bluuebunny/crossref_metadata_2025 huggingface dataset:
Assistive diagnostic indicators for infections related to lumbar posterior interbody fusion internal fixation: platelet count and mean platelet volume
Authors: Zhang Yadong , Li Houkun , Wang Wentao , Shan Lequn , Hao Dingjun
Published: November 2023

Background

The most severe complication after posterior single-segment lumbar interbody fusion and internal fixation (PIFIF) surgery for degenerative lumbar diseases is deep surgical site infection (DSSI). Preoperatively diagnosing such complications proves to be challenging. Platelets, as acute-phase reactants, undergo changes in response to infections and inflammation. This study aims to assess whether platelet indices can further aid in the diagnosis of DSSI.

Methods

A single-center retrospective study was conducted from January 2016 to February 2021 at Xi'an Jiaotong University-Affiliated Honghui Hospital, involving 83 patients who underwent revision surgery after PIFIF due to lumbar degenerative diseases. Among them, 24 patients were diagnosed with DSSI based on combined bacterial culture and imaging data. Preoperative complete serological indicators including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count and mean platelet volume ratio (P/M ratio) were analyzed using receiver operating characteristic (ROC) curve analysis to determine cutoff values, sensitivity, and specificity. This was done to further assess the ability of these serological indicators to identify the occurrence of DSSI after PIFIF.

Results

There were no significant differences in baseline demographic characteristics between the two patient groups (P > 0.05). The P/M ratio was 13.54 ± 5.05 in the aseptic revision group, while it was 19.21 ± 6.30 in the DSSI revision patients, showing a significant difference (P < 0.001). ROC curve analysis revealed that the optimal cutoff value for the P/M ratio was 17.50, with a sensitivity of 58.3% and a specificity of 78.6%. The areas under the curve (AUC) for ESR, CRP, and P/M ratio were 0.797, 0.845, and 0.756, respectively. The negative predictive value (NPV) was 87.04%, 89.47%, and 82.45%, respectively; the positive predictive value (PPV) was 58.62%, 69.23%, and 53.84%, respectively, for ESR, CRP, and P/M ratio, respectively. When P/M ratio is used in combination with ESR and CRP, the AUC is 0.887, with a sensitivity of 95.4%, specificity of 67.8%, NPV of 97.56%, PPV of 54.76%. The diagnostic performance of the model for evaluating DSSI is significantly improved compared to using ESR and CRP alone (P < 0.05).

Conclusion

Platelets and their related serum biomarkers are closely associated with DSSI. The P/M ratio can serve as a reliable test for screening DSSI and is worth considering for inclusion in the assessment of patients at risk of developing DSSI after potential PIFIF surgery.
Attenuation of estrogen and its receptors in the post-menopausal stage exacerbates dyslipidemia and leads to cognitive impairment
Authors: Meng Qinghai , Chao Ying , Zhang Shurui , Ding Xue , Feng Han , Zhang Chenyan , Liu Bowen , Zhu Weijie , Li Yu , Zhang Qichun , Tong Huangjin , Wu Lixing , Bian Huimin
Published: November 2023

Cognitive dysfunction increases as menopause progresses. We previously found that estrogen receptors (ERs) contribute to dyslipidemia, but the specific relationship between ERs, dyslipidemia and cognitive dysfunction remains poorly understood. In the present study, we analyzed sequencing data from female hippocampus and normal breast aspirate samples from normal and Alzheimer’s disease (AD) women, and the results suggest that abnormal ERs signaling is associated with dyslipidemia and cognitive dysfunction. We replicated a mouse model of dyslipidemia and postmenopausal status in LDLR−/− mice and treated them with β-estradiol or simvastatin, and found that ovariectomy in LDLR−/− mice led to an exacerbation of dyslipidemia and increased hippocampal apoptosis and cognitive impairment, which were associated with reduced estradiol levels and ERα, ERβ and GPER expression. In vitro, a lipid overload model of SH-SY-5Y cells was established and treated with inhibitors of ERs. β-estradiol or simvastatin effectively attenuated dyslipidemia-induced neuronal apoptosis via upregulation of ERs, whereas ERα, ERβ and GPER inhibitors together abolished the protective effect of simvastatin on lipid-induced neuronal apoptosis. We conclude that decreased estrogen and its receptor function in the postmenopausal stage promote neuronal damage and cognitive impairment by exacerbating dyslipidemia, and that estrogen supplementation or lipid lowering is an effective way to ameliorate hippocampal damage and cognitive dysfunction via upregulation of ERs.

Graphical Abstract
The long non-coding RNA NEAT1 promotes the progression of human ovarian cancer through targeting miR-214-3p and regulating angiogenesis
Authors: Liu Yang , Li Yan , Wu Yanzhi , Zhao Yiyue , Hu Xi , Sun Chunyi
Published: November 2023

Background

Angiogenesis and metastasis contributes substantially to the poor outcome of patients with ovarian cancer. We aimed to explore the role and mechanisms of the long non-coding RNA NEAT1 (nuclear enriched abundant transcript 1) in regulating angiogenesis and metastasis of human ovarian cancer. NEAT1 expression in human ovarian cancer tissues and cell lines including SKOV-3 and A2780 was investigated through in situ hybridization. Gene knockdown and overexpressing were achieved through lentivirus infection, transfection of plasmids or microRNA mimics. Cell viability was measured with the cell counting kit-8 assay, while apoptosis was determined by flow cytometry. Cell migration and invasion were evaluated by transwell experiments, and protein expression was determined by western blot assays or immunohistochemistry. Duo-luciferase reporter assay was employed to confirm the interaction between NEAT1 and target microRNA. In vivo tumor growth was evaluated in nude mice with xenografted SKOV-3/A2780 cells, and blood vessel formation in tumor was examined by histological staining.

