bluuebunny/crossref_metadata_2025 huggingface dataset:
Reassessing the role of magnetite during natural hydrogen generation
Authors: Geymond Ugo , Briolet Théo , Combaudon Valentine , Sissmann Olivier , Martinez Isabelle , Duttine Mathieu , Moretti Isabelle
Published: April 2023

Interactions between water and ferrous rocks are known to generate natural H2 in oceanic and continental domains via the oxidation of iron. Such generation has been mainly investigated through the alteration of Fe2+-silicate and some Fe2+-carbonates. So far, magnetite (α-Fe3O4) has never been considered as a potential source mineral for natural H2 since it is considered as a by-product of every known chemical reaction leading to the formation of H2, despite it bears 1/3 of Fe2+ in its mineral lattice. This iron oxide is rather seen as a good catalyst for the formation of H2. Recently, hydrogen emissions were observed in the surroundings of banded iron formations (BIF) that are constituted of, among other minerals, magnetite. Thus, this work is an attempt to constrain the true potential of magnetite by means of batch reactor experiments and additional thermodynamic calculations. It explores theoretical and experimental reaction pathways of magnetite during water-rock interactions, focusing on low temperatures (T < 200°C). For the purpose of the experiments, gold capsules filled with magnetite powders were run at 80°C and 200°C. Gas products were analyzed using gas chromatography (GC) while solid products were characterized by X-ray diffraction (XRD), Mössbauer spectroscopy, and scanning electron microscopy (SEM). After experimental alteration, high amounts of H2 were quantified while mineralogical transitions were observed by SEM. It showed self-reorganization of the primary iron oxide resulting in sharp-edge and better crystalized secondary minerals. In parallel, XRD analyses showed tiny changes between the patterns of the initial powder and the solid products of reaction. Finally, Mössbauer spectroscopy revealed that the starting magnetite was partly converted to maghemite (γ-Fe2O3), a metastable Fe-oxide only containing Fe3+. Major implications arise from these results. Concerning H2 exploration, this work provides evidence that natural hydrogen can be generated at near-ambient temperature. It also infers that magnetite-rich lithologies such as BIF should be targeted while looking for H2 source rocks. In addition, these outcomes could be of major interest for mining companies as they provide key elements to understand the formation of BIF-hosted iron ores.
Estimation of mechanics parameters of rock in consideration of confining pressure using monitoring while drilling data
Authors: Zhang Yonghao , Zhao Jianbin , Xiao Zhanshan , Gao Yanwu , Cui Shitao , Cheng Daojie , He Mingming , Fang Chaoqiang , Xue Haifang , Zhao Ying
Published: April 2023

During the drilling process, high-strength rock can lead to various issues such as drilling suppression, bit wear, and increased operational costs. To ensure safe and efficient drilling operations, it is crucial to accurately predict the strength parameters of the rock and recommend modifications to operational procedures. This paper proposes a low-cost and fast measurement method for predicting the strength parameters of rock in the field. To evaluate the effectiveness of this method, a drilling process monitoring experiment was conducted on sandstone, limestone, and granite. The experiment studied the effect of confining pressure on the response of cutting with an impregnated diamond bit. By analyzing the relationship between the thrust force, torque force, and penetration depth under different confining pressures, the researchers developed an analytical model for drilling that considers confining pressure, compressed crushed zone, and bit geometry. The results show that the confining pressure has a significant effect on the cutting response. As the confining pressure increases, the thrust force, torque force, and penetration depth at the cutting point also increase. Furthermore, a new measurement method was proposed to determine the strength parameters, such as cohesion, internal friction angle, and unconfined compressive strength. The estimated strength parameters for the three rock types using the drilling method were in good agreement with those of the standard laboratory test, with an error range of 10%. This method of estimating rock strength parameters is a practical tool for engineers. It can continuously and quickly obtain the drilling parameters of in-situ rocks.
Short-term weather patterns influence avian body condition during the breeding season
Authors: McCloy Michael W. D. , Grace Jacquelyn K.
Published: April 2023

Despite a large body of literature investigating the effects of long-term climate trends on birds, the effects of short-term weather on individual body condition are less established. Poor body condition is associated with declines in individual fitness for many avian species, thus changes to body condition may result in altered population productivity. We utilized a large existing dataset from the Monitoring Avian Productivity and Survivorship program to analyze the effects of daily maximum temperature, daily minimum temperature, and monthly precipitation on avian body condition over a 15-year period across 79 sampling sites in the southeastern United States. We used a model selection approach with generalized additive models at both species and guild levels and found largely nonlinear responses of avian body condition to weather variables. For many species and guilds, a threshold effect was evident, after which the relationship between body condition and weather changed drastically. As extreme weather becomes more common under climate change, species will be pushed further towards or away from these thresholds. Non-linear effects were also highly species-specific and not easily explained by expected effects on food availability. Thus, avian responses to altered weather may be difficult to predict across species. We discuss the implications of these results for individual fitness and population productivity.
Volatilomics of raspberry fruit germplasm by combining chromatographic and direct-injection mass spectrometric techniques
Authors: Farneti Brian , Khomenko Iuliia , Ajelli Matteo , Wells Karen Elizabeth , Betta Emanuela , Aprea Eugenio , Giongo Lara , Biasioli Franco
Published: April 2023

