bluuebunny/crossref_metadata_2025 huggingface dataset:
An international, open-access dataset of dental wear patterns and associated broad age classes in archaeological cattle mandibles
Authors: Hill Eden , Albarella Umberto
Published: July 2024

Zooarchaeologists investigate past interactions between animals, humans, and their environments by analyzing the remains of archaeological fauna. Age-at-death distributions are fundamental to faunal analysis and are often estimated by comparing exposed dentine patterns to standardized tooth wear stages that have been associated with relative age classes. We present Bubona, an international dataset of dental wear patterns and associated broad age classes in archaeological cattle mandibles. Our open-access dataset of 1460 data entries from nine counties is being used to create tooth-type specific reference tables of probable age class attribution for cattle mandibles lacking complete dentition. Bubona is a valuable resource for the innovation of new systems of age estimation for cattle and it is the creators hope that researchers will continue to both help expand the dataset by contributing their own data, as well as utilize the data to refine and innovate age-at-death estimation methods.
Tidings from the Tides–De novo transcriptome assembly of the endemic estuarine bivalve Villorita cyprinoides
Authors: Rahuman Summaya , N. S. Jeena , Sebastian Wilson , Varghese Eldho , P. K. Asokan
Published: July 2024

The Indian black clam Villorita cyprinoides Gray, 1825, is an economically valuable estuarine bivalve that faces challenges from multiple stressors and anthropogenic pressures. However, limited genomic resources have hindered molecular investigations into the impact of these stressors on clam populations. Here, we have generated the first transcriptomic reference datasets for V. cyprinoides to address this knowledge gap. A total of 25,040,592 and 22,486,217 million Illumina paired-end reads generated from two individuals were assembled using Trinity and rnaSPAdes. From the 47,607 transcripts identified as Coding Domain Sequences, 37,487 returned positive BLAST hits against six different databases. Additionally, a total of 14,063 Single Sequence Repeats were identified using GMATA. This study significantly enhances the genetic understanding of V. cyprinoides, a potential candidate for aquaculture that supports the livelihoods of many people dependent on small-scale fisheries. The data generated provides insights into broader genealogical connections within the family Cyrenidae through comparative transcriptomics. Furthermore, this transcriptional profile serves as baseline data for future studies in toxicological and conservation genetics.
A high-precision oasis dataset for China from remote sensing images
Authors: Lin Jingwu , Gui Dongwei , Liu Yunfei , Liu Qi , Zhang Siyuan , Liu Chuang
Published: July 2024

High-resolution oasis maps are imperative for understanding ecological and socio-economic development of arid regions. However, due to the late establishment and relatively niche nature of the oasis discipline, there are no high-precision datasets related to oases in the world to date. To fill this gap, detailed visual interpretation of remote sensing images on Google Earth Professional or Sentinel-2 was conducted in summer 2020, and for the first time, a high-precision dataset of China’s oases (abbreviation HDCO) with a resolution of 1 meter was constructed. HDCO comprises 1,466 oases with a total area of 277,375.56 km2. The kappa coefficient for this dataset validated by the field survey was 0.8686 and the AUC value for the ROC curve was 0.935. In addition, information on the geographic coordinates, climatic conditions, major landforms, and hydrological features of each oasis was added to the attribute table of the dataset. This dataset enables researchers to quantitatively monitor location and area of oases, fosters exploration of the relationship between oases and human under climate change and urbanization.
Urea intercalated encapsulated microalgae composite hydrogels for slow-release fertilizers
Authors: Sarhan Nada , Arafa Esraa G. , Elgiddawy Nada , Elsayed Khaled N. M. , Mohamed Fatma
Published: July 2024

In agriculture, hydrogels can be addressed for effective operation of water and controlled-release fertilizers. Hydrogels have a significant ability for retaining water and improving nutrient availability in soil, enhancing plant growth while reducing water and fertilizer usage. This work aimed to prepare a hydrogel composite based on microalgae and biopolymers including chitosan and starch for use as a soil conditioner. The hydrogel composite was characterized by FTIR, XRD, and SEM. All hydrogel properties were studied including swelling degree, biodegradability, water-holding capacity, water retention, and re-swelling capacity in soil and water. The urea fertilizer loading and releasing behavior of the prepared hydrogels were investigated. The results revealed that the range of the maximal urea loading was between 99 and 440%, and the kinetics of loading was fitted with Freundlich model. The urea release % exhibited 78–95%, after 30 days, and the kinetics of release was fitted with zero-order, Higuchi, and Korsmeyer–Peppas models. Furthermore, the prepared hydrogels obtained a significant water-holding capacity, after blending soil (50 g) with small amount of hydrogels (1 g), the capacity increased in the range of 99.4–101.5%. In sum, the prepared hydrogels have the potential to be applied as a soil conditioner.
Shotgun metagenomic insights into secondary metabolite biosynthetic gene clusters reveal taxonomic and functional profiles of microbiomes in natural farmland soil
Authors: Kifle Bezayit Amare , Sime Amsale Melkamu , Gemeda Mesfin Tafesse , Woldesemayat Adugna Abdi
Published: July 2024

