scholar doing disparities and equity focused health communication work and a white scholar engaging activist rhetorics and digital media equity scholarship, our joint recognition of economic and infrastructural privilege offered understanding of how forms of pattern design (techne) and cultural community infrastructure influenced our maker agencies and constraints. Reflecting on our immersive mask-making experiences, we recognized a value of creating alternative economic structures, yet also unmasked significant racial agencies within craftivist communities which required cultural historic materiality and knowledge, time to create and revise, networked access, and physical risk. Here, we offer insight into how a crisis revealed systemic biases as agency to reorient ourselves toward anti-racist processes and practices.
Uncertainty quantification of computational fluid dynamics-based predictions for fractional flow reserve and wall shear stress of the idealized stenotic coronary
Authors: Ho Nghia Nguyen , Lee Kwan Yong , Lee Sang-Wook
Published: November 2023

Introduction

In clinical practice, hemodynamics-based functional indices, such as fractional flow reserve (FFR) and wall shear stress (WSS), are useful in assessing the severity and risk of rupture of atherosclerotic lesions. Computational fluid dynamics (CFD) is widely used to predict these indices noninvasively.

Method

In this study, uncertainty quantification and sensitivity analysis are performed for the computational prediction of WSS and FFR directly from 3D–0D coupled CFD simulations on idealized stenotic coronary models. Five geometric parameters (proximal, mid, and distal lengths of stenosis; reference lumen diameter; and stenosis severity) and two physiological parameters (mean aortic pressure and microcirculation resistance) are considered as uncertain input variables.

Results

When employing the true values of stenosis severity and mean aortic pressure, a discernible reduction of 25% and 9.5% in the uncertainty of the computed proximal WSS, respectively. In addition, degree of stenosis, reference lumen diameter, and coronary resistance contributed the uncertainty of computed FFR, accounting for 41.2%, 31.9%, and 24.6%, respectively.

Conclusion

This study demonstrated that accurate measurement of the degree of stenosis and mean aortic pressure is crucial for improving the computational prediction of WSS. In contrast, the reference lumen diameter, degree of stenosis, and coronary resistance are the most impactful parameters for FFR.
Molecular characterization of novel and rare DNA variants in patients with galactosemia
Authors: Maroulis Vasileios , Agathangelidis Andreas , Skouma Anastasia , Sdogou Triantafyllia , Papadakis Manoussos N. , Papakonstantinou Evangelos , Girginoudis Panagiotis , Vorgias Constantinos E. , Aleporou Vassiliki , Kollia Panagoula
Published: November 2023

Introduction: Galactosemia is an inherited disorder caused by mutations in the three genes that encode enzymes implicated in galactose catabolism. Currently, the only available treatment for galactosemia is life-long dietary restriction of galactose/lactose, and despite treatment, it might result in long-term complications.

Methods: Here, we present five cases of newborn patients with elevated galactose levels, identified in the context of the newborn screening program. Genetic analysis concerned a next generation sequencing (NGS) methodology covering the exons and adjacent splice regions of the GALT, GALK1, and GALE genes.

Results: Our approach led to the identification of eight rare nonsynonymous DNA variants. Four of these variants, namely, p.Arg204Gln and p.Met298Ile in GALT, p.Arg68Leu in GALK1, and p.Ala180Thr in GALE, were already recorded in relevant databases, yet their clinical significance is uncertain. The other four variants, namely, p.Phe245Leu in GALT, p.Gly193Glu in GALK1, and p.Ile266Leu and p.Ala216Thr in the GALE gene, were novel. In silico analysis of the possible effect of these variants in terms of protein function and stability was performed using a series of bioinformatics tools, followed by visualization of the substituted amino acids within the protein molecule. The analysis revealed a deleterious and/or destabilizing effect for all the variants, supported by multiple tools in each case.