The application of direct-injection mass spectrometric (DI-MS) techniques, like Proton Transfer Reaction Time of Flight Mass Spectrometry (PTR-ToF-MS) has been suggested as a reliable phenotyping tool for fruit volatilome assessment in both genetic and quality-related studies. In this study the complexity of raspberry aroma was investigated by a comprehensive untargeted VOC analysis, done by combining SPME-GC-MS and PTR-ToF-MS assessments with multi-block discriminant analysis using the DIABLO mixOmics framework. The aim was to acquire an exhaustive characterization of the raspberry volatilome according to different fruit ripening stages (pink, ripe, and overripe) and genetic variances (50 accessions), as well as to investigate the potential of PTR-ToF-MS as a rapid and high throughput VOC phenotyping tool to address issues related to raspberry fruit quality. Results of this study demonstrated the complementarity between SPME-GC-MS and PTR-ToF-MS techniques to evaluate the raspberry aroma composition. PTR-ToF-MS generates reliable raspberry VOC fingerprints mainly due to a reduced compound fragmentation and precise content estimation. In addition, the high collinearity between isomers of monoterpenes and norisoprenoids, discovered by GC analysis, reduces the main analytic limitation of PTR-ToF-MS of not being able to separate isomeric molecules. The high similarity between the VOC matrices obtained by applying PTR-ToF-MS and SPME-GC-MS confirmed the possibility of using PTR-ToF-MS as a reliable high throughput phenotyping tool for raspberry volatiolome assessment. In addition, results provided by the germplasm collection investigation enabled to distinguish the best performing accessions, based on VOCs composition, to be used as superior parental lines for future breeding programs.
Vision transformers for the prediction of mild cognitive impairment to Alzheimer’s disease progression using mid-sagittal sMRI
Authors: Hoang Gia Minh , Kim Ue-Hwan , Kim Jae Gwan
Published: April 2023

Background

Alzheimer’s disease (AD) is one of the most common causes of neurodegenerative disease affecting over 50 million people worldwide. However, most AD diagnosis occurs in the moderate to late stage, which means that the optimal time for treatment has already passed. Mild cognitive impairment (MCI) is an intermediate state between cognitively normal people and AD patients. Therefore, the accurate prediction in the conversion process of MCI to AD may allow patients to start preventive intervention to slow the progression of the disease. Nowadays, neuroimaging techniques have been developed and are used to determine AD-related structural biomarkers. Deep learning approaches have rapidly become a key methodology applied to these techniques to find biomarkers.

Methods

In this study, we aimed to investigate an MCI-to-AD prediction method using Vision Transformers (ViT) to structural magnetic resonance images (sMRI). The Alzheimer’s Disease Neuroimaging Initiative (ADNI) database containing 598 MCI subjects was used to predict MCI subjects’ progression to AD. There are three main objectives in our study: (i) to propose an MRI-based Vision Transformers approach for MCI to AD progression classification, (ii) to evaluate the performance of different ViT architectures to obtain the most advisable one, and (iii) to visualize the brain region mostly affect the prediction of deep learning approach to MCI progression.

Results

Our method achieved state-of-the-art classification performance in terms of accuracy (83.27%), specificity (85.07%), and sensitivity (81.48%) compared with a set of conventional methods. Next, we visualized the brain regions that mostly contribute to the prediction of MCI progression for interpretability of the proposed model. The discriminative pathological locations include the thalamus, medial frontal, and occipital—corroborating the reliability of our model.

Conclusion

In conclusion, our methods provide an effective and accurate technique for the prediction of MCI conversion to AD. The results obtained in this study outperform previous reports using the ADNI collection, and it suggests that sMRI-based ViT could be efficiently applied with a considerable potential benefit for AD patient management. The brain regions mostly contributing to prediction, in conjunction with the identified anatomical features, will support the building of a robust solution for other neurodegenerative diseases in future.
Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43
Authors: Wang Xingqiao , Kong Fanqiang , Lin Zengbin
Published: April 2023

Background

Cerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia.

Purpose

This study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases.

Methods

Genes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments.

Results

The study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders.

Conclusion

The findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.
Influence of amyloid beta on impulse spiking of isolated hippocampal neurons
Authors: Yavorsky Volodymyr A. , Rozumna Nataliia M. , Lukyanetz Elena A.
Published: April 2023

