bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in muscle protein expression and DNA methylation in response to exercise training
Authors: Landen Shanie , Jacques Macsue , Hiam Danielle , Alvarez-Romero Javier , Schittenhelm Ralf B. , Shah Anup D. , Huang Cheng , Steele Joel R. , Harvey Nicholas R. , Haupt Larisa M. , Griffiths Lyn R. , Ashton Kevin J. , Lamon Séverine , Voisin Sarah , Eynon Nir
Published: September 2023

Background

Exercise training elicits changes in muscle physiology, epigenomics, transcriptomics, and proteomics, with males and females exhibiting differing physiological responses to exercise training. However, the molecular mechanisms contributing to the differing adaptations between the sexes are poorly understood.

Methods

We performed a meta-analysis for sex differences in skeletal muscle DNA methylation following an endurance training intervention (Gene SMART cohort and E-MTAB-11282 cohort). We investigated for sex differences in the skeletal muscle proteome following an endurance training intervention (Gene SMART cohort). Lastly, we investigated whether the methylome and proteome are associated with baseline cardiorespiratory fitness (maximal oxygen consumption;VO2max) in a sex-specific manner.

Results

Here, we investigated for the first time, DNA methylome and proteome sex differences in response to exercise training in human skeletal muscle (n = 78; 50 males, 28 females). We identified 92 DNA methylation sites (CpGs) associated with exercise training; however, no CpGs changed in a sex-dependent manner. In contrast, we identified 189 proteins that are differentially expressed between the sexes following training, with 82 proteins differentially expressed between the sexes at baseline. Proteins showing the most robust sex-specific response to exercise include SIRT3, MRPL41, and MBP. Irrespective of sex, cardiorespiratory fitness was associated with robust methylome changes (19,257 CpGs) and no proteomic changes. We did not observe sex differences in the association between cardiorespiratory fitness and the DNA methylome. Integrative multi-omic analysis identified sex-specific mitochondrial metabolism pathways associated with exercise responses. Lastly, exercise training and cardiorespiratory fitness shifted the DNA methylomes to be more similar between the sexes.

Conclusions

We identified sex differences in protein expression changes, but not DNA methylation changes, following an endurance exercise training intervention; whereas we identified no sex differences in the DNA methylome or proteome response to lifelong training. Given the delicate interaction between sex and training as well as the limitations of the current study, more studies are required to elucidate whether there is a sex-specific training effect on the DNA methylome. We found that genes involved in mitochondrial metabolism pathways are differentially modulated between the sexes following endurance exercise training. These results shed light on sex differences in molecular adaptations to exercise training in skeletal muscle.
RUN(X) out of blood: emerging RUNX1 functions beyond hematopoiesis and links to Down syndrome
Authors: Rozen Esteban J. , Ozeroff Christopher D. , Allen Mary Ann
Published: September 2023

Background

RUNX1 is a transcription factor and a master regulator for the specification of the hematopoietic lineage during embryogenesis and postnatal megakaryopoiesis. Mutations and rearrangements on RUNX1 are key drivers of hematological malignancies. In humans, this gene is localized to the ‘Down syndrome critical region’ of chromosome 21, triplication of which is necessary and sufficient for most phenotypes that characterize Trisomy 21.

Main body

Individuals with Down syndrome show a higher predisposition to leukemias. Hence, RUNX1 overexpression was initially proposed as a critical player on Down syndrome-associated leukemogenesis. Less is known about the functions of RUNX1 in other tissues and organs, although growing reports show important implications in development or homeostasis of neural tissues, muscle, heart, bone, ovary, or the endothelium, among others. Even less is understood about the consequences on these tissues of RUNX1 gene dosage alterations in the context of Down syndrome. In this review, we summarize the current knowledge on RUNX1 activities outside blood/leukemia, while suggesting for the first time their potential relation to specific Trisomy 21 co-occurring conditions.

Conclusion

Our concise review on the emerging RUNX1 roles in different tissues outside the hematopoietic context provides a number of well-funded hypotheses that will open new research avenues toward a better understanding of RUNX1-mediated transcription in health and disease, contributing to novel potential diagnostic and therapeutic strategies for Down syndrome-associated conditions.
Core decompression combined with local DFO administration loaded on polylactic glycolic acid scaffolds for the treatment of osteonecrosis of the femoral head: a pilot study
Authors: Gharanizadeh Kaveh , Sharifi Ali Mohammad , Tayyebi Hamed , Heidari Razieh , Amiri Shayan , Noorigaravand Sajad
Published: September 2023

Background

Deferoxamine (DFO) angiogenesis induction potential has been demonstrated in earlier studies, but not in the osteonecrosis of the femoral head (ONFH). In this study, we evaluated the outcome of ONFH treated with combined core decompression and local DFO administration loaded on Polylactic Glycolic Acid (PLGA).

Patients and methods

In a pilot experimental study, six patients (10 hips) with early-stage non-traumatic ONFH were treated by core decompression, and concurrent injection of local DFO loaded on PLGA scaffold into the subchondral femoral head. Outcome measures were evaluated before the surgery and 12 and 24 months after the surgery and included visual analog scale (VAS) for pain, modified Merle d’Aubigné-Postel (MAP) score for hip function by MRI, and rate of osteonecrosis assessed by the modified.

Results

The mean MPA score was 14.7 ± 1.16 before the surgery and 16.7 ± 1.41 one year after the surgery (P = 0.004). The mean VAS for pain was 4.7 ± 1.25 before the surgery and 1.8 ± 1.03 one year after the surgery (P = 0.005). The mean Kerboul angle was 219 ± 58.64 before the operation and 164.6 ± 41.82 one year after the operation (P < 0.001). Osteonecrosis progression or collapse was not seen in any of the patients at the final follow-up. No postoperative side effect attributed to the DFO was noticed, as well.