Results

NEAT1 was highly expressed in ovarian cancer tissues of patients and cell lines. MiR-214-3p was identified as a sponging target of NEAT1, and they antagonizedeach other in a reciprocal manner. NEAT1-overexpressing SKOV-3 and A2780 cells had significantly increased proliferation, reduced apoptosis, and augmented abilities of migration and invasion, while cells with NEAT1-knockdown displayed markedly attenuated traits of malignancies. Additionally, the levels of NEAT1 appeared to be positively correlated with the expression levels of angiogenesis-related molecules, including Semaphorin 4D (Sema4D), Sema4D receptor Plexin B1, T-lymphoma invasion and metastasis-inducing protein-1 (Tiam1), and Rho-like GTPases Rac1/2/3. In the xenograft mouse model, more NEAT1 expression resulted in faster in vivo tumor growth, more blood vessel formation in tumor tissues, as well as higher expression levels of angiogenesis-related molecules and CD31.

Conclusions

NEAT1 promotes angiogenesis and metastasis in human ovarian cancer. NEAT1 and miR-214-3p are promising targets for developing therapeutics to treat human ovarian cancer.
Phenolic content, antioxidant and antimicrobial activities evaluation and relationship of commercial spices in the lebanese market
Authors: Rayess Youssef El , Nehme Lea , Ghanem Chantal , Beyrouthy Marc El , Sadaka Carmen , Azzi-Achkouty Samar , Nehme Nancy , Gürer Eda Sönmez , Sharifi-Rad Javad
Published: November 2023

Lebanese cuisine is renowned for its distinctive flavours and vibrant aromas. In Lebanese cuisine, spices are not just used for their flavour; they are also valued for their medicinal properties. This study consists of evaluating and comparing the total phenolic content and the antioxidant capacity of 21 samples of spices used in the Lebanese daily diet, such as cinnamon, allspice, coriander, cloves, etc. and the mixtures prepared in well-defined proportions. Several solvents were tested for the extraction of the phenolic compounds from spices, and the water and ethanol (v/v) mixture were retained for this study. Results showed that clove presented the highest polyphenol content (173.7 ± 2.98 mg Gallic Acid Equivalent (GAE)/g Dry Matter (DM)) and the highest antioxidant capacity by ABTS test (4875.68 ± 480.40 µmol trolox / g DM). and DPPH test (85.84 ± 0.5%). The examination of the results showed a positive significant correlation between the polyphenol contents and the antioxidant activity of the spices. The antimicrobial activity tested by the broth microdilution method was determined against Escherichia coli, Listeria monocytogenes, Staphylococcus aureus and Salmonella Enteritidis. The results showed high antimicrobial activity manifested by low value of minimum inhibitory concentration (MIC) (MIC < 2.4 µg/mL) for cinnamon, turmeric, white pepper, red pepper, allspice, clove and nutmeg. In conclusion, spices used in Lebanese cuisine, such as clove, cinnamon, allspice and spices, were rich in phenolic compounds and presented important potential health benefits.
An observational pilot evaluation of the Walk with Ease program for reducing fall risk among older adults
Authors: Lamoureux Nicholas R. , Lansing Jeni , Welk Gregory J.
Published: November 2023

Background

Physical activity is an effective method of reducing fall risk among older adults. Previous evaluations of the six-week Walk with Ease (WWE) program have documented benefits to functional outcomes, but the potential effects on reducing fall risk have not been evaluated. This pilot study evaluates outcomes of a community delivered WWE program for potential suitability as a fall risk reduction program.

Methods

A total of 59 older adults (age > 60) enrolled in a group version of WWE delivered by trained community-based leaders. Complete data (pre- and post-program) from functional fitness tests and behavioral instruments were obtained from 41 participants (aged 74.4 ± 6.6 years, 70% female). Functional outcomes included the 10-foot timed up and go (TUG), 30-second chair stand (CST) and 4-stage balance test (BT) included as part of STEADI, as well as a two-minute step test (ST) and normal gait speed test (GST). Survey assessments included STEADI fall risk screening, self-reported physical activity, and fear of falling measures. Analyses focused on reporting pre-post effect sizes, but paired t-tests were used to test statistical significance of differences.

Results

Improvements in functional performance approached significance for both CST (d = 0.31, p = 0.06) and ST (d = 0.26, p = 0.12), but all other tests were nonsignificant. Survey results demonstrated significant increases in self-reported walking (d = 0.54, p = 0.02) and moderate-to-vigorous physical activity (MVPA; d = 0.56, p = 0.004), but perceived fear of falling and overall fall risk scores had smaller, non-significant, effects (d ranging from 0.01 to 0.31). Stratified analysis suggested that participants screened at an elevated risk for falls at baseline consistently had larger effects on all functional and survey assessments, though the analysis was underpowered to test significance.

Conclusions

Walk with Ease participation significantly increased self-reported physical activity but did not significantly improve physical function or reduce fall risk. However, consistently larger effect sizes among participants screened as at-risk for falls suggest that the program may be beneficial for those with elevated risk for falls or functional limitations. Further research is needed to document the consistency of these effects among participants with elevated fall risk status.
Identifying individualized prognostic signature and unraveling the molecular mechanism of recurrence in early-onset colorectal cancer
Authors: Yang Jia , Zhao Yuting , Yuan Rongqiang , Wang Yongtong , Wang Shiyi , Chang Zhiqiang , Zhao Wenyuan
Published: November 2023

Background

The incidence and mortality of early-onset colorectal cancer (EOCRC; < 50 years old) is increasing worldwide, with a high recurrence rate. The inherent heterogeneity of EOCRC makes its treatment challenging. Hence, to further understand the biology and reveal the molecular mechanisms of EOCRC, a recurrence risk signature is needed to guide clinical management.