One of the signs of Alzheimer’s disease (AD) is the formation of β-amyloid plaques, which ultimately lead to the dysfunction of neurons with subsequent neurodegeneration. Although extensive researches have been conducted on the effects of different amyloid conformations such as oligomers and fibrils on neuronal function in isolated cells and circuits, the exact contribution of extracellular beta-amyloid on neurons remains incompletely comprehended. In our experiments, we studied the effect of β-amyloid peptide (Aβ1–42) on the action potential (APs) generation in isolated CA1 hippocampal neurons in perforated patch clamp conditions. Our findings demonstrate that Aβ1–42 affects the generation of APs differently in various hippocampal neurons, albeit with a shared effect of enhancing the firing response of the neurons within a minute of the start of Aβ1–42 application. In the first response type, there was a shift of 20–65% toward smaller values in the firing threshold of action potentials in response to inward current. Conversely, the firing threshold of action potentials was not affected in the second type of response to the application of Aβ1–42. In these neurons, Aβ1-42 caused a moderate increase in the frequency of spiking, up to 15%, with a relatively uniform increase in the frequency of action potentials generation regardless of the level of input current. Obtained data prove the absence of direct short-term negative effect of the Aβ1–42 on APs generation in neurons. Even with increasing the APs generation frequency and lowering the neurons’ activation threshold, neurons were functional. Obtained data can suggest that only the long-acting presence of the Aβ1–42 in the cell environment can cause neuronal dysfunction due to a prolonged increase of APs firing and predisposition to this process.
Effect of Theta Burst Stimulation-Patterned rTMS on Motor and Nonmotor Dysfunction of Parkinson's Disease: A Systematic Review and Metaanalysis
Authors: Cheng Bo , Zhu Tao , Zhao Wenhao , Sun Ling , Shen Yao , Xiao Wei , Zhang Shushan
Published: April 2023

Background: Theta burst stimulation (TBS), a type of patterned repetitive transcranial magnetic stimulation (rTMS), has several advantages, such as short time of single treatment and low stimulation intensity compared with traditional rTMS. Since the efficacy of TBS on the symptoms of Parkinson's disease (PD) was inconsistent among different studies, we systematically searched these studies and quantitatively analyzed the therapeutic effect of TBS for patients with PD.

Methods: We followed the recommended PRISMA guidelines for systematic reviews. Studies from PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov from January 1, 2005 of each database to September 30, 2021 were analyzed. We also manually retrieved studies of reference.

Results: Eight eligible studies with 189 participants (received real TBS and/or sham TBS) were included. This metaanalysis found that TBS did not significantly improve Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score in the “on” medicine state (SMD = −0.06; 95% CI, −0.37 to 0.25; p = 0.69; I2 = 0%), while, it brought significant improvement of UPDRS-III scores in the “off” medicine state (SMD = −0.37; 95% CI, −0.65 to −0.09; p < 0.01; I2 = 19%). Subgroup analysis found that merely continuous TBS (cTBS) over the supplementary motor area (SMA) brought significant improvement of UPDRS-III score (SMD = −0.63; 95% CI, −1.02 to −0.25; p < 0.01). TBS had insignificant effectiveness for upper limb movement disorder both in the “on” and “off” medicine status (SMD = −0.07; 95% CI, −0.36 to 0.22; p = 0.64; I2 = 0%; SMD = −0.21; 95% CI, −0.57 to 0.15; p = 0.26; I2 = 0%; respectively). TBS significantly improved slowing of gait in the “off” medicine status (SMD = −0.37; 95% CI, −0.71 to −0.03; p = 0.03; I2 = 0%). Subgroup analysis suggested that only intermittent TBS (iTBS) over the primary motor cortex (M1) + dorsolateral prefrontal cortex (DLPFC) had significant difference (SMD = −0.57; 95% CI, −1.13 to −0.01; p = 0.04). Additionally, iTBS over the M1+ DLPFC had a short-term (within 2 weeks) therapeutic effect on PD depression (MD = −2.93; 95% CI, −5.52 to −0.33; p = 0.03).

Conclusion: Our study demonstrated that cTBS over the SMA could significantly improve the UPDRS-III score for PD patients in the “off,” not in the “on,” medicine state. TBS could not bring significant improvement of upper limb movement dysfunction. ITBS over the M1+DLPFC could significantly improve the slowing of gait in the “off” medicine status. Additionally, iTBS over the M1+DLPFC has a short-term (within 2 weeks) therapeutic effect on PD depression. Further RCTs of a large sample, and excellent design are needed to confirm our conclusions.
Low-Density Lipoprotein Cholesterol and Mortality in Patients With Intracerebral Hemorrhage in Taiwan
Authors: Wen Chi-Pang , Lee Yi-Che , Sun Yuan-Ting , Huang Chih-Yuan , Tsai Chon-Haw , Chen Po-Lin , Chang Wei-Lun , Yeh Po-Yen , Wei Cheng-Yu , Tsai Ming-Jun , Sun Yu , Lin Chih-Hao , Lee Jiunn-Tay , Lai Ta-Chang , Lien Li-Ming , Lin Mei-Chen , Lin Cheng-Li , Lee June-Han , Wang Hao-Kuang , Hsu Chung Y. ,   Taiwan Stroke Registry Investigators
Published: April 2023

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.

Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.

Results: Low cholesterol (LDL-C <100 mg/dL), found in 1/4 of the MJ cohort, was highly prevalent (36%) among young adults (age 20–39). There was a graded relationship between cholesterol and mortality for ICH [Hazard ratio, 1.56; 95% confidence interval (CI), 1.13–2.16]. Compared with patients with an LDL-C of 110–129 mg/dL in TSR, the risk for mortality was 1.84 (95% CI, 1.28–2.63) with an LDL-C of <100 mg/dL.