Conclusion

In short-term follow-up, combined core decompression and local DFO administration not only prevent the progression of ONFH but also reduces the rate of osteonecrosis significantly. However, future controlled studies are required to confirm the present results.

Trial registration

IRCT20161121031003N3, 16/04/2019.
S100A6: molecular function and biomarker role
Authors: Wang Yidian , Kang Xuewen , Kang Xin , Yang Fengguang
Published: September 2023

S100A6 (also called calcyclin) is a Ca2+-binding protein that belongs to the S100 protein family. S100A6 has many functions related to the cytoskeleton, cell stress, proliferation, and differentiation. S100A6 also has many interacting proteins that are distributed in the cytoplasm, nucleus, cell membrane, and outside the cell. Almost all these proteins interact with S100A6 in a Ca2+-dependent manner, and some also have specific motifs responsible for binding to S100A6. The expression of S100A6 is regulated by several transcription factors (such as c-Myc, P53, NF-κB, USF, Nrf2, etc.). The expression level depends on the specific cell type and the transcription factors activated in specific physical and chemical environments, and is also related to histone acetylation, DNA methylation, and other epigenetic modifications. The differential expression of S100A6 in various diseases, and at different stages of those diseases, makes it a good biomarker for differential diagnosis and prognosis evaluation, as well as a potential therapeutic target. In this review, we mainly focus on the S100A6 ligand and its transcriptional regulation, molecular function (cytoskeleton, cell stress, cell differentiation), and role as a biomarker in human disease and stem cells.
Designing and validating an assessment agency questionnaire for EFL teachers: an ecological perspective
Authors: Ghiasvand Farhad , Jahanbakhsh Akbar A. , Sharifpour Pardis
Published: September 2023

Teacher agency is a pivotal element of professionalism and second/foreign language (L2) education. However, its role in L2 assessment has remained under-researched. Part of this negligence is due to the absence of a validated questionnaire to measure the construct and its underlying components. To address this gap, drawing on the ecological perspective, the present study developed a scale on teacher ecological assessment agency (TEAA) by gleaning data from 539 Iranian EFL teachers. The results of exploratory and confirmatory factor analysis (EFA, CFA) culminated in 5 components and 32 items in the scale. The components were labelled “Iterational”, “Projective”, “Teachers’ Practical-Evaluative View”, “Schools’ Practical-Evaluative Effect”, and “Professional/Democratic Community’s Practical-Evaluative Effect”. Furthermore, the convergent validity and reliability of the scale were statistically approved (p > .05). The study presents some implications for EFL teachers, teacher trainers, and assessment policy-makers in that they can understand and highlight the pivotal role of teacher agency in L2 assessment practices.
Spatio-temporal evolution and distribution of cultural heritage sites along the Suzhou canal of China
Authors: Huang Yan , Yang Shengdan
Published: September 2023

The Grand Canal is one of the most important hydraulic engineering projects in Chinese history. The city of Suzhou has abundant and concentrated cultural heritage sites in the southern section of the Grand Canal. However, due to natural hazards, anthropogenic damage, and lack of human management, the cultural heritage sites have suffered irreversible damage. Digital preservation of these sites will make it possible to maintain their aesthetic and cultural value. This paper takes cultural heritage sites along the Suzhou Canal as its research subject and establishes a cultural heritage dataset using geographical information system (GIS). The paper uses geocoding and spatial analysis methods based on GIS, including nearest neighbor analysis, kernel density analysis, center of gravity analysis, and standard deviation ellipse. The paper explores the distribution of 104 cultural heritage sites along the Suzhou Canal across six historical periods and discusses the influencing factors for evolution of the distribution. The results show that: (1) major constructions on the Grand Canal water system were started in the Pre-Sui period and completed in the Sui and Tang Dynasties; (2) the degree of clustering of the distribution has increased since the Sui and Tang Dynasties until Modern Times; (3) the high-density area has been centered around the ancient city since the Pre-Sui period, and has shown a migration trend towards the Shantang Canal since the Ming Dynasty; (4) the center of gravity first moved from northwest to southeast along the Canal and then moved northeast towards the ancient city; (5) the aggregation of the sites peaked in the Qing dynasty (1636 CE-1911 CE), and the elliptical direction of distribution has become stable since then; and (6) the types of the cultural heritage in the evolution process are affected by the joint effects of natural and human factors, namely, elevation, canals, population, water transportation, and intangible cultural heritage, among which the canal characteristics play the decisive role. This study reveals the internal evolution mechanisms of the cultural heritage in the Suzhou Canal area and presents a scientific basis for the protection and utilization of the cultural heritage in other parts of the world.
Anticandidal effects and chemical compositions of volatile oils extracted from Origanum syriacum, Clinopodium serpyllifolium subsp. fruticosum and Thymbra capitata from Palestine
Authors: Qadi Mohammad , Jaradat Nidal , Al-Maharik Nawaf , Hawash Mohammed , Abdalrazeq Manar , Fuqha Ayat , Jabareen Deema , Atamni Nayruz , Zarour Abdulraziq
Published: September 2023

Background

Over the past decade, researchers have been exploring the potential therapeutic benefits of volatile oils (VOs) in addressing various disorders, particularly those associated with an increase in fungal infections. This study aimed to analyze the chemical compositions of three different thyme species growing in Palestine using gas chromatography–mass spectroscopy (GC–MS) and explore their antifungal characteristics. The thyme species investigated in this research encompass Origanum syriacum L., Clinopodium serpyllifolium subsp. fruticosum (L.) Bräuchler, and Thymbra capitata (L.) Cav.