Methods

Based on the relative expression orderings (REOs) of genes in each sample, a prognostic signature was developed and validated utilizing multiple independent datasets. The underlying molecular mechanisms between distinct prognostic groups were explored via integrative analysis of multi-omics data.

Results

The prognostic signature consisting of 6 gene pairs (6-GPS) could predict the recurrence risk for EOCRC at the individual level. High-risk EOCRC classified by 6-GPS showed a poor prognosis but a good response to adjuvant chemotherapy. Moreover, high-risk EOCRC was characterized by epithelial-mesenchymal transition (EMT) and enriched angiogenesis, and had higher mutation burden, immune cell infiltration, and PD-1/PD-L1 expression. Furthermore, we identified four genes associated with relapse-free survival in EOCRC, including SERPINE1, PECAM1, CDH1, and ANXA1. They were consistently differentially expressed at the transcriptome and proteome levels between high-risk and low-risk EOCRCs. They were also involved in regulating cancer progression and immune microenvironment in EOCRC. Notably, the expression of SERPINE1 and ANXA1 positively correlated with M2-like macrophage infiltration.

Conclusion

Our results indicate that 6-GPS can robustly predict the recurrence risk of EOCRC, and that SERPINE1, PECAM1, CDH1, and ANXA1 may serve as potential therapeutic targets. This study provides valuable information for the precision treatment of EOCRC.
Exploring the dynamics of mobile app addiction: the interplay of communication, affective factors, flow, perceived enjoyment, and habit
Authors: Jo Hyeon , Baek Eun-Mi
Published: November 2023

The rapid proliferation of mobile apps and their increasing usage have led to growing concerns about potential addiction among users. Previous research has identified several factors that contribute to addiction, including flow, perceived enjoyment, and habit. However, the underlying mechanisms and the role of affective factors remain unclear. This study aims to elucidate the key factors that affect mobile app addiction by proposing a theoretical framework incorporating communication, affective factors, flow, perceived enjoyment, and habit. Data were collected from 320 mobile app users through a questionnaire survey. The research employed partial least squares structural equation modeling (PLS-SEM) to analyze the data and test the proposed relationships. The analysis indicates that communication is significantly associated with perceived enjoyment but does not directly affect flow and habit. The research unveils that positive affect significantly influences both flow and perceived enjoyment, but does not influence habit. Negative affect was found to have no significant effect on flow, perceived enjoyment, and habit. The results demonstrate that flow, perceived enjoyment, and habit are significantly related to addiction. The findings reveal that perceived enjoyment has a substantial impact on both flow and habit. These findings offer valuable guidelines for future research and practical implications for developers and policymakers in addressing the challenges associated with mobile app addiction.
Copeptin: a novel prognostic biomarker in trauma: a review article
Authors: Sarkarinejad Artin , Paydar Shahram , Khosrojerdi Arezou , Hosseini Maryam
Published: November 2023

Background

Trauma has a significant impact on the overall health of individuals worldwide, being a leading cause of morbidity and mortality with long-lasting effects. The identification of suitable biomarkers is crucial to predict patient outcomes, providing information about the severity of a condition or the probability of a specific outcome. Hence, in this study, we addressed a new biomarker, copeptin, and discussed its prognostic roles in various trauma researches.

Main body

Copeptin is a peptide derived from the precursor of the hormone vasopressin, which is released in response to stress. Copeptin can serve as a valuable biomarker for determining the severity, prognosis, and outcome of trauma patients. Elevated levels of copeptin are associated with increased mortality and poor clinical outcomes in patients with severe injuries or bleeding. Implementing copeptin measurements in clinical practice can enable healthcare providers to more accurately gauge the degree of trauma and predict patient mortality and morbidity outcomes facilitating prompt interventions and personalized treatment.

Conclusion

The measurement of novel biomarker copeptin can serve as a prognostic molecule for further outcomes in trauma patients. Nevertheless, supplementary research is needed to fully comprehend its role in the development and progression of traumatic injuries.
Association between body mass index (BMI) and [123I]Ioflupane (DaTSCAN) availabilities in patients with parkinsonism using single-photon emission computed tomography–computed tomography (SPECT-CT)
Authors: Parekh Puja , Begley Patrick , Jessop Maryam , Aplin Mark , Missir Elena , McMeekin Helena , Raczek Gosia , Singh Nitasha , Dizdarevic Sabina
Published: November 2023

Aim

[123I]Ioflupane (DaTSCAN) has a high binding affinity to the dopamine (DA) transporter (DaT) and tenfold less affinity to serotonin (5-HT) transporter (SERT). Both neurotransmitters are considered to contribute to body weight regulation. This study assesses the association between body mass index (BMI) and DaTSCAN availability in brain.

Method

Scans from 74 consecutive patients who had undergone DaTSCAN single-photon emission computed tomography–computed tomography (SPECT-CT) were used to obtain semi- and absolute quantitative data in several volumes of interest (VOIs). Relative semi-quantitative specific binding ratios (SBRs) from Chang attenuated SPECT were obtained from GE DaTQUANT. Absolute normalised concentration (NC) was calculated from attenuation/scatter corrected SPECT-CT images, using an adapted version of the EARL Ltd (European Association of Nuclear Medicine (EANM) Research 4 Life) template. Scans were subdivided into either degenerative parkinsonism (abnormal = 49), borderline (n = 14) or scan without evidence of dopaminergic deficit (SWEDD = 11) using visual assessment and SBR values by two nuclear medicine consultants.

Results

SBRs did not correlate with BMI. However, NC values correlated negatively in the entire cohort, with the strongest correlation in the frontal (r = − 0.649. p = 0.000), occipital (r = − 0.555, p = 0.000) regions and pons (r = − 0.555, p = 0.000). In the abnormal (n = 49) and SWEDD group (n = 11), NC of the frontal region was the most correlated with BMI (r = − 0.570, p = 0.000; r = − 0.813, p = 0.002, respectively). In the borderline group (n = 14), the left posterior putamen displayed the strongest correlation (r = − 0.765, p = 0.001).

