bluuebunny/crossref_metadata_2025 huggingface dataset:
YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2
Authors: Wang Xiaotang , Fan Wei , Li Na , Ma Yan , Yao Mudi , Wang Guoqing , He Siyuan , Li Wanqian , Tan Jun , Lu Qi , Hou Shengping
Published: April 2023

Background

Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying mechanisms are not entirely clear. Lactylation is a novel lactate-derived posttranslational modification that plays key roles in multiple cellular processes. Since hypoxia in ischemic retinopathy is a precipitating factor for retinal neovascularization, lactylation is very likely to be involved in this process. The present study aimed to explore the role of lactylation in retinal neovascularization and identify new therapeutic targets for retinal neovascular diseases.

Results

Microglial depletion by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 suppresses retinal neovascularization in oxygen-induced retinopathy. Hypoxia increased lactylation in microglia and accelerates FGF2 expression, promoting retinal neovascularization. We identify 77 sites of 67 proteins with increased lactylation in the context of increased lactate under hypoxia. Our results show that the nonhistone protein Yin Yang-1 (YY1), a transcription factor, is lactylated at lysine 183 (K183), which is regulated by p300. Hyperlactylated YY1 directly enhances FGF2 transcription and promotes angiogenesis. YY1 mutation at K183 eliminates these effects. Overexpression of p300 increases YY1 lactylation and enhances angiogenesis in vitro and administration of the p300 inhibitor A485 greatly suppresses vascularization in vivo and in vitro.

Conclusions

Our results suggest that YY1 lactylation in microglia plays an important role in retinal neovascularization by upregulating FGF2 expression. Targeting the lactate/p300/YY1 lactylation/FGF2 axis may provide new therapeutic targets for proliferative retinopathies.
Intravenous antibiotics in preterm infants have a negative effect upon microbiome development throughout preterm life
Authors: Hutchinson R. A. , Costeloe K. L. , Wade W. G. , Millar M. R. , Ansbro K. , Stacey F. , Fleming P. F.
Published: April 2023

Background

Intestinal dysbiosis is implicated in the origins of necrotising enterocolitis and late-onset sepsis in preterm babies. However, the effect of modulators of bacterial growth (e.g. antibiotics) upon the developing microbiome is not well-characterised.

In this prospectively-recruited, retrospectively-classified, case–control study, high-throughput 16S rRNA gene sequencing was combined with contemporaneous clinical data collection, to assess the within-subject relationship between antibiotic administration and microbiome development, in comparison to preterm infants with minimal antibiotic exposure.

Results

During courses of antibiotics, diversity progression fell in comparison to that seen outside periods of antibiotic use (-0.71units/week vs. + 0.63units/week, p < 0.01); Enterobacteriaceae relative abundance progression conversely rose (+ 10.6%/week vs. -8.9%/week, p < 0.01). After antibiotic cessation, diversity progression remained suppressed (+ 0.2units/week, p = 0.02).

Conclusions

Antibiotic use has an acute and longer-lasting impact on the developing preterm intestinal microbiome. This has clinical implications with regard to the contribution of antibiotic use to evolving dysbiosis, and affects the interpretation of existing microbiome studies where this effect modulator is rarely accounted for.
The association between different physical activity levels and flexion-relaxation phenomenon in women: a cross-sectional study
Authors: Li Yangzheng , Pei Junjie , Li Changsheng , Wu Fangchao , Tao Yechao
Published: April 2023

Background

To investigate whether the flexion-relaxation phenomenon differs in women with different physical activity levels.

Methods

Seventy-two subjects were recruited for this study. The electromyographic activity of the erector spinae and multifidus muscles was recorded during a flexion task using a surface electromyographic device. The flexion-relaxation and extension-relaxation ratios were calculated. Participants were classified into different physical activity level groups based on their responses to the International Physical Activity Questionnaire. A Welch analysis of variance was conducted to compare the flexion-relaxation ratio and extension-relaxation ratio between groups.

Results

A significant difference in the flexion-relaxation and extension-relaxation ratio was observed in both the erector spinae and multifidus muscles between different levels of physical activity.

Conclusions

In this study, we observed that female participants with high levels of physical activity showed a more pronounced flexion-relaxation phenomenon compared to those with moderate and low levels of physical activity. No significant difference was found between moderate and low physical activity levels. The findings of our study highlight the association between physical activity and the mechanics of the spinal stabilising muscles.
First draft genome and transcriptome of Cercosporidium personatum, causal agent of late leaf spot disease of peanut
Authors: Arias Renee S. , Dobbs John T. , Stewart Jane E. , Cantonwine Emily G. , Orner Valerie A. , Sobolev Victor S. , Lamb Marshall C. , Massa Alicia N.
Published: April 2023

Objective

Two main fungal leaf spot diseases occur in peanut, namely early leaf spot (ELS) and late leaf spot (LLS), these cause a yearly average of $44 million losses. Limited genetic information, 3534 bp of sequencing, exists about the causal agent of LLS,Cercosporidium personatum(syn.Nothopassalora personata, syn.Phaeoisariopsis personata). The extremely slow growth of this fungus, approximately 1 cm colony in 6 months, and challenges in nucleic acid extractions have hindered research on LLS. Our goal in this work is to provide a reference genome for research on this pathogen.