Methods

The VOs of the investigated plants were extracted by hydrodistillation technique equipped with Cleavenger apparatus and characterized by utilizing GC–MS equipment. Moreover, the extracted VOs were evaluated for their antifungal activity using the broth microdilution assay against several clinically isolated Candida species and one ATCC strain.

Results

The GC–MS characterization results of O. syriacum VO revealed the presence of 22 components and the abundant molecules were thymol (37.36%), carvacrol (27.71%), γ-terpinene (17.47%), and p-cymene (7.80%), while 19 compounds were characterized in the C. serpyllifolium VO and the major components were p-cymene (37.58%), carvacrol (22.93%), and γ-terpinene (21.91%). In addition, 23 compounds were identified in T. capitata VO and the main components were carvone (59.45%), pulegone (21.59%), menthone (4.24%), and isomenthone (3.71%). According to the antifungal assay results, VO extracted from O. syriacum has the highest activity among all the screened VOs.

Conclusion

All the VOs screened in this study exhibit promising antifungal activities for various potential medical applications. Consequently, we strongly advocate for further biological investigations of these oils in the near future.

Graphical Abstract
One Velocity Loss Threshold Does Not Fit All: Consideration of Sex, Training Status, History, and Personality Traits When Monitoring and Controlling Fatigue During Resistance Training
Authors: Jukic Ivan , Prnjak Katarina , McGuigan Michael R. , Helms Eric R.
Published: September 2023

Purpose

This study aimed to quantify the potential variability in the volume of work completed after reaching different velocity loss (VL) thresholds and determine the effects of sex, training status and history, as well as psychological traits on the reliability and magnitude of the amount of work completed after reaching different VL thresholds using different loads in the back-squat exercise.

Methods

Forty-six resistance-trained people (15 females and 31 males; 18 to 40 years of age) with a wide range of strength levels, training experience, and different training practices were recruited and performed a one-repetition maximum (1RM) test, and two repetitions to failure (RTF) tests 72 h apart. RTF tests were performed with 70, 80, and 90% of 1RM with 10 min of rest between sets. The Bland–Altman analysis for multiple observations per participant and equivalence tests were used to quantify the variability in the volume of work completed after reaching different VL thresholds, whereas linear and generalised mixed-effects models were used to examine the effects of different moderators on the stability and magnitude of the amount of work completed after reaching different VL thresholds.

Results

The findings of the present study question the utility of using VL thresholds to prescribe resistance training (RT) volume as the agreement in the amount of work completed across two consecutive testing sessions was not acceptable. Regardless of the load used, females completed more repetitions than males across VL thresholds, while males performed repetitions at higher velocities. In addition, individuals with higher levels of emotional stability also tended to perform more repetitions across VL thresholds. Finally, sex, choice of load, strength levels and training practices, as well as emotional stability affected the linearity of the repetition–velocity relationship and when sets terminated.

Conclusion

Using the same VL thresholds for all individuals, while assuming generalisability of the stimuli applied, would likely lead to variable acute physiological responses to RT and divergent neuromuscular adaptations over long term. Therefore, VL monitoring practices could be improved by considering sex, training status, history, and psychological traits of individuals due to their effects on the variability in responses to different VL thresholds.
The evaluation of the social functioning of schizophrenia patients followed up in the health center My El Hassan of Kenitra, Morocco
Authors: Fitah Ilhame , Chakit Miloud , El Kadiri Mohamed , Brikat Sara , El Hessni Aboubaker , Mesfioui Abdelhalim
Published: September 2023

Background

Difficulties in interacting in and adapting to the social world are the central complaint faced by patients with schizophrenia. These people are often socially isolated, unemployed and may find it difficult to live independently.

Aim

This study aims to evaluate the social functioning of schizophrenic patients, and to highlight the various factors associated with the alteration of the social functioning of schizophrenic patients.

Methods

We conducted a prospective descriptive and analytical study of a population of 72 patients with schizophrenia. These are patients between 19 and 59 years old, clinically stabilized, diagnosed and followed at the My EL Hassan health center in Kenitra (Morocco). Symptom assessment is measured using a standardized Positive and Negative Syndrome Scale (PANSS), and social functioning is assessed using a Social Functioning Questionnaire (SFQ).

Results

Statistical analysis shows that of 72 schizophrenic patients, 33.3% had good social functioning, 59.7% had moderate social functioning, while 6.9% of patients had altered social functioning (the average score of all SFQ items less than 2.4). 6.9% with altered social functioning, are patients aged 19 to 49, were male (p < 0.35), come from an urban areas (p < 0.17), without professional activity (p < 0.00), and have a progressive onset of the disease (p < 0.31). 5.5% (n = 4) of them were single (p < 0.12), caught this disease at an age greater than or equal to 20 years, and have the mixed type of symptoms (positive/negative) (p < 0.15). The altered social functioning of our patients is correlated to five factors: professional activity (p < 0.00), family situation (p < 0.03), family care (p < 0.02), family awareness (p < 0.01), and the negative subtype of psychotic symptomatology (p < 0.02).