Antibiotic resistance is a worldwide problem that imposes a devastating effect on developing countries and requires immediate interventions. Initially, most of the antibiotic drugs were identified by culturing soil microbes. However, this method is prone to discovering the same antibiotics repeatedly. The present study employed a shotgun metagenomics approach to investigate the taxonomic diversity, functional potential, and biosynthetic capacity of microbiomes from two natural agricultural farmlands located in Bekeka and Welmera Choke Kebelle in Ethiopia for the first time. Analysis of the small subunit rRNA revealed bacterial domain accounting for 83.33% and 87.24% in the two selected natural farmlands. Additionally, the analysis showed the dominance of Proteobacteria representing 27.27% and 28.79% followed by Actinobacteria making up 12.73% and 13.64% of the phyla composition. Furthermore, the analysis revealed the presence of unassigned bacteria in the studied samples. The metagenome functional analysis showed 176,961 and 104, 636 number of protein-coding sequences (pCDS) from the two samples found a match with 172,655 and 102, 275 numbers of InterPro entries, respectively. The Genome ontology annotation suggests the presence of 5517 and 3293 pCDS assigned to the “biosynthesis process”. Numerous Kyoto Encyclopedia of Genes and Genomes modules (KEGG modules) involved in the biosynthesis of terpenoids and polyketides were identified. Furthermore, both known and novel Biosynthetic gene clusters, responsible for the production of secondary metabolites, such as polyketide synthases, non-ribosomal peptide synthetase, ribosomally synthesized and post-translationally modified peptides (Ripp), and Terpene, were discovered. Generally, from the results it can be concluded that the microbiomes in the selected sampling sites have a hidden functional potential for the biosynthesis of secondary metabolites. Overall, this study can serve as a strong preliminary step in the long journey of bringing new antibiotics to the market.
Age-appropriate BMI cut-offs for malnutrition among older adults in India
Authors: Singh Akancha , Chattopadhyay Aparajita
Published: July 2024

With the increasing prevalence of obesity in India, body mass index (BMI) has garnered importance as a disease predictor. The current World Health Organization (WHO) body mass index (BMI) cut-offs may not accurately portray these health risks in older adults aged 60 years and above. This study aims to define age-appropriate cut-offs for older adults (60–74 years and 75 years and above) and compare the performance of these cut-offs with the WHO BMI cut-offs using cardio-metabolic conditions as outcomes. Using baseline data from the Longitudinal Ageing Study in India (LASI), classification and regression tree (CART) cross-sectional analysis was conducted to obtain age-appropriate BMI cut-offs based on cardio-metabolic conditions as outcomes. Logistic regression models were estimated to compare the association of the two sets of cut-offs with cardio-metabolic outcomes. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were estimated. Agreement with waist circumference, an alternate measure of adiposity, was conducted. For older adults aged 60–74 years and 75 years and above, the cut-off for underweight reduced from < 18.5 to < 17.4 and < 13.3 respectively. The thresholds for overweight and obese increased for older adults aged 60–74 years old from >  = 25 to > 28.8 and >  = 30 to > 33.7 respectively. For older adults aged 75 years and above, the thresholds decreased for both categories. The largest improvement in AUC was observed in older adults aged 75 years and above. The newly derived cut-offs also demonstrated higher sensitivity and specificity among all age-sex stratifications. There is a need to adopt greater rigidity in defining overweight/obesity among older adults aged 75 years and above, as opposed to older adults aged 60–74 years old among whom the thresholds need to be less conservative. Further stratification in the low risk category could also improve BMI classification among older adults. These age-specific thresholds may act as improved alternatives of the current WHO BMI thresholds and improve classification among older adults in India.
Construction of a novel prognostic scoring model for HBV-ACLF liver failure based on dynamic data
Authors: Cai Qun , Wang Hao , Zhu Mingyan , Xiao Yixin , Zhuo Tingting
Published: July 2024

Early prognostic assessment of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important for guiding clinical management and reducing mortality. The aim of this study was to dynamically monitor the clinical characteristics of HBV-ACLF patients, thereby allowing the construction of a novel prognostic scoring model to predict the outcome of HBV-ACLF patients. Clinical data was prospectively collected for 518 patients with HBV-ACLF and randomly divided into training and validation sets. We constructed day-1, day-2, and day-(1 + 3) prognostic score models based on dynamic time points. The prognostic risk score constructed for day-3 was found to have the best predictive ability. The factors included in this scoring system, referred to as DSM-ACLF-D3, were age, hepatic encephalopathy, alkaline phosphatase, total bilirubin, triglycerides, very low-density lipoprotein, blood glucose, neutrophil count, fibrin, and INR. ROC analysis revealed the area under the curve predicted by DSM-ACLF-D3 for 28-day and 90-day mortality (0.901 and 0.889, respectively) was significantly better than those of five other scoring systems: COSSH-ACLF IIs (0.882 and 0.836), COSSH-ACLFs (0.863 and 0.832), CLIF-C ACLF (0.838 and 0.766), MELD (0.782 and 0.762) and MELD-Na (0.756 and 0.731). Dynamic monitoring of the changes in clinical factors can therefore significantly improve the accuracy of scoring models. Evaluation of the probability density function and risk stratification by DSM-ACLF-D3 also resulted in the best predictive values for mortality. The novel DSM-ACLF-D3 prognostic scoring model based on dynamic data can improve early warning, prediction and clinical management of HBV-ACLF patients.
Impact of baseline ECG characteristics on changes in cardiac biomarkers and echocardiographic metrices after acute myocardial infarction treated with Empagliflozin
Authors: Benedikt Martin , Aziz Faisal , Fröschl Thomas , Strohhofer Christoph , Kolesnik Ewald , Tripolt Norbert , Pferschy Peter , Wallner Markus , Bugger Heiko , Zirlik Andreas , Scherr Daniel , Sourij Harald , von Lewinski Dirk
Published: July 2024