Results

Whole genome and transcriptome sequencing of the LLS fungus were obtained. A total of 233,542,110 reads of the genome were de novo assembled resulting in 1061 scaffolds, and estimated genome size 27,597,787 bp. RNA sequencing resulted in 11,848,198 reads that were de novo assembled into 13,343 contigs. Genome annotation resulted in 10,703 putative genes. BUSCO analysis of the genome and annotation resulted in 91.1% and 89.5% completeness, respectively. Phylogenetic dendrograms for 5442 bp and 4401 bp of RNA Polymerase II largest and second largest subunits, and for 5474 bp of the ribosomal RNA cistron ofC. personatumare presented in relation to closely related fungi.
Right-side diaphragmatic eventration with atrial septa defect and cleft palate in an infant: a case report
Authors: Aslamzai Mansoor , Rahmani Fazal Rahman , Hakimi Turyalai , Mukhlis Abdul Hakim , Froogh Basir Ahmad
Published: April 2023

Background

Congenital right-side diaphragmatic eventration with atrial septal defect and cleft palate is a rare congenital anomaly.

Case presentation

We present a rare case of congenital right-sided diaphragmatic eventration along with atrial septal defect, cleft palate, pneumonia, and undernutrition in a 3-month-old Asian and Afghan girl. The clinical features were observed in the third month of life, and the diagnosis of these anomalies was established by the patient’s history, physical examination, chest X-ray, thoracic computed tomography, and echocardiography. Her condition was good after supportive treatment. Since the index case of diaphragmatic eventration was associated with congenital heart disease, cleft palate, and parental consanguinity, a genetic basis may have played an important role in the pathogenesis of this anomaly.

Conclusion

Eventration of the diaphragm may be diagnosed in early infancy, and genetic factors may contribute to its pathogenesis.
Metabolic profile of mesenchymal stromal cells and macrophages in the presence of polyethylene particles in a 3D model
Authors: Teissier Victoria , Gao Qi , Shen Huaishuang , Li Jiannan , Li Xueping , Huang Elijah Ejun , Kushioka Junichi , Toya Masakazu , Tsubosaka Masanori , Hirata Hirohito , Alizadeh Hossein Vahid , Maduka Chima V. , Contag Christopher H. , Yang Yunzhi Peter , Zhang Ning , Goodman Stuart B.
Published: April 2023

Background

Continuous cross talk between MSCs and macrophages is integral to acute and chronic inflammation resulting from contaminated polyethylene particles (cPE); however, the effect of this inflammatory microenvironment on mitochondrial metabolism has not been fully elucidated. We hypothesized that (a) exposure to cPE leads to impaired mitochondrial metabolism and glycolytic reprogramming and (b) macrophages play a key role in this pathway.

Methods

We cultured MSCs with/without uncommitted M0 macrophages, with/without cPE in 3-dimensional gelatin methacrylate (3D GelMA) constructs/scaffolds. We evaluated mitochondrial function (membrane potential and reactive oxygen species—ROS production), metabolic pathways for adenosine triphosphate (ATP) production (glycolysis or oxidative phosphorylation) and response to stress mechanisms. We also studied macrophage polarization toward the pro-inflammatory M1 or the anti-inflammatory M2 phenotype and the osteogenic differentiation of MSCs.

Results

Exposure to cPE impaired mitochondrial metabolism of MSCs; addition of M0 macrophages restored healthy mitochondrial function. Macrophages exposed to cPE-induced glycolytic reprogramming, but also initiated a response to this stress to restore mitochondrial biogenesis and homeostatic oxidative phosphorylation. Uncommitted M0 macrophages in coculture with MSC polarized to both M1 and M2 phenotypes. Osteogenesis was comparable among groups after 21 days.

Conclusion

This work confirmed that cPE exposure triggers impaired mitochondrial metabolism and glycolytic reprogramming in a 3D coculture model of MSCs and macrophages and demonstrated that macrophages cocultured with MSCs undergo metabolic changes to maintain energy production and restore homeostatic metabolism.
Online learning for WHO priority diseases with pandemic potential: evidence from existing courses and preparing for Disease X
Authors: Utunen Heini , Tokar Anna , Dancante Mafalda , Piroux Corentin
Published: April 2023

Background

OpenWHO is the open-access learning platform of the World Health Organization (WHO) that provides online learning for health emergencies with essential health knowledge for emergencies. There is emphasis for courses on severe emerging diseases with epidemic and pandemic potential to help frontline health workers prevent, control and respond to infectious diseases. This research addresses the question of how the existing OpenWHO online courses on infectious disease were used in the countries of disease occurrence and how to prepare for disease X, a novel or unknown pathogen with pandemic potential.

Methods

OpenWHO collects self-declared demographic data from learners among which there is data on geographical location of learners. Data in infectious disease courses use on OpenWHO was collected and examined and additionally information languages used in the outbreak locations was collected.

Results

For most diseases in focus the online learning materials were used in countries with burden of disease. This suggests the learning material production needs to be targeted for outbreak and epidemic events.

Conclusions

Findings inform the use of learning materials in disease outbreaks. Further, this use case data confirms learning providers need to add offerings in languages spoken in outbreak impacted areas.
Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia
Authors: Rutten Martijn G. S. , Lei Yu , Hoogerland Joanne H. , Bloks Vincent W. , Yang Hong , Bos Trijnie , Krishnamurthy Kishore A. , Bleeker Aycha , Koster Mirjam H. , Thomas Rachel E. , Wolters Justina C. , van den Bos Hilda , Mithieux Gilles , Rajas Fabienne , Mardinoglu Adil , Spierings Diana C. J. , de Bruin Alain , van de Sluis Bart , Oosterveer Maaike H.
Published: April 2023

Background

Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP activation limits non-alcoholic fatty liver disease (NAFLD) in hepatic GSD Ia. As ChREBP has been proposed as a pro-oncogenic molecular switch that supports tumour progression, we hypothesized that ChREBP normalization protects against liver disease progression in hepatic GSD Ia.

