bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracortical mechanisms of single pulse electrical stimulation (SPES) evoked excitations and inhibitions in humans
Authors: Hajnal Boglárka , Szabó Johanna Petra , Tóth Emília , Keller Corey J. , Wittner Lucia , Mehta Ashesh D. , Erőss Loránd , Ulbert István , Fabó Dániel , Entz László
Published: June 2024

Cortico-cortical evoked potentials (CCEPs) elicited by single-pulse electric stimulation (SPES) are widely used to assess effective connectivity between cortical areas and are also implemented in the presurgical evaluation of epileptic patients. Nevertheless, the cortical generators underlying the various components of CCEPs in humans have not yet been elucidated. Our aim was to describe the laminar pattern arising under SPES evoked CCEP components (P1, N1, P2, N2, P3) and to evaluate the similarities between N2 and the downstate of sleep slow waves. We used intra-cortical laminar microelectrodes (LMEs) to record CCEPs evoked by 10 mA bipolar 0.5 Hz electric pulses in seven patients with medically intractable epilepsy implanted with subdural grids. Based on the laminar profile of CCEPs, the latency of components is not layer-dependent, however their rate of appearance varies across cortical depth and stimulation distance, while the seizure onset zone does not seem to affect the emergence of components. Early neural excitation primarily engages middle and deep layers, propagating to the superficial layers, followed by mainly superficial inhibition, concluding in a sleep slow wave-like inhibition and excitation sequence.
Rapid detection of FadA in Fusobacterium nucleatum using the quantitative LAMP colorimetric phenol red method in stool samples from colorectal cancer patients
Authors: Zuraik Abdulrahman A. , Daboul Yaman , Awama M. Ayman , Yazigi Haitham , Kayasseh Moh’d Azzam , Georges Michael
Published: June 2024

The study aimed to develop a quantitative colorimetric loop-mediated isothermal amplification technique using the phenol red indicator (QLAMP-PhR) for detecting Fusobacterium nucleatum (Fn) levels in colorectal cancer (CRC) patients and healthy individuals. QLAMP-PhR assays were conducted on 251 stool samples specific for the Fn FadA gene. Six primers were synthesized and utilized with master mix reagents, and a phenol red indicator was employed to enhance the QLAMP-PhR technique. A standard quantitative analysis curve was generated using a logarithmic function (absorbance vs. concentration) by serially diluting the copy number of genomic DNA templates (Fn ATCC25586). The CRC group exhibited a significantly higher abundance of Fn compared to the healthy control group (P < 0.001). These findings suggest that the QLAMP-PhR technique effectively identifies Fn specifically by its gene for the key virulence factor FadA. Additionally, ideas for developing a real-time QLAMP-PhR test were presented. Compared to the traditional polymerase chain reaction (PCR) technique, QLAMP-PhR offers several advantages including rapidity, simplicity, specificity, sensitivity, and cost-effectiveness method that can quantitatively screen for Fn presence in normal populations. The QLAMP-PhR method represents a sensitive and specific amplification assay for the rapid detection of the Fn pathogen. To the best of our knowledge, this study is the first to report the application of QLAMP-PhR for detecting FadA in Fn.
Design and fabrication of porous three‐dimensional Ag-doped reduced graphene oxide (3D Ag@rGO) composite for interfacial solar desalination
Authors: Bezza Fisseha A. , Iwarere Samuel A. , Brink Hendrik G. , Chirwa Evans M. N.
Published: June 2024

Solar-driven interfacial desalination technology has shown great promise in tackling the urgent global water scarcity crisis due to its ability to localize heat and its high solar-to-thermal energy conversion efficiency. For the realization of sustainable saline water desalination, the exploration of novel photothermal materials with higher water vapor generation and photothermal conversion efficiency is indispensable. In the current study, a novel 3D interconnected monolithic Ag-doped rGO network was synthesized for efficient photothermal application. The Ultraviolet–Visible-Near Infrared (UV–Vis-NIR) and FTIR analyses demonstrated that the controlled hydrothermal reduction of GO enabled the restoration of the conjugated sp2 bonded carbon network and the subsequent electrical and thermal conductivity through a significant reduction of oxygen-containing functional groups while maintaining the hydrophilicity of the composite photothermal material. In the solar simulated interfacial desalination study conducted using 3.5 wt.% saline water, the average surface temperatures of the 3D material increased from 27.1 to 54.7 °C in an hour, achieving an average net dark-excluded evaporation rate of 1.40 kg m−2 h−1 and a photothermal conversion efficiency of ~ 97.54% under 1 sun solar irradiance. In the outdoor real-world application test carried out, the surface temperature of the 3D solar evaporator reached up to 60 °C and achieved a net water evaporation rate of 1.50 kg m−2 h−1 under actual solar irradiation. The 3D interwoven porous hierarchical evaporator displayed no salt precipitation over the 54-h period monitored, demonstrating the promising salt rejection and real-world application potential for efficient desalination of saline water.
Probing intracellular potassium dynamics in neurons with the genetically encoded sensor lc-LysM GEPII 1.0 in vitro and in vivo
Authors: Groschup Bernhard , Calandra Gian Marco , Raitmayr Constanze , Shrouder Joshua , Llovera Gemma , Zaki Asal Ghaffari , Burgstaller Sandra , Bischof Helmut , Eroglu Emrah , Liesz Arthur , Malli Roland , Filser Severin , Plesnila Nikolaus
Published: June 2024