Conclusion: Lower serum LDL-C level independently predicts higher mortality after acute ICH. While its causative role may vary, low cholesterol may pose potential harms in Taiwan.
Randomized trial of transcutaneous auricular vagus nerve stimulation on patients with disorders of consciousness: A study protocol
Authors: Cheng Lijuan , Sun Lingxiu , Xu Lu , Zhao Falin , Liu Xiaochen , Wang Anqi , Di Haibo , Cong Yu-Sheng
Published: April 2023

Background

Transcutaneous auricular vagus nerve stimulation (taVNS) has recently been explored for the treatment of Disorders of consciousness (DoC) caused by traumatic brain injury. The evidence of taVNS during the consciousness recovery has been recently reported. However, the mechanism of taVNS in the recovery of consciousness is not clear. This study attempts to investigate the effectiveness of taVNS in DoC by means of Coma Recovery Scale-Revised (CRS-R), Magnetic resonance imaging (MRI), Electrophysiology (EEG), and Single-molecular array (Simoa).

Methods/design

Nighty patients with DoC acquired brain injury are randomized into one of three groups receiving sham taVNS or active taVNS (just left and left or right), respectively. Each of the three groups will experience a 40 days cycle (every 10 days for a small period, baseline 2 weeks, intervention 2 weeks, 40 min per day, 5 days per week, then no intervention for 2 weeks, intervention 2 weeks, 40 min per day, and 5 days per week). Primary outcomes (CRS-R) will be recorded five times during every period. Secondary outcomes will be recorded at the first and at the last period [MRI, EEG, Phosphorylated tau (P-tau), and Neurofilament light chain (NFL)]. We will take notes the adverse events and untoward effects during all cycles.

Discussion

Transcutaneous auricular vagus nerve stimulation as a painless, non-invasive, easily applied, and effective therapy was applied for treatment of patients with depression and epilepsy several decades ago. Recent progress showed that taVNS has behavioral effects in the consciousness recovery. However, there is no clinical evidence to support the effects of taVNS on brain activity. Therefore, we will design a randomized controlled trial to evaluate the effectiveness and safety of taVNS therapy for DoC, and explore neural anatomy correlated to taVNS during the consciousness recovery. Finally, this protocol also tests some biomarkers along with the recovery of consciousness.

Clinical Trial Registration

Chinese Clinical Trial Registry, ChiCTR2100045161. Registered on 9 April 2021.
Combined multidisciplinary in/outpatient rehabilitation delays definite nursing home admission in advanced Parkinson’s disease patients
Authors: Steendam-Oldekamp Elien , Weerkamp Nico , Vonk Judith M. , Bloem Bastiaan R. , van Laar Teus
Published: April 2023

Introduction

Advanced Parkinson’s disease (aPD) patients have a high risk on definite nursing home admission. We analyzed the effectiveness of an in-and outpatient multidisciplinary rehabilitation, focusing on activities of daily living (ADL) and delaying definite nursing home admission.

Methods

This study included 24 aPD patients, who received a 6-week inpatient multidisciplinary rehabilitation program, including optimization of pharmacotherapy, which was followed by an individualized outpatient support program during 2 years (intervention group). A non-randomized matched control group (n = 19), received care as usual. Primary endpoints consisted of the Amsterdam Linear Disability Scale (ALDS) and percentage of patients being able to live independently at home after 2 years. Secondary endpoints included changes in medication (LEDD), motor performance (SCOPA-SPES), cognition (SCOPA-COG), hallucinations (NPI) and depression (BDI).

Results

Overall, 83% of patients were able to return home after the 6-week inpatient intervention, and 65% still lived at home at 2 years follow-up. Median ALDS scores after 2 years in the intervention group were significantly better, compared to the control group (p = 0.002). All secondary endpoints had improved significantly vs. baseline directly after the 6-week inpatient rehabilitation, which had disappeared at 2 years follow-up, with the exception of the daily dose of medication, which was significantly higher in the intervention group.

Conclusion

This 2-year follow-up study showed that a combined multidisciplinary in/outpatient rehabilitation program for aPD patients, was able to stabilize ADL functions, and finally delayed definite nursing home admissions in 65% of treated patients.

Trial registration

filenumber M10.091051; ABR code NL32699.042.10.
Presence of corrective saccades in patients with normal vestibulo-ocular reflex gain in video head impulse test
Authors: Kabaya Kayoko , Fukushima Akina , Katsumi Sachiyo , Minakata Toshiya , Iwasaki Shinichi
Published: April 2023

Background

The video head impulse test (vHIT) is a valuable clinical tool that can help identify dysfunction of the semicircular canals. While in cases with semicircular canal dysfunction, both decreased vestibulo-ocular reflex (VOR) gain and corrective saccades (CS) are usually observed, there are cases which show CS despite normal VOR gain in vHIT.

Objective

This study aimed to investigate the clinical characteristics of patients who showed CS with normal VOR gain in vHIT.

Materials and methods

Among 390 patients who underwent vHIT, 51 patients (20 males and 31 females, age 31–87 years, average 61.3 years old) who showed CS with normal VOR gain unilaterally during horizontal vHIT were included. All patients had normal vHIT (normal VOR gain and absent CS) on the contralateral side.

The VOR gain of vHIT, the maximum slow phase velocity in the caloric test, and the amplitude of cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were analyzed.

