bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)
Authors: Eltoft Agnethe , Wilsgaard Tom , Roaldsen Melinda B. , Søyland Mary-Helen , Lundström Erik , Petersson Jesper , Indredavik Bent , Putaala Jukka , Christensen Hanne , Kõrv Janika , Jatužis Dalius , Engelter Stefan T. , De Marchis Gian Marco , Werring David J. , Robinson Thompson , Tveiten Arnstein , Mathiesen Ellisiv B.
Published: May 2022

Background

Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings.

Objective

To publish the detailed statistical analysis plan for TWIST prior to unblinding.

Methods

The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting.

Discussion

Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.

Trial registration

ClinicalTrials.govNCT03181360. EudraCT Number 2014-000096-80. WHO ICRTP registry number ISRCTN10601890.
Randomized double-blind, placebo-controlled study of topical diclofenac in the prevention of hand-foot syndrome in patients receiving capecitabine (the D-TORCH study)
Authors: Santhosh Akhil , Kumar Akash , Pramanik Raja , Gogia Ajay , Prasad Chandra Prakash , Gupta Ishaan , Gupta Nishkarsh , Cheung Winson Y. , Pandey Ravindra Mohan , Sharma Atul , Batra Atul
Published: May 2022

Introduction

Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS.

Methods

This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS)

Discussion

The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention.

Trial registration

Clinical Trials Registry of India CTRI/2021/01/030592. Prospectively registered on January 19, 2021
Multiple biochemical indices and metabolomics of Clonorchis sinensis provide a novel interpretation of biomarkers
Authors: Qiu Yang-Yuan , Chang Qiao-Cheng , Gao Jun-Feng , Bao Ming-Jia , Luo Hai-Tao , Song Jin-Ho , Hong Sung-Jong , Mao Rui-Feng , Sun Yun-Yi , Chen Ying-Yu , Liu Ming-Yuan , Wang Chun-Ren , Liu Xiao-Lei
Published: May 2022

Background

Clonorchiasis, an infectious disease caused by the liver fluke Clonorchis sinensis, may lead to the development of liver and gallbladder diseases, and even cholangiocarcinoma (CCA). However, the pathogenesis, host-pathogen interaction, and diagnostic markers for clonorchiasis remain unclear.

Methods

Eighteen rabbits were randomly divided into control group (n = 9) and C. sinensis-infected group (n = 9), and their plasma samples were collected at 7, 14, 28, and 63 days post-infection (dpi). Biochemical indices and metabolites in different infection periods were detected. A non-targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was employed to investigate the metabolic profiles of plasma in rabbits, and related metabolic pathways of differential metabolites and correlation between candidate biochemical indices and differential metabolites were analyzed. Finally, the candidate biomarkers were verified with human samples using a targeted metabolomics method.

Results

The result of biochemical indices indicated C. sinensis infection would affect the liver function biochemical indices, especially alanine aminotransferase, aspartate transaminase (AST), glutamyl transpeptidase (GGT), total bile acid, high-density lipoprotein, and cholinesterase. The metabonomic results showed that 58, 212, 23, and 21 differential metabolites were identified in different phases of the infection. Multivariate statistical analysis of differential metabolites revealed distinct metabolic signatures during different phases of infection, with most of these signatures being observed at 14 dpi, which mainly influences the amino acid metabolisms. For metabolites and biochemical indices, AST, GGT, hypoxanthine, l-pipecolic acid, and d-glucuronate represented potential noninvasive biomarkers for the diagnosis of C. sinensis (P < 0.05 and AUC > 0.8). Furthermore, GGT and d-glucuronate levels were positively correlated with the infection (r(28) = 0.98, P < 0.0001) and showed excellent diagnostic performance (AUC = 0.972; 95% confidence interval, 0.921 to 1.000).

Conclusions

The present results provide new insights into plasma metabolic changes in rabbits during C. sinensis infection, and the potential biomarker may be used for developing an effective method to diagnose clonorchiasis in the future.

Graphical Abstract
Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG
Authors: Lewis Nichole A. , Klein Rachel Herndon , Kelly Cailin , Yee Jennifer , Knoepfler Paul S.
Published: May 2022

Background

The histone variant H3.3 K27M mutation is a defining characteristic of diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). This histone mutation is responsible for major alterations to histone H3 post-translational modification (PTMs) and subsequent aberrant gene expression. However, much less is known about the effect this mutation has on chromatin structure and function, including open versus closed chromatin regions as well as their transcriptomic consequences.

Results

Recently, we developed isogenic CRISPR-edited DIPG cell lines that are wild-type for histone H3.3 that can be compared to their matched K27M lines. Here we show via ATAC-seq analysis that H3.3K27M glioma cells have unique accessible chromatin at regions corresponding to neurogenesis, NOTCH, and neuronal development pathways and associated genes that are overexpressed in H3.3K27M compared to our isogenic wild-type cell line. As to mechanisms, accessible enhancers and super-enhancers corresponding to increased gene expression in H3.3K27M cells were also mapped to genes involved in neurogenesis and NOTCH signaling, suggesting that these pathways are key to DIPG tumor maintenance. Motif analysis implicates specific transcription factors as central to the neuro-oncogenic K27M signaling pathway, in particular, ASCL1 and NEUROD1.