Neuronal activity is accompanied by a net outflow of potassium ions (K+) from the intra- to the extracellular space. While extracellular [K+] changes during neuronal activity are well characterized, intracellular dynamics have been less well investigated due to lack of respective probes. In the current study we characterized the FRET-based K+ biosensor lc-LysM GEPII 1.0 for its capacity to measure intracellular [K+] changes in primary cultured neurons and in mouse cortical neurons in vivo. We found that lc-LysM GEPII 1.0 can resolve neuronal [K+] decreases in vitro during seizure-like and intense optogenetically evoked activity. [K+] changes during single action potentials could not be recorded. We confirmed these findings in vivo by expressing lc-LysM GEPII 1.0 in mouse cortical neurons and performing 2-photon fluorescence lifetime imaging. We observed an increase in the fluorescence lifetime of lc-LysM GEPII 1.0 during periinfarct depolarizations, which indicates a decrease in intracellular neuronal [K+]. Our findings suggest that lc-LysM GEPII 1.0 can be used to measure large changes in [K+] in neurons in vitro and in vivo but requires optimization to resolve smaller changes as observed during single action potentials.
HIF1A protein expression is correlated with clinical features in gastric cancer: an updated systematic review and meta-analysis
Authors: Nam Seungyoon , Lee Yeeun
Published: June 2024

To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science for studies on GC and HIF1A, covering studies published until January 31st, 2022. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for clinical characteristics based on high and low HIF1A protein levels. We used random-effects and fixed-effects meta-analysis methods to determine mean effect sizes of ORs and evaluated publication heterogeneity with τ2, I2, and Q values. Additionally, we generated funnel plots to inspect publication bias. Our meta-analysis included 20 publications with 3416 GC patients to estimate the association between high or low HIF1A expression and clinical characteristics. Positive HIF1A expression was significantly associated with T stage progression (OR: 2.46; 95% CI 1.81–3.36; P < 0.01), TNM stage progression (OR: 2.50; 95% CI 1.61–3.87; P < 0.01), lymph node metastasis (OR: 2.06; 95% CI 1.44–2.94; P < 0.01), undifferentiated status (OR: 1.83; 95% CI 1.45–2.32; P < 0.01), M stage progression (OR: 2.34; 95% CI 1.46–3.77; P < 0.01), Borrmann stage progression (OR: 1.48; 95% CI 1.02–2.15; P = 0.04), larger tumor size (OR: 1.27; 95% CI 1.06–1.52; P < 0.01), vascular invasion (OR: 1.94; 95% CI 1.38–2.72; P < 0.01), and higher vascular endothelial growth factor (VEGF) protein expression (OR: 2.61; 95% CI 1.79–3.80; P < 0.01) in our meta-analysis. GC Patients highly expressing HIF1A protein might be prone to tumor progression, poorly differentiated GC cell types, and a high VEGF expression.
Design of chemobrionic and biochemobrionic scaffolds for bone tissue engineering
Authors: Aslanbay Guler Bahar , Morçimen Zehra Gül , Taşdemir Şeyma , Demirel Zeliha , Turunç Ezgi , Şendemir Aylin , Imamoglu Esra
Published: June 2024

Chemobrionic systems have attracted great attention in material science for development of novel biomimetic materials. This study aims to design a new bioactive material by integrating biosilica into chemobrionic structure, which will be called biochemobrionic, and to comparatively investigate the use of both chemobrionic and biochemobrionic materials as bone scaffolds. Biosilica, isolated from Amphora sp. diatom, was integrated into chemobrionic structure, and a comprehensive set of analysis was conducted to evaluate their morphological, chemical, mechanical, thermal, and biodegradation properties. Then, the effects of both scaffolds on cell biocompatibility and osteogenic differentiation capacity were assessed. Cells attached to the scaffolds, spread out, and covered the entire surface, indicating the absence of cytotoxicity. Biochemobrionic scaffold exhibited a higher level of mineralization and bone formation than the chemobrionic structure due to the osteogenic activity of biosilica. These results present a comprehensive and pioneering understanding of the potential of (bio)chemobrionics for bone regeneration.
A novel multi-model estimation of phosphorus in coal and its ash using FTIR spectroscopy
Authors: Vinod Arya , Prasad Anup Krishna , Mishra Sameeksha , Purkait Bitan , Mukherjee Shailayee , Shukla Anubhav , Desinayak Nirasindhu , Sarkar Bhabesh Chandra , Varma Atul Kumar
Published: June 2024