The EMMY trial was a multicentre, investigator-initiated, placebo-controlled, double-blind trial, which enrolled 476 patients immediately following AMI and the first study demonstrating a significant reduction in NT-proBNP-levels as well as significant improvements in cardiac structure and function in patients after acute myocardial infarction treated with empagliflozin vs. placebo. However, hardly any data are available investigating the prognostic role of baseline electrocardiogram metrics in SGLT2-inhibitor-treated patients. This post-hoc analysis investigated the association of baseline ECG metrics collected in one centre of the trial (181 patients) with changes in structural and functional cardiac parameters as well as cardiac biomarkers in response to Empagliflozin treatment. A total of 181 patients (146 men; mean age 58 ± 14 years) were included. Median PQ-interval was 156 (IQR 144–174) milliseconds (ms), QRS width 92 (84–98) ms, QTc interval 453 (428–478) ms, Q-wave duration 45 (40–60) ms, Q-wave amplitude 0.40 (0.30–0.70) millivolt (mV), and heart rate was 71 (64–85) bpm. For functional cardiac parameters (LVEF and E/eʹ) of the entire cohort, a greater decrease of E/eʹ from baseline to week 26 was observed in shorter QRS width (P = 0.005).Structural cardiac endpoints were only found to have a significant positive correlation between LVEDD and Q wave duration (P = 0.037). Higher heart rate was significantly correlated with better response in LVEF (P = 0.001), E/eʹ (P = 0.021), and NT-proBNP (P = 0.005). Empagliflozin-treatment showed no interaction with the results. Baseline ECG characteristics post AMI are neither predictive for beneficial NTproBNP effects of Empagliflozin post AMI, nor for functional or structural changes within 26 weeks post AMI.
A streamlined approach for intelligent ship object detection using EL-YOLO algorithm
Authors: Yang Defu , Solihin Mahmud Iwan , Ardiyanto Igi , Zhao Yawen , Li Wei , Cai Bingyu , Chen Chaoran
Published: July 2024

Maritime objects frequently exhibit low-quality and insufficient feature information, particularly in complex maritime environments characterized by challenges such as small objects, waves, and reflections. This situation poses significant challenges to the development of reliable object detection including the strategies of loss function and the feature understanding capabilities in common YOLOv8 (You Only Look Once) detectors. Furthermore, the widespread adoption and unmanned operation of intelligent ships have generated increasing demands on the computational efficiency and cost of object detection hardware, necessitating the development of more lightweight network architectures. This study proposes the EL-YOLO (Efficient Lightweight You Only Look Once) algorithm based on YOLOv8, designed specifically for intelligent ship object detection. EL-YOLO incorporates novel features, including adequate wise IoU (AWIoU) for improved bounding box regression, shortcut multi-fuse neck (SMFN) for a comprehensive analysis of features, and greedy-driven filter pruning (GDFP) to achieve a streamlined and lightweight network design. The findings of this study demonstrate notable advancements in both detection accuracy and lightweight characteristics across diverse maritime scenarios. EL-YOLO exhibits superior performance in intelligent ship object detection using RGB cameras, showcasing a significant improvement compared to standard YOLOv8 models.
Enhancement of endothelial function and attenuation of portal vein injury using mesenchymal stem cells carrying miRNA-25-3p
Authors: Nie Guole , Zhang Honglong , Luo Wei , Zhu Xingwang , Xie Danna , Yan Jun , Wang Haiping , Li Xun
Published: July 2024

