bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal activation of MAPKs pathways and inhibition of autophagy in a group of patients with Zellweger spectrum disorders and X-linked adrenoleukodystrophy
Authors: Gragnaniello Vincenza , Gueraldi Daniela , Puma Andrea , Commone Anna , Cazzorla Chiara , Loro Christian , Porcù Elena , Stornaiuolo Maria , Miglioranza Paolo , Salviati Leonardo , Wanders Ronald J. A. , Burlina Alberto
Published: November 2023

Background

Zellweger spectrum disorders (ZSD) and X-linked adrenoleukodystrophy (X-ALD) are inherited metabolic diseases characterized by dysfunction of peroxisomes, that are essential for lipid metabolism and redox balance. Oxidative stress has been reported to have a significant role in the pathogenesis of neurodegenerative diseases such as peroxisomal disorders, but little is known on the intracellular activation of Mitogen-activated protein kinases (MAPKs). Strictly related to oxidative stress, a correct autophagic machinery is essential to eliminated oxidized proteins and damaged organelles. The aims of the current study are to investigate a possible implication of MAPK pathways and autophagy impairment as markers and putative therapeutic targets in X-ALD and ZSDs.

Methods

Three patients with ZSD (2 M, 1 F; age range 8–17 years) and five patients with X-ALD (5 M; age range 5- 22 years) were enrolled. A control group included 6 healthy volunteers. To evaluate MAPKs pathway, p-p38 and p-JNK were assessed by western blot analysis on peripheral blood mononuclear cells. LC3II/LC3I ratio was evaluated ad marker of autophagy.

Results

X-ALD and ZSD patients showed elevated p-p38 values on average 2- fold (range 1.21- 2.84) and 3.30-fold (range 1.56- 4.26) higher when compared with controls, respectively. p-JNK expression was on average 12-fold (range 2.20–19.92) and 2.90-fold (range 1.43–4.24) higher in ZSD and X-ALD patients than in controls. All patients had altered autophagic flux as concluded from the reduced LC3II/I ratio.

Conclusions

In our study X-ALD and ZSD patients present an overactivation of MAPK pathways and an inhibition of autophagy. Considering the absence of successful therapies and the growing interest towards new therapies with antioxidants and autophagy inducers, the identification and validation of biomarkers to monitor optimal dosing and biological efficacy of the treatments is of prime interest.
Medication compliance of children with epilepsy: a cross-sectional survey
Authors: Wang Shanshan , Zhang Xu , Wang Yongqian , Zhou Jinfang
Published: November 2023

Background

Good medication compliance is very important for the prognosis of children with epilepsy. We aimed to evaluate the status and influencing factors of medication compliance in children with epilepsy and to provide insights to the clinical nursing care of children with epilepsy.

Methods

We selected epileptic children admitted to Children’s Hospital of Nanjing Medical University from February 1, 2022 to August 31, 2022. Self-designed questionnaire and medication compliance scale were used to evaluate the characteristics and medication compliance of children with epilepsy. Pearson correlation analysis and multivariate logistic regression were used to analyze the influencing factors of medication compliance.

Results

A total of 156 children with epilepsy were included, the incidence of poor compliance in children with epilepsy was 37.18%. Pearson correlation analysis indicated that age(r = 0.622), courses of epilepsy(r = 0.553), parental education level(r = 0.506), monthly household income(r = 0.652) and number of drugs taken(r = 0.577) were correlated with the compliance(all P<0.05). Logistic regression analyses indicated that age ≤ 6 y(OR = 2.104, 95%CI: 1.712 ~ 2.527), courses of epilepsy ≤ 3 years(OR = 2.661, 95%CI: 2.089 ~ 2.941), low parental education level(OR = 1.977, 95%CI: 1.314 ~ 2.351), monthly household income ≤ 5000 RMB(OR = 2.812, 95%CI: 2.194 ~ 3.181), number of drugs taken ≥ 3(OR = 3.025, 95%CI: 2.336 ~ 3.475) were the influencing factors of medication compliance in children with epilepsy(all P<0.05).

Conclusions

The medication compliance of children with epilepsy needs to be improved, and the medication compliance of children is affected by age, courses of epilepsy, parental education level, monthly household income and number of drugs taken. Clinical medical personnel take targeted nursing measures against these factors to improve the medication compliance of children with epilepsy.
Evaluating the effectiveness of video-game based swallowing function training in patients with dysphagia: study protocol for a randomized controlled trial
Authors: Zhang Bohan , Guo Cai , Hui Vivian , Wong Ka Po , Liu Yue , Liu Zihan , Xu Yanan , Xiao Qian , Chen Shu-Cheng , Qin Jing
Published: November 2023

Background

Dysphagia can lead to serious complications such as aspiration and aspiration pneumonia, timely and effective rehabilitation training can improve the swallowing function of patients. However, the conventional rehabilitation training methods used in clinical settings have shortcomings such as poor adherence of patients. We present the study design of a randomized controlled trial that evaluated whether video-game based swallowing rehabilitation training can effectively improve swallowing in patients with dysphagia and whether it has additional benefits compared with conventional training methods to improve swallowing function and training compliance among patients with dysphagia.