The level of phosphorus must be carefully monitored for proper and effective utilization of coal and coal ash. The phosphorus content needs to be assessed to optimize combustion efficiency and maintenance costs of power plants, ensure quality, and minimize the environmental impact of coal and coal ash. The detection of low levels of phosphorus in coal and coal ash is a significant challenge due to its complex chemical composition and low concentration levels. Effective monitoring requires accurate and sensitive equipment for the detection of phosphorus in coal and coal ash. X-ray fluorescence (XRF) is a commonly used analytical technique for the determination of phosphorus content in coal and coal ash samples but proves challenging due to their comparatively weak fluorescence intensity. Fourier Transform Infrared spectroscopy (FTIR) emerges as a promising alternative that is simple, rapid, and cost-effective. However, research in this area has been limited. Until now, only a limited number of research studies have outlined the estimation of major elements in coal, predominantly relying on FTIR spectroscopy. In this article, we explore the potential of FTIR spectroscopy combined with machine learning models (piecewise linear regression—PLR, partial least square regression—PLSR, random forest—RF, and support vector regression—SVR) for quantifying the phosphorus content in coal and coal ash. For model development, the methodology employs the mid-infrared absorption peak intensity levels of phosphorus-specific functional groups and anionic groups of phosphate minerals at various working concentration ranges of coal and coal ash. This paper proposes a multi-model estimation (using PLR, PLSR, and RF) approach based on FTIR spectral data to detect and rapidly estimate low levels of phosphorus in coal and its ash (R$$^2$$

2

of 0.836, RMSE of 0.735 ppm, RMSE (%) of 34.801, MBE of − 0.077 ppm, MBE (%) of 5.499, and MAE of 0.528 ppm in coal samples and R$$^2$$

2

of 0.803, RMSE of 0.676 ppm, RMSE (%) of 38.050, MBE of − 0.118 ppm, MBE (%) of 4.501, and MAE of 0.474 ppm in coal ash samples). Our findings suggest that FTIR combined with the multi-model approach combining PLR, PLSR, and RF regression models is a reliable tool for rapid and near-real-time measurement of phosphorus in coal and coal ash and can be suitably modified to model phosphorus content in other natural samples such as soil, shale, etc.
Positive and negative facial valence perception are modulated differently by eccentricity in the parafovea: Replication from KDEF to NimStim
Authors: Akselevich Vasilisa , Gilaie-Dotan Sharon
Published: June 2024

While perceiving the emotional state of others may be crucial for our behavior even when this information is present outside of central vision, emotion perception studies typically focus on central visual field. We have recently investigated emotional valence (pleasantness) perception across the parafovea (≤ 4°) and found that for briefly presented (200 ms) emotional face images (from the established KDEF image-set), positive (happy) valence was the least affected by eccentricity (distance from the central visual field) and negative (fearful) valence the most. Furthermore, we found that performance at 2° predicted performance at 4°. Here we tested (n = 37) whether these effects replicate with face stimuli of different identities from a different well-established image-set (NimStim). All our prior findings replicated and eccentricity-based modulation magnitude was smaller with NimStim (~ 16.6% accuracy reduction at 4°) than with KDEF stimuli (~ 27.3% reduction). Our current investigations support our earlier findings that for briefly presented parafoveal stimuli, positive and negative valence perception are differently affected by eccentricity and may be dissociated. Furthermore, our results highlight the importance of investigating emotions beyond central vision and demonstrate commonalities and differences across different image sets in the parafovea, emphasizing the contribution of replication studies to substantiate our knowledge about perceptual mechanisms.
Design and analysis of a mobile robot with novel caster mechanism for high step-overcoming capability
Authors: Lee Woojae , Kim Jeongeun , Seo Taewon
Published: June 2024

The mobile robot market is experiencing rapid growth, playing a pivotal role in various human-centric environments like restaurants, offices, hotels, hospitals, apartments, and factories. However, current differential-driven mobile robots, employing conventional casters and wheel motors, encounter limitations in surmounting uneven surfaces and high steps due to constraints caused by wheel and caster dimensions. While some robots address these challenges by incorporating optimized wheel shapes and additional motors, this invariably leads to an increase in both size and cost. This research introduces an innovative solution; a novel caster-wheel mechanism designed to enhance the high-step overcoming capability of mobile robots without necessitating alterations to their overall size and structure. By incorporating a sub-wheel linked to a passive joint, the driving force is effeciently converted into a vertical force, thereby empowering the mobile robot to navigate obstacles 85% larger than its caster-wheel radius. Crucially, this innovative caster can be seamlessly manufactured and integrated, offering the potential for widespread adoption as a replacement for conventional casters. Validation through comprehensive simulations and experiments conducted on a prototype robot has been presented in this article, demonstrating its effectiveness even at a robot velocity of 0.1 m/s. This pioneering solution holds significant promise for diverse applications across various mobile robot configurations, presenting a compelling avenue for further exploration and implementation in the field.
Elevated atmospheric CO2 has small, species-specific effects on pollen chemistry and plant growth across flowering plant species
Authors: Bernauer Olivia M. , Jain Anupreksha , de Bivort Benjamin , Holbrook N. Michele , Myers Samuel S. , Ziska Lewis H. , Crall James D.
Published: June 2024