The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote venous endothelial cell proliferation and attenuate portal endothelial cell injury. HucMSCs and human umbilical vein endothelial cells (HUVEC) were isolated and cultured from human umbilical cord and characterized. Lentiviral vectors expressing miRNA-25-3p were transfected into hucMSCs and confirmed by PCR. We verified the effect of miR-25-3p-modified hucMSCs on HUVEC by cell co-culture and cell supernatant experiments. Subsequently, exosomes of miR-25-3p-modified hucMSCs were isolated from cell culture supernatants and characterized by WB, NTA and TEM. We verified the effects of miR-25-3p-modified exosomes derived from hucMSCs on HUVEC proliferation, migration, and angiogenesis by in vitro cellular function experiments. Meanwhile, we further examined the downstream target genes and signaling pathways potentially affected by miR-25-3p-modified hucMSC-derived exosomes in HUVEC. Finally, we established a rat portal vein venous thrombosis model by injecting CM-DiR-labeled hucMSCs intravenously into rats and examining the homing of cells in the portal vein by fluorescence microscopy. Histological and immunohistochemical experiments were used to examine the effects of miRNA-25-3p-modified hucMSCs on the proliferation and damage of portal vein endothelial cells. Primary hucMSCs and HUVECs were successfully isolated, cultured and characterized. Primary hucMSCs were modified with a lentiviral vector carrying miR-25-3p at MOI 80. Co-culture and cell supernatant intervention experiments showed that overexpression of miRNA-25-3p in hucMSCs enhanced HUVEC proliferation, migration and tube formation in vitro. We successfully isolated and characterized exosomes of miR-25-3p-modified hucMSCs, and exosome intervention experiments demonstrated that miR-25-3p-modified exosomes derived from hucMSCs similarly enhanced the proliferation, migration, and angiogenesis of HUVECs. Subsequent PCR and WB analyses indicated PTEN/KLF4/AKT/ERK1/2 as potential pathways of action. Analysis in a rat portal vein thrombosis model showed that miR-25-3p-modified hucMSCs could homing to damaged portal veins. Subsequent histological and immunohistochemical examinations demonstrated that intervention with miR-25-3p overexpression-modified hucMSCs significantly reduced damage and attenuated thrombosis in rat portal veins. The above findings indicate suggest that hucMSCs based on miR-25-3p modification may be a promising therapeutic approach for use in venous thrombotic diseases.
P4HA2 promotes proliferation, invasion, and metastasis through regulation of the PI3K/AKT signaling pathway in oral squamous cell carcinoma
Authors: Chi Zengpeng , Wang Qimin , Wang Xin , Li Dagang , Tong Lei , Shi Yu , Yang Fang , Guo Qingyuan , Zheng Jiawei , Chen Zhenggang
Published: July 2024

Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under physiological conditions. Although its overexpression influences a wide variety of malignant tumors' occurrence and development, its specific effects and mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. This study focused on investigating the expression patterns, carcinogenic functions, and underlying mechanisms of P4HA2 in OSCC cells. Various databases, including TCGA, TIMER, UALCAN, GEPIA, and K-M plotter, along with paraffin-embedded samples, were used to ascertain P4HA2 expression in cancer and its correlation with clinicopathological features. P4HA2 knockdown and overexpression cell models were developed to assess its oncogenic roles and mechanisms. The results indicated that P4HA2 was overexpressed in OSCC and inversely correlated with patient survival. Knockdown of P4HA2 suppressed invasion, migration, and proliferation of OSCC cells both in vitro and in vivo, whereas overexpression of P4HA2 had the opposite effects. Mechanistically, the phosphorylation levels of the PI3K/AKT pathway were reduced following P4HA2 silencing. The study reveals that P4HA2 acts as a promising biomarker for predicting prognosis in OSCC and significantly affects metastasis, invasion, and proliferation of OSCC cells through the regulation of the PI3K/AKT signaling pathway.
A simple psychophysical procedure separates representational and noise components in impairments of speech prosody perception after right-hemisphere stroke
Authors: Adl Zarrabi Aynaz , Jeulin Mélissa , Bardet Pauline , Commère Pauline , Naccache Lionel , Aucouturier Jean-Julien , Ponsot Emmanuel , Villain Marie
Published: July 2024

After a right hemisphere stroke, more than half of the patients are impaired in their capacity to produce or comprehend speech prosody. Yet, and despite its social-cognitive consequences for patients, aprosodia following stroke has received scant attention. In this report, we introduce a novel, simple psychophysical procedure which, by combining systematic digital manipulations of speech stimuli and reverse-correlation analysis, allows estimating the internal sensory representations that subtend how individual patients perceive speech prosody, and the level of internal noise that govern behavioral variability in how patients apply these representations. Tested on a sample of N = 22 right-hemisphere stroke survivors and N = 21 age-matched controls, the representation + noise model provides a promising alternative to the clinical gold standard for evaluating aprosodia (MEC): both parameters strongly associate with receptive, and not expressive, aprosodia measured by MEC within the patient group; they have better sensitivity than MEC for separating high-functioning patients from controls; and have good specificity with respect to non-prosody-related impairments of auditory attention and processing. Taken together, individual differences in either internal representation, internal noise, or both, paint a potent portrait of the variety of sensory/cognitive mechanisms that can explain impairments of prosody processing after stroke.
Evaluation of the optical and magnetic properties of novel Nd0.9Zn0.1FeO3 perovskite nanoparticles and their adsorption of Pb2+ ions from water
Authors: Arman M. M.
Published: July 2024