Conclusion

Absolute NC values demonstrate a strong inverse correlation with BMI, strongest in the extrastriatal regions. Due to the predominately non-overlapping distribution of DaT and SERT, this study suggests greater involvement of SERT in obesity with possible interplay with DA transmission.
3D flow and fibre orientation modelling of compression moulding of A-SMC: simulations and experimental validation in squeeze flow
Authors: Alnersson Gustaf , Lejon Erik , Zrida Hana , Aitomäki Yvonne , Ljung Anna-Lena , Lundström T. Staffan
Published: November 2023

Sheet Moulding Compound (SMC) based composites have a large potential in industrial contexts due to the possibility of achieving comparatively short manufacturing times. It is however necessary to be able to numerically predict both mechanical properties as well as manufacturability of parts.

In this paper a fully 3D, semi-empirical model based on fluid mechanics for the compression moulding of SMC is described and discussed, in which the fibres and the resin are modelled as a single, inseparable fluid with a viscosity that depends on volume fraction of fibres, shear strain rate and temperature. This model is applied to an advanced carbon-fibre SMC with a high fibre volume fraction (35%). Simulations are run on a model of a squeeze test rig, allowing comparison to experimental results from such a rig. The flow data generated by this model is then used as input for an Advani-Tucker type of model for the evolution of the fibre orientation during the pressing process. Numerical results are also obtained from the software 3DTimon. The resulting fibre orientation distributions are then compared to experimental results that are obtained from microscopy. The experimental measurement of the orientation tensors is performed using the Method of Ellipses. A new, automated, accurate and fast method for the ellipse fitting is developed using machine learning. For the studied case, comparison between the experimental results and numerical methods indicate that 3D Timon better captures the random orientation at the outer edges of the circular disc, while 3D CFD show larger agreement in terms of the out-of-plane component. One of the advantages of the new image technique is that less work is required to obtain microscope images with a quality good enough for the analysis.
Establishing the link between microbial communities in bovine liver abscesses and the gastrointestinal tract
Authors: Pinnell Lee J. , Young J. Daniel , Thompson Tyler W. , Wolfe Cory A. , Bryant Tony C. , Nair Mahesh N. , Richeson John T. , Morley Paul S.
Published: November 2023

Background

Liver abscesses (LAs) are one of the most common and important problems faced by the beef industry. The most efficacious method for the prevention of LAs in North America is through dietary inclusion of low doses of antimicrobial drugs such as tylosin, but the mechanisms by which this treatment prevents LAs are not fully understood. LAs are believed to result from mucosal barrier dysfunction in the gastrointestinal tract (GIT) allowing bacterial translocation to the liver via the portal vein, yet differences in the GIT microbiome of cattle with and without LAs have not been explored. Here, we characterized microbial communities from LAs, rumen, ileum, and colon from the same cattle for the first time.

Results

Results demonstrate that tylosin supplementation was associated with differences in microbial community structure in the rumen and small intestine, largely because of differences in the predominance of Clostridia. Importantly, we show for the first time that microbial communities from multiple LAs in one animal’s liver are highly similar, suggesting that abscesses found at different locations in the liver may originate from a localized source in the GIT (rather than disparate locations). A large portion of abscesses were dominated by microbial taxa that were most abundant in the hindgut. Further, we identified taxa throughout the GIT that were differentially abundant between animals with and without liver abscesses. Bifidobacterium spp.—a bacteria commonly associated with a healthy GIT in several species—were more abundant in the rumen and ileum of animals without LAs compared to those with LAs.

Conclusions

Together these results provide the first direct comparison of GIT and LA microbial communities within the same animal, add considerable evidence to the hypothesis that some LA microbial communities arise from the hindgut, and suggest that barrier dysfunction throughout the GIT may be the underlying cause of LA formation in cattle.
Urban built heritage protection and realistic dilemmas: the development process, protection system, and critical thinking of historic districts in Dalian
Authors: Zhang Hongchi , Wang Fenglin , Guo Fei , Cai Jun , Dong Jing
Published: November 2023

In China, the northeastern region has preserved many valuable modern built heritage buildings, which are undergoing difficult exploratory protection during the industrial and urbanisation process. Taking Dalian city as a case study, this article retraces the history of Dalian’s opening up and colonial management from the perspective of urban planning and historic district protection and management systems. This article sorts out the influence of national and local institutional policies on Dalian’s urban construction and development to analyse the past evolution, current problems and internal causes of the renovation and protection of Dalian’s typical historic districts. This influence is mainly reflected in the lack of protection and damage done to unofficial heritage, the disconnection between historic districts and the surrounding environments and urban textures, and the Chinese-style transformation and economic decline of exotic areas. This paper calls for attention to and the rapid clarification of the built heritage list, the improvement of planning and protection systems and related supporting policies, and a focus on the protection of the authenticity of colonial heritage. This paper provides strategic guidance for improving the protection of historic districts in Dalian in Northeast China and hopes to serve as a reference for the protection of built heritage in other nonfamous historic and cultural cities.
Modelling of asymmetric channel plasmonic polariton waveguides
Authors: Imad Saja , Mansoor Riyadh , Ali Rasha , Hussain Fras
Published: November 2023