Conclusions

Altogether our findings indicate that H3.3K27M causes chromatin to take on a more accessible configuration at key regulatory regions for NOTCH and neurogenesis genes resulting in increased oncogenic gene expression, which is at least partially reversible upon editing K27M back to wild-type.
Biomineralization of cyanobacteria Synechocystis pevalekii improves the durability properties of cement mortar
Authors: Sidhu Navneet , Goyal Shweta , Reddy M. Sudhakara
Published: May 2022

Microbially induced calcium carbonate precipitation (MICCP) is considered a novel eco-friendly technique to enhance the structural properties of cementitious-based material. Maximum studies have emphasized using ureolytic bacteria to improve the durability properties of building structures. In this study, the role of photoautotrophic bacteria Synechocystis pevalekii BDHKU 35101 has been investigated for calcium carbonate precipitation in sand consolidation, and enhancing mechanical and permeability properties of cement mortar. Both live and UV-treated S. pevalekii cells were used to treat the mortar specimens, and the results were compared with the control. The compressive strength of mortar specimens was significantly enhanced by 25.54% and 15.84% with live and UV-treated S. pevalekii cells at 28-day of curing. Water absorption levels were significantly reduced in bacterial-treated mortar specimens compared to control at 7 and 28-day curing. Calcium carbonate precipitation was higher in live-treated cells than in UV-treated S. pevalekii cells. Calcium carbonate precipitation by S. pevalekii cells was confirmed with SEM-EDS, XRD, and TGA analysis. These results suggest that S. pevalekii can serve as a low-cost and environment friendly MICCP technology to improve the durability properties of cementitious materials.
Physiological effects of high-intensity versus low-intensity noninvasive positive pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease: a randomised controlled trial
Authors: Luo Zujin , Cao Zhixin , Li Yichong , Jin Jiawei , Sun Wei , Zhu Jian , Zhao Na , Liu Jichen , Wei Bing , Hu Yue , Zhang Ying , Ma Yingmin , Wang Chen
Published: May 2022

Background

High-intensity noninvasive positive pressure ventilation (NPPV) is a novel ventilatory approach to maximally decreasing elevated arterial carbon dioxide tension (PaCO2) toward normocapnia with stepwise up-titration of pressure support. We tested whether high-intensity NPPV is more effective than low-intensity NPPV at decreasing PaCO2, reducing inspiratory effort, alleviating dyspnoea, improving consciousness, and improving NPPV tolerance in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

In this physiological, randomised controlled trial, we assigned 24 AECOPD patients to undergo either high-intensity NPPV (n = 12) or low-intensity NPPV (n = 12). The primary outcome was PaCO2 24 h after randomisation. Secondary outcomes included gas exchange other than PaCO2 24 h after randomisation, inspiratory effort, dyspnoea, consciousness, NPPV tolerance, patient–ventilator asynchrony, cardiac function, ventilator-induced lung injury (VILI), and NPPV-related adverse events.

Results

Inspiratory positive airway pressure 24 h after randomisation was significantly higher (28.0 [26.0–28.0] vs. 15.5 [15.0–17.5] cmH2O; p = 0.000) and NPPV duration within the first 24 h was significantly longer (21.8 ± 2.1 vs. 15.3 ± 4.7 h; p = 0.001) in the high-intensity NPPV group. PaCO2 24 h after randomisation decreased to 54.0 ± 11.6 mmHg in the high-intensity NPPV group but only decreased to 67.4 ± 10.6 mmHg in the low-intensity NPPV group (p = 0.008). Inspiratory oesophageal pressure swing, oesophageal pressure–time product (PTPes)/breath, PTPes/min, and PTPes/L were significantly lower in the high-intensity group. Accessory muscle use and dyspnoea score 24 h after randomisation were also significantly lower in that group. No significant between-groups differences were observed in consciousness, NPPV tolerance, patient–ventilator asynchrony, cardiac function, VILI, or NPPV-related adverse events.

Conclusions

High-intensity NPPV is more effective than low-intensity NPPV at decreasing elevated PaCO2, reducing inspiratory effort, and alleviating dyspnoea in AECOPD patients.

Trial registration: ClinicalTrials.gov (NCT04044625; registered 5 August 2019).
A diffusive plankton system with time delay and habitat complexity effects under Neumann boundary condition
Authors: Li Yanfeng
Published: May 2022

In this paper, we establish a delayed semilinear plankton system with habitat complexity effect and Neumann boundary condition. Firstly, by using the eigenvalue method and geometric criterion, the stability of the equilibria and some conditions for determining the existence of Hopf bifurcation are studied. Through analyzing the stability of positive equilibrium, we found that at the positive equilibrium the system may switch finitely many times from stable to unstable, then from unstable to stable, finally becoming unstable, i.e., the time delay induces a “stability switch” phenomenon. Secondly, the properties of Hopf bifurcation are derived by applying the normal form method and center manifold theory, including the bifurcation direction and the stability of bifurcating periodic solutions. Finally, some numerical simulations are given to illustrate the theoretical results, and a biological explanation is given.
Spatial heterogeneities in acute lower respiratory infections prevalence and determinants across Ethiopian administrative zones
Authors: Fetene Meseret Tadesse , Fenta Haile Mekonnen , Tesfaw Lijalem Melie
Published: May 2022

Background

Acute lower respiratory infections (ALRI) are a major cause of mortality among children under five. This study aimed to investigate the spatiotemporal pattern of ALRI in Ethiopian administrative zones.

Methods

In this study, a total of 29,599 under-five children from 2299 geographical units in 2000, 2005, 2011, and 2016 Ethiopian Demographic and Health Surveys (EDHSs) were involved. The generalized multilevel mixed model to analyze the effect of child-household level characteristics on ALRI was adopted.