Methods

Hepatocyte-specific G6pc knockout (L-G6pc−/−) mice were treated with AAV-shChREBP to normalize hepatic ChREBP activity.

Results

Hepatic ChREBP normalization in GSD Ia mice induced dysplastic liver growth, massively increased hepatocyte size, and was associated with increased hepatic inflammation. Furthermore, nuclear levels of the oncoprotein Yes Associated Protein (YAP) were increased and its transcriptional targets were induced in ChREBP-normalized GSD Ia mice. Hepatic ChREBP normalization furthermore induced DNA damage and mitotic activity in GSD Ia mice, while gene signatures of chromosomal instability, the cytosolic DNA-sensing cGAS-STING pathway, senescence, and hepatocyte dedifferentiation emerged.

Conclusions

In conclusion, our findings indicate that ChREBP activity limits hepatomegaly while decelerating liver disease progression and protecting against chromosomal instability in hepatic GSD Ia. These results disqualify ChREBP as a therapeutic target for treatment of liver disease in GSD Ia. In addition, they underline the importance of establishing the context-specific roles of hepatic ChREBP to define its therapeutic potential to prevent or treat advanced liver disease.
METTL3 facilitates immunosurveillance by inhibiting YTHDF2-mediated NLRC5 mRNA degradation in endometrial cancer
Authors: Zhan Lei , Zhang Jing , Zhang Jun-Hui , Liu Xiao-Jing , Guo Bao , Chen Jia-Hua , Tang Zhen-Hai , Wang Wen-Yan , Wang Qing-Yuan , Wei Bing , Cao Yun-Xia
Published: April 2023

Background

N6-methyladenosine (m6A) methylation is the most abundant chemical posttranscriptional modification of mRNA, and it is associated with the regulation of the immune response to tumors. However, the function of m6A modification in the immune response to endometrial cancer (EC) remains unknown. Our study investigated the immunological role of methyltransferase-like 3 (METTL3) in EC and the underlying molecular mechanism.

Methods

We investigated the correlation between the expression of METTL3 and CD8 by using an endometrial tissue microarray cohort. Next, we investigated the role and mechanism of METTL3 in the immune response to EC using a mouse tumor model and a CD8+ T cell-EC cell coculture system after METTL3 overexpression or depletion. Additionally, RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were used to investigate the mechanism underlying the function of METTL3 in immunosurveillance of EC.

Results

METTL3 levels were downregulated in EC patients, low levels of METTL3 were correlated with poor prognosis in EC patients. There was a positive correlation between METTL3 expression and CD8 expression. Overexpression of METTL3 in the EC cell and CD8+ T cell coculture system inhibited EC cell proliferation, migration, and promoted CD8+ T-cell proliferation, and in vivo, METTL3 overexpression increased CD8+ T cell proportions and inhibited EC progression; however, genetic depletion of METTL3 exerted the opposite effects. NLR family CARD domain-containing 5 (NLRC5) was identified as a target of METTL3-mediated m6A modification. The degradation of NLRC5 was increased by YTH domain-containing family 2 (YTHDF2).

Conclusions

Overall, METTL3, YTHDF2, and NLRC5 have potential to be the diagnostic and prognostic biomarkers for EC. METTL3 facilitated the m6A modifications of NLRC5 and inhibited its degradation through a YTHDF2-dependent mechanism in EC. Genetic overexpression of METTL3 attenuated the immune evasion of EC by promoting NLRC5-mediated immunosurveillance, suggesting that the METTL3/YTHDF2/NLRC5 axis is a promising target of immunotherapy in EC.
Identification and validation of autophagy-related genes in Kawasaki disease
Authors: Zhu Hao , Xu Biao , Hu Cunshu , Li Aimin , Liao Qing
Published: April 2023

Background

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology affecting mainly children. Studies have shown that the pathogenesis of KD may be related to autophagy. Using bioinformatics analysis, we assessed the significance of autophagy-related genes (ARGs) in KD.

Methods

Common ARGs were identified from the GeneCards Database, the Molecular Signatures Database (MSigDB), and the Gene Expression Omnibus (GEO) database. ARGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein–protein interaction (PPI) network analysis. Furthermore, related microRNAs (miRNAs), transcription factors (TFs), and drug interaction network were predicted. The immune cell infiltration of ARGs in tissues was explored. Finally, we used receiver operating characteristic (ROC) curves and quantitative real-time PCR (qRT-PCR) to validate the diagnostic value and expression levels of ARGs in KD.

Results

There were 20 ARGs in total. GO analysis showed that ARGs were mainly rich in autophagy, macro-autophagy, and GTPase activity. KEGG analysis showed that ARGs were mainly rich in autophagy—animal and the collecting duct acid secretion pathway. The expression of WIPI1, WDFY3, ATP6V0E2, RALB, ATP6V1C1, GBA, C9orf72, LRRK2, GNAI3, and PIK3CB is the focus of PPI network. A total of 72 related miRNAs and 130 related TFs were predicted by miRNA and TF targeting network analyses. Ten pairs of gene–drug interaction networks were also predicted; immune infiltration analysis showed that SH3GLB1, ATP6V0E2, PLEKHF1, RALB, KLHL3, and TSPO were closely related to CD8 + T cells and neutrophils. The ROC curve showed that ARGs had good diagnostic value in KD. qRT-PCR showed that WIPI1 and GBA were significantly upregulated.