Results

The VOR gain on the affected side (0.95 ± 0.08) was significantly smaller than that on the contralateral side (1.03 ± 0.13) in horizontal vHIT (p < 0.001). The maximum slow phase velocity in the caloric test on the affected side (17.9 ± 17.8 degrees/s) was significantly smaller than that on the contralateral side (21.3 ± 16.6 degrees/s, p = 0.020). There were no significant differences in the amplitude of cVEMPs or oVEMPs between the affected side and the contralateral side (p = 0.096 for cVEMP; p = 0.770 for oVEMP).

Conclusion

The side that showed CS with normal VOR gain in horizontal vHIT showed significantly smaller VOR gain as well as smaller caloric responses compared to the contralateral side. Having CS with normal VOR gain could be a sensitive indicator of mild dysfunction of the semicircular canals.
STGATE: Spatial-temporal graph attention network with a transformer encoder for EEG-based emotion recognition
Authors: Li Jingcong , Pan Weijian , Huang Haiyun , Pan Jiahui , Wang Fei
Published: April 2023

Electroencephalogram (EEG) is a crucial and widely utilized technique in neuroscience research. In this paper, we introduce a novel graph neural network called the spatial-temporal graph attention network with a transformer encoder (STGATE) to learn graph representations of emotion EEG signals and improve emotion recognition performance. In STGATE, a transformer-encoder is applied for capturing time-frequency features which are fed into a spatial-temporal graph attention for emotion classification. Using a dynamic adjacency matrix, the proposed STGATE adaptively learns intrinsic connections between different EEG channels. To evaluate the cross-subject emotion recognition performance, leave-one-subject-out experiments are carried out on three public emotion recognition datasets, i.e., SEED, SEED-IV, and DREAMER. The proposed STGATE model achieved a state-of-the-art EEG-based emotion recognition performance accuracy of 90.37% in SEED, 76.43% in SEED-IV, and 76.35% in DREAMER dataset, respectively. The experiments demonstrated the effectiveness of the proposed STGATE model for cross-subject EEG emotion recognition and its potential for graph-based neuroscience research.
The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
Authors: Schmutzhard Joachim , Bader Werner , Gottfried Timo , Dejaco Daniel , Glückert Rudolf , Dudas Joszef , Schrott-Fischer Annelies
Published: April 2023

Introduction

Local therapeutic hypothermia (32°C) has been linked experimentally to an otoprotective effect in the electrode insertion trauma. The pathomechanism of the electrode insertion trauma is connected to the activation of apoptosis and necrosis pathways, pro-inflammatory and fibrotic mechanisms. In a whole organ cochlea culture setting the effect of therapeutic hypothermia in an electrode insertion trauma model is evaluated.

Material and Methods

The cochleae of C57Bl6/J mice (Charles River®, Freiburg, Germany) are cultured for 24 hours at 37°C and 32°C after inserting a fishing line through the round window simulating an insertion trauma. The resulting effect was evaluated for the apoptotic reaction – B-cell-Lymphoma-2-Associated-X-Protein (BAX), B-Cell-Lymphoma-2-Protein (BCL2) and Cleaved-Caspase-3 (CC3) –, the inflammatory response – Tumor-Necrosis-Factor-Alpha (TNFα), Interleukin-1-Beta (IL-1Imm) and Cyclooxygenase-2 (COX2) – and proliferation process – Transforming-Growth-Factor-Beta-1 (TGFβ1) – using immunohistochemistry and real-time PCR technique. A minimum of 12 cochlea per experiment were used.

Results

A pro-apoptotic situation was observed in the normothermic group (BAX, CC3 ˃ Bcl2) whereas an anti-apoptotic constellation was found at 32°C culture conditions (BAX, CC3 < Bcl2). Furthermore the effect of the IT knowing to effect the pro-inflammatory cytokine (TNFα, Il1β) and enzyme (COX2) expression has been reproduced. This reaction was reversed with the application of therapeutic hypothermia resulting in significant lower pro-inflammatory cytokine (TNFα, Il1β) and enzyme (COX2) expression. TGFβ1 was increased by hypothermia.

Discussion

Concluding a protective effect of hypothermia on the experimental electrode insertion trauma can be described by an anti-apoptotic and anti-inflammatory reaction.
The thalamus in psychosis spectrum disorder
Authors: Anticevic Alan , Halassa Michael M.
Published: April 2023

Psychosis spectrum disorder (PSD) affects 1% of the world population and results in a lifetime of chronic disability, causing devastating personal and economic consequences. Developing new treatments for PSD remains a challenge, particularly those that target its core cognitive deficits. A key barrier to progress is the tenuous link between the basic neurobiological understanding of PSD and its clinical phenomenology. In this perspective, we focus on a key opportunity that combines innovations in non-invasive human neuroimaging with basic insights into thalamic regulation of functional cortical connectivity. The thalamus is an evolutionary conserved region that forms forebrain-wide functional loops critical for the transmission of external inputs as well as the construction and update of internal models. We discuss our perspective across four lines of evidence: First, we articulate how PSD symptomatology may arise from a faulty network organization at the macroscopic circuit level with the thalamus playing a central coordinating role. Second, we discuss how recent animal work has mechanistically clarified the properties of thalamic circuits relevant to regulating cortical dynamics and cognitive function more generally. Third, we present human neuroimaging evidence in support of thalamic alterations in PSD, and propose that a similar “thalamocortical dysconnectivity” seen in pharmacological imaging (under ketamine, LSD and THC) in healthy individuals may link this circuit phenotype to the common set of symptoms in idiopathic and drug-induced psychosis. Lastly, we synthesize animal and human work, and lay out a translational path for biomarker and therapeutic development.
Characterization of the Antimicrobial Edible Film Based on Grasshopper Protein/Soy Protein Isolate/Cinnamaldehyde Blend Crosslinked With Xylose
Authors: Zhang Zisen , Zhou Xing , Fang Changqing , Wang Dong
Published: April 2023