Methods

A randomized controlled trial with 4 weeks of intervention and 4 weeks of follow-up will be conducted in a rehabilitation center in Beijing, China. We will enroll 78 patients aged 18–80 years with dysphagia. Participants will be randomly assigned to the experimental group (video-game based swallowing function training) and the control group (conventional swallowing function training). All participants will receive 30 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcome is swallowing function. Secondary outcomes include patients' quality of life, training compliance, and training satisfaction. Outcomes are assessed at baseline (pre-treatment), 4 weeks of treatment (post-treatment), and 8 weeks (follow-up), and the assessor is not aware of the participants’ grouping.

Discussion

The protocol describes a new rehabilitation training method for dysphagia, which involves participant eligibility recruitment, recruitment strategies, and data analysis plan. The results of the study will inform the rehabilitation training and clinical care management of swallowing function in patients with dysphagia.

Trial registration

ClinicalTrials.gov, NCT05978700. Registered on 28 July 2023.
The Promotoer, a brain-computer interface-assisted intervention to promote upper limb functional motor recovery after stroke: a statistical analysis plan for a randomized controlled trial
Authors: Cipriani Marta , Pichiorri Floriana , Colamarino Emma , Toppi Jlenia , Tamburella Federica , Lorusso Matteo , Bigioni Alessandra , Morone Giovanni , Tomaiuolo Francesco , Santoro Filippo , Cordella Daniele , Molinari Marco , Cincotti Febo , Mattia Donatella , Puopolo Maria
Published: November 2023

Background

Electroencephalography (EEG)-based brain-computer interfaces (BCIs) allow to modulate the sensorimotor rhythms and are emerging technologies for promoting post-stroke motor function recovery. The Promotoer study aims to assess the short and long-term efficacy of the Promotoer system, an EEG-based BCI assisting motor imagery (MI) practice, in enhancing post-stroke functional hand motor recovery. This paper details the statistical analysis plan of the Promotoer study.

Methods

The Promotoer study is a randomized, controlled, assessor-blinded, single-centre, superiority trial, with two parallel groups and a 1:1 allocation ratio. Subacute stroke patients are randomized to EEG-based BCI-assisted MI training or to MI training alone (i.e. no BCI). An internal pilot study for sample size re-assessment is planned. The primary outcome is the effectiveness of the Upper Extremity Fugl-Meyer Assessment (UE-FMA) score. Secondary outcomes include clinical, functional, and user experience scores assessed at the end of intervention and at follow-up. Neurophysiological assessments are also planned. Effectiveness formulas have been specified, and intention-to-treat and per-protocol populations have been defined. Statistical methods for comparisons of groups and for development of a predictive score of significant improvement are described. Explorative subgroup analyses and methodology to handle missing data are considered.

Discussion

The Promotoer study will provide robust evidence for the short/long-term efficacy of the Promotoer system in subacute stroke patients undergoing a rehabilitation program. Moreover, the development of a predictive score of response will allow transferring of the Promotoer system to optimal clinical practice. By carefully describing the statistical principles and procedures, the statistical analysis plan provides transparency in the analysis of data.

Trial registration

ClinicalTrials.gov NCT04353297. Registered on April 15, 2020.
Echinococcus granulosus cyst fluid inhibits KDM6B-mediated demethylation of trimethylated histone H3 lysine 27 and interleukin-1β production in macrophages
Authors: Lin Ruolin , Wang Xiaopeng , Ni Caiya , Fu Chunxue , Yang Chun , Dong Dan , Wu Xiangwei , Chen Xueling , Wang Lianghai , Hou Jun
Published: November 2023

Background

Echinococcus granulosus can manipulate its host's immune response to ensure its own survival. However, the effect of histone modifications on the regulation of the NOD-like receptor protein 3 (NLRP3) inflammasome and downstream interleukin-1β (IL-1β) production in response to the parasite is not fully understood.

Methods

We evaluated IL-1β secretion through enzyme-linked immunosorbent assay and assessed reactive oxygen species levels using the dichlorodihydrofluorescein diacetate probe. Western blotting and quantitative real-time polymerase chain reaction were performed to examine the expression of NLRP3 and IL-1β in mouse peritoneal macrophages and Tohoku Hospital Pediatrics-1 cells, a human macrophage cell line. The presence of trimethylated histone H3 lysine 27 (H3K27me3) modification on NLRP3 and IL-1β promoters was studied by chromatin immunoprecipitation.

Results

Treatment with E. granulosus cyst fluid (EgCF) considerably reduced IL-1β secretion in mouse and human macrophages, although reactive oxygen species production increased. EgCF also suppressed the expression of NLRP3 and IL-1β. Mechanistically, EgCF prompted the enrichment of repressive H3K27me3 modification on the promoters of both NLRP3 and IL-1β in macrophages. Notably, the presence of EgCF led to a significant reduction in the expression of the H3K27me3 demethylase KDM6B.

Conclusions

Our study revealed that EgCF inhibits KDM6B expression and H3K27me3 demethylation, resulting in the transcriptional inhibition of NLRP3 and IL-1β. These results provide new insights into the immune evasion mechanisms of E. granulosus.