Results

Overall prevalence of ALRI among Ethiopian under-five children is found to be 15%, with 2000, recording the highest prevalence of 24.44% while 2016 had the lowest prevalence of 11.07%. Being in the higher age group of children and having no experience of undernutrition status showed significantly lower ALRI prevalence than their counterparts. Among the household characteristics children from uneducated parents, unimproved household sanitation, lower wealth index, and rural residents were more likely to have ALRI than their counterparts. Based on the best linear unbiased prediction (BLUP) for the zonal-level random effect, the performance of Zones was ranked.

Conclusions

Between and within the Ethiopian administrative Zones disparities in ALRI were observed. The ranking of the performance of the Zones may help to target the worst performing Zones for immediate intervention strategy and the best performing Zones as a role model to adopt their best practice in the Ethiopian strategy to achieve the Sustainable Development Goal by the year 2030.
Impacts of gain versus loss frame messages about beverages on boy students, an application of extended parallel process model
Authors: Zareharofteh Fateme , Karimi Masoud
Published: May 2022

Background

Unhealthy diet including consumption of high amounts of sugar-sweetened beverages is a key modifiable risk factor for obesity and NCDs which begin in childhood and adolescence. The study aimed to compare the effect of gain frame vs. loss frame messages on SSBs consumption intention and behavior of high school boy students.

Methods

In this quasi-experimental study, 270 students from three boy’s high schools were selected through a multistage random sampling. Data collection was done through a 15 items self-reported questionnaire before and two months after the intervention. Each of the two intervention groups received one of the two types of gain frame or loss frame designed pamphlets inspired with extended parallel process model. The control group received no pamphlet.

Results

In control, GFM and LFM groups 91, 86 and 89 students participated in the study, respectively. After the intervention, significant differences were observed in perceived efficacy and threat of the GFM group and perceived efficacy, threat and intention in the LFM group compared with before the intervention. The GFM group had higher perceived self-efficacy than the control group and lower perceived severity than the LFM group. Intention to consume SSBs reduced significantly in LFM group, compared with the control group.

Conclusions

A combination of LFM and GFM messages could more effectively lead to nutritional behavior change regarding the consumption of SSBs. Results help to design messages for educational programs and nutritional campaigns.
Insights on the introduction of autonomous vessels to liner shipping networks
Authors: Nguyen Gam Thi Hong , Ruzaeva Daria , Góez Julio Cesar , Guajardo Mario
Published: May 2022

This article investigates economic and operational effects of introducing autonomous vessels to liner shipping networks. By the formulation of optimization models, we analyze how fleet configurations with vessels of different capacity affect the cost and service level of liner shipping networks in both static and dynamic settings. We implement the model in a data instance that extends a data instance on the Baltic trade from conventional to autonomous vessels. Our results show that the introduction of autonomous vessels might lead to cost savings of 7.1% with respect to the fleet of conventional vessels. The main savings come from lower time charter costs and lower bunker costs. The results also suggest that a fleet configuration combining large with small vessels perform better, because of its better ability to accommodate to the asymmetry of the trade. The implementation of a flexible sailing schedule in the dynamic setting might lead to a great increase in the service level of the network, but at the expense of an increase in costs.
Splenomegaly versus pathological lung volume during COVID-19 infection with or without cytokine storm; a linear regression analysis using CT volumetry
Authors: Samir Ahmed , Gharraf Heba Said , Baess Ayman Ibrahim , Sweed Rania Ahmed , Matrawy Khaled , Geijer Mats , Shalabi Adel , Tarek Yasmine
Published: May 2022

Background

Due to the paucity of scientific evidence, it is unclear among pulmonologists and physicians in critical care units if and when splenomegaly in novel coronavirus disease (2019) (COVID-19) patients is worrisome. This study aims to evaluate the significance of splenic volume during COVID-19 infection with or without cytokine storm and correlates splenic volume to the volume of pathological lung changes through linear regression analysis.

Results

A retrospective study collected 509 polymerase chain reaction proved COVID-19 patients (399 males, 110 females; mean age 48 years, age range 24–78 years) between June and November 2021, without a history of splenic pathology. A control group of age and sex-matched 509 healthy subjects was used and analyzed according to the splenic volume. Five consulting radiologists evaluated initial and follow-up computed tomography (CT) examinations using lung CT volumetry and splenic volume calculation in consensus. Three consulting pulmonologists correlated the severity of clinical and laboratory findings, including oxygen requirements and interleukin-6 (IL-6) levels. The T test results for comparison between the COVID-19 patients and the healthy subjects control group regarding the splenic volume were significant (T value was − 4.731452 and p value was 0.00002). There was no significant correlation between the severity of the disease and normal-sized spleen (26% of patients, p = 0.916) or splenomegaly (24% of patients, p = 0.579). On the other hand, all patients with a small spleen or progressive splenomegaly during serial follow-up imaging had clinically severe disease with a statistically significant correlation (p = 0.017 and 0.003, respectively). Ninety-seven percent of patients with clinically mild disease and splenomegaly had 0–20% lung involvement (CT-severity score 1) while all patients with clinically severe disease and splenomegaly had 27–73% lung involvement (CT-severity score 2 and 3) (r = 0.305, p = 0.030).