Nd0.9Zn0.1FeO3 was prepared in a single-phase with an average crystallite size of 25.82 nm using a citrate combustion technique. The energy dispersive X-ray assures the chemical formula of the sample. The elemental mapping of Zn-doped NdFeO3 illustrates the good homogeneous distribution of the elements in the sample. Nd0.9Zn0.1FeO3 has antiferromagnetic properties with weak ferromagnetic components and has good UV absorbance. The values of the band gap for the direct and indirect transitions are 1.473 eV and 1.250 eV, respectively. The adsorption of nickel(II), cobalt(II), chrome(VI), cadmium(II), and lead(II) ions has been studied at pH 7. The highest removal efficiency (η = 73.72%) was observed for the lead ions from water. The current study has examined the kinetics, recoveries, and mechanisms of utilizing Nd0.90Zn0.10FeO3 to remove Pb2+ ions from water. The optimum conditions for the absorbing Pb2+ are pH 7 and a contact time of 60 min. The Freundlich isotherm model is the best model for the absorption of Pb2+ ions. While, the pseudo-second-order kinetic model describes the kinetic adsorption data. The sample has a good efficiency for removing Pb2+ ions from water several times.
Speckled-speckle field as a resource for imaging techniques
Authors: Cassina Silvia , Cenedese Gabriele , Allevi Alessia , Bondani Maria
Published: July 2024

Correlated states of light, both classical and quantum, can find useful applications in the implementation of several imaging techniques. Among the employed sources, pseudo-thermal states, generated by the passage of a laser beam through a diffuser, represent the standard choice. To produce light with a higher level of correlation, in this work we consider and characterize the speckled-speckle field obtained with two diffusers using both a numerical simulation and an experimental implementation. In order to discuss the potential usefulness of super-thermal light in imaging protocols, we analyze the behavior of some figures of merit, namely the contrast, the signal-to-noise ratio and the image resolution. The obtained results clarify the possible advantages offered by this kind of light, and at the same time better emphasize the reasons why it does not outperform pseudo-thermal light.
Improved chaotic Bat algorithm for optimal coordinated tuning of power system stabilizers for multimachine power system
Authors: Tadj Mohammed , Chaib Lakhdar , Choucha Abdelghani , Alhazmi Mohannad , Alwabli Abdullah , Bajaj Mohit , Dost Mohammadi Shir Ahmad
Published: July 2024

Power systems exhibit nonlinearity. causing dynamic instability and complex power oscillations. This research proposes an innovative strategy using the Novel Bat Algorithm (NBA) to achieve ideal Power System Stabilizers (PSSs) in a multimachine power system. The approach shifts electromechanical modes to specific areas in the s-plane. Enhancing the multi-machine power system and establishing stabilizer parameters for dynamic performance. The study examines the designed approach aptitude for standard lead-lag PSSs configurations. In order to elevate the global search problem and transfer some static operators for the optimum optimization process. the chaos mapping. also known as CNBA. is introduced into NBA. Four different forms of chaos maps are compared in experiments to resolve unconstrained mathematical issues in order to illustrate CNBA performance. In any other case. the challenge of designing PSS under a wide range of loading situations is transformed into an optimization challenge with the damping ratio of electromechanical modes with low damping as the target function. The optimal stabilizers’ gains are gotten by employing the CNBA algorithm. Second plan. an effective technique is astutely established to delineate the PSS location and quantity using CNBA and another side using participation factor. To examine the efficacy of the proposed CNBA-based PSS on a large system; it is tested on the interconnected of New-England/New-York (16 generators and 68 buses) power grid. and verified by comparative study with NBA through eigenvalue analysis and nonlinear simulation to provide evidence the algorithmic competence of CNBA. The CNBA approach yields a minimum damping ratio of 37%. which is consistent with the its eigenvalue. In contrast, the NBA approach achieves a minimum damping ratio of 31%. The simulation results reveal the fine performance of the proposed CNBA-PSS in a convincing manner and its capacity to provide an excellent damping for inter-area and local oscillations under diverse operating cases compared to NBA-PSS then in the case of PSS location.
Identifying Bayesian optimal experiments for uncertain biochemical pathway models
Authors: Isenberg Natalie M. , Mertins Susan D. , Yoon Byung-Jun , Reyes Kristofer G. , Urban Nathan M.
Published: July 2024

Pharmacodynamic (PD) models are mathematical models of cellular reaction networks that include drug mechanisms of action. These models are useful for studying predictive therapeutic outcomes of novel drug therapies in silico. However, PD models are known to possess significant uncertainty with respect to constituent parameter data, leading to uncertainty in the model predictions. Furthermore, experimental data to calibrate these models is often limited or unavailable for novel pathways. In this study, we present a Bayesian optimal experimental design approach for improving PD model prediction accuracy. We then apply our method using simulated experimental data to account for uncertainty in hypothetical laboratory measurements. This leads to a probabilistic prediction of drug performance and a quantitative measure of which prospective laboratory experiment will optimally reduce prediction uncertainty in the PD model. The methods proposed here provide a way forward for uncertainty quantification and guided experimental design for models of novel biological pathways.
Local field potential sharp waves with diversified impact on cortical neuronal encoding of haptic input
Authors: Kristensen Sofie S. , Jörntell Henrik
Published: July 2024