Conclusion

Twenty potential ARGs were identified by bioinformatics analysis, and WIPI1 and GBA may be used as potential drug targets and biomarkers.
Insecticide resistance status of Aedes aegypti and Aedes albopictus mosquitoes in southern Benin, West Africa
Authors: Konkon Alphonse Keller , Padonou Germain Gil , Osse Razaki , Salako Albert Sourou , Zoungbédji David Mahouton , Sina Haziz , Sovi Arthur , Tokponnon Filemon , Aïkpon Rock , Noukpo Herbert , Baba-Moussa Lamine , Akogbéto Martin Codjo
Published: April 2023

Background

The emergence of insecticide resistance in Aedes mosquitoes could undermine efforts to control arboviruses. The present study aims to assess in some communes of Southern Benin, the susceptibility level of Aedes aegypti (Linnaeus, 1762) and Aedes albopictus (Skuse, 1894) to insecticides commonly used in public health, as well as mechanisms involved.

Methods

Females Ae. albopictus and Ae. aegypti collected in Ifangni, Porto-Novo, Avrankou, Adjarra and Kétou from June 2021 to October 2022, were exposed to: deltamethrin 0.05%, permethrin 0.75%, alpha-cypermethrin 0.05%, pirimiphos methyl 0.25% and bendiocarb 0.1%, following the standard WHO susceptibility tube test protocol. In some sites, pre-exposure to the synergist PBO was used to verify if pyrethroid resistance of populations of Aedes was mediated by oxidases.

Results

Full susceptibility to deltamethrin and permethrin was observed in all tested populations of Ae. albopictus. However, with alphacypermethrin, a suspected resistance was observed in Adjarra (94.67%), Ifangni (93%) and Porto-Novo (94%), and a resistance in Avrankou (83%). The PBO-alphacypermethrin tests performed, led to a full susceptibility (100%) in all four sites, which confirms the full involvement of oxidases in resistance of all tested populations of Ae. albopictus to alphacypermethrin. At the opposite, Aedes aegypti was either resistant or suspected of being resistant to all tested pyrethroids in all four sites, except in Ifangni where a full susceptibility to alphacypermethrin was observed. The full susceptibility of Ae. aegypti to bendiocarb and pirimiphos-methyl in all communes suggests that these two insecticides can be good candidates for an effective control of pyrethroid-resistant Aedes vector populations. Use of permethrin and deltamethrin could also be considered for controlling populations of Ae. albopictus.

Conclusion

Results of the present study will help guide strategy to implement for an effective control of Aedes vector populations in Benin.
Sleep Patterns, Plasma Metabolome, and Risk of Incident Type 2 Diabetes Mellitus
Authors: Zhuang Zhenhuang , Dong Xue , Jia Jinzhu , Liu Zhonghua , Huang Tao , Qi Lu
Published: April 2023

Context

A healthy sleep pattern has been related to a lower risk of type 2 diabetes mellitus (T2DM).

Objective

We aimed to identify the metabolomic signature for the healthy sleep pattern and assess its potential causality with T2DM.

Methods

This study included 78 659 participants with complete phenotypic data (sleep information and metabolomic measurements) from the UK Biobank study. Elastic net regularized regression was applied to calculate a metabolomic signature reflecting overall sleep patterns. We also performed genome-wide association analysis of the metabolomic signature and one-sample mendelian randomization (MR) with T2DM risk.

Results

During a median of 8.8 years of follow-up, we documented 1489 incident T2DM cases. Compared with individuals who had an unhealthy sleep pattern, those with a healthy sleep pattern had a 49% lower risk of T2DM (multivariable-adjusted hazard ratio [HR], 0.51; 95% CI, 0.40-0.63). We further constructed a metabolomic signature using elastic net regularized regressions that comprised 153 metabolites, and robustly correlated with sleep pattern (r = 0.19; P = 3×10−325). In multivariable Cox regressions, the metabolomic signature showed a statistically significant inverse association with T2DM risk (HR per SD increment in the signature, 0.56; 95% CI, 0.52-0.60). Additionally, MR analyses indicated a significant causal relation between the genetically predicted metabolomic signature and incident T2DM (P for trend < .001).

Conclusion

In this large prospective study, we identified a metabolomic signature for the healthy sleep pattern, and such a signature showed a potential causality with T2DM risk independent of traditional risk factors.
Association of Resting Heart Rate Trajectories With Cardiovascular Disease and Mortality in Patients With Diabetes Mellitus
Authors: Wang Chi , Xin Qian , Zheng Mengyi , Liu Shihe , Yao Siyu , Li Yanjie , Tian Lu , Feng Zekun , Wang Miao , Zhao Maoxiang , Chen Shuohua , Wu Shouling , Xue Hao
Published: April 2023

Context

Longitudinal patterns of resting heart rate (RHR) in patients with diabetes mellitus and their association with health outcomes are not well-characterized.

Objective

We sought to explore the RHR trajectories in patients with diabetes mellitus and their association with cardiovascular disease (CVD) and all-cause mortality.

Design

The Kailuan Study is a prospective cohort study. Participants underwent health examinations biennially starting in 2006 and were followed until December 31, 2020.

Setting

General community.

Participants

A total of 8218 diabetic participants who attended at least 3 of the examinations conducted in 2006, 2008, 2010, and 2012 were included.

Main outcome measures

CVD and all-cause mortality.