Elevated atmospheric carbon dioxide (eCO2) can affect plant growth and physiology, which can, in turn, impact herbivorous insects, including by altering pollen or plant tissue nutrition. Previous research suggests that eCO2 can reduce pollen nutrition in some species, but it is unknown whether this effect is consistent across flowering plant species. We experimentally quantified the effects of eCO2 across multiple flowering plant species on plant growth in 9 species and pollen chemistry (%N an estimate for protein content and nutrition in 12 species; secondary chemistry in 5 species) in greenhouses. For pollen nutrition, only buckwheat significantly responded to eCO2, with %N increasing in eCO2; CO2 treatment did not affect pollen amino acid composition but altered secondary metabolites in buckwheat and sunflower. Plant growth under eCO2 exhibited two trends across species: plant height was taller in 44% of species and flower number was affected for 63% of species (3 species with fewer and 2 species with more flowers). The remaining growth metrics (leaf number, above-ground biomass, flower size, and flowering initiation) showed divergent, species-specific responses, if any. Our results indicate that future eCO2 is unlikely to uniformly change pollen chemistry or plant growth across flowering species but may have the potential to alter ecological interactions, or have particularly important effects on specialized pollinators.
Predicting brain age using Tri-UNet and various MRI scale features
Authors: Pang Yu , Cai Yihuai , Xia Zonghui , Gao Xujie
Published: June 2024

In the process of human aging, significant age-related changes occur in brain tissue. To assist individuals in assessing the degree of brain aging, screening for disease risks, and further diagnosing age-related diseases, it is crucial to develop an accurate method for predicting brain age. This paper proposes a multi-scale feature fusion method called Tri-UNet based on the U-Net network structure, as well as a brain region information fusion method based on multi-channel input networks. These methods address the issue of insufficient image feature learning in brain neuroimaging data. They can effectively utilize features at different scales of MRI and fully leverage feature information from different regions of the brain. In the end, experiments were conducted on the Cam-CAN dataset, resulting in a minimum Mean Absolute Error (MAE) of 7.46. The results demonstrate that this method provides a new approach to feature learning at different scales in brain age prediction tasks, contributing to the advancement of the field and holding significance for practical applications in the context of elderly education.
Associations between oxidative balance score and chronic kidney disease events in US adults: a population-based study
Authors: Yin Yuewei , Zhao Chenming , Niu Yalin , Qi Jinchun , Zhang Yanping , Lu Baosai
Published: June 2024

Oxidative Balance Scores (OBS) are utilized to assess an individual's antioxidant status, encompassing both dietary and lifestyle factors that contribute to oxidative balance. This study investigates the relationship between OBS and chronic kidney disease (CKD) prevalence among U.S. adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. The study involved a cross-sectional analysis of 13,373 individuals from NHANES, focusing on adults aged 20 years or older. OBS was calculated using 20 components, including dietary and lifestyle factors. CKD was identified based on albumin-to-creatinine ratio and estimated glomerular filtration rate, with patients stratified into mild, moderate, and high-risk groups. Statistical analysis included logistic regression models and restricted cubic splines to explore the OBS-CKD relationship. Our findings indicate a statistically significant negative correlation between OBS and CKD prevalence, particularly in mild and moderate-risk groups. Higher OBS quartiles were associated with a decreased likelihood of CKD (OR 0.70; 95% CI 0.53–0.92; P = 0.013). Restricted cubic splines indicated a non-linear, inverse association between OBS and CKD odds for the overall population (P for nonlinearity = 0.017). For mild and moderate CKD risk groups, the relationships were less pronounced (P for nonlinearity = 0.053 and 0.184, respectively), suggesting variability in the OBS-CKD link across different risk levels. The study highlights the potential of elevated OBS as a primary prevention measure for CKD, particularly in individuals with mild to moderate risk. These findings underscore the importance of antioxidant status in CKD risk management and encourage further research into the role of dietary and lifestyle factors in CKD prevention.
Screening of co-expressed genes in hypopharyngeal carcinoma with esophageal carcinoma based on RNA sequencing and Clinical Research
Authors: Zhang Jianing , Zou Liangyu , Tan Fuxian , Wang Hongmin , Wen Zhenlei , Wang Hongmei , Li Lianhe
Published: June 2024

To explore the hub comorbidity genes and potential pathogenic mechanisms of hypopharyngeal carcinoma with esophageal carcinoma, and evaluate their diagnostic value for hypopharyngeal carcinoma with co-morbid esophageal carcinoma. We performed gene sequencing on tumor tissues from 6 patients with hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma (hereafter referred to as “group A”) and 6 patients with pure hypopharyngeal squamous cell carcinoma (hereafter referred to as “group B”). We analyzed the mechanism of hub genes in the development and progression of hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma through bioinformatics, and constructed an ROC curve and Nomogram prediction model to analyze the value of hub genes in clinical diagnosis and treatment. 44,876 genes were sequenced in 6 patients with group A and 6 patients with group B. Among them, 76 genes showed significant statistical differences between the group A and the group B.47 genes were expressed lower in the group A than in the group B, and 29 genes were expressed higher. The top five hub genes were GABRG2, CACNA1A, CNTNAP2, NOS1, and SCN4B. GABRG2, CNTNAP2, and SCN4B in the hub genes have high diagnostic value in determining whether hypopharyngeal carcinoma patients have combined esophageal carcinoma (AUC: 0.944, 0.944, 0.972). These genes could possibly be used as potential molecular markers for assessing the risk of co-morbidity of hypopharyngeal carcinoma combined with esophageal carcinoma.
Urban virtual environment landscape design and system based on PSO-BP neural network
Authors: Liu Yating , Fan Lingyan , Wang Lan
Published: June 2024