Graphical Abstract
Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore
Authors: Heston Sarah M. , Lim Charis Shu En , Ong Chengsi , Chua Mei Chien , Kelly Matthew S. , Yeo Kee Thai
Published: November 2023

Background

Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis.

Methods

We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains.

Results

Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R2 = 0.017, p = 0.001) and postnatal age (R2 = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria.

Conclusions

Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants.
High prevalence of TB multimorbidity among adults of a tertiary hospital in Sierra Leone: a cross-sectional study
Authors: Lakoh Sulaiman , Vamboi Patricia Lombeh , Ouédraogo Abdoul Risgou , Adekanmbi Olukemi , Deen Gibrilla F. , Russell James B. W. , Sankoh-Hughes Ahmed , Kamara Joseph B. , Kanu Joseph Edwin , Yendewa George A. , Firima Emmanuel , Amaral André F. S.
Published: November 2023

Objective

Tuberculosis (TB) is a leading cause of death globally, with approximately 1.5 million deaths in 2020. TB often coexists with chronic communicable and non-communicable diseases, but data to determine the extent of comorbid diseases are limited. In this study, we aimed to assess the prevalence of TB multimorbidity and its risk factors in a tertiary hospital in Sierra Leone. This is a cross-sectional study of 240 adults with microbiologically-confirmed TB at Connaught Hospital in Freetown, between March and May 2022. Logistic regression analysis was used to identify factors associated with TB multimorbidity.

Results

The mean age of the patients was 37 years. More than two-thirds were males and about the same number had two or more chronic diseases. The most common were hypertension (47.9%) and diabetes (24.2%). Patients under 35 years of age were less likely to have TB multimorbidity (< 25 years: adjusted OR 0.07, 95%CI 0.01–0.6; 25–34 years: adjusted OR 0.2, 95%CI 0.01–0.9). We report a high prevalence of comorbid diseases among TB patients in the largest treatment center in Sierra Leone, with hypertension and diabetes being the most common. These findings support the current call for addressing comorbid non-communicable diseases in TB patients through integrated care.
Epidemiological description and trajectories of patients with prostate cancer in Denmark: an observational study of 7448 patients
Authors: Blanes-Vidal Victoria , Tashk Ashkan , Cantuaria Manuella Lech , Hansen Rasmus Søgaard , Poulsen Charlotte A. , Poulsen Mads H. , Krogh Marie-Louise , Sheikh Søren P. , Nadimi Esmaeil S.
Published: November 2023

Objective

Identification of patients at high risk of aggressive prostate cancer is a major clinical challenge. With the view of developing artificial intelligence-based methods for identification of these patients, we are constructing a comprehensive clinical database including 7448 prostate cancer (PCa) Danish patients. In this paper we provide an epidemiological description and patients’ trajectories of this retrospective observational population, to contribute to the understanding of the characteristics and pathways of PCa patients in Denmark.

Results

Individuals receiving a PCa diagnosis during 2008–2014 in Region Southern Denmark were identified, and all diagnoses, operations, investigations, and biochemistry analyses, from 4 years prior, to 5 years after PCa diagnosis were obtained. About 85.1% were not diagnosed with metastatic PCa during the study period (unaggressive PCa); 9.2% were simultaneously diagnosed with PCa and metastasis (aggressive-advanced PCa), while 5.7% were not diagnosed with metastatic PCa at first, but they were diagnosed with metastasis at some point during the 5 years follow-up (aggressive-not advanced PCa). Patients with unaggressive PCa had more clinical investigations directly related to PCa detection (prostate ultrasounds and biopsies) during the 4 years prior to PCa diagnosis, compared to patients with aggressive PCa, which may have contributed to the early detection of PCa.
Mosaic environment-driven evolution of the deep-sea mussel Gigantidas platifrons bacterial endosymbiont
Authors: Sun Yan , Wang Minxiao , Cao Lei , Seim Inge , Zhou Li , Chen Jianwei , Wang Hao , Zhong Zhaoshan , Chen Hao , Fu Lulu , Li Mengna , Li Chaolun , Sun Song
Published: November 2023

Background

The within-species diversity of symbiotic bacteria represents an important genetic resource for their environmental adaptation, especially for horizontally transmitted endosymbionts. Although strain-level intraspecies variation has recently been detected in many deep-sea endosymbionts, their ecological role in environmental adaptation, their genome evolution pattern under heterogeneous geochemical environments, and the underlying molecular forces remain unclear.

Results

Here, we conducted a fine-scale metagenomic analysis of the deep-sea mussel Gigantidas platifrons bacterial endosymbiont collected from distinct habitats: hydrothermal vent and methane seep. Endosymbiont genomes were assembled using a pipeline that distinguishes within-species variation and revealed highly heterogeneous compositions in mussels from different habitats. Phylogenetic analysis separated the assemblies into three distinct environment-linked clades. Their functional differentiation follows a mosaic evolutionary pattern. Core genes, essential for central metabolic function and symbiosis, were conserved across all clades. Clade-specific genes associated with heavy metal resistance, pH homeostasis, and nitrate utilization exhibited signals of accelerated evolution. Notably, transposable elements and plasmids contributed to the genetic reshuffling of the symbiont genomes and likely accelerated adaptive evolution through pseudogenization and the introduction of new genes.