Conclusions

Splenomegaly is a non-specific sign that may be found during mild and severe COVID-19 infection, it was not statistically correlated with the clinical severity and a weak positive relationship was found between the splenic size and the CT-severity score of the pathological lung volume. On the other hand, the presence of splenic atrophy or progressive splenomegaly was correlated with severe COVID-19 presentation and “cytokine storm”. Therefore, the splenic volume changes should not be overlooked in COVID-19 serial CT examinations, particularly in severe or critically ill patients with cytokine storms.
Joint use of multiseismic information for lithofacies prediction via supervised convolutional neural networks
Authors: Xu Minghui , Zhao Luanxiao , Gao Shunli , Zhu Xuanying , Geng Jianhua
Published: May 2022

Lithology prediction from seismic data is of great significance for sweet-spot detection, reservoir structure delineation, and geologic model building, hence it is important in reducing the risk of exploration and development. Traditional lithofacies prediction methods often are limited by the seismic inversion accuracy and reliability of the rock-physics relationships, which are challenging to be applied in complex reservoirs (such as those containing coal-bearing strata or thin layers). Convolutional neural networks (CNNs) can represent the coupling relationship of seismic characteristics in the time domain through multilayer convolution and effectively manipulate multitype and multidimensional seismic data. Under the framework of a supervised CNN, we jointly integrate prestack seismic gathers (Pre-SGs), seismic inversion results (P-impedance and [Formula: see text] ratio), multiseismic attributes (amplitude-variation-with-offset [AVO] intercept, AVO gradient, instantaneous amplitude, instantaneous frequency, and instantaneous phase), and spectral decomposition attributes (SDA) to predict lithofacies in a complex clastic reservoir interbedded with thin-layer coal. We determine that the fusion model with multiseismic information containing different perspectives and complementary information of seismic data is capable of achieving better prediction performance than only using one type of input feature. In particular, using the proposed methodology, the angle-dependent Pre-SG is essential to decipher the rich information of lithologic details. The models using only poststack seismic data or inversion results cannot reliably describe lithologic details (especially the thin-coal layers). In addition, by including the SDA into model inputs, the model’s ability to recognize thin layers has been further improved but lead to the slight sacrifice of overall prediction accuracy.
Differences in the Distribution of IGF-I Concentrations Between European and US Populations
Authors: Bidlingmaier Martin , Valcour Andre , Schilbach Katharina , Kuehnle Tim , Diederich Sven , Rogge Thomas , Cavalier Etienne , Katayev Alex
Published: May 2022

Context

Method-specific reference intervals (RIs) determine utility of IGF-I as a biomarker in GH-related diseases. Differences between populations might affect applicability of RIs.

Objective

To compare population-specific RIs derived from IGF-I routine testing in laboratories in the United States and Europe using the same assay.

Design and setting

Uncensored routine IGF-I testing results generated over 5 years in 4 accredited laboratories (US, n = 778 173 males/710 752 females; Europe, n = 23 220 males/40 183 females).

Main outcome measures

Construction of RIs by indirect statistical methods designed to use routine testing data (modified Hoffmann approach). Comparison to published RIs, between the US and Europe, and between regions in the United States with lower and higher mean body mass indexes (BMIs).

Results

Lower limits (LLs) of RIs calculated from all routine data sets do not differ from the published LLs. The same is true for upper limits (ULs) calculated from European routine data. ULs derived from US routine data are significantly higher (children, 10-18 years [mean, %]: boys + 149.3 ng/mL [+34.6%]; girls + 94.9 ng/mL [+19.8%]); adults (19-95 years: males + 45 ng/mL [+20.3%]; and females + 29.7 ng/mL [+13.8%]). Average IGF-I is higher in samples from Colorado (lower mean BMI) compared with Alabama (P < 0.0001), although the difference is smaller than between each of them and Europe.

Conclusions

We provide evidence that in large datasets from the same population, direct sampling and the indirect Hoffmann approach provide comparable RIs. Although LLs are comparable between Europe and the United States, the UL is significantly higher in the United States. We suggest use of adapted RIs for the United States.
Dorsal Root Ganglion Stimulation to Treat Focal Postsurgical and Diffuse Chronic Pain: A Case Report
Authors: Akuamoah Latrice A. , Tupper Connor , Nagrani Sohan , Chapman Kenneth B.
Published: May 2022

Dorsal root ganglion stimulation (DRG-S) is widely accepted for treating focal pain syndromes. We present the case of a 46-year-old woman with severe lumbar radiculopathy with an implanted spinal cord stimulator (SCS) that had lost efficacy. She developed an incisional hernia after undergoing a minimally invasive, extreme lateral interbody fusion and SCS explant. After herniorrhaphy, she presented with severe pain at the T10-T11 dermatomes, which we treated with DRG-S. One-year after lumbar fusion, her refractory lumbar and radicular pain returned, which we ultimately treated with bilateral T12+S1 DRG-S. DRG-S was thus used to successfully treat focal postsurgical and diffuse chronic pain.
Uncoupling transcription and translation through miRNA-dependent poly(A) length control in haploid male germ cells
Authors: Guo Mei , Luo Chunhai , Wang Zhuqing , Chen Sheng , Morris Dayton , Ruan Fengying , Chen Zhichao , Yang Linfeng , Wei Xiongyi , Wu Chuanwen , Luo Bei , Lv Zhou , Huang Jin , Zhang Dong , Yu Cong , Gao Qiang , Wang Hongqi , Zhang Ying , Sun Fei , Yan Wei , Tang Chong
Published: May 2022

As one of the post-transcriptional regulatory mechanisms, uncoupling of transcription and translation plays an essential role in development and adulthood physiology. However, it remains elusive how thousands of mRNAs get translationally silenced while stability is maintained for hours or even days before translation. In addition to oocytes and neurons, developing spermatids display significant uncoupling of transcription and translation for delayed translation. Therefore, spermiogenesis represents an excellent in vivo model for investigating the mechanism underlying uncoupled transcription and translation. Through full-length poly(A) deep sequencing, we discovered dynamic changes in poly(A) length through deadenylation and re-polyadenylation. Deadenylation appeared to be mediated by microRNAs (miRNAs), and transcripts with shorter poly(A) tails tend to be sequestered into ribonucleoprotein (RNP) granules for translational repression and stabilization. In contrast, re-polyadenylation might allow for translocation of the translationally repressed transcripts from RNP granules to polysomes. Overall, our data suggest that miRNA-dependent poly(A) length control represents a previously unreported mechanism underlying uncoupled translation and transcription in haploid male mouse germ cells.
Embryonic vascular establishment requires protein C receptor-expressing endothelial progenitors
Authors: Cissy Yu Qing , Bai Lanyue , Chen Yingying , Chen Yujie , Peng Guangdun , Wang Daisong , Yang Guowei , Cui Guizhong , Jing Naihe , Arial Zeng Yi
Published: May 2022