Results

We identified 4 RHR trajectories in participants with diabetes mellitus between 2006 and 2012: low-stable (range, 66.83-64.91 beats/min; n = 1705), moderate-stable (range, 76.30-76.95 beats/min; n = 5437), high-decreasing (mean decreased from 92.14 to 85.60 beats/min; n = 862), and high-increasing (mean increased from 84.03 to 111.62 beats/min; n = 214). During an average follow-up of 7.25 years, 977 cases of CVD and 1162 deaths were identified. Compared with the low-stable trajectory, adjusted hazard ratios (HRs) for CVD were 1.48 (95% CI, 1.02-2.14; P = .04) for the high-increasing trajectory, adjusted HRs for all-cause mortality were 1.34 (95% CI, 1.14-1.58; P < .01) for the moderate-stable trajectory, 1.68 (95% CI, 1.35-2.10; P < .01) for the high-decreasing trajectory, and 2.47 (95% CI, 1.85-3.31; P < .01) for the high-increasing trajectory.

Conclusions

RHR trajectories were associated with the subsequent risks of CVD and all-cause mortality in patients with diabetes mellitus.
Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline
Authors: Zhou Xin , Iwama Shintaro , Kobayashi Tomoko , Ando Masahiko , Arima Hiroshi
Published: April 2023

Context

Positive antithyroglobulin (TgAb) and/or antithyroid peroxidase antibodies (TPOAb) at baseline indicate a high risk of thyroid immune-related adverse events (irAEs) induced by antiprogrammed cell death-1 antibodies (anti-PD-1-Ab). However, whether the positivity patterns of both antibodies are associated with the risk of thyroid irAEs is unknown.

Objective

The aim of the present study was to clarify the association of the pattern of TgAb and TPOAb positivity at baseline with the risk of thyroid irAEs induced by anti-PD-1-Ab.

Methods

Patients (n = 516) were evaluated for TgAb and TPOAb at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after initiating anti-PD-1-Ab.

Results

Fifty-one (9.9%) patients developed thyroid irAEs (thyrotoxicosis in 34, hypothyroidism without prior thyrotoxicosis in 17). Twenty-five patients subsequently developed hypothyroidism following thyrotoxicosis. The cumulative incidence of thyroid irAEs differed among 4 groups classified by the presence of TgAb/TPOAb at baseline (group 1: TgAb-(−)/TPOAb-(−), 4.6% [19/415]; group 2: TgAb-(−)/TPOAb-(+), 15.8% [9/57]; group 3: TgAb-(+)/TPOAb-(−), 42.1% [8/19]; group 4: TgAb-(+)/TPOAb-(+), 60.0% [15/25]) as follows: groups 1 vs 2-4 (P ≤ .001) and groups 2 vs 3 (P = .008) and 4 (P < .001). There were different incidences of thyrotoxicosis (groups 1-4, 3.1%, 5.3%, 31.6%, 48.0%, respectively; P < .001) in groups 1 vs 3 and 4, and groups 2 vs 3 and 4, and of hypothyroidism (groups 1-4: 2.9%, 15.8%, 31.6%, 60.0%, respectively; P < .001) in groups 1 vs 2 to 4, and groups 2 vs 4.

Conclusion

The risk of thyroid irAEs was affected by the pattern of TgAb and TPOAb positivity at baseline; there were high risks of thyrotoxicosis in patients with TgAb-(+) and of hypothyroidism in patients with TgAb-(+) and those with TPOAb-(+).
DOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement
Authors: Malla Aushaq B. , Rainsford Shannon R. , Smith Zachary D. , Lesch Bluma J.
Published: April 2023

Unique chromatin remodeling factors orchestrate dramatic changes in nuclear morphology during differentiation of the mature sperm head. A crucial step in this process is histone-to-protamine exchange, which must be executed correctly to avoid sperm DNA damage, embryonic lethality and male sterility. Here, we define an essential role for the histone methyltransferase DOT1L in the histone-to-protamine transition. We show that DOT1L is abundantly expressed in mouse meiotic and postmeiotic germ cells, and that methylation of histone H3 lysine 79 (H3K79), the modification catalyzed by DOT1L, is enriched in developing spermatids in the initial stages of histone replacement. Elongating spermatids lacking DOT1L fail to fully replace histones and exhibit aberrant protamine recruitment, resulting in deformed sperm heads and male sterility. Loss of DOT1L results in transcriptional dysregulation coinciding with the onset of histone replacement and affecting genes required for histone-to-protamine exchange. DOT1L also deposits H3K79me2 and promotes accumulation of elongating RNA Polymerase II at the testis-specific bromodomain gene Brdt. Together, our results indicate that DOT1L is an important mediator of transcription during spermatid differentiation and an indispensable regulator of male fertility.
The bumpy road ahead: the role of substrate roughness on animal walking and a proposed comparative metric
Authors: Clifton Glenna , Stark Alyssa Y. , Li Chen , Gravish Nicholas
Published: April 2023

Outside laboratory conditions and human-made structures, animals rarely encounter flat surfaces. Instead, natural substrates are uneven surfaces with height variation that ranges from the microscopic scale to the macroscopic scale. For walking animals (which we define as encompassing any form of legged movement across the ground, such as walking, running, galloping, etc.), such substrate ‘roughness’ influences locomotion in a multitude of ways across scales, from roughness that influences how each toe or foot contacts the ground, to larger obstacles that animals must move over or navigate around. Historically, the unpredictability and variability of natural environments has limited the ability to collect data on animal walking biomechanics. However, recent technical advances, such as more sensitive and portable cameras, biologgers, laboratory tools to fabricate rough terrain, as well as the ability to efficiently store and analyze large variable datasets, have expanded the opportunity to study how animals move under naturalistic conditions. As more researchers endeavor to assess walking over rough terrain, we lack a consistent approach to quantifying roughness and contextualizing these findings. This Review summarizes existing literature that examines non-human animals walking on rough terrain and presents a metric for characterizing the relative substrate roughness compared with animal size. This framework can be applied across terrain and body scales, facilitating direct comparisons of walking over rough surfaces in animals ranging in size from ants to elephants.
Biomechanics, motor control and dynamic models of the soft limbs of the octopus and other cephalopods
Authors: Flash Tamar , Zullo Letizia
Published: April 2023