Discussion: These results, given the extreme rarity of the variants and the specific phenotype of the respective cases, support a pathogenic effect for each individual variant. Altogether, our study shows that targeted NGS methodologies may offer a time- and cost-effective approach for the genetic investigation of galactosemia and can assist in elucidating the complex genetic background of this disorder.
Machine learning-based integrated identification of predictive combined diagnostic biomarkers for endometriosis
Authors: Zhang Haolong , Zhang Haoling , Yang Huadi , Shuid Ahmad Naqib , Sandai Doblin , Chen Xingbei
Published: November 2023

Background: Endometriosis (EM) is a common gynecological condition in women of reproductive age, with diverse causes and a not yet fully understood pathogenesis. Traditional diagnostics rely on single diagnostic biomarkers and does not integrate a variety of different biomarkers. This study introduces multiple machine learning techniques, enhancing the accuracy of predictive models. A novel diagnostic approach that combines various biomarkers provides a new clinical perspective for improving the diagnostic efficiency of endometriosis, holding significant potential for clinical application.

Methods: In this study, GSE51981 was used as a test set, and 11 machine learning algorithms (Lasso, Stepglm, glmBoost, Support Vector Machine, Ridge, Enet, plsRglm, Random Forest, LDA, XGBoost, and NaiveBayes) were employed to construct 113 predictive models for endometriosis. The optimal model was determined based on the AUC values derived from various algorithms. These genes were then evaluated using nine machine learning algorithms (Random Forest, SVM, Gradient Boosting Machine, LASSO, XGB, NNET, Generalized Linear Model, KNN, and Decision Tree) to assess significance scores and identify diagnostic genes for each algorithm. The diagnostic value of these genes was further validated in external datasets from GSE7305, GSE11691, and GSE120103.

Results: Analysis of the GSE51981 dataset revealed 62 DEGs. The Stepglm [Both] and plsRglm algorithms identified 30 genes with the most potential using the AUC evaluation. Subsequently, nine machine learning algorithms were applied to select diagnostic genes, leading to the identification of five key diagnostic genes using the LASSO algorithm. The ADAT1 gene exhibited the best single-gene predictive performance, with an AUC of 0.785. A combination of genes (FOS, EPHX1, DLGAP5, PCSK5, and ADAT1) achieves an AUC of 0.836 in the test dataset. Moreover, these genes consistently exhibited an AUC exceeding 0.78 in all validation datasets, demonstrating superior predictive performance. Furthermore, correlation analysis with immune infiltration strengthened their predictive value by demonstrating the close relationship of the diagnostic genes with immune infiltrating cells.

Conclusion: A combination of biomarkers consisting of FOS, EPHX1, DLGAP5, PCSK5, and ADAT1 can serve as a diagnostic tool for endometriosis, enhancing diagnostic efficiency. The association of these genes with immune infiltrating cells reveals their potential role in the pathogenesis of endometriosis, providing new insights for early detection and treatment.
Metabolic reprogramming involves in transition of activated/resting CD4+ memory T cells and prognosis of gastric cancer
Authors: Sun Yue , Liu Li , Fu Yuanyuan , Liu Yaoyao , Gao Xuan , Xia Xuefeng , Zhu Dajian , Wang Xiaping , Zhou Xin
Published: November 2023

Background

Little is known on how metabolic reprogramming potentially prompts transition of activated and resting CD4+ memory T cells infiltration in tumor microenvironment of gastric cancer (GC). The study aimed to evaluate their interactions and develop a risk model for predicting prognosis in GC.

Methods

Expression profiles were obtained from TCGA and GEO databases. An immunotherapeutic IMvigor210 cohort was also enrolled. CIBERSORT algorithm was used to evaluate the infiltration of immune cells. The ssGSEA method was performed to assess levels of 114 metabolism pathways. Prognosis and correlation analysis were conducted to identify metabolism pathways and genes correlated with activated CD4+ memory T cells ratio (AR) and prognosis. An AR-related metabolism gene (ARMG) risk model was constructed and validated in different cohorts. Flow cytometry was applied to validate the effect of all-trans retinoic acid (ATRA) on CD4+ memory T cells.