Vascular establishment is one of the early events in embryogenesis. It is believed that vessel-initiating endothelial progenitors cluster to form the first primitive vessel. Understanding the molecular identity of these progenitors is crucial in order to elucidate lineage hierarchy. In this study, we identify protein C receptor (Procr) as an endothelial progenitor marker and investigate the role of Procr+ progenitors during embryonic vascular development. Using a ProcrmGFP-2A-lacZ reporter, we reveal a much earlier Procr expression (embryonic day 7.5) than previously acknowledged (embryonic day 13.5). Genetic fate-mapping experiments using ProcrCre and ProcrCreER demonstrate that Procr+ cells give rise to blood vessels throughout the entire embryo proper. Single-cell RNA-sequencing analyses place Procr+ cells at the start of endothelial commitment and maturation. Furthermore, targeted ablation of Procr+ cells results in failure of vessel formation and early embryonic lethality. Notably, genetic fate mapping and scRNA-seq pseudotime analysis support the view that Procr+ progenitors can give rise to hemogenic endothelium. In this study, we establish a Procr expression timeline and identify Procr+ vessel-initiating progenitors, and demonstrate their indispensable role in establishment of the vasculature during embryo development.
Identification of fibroblast progenitors in the developing mouse thymus
Authors: Ferreirinha Pedro , Pinheiro Ruben G. R. , Landry Jonathan J. M. , Alves Nuno L.
Published: May 2022

The thymus stroma constitutes a fundamental microenvironment for T-cell generation. Despite the chief contribution of thymic epithelial cells, recent studies emphasize the regulatory role of mesenchymal cells in thymic function. Mesenchymal progenitors are suggested to exist in the postnatal thymus; nonetheless, an understanding of their nature and the mechanism controlling their homeostasis in vivo remains elusive. We resolved two new thymic fibroblast subsets with distinct developmental features. Whereas CD140αβ+GP38+SCA-1− cells prevailed in the embryonic thymus and declined thereafter, CD140αβ+GP38+SCA-1+ cells emerged in the late embryonic period and predominated in postnatal life. The fibroblastic-associated transcriptional programme was upregulated in CD140αβ+GP38+SCA-1+ cells, suggesting that they represent a mature subset. Lineage analysis showed that CD140αβ+GP38+SCA-1+ maintained their phenotype in thymic organoids. Strikingly, CD140αβ+GP38+SCA-1− generated CD140αβ+GP38+SCA-1+, inferring that this subset harboured progenitor cell activity. Moreover, the abundance of CD140αβ+GP38+SCA-1+ fibroblasts was gradually reduced in Rag2−/− and Rag2−/−Il2rg−/− thymi, indicating that fibroblast maturation depends on thymic crosstalk. Our findings identify CD140αβ+GP38+SCA-1− as a source of fibroblast progenitors and define SCA-1 as a marker for developmental stages of thymic fibroblast differentiation.
Ανάλυση βακτηριακών γονιδιωμάτων και εκκρινόμενων πρωτεϊνικών τελεστών για την μελέτη των μοριακών μηχανισμών παθογένειας της Ξανθομονάδας
Authors: Μιχαλοπούλου Βασιλική
Published: May 2022

Τα τελευταία χρόνια γίνονται εντατικές προσπάθειες για την κατανόηση των μοριακών μηχανισμών αλληλεπίδρασης των παθογόνων με τους ξενιστές τους. Οι προσπάθειες αυτές εστιάζουν τόσο στη διαλεύκανση των μηχανισμών παθογένειας των μικροοργανισμών, όσο και στους μηχανισμούς άμυνας που έχουν αναπτύξει οι οργανισμοί – ξενιστές τους. Όσον αφορά στα βακτηριακά παθογόνα, η αλληλούχιση ολοένα και περισσότερων γονιδιωμάτων την τελευταία πενταετία οδηγεί στην καλύτερη κατανόηση των βασικών και εξειδικευμένων μηχανισμών παθογένειας που αυτά φέρουν.Η παρούσα Διδακτορική Διατριβή χωρίζεται σε δυο κεφάλαια. Στο πρώτο μέρος της παρούσας εργασίας παρουσιάζεται η εύρεση νέων αλληλεπιδράσεων μεταξύ των τελεστών παθογένειας βακτηρίων και των πιθανών στόχων τους στον ξενιστή. Ακολουθούν τα αποτελέσματα της ανάλυση ενός ζεύγους αλληλεπίδρασης, του βακτηριακού συντηρημένου τελεστή XopP της Xanthomonas campestris παθότυπου campestris και του παράγοντα EXO70B1 του συμπλέγματος εξωκύττωσης του Arabidopsis thaliana, η οποία φαίνεται ότι είναι ειδική και ισχυρή. Στη συνέχεια, αναλύονται τα ευρήματά μας, όσον αφορά το μηχανισμό παθογένειας του XccXopP. Ο συγκεκριμένος τελεστής φαίνεται πως προκαλεί την καταστολή της βασικής άμυνας του ξενιστή του, μέσω αλληλεπίδρασης με διάφορα μέλη του συμπλόκου εξωκύττωσης, χωρίς να ενεργοποιεί την ειδική άμυνα του ξενιστή.Στο δεύτερο κεφάλαιο, παρουσιάζονται τα αποτελέσματα από την αλληλούχιση του γονιδιώματος τριών ειδών της ξανθομονάδας, αντιπροσωπευτικών για το είδος τους. Συγκεκριμένα, αναλύονται τα χαρακτηριστικά που ευρέθησαν από τα γονιδιώματα των Xanthomonas oryzae παθότυπο oryzicola, Xanthomonas hortorum παθότυπο hederae και Xanthomonas citri υποείδος malvacearum. Φαίνεται πως και τα τρία βακτήρια αυτά, διαθέτουν αρκετούς από τους συντηρημένους τελεστές, που εκκρίνονται από το εκκριτικό σύστημα τύπου ΙΙΙ, καθώς επίσης και δομικές και εκκρινόμενες πρωτεΐνες των εκκριτικών συστημάτων τύπου Ι, ΙΙ, IV και VI.
Μελέτη της αύξησης μικροφυκών σε ανακυκλώσιμα νερά ιχθυοτροφείων και παραγωγή προϊόντων υψηλής προστιθέμενης αξίας
Authors: Ντούρου Μαριάννα
Published: May 2022