Channel plasmonic polariton (CPP) waveguides are a promising technology for integrated photonics. They offer several advantages over other plasmonic waveguides and are well-suited for various applications. In this research, a new design of asymmetric double-trenched CPP waveguide is suggested and examined. This design consists of two silicon trenches etched into a silicon dioxide substrate layer; with a gold layer sandwiched in between. The trenches are asymmetric, with one trench being wider than the other. This asymmetry creates a spatially varying surface plasmon polariton (SPP) field, which can guide light along the waveguide. The polarization characteristics of this proposed design are analyzed over a specific wavelength range (0.7 $$-$$
-
1.7 µm) to evaluate the mode confinement of the light within the structure. The design performance was optimized by changing the gold layer thickness and the dimensions of the lower trench. Different scenarios are examined to observe TE and TM-polarized modes’ behavior within the groove. A 1867.119 dB/µm suppression level at 0.92 µm wavelength is achieved which offers a small-size component for compact photonic logic gates, enabling the development of next-generation photonic devices.
A Research Note on Trends in the Stock and Flow of Child Support Agreements
Authors: Cancian Maria , Costanzo Molly A. , Meyer Daniel R.
Published: November 2023

In this research note, we demonstrate that trends in the likelihood of child support agreements differ by marital history (i.e., never-married vs. ever-married) and by whether measures rely on the stock of families (i.e., all those in which children live apart from a parent) or the flow (i.e., those that include children who newly live apart from a parent) in a given year. While previous research has highlighted difference by marital history, the contrast between stock and flow is a new contribution. Trends are typically measured with reference to the stock of cases, even while the flow of cases, which more immediately reflects concurrent policy changes, is more relevant in many contexts. Interpretations of recent declines in child support agreements in the stock of cases—referenced as evidence for both mandating participation and the impracticality of requiring child support—may be better informed by considering the flow of cases. We find the flow of previously married mothers increasingly likely to have child support agreements while the likelihood is relatively consistent over time for never-married mothers. For both groups, using the flow measure, we find notable increases in agreements without payments due in the most recent period. These findings underscore the importance of differentiating stock and flow, and by marital history, in considering the proportion with agreements as an indicator of the effectiveness of current policy.
Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale
Authors: Imaz-Rosshandler Ivan , Rode Christina , Guibentif Carolina , Harland Luke T. G. , Ton Mai-Linh N. , Dhapola Parashar , Keitley Daniel , Argelaguet Ricard , Calero-Nieto Fernando J. , Nichols Jennifer , Marioni John C. , de Bruijn Marella F. T. R. , Göttgens Berthold
Published: November 2023

Early organogenesis represents a key step in animal development, during which pluripotent cells diversify to initiate organ formation. Here, we sampled 300,000 single-cell transcriptomes from mouse embryos between E8.5 and E9.5 in 6-h intervals and combined this new dataset with our previous atlas (E6.5-E8.5) to produce a densely sampled timecourse of >400,000 cells from early gastrulation to organogenesis. Computational lineage reconstruction identified complex waves of blood and endothelial development, including a new programme for somite-derived endothelium. We also dissected the E7.5 primitive streak into four adjacent regions, performed scRNA-seq and predicted cell fates computationally. Finally, we defined developmental state/fate relationships by combining orthotopic grafting, microscopic analysis and scRNA-seq to transcriptionally determine cell fates of grafted primitive streak regions after 24 h of in vitro embryo culture. Experimentally determined fate outcomes were in good agreement with computationally predicted fates, demonstrating how classical grafting experiments can be revisited to establish high-resolution cell state/fate relationships. Such interdisciplinary approaches will benefit future studies in developmental biology and guide the in vitro production of cells for organ regeneration and repair.
Mesenchyme governs hair follicle induction
Authors: Mäkelä Otto J. M. , Mikkola Marja L.
Published: November 2023

Tissue interactions are essential for guiding organ development and regeneration. Hair follicle formation relies on inductive signalling between two tissues, the embryonic surface epithelium and the adjacent mesenchyme. Although previous research has highlighted the hair-inducing potential of the mesenchymal component of the hair follicle – the dermal papilla and its precursor, the dermal condensate – the source and nature of the primary inductive signal before dermal condensate formation have remained elusive. Here, we performed epithelial-mesenchymal tissue recombination experiments using hair-forming back skin and glabrous plantar skin from mouse embryos to unveil that the back skin mesenchyme is inductive even before dermal condensate formation. Moreover, the naïve, unpatterned mesenchyme was sufficient to trigger hair follicle formation even in the oral epithelium. Building on previous knowledge, we explored the hair-inductive ability of the Wnt agonist R-spondin 1 and a Bmp receptor inhibitor in embryonic skin explants. Although R-spondin 1 instigated precocious placode-specific transcriptional responses, it was insufficient for hair follicle induction, either alone or in combination with Bmp receptor inhibition. Our findings pave the way for identifying the hair follicle-inducing cue.
Identification of distinct active pools of yeast serine palmitoyltransferase in sub-compartments of the ER
Authors: Esch Bianca M. , Walter Stefan , Schmidt Oliver , Fröhlich Florian
Published: November 2023

Sphingolipids (SPs) are one of the three major lipid classes in eukaryotic cells and serve as structural components of the plasma membrane. The rate-limiting step in SP biosynthesis is catalyzed by the serine palmitoyltransferase (SPT). In budding yeast (Saccharomyces cerevisiae), SPT is negatively regulated by the two proteins, Orm1 and Orm2. Regulating SPT activity enables cells to adapt SP metabolism to changing environmental conditions. Therefore, the Orm proteins are phosphorylated by two signaling pathways originating from either the plasma membrane or the lysosome (or vacuole in yeast). Moreover, uptake of exogenous serine is necessary for the regulation of SP biosynthesis, which suggests the existence of differentially regulated SPT pools based on their intracellular localization. However, measuring lipid metabolic enzyme activity in different cellular sub-compartments has been challenging. Combining a nanobody recruitment approach with SP flux analysis, we show that the nuclear endoplasmic reticulum (ER)-localized SPT and the peripheral ER localized SPT pools are differentially active. Thus, our data add another layer to the complex network of SPT regulation. Moreover, combining lipid metabolic enzyme re-localization with flux analysis serves as versatile tool to measure lipid metabolism with subcellular resolution.
Νίκος Καρβούνης (Ιθάκη, 1880 - Αθήνα, 1947)
Authors: Μούτσιανου Όλγα
Published: November 2023