Cortical sensory processing is greatly impacted by internally generated activity. But controlling for that activity is difficult since the thalamocortical network is a high-dimensional system with rapid state changes. Therefore, to unwind the cortical computational architecture there is a need for physiological ‘landmarks’ that can be used as frames of reference for computational state. Here we use a waveshape transform method to identify conspicuous local field potential sharp waves (LFP-SPWs) in the somatosensory cortex (S1). LFP-SPW events triggered short-lasting but massive neuronal activation in all recorded neurons with a subset of neurons initiating their activation up to 20 ms before the LFP-SPW onset. In contrast, LFP-SPWs differentially impacted the neuronal spike responses to ensuing tactile inputs, depressing the tactile responses in some neurons and enhancing them in others. When LFP-SPWs coactivated with more distant cortical surface (ECoG)-SPWs, suggesting an involvement of these SPWs in global cortical signaling, the impact of the LFP-SPW on the neuronal tactile response could change substantially, including inverting its impact to the opposite. These cortical SPWs shared many signal fingerprint characteristics as reported for hippocampal SPWs and may be a biomarker for a particular type of state change that is possibly shared byboth hippocampus and neocortex.
Electrical stimulation enhances sciatic nerve regeneration using a silk-based conductive scaffold beyond traditional nerve guide conduits
Authors: Soltani Khaboushan Alireza , Azimzadeh Ashkan , Behboodi Tanourlouee Saman , Mamdoohi Melina , Kajbafzadeh Abdol-Mohammad , Slavin Konstantin V. , Rahimi-Movaghar Vafa , Hassannejad Zahra
Published: July 2024

Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p < 0.0001) and neurofilament (p < 0.001) expression was seen after 6 weeks. Ultrastructural evaluations showed that conductive scaffolds with ES minimized Wallerian degeneration. Furthermore, the conductive conduit with ES group demonstrated significantly increased myelin sheet thickness and decreased G. ratio compared to the autograft. Immunofluorescent images confirmed the presence of GFP-positive ADSCs by the 6th week. Locomotor recovery assessments revealed improved function in the conductive conduit with ES group compared to the control group and groups without ES. These results show that a Silk/AuNPs conduit filled with ADSC-seeded collagen hydrogel can function as a nerve conduit, aiding in the restoration of substantial gaps in the sciatic nerve with ES. Histological and locomotor evaluations indicated that ES had a greater impact on functional recovery compared to using a conductive conduit alone, although the use of conductive conduits did enhance the effects of ES.
Lower urinary dysfunction as a long-term effect of childhood vincristine treatment, with potential influences by sex and dose
Authors: Iguchi Nao , Teimouri Ali , Wilcox Duncan T. , Malykhina Anna P. , Cost Nicholas G.
Published: July 2024

Vincristine (VCR) is one of the most widely used chemotherapy agents in treating pediatric cancer. Nonetheless, it is known to cause dose-dependent neurotoxicity which can impact virtually every organ system. Despite its widespread use, the precise impact of VCR on the lower urinary tract (LUT) remains inadequately elucidated. Our initial clinical and translational investigations suggest a sex-specific influence of childhood VCR exposure on LUT function. Thus, the current study aimed to investigate the late effects of systemic VCR exposure on LUT physiology and the underlying mechanisms, focusing on dosage and male-sex, employing juvenile CD-1 mice as a model. Male mice subjected to VCR exhibited augmented functional bladder capacity accompanied by frequent non-void contractions during awake cystometry, alongside mast cell accumulation within the bladder, compared to the saline-treated control group. Noteworthy functional changes were observed in bladder strips from the VCR group, including decreased nerve-mediated contraction, heightened contractile responses to cholinergic and purinergic agonists, enhanced responsiveness to histamine—primarily via histamine receptor 1 (Hrh1)—and an augmented relaxation effect with compound 48/80 (a mast cell degranulator), relative to the control group. Significant changes in gene expression levels associated with neuroinflammation and nociception were observed in both the bladder and lumbosacral dorsal root ganglia (Ls-DRG) of the VCR group. These findings suggest that VCR exposure during childhood, particularly in males, triggers neuroimmune responses in the bladder and Ls-DRG, amplifying responsiveness to neurotransmitters in the bladder, thereby contributing to LUT dysfunction characterized by a mixed bladder phenotype as a late effect during survivorship.
Preoperative visualization of the greater occipital nerve with magnetic resonance imaging in candidates for occipital nerve decompression for headaches
Authors: Saad Mariam , Manzanera Esteve Isaac V. , Evans Adam G. , Karagoz Huseyin , Kesayan Tigran , Brooks-Horrar Krista , Sengupta Saikat , Robison Ryan , Johnson Brian , Dortch Richard , Thayer Wesley P. , Assi Patrick , Gfrerer Lisa , Kassis Salam
Published: July 2024