H βιομάζα των μικροφυκών είναι πλούσια σε βιοδραστικές ενώσεις υψηλού βιοτεχνολογικού ενδιαφέροντος, με πολλαπλές εμπορικές εφαρμογές κι έτσι τα τελευταία χρόνια η καλλιέργειά τους σε μεγάλη κλίμακα έχει προσελκύσει το ενδιαφέρον ερευνητών και παραγωγικών μονάδων. Ωστόσο, η βιωσιμότητα της διαδικασίας επηρεάζεται αρνητικά από το υψηλό κόστος του μέσου καλλιέργειας και από τους τεράστιους όγκους νερού οι οποίοι απαιτούνται για την καλλιέργεια μικροφυκών. Από την άλλη, ο κλάδος της υδατοκαλλιέργειας, ολοένα και αυξανόμενος, συνδέεται με επιβλαβείς επιπτώσεις στους υδροφόρους ορίζοντες, εξαιτίας των υγρών αποβλήτων τα οποία παράγει. Αποτελεσματική εναλλακτική προσέγγιση για την αύξηση της βιωσιμότητας της διαδικασίας αποτελεί η αξιοποίηση των υγρών αποβλήτων υδατοκαλλιέργειας ως μέσο ανάπτυξης μικροφυκών. Για τους σκοπούς της παρούσας διατριβής, παραλήφθηκαν τρία υγρά απόβλητα από δεξαμενές εκτροφής ιχθύων διαφορετικού σωματικού βάρους από Ελληνική μονάδα ιχθυοκαλλιέργειας και ένα ακόμη από την κεντρική δεξαμενή καθίζησης της ιδίας εταιρίας. Σύμφωνα με τα προκαταρκτικά πειράματα, το απόβλητο προερχόμενο από τη δεξαμενή καθίζησης (effluent from the sedimentation tank, EST) αποδείχθηκε το καταλληλότερο να υποστηρίξει την αύξηση του μικροφύκους Nannochloropsis gaditana, σε καλλιέργειές του σε κωνικές φιάλες. Η χημική του σύσταση εμφάνισε εξάρτηση από το μέγεθος των εκτρεφόμενων ιχθύων. Πιο συγκεκριμένα, μήνες κατά τους οποίους στη μονάδα εκτρέφονταν ιχθύες μικρού σωματικού βάρους, στη δεξαμενή καθίζησης κατέληγαν λύματα πλούσια σε φώσφορο (phosphorus, P), έτσι ο ο λόγος Ν/P του αποβλήτου σε μία περίοδο παραλαβής ήταν 20,9 (μοναδική τιμή).
Τουριστική ανάπτυξη και τοπική αγροδιατροφή
Authors: Τσακοπούλου Κωνσταντίνα
Published: May 2022