In the last few years, with the fast growing of neural network field such as those for virtual reception and enhanced nature, the practice and theory of conventional landscape are impacted and challenged by virtual landscape based on these sorts of neural network technologies. On the one hand, the virtual landscape changes the carrier of landscape design from material real world to the networked virtual world, which breaks the traditional way of generating landscape and the way of expression of results. On the other hand, the virtualized and networked morphological characteristics of the virtual landscape itself and its capacity that can offer users a sense of immertion, interplay and enjoyment of the experience provide a way of extending and deepening the realm of scenery. It is also a new type of landscape that conforms to the trend of the times created in the background of the fast evolution of scientific and technical development. Virtual landscape brings new construction thinking and practical means for the application of digital city, the construction of urban context, and the development and utilization of relics. It provides an important research source for thinking about the relationship between current humanities and science, material and virtual, history and contemporary. After the research and experiment on the urban environment landscape design of PSO-BP neural network, the experimental data showed that before using the neural network method to improve Yanta East Garden, 57% of the crowd were satisfied with the overall impression of Yanta East Garden, and 17% were dissatisfied. After the improvement, 67% were satisfied with the landscape of Yanta East Garden, only 5% were dissatisfied, and the landscape satisfaction increased by 10%. The survey group believed that the landscape color of Yanta East Garden was full of historical flavor, especially the small sculptures convey the unique Qin Opera culture. The above data show that the method based on neural network is very suitable for the improvement and development of urban landscape design.
Mechanical resistance of the environment affects root hair growth and nucleus dynamics
Authors: Pereira David , Alline Thomas , Cascaro Léa , Lin Emilie , Asnacios Atef
Published: June 2024

Root hair (RH) cells are important for the growth and survival of seedlings. They favor plant–microbe interactions and nutrients uptake. When invading the soil, RH cells have to penetrate a dense medium exhibiting a variety of physical properties, such as mechanical resistance, that impact the growth and survival of plants. Here we investigate the effect of the mechanical resistance of the culture medium on RH-physical and phenotypical parameters such as length, time, and speed of growth. We also analyze the impact of the environment on nuclear dynamics. We show that the RH growth rate and the nucleus speed decrease similarly as mechanical resistance increases while the time of growth of RH cells is invariable. Moreover, during RH growth, the nucleus-to-tip distance was found to decrease when the stiffness of the environment was increased. Along this line, using Latrunculin B treatment in liquid growth media, we could internally slow down RH growth to reach speeds similar to those observed in stiff solid media while the nucleus-to-tip distance was only slightly affected, supporting thus the idea of a specific effect of mechanical resistance of the environment on nucleus dynamics.
Nanobiopsy investigation of the subcellular mtDNA heteroplasmy in human tissues
Authors: Bury Alexander , Pyle Angela , Vincent Amy E. , Actis Paolo , Hudson Gavin
Published: June 2024

Mitochondrial function is critical to continued cellular vitality and is an important contributor to a growing number of human diseases. Mitochondrial dysfunction is typically heterogeneous, mediated through the clonal expansion of mitochondrial DNA (mtDNA) variants in a subset of cells in a given tissue. To date, our understanding of the dynamics of clonal expansion of mtDNA variants has been technically limited to the single cell-level. Here, we report the use of nanobiopsy for subcellular sampling from human tissues, combined with next-generation sequencing to assess subcellular mtDNA mutation load in human tissue from mitochondrial disease patients. The ability to map mitochondrial mutation loads within individual cells of diseased tissue samples will further our understanding of mitochondrial genetic diseases.
All three MutL complexes are required for repeat expansion in a human stem cell model of CAG-repeat expansion mediated glutaminase deficiency
Authors: Hayward Bruce , Kumari Daman , Santra Saikat , van Karnebeek Clara D. M. , van Kuilenburg André B. P. , Usdin Karen
Published: June 2024

The Repeat Expansion Diseases (REDs) arise from the expansion of a disease-specific short tandem repeat (STR). Different REDs differ with respect to the repeat involved, the cells that are most expansion prone and the extent of expansion. Furthermore, whether these diseases share a common expansion mechanism is unclear. To date, expansion has only been studied in a limited number of REDs. Here we report the first studies of the expansion mechanism in induced pluripotent stem cells derived from a patient with a form of the glutaminase deficiency disorder known as Global Developmental Delay, Progressive Ataxia, And Elevated Glutamine (GDPAG; OMIM# 618412) caused by the expansion of a CAG-STR in the 5′ UTR of the glutaminase (GLS) gene. We show that alleles with as few as ~ 120 repeats show detectable expansions in culture despite relatively low levels of R-loops formed at this locus. Additionally, using a CRISPR-Cas9 knockout approach we show that PMS2 and MLH3, the constituents of MutLα and MutLγ, the 2 mammalian MutL complexes known to be involved in mismatch repair (MMR), are essential for expansion. Furthermore, PMS1, a component of a less well understood MutL complex, MutLβ, is also important, if not essential, for repeat expansion in these cells. Our results provide insights into the factors important for expansion and lend weight to the idea that, despite some differences, the same mechanism is responsible for expansion in many, if not all, REDs.
Effectiveness of a novel diet in attenuation of clinical activity of disease in patients with ulcerative colitis: a randomized, clinical trial
Authors: Narimani Behnaz , Sadeghi Amir , Daryani Nasser Ebrahimi , Shahrokh Shabnam , Nilghaz Maryam , Ghods Maryam , Shafiee Mahshad , Shahparvari Mohammad Reza , Hekmatdoost Azita
Published: June 2024