Results

Since significantly inverse prognostic value and negative correlation of resting and activated CD4+ memory T cells, high AR level was associated with favorable overall survival (OS) in GC. Meanwhile, 15 metabolism pathways including retinoic acid metabolism pathway were significantly correlated with AR and prognosis. The ARMG risk model could classify GC patients with different outcomes, treatment responses, genomic and immune landscape. The prognostic value of the model was also confirmed in the additional validation, immunotherapy and pan-cancer cohorts. Functional analyses revealed that the ARMG model was positively correlated with pro-tumorigenic pathways. In vitro experiments showed that ATRA could inhibit levels of activated CD4+ memory T cells and AR.

Conclusion

Our study showed that metabolic reprogramming including retinoic acid metabolism could contribute to transition of activated and resting CD4+ memory T cells, and affect prognosis of GC patients. The ARMG risk model could serve as a new tool for GC patients by accurately predicting prognosis and response to treatment.
Bile acids induce IL-1α and drive NLRP3 inflammasome-independent production of IL-1β in murine dendritic cells
Authors: Oleszycka Ewa , O’Brien Eoin C. , Freeley Michael , Lavelle Ed C. , Long Aideen
Published: November 2023

Bile acids are amphipathic molecules that are synthesized from cholesterol in the liver and facilitate intestinal absorption of lipids and nutrients. They are released into the small intestine upon ingestion of a meal where intestinal bacteria can modify primary into secondary bile acids. Bile acids are cytotoxic at high concentrations and have been associated with inflammatory diseases such as liver inflammation and Barrett’s Oesophagus. Although bile acids induce pro-inflammatory signalling, their role in inducing innate immune cytokines and inflammation has not been fully explored to date. Here we demonstrate that the bile acids, deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) induce IL-1α and IL-1β secretion in vitro in primed bone marrow derived dendritic cells (BMDCs). The secretion of IL-1β was found not to require expression of NLRP3, ASC or caspase-1 activity; we can’t rule out all inflammasomes. Furthermore, DCA and CDCA were shown to induce the recruitment of neutrophils and monocytes to the site of injection an intraperitoneal model of inflammation. This study further underlines a mechanistic role for bile acids in the pathogenesis of inflammatory diseases through stimulating the production of pro-inflammatory cytokines and recruitment of innate immune cells.
Complex temperature mosaics across space and time in estuaries: implications for current and future nursery function for Pacific salmon
Authors: Gross Phoebe L. , Gan Julian C.L. , Scurfield Daniel J. , Frank Cory , Frank Cedar , McLean Caelan , Bob Chris , Moore Jonathan W.
Published: November 2023

Water temperature is a key dimension of estuaries that can influence important biological processes including organismal growth, survival, and habitat use. For example, juvenile Pacific salmon rely on temperature-mediated growth opportunities in estuaries during seaward migration in the spring and summer. However, oncoming climate change is warming estuary temperatures and transforming growth potential. Yet, it is likely that estuary water temperatures are complex and dynamic across space and time. Here we investigated spatial and temporal patterns of water temperature across two contrasting estuaries on Vancouver Island, BC, and used these data to simulate juvenile Chinook salmon growth potential under both present conditions and a simplified scenario of climate warming. Summer temperatures were warmer and more spatially homogeneous across the Englishman River estuary relative to the Salmon River estuary. Within each system, temperature was variable across habitats and sites, appearing to be driven by a combination of local climate, river and ocean temperatures, tidal fluctuations, and habitat features. This shifting mosaic of temperatures generated a complex portfolio of growth opportunities for juvenile Chinook salmon. There were broad patterns of increasing growth potential across both systems as temperatures warmed in early summer. However, excessively hot late summer temperatures drove steep declines in growth potential across the Englishman River estuary, while positive trends continued through August in the Salmon River estuary. A simple climate change scenario revealed that estuaries and habitats may have differing vulnerabilities to increasing temperatures—with climate warming, favorable growth opportunities were even more constricted to early summer in the Englishman River estuary, but expanded across most habitats and times in the Salmon River estuary given lower baseline temperatures and higher habitat complexity. Collectively, this work underscores the importance of habitat complexity and local climate for maintaining diverse growth opportunities across estuaries, which may confer resilience to the nursery function of estuaries as temperature mosaics warm.
An electronically conductive 3D architecture with controlled porosity for LiFePO4 cathodes
Authors: Nguyen Martin , Liang Zhiming , Garman Kaitlin , Wang Yangyang , Gestos Adrian , Mo Michael , Ban Chunmei
Published: November 2023