Conclusions

The current study uncovers the environment-driven evolution of deep-sea symbionts mediated by mobile genetic elements. Its findings highlight a potentially common and critical role of within-species diversity in animal-microbiome symbioses.
Psychometric properties of the Problematic Online Gaming Questionnaire (POGQ) in a Moroccan sample of university students
Authors: Abbouyi Samira , Bouazza Samira , El Hilaly Jaouad , Ragala Mohammed El Amine , El Rhazi Karima , Zarrouq Btissame
Published: November 2023

Background

The Problematic Online Gaming Questionnaire (POGQ) instrument consists of 18 items with a six-factor structure. This questionnaire is widely utilized to measure the degree of problematic online gaming, but the scale has not, up to date, been validated in Arabic language. This study aimed to assess POGQ scale validity and reliability in Moroccan context.

Methods

The research was conducted from April to June 2023 using an online questionnaire. The selected sample involved Moroccan university students. Data were analyzed in two successive phases. First, exploratory factor analysis (EFA) was used to assess the factor structure in the first sample (n1 = 143). Then, this structure was confirmed in the second sample (n2 = 313) using confirmatory factor analysis (CFA).

Results

The EFA and CFA results demonstrated that the POGQ has a six-factor structure explained 72% of the total variance. The results of this analysis provided an optimal fit to the data confirming a good performance of the measurement model (χ² = 243.6; CFI = 0.981; TLI = 0.976; RMSEA = 0.048; NFI = 0.964; IFI = 0. 981; SRMR = 0.022). The instrument showed sufficient reliability and convergent validity demonstrated by acceptable values of composite reliability (CR = 0.68–0.90), and average variance extracted (AVE = 0.50–0.75), respectively. Finally, the Arabic version of POGQ was found to have a high test–retest reliability.

Conclusions

The Arabic version of POGQ revealed adequate psychometric properties. As a result, the instrument might be used to measure the degree of problematic online gaming. The use of the POGQ is expected to further promote research on online game dependence treatment and prevention.
Macrokinetics of the deterioration of cement-based grouting material for predicting its service life under acid rain attack
Authors: Hu Wenjing , Fang Shiqiang , Xie Lina , Chen Xueqiang , Zhang Bingjian
Published: November 2023

Cement-based grouting material is widely used to reinforce the unsafe rock and control seepage of rock-carved relics although it is considered inappropriate in protection of ancient sites. As this approach is irreversible, a longer service life is desirable for the grouting material and methods to predict the service life are needed. Here we propose a universal formula based on the dissolved amount of calcium ion to predict the deterioration rate of cement-based grout caused by acid deposition in the laboratory. The experimental results showed that the dissolved amount of calcium ion had a linear relationship with lnT and the pH value, with better accuracy when the pH value was greater than 3.0. This work maybe could provide a facile and quantitative method to help us predict the service life of cement-based grouting material under acid rain attack outdoors.
Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
Authors: Saito Tomoyo , Hayakawa Mineji , Kumano Osamu , Honma Yoshinori , Murashita Mone , Kato Jun , Fukui Syouki , Takahashi Masaki , Takahashi Yuki , Tsuchida Takumi , Mizugaki Asumi , Takauji Shuhei , Hayamizu Mariko , Yoshida Tomonao , Katabami Kenichi , Wada Takeshi , Maekawa Kunihiko
Published: November 2023

Background

Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes.

Methods

This study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group (< 80%), the concordant group (80–120%), and the upper group (> 120%).

Results

The overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups.

Conclusions

Discrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients.

Trial registration: Not applicable.
A practical guide to the implementation of AI in orthopaedic research – part 1: opportunities in clinical application and overcoming existing challenges
Authors: Zsidai Bálint , Hilkert Ann‐Sophie , Kaarre Janina , Narup Eric , Senorski Eric Hamrin , Grassi Alberto , Ley Christophe , Longo Umile Giuseppe , Herbst Elmar , Hirschmann Michael T. , Kopf Sebastian , Seil Romain , Tischer Thomas , Samuelsson Kristian , Feldt Robert ,   ESSKA Artificial Intelligence Working Group
Published: November 2023

Artificial intelligence (AI) has the potential to transform medical research by improving disease diagnosis, clinical decision‐making, and outcome prediction. Despite the rapid adoption of AI and machine learning (ML) in other domains and industry, deployment in medical research and clinical practice poses several challenges due to the inherent characteristics and barriers of the healthcare sector. Therefore, researchers aiming to perform AI‐intensive studies require a fundamental understanding of the key concepts, biases, and clinical safety concerns associated with the use of AI. Through the analysis of large, multimodal datasets, AI has the potential to revolutionize orthopaedic research, with new insights regarding the optimal diagnosis and management of patients affected musculoskeletal injury and disease. The article is the first in a series introducing fundamental concepts and best practices to guide healthcare professionals and researcher interested in performing AI‐intensive orthopaedic research studies. The vast potential of AI in orthopaedics is illustrated through examples involving disease‐ or injury‐specific outcome prediction, medical image analysis, clinical decision support systems and digital twin technology. Furthermore, it is essential to address the role of human involvement in training unbiased, generalizable AI models, their explainability in high‐risk clinical settings and the implementation of expert oversight and clinical safety measures for failure. In conclusion, the opportunities and challenges of AI in medicine are presented to ensure the safe and ethical deployment of AI models for orthopaedic research and clinical application.