Conclusion

This study underlines the interest of psycho-social treatment as specific care which would complement symptomatic treatment and improve the social functioning of patients with schizophrenia.
Fucose as a nutrient ligand for Dikarya and a building block of early diverging lineages
Authors: Orłowska Małgorzata , Barua Drishtee , Piłsyk Sebastian , Muszewska Anna
Published: September 2023

Fucose is a deoxyhexose sugar present and studied in mammals. The process of fucosylation has been the primary focus in studies relating to fucose in animals due to the presence of fucose in Lewis antigens. Very few studies have reported its presence in Fungi, mostly in Mucoromycotina. The constitution of 25% and 12% of this sugar in the carbohydrates of cell wall in the respective Umbelopsis and Mucorales strains boosts the need to bridge the gap of knowledge on fucose metabolism across the fungal tree of life. In the absence of a network map involving fucose proteins, we carried out an in-silico approach to construct the fucose metabolic map in Fungi. We analyzed the taxonomic distribution of 85 protein families in Fungi including diverse early diverging fungal lineages. The expression of fucose-related protein-coding genes proteins was validated with the help of transcriptomic data originating from representatives of early diverging fungi. We found proteins involved in several metabolic activities apart from fucosylation such as synthesis, transport and binding. Most of the identified protein families are shared with Metazoa suggesting an ancestral origin in Opisthokonta. However, the overall complexity of fucose metabolism is greater in Metazoa than in Fungi. Massive gene loss has shaped the evolutionary history of these metabolic pathways, leading to a repeated reduction of these pathways in most yeast-forming lineages. Our results point to a distinctive mode of utilization of fucose among fungi belonging to Dikarya and the early diverging lineages. We speculate that, while Dikarya used fucose as a source of nutrients for metabolism, the early diverging group of fungi depended on fucose as a building block and signaling compound.

Graphical abstract
The prognostic role of urea-to-creatinine ratio in patients with acute heart failure syndrome: a case–control study
Authors: Sakr Ahmed Refaat Mohamed , Gomaa Gamal Fahim Elsayed , Wasif Salwa Mahmoud El , Eladawy Ahmed Hassan Hosny
Published: September 2023

Background

Recent research has shown that the blood urea/creatinine ratio (BUN/Cr) rather than BUN or Cr alone can predict the prognosis of individuals with acute heart failure (AHF). The objective of this study was to estimate the urea-to creatinine serum ratio (BUN/Cr) in patients with acute decompensated heart failure (ADHF) and correlate the results with patient outcome, length of hospitalization, and mortality.

Results

Sixty ADHF patients were included and categorized into four groups; Group I: non-AKI with low BUN/Cr (n = 25); Group II: non-AKI with high BUN/Cr (n = 5); Group III: AKI with low BUN/Cr (n = 14); Group IV: AKI with high BUN/Cr (n = 16). Regarding urea and BUN levels, the first reading showed a considerable rise in urea and BUN levels in groups III and IV compared to group 1 and in group IV compared to groups I and III. Similar results were recorded in the second and third readings. Regarding the BUN/Cr ratio, the three readings revealed a significant elevation in group IV compared to groups I and II and in group IV compared to group III. Mortality was significantly higher in group IV compared to group I. Additionally, MACE was significantly more frequent in group IV compared to groups I and III. Multivariable logistic regression analysis revealed that hypertension, creatinine, and BUN were independent predictors of AKI.

Conclusions

BUN/Cr may predict prognosis in AHF patients since AHF with an elevated BUN/Cr is associated with a higher death rate.
Are public health researchers designing for dissemination? Findings from a national survey in China
Authors: Hu Yiluan , Yin Xuejun , Gong Enying , Liu Jing , Liu Xia , Shao Ruitai , Zhang Juan , Brownson Ross C
Published: September 2023

Background

Research findings are not always disseminated in ways preferred by audiences, and research dissemination is not always considered a priority by researchers. While designing for dissemination (D4D) provides an active process to facilitate effective dissemination, use of these practices in China is largely unknown. We aimed to describe the designing for dissemination activities and practices among public health researchers in China.

Methods

In January 2022, we conducted a cross-sectional survey in 61 sub-committees of four national academic societies which include a wide range of health disciplines. The sample mainly involved researchers at universities or research institutions, the Centers for Disease Control and Prevention at national or regional levels, and hospitals. Participants completed a 42-item online questionnaire. Respondent characteristics, dissemination routes, dissemination barriers, organizational support, and personal practice of D4D were examined with descriptive analyses.

Results

Of 956 respondents, 737 were researchers. Among these researchers, 58.1% had disseminated their research findings. Although there were some variation in the commonly used routes among different groups, academic journals (82.2%) and academic conferences (73.4%) were the most frequently used routes. Barriers to dissemination to non-research audiences existed at both organizational level (e.g., a lack of financial resources, platforms, and collaboration mechanisms) and individual level (e.g., a lack of time, knowledge, and skills, and uncertainty on how to disseminate). About a quarter of respondents (26.7%) had a dedicated person or team for dissemination in their unit or organization, with university researchers reporting a significantly higher proportion than their counterparts (P < 0.05). Only 14.2% of respondents always or usually used frameworks or theories to plan dissemination activities, 26.2% planned dissemination activities early, and 27.1% always or usually involved stakeholders in the research and dissemination process. Respondents with working experience in a practice or policy setting or dissemination and implementation training experience were more likely to apply these D4D strategies (P < 0.05).

Conclusion

Considerable room exists for improvement in using impactful dissemination routes, tackling multiple barriers, providing organizational support, and applying D4D strategies among Chinese public health researchers. Our findings have implications for structural changes in academic incentive systems, collaborations and partnerships, funding priorities, and training opportunities.
Big data in relation with business intelligence capabilities and e-commerce during COVID-19 pandemic in accountant’s perspective
Authors: Huy Pham Quang , Phuc Vu Kien
Published: September 2023

This research aims at producing a thorough and accurate analysis on how big data as a service and business intelligence capabilities provide a series of opportunities for small and medium enterprises to succeed in E-commerce. The statistical data were drawn from samples of accountants within small and medium enterprises, spanning two periods, the period of COVID-19 pandemic and the period of new normal. The structural equation modeling was applied in this study. The value of fine-grained insights in this work could guide policy-makers and practitioners to sense and seize how to implement E-commerce in an efficient and effective manner.
Emulsomes: new lipidic carriers for drug delivery with special mention to brain drug transport
Authors: Singh Shivam , Khurana Kunal , Chauhan Shikha Baghel , Singh Indu
Published: September 2023