Η διατριβή διερευνά τη ζωή και το έργο του Νίκου Καρβούνη (1880-1947), ο οποίος υπήρξε μια αντιπροσωπευτική περίπτωση της εποχής. Ο Καρβούνης έζησε στη μεταιχμιακή εποχή, όπου η διάβρωση του μύθου της προόδου διασταυρώθηκε με τη νεωτερική αντίληψη για τον χρόνο και την ιστορία και έφερε την κοινωνία σε οριακή κατάσταση (liminal). Η περίπτωση του Νίκου Καρβούνη, συνδέεται άμεσα με όλες τις διεργασίες που συντελούνται τόσο στον ελληνικό χώρο όσο και στον ευρωπαϊκό, μελετάται δε σε συνάρτηση με τη γενεαλογία των ιδεών του και κατ´επέκταση της ιστορίας. Μέσω της μελέτης του έργου του, αναδεικνύεται το πλήρες εύρος των τεχνοτροπικών, ιδεολογικών, γλωσσολογικών μεταβολών που συντελέστηκε καθόλη την πορεία του. Ένας ακόμη θέμα της μελέτης είναι η ανίχνευση των ιδεολογικών και καλλιτεχνικών τάσεων της υπό εξέταση περιόδου και η πρόσληψή τους από το υποκείμενο της μελέτης, ώστε να αναδειχθεί η αντιφατικότητα της μεσοπολεμικής περιόδου. Η εποχή που ζει και δημιουργεί δίνει έκφραση σε διάφορα κινήματα και ρεύματα συχνά αντιφατικά και πολύμορφα. Η σκιαγράφηση και η ερμηνεία της πορείας της ζωής του Νίκου Καρβούνη, με τη μελέτη του έργου του, της φιλοσοφίας του και της πολυσύνθετης διαδρομής του, καταδεικνύει πώς επηρέασε το κοινωνικό και πολιτικό γίγνεσθαι της εποχής του, και ποιο ήταν το πλαίσιο υποδοχής και διάχυσης του έργου του στην Ελλάδα και στην Ευρώπη μέχρι το 1945. Παράλληλα, μέσα από το βίο του Καρβούνη παρακολουθούμε πώς διαμορφώνεται η φιγούρα του διανοούμενου, μέσα από την ετερογενή πρόσληψη της κοινωνικής και ιδεολογικής δυναμικής, και πώς διαμορφώνεται η εμβληματική περίπτωση του Καρβούνη, σε μια περίοδο που χαρακτηρίζεται από ισχυρές αντιφάσεις, πολύπλοκες ερμηνείες της κοινωνικής πραγματικότητας και διαρκείς ιδεολογικές αναθεωρήσεις. Τελικά, η μελέτη της περίπτωσης του Νίκου Καρβούνη, του μεταβατικού αυτού υποκειμένου, εστιάζει στο πως αναπλάθεται η προσωπικότητά του σε όλη του την πορεία, ως φαινόμενο της νεωτερικής κοινωνίας με οικουμενικές συνδέσεις, και σε ολόκληρο το φάσμα της ιδεολογικής, καλλιτεχνικής και πολιτικής παραγωγής του. Η μελέτη καταδεικνύει την διαμόρφωση ενός σημαντικού διανοούμενου, που έζησε σε μια εποχή συλλογικών προσδοκιών και με τη συγκρουσιακή του διάσταση, έμεινε αφανής στις δέλτους της Ιστορίας σε μια προσπάθεια επιλεκτικής αποσιώπησης.
The role of SOX2 in regulation of pluripotency and early cell fate decisions in embryos and embryonic stem cells
Authors: Κεραμάρη Μαρία
Published: November 2023