Dietary intake plays a pivotal role in ulcerative colitis (UC) initiation and prognosis. The aim of this study was to investigate the effect of a combined Mediterranean, low-FODMAP diet accompanied with partial enteral nutrition (PEN) on clinical and para-clinical characteristics of patients with UC. Fifty patients with active mild to moderate UC were received either a combined diet or a regular diet for 6 weeks. Before and after the intervention, disease activity index, quality of life and some inflammatory and oxidative stress factors were measured using valid and reliable questionnaires and blood sampling. Disease activity index was significantly decreased in the combined diet group in comparison to control diet group (p = 0.043), and baseline data (p < 0.001). Moreover, the quality of life score increased significantly in the combined diet group compared to the control group, and the baseline data (p < 0.001). Serum level of high sensitive C-reactive protein (hs-CRP) decreased significantly in the combined group (p < 0.01), while it increased in the control group non-significantly. Serum total anti-oxidant capacity (TAC) changes were not statistically significant in two groups. This study indicates that this combination diet has the potential to be used as a safe and highly effective approach in patients with significant intestinal symptoms. Further clinical trial studies with different duration of intervention are needed to confirm these results.

Trial registration: The study was registered on IRCT.ir with registration number of IRCT20100524004010N38, on 25/04/2023.
An online, two-day educational seminar had no impact on disease-specific knowledge in patients with systemic sclerosis
Authors: Garbe Nancy , Raberger Katja , Wienke Andreas , Keyßer Gernot , Schäfer Christoph
Published: June 2024

Systemic sclerosis (SSc) is a multifaceted disease, and its diagnosis triggers substantial anxiety and uncertainty for those affected. Currently, there are no valid data describing the impact of disease-specific patient education on the disease knowledge available. We created a two-day, online educational seminar to provide SSc patients with disease-specific information. The primary objective of the study was to observe the change in the disease-specific knowledge of the patients. A total of 118 patients were randomized into an intervention group and a waiting list control group. The change in knowledge was assessed using a multiple-choice test. The intervention group completed the questionnaire before, directly after, and 3 months after the seminar, while the waiting list control group also took the test 3 months before the seminar to rule out nonspecific learning. The primary outcome measure was the score difference between baseline and 3 months after baseline. The study was registered in the German Clinical Trials Register (protocol code DRKS00024915). The educational seminar resulted in a small, but measurable, increase in knowledge. While the two tests in the waiting list control group prior to the seminar did not show a nonspecific increase in disease knowledge, the intervention led to a numerical increase in knowledge (mean ± sd score difference 0.34 ± 1.31, 95% CI (− 0.23; 0.86), p = 0.26) that did not reach statistical significance. Multiple linear regression analysis showed that being a member of a self-help group (β = 1.12; p = 0.03) is a positive predictor of a higher disease knowledge. Although highly appreciated by participants, a two-day online seminar may not be the most appropriate format to generate measurable disease-specific knowledge. Self-help group membership was a positive predictor of a higher level of disease-specific knowledge prior to the educational seminar and should be recommended to every affected person.
A larger TatBC complex associates with TatA clusters for transport of folded proteins across the bacterial cytoplasmic membrane
Authors: Werner Max-Hinrich , Mehner-Breitfeld Denise , Brüser Thomas
Published: June 2024

The twin-arginine translocation (Tat) system transports folded proteins across energized biological membranes in bacteria, plastids, and plant mitochondria. In Escherichia coli, the three membrane proteins TatA, TatB and TatC associate to enable Tat transport. While TatB and TatC together form complexes that bind Tat-dependently transported proteins, the TatA component is responsible for the permeabilization of the membrane during transport. With wild type Tat systems, the TatB- and TatC-containing Tat complexes TC1 and TC2 can be differentiated. Their TatA content has not been resolved, nor could they be assigned to any step of the translocation mechanism. It is therefore a key question of current Tat research to understand how TatA associates with Tat systems during transport. By analyzing affinity-purified Tat complexes with mutations in TatC that selectively enrich either TC1 or TC2, we now for the first time demonstrate that both Tat complexes associate with TatA, but the larger TC2 recruits significantly more TatA than the smaller TC1. Most TatA co-purified as multimeric clusters. Using site-specific photo cross-linking, we could detect TatA–TatC interactions only near TatC transmembrane helices 5 and 6. Substrate-binding did not change the interacting positions but affected the stability of the interaction, pointing to a substrate-induced conformational transition. Together, our findings indicate that TatA clusters associate with TatBC without being integrated into the complex by major rearrangements. The increased TatA affinity of the larger Tat complex TC2 suggests that functional assembly is advanced in this complex.
Cervical cancer trend in the Republic of Kazakhstan and attitudes towards cervical cancer screening in urban and rural areas
Authors: Zhetpisbayeva Indira , Rommel Alexander , Kassymbekova Fatima , Semenova Yuliya , Sarmuldayeva Sholpan , Giniyat Azhar , Tanatarova Gulnaz , Dyussupova Azhar , Faizova Raida , Rakhmetova Venera , Glushkova Natalya
Published: June 2024