Muscular hydrostats are organs composed entirely of packed arrays of incompressible muscles and lacking any skeletal support. Found in both vertebrates and invertebrates, they are of great interest for comparative biomechanics from engineering and evolutionary perspectives. The arms of cephalopods (e.g. octopus and squid) are particularly interesting muscular hydrostats because of their flexibility and ability to generate complex behaviors exploiting elaborate nervous systems. Several lines of evidence from octopus studies point to the use of both brain and arm-embedded motor control strategies that have evolved to simplify the complexities associated with the control of flexible and hyper-redundant limbs and bodies. Here, we review earlier and more recent experimental studies on octopus arm biomechanics and neural motor control. We review several dynamic models used to predict the kinematic characteristics of several basic motion primitives, noting the shortcomings of the current models in accounting for behavioral observations. We also discuss the significance of impedance (stiffness and viscosity) in controlling the octopus's motor behavior. These factors are considered in light of several new models of muscle biomechanics that could be used in future research to gain a better understanding of motor control in the octopus. There is also a need for updated models that encompass stiffness and viscosity for designing and controlling soft robotic arms. The field of soft robotics has boomed over the past 15 years and would benefit significantly from further progress in biomechanical and motor control studies on octopus and other muscular hydrostats.
A Dietary Strategy for Optimizing the Visual Range of Athletes
Authors: Harth Jacob B. , Renzi-Hammond Lisa M. , Hammond Billy R.
Published: April 2023

Visual range is quantified by assessing how far one can see clearly (an ability crucial to many athletes). This ability tends to vary significantly across individuals despite similar personal characteristics. We hypothesize that the primary driver of these differences is the individual response to scattered short-wave light in the environment moderated by the dietarily derived retinal pigments lutein and zeaxanthin.
Το μυθοπλαστικό βίντεο «Το νήμα» ως διδακτικό εργαλείο ευαισθητοποίησης των εφήβων στο πλαίσιο της Ανάπτυξης Ψηφιακού Οπτικοακουστικού Υλικού
Authors: Πλατανιώτη Χριστίνα , Σοφός Αλιβίζος (Λοΐζος)
Published: April 2023

Γενικός στόχος του παρόντος άρθρου είναι η διερεύνηση της μυθοπλαστικής ταινίας μικρού μήκους εκπαιδευτικού περιεχομένου «Το νήμα -μιλάς με τη σιωπή σου-» που δημιουργήθηκε στα πλαίσια του μαθήματος «Ανάπτυξη Ψηφιακού Οπτικοακουστικού Υλικού» με διδάσκοντα τον κύριο Σοφό Αλιβίζο. Η συγκεκριμένη ταινία μυθοπλασίας, η οποία συμπεριλαμβάνει και στοιχεία ντοκιμαντέρ, καθώς και η εκπαιδευτική αξιοποίηση της άνω ταινίας προσεγγίζουν τον εθισμό στο gaming μέσα από τη σκιαγράφηση της καθημερινότητας του ήρωα. Ταυτοχρόνως όμως παρουσιάζονται τα βασικά συμπτώματα του εθισμού καθώς και στατιστικά δεδομένα που έχουν αντληθεί από επιστημονικές μελέτες σε συνεργασία με την επιστημονική ομάδα του ΚΕΘΕΑ. Πρόκειται για ένα φαινόμενο που αποκτά όλο και μεγαλύτερες διαστάσεις τα τελευταία χρόνια με τις έρευνες να αναδεικνύουν ανησυχητικά στοιχεία για τις επιπτώσεις στους νέους. Η  εύκολη πρόσβαση στο Διαδίκτυο και η υπερβολική χρήση από τους εφήβους δημιουργεί ένα αυξανόμενο κλίμα ανησυχίας. Στόχος της ταινίας και των δραστηριοτήτων που προτείνονται είναι η ενημέρωση, η ευαισθητοποίηση και ο προβληματισμός των νέων σχετικά με τον εθισμό στο διαδίκτυο και συγκεκριμένα τον εθισμό στο gaming.
Η μαθητική διαρροή στην Περιφέρεια Θεσσαλίας: μία εμπειρική συγκριτική ανάλυση του πληθυσμού των ενήλικων εκπαιδευόμενων σε Σχολεία Δεύτερης Ευκαιρίας και Σχολεία Δεύτερης Ευκαιρίας Καταστημάτων Κράτησης
Authors: Μπιτσάκος Νικόλαος
Published: April 2023