Αντικείμενο της διατριβής αποτελεί η σχέση του τουρισμού, και ειδικότερα του γαστρονομικού τουρισμού, με το τοπικό σύστημα αγροδιατροφής. Σκοπός είναι να διαπιστωθεί κατά πόσο είναι δυνατές οι συνέργειες μεταξύ του τοπικού αγροδιατροφικού και του τουριστικού τομέα στο περιβάλλον των τουριστικά ανεπτυγμένων μικρών ελληνικών νησιών. Επιχειρεί να απαντήσει σε ερωτήματα σχετικά με: α) τις δυνατότητες διασύνδεσης του συμβατικού τουριστικού προτύπου με το τοπικό αγροδιατροφικό σύστημα, β) τα όρια της στρατηγικής για την ανάπτυξη του γαστρονομικού τουρισμού ως εναλλακτική οδό βιώσιμης τουριστικής ανάπτυξης με σκοπό την υπέρβαση των προβλημάτων στα οποία προσέκρουσαν τόσο το συμβατικό τουριστικό πρότυπο όσο και το συμβατικό αγροδιατροφικό σύστημα, γ) τις ευκαιρίες και τις δυσχέρειες για την ανάπτυξη των συνεργειών στο ιδιαίτερο περιβάλλον των τουριστικά ανεπτυγμένων νησιών, δ) τον ορισμό του τοπικού ως πεδίο διαπραγμάτευσης για τον επιχειρηματικό κόσμο και την κοινότητα, καθώς και ε) τις αναγκαίες κατευθύνσεις πολιτικής. Η διατριβή βασίζεται στην ερευνητική στρατηγική της θεωρητικά ενημερωμένης εμπειρικής έρευνας πεδίου. Το θεωρητικό σκέλος υιοθετεί την ολιστική προσέγγιση της ανθρωπογεωγραφίας υπό το πρίσμα της οποίας αναλύονται η ανάπτυξη του συμβατικού τουριστικού προτύπου και η αμφισβήτησή του, η ανάδυση των επιμέρους μορφών του γαστρονομικού τουρισμού, η χωρική και κοινωνική ενθήκευση των τοπικών συστημάτων αγροδιατροφής και οι προϋποθέσεις ανάπτυξης συνεργειών μεταξύ των δύο τομέων για τη δημιουργία τοπικής προστιθέμενης αξίας. Η επισκόπηση της ακαδημαϊκής συζήτησης συμπληρώνεται με την εξέταση των σχετικών πολιτικών σε διεθνές, ευρωπαϊκό και εθνικό επίπεδο. Η έρευνα πεδίου σε έναν εμβληματικό ελληνικό προορισμό, τη Σαντορίνη, ανέδειξε τη σημασία του μεγέθους της τουριστικής αγοράς για την διαμόρφωση υπηρεσιών γαστρονομικού τουρισμού στο ιδιαίτερο περιβάλλον της μικρής νησιωτικής οικονομίας, τις αποκλίνουσες στρατηγικές που αναπτύσσουν γύρω από τον γαστρονομικό τουρισμό οι τοπικοί εταίροι και τις δυνατότητες εναρμόνισης του γαστρονομικού τουρισμού με τα χαρακτηριστικά της νησιωτικής αγροτικής παραγωγής.
The Inclusion Paradigm in Greek schools: does just also mean justified?
Authors: Stergiadou Aristi
Published: May 2022

This article aims to clarify the term "inclusion" and to highlight its value within the school environment, as well as to promote inclusive education in Greece. First, an attempt is made to define the term followed by the presentation of the relevant legal framework. Next the differences between Special Education and Co-Education are pinpointed in order for the reader to identify their basic differentiating elements. Then the problems that hinder the implementation of inclusion in schools are presented and ways to solve them are suggested. Finally, the terms of “Inclusive” and “Intercultural Education” are analyzed and compared. Inclusion in Greece, despite the obstacles it faces, can become a dominant and constructive way of learning.
Student teachers' perceptions of the collaborative relationships form between universities and inclusive elementary schools in Indonesia
Authors: Rasmitadila Rasmitadila , Humaira Megan Asri , Rachmadtullah Reza
Published: May 2022

Background: The collaborative relationship between universities and inclusive elementary schools has not been maximally practiced. The form of collaboration that universities with inclusive elementary schools have carried out is still limited to the need to complete lecture materials during the semester. There is a gap between the theory and practice obtained by student teachers at universities when they have to teach in inclusive elementary schools. As a result, they have not contributed to solving problems that occur in inclusive elementary schools. The collaborative relationship between inclusive elementary schools and universities directly implies that the success of inclusive education is determined by the competence of student teachers whose lecturers have successfully educated them in order to teach in inclusive elementary schools. Compared to the background that the inclusive education system is developing in Indonesia, the researchers investigated student teachers' perceptions at universities regarding inclusive university-inclusive elementary school collaborative relationships.

Methods: During data collection, an online survey and in-depth interviews of student teachers about individual experiences and their ideas about the form of inclusive elementary schools-university partnerships was conducted. The data analysis used was a thematic analysis technique.

Result: The result summarizes student teachers' statements, revealed three main themes: provision of inclusive education needs, research, and field practice. The student teachers revealed that the collaborative relationship between universities and inclusive elementary schools is essential in order to develop holistic, inclusive practices in a collaborative partnership based on input-needs, which has a two-way impact or benefit for both parties.

Conclusions: Furthermore, collaborative relationships must be in the form of long-term programs, such as continuous assistance, and adaptation to the development of inclusive education through lecture materials. To achieve successful inclusive education in Indonesia, we also recommended that the government make policies on multi-sectoral collaboration in order to support inclusive education.
CONVERSACIONES EN EL TRÓPICO. EL DIÁLOGO ARQUITECTÓNICO ENTRE FERNANDO HIGUERAS Y CÉSAR MANRIQUE
Authors: Navarro–de–Pablos Javier , Mayora–Campa Esther
Published: May 2022

El punto de partida de este artículo son la amistad, las inquietudes compartidas y las colaboraciones profesionales mantenidas durante 25 años por Fernando Higueras y César Manrique. Ambos creadores establecen una fructífera conversación en torno a la amistad, el arte, la arquitectura y el paisaje con numerosos intereses y lugares comunes. Desde que se conociesen en los años sesenta del pasado siglo, surge una complicidad forjada en una forma de ver la vida similar, un posicionamiento apasionado, hedonista y comprometido, cimentado en una especial sensibilidad con el entorno y la preocupación por crear para las personas y no para la crítica. Iconoclastas y contradictorios, recrearán el sueño de una forma alternativa de habitar el mundo ligada a la tradición de la arquitectura anónima, a la naturaleza y al paisaje con una fuerza salvaje. Esta posición casi ancestral los acerca a los animales y a sus formas esenciales de construir un refugio, atentos a las condiciones del lugar y el clima, a la vez que se alejan del discurso intelectual elitista para encontrar en el espacio y en la técnica constructiva la esencia de su discurso. El artículo plantea como objetivo desvelar aquellos aspectos más determinantes de esa conversación teniendo como escenario la isla de Lanzarote, profundizando en algunas de sus arquitecturas residenciales, sus incursiones en el diseño de alojamientos turísticos y el desarrollo de los espacios más íntimos de la casa. En esta motivación por desvelar alternativas a la producción industrial y alienada, en la obra de Higueras y Manrique se reconocen características del “artesano”, término definido por el sociólogo Richard Sennett como figura de resistencia a las dinámicas capitalistas, situándolos en una posición de contemporaneidad manifiesta.
Paternalismo y control social. La caja de invalidez de Martín Montaner, industrial corchero (1900-1912).
Authors: ALVARADO Joaquim
Published: May 2022