Thick LiFePO4 (LFP) cathodes offer a promising solution to increasing the areal capacity and reducing the cost of Li-ion batteries while retaining the qualities intrinsic to LFP, including long cycle lifetimes and thermal stability required for electric vehicles and stationary energy storage applications. However, the primary challenges of thick LFP cathodes are poor rate capability and cycling stability due to LFP’s electronically insulating material property, poor electronic conductivity, and long diffusion length at high electrode thicknesses. Herein, we propose an electrode architecture composed of vertically aligned carbon fibers (CFs) attached to a plasticized current collector (PCC) to promote rate capability, cycle life, and further enhance the safety of thick LFP cathodes. The effectiveness of the CF-PCC architecture is demonstrated by electrochemical analysis with a good areal capacity of 3.5 mA cm-2, excellent cycling stability at C/3, and good rate capability up to 1C. These results are confirmed by investigating the architecture’s impact on ionic diffusivity via electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) compared to the conventional slurry cast LFP cathode.
Insights into the genomic architecture of a newly discovered endophytic Fusarium species belonging to the Fusarium concolor complex from India
Authors: Rana Shiwali , Singh Sanjay K.
Published: November 2023

In this study, a new species Fusarium indicum belonging to the Fusarium concolor species complex is established to accommodate an endophytic fungus isolated from Bambusa sp. and collected from Himachal Pradesh. The identity of this isolate was confirmed based on the asexual morphs, its cultural characteristics, and phylogenetic analyses. This isolate revealed out to be distinct by showing less similarity with described species in the genus Fusarium based on molecular sequence data, approximately 93.9% similarity based on translation elongation factor 1-alpha, and 94.2% similarity based on RNA polymerase II subunit. Furthermore, to increase knowledge about this novel species, whole-genome sequencing was carried out. The results displayed that Fusarium indicum NFCCI 5145 possesses a 40.2 Mb genome and 48.39% of GC content. Approximately 12,963 functional protein-coding genes were carefully predicted and annotated using different BLAST databases, such as Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Pathogen Host Interactions (PHI), Clusters of Orthologous Groups (COG), and Carbohydrate-Active enzymes (CAZy). The orthologous proteins were identified using OrthoFinder and used for the phylogenetic analysis. ANIb confirmed that the isolate is closely related to the F. concolor species complex. It is known that Fusarium strains can produce a wide range of bioactive secondary metabolites. Therefore, in-depth mining for biosynthetic gene clusters for secondary metabolite biosynthesis of Fusarium indicum NFCCI 5145 was investigated using Antibiotics and Secondary Metabolites Analysis Shell (AntiSMASH) annotation. AntiSMASH results displayed that this isolate possesses 45 secondary metabolites of biosynthetic gene clusters (BGCs). These findings significantly improved our understanding of the strain Fusarium indicum NFCCI 5145 and its possible applications in different sectors including industry for the secondary metabolites and enzymes it can produce.
Best practice: setting up and operating a mid-sized cryo-EM facility
Authors: Meng Xing , Ratnayake Ishara , Escobar Galvis Martha L. , Kotecki Jason , Ramjan Zack , Zhao Gongpu
Published: November 2023