Occipital nerve decompression is effective in reducing headache symptoms in select patients with migraine and occipital neuralgia. Eligibility for surgery relies on subjective symptoms and responses to nerve blocks and Onabotulinum toxin A (Botox) injections. No validated objective method exists for detecting occipital headache pathologies. The purpose of the study is to explore the potential of high-resolution Magnetic Resolution Imaging (MRI) in identifying greater occipital nerve (GON) pathologies in chronic headache patients. The MRI protocol included three sequences targeting fat-suppressed fluid-sensitive T2-weighted signals. Visualization of the GON involved generating 2-D image slices with sequential rotation to track the nerve course. Twelve patients underwent pre-surgical MRI assessment. MRI identified four main pathologies that were validated against intra-operative examination: GON entanglement by the occipital artery, increased nerve thickness and hyperintensity suggesting inflammation compared to the non-symptomatic contralateral side, early GON branching with rejoining at a distal point, and a connection between the GON and the lesser occipital nerve. MRI possesses the ability to visualize the GON and identify suspected trigger points associated with headache symptoms. This case series highlights MRI's potential to provide objective evidence of nerve pathology. Further research is warranted to establish MRI as a gold standard for diagnosing extracranial contributors in headaches.
miR-15a targets the HSP90 co-chaperone Morgana in chronic myeloid leukemia
Authors: Poggio Pietro , Rocca Stefania , Fusella Federica , Ferretti Roberta , Ala Ugo , D’Anna Flora , Giugliano Emilia , Panuzzo Cristina , Fontana Diletta , Palumbo Valeria , Carrà Giovanna , Taverna Daniela , Gambacorti-Passerini Carlo , Saglio Giuseppe , Fava Carmen , Piazza Rocco , Morotti Alessandro , Orso Francesca , Brancaccio Mara
Published: July 2024

Morgana is a ubiquitous HSP90 co-chaperone protein coded by the CHORDC1 gene. Morgana heterozygous mice develop with age a myeloid malignancy resembling human atypical myeloid leukemia (aCML), now renamed MDS/MPN with neutrophilia. Patients affected by this pathology exhibit low Morgana levels in the bone marrow (BM), suggesting that Morgana downregulation plays a causative role in the human malignancy. A decrease in Morgana expression levels is also evident in the BM of a subgroup of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients showing resistance or an incomplete response to imatinib. Despite the relevance of these data, the mechanism through which Morgana expression is downregulated in patients’ bone marrow remains unclear. In this study, we investigated the possibility that Morgana expression is regulated by miRNAs and we demonstrated that Morgana is under the control of four miRNAs (miR-15a/b and miR-26a/b) and that miR-15a may account for Morgana downregulation in CML patients.
Effects of temporary access to environmental enrichment on measures of laboratory mouse welfare
Authors: Ratuski A. S. , Améndola L. , Makowska I. J. , Weary D. M.
Published: July 2024

Laboratory mice are typically housed in “shoebox” cages with limited opportunities to engage in natural behaviour. Temporary access to environments with increased space and complexity (playpens) may improve mouse welfare. Previous work by our group has shown that mice are motivated to access and use these environments, but it is unknown how other aspects of welfare are impacted. Female C57BL/6J, BALB/cJ, and DBA/2J mice (n = 21; 7 mice per strain) were housed in mixed-strain trios and given temporary access to a large playpen with their cage mates three times per week. Control mice (n = 21; 7 mice per strain) remained in their home cages. Home cage behaviour (development of stereotypic behaviour over time, aggression following cage-changing) and anxiety tests were used to assess how playpen access impacted welfare. Contrary to our predictions, we found increased time spent performing stereotypies in playpen mice; this difference may be related to negative emotional states, increased motivation to escape the home cage, or active coping strategies. Playpen access resulted in strain-dependent improvements in aggression and some measures of anxiety. Aggression was lower for C57BL/6J mice in the playpen treatment following cage changing than it was for C57BL/6J control mice, while playpen mice, and particularly the C57BL/6J strain, spent more time in the center of the open field test and produced fewer fecal boli during anxiety testing, supporting other research showing that strain differences play an important role in behaviour and stress resiliency.
A clinical tool to predict overall survival of elderly patients with soft tissue sarcoma after surgical resection
Authors: Lv Xianmei , Zhu Lujian , Lan Gaochen , Huang Zhangheng , Guo Qiusheng
Published: July 2024

With the aging world population, the incidence of soft tissue sarcoma (STS) in the elderly gradually increases and the prognosis is poor. The primary goal of this research was to analyze the relevant risk factors affecting the postoperative overall survival in elderly STS patients and to provide some guidance and assistance in clinical treatment. The study included 2,353 elderly STS patients from the Surveillance, Epidemiology, and End Results database. To find independent predictive variables, we employed the Cox proportional risk regression model. R software was used to develop and validate the nomogram model to predict postoperative overall survival. The performance and practical value of the nomogram were evaluated using calibration curves, the area under the curve, and decision curve analysis. Age, tumor primary site, disease stage, tumor size, tumor grade, N stage, and marital status, are the risk variables of postoperative overall survival, and the prognostic model was constructed on this basis. In the two sets, both calibration curves and receiver operating characteristic curves showed that the nomogram had high predictive accuracy and discriminative power, while decision curve analysis demonstrated that the model had good clinical usefulness. A predictive nomogram was designed and tested to evaluate postoperative overall survival in elderly STS patients. The nomogram allows clinical practitioners to more accurately evaluate the prognosis of individual patients, facilitates the progress of individualized treatment, and provides clinical guidance.
Major vault protein is part of an extracellular cement material in the Atlantic salmon louse (Lepeophtheirus salmonis)
Authors: Slinning Malene Skuseth , Nthiga Thaddaeus Mutugi , Eichner Christiane , Khadija Syeda , Rome Leonard H. , Nilsen Frank , Dondrup Michael
Published: July 2024