Level of evidence IV
A review of the genus Muusoctopus (Cephalopoda: Octopoda) from Arctic waters
Authors: Golikov Alexey V. , Gudmundsson Gudmundur , Blicher Martin E. , Jørgensen Lis L. , Korneeva Ekaterina I. , Olafsdottir Steinunn H. , Shagimardanova Elena I. , Shigapova Leyla H. , Zakharov Denis V. , Zimina Olga L. , Sabirov Rushan M.
Published: November 2023

We report two Arctic species of incirrate octopods new to science. One is formally described here as Muusoctopus aegir Golikov, Gudmundsson & Sabirov sp. nov. while the other, Muusoctopus sp. 1, is not formally described due to a limited number of samples (all are immature individuals). These two species differ from each other, and from other Muusoctopus, especially in: 1) absence of stylets (in M. aegirsp. nov.); 2) proportions of mantle and head; 3) funnel organ morphology (W-shaped with medial and marginal limbs of equal length in M. aegirsp. nov., or medial are slightly longer; V V-shaped with medial limbs slightly longer and broader than marginal in Muusoctopus sp. 1); 4) sucker and gill lamellae counts; 5) relative arm length and sucker diameter; and 6) male reproductive system relative size and morphology. Species of Muusoctopus now comprise four of 12 known Arctic cephalopods. Additionally, this study provides: a) new data on the morphology and reproductive biology of M. johnsonianus and M. sibiricus, and a diagnosis of M. sibiricus; b) the equations to estimate mantle length and body mass from beak measurements of M. aegirsp. nov. and M. johnsonianus; c) a cytochrome c oxidase subunit I gene barcode for M. sibiricus; d) new data on the ecology and distribution of all studied species; and e) a data table for the identification of northern North Atlantic and Arctic species of Muusoctopus.
Apparent diffusion coefficient value of brain metastasis from lung carcinoma as potential predictor of epidermal growth factor receptor mutation
Authors: Hanafi Muchtar , Rahayu Rachmi Fauziah , Ardyanto Tonang Dwi
Published: November 2023

Background

Lung carcinoma metastases to the brain occurred in 40% of all lung carcinoma cases and it occupied the top ranking of mortality of cancers. MRI plays an important role in predicting mutations of lung carcinoma.

Objective

This study aimed to compare apparent diffusion coefficient (ADC) values ​​from brain MRI among lung carcinoma patients with and without epidermal growth factor receptor (EGFR) mutations which result in brain metastases.

Methods

Data of fifty-two patients with brain metastasis from lung carcinoma during 2019 to 2022 were taken. The three regions of interest (ROI) were placed to the mutation, non-mutation, and non-lesion groups to predict ADC values.

Results

The ADC values of the EGFR mutation group were not significantly different from either the non-EGFR mutation group or the non-lesion group. The average ADC value of the EGFR mutation group was the lowest, followed by the non-EGFR mutation group and the non-lesion group. The prediction of ADC values ​in the EGFR mutation group ranged 0,773–0,815 × 10−3 mm2/s, followed by the non-EGFR mutation group 0,82 × 10−3 mm2/s, and non-lesion group 0.841 × 10−3 mm2/s.

Conclusions

The ADC values in contrast-brain-MRI can be used as a predictor of EGFR mutations in lung carcinoma with lower prediction value than non-EGFR mutation patients. The ADC values in MRI can contribute in diagnosing and planning further management for lung carcinoma towards precision therapy era.
Clinical Bridging Studies and Modeling Approach for Implementation of a Patient Centric Sampling Technique in Padsevonil Clinical Development
Authors: Kramer Hester , Bicer Ceyhun , Otoul Christian , Rospo Chiara , Macpherson Merran , Watling Mark , Bani Massimo , Sciberras David , Chanteux Hugues
Published: November 2023

Volumetric absorptive microsampling (VAMS) techniques have gained popularity these last years as innovative tool for collection of blood pharmacokinetic (PK) samples in clinical trials as they offer many advantages over dried blood spot and conventional venous blood sampling. The use of Mitra®, a blood collection device based on volumetric absorptive microsampling (VAMS) technology, was implemented during clinical development of padsevonil (PSL), an anti-seizure medication (ASM) candidate. The present study describes the approach used to bridge plasma (obtained from conventional venous blood sampling) and blood exposures (obtained with Mitra®) to support the use of Mitra as sole blood PK sampling method in clinical trials. Paired blood (using Mitra®) and plasma samples (using conventional venous blood sampling) were collected in healthy volunteers as well as in patients with epilepsy. PSL concentration in plasma and blood were analyzed using different approaches which included evaluation of blood-to-plasma ratios (B/P) over time, linear regression, Bland-Altman analysis as well as development of a linear-mixed effect model based on clinical pharmacology studies. Results showed that the observed in vivo B/P and the measured bias between the 2 collection methods were consistent with the measured in vitro B/P. Graphical analysis demonstrated a clear time effect on the B/P which was confirmed in the linear mixed effect model with sampling time identified as significant covariate. Finally, the built-in model was validated using independent datasets and was shown to adequately predict plasma concentration based on blood concentration with a mean bias of less than 9% (predicted versus observed plasma concentration).