Background

Emulsomes are a type of lipid-based nanoparticle that consists of a solid lipid core surrounded by a phospholipid bilayer and have shown promise as drug delivery systems for a variety of applications. The major advantageous aspect of employing lipid-based carriers is their ability to enhance the solubility and bioavailability of poorly water-soluble drugs, mandatorily in case of intranasal drug delivery. These structures have portrayed significant ability to encapsulate drug with poor water solubility and low oral bioavailability, further leading to a completely enhanced drug delivery systems for achieving stability and controlled release of drug. The selection of lipid components and their physiochemical properties can be tailored to optimize drug solubility, blood brain barrier permeability, and enhanced targeting.

Main body of abstract

Intranasal drug delivery systems offer several advantages over other routes of administration. Intranasal delivery of drugs can provide rapid and efficient absorption into the bloodstream, bypassing first-pass metabolism in the liver and potentially reducing the risk of systemic side effects. Nasal mucosa comprises of dense network of blood vessels, that allow much enhanced rapid drug absorption and direct systemic delivery once the medication is being insufflated through the nasal route. Emulsomes can be used to encapsulate a wide range of drugs, including hydrophobic compounds that are difficult to formulate using traditional delivery methods. By incorporating targeting ligands or other components into the emulsome structure, it is possible to create formulations that are highly selective for specific tissues or cells. The characterization parameters majorly particle size, zeta potential, and encapsulation efficiency play a significant role while demonstrating the effectiveness of emulsome formulation and further its nasal route of administration. Therefore, by assessing and evaluating the parameters, researchers could effectively gain insights into the quality, stability, and enhanced therapeutic effects of emulsome drug carrier, leading to impactful information which would help in future intranasal emulsome preparation preparations, optimization and ensuring the overall effectiveness of the drug delivery systems.

Short conclusion

This review discusses the idea of emulsomes drug delivery systems, reviews the effectiveness of emulsomes for the delivery of small molecules, and pays particular attention to its structural and formulation design including benefits of intranasal emulsome delivery with recent advancements, stability aspects, and various considerations related to drug delivery and comprising of future prospects.
E-cadherin expression pattern in head and neck squamous cell carcinoma and its association with clinico-pathological predictors
Authors: Devaraja K. , Pillai Suresh , Valiathan Manna , Geetha V. , Pujary Kailesh
Published: September 2023

Background

The molecular makeup of a head and neck squamous cell carcinoma (HNSCC) could vary as per the geography and corresponding variability in prevalent etiopathological factors. The objective of this study was to analyze the expression pattern of E-cadherin (E-cad), a transmembrane glycoprotein with tumour suppressor function, in a cohort of HNSCC treated at a tertiary care medical centre in the southern part of India.

Material and methods

After obtaining the institutional ethics committee’s permission, the expression of E-cad in HNSCC was assessed by using immunohistochemistry on retrospectively collected tumour specimens, obtained by a surgical cohort of cases operated between September 2018 and July 2019. The E-cad expression was then correlated with various clinical and pathological characteristics of HNSCC, retrieved via the medical records of corresponding patients.

Results

A total of 60 patients of HNSCC were included, most of whom had lesion in the oral cavity, in an advanced stage. The majority had a strong or moderate expression of E-cad on the surface. On analyzing further, oral cavity tumours had significantly less expression of E-cad compared to laryngeal and hypopharyngeal tumours taken together, and primary tumours had less E-cad expression than recurrent cases. Multivariate analysis with proportional odds regression showed the significant associations of low expression of E-cad expression with the moderate/poor differentiation of tumours and with the extranodal extension.

Conclusions

Among the HNSCC, the loss of E-cad expression was mostly associated with primary tumours of the oral cavity, moderate/poorly differentiated tumours, and in those HNSCCs that had an extranodal extension.
Prevalence and correlates of meeting the Canadian 24-hour movement guidelines among a sample of Canadian parents during the COVID-19 pandemic
Authors: Rollo Scott , Sckrapnick Abigail , Campbell Julie E , Moore Sarah A , Faulkner Guy , Tremblay Mark S
Published: September 2023

Background

Parents’ own movement behaviours can influence those of their children, thus contributing to the health and well-being of the whole family. Parents experienced a shift in work and childcare responsibilities during the COVID-19 pandemic. This may have led to a reduction in their healthy movements. This study examined the prevalence and correlates of meeting vs. not meeting the individual and combined recommendations within the Canadian 24-hour movement guidelines for adults among a sample of Canadian parents during the second wave (October 2020) of the COVID-19 pandemic.

Methods

Parents of children aged 5–17 years (n = 1,477) responded to a cross-sectional survey conducted in October 2020. A total of 21 self-reported correlates, including parental and child demographics, and change in family movement behaviours/characteristics were assessed. Parental movement behaviours were reported and classified as meeting or not meeting each of the guidelines. Associations between correlates and meeting each of the guidelines were examined using multiple logistic regression.

Results

The proportion of parents who met the moderate-vigorous physical activity (MVPA), recreational screen time, sleep duration and combined guidelines were 21.2, 51.0, 66.1, and 9.1%, respectively. Being a parent ≥ 45 years old, having a university education, and higher levels of outdoor play were associated with meeting the combined guidelines. Age, dwelling type, family hobbies, and outdoor play were associated with meeting the MVPA recommendation. Employment status, education level, dog ownership, children’s age, family physical activity, and levels of distress were associated with meeting the recreational screen time recommendation. Geographical region, dwelling type, and levels of distress were associated with meeting the sleep duration recommendation.