Ever since the resolution revolution in 2013, cryo-electron microscopy (cryo-EM) has become a powerful methodology in structural biology that is especially suited to study the structure of large flexible molecular complexes. Since then, the need of setting up state-of-the-art cryo-EM facilities around the world has increased tremendously. Access to high-end cryo-EM instrumentation is however expensive and requires expertise. The establishment of large cryo-EM centers worldwide, many of which provide academic users free access for both data collection and user training, has been possible with the support of government agencies across the globe. In addition, many universities, and private institutions like the Van Andel Institute (VAI) have made significant investments to establish their own cryo-EM core facilities, ensuring on-site access to their researchers. This paper aims to serve as a blueprint for establishing a new mid-sized cryo-EM facility, as it provides key information based on our experience at VAI and discusses strategies used to optimize routine operation towards high performance and efficiency for single-particle cryo-EM. Information regarding initial planning, selection of equipment as well as the development of IT solutions that were required to improve data collection and analysis are included. In addition, we present an account of the most common issues affecting operation as well as the needs for maintenance over a 6-year period, which can help interested parties to estimate the long-term costs of running this type of facility. Lastly, a brief discussion on the pros and cons of establishing the facility is also included.
Effects of acupoints-based TENS combined with tDCS on spasticity and motor function in ischemic stroke with spastic hemiplegia: study protocol for a randomized controlled trial
Authors: Qian Xu , Ma Liang-Xiao , Ma Ling-Hui , Zhang Qin-Yong , Xiu Jing-Yun , Wang Xiu-Yan , Sun Tian-Yi
Published: November 2023

Background

Spastic hemiplegia following ischemic strokes seriously impedes the recovery of motor function posing a vast rehabilitation challenge. As the uncertain effects of recommended conventional treatments such as botulinum toxin injections on active functional improvement and potential adverse effects cannot be bypassed, there is an increasing need in alternative, more effective and safer modalities. Acupoints-based transcutaneous electrical nerve stimulation (Acu-TENS) and transcranial direct current stimulation (tDCS) are effective non-invasive modalities for stroke rehabilitation, particularly showing anti-spastic effect and functional improvements as well. However, the optimal stimulation frequency of Acu-TENS and whether combination of Acu-TENS and tDCS exert synergistic effect remain to be investigated.

Objective

To evaluate the effects of Acu-TENS combined with tDCS on spasticity and motor function in ischemic stroke patients with spastic hemiplegia and screen the optimal frequency of Acu-TENS.

Methods

A total of 90 post-ischemic stroke patients with spastic hemiplegia will be intervened for 4 weeks and followed up for 4 weeks. They will be randomly assigned to three groups including two observation groups and a standard care control group in a 1:1:1 ratio. All patients will receive standard care and regular rehabilitation accordingly. In addition, the two observation groups will receive 12 sessions of Acu-TENS at 20 Hz or 100 Hz for 30 min combined with 1 mA tDCS for 20 min, three times a week, for 4 weeks. The primary outcome is the change in total modified Ashworth scale (MAS) score from baseline to week 4. Secondary outcomes include changes in surface electromyography (SEMG), Fugl-Meyer Motor Function Scale, Modified Barthel Index (MBI), and 10-meter walk test from baseline to week 4. MAS score will also be measured after 4 weeks of follow-up. Adverse events throughout the study will be recorded.

Discussion

This trial will evaluate, for the first time, the therapeutic potentials and safety of Acu-TENS combined with tDCS on spasticity and motor function in stroke patients. It will provide evidence for frequency-dependent anti-spastic effect of Acu-TENS, and a reference for rated parameter setting of new mixed transcutaneous and transcranial stimulation system for stroke rehabilitation, thereby promoting proactive healthcare consequently.