Cervical cancer (CC) continues to be a significant global health issue, which in part can be attributed to disparities in access to CC screening services. This study aims to conduct a trend of CC in Kazakhstan and to compare attitudes towards the screening program between women living in urban and rural areas. In the first stage, we conducted a trend study of CC indicators in Kazakhstan using official statistics. In the second stage, a cross-sectional study was conducted using a structured questionnaire to assess adherence to screening. The trend study reveals a decline in cervical cancer mortality rates (from 7.15 to 5.93 per 100,000 female inhabitants) over the period studied, while the incidence remains stable (from 18.51 to 19.38 per 100,000 female inhabitants). Regional variations in Period Prevalence rates were observed. Significant differences were found in screening participation rates between urban n = 41 (74%) and rural n = 23 (38%) women, p < 0.001, as well as awareness of the screening program (urban: n = 15 (27%), rural: n = 35 (58%), p < 0.001). The trend study highlights a decrease in cervical cancer mortality rates over the specified period, accompanied by a consistent incidence rate. Additionally, regional disparities in period prevalence rates of cervical cancer were observed. The primary factor contributing to the low adherence of rural women to screening was found to be a lack of awareness regarding the screening program. Therefore, increasing awareness about the importance of screening is crucial for improving adherence rates among rural women in Kazakhstan.
Examining spatiotemporal crowdsensing and caching for population-dynamic OTT content delivery
Authors: Kim Hee Soo , Jang Yumi , Choi Yun Jae , Kim Hong Ki , Kim Seongcheol , Lee Sang Hyun
Published: June 2024

This study proposes a novel spatiotemporal crowdsensing and caching (SCAC) framework to address the surging demands of urban wireless network traffic. In the context of rampant urbanization and ubiquitous digitization in cities, effective data traffic management is crucial for maintaining a dynamic urban ecosystem. Leveraging user mobility patterns and content preferences, this study formulates an offloading policy to alleviate congestion across urban areas. Our approach uses an AI-based method at the cell level, providing a practical and scalable solution that can be readily adapted to bustling metropolitan areas. The implementation of our model demonstrated its effectiveness in reflecting real-world urban dynamics, resulting in significant reductions in peak-hour traffic and robust performance across diverse urban settings. The deployment strategy initiates from densely populated transportation hubs, gradually expanding to broader urban areas. This systematic expansion adheres to a policy framework that emphasizes data privacy and sustainable urban development, ensuring alignment with societal needs and regulatory frameworks. By addressing technological efficacy and societal impact, this study enhances the understanding of urban wireless traffic management. It offers mobile network operators, policymakers, and urban planners a comprehensive strategy to harness the potential of spatiotemporal technology, thereby ensuring that cities remain dynamic, efficient, and well-prepared for the future of digital connectivity.
Loss of connectin novex-3 leads to heart dysfunction associated with impaired cardiomyocyte proliferation and abnormal nuclear mechanics
Authors: Hashimoto Ken , Ohira Momoko , Kodama Aya , Kimoto Misaki , Inoue Mariko , Toné Shigenobu , Usui Yuu , Hanashima Akira , Goto Takato , Ogura Yuhei , Ujihara Yoshihiro , Mohri Satoshi
Published: June 2024

Connectin (also known as titin) is a giant striated muscle protein that functions as a molecular spring by providing elasticity to the sarcomere. Novex-3 is a short splice variant of connectin whose physiological function remains unknown. We have recently demonstrated using in vitro analyses that in addition to sarcomere expression, novex-3 was also expressed in cardiomyocyte nuclei exclusively during fetal life, where it provides elasticity/compliance to cardiomyocyte nuclei and promotes cardiomyocyte proliferation in the fetus, suggesting a non-sarcomeric function. Here, we analyzed novex-3 knockout mice to assess the involvement of this function in cardiac pathophysiology in vivo. Deficiency of novex-3 compromised fetal cardiomyocyte proliferation and induced the enlargement of individual cardiomyocytes in neonates. In adults, novex-3 deficiency resulted in chamber dilation and systolic dysfunction, associated with Ca2+ dysregulation, resulting in a reduced life span. Mechanistic analyses revealed a possible association between impaired proliferation and abnormal nuclear mechanics, including stiffer nuclei positioned peripherally with stabilized circumnuclear microtubules in knockout cardiomyocytes. Although the underlying causal relationships were not fully elucidated, these data show that novex-3 has a vital non-sarcomeric function in cardiac pathophysiology and serves as an early contributor to cardiomyocyte proliferation.
Thrombospondin 2, matrix Gla protein and digital analysis identified distinct fibroblast populations in fibrostenosing Crohn’s disease
Authors: Jerala Miha , Remic Tinkara , Hauptman Nina , Homan Pia , Zajšek Neža , Petitjean Mathieu , Chen Li , Zidar Nina
Published: June 2024