Graphical Abstract
Revisiting the metal-to-metal transition in 2H-AgNiO2
Authors: Gondolf Jannik , Eremin Ilya M. , Lechermann Frank
Published: November 2023

The layered delafossite compound AgNiO2 with

stacking symmetry undergoes a structural metal-to-metal transition at

. It has been described in the past as a charge-ordering transition, where local S = 1 spins are formed on part of the Ni sites. By means of first-principles many-body calculations, we show that the transition is in fact a site-selective Mott transition on the Ni sublattice with only minor charge differentiation. Key to this finding is the uncovering of ligand-hole physics, rendering a Ni2+ instead of a formal Ni3+ oxidation state, in conjunction with strong local Coulomb repulsions.
Increased OCT3 Expression in Adipose Tissue With Aging: Implications for Catecholamine and Lipid Turnover and Insulin Resistance in Women
Authors: Ahmed Fozia , Vranic Milica , Hetty Susanne , Mathioudaki Argyri , Patsoukaki Vagia , Fanni Giovanni , Pereira Maria J , Eriksson Jan W
Published: November 2023

Background

Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women.

Methods

SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed.

Results

OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides).

Conclusion

OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.
Dysregulation of the endoplasmic reticulum blocks recruitment of centrosome-associated proteins resulting in mitotic failure
Authors: Rollins Katherine R. , Blankenship J. Todd
Published: November 2023

The endoplasmic reticulum (ER) undergoes a remarkable transition in morphology during cell division to aid in the proper portioning of the ER. However, whether changes in ER behaviors modulate mitotic events is less clear. Like many animal embryos, the early Drosophila embryo undergoes rapid cleavage cycles in a lipid-rich environment. Here, we show that mitotic spindle formation, centrosomal maturation, and ER condensation occur with similar time frames in the early syncytium. In a screen for Rab family GTPases that display dynamic function at these stages, we identified Rab1. Rab1 disruption led to an enhanced buildup of ER at the spindle poles and produced an intriguing ‘mini-spindle’ phenotype. ER accumulation around the mitotic space negatively correlates with spindle length/intensity. Importantly, centrosomal maturation is defective in these embryos, as mitotic recruitment of key centrosomal proteins is weakened after Rab1 disruption. Finally, division failures and ER overaccumulation is rescued by Dynein inhibition, demonstrating that Dynein is essential for ER spindle recruitment. These results reveal that ER levels must be carefully tuned during mitotic processes to ensure proper assembly of the division machinery.
Heparin-binding epidermal growth factor and fibroblast growth factor 2 rescue Müller glia-derived progenitor cell formation in microglia- and macrophage-ablated chick retinas
Authors: El-Hodiri Heithem M. , Bentley James R. , Reske Alana G. , Taylor Olivia B. , Palazzo Isabella , Campbell Warren A. , Halloy Nicklaus R. , Fischer Andy J.
Published: November 2023

Recent studies have demonstrated the impact of pro-inflammatory signaling and reactive microglia/macrophages on the formation of Müller glial-derived progenitor cells (MGPCs) in the retina. In chick retina, ablation of microglia/macrophages prevents the formation of MGPCs. Analyses of single-cell RNA-sequencing chick retinal libraries revealed that quiescent and activated microglia/macrophages have a significant impact upon the transcriptomic profile of Müller glia (MG). In damaged monocyte-depleted retinas, MG fail to upregulate genes related to different cell signaling pathways, including those related to Wnt, heparin-binding epidermal growth factor (HBEGF), fibroblast growth factor (FGF) and retinoic acid receptors. Inhibition of GSK3β, to simulate Wnt signaling, failed to rescue the deficit in MGPC formation, whereas application of HBEGF or FGF2 completely rescued the formation of MGPCs in monocyte-depleted retinas. Inhibition of Smad3 or activation of retinoic acid receptors partially rescued the formation of MGPCs in monocyte-depleted retinas. We conclude that signals produced by reactive microglia/macrophages in damaged retinas stimulate MG to upregulate cell signaling through HBEGF, FGF and retinoic acid, and downregulate signaling through TGFβ/Smad3 to promote the reprogramming of MG into proliferating MGPCs.
Among the trees: shade promotes the growth and higher survival of juvenile toads
Authors: Kaczmarski Mikołaj , Dylewski Łukasz , Maliński Tomasz , Tryjanowski Piotr
Published: November 2023