Trial registration:

Chinese Clinical Trials Register ChiCTR2200067186.
Causal associations of thyroid function and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study
Authors: Chen Jialei , Wu Chao , He Jing , Wu Linsui , Yang Yongkang , Zhong Shixun , Luo Jing
Published: November 2023

Background

Observational studies have indicated a potential association between thyroid dysfunction and the risk of sudden sensorineural hearing loss (SSNHL). However, the precise causal relationship between the two remains uncertain. The objective of our study was to assess the causal influence of thyroid function on SSNHL by employing a bidirectional and multivariable Mendelian randomization (MR) approach.

Methods

Single-nucleotide polymorphisms (SNPs) associated with free thyroid (FT4) and thyroid stimulating hormone (TSH) were selected from the summary data of a large genome-wide association study (GWAS) conducted on European individuals. The summary-level data of SSNHL were also obtained from a GWAS, which included 196,592 participants (1,491 cases and 195,101 controls). The MR analysis primarily utilized the inverse variance weighted (IVW) method, with sensitivity analyses performed using the weighted median, MR-Egger, and MR-PRESSO approaches.

Results

In the IVW method, an elevated genetically predicted FT4 level was found to effectively reduce the risk of SSNHL (OR = 0.747, 95% CI = 0.565–0.987, P = 0.04). These findings were consistent when conducting multivariate MR analysis, which adjusted for TSH levels (OR = 0.929, 95% CI = 0.867–0.995, P = 0.036). However, genetically predicted TSH levels did not emerge as a risk factor for SSNHL (OR = 1.409, 95% CI = 0.895–1.230, P = 0.547). Furthermore, even after adjusting for FT4 levels in the multivariate MR analysis, no evidence of a direct causal relationship between TSH levels and the risk of SSNHL was observed (OR = 1.011, 95% CI = 0.880–1.161, P = 0.867). The reverse MR analysis showed that there was no evidence of a direct causal relationship between SSNHL and the risk of FT4 level (OR = 1.026, 95% CI = 0.999–1.054, P = 0.056) or TSH level (OR = 1.002, 95% CI = 0.989–1.015, P = 0.702).

Conclusion

Within the normal range, genetic variants associated with higher FT4 levels demonstrate a potential protective effect against SSNHL, whereas there is no direct causal relationship between TSH levels and the risk of SSNHL.
Computed tomography perfusion imaging-guided intravenous thrombolysis in acute minor ischemic stroke
Authors: Sartor-Pfeiffer Jennifer , Lingel Mirjam , Stefanou Maria-Ioanna , Krumbholz Markus , Hennersdorf Florian , Ernemann Ulrike , Poli Sven , Feil Katharina , Ziemann Ulf , Mengel Annerose
Published: November 2023

Background

Over 50% of acute ischemic stroke (AIS) patients present with minor neurological deficits, and optimal treatment is still debated. The randomized PRISMS trial did not show beneficial effects of intravenous thrombolysis (IVT) in unselected patients with minor stroke and non-disabling neurological deficits.

Purpose

The study aimed to evaluate if AIS patients with minor stroke may benefit from computed-tomography-perfusion (CTP)-guided IVT. The primary endpoint was good functional outcomes, defined as a modified Rankin Scale score of 0–2 at 90 days.

Methods

AIS patients with a NIHSS of ≤5 presenting within 4.5 h underwent multimodal CT-imaging including CTP. CTP mismatch was defined as hypoperfusion on CTP with time-to-peak delay >6 s without corresponding hypoperfusion in cerebral blood volume. IVT decision was left to the attending stroke physicians. Patients with large vessel occlusion (LVO) and absolute contraindications to IVT were excluded.

Results

In total, 267 consecutive patients were included [mean age: 72 ± 14 years, 45.3% female patients, 75.3% received IVT, median NIHSS on admission: 3 (IQR 2, 4)]. CTP mismatch was detected in 41.8% of IVT− treated patients (IVT+) and 28.8% of standard treatment patients (IVT−) (p = 0.06). IVT+ had favorable outcomes at 90 days compared to IVT− (p = 0.006), but no interaction with an existing CTP mismatch was detected (ORadj: 1.676; 95% CI: 0.644–4.364). No symptomatic intracranial hemorrhage according to ECASS-III criteria occurred.