A composite material based on a new insect-based grasshopper protein (GP)/soy protein isolate (SPI) blend has been studied by solution casting using xylose as a crosslinker and cinnamaldehyde (CIN) as an antimicrobial agent to develop a novel antimicrobial edible packaging. In this paper, the effects of SPI, xylose, and CIN content on the properties of edible film were studied. The tensile test confirmed that 30% SPI incorporation content had the best blending effect with the mechanical properties and barrier properties improving obviously. After adding 10% xylose to form crosslinking network, the tensile strength and elongation at the break of the film showed the best state increasing to 3.4 Mpa and 38%, respectively. The 30% CIN enabled the film to be resistant to Escherichia coli and Staphylococcus aureus strongly and decreased the water vapor permeability to 1.8 × 1011 (g/cm·s·Pa) but had a negative effect on the mechanical properties. This is the first time that edible insects have been used to produce the natural edible antimicrobial packaging, proving edible insects, an excellent protein source, are tipped to be a potential source of raw materials for biomaterials.
Simultaneous determination of nine phenolic compounds in imitation wild Dendrobium officinale samples using ultrahigh-performance liquid chromatography–tandem mass spectrometry
Authors: Mu Yingsu , Cheng Li , Gong Xiaojian , Ma Jiangxiong , Zhang Shiyu , Mu Yinghua , Liang Kang , Zhou Xin , Zhao Chao
Published: April 2023

Dendrobium officinale Kimura et Migo (D. officinale), one of the nine everlasting types of grass, has gained increasing attention owing to its important roles in alternative medicines and drug discovery. Due to its natural resources being in danger of being extinct, imitation wild planting is becoming increasingly common. To assess the product’s quality completely, an efficient ultrahigh performance liquid chromatography-triple quadrupole tandem mass spectrometry (UHPLC-QQQ-MS/MS) method was established to simultaneously quantify nine phenolic compounds in D. officinale samples. The extraction parameters, including solvent, solvent concentration, solid–liquid ratio, and extraction time, were systematically optimized with the single-factor test. The results demonstrated that extraction with a 1:200 solid-to-liquid ratio of 80% methanol for 1.5 h was the most efficient condition for the extraction of flavonoids. Satisfactory retention times and resolution of the nine analytes were acquired on the Thermo Scientific Hypersil GOLD column with multiple reaction monitoring in negative ion scanning mode. The method was validated to demonstrate its selectivity, linearity, precision, accuracy, and robustness. Thus, the verified UHPLC-QQQ-MS/MS method was successfully applied to the quantification of phenolic components present in D. officinale samples. The results indicated that the quantity and composition of phenolic components in D. officinale from various provenances were significantly different. This work provides a theoretical foundation for the cultivation and assessment of wild D. officinale quality.
Incidence of death and its predictors among neonates admitted with sepsis in referral hospitals, northwest Ethiopia, a prospective cohort study
Authors: Abiy Saron Abeje , Animut Yaregal , Ambaw Worku Mequannt , Aragaw Getie Mihret , Rade Bayew Kelkay
Published: April 2023

Background

Each year, approximately 2.7 million neonates die in their first month of life worldwide, and the majority of these deaths occur in low-income countries. According to the Global Burden of Disease estimation, 1.3 million annual incident cases of neonatal sepsis were reported worldwide, resulting in 203,000 sepsis-attributable deaths. Little is known about the time to death of neonates and predictors after admission with a diagnosis of sepsis. This study aimed to assess the incidence and predictors of death among neonates admitted to the neonatal intensive care unit with a diagnosis of sepsis in referral hospitals in Northwest Ethiopia.

Methods

A multicenter prospective follow-up study was conducted from November 11 to December 7, 2021. A stratified random sampling technique was employed to select 412 neonates. Neonates admitted with sepsis were followed until they develop event for a maximum of 28 days of age. A face-to-face interview was conducted with the mother of the neonate using a pretested and structured questionnaire, and neonatal charts were reviewed to collect baseline factors. Data were entered into Epi-data version 4.6 and exported to STATA version 14 for analysis. A bivariable and multivariable exponential Cox regression model was fitted to identify predictors of death. The adjusted hazard ratio (AHR) with 95% CI was calculated, and statistical significance was declared at a P-value of 0.05 in the multivariable analysis.