Presentación, análisis y objetivos de un proyecto desarrollado por el industrial corchero Martín Montaner Coris de un fondo de pensiones privado, financiado en su integridad por él mismo, para cubrir las necesidades económicas de sus obreros por enfermedad o retiro. El objetivo era evitar la intromisión de sindicatos ajenos a sus fábricas e intentar solucionar los problemas internamente, una solución que consideramos paternalista.

Palabras clave: Industria corchera, paternalismo, condiciones de vida obreras, pensiones, huelga
Mobiliario marmóreo en ámbito termal. El caso de las termas de "Aquinum".
Authors: CUADRA RUBIO Rocío
Published: May 2022

Las excavaciones de las termas centrales de la antigua ciudad romana de Aquinum[1] han traído a la luz una serie de fragmentos de mármol identificados como pertenecientes a objetos decorativos y funcionales los cuales formaban parte del mobiliario escultórico de esta importante estructura. Hasta ahora los trabajos arqueológicos se han concentrado en el estudio sistemático de los muros, la identificación del uso de los ambientes y la delimitación del complejo, además ha interesado la búsqueda de los accesos a las termas. El complejo termal, dividido entre área masculina y área femenina, representa uno de los mayores en el territorio italiano y cuenta hasta hoy con un área de más de 9000m2.[2] El trabajo realizado sobre el mobiliario marmóreo[3] se ha concentrado en la búsqueda, la identificación y el estudio del mobiliario recuperado en los estratos de abandono de las termas. De este primer estudio el objetivo principal es el de comprender y completar, en la medida de lo posible, cuál era la disposición aproximada del mobiliario estudiado y de qué manera los visitantes han podido interactuar con estos objetos. A partir de este primer análisis hemos podido identificar diferentes bañeras o alvei, candelabros monumentales y una gran cantidad de objetos de pequeño formato. Cada uno de estos objetos se presenta en un primer catálogo que da protagonismo finalmente a esta tipología de hallazgos en las termas centrales de Aquinum.

Palabras clave: Aquinum, termas centrales, mobiliario marmóreo, escultura.
High-speed 3D imaging flow cytometry with optofluidic spatial transformation
Authors: Ugawa Masashi , Ota Sadao
Published: May 2022

Three-dimensional (3D) fluorescence imaging is important to accurately capture and understand biological structures and phenomena. However, because of its slow acquisition speed, it was difficult to implement 3D fluorescence imaging for imaging flow cytometry. Especially, modern flow cytometers operate at a flow velocity of 1–10 m/s, and no 3D fluorescence imaging technique was able to capture cells at such high velocity. Here, we present a high-speed 3D fluorescence imaging technique in which a set of optical cross sections of a cell is captured within a single frame of a camera by combining strobe light-sheet excitation and optofluidic spatial transformation. Using this technique, we demonstrated 3D fluorescence imaging of cells flowing at a velocity of over 10 m/s, which is the fastest to our knowledge. Such technology can allow integration of 3D imaging with flow systems of common flow cytometers and cell sorters.
Low threshold optical bistability based on topological edge state in photonic crystal heterostructure with Dirac semimetal
Authors: Long Xin , Bao Yuwen , Yuan Hongxia , Zhang Huayue , Dai Xiaoyu , Li Zhongfu , Jiang Leyong , Xiang Yuanjiang
Published: May 2022

The special band structure of three-dimensional Dirac semimetal (3D DSM) makes it show strong nonlinear optical characteristics in the terahertz region, which provides a new way to develop terahertz nonlinear devices with low threshold. In this paper, we theoretically study the optical bistability (OB) of transmitted light in a multilayer structure with 3D DSM embedded in two one-dimensional photonic crystals (1D PhC). The topological edge state (TES) excited by the 1D PhC heterostructure significantly enhances the local electric field near the nonlinear 3D DSM, which provides a positive condition for the realization of low threshold OB. Through parameter optimization, we obtain a threshold electric field with an incident electric field of 106 V/m levels. Furthermore, the influences of the Fermi energy and thickness of 3D DSM and the angle of the incident light on the hysteretic behavior as well as the threshold of OB are clarified. 3D DSM-based optical devices with intrinsic OB provide a building block for future integrated optical and all-optical networks.
Polymer-based planar waveguide chirped Bragg grating for high-resolution tactile sensing
Authors: Lin Huagang , Xing Yuxin , Chen Xiaolu , Zhang Shuo , Forsberg Erik , He Sailing
Published: May 2022

A novel tactile sensor for two-dimensional force location measurements, based on polymer-based planar waveguide chirped Bragg gratings (PPCBGs) fabricated on sheet PMMA substrate, is presented. The planar waveguide and chirped Bragg grating are simultaneously generated using a KrF excimer laser and a phase mask covered by a quartz chrome mask. Location and magnitude of an applied force is measured by observing the change of the wavelength of a dip in the measured spectrum and a change in the reflectivity intensity. Experimental characterization indicates submillimeter spatial resolution of applied force in the range of 1-4 N with a sensitivity of 947.02 pm/mm.