getation, including trees, significantly shapes microhabitats for amphibians due to the leaf litter input, providing stable shelter, creating a microclimate or indirectly through trophic interactions. It is known that some species can survive in a highly modified urban environment. Species associated with open space can find stable habitats in urban and human-transformed areas, but is the impact of shading (presence of canopy cover) significant in their case? We focus on the effect of solar exposure on the growth rate of juvenile green toads Bufotes viridis in fruit and canopy manipulation treatments. The main aim of the study was to examine the selected habitat traits promoting post-metamorphic growth of the green toad in semi-open enclosures. We investigated differences between exposure/land cover variants, i.e., sunny site (open area with direct solar exposure) and shadow site (shady site with a tree canopy cover). Using imitation fruits and real cherry plum Prunus cerasifera fruits (non-native tree species), we checked wheth­er amphibian growth is related to the additional structure that fruit lying on the ground created (a more heterogeneous surface structure) or to a trophic character (additional food source due to attracting inver­tebrates). We conducted a 40-day rearing experiment in three variants with two replications in semi-open enclosures with 20 juvenile toads each. We found differences in snout-vent length and body mass index in­vestigated due to site exposure during post-metamorphic growth. The survival rate of juvenile toads in the shaded site was higher than in sunny sites. We demonstrated a positive effect of the tree’s shade, regardless of the fleshy fruit’s presence on the ground. Toads benefit from developing at sites with reduced solar ex­posure (i.e., with a tree canopy), resulting in intensive growth and higher survival rate. Thus, there is an opportunity for planners and urban authorities to manage habitats for amphibian conservation purposes by creating a shaded zone, even for open habitat species, especially in transformed areas such as cities. Our results indicate that the beneficial effect of the lying fruit on the growth of juveniles is limited to specific conditions, and understanding this requires further research.
Μελέτη χαρακτηριστικών και ανάλυση παραμέτρων, που σχετίζονται με την επιτυχία της έκβασης και το φαρμακοοικονομικό κόστος της εμπειρικής αντιβιοτικής αγωγής
Authors: Κουτσούρη Χριστίνα-Παναγιώτα
Published: November 2023

Τι είναι γνωστό και αντικείμενο: Η έγκαιρη και κατάλληλη εμπειρική αντιβιοτική θεραπεία (EAΘ) παραμένει ο ακρογωνιαίος λίθος της επιτυχούς έκβασης, ενώ η πλειονότητα των καλλιεργειών αίματος δεν προσδιορίζει το παθογόνο. Στόχος μας ήταν να μελετήσουμε τα χαρακτηριστικά της EAΘ και τον αντίκτυπό της στις κλινικές εκβάσεις και στις σχετικές ιατρικές δαπάνες, ενώ παράλληλα διερευνήσαμε τους προγνωστικούς παράγοντες της επιτυχίας της σε ένα περιβάλλον πραγματικών συνθηκών (real world). Μέθοδοι: Αξιοποιήσαμε αναδρομικά το μητρώο της Παθολογικής Κλινικής του τριτοβάθμιου πανεπιστημιακού νοσοκομείου, συμπεριλαμβανομένων των ασθενών που εισήχθησαν με διάγνωση λοίμωξης μεταξύ της 1ης Μαΐου 2016 και της 1ης Μαΐου 2018. Το κόστος νοσηλείας και η μονάδα αντιβιοτικού σχήματος ανακτήθηκαν από μια βάση δεδομένων που αφορά τα ελληνικά νοσοκομεία και περιέχει δεδομένα κόστους νοσηλείας για κάθε κωδικό ICD-10 και το εθνικό συνταγολόγιο, αντίστοιχα. Αποτελέσματα: Συνολικά 489 ασθενείς συμπεριλήφθηκαν στην παρούσα μελέτη. Η μέση ηλικία ήταν 61,3 έτη, το 53% ήταν άνδρες, ενώ επικράτησαν οι ενδοκοιλιακές λοιμώξεις (55%). Η πιο συχνά χορηγούμενη ΕΑΘ περιελάμβανε κινολόνες (48%), ακολουθούμενη από πιπερακιλλίνη/ταζομπακτάμη (18%), ή άλλα σχήματα μόνα τους ή σε συνδυασμό. Η ΕΑΘ ήταν επιτυχής στο 67% και αποτυχημένη στο 33% των περιπτώσεων. 14 ασθενείς πέθαναν από τη λοίμωξη πριν από την αλλαγή της ΕΑΘ, ενώ μεταξύ των 55 ασθενών που χρειάστηκε να τροποποιηθεί η ΕΑΘ, η θνησιμότητα ήταν 22%. Η παρουσία λοίμωξης του ουροποιητικού συστήματος και η χρήση κινολονών, αποτελούσαν θετικό προγνωστικό παράγοντα για την επιτυχία της ΕΑΘ [OR:0,15 (0,07-0,35), p < 0,0001, OR:0,53 (0,32-0,90), p = 0,019, αντίστοιχα], σε αντίθεση με την παρουσία σήψης [OR:3,11 (1,79-5,40), p < 0,0001]. Οι ασθενείς με μη επιτυχή έκβαση είχαν μεγαλύτερη διάρκεια νοσηλείας [7(5-11) έναντι 4 (3-6) ημερών], υψηλότερο κόστος αντιβιοτικών [201,9 (97,8- 471,8) έναντι 104,6 (60,2-187,7) ευρώ] και νοσηλείας [1409,3 (945,4-2311,6) έναντι 759,4 (516,5-1036,5) ευρώ](p < 0,0001). Συζήτηση: Παρατηρήσαμεσημαντικάαυξημένοκόστοςπουσχετίζεταιμε αντιβιοτικά, κόστος που σχετίζεται με την υγειονομική περίθαλψη και διάρκεια νοσηλείας σε ασθενείς με αποτυχία της ΕΑΘ. Επιπλέον, στη δική μας κοόρτη, η απουσία σήψης, η παρουσία λοίμωξης του ουροποιητικού και η χρήση κινολονών αποτελούσαν καλύτεροι προγνωστικοί παράγοντες της επιτυχούς ΕΑΘ.
K-nearest-neighbor algorithm to predict the survival time and classification of various stages of oral cancer: a machine learning approach
Authors: Siddalingappa Rashmi , Kanagaraj Sekar
Published: November 2023