Results

A total of 75 (18.47%) neonates died during the study period, with a 95% CI of 14.82–22.60. The incidence rate of death was 28 (95% CI, 22, 35) per 1,000 person-days of observation, with a total follow-up time of 2,677 person-days of observation. Birth weight (<2,500 g) (AHR = 2.12, 95% CI: 1.01, 4.43), prematurity (AHR = 2.06, 95% CI: 1.02, 4.15), duration of labor >24 h (AHR = 3.89, 95% CI: 1.38, 11.01), breast feeding (AHR = 0.43, 95% CI: 0.23, 0.80), having respiratory distress syndrome (AHR = 1.77, 95% CI: 1.02, 306), oxygen saturation less than 90% (AHR = 2.23, 95% CI: 1.02, 306) were significant predictors of death among neonates admitted with sepsis.

Conclusion and recommendation

The incidence of neonatal mortality in this study was high. Early detection and appropriate management of patients’ presentations like respiratory distress syndrome and low oxygen saturation are necessary to reduce neonatal sepsis-related mortality. Special attention should be given to low birth weight and premature neonates and mothers should be encouraged to breastfeed their newborns after delivery.
Pharmacogenetics in Primary Headache Disorders
Authors: Belyaeva Irina I. , Subbotina Anna G. , Eremenko Ivan I. , Tarasov Vadim V. , Chubarev Vladimir N. , Schiöth Helgi B. , Mwinyi Jessica
Published: April 2023

Primary headache disorders, such as migraine, tension-type headache (TTH), and cluster headache, belong to the most common neurological disorders affecting a high percentage of people worldwide. Headache induces a high burden for the affected individuals on the personal level, with a strong impact on life quality, daily life management, and causes immense costs for the healthcare systems. Although a relatively broad spectrum of different pharmacological classes for the treatment of headache disorders are available, treatment effectiveness is often limited by high variances in therapy responses. Genetic variants can influence the individual treatment success by influencing pharmacokinetics or pharmacodynamics of the therapeutic as investigated in the research field of pharmacogenetics. This review summarizes the current knowledge on important primary headache disorders, including migraine, TTH, and cluster headache. We also summarize current acute and preventive treatment options for the three headache disorders based on drug classes and compounds taking important therapy guidelines into consideration. Importantly, the work summarizes and discusses the role of genetic polymorphisms regarding their impact on metabolism safety and the effect of therapeutics that are used to treat migraine, cluster headache, and TTH exploring drug classes such as nonsteroidal anti-inflammatory drugs, triptans, antidepressants, anticonvulsants, calcium channel blockers, drugs with effect on the renin–angiotensin system, and novel headache therapeutics such as ditans, anti-calcitonin-gene-related peptide antibodies, and gepants. Genetic variants in important phase I-, II-, and III-associated genes such as cytochrome P450 genes, UGT genes, and different transporter genes are scrutinized as well as variants in genes important for pharmacodynamics and several functions outside the pharmacokinetic and pharmacodynamic spectrum. Finally, the article evaluates the potential and limitations of pharmacogenetic approaches for individual therapy adjustments in headache disorders.
Simultaneous determination of multiple components in rat plasma by UHPLC-sMRM for pharmacokinetic studies after oral administration of Qingjin Yiqi Granules
Authors: Yang Xiaohua , Chen Shujing , Du Kunze , Shang Ye , Fang Shiming , Li Jin , Zhang Han , Chang Yanxu
Published: April 2023

As a Traditional Chinese Medicine prescription, Qingjin Yiqi Granules (QJYQ) provides an effective treatment for patients recovering from COVID-19. However, the pharmacokinetics characteristics of the main components of QJYQ in vivo are still unknown. An efficacious ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous determination of 33 components in rat plasma after oral administration of QJYQ. The plasma samples were precipitated with 400 µL methanol/acetonitrile (1/1, v/v) and analyzed in scheduled multiple reaction monitoring mode. The linear relationship of the 33 components was good (r > 0.9928). The lower limit of quantification for 33 components ranged from 0.4–60.5 ng/mL. The average recoveries and matrix effects of the analytes ranged from 72.9% to 115.0% with RSD of 1.4%–15.0%. All inter-day and intra-day RSDs were within 15.0%. After oral administration (3.15 g/kg), the validated approach was effectively applied to the pharmacokinetics of main components of QJYQ. Finally, fifteen main constituents of QJYQ with large plasma exposure were obtained, including baicalin, wogonoside, wogonin, apigenin-7-O-glucuronide, verbenalin, isoferulic acid, hesperidin, liquiritin, harpagide, protocatechuic acid, p-Coumaric acid, ferulic acid, sinapic acid, liquiritin apioside and glycyrrhizic acid. The present research lays a foundation for clarifying the therapeutic material basis of QJYQ and provides a reference for further scientific research and clinical application of QJYQ.
Gut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke
Authors: Gao Lin , Xia Xiuwen , Shuai Yinqi , Zhang Hong , Jin Wei , Zhang Xiaoyun , Zhang Yi
Published: April 2023