Conclusions

Few Canadian parents were meeting the combined 24-hour movement guidelines recommendations for MVPA, recreational screen time, and sleep six months into the COVID-19 pandemic. Several socio-demographic, behavioural, and COVID-19-related factors emerged as significant correlates of meeting vs. not meeting the individual and/or combined recommendations within the guidelines. The findings provide various avenues for which to target future movement behaviour interventions and guideline adoption for parents.
Human Brain Penetration Prediction Using Scaling Approach from Animal Machine Learning Models
Authors: Liu Siyu , Kosugi Yohei
Published: September 2023

Machine learning (ML) approaches have been applied to predicting drug pharmacokinetic properties. Previously, we predicted rat unbound brain-to-plasma ratio (Kpuu,brain) by ML models. In this study, we aimed to predict human Kpuu,brain through animal ML models. First, we re-evaluated ML models for rat Kpuu,brain prediction by using trendy open-source packages. We then developed ML models for monkey Kpuu,brain prediction. Leave-one-out cross validation was utilized to rationally build models using a relatively small dataset. After establishing the monkey and rat ML models, human Kpuu,brain prediction was achieved by implementing the animal models considering appropriate scaling methods. Mechanistic NeuroPK models for the identical monkey and human dataset were treated as the criteria for comparison. Results showed that rat Kpuu,brain predictivity was successfully replicated. The optimal ML model for monkey Kpuu,brain prediction was superior to the NeuroPK model, where accuracy within 2-fold error was 78% (R2 = 0.76). For human Kpuu,brain prediction, rat model using relative expression factor (REF), scaled transporter efflux ratios (ERs), and monkey model using in vitro ERs can provide comparable predictivity to the NeuroPK model, where accuracy within 2-fold error was 71% and 64% (R2 = 0.30 and 0.52), respectively. We demonstrated that ML models can deliver promising Kpuu,brain prediction with several advantages: (1) predict reasonable animal Kpuu,brain; (2) prospectively predict human Kpuu,brain from animal models; and (3) can skip expensive monkey studies for human prediction by using the rat model. As a result, ML models can be a powerful tool for drug Kpuu,brain prediction in the discovery stage.

Graphical abstract
Clinical and Molecular Characteristics and Long-term Follow-up of Children With Pseudohypoparathyroidism Type IA
Authors: Ludar Hanna , Levy-Shraga Yael , Admoni Osnat , Majdoub Hussein , Aronovitch Kineret Mazor , Koren Ilana , Rath Shoshana , Elias-assad Ghadir , Almashanu Shlomo , Mantovani Giovanna , Hamiel Orit Pinhas , Tenenbaum-Rakover Yardena
Published: September 2023

Context

Pseudohypoparathyroidism type IA (PHPIA) is a rare genetic disorder characterized by hormone resistance and a typical phenotype named Albright hereditary osteodystrophy. Unawareness of this rare disease leads to delays in diagnosis.

Objective

The aims of this study were to describe the clinical and molecular characteristics of patients with genetically confirmed GNAS mutations and to evaluate their long-term outcomes.

Methods

A retrospective search for all patients diagnosed with PHPIA in 2 referral centers in Israel was conducted.

Results

Nine children (8 females) belonging to 6 families were included in the study. Five patients had GNAS missense mutations, 2 had deletions, and 2 had frameshift mutations. Four mutations were novel. Patients were referred at a mean age of 2.4 years due to congenital hypothyroidism (5 patients), short stature (2 patients), or obesity (2 patients), with a follow-up duration of up to 20 years. Early obesity was observed in the majority of patients. Elevated parathyroid hormone was documented at a mean age of 3 years; however, hypocalcemia became evident at a mean age of 5.9 years, about 3 years later. All subjects were diagnosed with mild to moderate mental retardation. Female adult height was very short (mean −2.5 SD) and 5 females had primary or secondary amenorrhea.

Conclusion

Long-term follow-up of newborns with a combination of congenital hypothyroidism, early-onset obesity, and minor dysmorphic features associated with PHPIA is warranted and molecular analysis is recommended since the complete clinical phenotype may develop a long time after initial presentation.
Navigated Radiofrequency Ablation Peripheral Rhizotomy for Lumbosacral Hypertonia in a Nonambulatory Patient With Spinal Fusion: Indications, Surgical Techniques, and Lessons Learned
Authors: LoPresti Melissa A. , Horak V. Jane , Trierweiler Robin , Stone Lauren E. , Krater Timothy , Raskin Jeffrey S.
Published: September 2023

BACKGROUND AND OBJECTIVES:

Radiofrequency ablation (RFA) is a destructive therapy which causes target tissue destruction by application of a thermal dose. Neurosurgical applications of RFA are well-described for myriad chronic pain and movement disorder diagnoses. In fact, RFA pallidotomy and thalamotomy are the initial procedures from which the field of neurosurgical management for movement disorders emerged. RFA rhizotomy for post-traumatic spasms was popular in the 1970s and 1980s, although it was largely abandoned after the invention and Food and Drug Administration approval of intrathecal baclofen therapy. RFA has not been described as a primary treatment of hypertonia in nonambulatory children.

METHODS:

We report a case of computer-navigated, nonselective RFA peripheral rhizotomy for a nonambulatory child with a history of severe scoliosis and spinal fusion, where an open rhizotomy was technically impractical.

RESULTS:

Navigation to and ablation of the bilateral L1–L5 peripheral nerves with this approach was successful, and the patient experienced bilateral lower extremity tone improvement.