Fibrosis is an important complication in inflammatory bowel diseases. Previous studies suggest an important role of matrix Gla protein (MGP) and thrombospondin 2 (THBS2) in fibrosis in various organs. Our aim was to analyse their expression together with regulatory miRNAs in submucosal and subserosal fibroblasts in ulcerative colitis (UC) and Crohn’s disease (CD) using immunohistochemistry and qPCR. Digital pathology was used to compare collagen fibre characteristics of submucosal and subserosal fibrosis. Immunohistochemistry showed expression of MGP, but not THBS2 in submucosa in UC and CD. In the subserosa, there was strong staining for both proteins in CD but not in UC. qPCR showed significant upregulation of THBS2 and MGP genes in CD subserosa compared to the submucosa. Digital pathology analysis revealed higher proportion of larger and thicker fibres that were more tortuous and reticulated in subserosal fibrosis compared to submucosal fibrosis. These results suggest distinct fibroblast populations in fibrostenosing CD, and are further supported by image analysis showing significant differences in the morphology and architecture of collagen fibres in submucosal fibrosis in comparison to subserosal fibrosis. Our study is the first to describe differences in submucosal and subserosal fibroblast populations, contributing to understanding of the pathogenesis of fibrostenosis in CD.
Single-pixel Fresnel incoherent correlation holography compressed imaging using a Trumpet network
Authors: Li Jiaosheng , Chen Yifei , Liu Tianyun , Wu Bo , Zhang Qinnan
Published: June 2024

Fresnel incoherent correlation holography (FINCH) can achieve high-precision and non-scanning 3D imaging. However, as a holographic imaging technology, the huge bandwidth requirements and the amount of holographic data transmitted have always been one of the important factors limiting its application. In addition, the hardware cost of pixel array-based CCD or CMOS imaging is very high under high resolution or specific wavelength conditions. Accordingly, a single-pixel Fresnel incoherent correlation holography (SP-FINCH) compressed imaging method is proposed, which replaces pixel array detector with single-pixel detector and designs a Trumpet network to achieve low-cost and high-resolution imaging. Firstly, a modified FINCH imaging system is constructed and data acquisition is carried out using a single-pixel detector. Secondly, a Trumpet network is constructed to directly map the relationship between one-dimensional sampled data and two-dimensional image in an end-to-end manner. Moreover, by comparing the reconstructed images using neural network with that using commonly used single-pixel reconstruction methods, the results indicate that the proposed SP-FINCH compressed imaging method can significantly improve the quality of image reconstruction at lower sampling rate and achieve imaging without phase-shifting operation. The proposed method has been shown to be feasible and advantageous through numerical simulations and optical experiment results.
Evaluation of digit ratio (2D:4D) in breast cancer patients
Authors: Yıldırım Dişli Şafak , Özdöver Ali Caner , Yüce Elif , Dişli Ahmet Kürşad , Fidan Evren
Published: June 2024

Breast cancer is a hormone-dependent cancer. Hormonal exposure begins in the intrauterine period and continues in later years of life. 2D:4D ratio is accepted as an indicator of this exposure. The aim of this study was to investigate whether there is a difference in 2D:4D ratio between pathological subgroups of breast cancer and healthy control group. In this study, 204 participants, 154 breast cancer patients and 50 healthy control volunteers with similar age distribution, were included. Both hands of all participants were scanned using a digital scanner. The second and fourth finger lengths were measured using a digital measuring ruler with an accuracy of 0.05 mm. The 2D:4D ratio was calculated as the length of the second finger divided by the length of the fourth finger. A total of 204 patients (55 triple negative, 52 luminal B, 33 luminal A, 14 HER2-overexpessing and 50 healthy control volunteers) were subjected to finger scanning. There was no statistically significant difference in mean age between the groups. The right hand 2D:4D ratio was significantly lower in the Luminal A group compared to the other groups (p < 0.048). Although prenatal hormonal exposure is accepted as a risk factor for breast cancer, no study has evaluated patients in pathological subgroups. The 2D:4D ratio may be associated with breast cancer especially in the luminal A group in which hormone receptors are strongly positive and which has a better prognosis compared to the other groups.
Secretome profiling of human epithelial cells exposed to cigarette smoke extract and their effect on human lung microvascular endothelial cells
Authors: Seenak Porrnthanate , Nernpermpisooth Nitirut , Kumphune Sarawut , Songjang Worawat , Jiraviriyakul Arunya , Jumroon Noppadon , Pankhong Panyupa , Roytrakul Sittiruk , Thaisakun Siriwan , Phaonakrop Narumon , Nuengchamnong Nitra
Published: June 2024

Cigarette smoke (CS) is one of the leading causes of pulmonary diseases and can induce lung secretome alteration. CS exposure-induced damages to human pulmonary epithelial cells and microvascular endothelial cells have been extensively demonstrated; however, the effects of the secretome of lung epithelial cells exposed to CS extracts (CSE) on lung microvascular endothelial cells are not fully understood. In this study, we aimed to determine the effects of the secretome of lung epithelial cells exposed to CSE on lung microvascular endothelial cells. Human lung epithelial cells, A549, were exposed to CSE, and the secretome was collected. Human lung microvascular endothelial cells, HULEC-5a, were used to evaluate the effect of the secretome of A549 exposed to CSE. Secretome profile, endothelial cell death, inflammation, and permeability markers were determined. CSE altered the secretome expression of A549 cells, and secretome derived from CSE-exposed A549 cells caused respiratory endothelial cell death, inflammation, and moderately enhanced endothelial permeability. This study demonstrates the potential role of cellular interaction between endothelial and epithelial cells during exposure to CSE and provides novel therapeutic targets or beneficial biomarkers using secretome analysis for CSE-related respiratory diseases.