Σκοπός της παρούσας εργασίας είναι η συγκριτική ανάλυση του φαινομένου της Μαθητικής Διαρροής μεταξύ των Νομών της Περιφέρειας Θεσσαλίας, μία περιφέρεια με υψηλά ποσοστά εγκατάλειψης του σχολείου. Αποτελεί μία εμπειρική συγκριτική ανάλυση ανάμεσα σε ενήλικους εκπαιδευόμενους, οι οποίοι ως ανήλικοι είχαν εγκαταλείψει πρόωρα την εκπαίδευση και πλέον φοιτούν σε Σχολεία Δεύτερης Ευκαιρίας και Σχολεία Δεύτερης Ευκαιρίας Καταστημάτων Κράτησης. Συγκεκριμένα εξετάζονται τα αίτια της αρχικής Μαθητικής Διαρροής κατά τη διάρκεια της πρωτοβάθμιας ή δευτεροβάθμιας εκπαίδευσης, καθώς και συγκρίνονται οι πληθυσμοί των εκπαιδευόμενων στις δομές εκπαίδευσης ενηλίκων των Νομών της περιφέρειας. Το μοντέλο της έρευνας επιβεβαιώθηκε κατά την επιβεβαιωτική παραγοντική ανάλυση με την προτεινόμενη κατηγοριοποίηση των αιτιών της Μαθητικής Διαρροής σε οικονομικούς, κοινωνικούς, ατομικούς και εκπαιδευτικούς παράγοντες. Τα αποτελέσματα της έρευνας έδειξαν ότι όσον αφορά τα αίτια της πρόωρης εγκατάλειψης του σχολείου παρουσιάζονται διαφοροποιήσεις ανάμεσα στους Νομούς της ίδιας Περιφέρειας. Επιπλέον, όσον αφορά τη σύγκριση των πληθυσμών των εκπαιδευόμενων των δομών εκπαίδευσης δεύτερης ευκαιρίας των Νομών που λειτουργούν εντός και εκτός καταστημάτων κράτησης, η μελέτη καταλήγει ότι παρότι ο πληθυσμός των ενήλικων εκπαιδευόμενων που επιστρέφουν στην εκπαίδευση αποτελούν μία ετερογενή πληθυσμιακή ομάδα, ως προς το φύλο και τη χώρα προέλευσης, δεν εμφανίζουν διαφορές ως προς τα αρχικά αίτια εγκατάλειψης της εκπαίδευσης.
penalty of imprisonment and its impact on the health of inmates - preliminary results
Authors: Dąbek Józefa , Kulik Halina , Zdrzałek Rafał , Stolorz Karolina , Sierka Oskar
Published: April 2023

Introduction and purpose
The prison system is an extremely important element of the country's penal structure. Restrictions related to serving a sentence of imprisonment adversely affect the physical health and the mental health of inmates. The main goal of the study was to assess selected areas of health of respondents in prison and changes in them depending on the time spent in prison.
Material and methods
The study included 153 (100%) men aged 18 to 55 staying in the Penitentiary Institution in Racibórz. An original questionnaire consisting of questions concerning the described issues was used to conduct the study. All respondents provided informed consent to participate. Obtained results in each category were converted into 5-point Likert Scale. Statistical analysis was carried out using the Chi2 test to investigate the relationship between the obtained results and the time spent in prison.
Results
Almost 30% of respondents declared the presence of chronic diseases before imprisonment, and more than half of the most common ailments after imprisonment included heartburn. Conducted analysis showed that even though more than 60% of the respondents assessed their general health positively there was a significant difference (Chi2=13.8; p=0.0083) between obtained results and inmates’ self-assessment. Time spent in prison was not influencing significantly physical health (Chi2=9,9 p=0,624) and inmates’ pro-health behaviors (Chi2=18,0 p=0,3232), but it influenced mental health (Chi2=28.3; p=0.047) and lifestyle (Chi2=37.4; p=0.0052).
Conclusion
The conducted evaluation shows how inmates’ health and its determinants are changing during time spent in prison. Moreover, it shows the problems that have to be resolved to maintain health during time spent in prison. It also highlights the importance of taking actions leading to inmates’ health improvement.
Human Gut Microbiome – how intestinal bacteria influence our health
Authors: Kuźniar Aleksandra , Szawica Dominik , Wąsiewicz Edward , Fularska Kamila , Oleszko Michał
Published: April 2023

Introduction: Gut microbiome is composed of hundreds of different bacterial species.Possibly every type of bacteria can affect many different aspects of human healthGut bacterial composition varies immensely between healthy and sick people and there are many factors which can influence micriobiota balance in our intestines.

Aim of study: The purpose of the study was to review the latest literature on the gut bacteria importance and to discover what factors can influence gut microbiome composition.

Matherials and methods: A systemic review was conducted using Google Scholar, PubMed and ScienceDirect databases and the search was limited to studies published between 2000 and 2023. The search strategy was based on following terms: microbiome, gut bacteria, health and microbiome, gut microflora, human intestinal microbiota

Results: We found many different studies which show importance of gut microflora in various different ailments and diseases, we have also found many showing  factors that influence intestinal microbiota composition.Conclusions: Gut microbiota is very broad topic – it can affect many different aspects of human health, starting from lowering the risk of developing allergy or affecting weight loss to affecting risk of colorectal cancer development . It can be affected by many different factors – lots of them are still uknown and need further studies.
Influence of Epstein-Barr virus infection on developing multiple sclerosis
Authors: Ołownia Aleksandra , Orczyk Jakub , Kozioł Małgorzata
Published: April 2023

Multiple sclerosis (MS) is the most common inflammatory-demyelinating disease. MS leads to the multifocal damage of the central nervous system, which causes the gradual deterioration of sensory, motor and cognitive functions. The etiology of this disease is not fully understood, but genetic and environmental factors (including the EBV infection) are suspected. In this review, we would like to summarize the state of knowledge over the effect of Epstein-Barr virus infection on developing multiple sclerosis.