CONCLUSION:

We use this case to highlight considerations in indications, our applied operative technique, and lessons learned from this novel application of RFA peripheral rhizotomy in children.
Shock drives a STAT3 and JunB-mediated coordinated transcriptional and DNA methylation response in the endothelium
Authors: Ramos Ramon Bossardi , Martino Nina , Chuy Dareen , Lu Shuhan , Zuo Mei Xing G. , Balasubramanian Uma , Di John Portela Iria , Vincent Peter A. , Adam Alejandro P.
Published: September 2023

Endothelial dysfunction is a crucial factor in promoting organ failure during septic shock. However, the underlying mechanisms are unknown. Here, we show that kidney injury after lipopolysaccharide (LPS) insult leads to strong endothelial transcriptional and epigenetic responses. Furthermore, SOCS3 loss leads to an aggravation of the responses, demonstrating a causal role for the STAT3-SOCS3 signaling axis in the acute endothelial response to LPS. Experiments in cultured endothelial cells demonstrate that IL-6 mediates this response. Furthermore, bioinformatics analysis of in vivo and in vitro transcriptomics and epigenetics suggests a role for STAT, AP1 and interferon regulatory family (IRF) transcription factors. Knockdown of STAT3 or the AP1 member JunB partially prevents the changes in gene expression, demonstrating a role for these transcription factors. In conclusion, endothelial cells respond with a coordinated response that depends on overactivated IL-6 signaling via STAT3, JunB and possibly other transcription factors. Our findings provide evidence for a critical role of IL-6 signaling in regulating shock-induced epigenetic changes and sustained endothelial activation, offering a new therapeutic target to limit vascular dysfunction.
Putting a new spin on insect jumping performance using 3D modeling and computer simulations of spotted lanternfly nymphs
Authors: Li Chengpei , Xu Aaron J. , Beery Eric , Hsieh S. Tonia , Kane Suzanne Amador
Published: September 2023

How animals jump and land on diverse surfaces is ecologically important and relevant to bioinspired robotics. Here, we describe the jumping biomechanics of the planthopper Lycorma delicatula (spotted lanternfly), an invasive insect in the USA that jumps frequently for dispersal, locomotion and predator evasion. High-speed video was used to analyze jumping by spotted lanternfly nymphs from take-off to impact on compliant surfaces. These insects used rapid hindleg extensions to achieve high take-off speeds (2.7–3.4 m s−1) and accelerations (800–1000 m s−2), with mid-air trajectories consistent with ballistic motion without drag forces or steering. Despite rotating rapidly (5–45 Hz) about time-varying axes of rotation, they landed successfully in 58.9% of trials. They also attained the most successful impact orientation significantly more often than predicted by chance, consistent with their using attitude control. Notably, these insects were able to land successfully when impacting surfaces at all angles, pointing to the importance of collisional recovery behaviors. To further understand their rotational dynamics, we created realistic 3D rendered models of spotted lanternflies and used them to compute their mechanical properties during jumping. Computer simulations based on these models and drag torques estimated from fits to tracked data successfully predicted several features of the measured rotational kinematics. This analysis showed that the rotational inertia of spotted lanternfly nymphs is predominantly due to their legs, enabling them to use posture changes as well as drag torque to control their angular velocity, and hence their orientation, thereby facilitating predominately successful landings when jumping.
Catalyst Design with Small Organic Ion Pairs
Authors: Ohmatsu Kohsuke
Published: September 2023

Cations and anions are fundamental species whose interactions have been thoroughly studied and widely applied in organic synthesis, particularly to control the selectivity in chemical transformations. Strategies exploiting ion pairing have proven to be applicable to a broad range of reactions that proceed via anionic intermediates and cationic species. Considering the general versatility of ion pairs in constructing well-organized transition structures, we utilized these powerful attractive interactions to construct catalyst structures. This account summarizes the design and applications of ion-paired chiral ligands and chiral 1,2,3-triazolium salts.
Μελέτη γενετικών βιοδεικτών σε ασθενείς με πολλαπλή σκλήρυνση
Authors: Τσούρης Ζήσης
Published: September 2023