Acute ischemic stroke (AIS) is one of the leading diseases causing death and disability worldwide, and treatment options remain very limited. Traditional Chinese Medicine (TCM) has been used for thousands of years to treat ischemic stroke and has been proven to have significant efficacy, but its mechanism of action is still unclear. As research related to the brain-gut-microbe axis progresses, there is increasing evidence that the gut microbiota plays an important role during AIS. The interaction between TCM and the gut microbiota has been suggested as a possible key link to the therapeutic effects of TCM. We have compiled and reviewed recent studies on the relationship between AIS, TCM, and gut microbiota, with the expectation of providing more ideas to elucidate the mechanism of action of TCM in the treatment of AIS.
Red Blood Cell Abnormalities as the Mirror of SARS-CoV-2 Disease Severity: A Pilot Study
Authors: Bouchla Anthi , Kriebardis Anastasios G. , Georgatzakou Hara T. , Fortis Sotirios P. , Thomopoulos Thomas P. , Lekkakou Leoni , Markakis Konstantinos , Gkotzias Dimitrios , Panagiotou Aikaterini , Papageorgiou Effie G. , Pouliakis Abraham , Stamoulis Konstantinos E. , Papageorgiou Sotirios G. , Pappa Vasiliki , Valsami Serena
Published: April 2023

Graphical Abstract

SARS-CoV-2 infection has significant effects on red blood cells that seems to be associated with disease severity in these patients.(A)Non-Intensive care unit hospitalized patients due to severe COVID-19 disease were included in this study (n= 36).(B)The control group included healthy subjects without renal or hepatic impairment, no diagnosis of anemia or myeloid malignancy, and no blood transfusion over the past 3 months (n= 18).(C)Demographic data, clinical, laboratory and chest Computed Tomography (CT) findings at time of admission were recorded. Hematological tests, standard biochemical analysis of serum components were performed both in the patient and in the control group and coagulation analysis were evaluated in the patient group. A peripheral blood smear examination was also performed in all patients and control samples.(D)Plasma free hemoglobin and red blood cell (RBC) osmotic fragility and free hemoglobin (Free-Hb) after mechanical stress (MECH) by mechanical hemolysis were assesed in both patients and controls. Intracellular (i) calcium (iCa2 +) levels, RBCs phosphatidylserine exposure (PS), RBC membrane-bound immunoglobulins G (IgGs), and activate RBC caspase-3 levels as cell clearance and apoptotic markers were measured by flow cytometry. A spectrophotometric assay was used to quantify the activity of G6PD enzyme. Intracellular RBC reactive oxidative species (iROS) were assesed in both patients and controls.(E)Elevated hemolysis markers (Free-Hb) and Lactate Dehydrogenase (LDH) were observed in patients compared to the control group. Patients’ RBCs were more vulnerable to mechanical stress, and exhibited significantly elevated apoptotic markers (iCa2 + and RBC-PS+). Erythrocyte iROS levels were significantly lower in the patients’ group compared to healthy controls. This finding possibly correlates with the increased G6PDH activity levels in this group, suggesting a compensatory mechanism against the virus.(F)Patients’ D-Dimers correlated with RBC-PS +, implying a possible contribution of the erythrocytes in the thrombotic diathesis associated with the SARS-CoV-2 disease.(G)Free-Hb levels correlated with the extend of pulmonary infiltrates on chest CT in COVID-19 patients. RBC-IgGs+ correlated with the severity of pulmonary CT imaging features as well as the abnormality of lung function, expressed by the PO2/FiO 2 ratio. This finding suggests that hypoxia may lead to RBC senescence.
The sex effects on changes in jump performance following an isometric back squat conditioning activity in trained adults
Authors: Koźlenia Dawid , Domaradzki Jarosław
Published: April 2023

There are limited data concerning the disparity between males and females in post-activation performance enhancement (PAPE) based on isometry. Therefore, this study aimed to establish if sex differences exist in the PAPE effect on jump height. The study included 30 males and 15 females aged between 19 and 25, with relative strength in the back squat of at least 110% of body weight and a minimum of 3 years of resistance training experience. A baseline countermovement jump (CMJ) was performed, and the PAPE protocol, which involved three 4-s sets of isometric full-back squats with a 1-min rest interval, was introduced. Five CMJs were performed over the following 9 minutes in 2 minutes rest intervals. Changes (Δ) towards the baseline and each jump height results were calculated and analyzed in the absolute (cm) and relative (%) approach. The repeated measures ANOVA with sex as between-groups effect and time of the changes as within-group effect were conducted. Results showed statistically significant interaction (sex×time) in absolute changes (Δ cm) (F = 2.50, η2 = 0.05, p = 0.0447), which indicated that the sex effect has changed over time. Post-hoc test showed that during the first 3 minutes, men and women benefited equally, but in the fifth and seventh minutes, the observed changes were greater in men, thus close to significance (p = 0.0797, p = 0.0786), and in the last minute, the difference was statistically significant (p = 0.0309). Also, a statistically significant interaction effect was observed for relative changes (Δ %) (F = 4.22, η2 = 0.09, p = 0.0027). At the beginning (the first and third minutes), changes in females were greater than in males, but the differences were insignificant. However, after 5 minutes, the decrease in females was observed with statistically significant differences in the last minute compared to males (p = 0.0391). Chi-Squared analysis indicated that the time to peak performance was insignificant (χ2 = 7.45, p = 0.1140) in both sexes. The introduced PAPE protocol based on isometry improved jump height in both sexes, with performance enhancement recorded in the third-minute post-activation. However, performance decreased in females over the next 6 minutes, while it was maintained in the male group. Despite the generally positive short-term effects of the protocol on females, the usefulness of the protocol is limited.