Background:For years now, cancer treatments have entailed tried-and-true methods. Yet, oncologists and clinicians recommend a series of surgeries, chemotherapy, and radiation therapy. Yet, even amidst these treatments, the number of deaths due to cancer increases at an alarming rate. The prognosis of cancer patients is influenced by mutations, age, and various cancer stages. However, the association between these variables is unclear. Methods: The present work adopts a machine learning technique—k-nearest neighbor; for both regression and classification tasks, regression for predicting the survival time of oral cancer patients, and classification for classifying the patients into one of the predefined oral cancer stages. Two cross-validation approaches—hold-out and k-fold methods—have been used to examine the prediction results. Results: The experimental results show that the k-fold method performs better than the hold-out method, providing the least mean absolute error score of 0.015. Additionally, the model classifies patients into a valid group. Of the 429 records, 97 (out of 106), 99 (out of 119), 95 (out of 113), and 77 (out of 91) were classified to its correct label as stages – 1, 2, 3, and 4. The accuracy, recall, precision, and F-measure for each classification group obtained are 0.84, 0.85, 0.85, and 0.84. Conclusions: The study showed that aged patients with a higher number of mutations than young patients have a higher risk of short survival. Senior patients with a more significant number of mutations have an increased risk of getting into the last cancer stage
Promising images of love: a qualitative-ethnographic study about the mediatised memories of weddings
Authors: Mäder Marie-Therese
Published: November 2023

Background Digital media play a central role in contemporary weddings, be it during the preparation, the ritual itself or afterwards. Specific moments of the wedding day are made memorable through photographs and videos. But how do couples manage their wedding photos and videos and what role do these media play in awakening memories of religious and secular dimensions of the event? These questions are developed in the theoretical frame of mediatisation and memory processes. This paper argues that the mediatisation of weddings influences how a wedding is memorized and results in a partial standardization of memories of the event, in which neither cultural nor religious differences nor sexual orientation play a crucial role. Methods This interdisciplinary qualitative-ethnographic research is based on twenty-seven semi-structured video recorded interviews conducted in Italy, Germany, and Switzerland with homo- and heterosexual married couples from different cultural-religious backgrounds. The couples shared their wedding album or video and developed a wedding narrative by looking at the photographs and videos. Results Taking photos during the wedding becomes an important part of the ritual, independent of any cultural or religious background, gender, and sexual orientation. The ceremony itself is emphasized in the photos and the video. This homogenisation of the rite of passage equally occurs in the photographic representations of weddings and in turn influences how the wedding is remembered. The findings further reveal that heterosexual marriage representations reinforce gender stereotypes. The brides/wives of heterosexual couples are significantly more invested in the production and reception of wedding media, whereas homosexual couples participated in the conversation equally. Conclusions The homogenization of representation and memory becomes part of the rite of passage’s collective memory that connects the individual couples. The mediatisation of weddings strengthens the feeling of belonging to a community that transcends cultural-religious identities.
Teatr tańca Brama Chmur w poszukiwaniu chińskiej i tajwańskiej tożsamości kulturowej
Authors: Łabędzka Izabela
Published: November 2023

CLOUD GATE DANCE THEATRE IN SEARCH OF CHINESE AND TAIWANESE CULTURAL IDENTITYThis paper shows the dynamics of topical, aesthetical and political changes in the world-known contemporary dance group – Cloud Gate Dance Theatre of Taiwan (Yunmen Wuji), created by Lin Hwai-min in 1973. Those metamorphoses are observed in a broad socio political and cultural context, in the rapidly changing reality of Taiwan, Mainland China and the whole world at the turn of the 20th and 21st century. Short analyses of the most iconic dance compositions by Lin Hwai-min make it possible to trace the direction of the changes, starting from search for Chinese cultural identity, through the quest for definition of Taiwanese cultural and national identity, gaining the feeling of being rooted in traditional Chinese aesthetics and finally confirming the importance of local Taiwanese tradition as an equally meaningful source of creative inspiration.