Infectious mononucleosis (IM) which is caused by EBV and MS have similar epidemiology: both diseases mainly affect people at a young age, geographical prevalence is also identical. There are many theories that explain the mechanism of the EBV involvement in the development of MS including: the migration of EBV-infected B cells into the Central Nervous System, the theory of molecular mimicry, the induction of αB-crystallin by EBV in lymphoid cells or cooperation of the EBV and other viruses in the development of MS. Observations by physicians from around the world suggest that EBV infection is a strong factor in the development of multiple sclerosis. Epstein-Barr virus is prevalent in the population. There are a lot of evidences that suggest its involvement in the development of multiple sclerosis. Prevention of EBV infection could potentially reduce the amount of cases of MS. However, more researches are needed to clearly confirm the involvement of EBV in the etiopathogenesis of developing MS.
PRL w narracji muzealnej 1989-2017
Authors: Wąchała-Skindzier Maria
Published: April 2023

The main goal of this dissertation is to analyse the representation of the Polish People’s Republic in the museum narrative. The dissertation is written from a narrative perspective and from the point of view of new museology with the help of research categories such as the narrative museum, communicative, cultural, and collective memory, historical representation, heritage, historical policy, etc. The research method is twofold. First, a quantitative analysis is performed of statistical data, i.e. a list of temporary and permanent exhibitions devoted to the Polish People’s Republic and displayed in Polish museums between 1989 and 2017. The list was compiled on the basis of queries sent out to the Polish museums featured in the database of the National Institute for Museums and Public Collections and was verified by the author.
Managing the Hyflex Scheduling Activity Using Excel Dynamic Arrays
Authors: LeBlanc Larry J. , Grossman Thomas A. , Bartolacci Michael R.
Published: April 2023

The COVID-19 pandemic has forced the rapid adoption of remote teaching modalities including “hyflex” where students attend some class sessions in person and some online. Managing the hyflex course requires faculty to quickly generate several reports and to update these reports rapidly when the authorities adjust the rules, students add/drop, or the number of course sessions is changed. The creation of these reports is tedious and error-prone, so they need to be automated. However, the nature of the task precludes traditional Excel programming approaches. We use Excel’s new “dynamic array” capabilities (which are available only in Excel 365) to automate the creation and updating of the reports needed to manage the hyflex course. We show how to program the reports, and we discuss the importance of taking an iterative approach to creating effective, error-free cell formulas. To help the reader acquire genuine access to the dynamic array functions, we provide a practical tutorial on the principles and new concepts of dynamic arrays, explain how they relate to legacy array functions, and present selected dynamic array functions including SEQUENCE, FILTER, and XLOOKUP.
The role of the advanced clinical practitioner in arthroplasty care
Authors: Daw Rachael , Armstrong Catherine
Published: April 2023

Demand for joint arthroplasty surgery in the UK has increased significantly over the past 10 years. Advanced clinical practitioner (ACP) roles in arthroplasty care, typically fulfilled by expert nurses or physiotherapists, have been developed to alleviate service pressures and facilitate care for the growing number of patients undergoing arthroplasty surgery. There are numerous different models of ACP-led services both in the UK and internationally, driven by local service and population needs. ACPs in arthroplasty care will be involved throughout the patient journey, including pre-operative assessment, peri-operative care and long-term surveillance. ACPs in arthroplasty care will develop expertise across all four pillars of advanced clinical practice and have the potential to influence and contribute to the development of guidance and policy for the future of arthroplasty care delivery, ensuring best quality, evidence-based practice is achieved.
Dynamic Scale-free Graph Embedding via Self-attention
Authors: Duan Dingyang , Zha Daren , Yang Xiao , Shen Jiahui , Mu Nan
Published: April 2023

Graph neural networks (GNNs) have recently become increasingly popular due to their ability to learn node representations in complex graphs. Existing graph representation learning methods mainly target static graphs in Euclidean space, whereas many graphs in practical applications are dynamic and evolve continuously over time. Recent work has demonstrated that real-world graphs exhibit hierarchical properties. Unfortunately, many methods typically do not account for these latent hierarchical structures. In this work, we propose a dynamic network in hyperbolic space via self-attention, referred to as DynHAT, which leverages both the hyperbolic geometry and attention mechanism to learn node representations. More specifically, DynHAT captures hierarchical information by mapping the structural graph onto hyperbolic space, and time-varying dynamic evolution by flexibly weighting historical representations. Through extensive experiments on three real-world datasets, we show the superiority of our model in embedding dynamic graphs in hyperbolic space and competing methods in a link prediction task. In addition, our results show that embedding dynamic graphs in hyperbolic space has competitive performance when necessitating low dimensions.
The Case for Cross-entity Delta Encoding in Web Compression (Extended)
Authors: Wollmer Benjamin , Wingerath Wolfram , Ferrlein Sophie , Panse Fabian , Gessert Felix , Ritter Norbert
Published: April 2023

Delta encoding and shared dictionary compression (SDC) for accelerating Web content have been studied extensively in research over the last two decades, but have only found limited adoption in the industry so far; compression approaches that use a custom-tailored dictionary per website have all failed in practice due to lacking browser support and high overall complexity. General-purpose SDC approaches such as Brotli reduce complexity by shipping the same dictionary for all use cases, while most delta encoding approaches just consider similarities between versions of the same entity (but not between different entities). In this study, we investigate how much of the potential benefits of SDC and delta encoding are left on the table by these two simplifications. As our first contribution, we describe the idea of cross-entity delta encoding that uses cached assets from the immediate browser history for content encoding instead of a precompiled shared dictionary; this avoids the need to create a custom dictionary, but enables highly customized and efficient compression. Second, we present an experimental evaluation of compression efficiency to hold cross-entity delta encoding against state-of-the-art Web compression algorithms. We consciously compare algorithms some of which are not yet available in browsers to understand their potential value before investing resources to build them. Our results indicate that cross-entity delta encoding is over 50% more efficient for text-based resources than compression industry standards. We hope our findings motivate further research and development on this topic.

The extended version of our previously published paper [10] includes an additional section on the deltas of HTML files, a more detailed description of our approach (including a new visualization for the different dictionary strategies), a deeper discussion of compression efficiency, and details on additional future and ongoing work.