Major vault protein (MVP) is the main component of the vault complex, which is a highly conserved ribonucleoprotein complex found in most eukaryotic organisms. MVP or vaults have previously been found to be overexpressed in multidrug-resistant cancer cells and implicated in various cellular processes such as cell signaling and innate immunity. The precise function of MVP is, however, poorly understood and its expression and probable function in lower eukaryotes are not well characterized. In this study, we report that the Atlantic salmon louse expresses three full-length MVP paralogues (LsMVP1-3). Furthermore, we extended our search and identified MVP orthologues in several other ecdysozoan species. LsMVPs were shown to be expressed in various tissues at both transcript and protein levels. In addition, evidence for LsMVP to assemble into vaults was demonstrated by performing differential centrifugation. LsMVP was found to be highly expressed in cement, an extracellular material produced by a pair of cement glands in the adult female salmon louse. Cement is important for the formation of egg strings that serve as protective coats for developing embryos. Our results imply a possible novel function of LsMVP as a secretory cement protein. LsMVP may play a role in structural or reproductive functions, although this has to be further investigated.
Hemodialysis-induced positional changes in lamina cribrosa
Authors: Kim Ji Hong , Jeong Hyo Chan , Shin Yong Un , Lee Won June
Published: July 2024

This study is aimed to investigate the effect of hemodialysis (HD) on the lamina cribrosa (LC) of the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT) and other ophthalmological parameters in patients with end-stage kidney disease (ESKD). This prospective observational study included 29 patients who underwent HD for ESKD. ONH parameters including neural canal diameter (NCD), peripapillary vertical height (PVH), and anterior LC depth (LCD), were assessed using SS-OCT. Changes in the ONH parameters before and after HD were statistically analysed. Correlations between changes in the LCD and other ocular and systemic measurements were identified using Pearson’s correlation analyses. The mean anterior LCD significantly decreased from 441.6 ± 139.8 μm before HD to 413.5 ± 141.7 μm after HD (P = 0.001). Mean NCD and PVH did not show significant changes after HD (P = 0.841 and P = 0.574, respectively). A significant correlation was found between changes in the anterior LCD and the mean ocular perfusion pressure (r = 0.397, P = 0.036). We observed a significant decrease in anterior LCD after HD. Our study suggests that HD can influence the ONH, especially in the LC.
Caspase-9 suppresses metastatic behavior of MDA-MB-231 cells in an adaptive organoid model
Authors: Falahi Farzaneh , Akbari-Birgani Shiva , Mortazavi Yousef , Johari Behrooz
Published: July 2024

Caspase-9, a cysteine-aspartate protease traditionally associated with intrinsic apoptosis, has recently emerged as having non-apoptotic roles, including influencing cell migration—an aspect that has received limited attention in existing studies. In our investigation, we aimed to explore the impact of caspase-9 on the migration and invasion behaviors of MDA-MB-231, a triple-negative breast cancer (TNBC) cell line known for its metastatic properties. We established a stable cell line expressing an inducible caspase-9 (iC9) in MDA-MB-231 and assessed their metastatic behavior using both monolayer and the 3D organotypic model in co-culture with human Foreskin fibroblasts (HFF). Our findings revealed that caspase-9 had an inhibitory effect on migration and invasion in both models. In monolayer culture, caspase-9 effectively suppressed the migration and invasion of MDA-MB-231 cells, comparable to the anti-metastatic agent panitumumab (Pan). Notably, the combination of caspase-9 and Pan exhibited a significant additional effect in reducing metastatic behavior. Interestingly, caspase-9 demonstrated superior efficacy compared to Pan in the organotypic model. Molecular analysis showed down regulation of epithelial–mesenchymal transition and migratory markers, in caspase-9 activated cells. Additionally, flow cytometry analysis indicated a cell cycle arrest. Moreover, pre-treatment with activated caspase-9 sensitized cells to the chemotherapy of doxorubicin, thereby enhancing its effectiveness. In conclusion, the anti-metastatic potential of caspase-9 presents avenues for the development of novel therapeutic approaches for TNBC/metastatic breast cancer. Although more studies need to figure out the exact involving mechanisms behind this behavior.
A retrospective study of adjuvant albumin-bound paclitaxel plus S-1 after D2 gastrectomy versus oxaliplatin plus S-1 in gastric cancer
Authors: Li Ning , Wu Hui , Xu Xin , Wei Qinming , Ding Yongfeng , Liu Shan , Wu Jinqiong , Zheng Yulong , Xu Nong , Gao Yuan , Jiang Haiping
Published: July 2024

Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1–14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.