Ο μεταγραφικός παράγοντας Sox2 (SRY-σχετιζόμενο γονίδιο 2 με κουτί ομάδας υψηλής κινητικότητας) παίζει έναν καθοριστικό ρόλο στη διατήρηση της αναγεννητικότητας και ολοδυναμικότητας των εμβρυονικών βλαστοκυττάρων προερχόμενων από την εσωτερική κυτταρική μάζα του εμβρύου. Προηγουμένως είχε αποδειχθεί ότι Sox2 -/έμβρυα ποντικού πεθαίνουν λίγο μετά την εμφύτευση, ωστόσο, μητρικά μεταγραφικά προϊόντα του Sox2 μπορούν να επικαλύπτουν έναν νωρίτερο φαινότυπο. Η παρούσα μελέτη έχει δείξει ότι η αποσιώπηση του Sox2 με siRNA στο στάδιο των 2 κυττάρων του προεμφυτευτικού εμβρύου ποντικού έχει ως αποτέλεσμα διακοπή της ανάπτυξης στο στάδιο του μοριδίου, αυξημένη κυτταρική απόπτωση και απώλεια της ικανότητας δημιουργίας του πρώτου διαφοροποιημένου ιστού στο έμβρυο, του τροφοεξωδέρματος. Η απώλεια του τροφοεξωδέρματος πιθανά προκύπτει από την έλλειψη των μηνυμάτων Fgf4-Fgfr2 ή επειδή το Sox2 ενεργοποιεί απευθείας το Cdx2. Αυτό το καινοτόμο αποτέλεσμα προτείνει έναν πολύ νωρίτερο ρόλο για το Sox2 από ό,τι είχε προηγουμένως αναφερθεί. Ενώ η έκφραση βλαστο-σχετιζόμενων γονιδίων όπως το Oct4 και το Nanog διατηρήθηκε κατά την RNAi-επαγώμενη απώλεια του Sox2, μόρια απαιτούμενα για τη γένεση του τροφοεξωδέρματος (Cdx2, Eomes, Fgfr2 και Fgf4) ή την καθιέρωση του επιθηλίου της τροφοβλάστης (Occludin), χάθηκαν, και η διαμόρφωση της βλαστοκύστης αναχαιτίστηκε (μόνο το 18.7-21% των εμβρύων σχημάτισαν βλαστοκύστεις). Η αποσιώπηση του Sox2 σε εμβρυονικά βλαστοκύτταρα ποντικού, χρησιμοποιώντας πλασμιδιακούς φορείς shRNA, είχε ως συνέπεια τροποποιήσεις στην έκφραση αρκετών γονιδίων σχετιζόμενων με την ολοδυναμικότητα, τη γένεση του τροφοεξωδέρματος, του μεσο-/ενδοδέρματος, του νευροεξωδέρματος και τη ρύθμιση του κυτταρικού κύκλου. Το πιο εντυπωσιακό αποτύπωμα της αποσιώπησης του Sox2 σε εμβρυονικά βλαστοκύτταρα ποντικού ήταν η σημαντική αύξηση στα επίπεδα έκφρασης των δεικτών τροφοεξωδέρματος Cdx2 και Eomes, και των δεικτών μεσο-/ενδοδέρματος Mixl1, Goosecoid και Brachyury. Σε ένα περιβάλλον καλλιέργειας σχεδιασμένο να προωθεί τη νευρογένεση, τα Sox2 shRNA κύτταρα, απέκτησαν έναν φαινότυπο νευρογλοίας με περισσότερα αστροκύτταρα. Η απουσία του Sox2 είχε ως αποτέλεσμα μια σοβαρή αναχαίτιση του αυξητικού ρυθμού των εμβρυονικών βλαστοκυττάρων, απώλεια αναγεννητικότητας και διακοπή κυτταρικού κύκλου, απουσία αυξημένης απόπτωσης. Η αποσιώπηση με shRNA του SOX2 σε ανθρώπινα εμβρυονικά βλαστοκύτταρα, είχε ως συνέπεια την απώλεια δεικτών ολοδυναμικότητας και την αύξηση επιπέδων έκφρασης δεικτών τροφοεξωδέρματος και μεσο-/ενδοδέρματος. Τα παραπάνω ευρήματα προτείνουν ότι ενώ το Sox2 στο πρώιμο έμβρυο ποντικού επάγει τη διαμόρφωση του τροφοεξωδέρματος και είναι απαραίτητο για την αναπτυξιακή μετάβαση από το μορίδιο στο στάδιο της βλαστοκύστης, στα εμβρυονικά βλαστοκύτταρα ποντικού και ανθρώπου ενεργεί για να διατηρήσει την αναγεννητικότητα και να αναχαιτίσει τη διαφοροποίηση σε τροφοβλάστη και μεσό-ενδόδερμα.
Η συνεργασία σχολείου-οικογένειας μέσω της γονικής συμμετοχής στο πλαίσιο του αειφόρου σχολείου
Authors: Ναούμ Έλλη
Published: November 2023

Η Εκπαίδευση για το Περιβάλλον και την Αειφορία (ΕΠΑ) προτείνεται ως μια μετασχηματιστική παιδαγωγική διαδικασία, η οποία προσβλέπει στη δημιουργία ενός νέου εκπαιδευτικού πλαισίου αναφοράς. Το αειφόρο σχολείο υιοθετεί τις αρχές της ΕΠΑ και αναπτύσσεται ως οργανισμός μάθησης, σε τρία αλληλοεξαρτώμενα επίπεδα λειτουργίας, ενθαρρύνοντας συνεργατικές διεργασίες και  προωθώντας το άνοιγμα του σχολείου στην κοινότητα. Η συνεργασία σχολείου-οικογένειας μέσω της γονικής εμπλοκής μπορεί να αποτελέσει το όχημα που θα διευκολύνει το «άνοιγμα» αυτό. Η ερευνητική δραστηριότητα αναφορικά με τους παράγοντες που επηρεάζουν τη γονική συμμετοχή και τα οφέλη της στην εκπαίδευση των παιδιών, εξετάζεται σε συνδυασμό με το σφαιρικό μοντέλο και την τυπολογία γονικής εμπλοκής που προτείνει η Epstein και οι συνεργάτες της (2019). Τύποι, όπως, γονική μέριμνα, για τον προσδιορισμό κάθε οικογενειακού πλαισίου,  επικοινωνία, υποστήριξη του σχολείου στη μελέτη στο σπίτι, εθελοντική συμμετοχή των γονέων στα εκπαιδευτικά δρώμενα, διευκολύνουν τόσο την υπέρβαση των εμποδίων που δυσχεραίνουν τη συνεργασία σχολείου-οικογένειας όσο και τη δυνατότητα όλων των γονέων να συμμετέχουν στην εκπαίδευση των παιδιών τους με θετικά αποτελέσματα για όλους τους εμπλεκόμενους. Παρόμοια αποτελέσματα αναδείχτηκαν και στη διδακτορική διατριβή που υλοποιήθηκε με επιβλέπουσα την Ομότιμη Καθηγήτρια κ. Ε. Φλογαΐτη, με τίτλο, «Η συνεργασία σχολείου-οικογένειας στο πλαίσιο του αειφόρου σχολείου. Μια έρευνα δράσης σε νηπιαγωγείο».
Therapeutically applied Minecraft groups with neurodivergent youth
Authors: Kilmer Elizabeth , Spangler Johnny , Kilmer Jared
Published: November 2023