Conclusion

Although selected AIS patients with minor stroke may benefit from IVT, CTP mismatch does not correlate with functional outcomes. No benefit from CTP mismatch in guiding IVT was detected in patients without LVO presenting with minor neurological deficits.
Solids, colloids, and the hydrolysis of tetravalent uranium in chloride media
Authors: Grambow B. , Müller R. , Schild D. , Gaona X.
Published: November 2023

Understanding of the properties of dissolution and precipitation of Uranium under reducing geochemical conditions is important in radioactive waste management and assessments of natural uranium deposits. The mechanism of forming UO2+y from U(VI) and U(IV) containing aqueous solution (1 M NaCl) and the solubilities of the precipitates were studied under well-controlled reducing conditions as a function of pH, particle size, and supersaturation. The results show that tetramer and colloid formation are critical initial steps. Precipitation is not growth-controlled but appears to be nucleation-controlled, with critical nuclei dimensions of one unit cell of UO2. The precipitates were always crystalline, and amorphous UO2 was not observed.
The values of HER-2 expression in the non-muscle-invasive bladder cancer: a retrospective clinical study
Authors: Wang Shuo , Ji Yongpeng , Liu Yiqiang , Du Peng , Ma Jinchao , Yang Xiao , Yu Ziyi , Yang Yong
Published: November 2023

Purpose

The purpose of this research is to evaluate the association between HER-2 expression and clinicopathological features in patients with non-muscle-invasive bladder cancer (NMIBC).

Methods

Between 2019 and 2022, 204 patients treated with Transurethral resection of the bladder tumor (TURBT) were included in this study. Data of pathologic T (pT) stage, grades of the tumor, age, sex, tumor size and number of the tumors were collected and compared according to the expression level of the human epidermal growth factor 2 (HER-2). ROC curve analysis was performed to assess the discriminative ability of HER-2 expression for tumors grades and pT stage. Multivariable logistic regression analysis were used to evaluate the association between HER-2 expression and tumor grades and pT stage.

Results

Patients were divided into low grade (110, 53.9%) and high grade groups (94, 46.1%) according to the tumor grade. Pathologic stage consisted of pTa in 166 (81.4%) and pT1 in 38 (18.6%). HER-2 expression was semi quantitatively scored to 0 in 44 (21.6%), 1 in 58 (28.4%), 2 in 91 (44.6%), and 3 in 11 (5.4%) cases. HER-2 expression was significantly associated with tumor stages and histological grades, but not with sex, tumor size or number of tumors. The AUC for combination of HER-2 expression with tumor stages and histological grades was 0.652 (p < 0.003) and 0.727 (p < 0.001), respectively.

Conclusion

This study demonstrated that HER-2 expression is associated with tumor stages and histological grades in NMIBC. It has diagnostic value for cystoscopic biopsy.
Factors influencing the diagnostic and prognostic values of circulating tumor cells in breast cancer: a meta-analysis of 8,935 patients
Authors: Zhao Hongfang , Wang Luxuan , Fang Chuan , Li Chunhui , Zhang Lijian
Published: November 2023

Background

Circulating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging.

Methods

We searched published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages.

Results

In this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC+) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HROS, 3.09; 95% CI, 2.17–4.39; HRPFS/DFS, 2.06; 95% CI, 1.72–2.47). Moreover, CTC+ indicated poor survival irrespective of the treatment phases and sampling times (HROS, 2.43; 95% CI, 1.85–3.19; HRPFS/DFS, 1.82; 95% CI, 1.66–1.99). The CTC+ was associated with poor survival regardless of the continents of patients (HROS = 2.43; 95% CI, 1.85–3.19).

Conclusion

Our study suggested that CTC+ was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC+, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.