Εισαγωγή: Η πολλαπλή σκλήρυνση (ΠΣ) είναι μια χρόνια νόσος του κεντρικού νευρικού συστήματος (ΚΝΣ). Τα κύτταρα της μυελικής σειράς (μικρογλοιακά κύτταρα και μακροφάγα) μπορεί να συμμετέχουν στους παθογενετικούς μηχανισμούς της ΠΣ. Το CD33 rs3865444 είναι μια μετάλλαξη του υποκινητή που έχει συσχετιστεί με τη νόσο Alzheimer, του οποίου ο ρόλος στη ΠΣ παραμένει ασαφής. Ο υποδοχέας της αδενοσίνης A2a (ADORA2A) και το κυτόχρωμα P450 1A2 (CYP1A2) εμπλέκονται σε μονοπάτια όπως το οξειδωτικό στρες και ο μεταβολισμός της καφεΐνης, που σχετίζονται με τη νευροεκφύλιση και τη νευροφλεγμονή. Ο στόχος αυτής της μελέτης ήταν να διερευνήσει την πιθανή συσχέτιση μεταξύ των γενετικών παραλλαγών του CD33 rs3865444, του ADORA2A rs5760423 και του CYP1A2 rs762551 και της ΠΣ.Μέθοδοι: Συνολικά γονοτυπήθηκαν 1396 ασθενείς με ΠΣ και 400 υγιείς μάρτυρες για την παρουσία των μεταλλάξεων CD33 rs3865444, ADORA2A rs5760423 και CYP1A2 rs762551. Οι λόγοι πιθανοτήτων (ORs) με τα αντίστοιχα διαστήματα εμπιστοσύνης 95% (CIs), υπολογίστηκαν με το λογισμικό SNPStats, υποθέτοντας πέντε γενετικά μοντέλα (συν-επικρατητικό, επικρατητικό, υπολειπόμενο, υπερεπικρατητικό και log-additive), με το αλληλόμορφο G για το CD33 rs3865444 και ADORA2A rs5760423 ως αλληλόμορφο αναφοράς, και το Α για το CYP1A2 rs762551 ως αλληλόμορφο αναφοράς. Ως όριο στατιστικής σημαντικότητας ορίστηκε η τιμή 0,05.Αποτελέσματα: Το CD33 rs3865444 συσχετίστηκε με τον κίνδυνο ΠΣ στον επικρατητικό (GG έναντι GT + TT; OR (95% C.I.) = 0,79 (0,63–0,99), p = 0,041) και τον υπερεπικρατητικό (GG + TT έναντι GT ; Ή (95% C.I.) = 0,77 (0,61–0,97), p = 0,03) τρόπο κληρονομικότητας. Δεδομένου ότι ο γονότυπος GG ήταν πιο συχνός και ο γονότυπος GT ήταν λιγότερο συχνός σε ασθενείς με ΠΣ σε σύγκριση με τους μάρτυρες, η παρατηρούμενη διαφορά στον κίνδυνο ΠΣ μπορεί να προέρχεται είτε από τον γονότυπο GG (ως παράγοντας κινδύνου) είτε από τον GT (ως προστατευτικός παράγοντας) του CD33 rs3865444. Επιπλέον, οι μεταλλάξεις ADORA2A rs5760423 και CYP1A2 rs762551 δεν συσχετίστηκαν με κίνδυνο ΠΣ.Συμπεράσματα: Τα προκαταρκτικά μας αποτελέσματα υποδηλώνουν πιθανή εμπλοκή του CD33 rs3865444 στον κίνδυνο της ΠΣ. Ως εκ τούτου, είναι ανάγκη να διεξαχθούν μεγαλύτερες πολυκεντρικές μελέτες, για την περαιτέρω διερεύνηση του ρόλου του CD33 rs3865444 στην ΠΣ.
Μελέτη των προϊόντων προχωρημένης μη ενζυμικής γλυκοζυλίωσης (AGEs) του δέρματος σε σχέση με τη νευροπάθεια σε ασθενείς με σακχαρώδη διαβήτη τύπου 2
Authors: Παπαχρήστου Στέλλα
Published: September 2023

Σκοπός της μελέτης: Σκοπός της μελέτης ήταν η εξέταση των προϊόντων προχωρημένης μη ενζυμικής γλυκοζυλίωσης (AGEs) του δέρματος σε σχέση με τη νευροπάθεια σε άτομα με σακχαρώδη διαβήτη τύπου 2 (ΣΔτ2).Υλικό και μέθοδοι: Συμπεριελήφθησαν 132 άτομα (88 άνδρες, 44 γυναίκες) μέσης ηλικίας 64.57±8.21 ετών με ΣΔτ2. Τα AGEs μετρήθηκαν στο δέρμα με τη συσκευή AGE reader mu connect (Diagnoptics) στο επικρατητικό άνω άκρο. Η διαβητική περιφερική νευροπάθεια (ΔΠΝ), όπως και η δυσλειτουργία των μικρών και των μεγάλων νευρικών ινών, διαγνώστηκαν κλινικά με το δείκτη νευρολογικής ανικανότητας (ΔΝΑ). Η νευροπάθεια του αυτονόμου νευρικού συστήματος καρδιάς και αγγείων (ΚΑΝ), όπως και η δυσλειτουργία του συμπαθητικού νευρικού συστήματος (ΣΝΣ) και του παρασυμπαθητικού νευρικού συστήματος (ΠΝΣ), διαγνώστηκαν με τα καρδιαγγειακά αντανακλαστικά. Κύρια αποτελέσματα: Τα AGEs παρουσίαζαν υψηλότερη τιμή σε παρουσία της ΔΠΝ (p<0.001). Επίσης, παρουσίαζαν υψηλότερη τιμή (p<0.05), όταν υπήρχε διαταραχή της βλάβης των μικρών ή των μεγάλων νευρικών ινών. Τα AGEs παρουσίαζαν θετική συσχέτιση με την τιμή του ΔΝΑ. Τα AGEs παρουσίαζαν υψηλότερη τιμή σε παρουσία της ΚΑΝ (p<0.001). Επίσης, παρουσίαζαν υψηλότερη τιμή, όταν υπήρχε διαταραχή καθενός από τα καρδιαγγειακά αντανακλαστικά (δείκτης Valsalva: p=0.004, δείκτης E/I: p=0.001, δείκτης 30:15: p=0.011, ορθοστατική υπόταση: p<0.001). Ως δοκιμασία διαλογής, για τη ΔΠΝ τα AGEs παρουσίαζαν υψηλή ευαισθησία (82.8%) και αρνητική προγνωστική αξία (NPV) (80.4%). Για την ΚΑΝ παρουσίαζαν σχετικά υψηλή ευαισθησία (75.0%) και NPV (74.5%). Για τη δυσλειτουργία του ΣΝΣ τα AGEs παρουσίαζαν σχετικά υψηλή ευαισθησία (75.0%) και υψηλή NPV (84.3%). Για τη δυσλειτουργία του ΠΝΣ παρουσίαζαν υψηλή θετική προγνωστική αξία (PPV) (81.0%) με μετρίως υψηλή ευαισθησία (66.7%).Συμπεράσματα: Στο ΣΔτ2, τα AGEs του δέρματος παρουσιάζουν αύξηση σε παρουσία τόσο της ΔΠΝ όσο και της ΚΑΝ. Επίσης, παρουσιάζουν χρησιμότητα ως δοκιμασία διαλογής για τις επιπλοκές αυτές.