Background Therapeutically applied Minecraft groups are an intervention designed to support social engagement, confidence, and competence in youth. The flexible interaction format and use of a popular digital game support the fit of this intervention for use with neurodivergent youth. Minecraft is leveraged to support opportunities to build authentic relationships and social confidence in an engaging, low-stakes environment with peers. The group format allows for real-world social practice with peers, while the game environment can support motivation to interact with others, and provides multiple modes for such interaction (i.e., chat, building/movement with the avatar). Methods This article outlines the theoretical foundations of therapeutically applied Minecraft groups as well as practical considerations for implementation. The method outlined includes the justification for this method, process of creating support groups, check-in and check-out processes, and in-game activity examples for different situations. Use Cases Use cases are included to illustrate how the methods have been used in the past to support social growth with neurodivergent youth. Use cases include examples of different Minecraft servers, such as the habitat, and identifying stresses of social growth such as school anxiety and how the use of therapeutically applied Minecraft helped. Conclusions Therapeutically applied Minecraft groups can provide opportunities for peer connection and social practice in a facilitated environment. Though the use of Minecraft and other games to support learning and social connection is prevalent in the media, the academic research in this area is sparse. This article provides an example of Minecraft in use in a therapeutic context and calls for more formal research in this area of therapeutically applied games.
Digital teaching competence of higher education professors: self-perception study in an Ecuadorian university
Authors: Moreira-Choez Jenniffer Sobeida , Zambrano-Acosta Jimmy Manuel , López-Padrón Alexander
Published: November 2023

Background Teaching professionalization aimed at the digital transformation of educational scenarios and training processes for students in contemporary higher education requires the mastery of digital competence by the teaching staff. The objectives of the study were to analyze the self-perceived level of digital teaching competence (DTC) of the faculty of the Technical University of Manabí (UTM), Ecuador, and to establish the relationship between age, sex, and academic profile variables with digital teaching competence. Methods A quantitative methodological approach was adopted to develop a descriptive-correlational field study with a non-experimental design. The participants were 277 professors, selected through non-probabilistic and voluntary sampling, who completed the DigCompEdu Check-In questionnaire sent by e-mail. Results The data showed that the integrator and expert categories obtained high levels in all competencies. There is also a difference in the pedagogy variable by the interaction of sex and academic profile. Conclusions It is concluded that the competences self-perceived by the professors are within the intermediate categories such as integrator and expert. Likewise, the age, sex, and academic profile variables differ in the digital pedagogy level, which produces an inconsistent relationship, with the exception of the variable evaluates and provides feedback, where it was significant.
Corticosteroids and invasive fungal infections in hospitalized COVID-19 patients – A single-center cross-sectional study
Authors: Ramanathan Venkateswaran , Pari Thenmozhi Hariswar , Singh Rakesh , Bheemanathi Hanuman Srinivasan , Adithan Subathra
Published: November 2023

Background: During the coronavirus disease 2019 (COVID-19) epidemic, an increase in the incidence of fungal infections was observed.  However, the real magnitude of these fungal infections and their risk factors among COVID-19 patients in the Indian population is unknown.

Aim: To study the frequency, and spectrum of invasive fungal infections (IFI) among hospitalized COVID-19 patients, and the risk factors associated with invasive fungal infections.

Methods: We performed a retrospective, cross-sectional study; including all adult patients, admitted to Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), a tertiary care hospital in Southern India between April 2020 and August 2021, with COVID-19. Based on clinical-radiological features, patients with fungal infections were grouped into three diagnostic categories. Demographics, clinical, and laboratory features of patients with fungal infections were analyzed to identify the risk factors.

Results: About 10% (449 out of 4650) of the admitted patients with recent COVID-19, had some form of IFI. Among the patients with IFI, 80% (366 out of 449) were hospitalized for active COVID-19, whereas almost all the patients admitted with post-COVID complications had IFI. Of the 449 patients with IFI, 377 had mold infections and 88 had invasive candidiasis. Mucormycosis was the most common mold infection. Diabetes and diabetic ketoacidosis were strong independent predictors of IFI. We also found an association between end-stage renal disease, central venous catheterization, antibiotic usage, prior stroke, and corticosteroid therapy with IFI.

Conclusions: The frequency of fungal infections among hospitalized COVID-19 patients was high. Special precautions in COVID-19 patients with diabetes mellitus, corticosteroid therapy, and prior antibiotic usage may help to reduce invasive fungal infections.
Borders, cross-border cooperation and depopulation: the case of the Spanish-Portuguese North-Central Border
Authors: PODADERA-RIVERA PABLO , CALDERON-VAZQUEZ FRANCISCO J.
Published: November 2023

Background Cross-border cooperation has been (and still is) one of the main assets of the acquis communitiare in everything that refers to cross-border development. In fact, development initiatives aimed at addressing the problems of intra-European border areas could have better results if they were concerted (horizontally coordinated) and executed jointly by the governments, national, and local actors from both border sides, to improve their populations’ quality of life. The study goal is to provide new contributions that enrich critical reflection and debate on the issue of depopulation, in order to propose economic policy recommendations within a framework of cross-border institutional cooperation and inter- and intra-governmental coordination of political actors involved. Methods We prepared a descriptive analysis of its evolution during the period 1960-2020, with three essential variables: a) population evolution border based on the losses or gains verified with respect to 1960; b) critical population mass existing in 2020 based on the indicator of population density (inhabitants per square kilometer), and c) level of population aging based on the indicator percentage of population over 65 years of age over total population. Our descriptive analysis exclusively covers the border municipalities located along the both sides of the Spanish-Portuguese north-central border line, a total of 49 border municipalities (nine Portuguese and 40 spanish). Results The results show the existence of this recessive demographic continuum, which extends to both sides of the border, causes the need to face the depopulating phenomenon from a transnational and European perspective, in the sense that ‘national’ solutions to the phenomenon will not be able to offer answers common and consistent to a phenomenon as complex as depopulation. Conclusions It is necessary to reinforce the existing cross-border cooperation, providing it with greater operability at the level of institutional and administrative coordination, deepening the multilevel governance of the territory.