bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular mechanisms of mitochondria-mediated ferroptosis: a potential target for antimalarial interventions
Authors: Adegboro Adegbolagun Grace , Afolabi Israel Sunmola
Published: April 2024

Ferroptosis is an iron-dependent form of regulated cell death characterized by glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) inactivation, and the build-up of lipotoxic reactive species. Ferroptosis-targeted induction is a promising therapeutic approach for addressing antimalarial drug resistance. In addition to being the primary source of intracellular energy supply and reactive oxygen species (ROS) generation, mitochondria actively participate in diverse forms of regulated cell death, including ferroptosis. Altered mitochondrial morphology and functionality are attributed to ferroptosis. Diverse mitochondria-related proteins and metabolic activities have been implicated in fine-tuning the action of ferroptosis inducers. Herein, we review recent progress in this evolving field, elucidating the numerous mechanisms by which mitochondria regulate ferroptosis and giving an insight into the role of the organelle in ferroptosis. Additionally, we present an overview of how mitochondria contribute to ferroptosis in malaria. Furthermore, we attempt to shed light on an inclusive perspective on how targeting malaria parasites’ mitochondrion and attacking redox homeostasis is anticipated to induce ferroptosis-mediated antiparasitic effects.
Chitosan nanoparticle applications in dentistry: a sustainable biopolymer
Authors: Mascarenhas Roma , Hegde Shreya , Manaktala Nidhi
Published: April 2024

The epoch of Nano-biomaterials and their application in the field of medicine and dentistry has been long-lived. The application of nanotechnology is extensively used in diagnosis and treatment aspects of oral diseases. The nanomaterials and its structures are being widely involved in the production of medicines and drugs used for the treatment of oral diseases like periodontitis, oral carcinoma, etc. and helps in maintaining the longevity of oral health. Chitosan is a naturally occurring biopolymer derived from chitin which is seen commonly in arthropods. Chitosan nanoparticles are the latest in the trend of nanoparticles used in dentistry and are becoming the most wanted biopolymer for use toward therapeutic interventions. Literature search has also shown that chitosan nanoparticles have anti-tumor effects. This review highlights the various aspects of chitosan nanoparticles and their implications in dentistry.
Oral-to-rectum microbial transmission in orthopedic patients without a history of intestinal disorders
Authors: Lin Ge , Kageyama Shinya , Maeda Aiko , Sakamoto Eiji , Ma Jiale , Asakawa Mikari , Furuta Michiko , Yamashita Yoshihisa , Takeshita Toru
Published: April 2024

The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%–9.37% of the rectal microbiota. Particularly, Streptococcus salivarius, Fusobacterium nucleatum, and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis, formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota.
Microscopic pore structure characteristics and controlling factors of marine shale: a case study of Lower Cambrian shales in the Southeastern Guizhou, Upper Yangtze Platform, South China
Authors: Wang Ruyue , Liu Yuejiao , Li Zhi , Wang Dahai , Wang Guanping , Lai Fuqiang , Li Zhihao , He Jianhua
Published: April 2024

A systematic study of the pore structure characteristics of Lower Cambrian shales in the southeastern Upper Yangtze Platform, was conducted using organic geochemistry, mineralogy, nitrogen adsorption, physical property analysis, and scanning electron microscopy. The results indicate that: 1) The Total organic carbon (TOC) content shows a strong correlation with quartz and clay minerals. Shales with low TOC content and rich in clay minerals primarily exhibit slit-shaped and narrow slit-like inter-clay particle pores with pore size distribution is dominated by mesopores and macropores. Shales with high TOC content predominantly feature narrow slit-like and ink bottle-shaped pores with pore size distribution dominated by micropores and mesopores. 2) Shale pore structures vary significantly under different gas content and preservation conditions. Shales under favorable preservation conditions exhibit a relatively “high porosity, low permeability, and high gas content” pattern, with well-developed organic pores and a strong pore-permeability correlation. In contrast, shales under unfavorable preservation conditions appear dense, with excessively developed fractures increasing both average pore size and local permeability. The pore-permeability correlation is weak, presenting a relatively “low porosity, high permeability, and low gas content” pattern. 3) TOC content plays a crucial role in controlling pore structure, showing overall positive correlations with pore volume, specific surface area, and porosity, and negative correlations with pore size. High TOC content enhances shale plasticity, resulting in lower pore diameters. Factors such as compaction and unfavorable preservation conditions lead to the shrinkage, collapse, and closure of some narrow pore throats, negatively impacting pore volume, specific surface area, brittleness, and fractal dimension, exhibiting a negative correlation with TOC content. 4) The pore structure of Lower Cambrian shales is complex, with fractal dimensions D1 and D2 exhibiting negative correlations with average pore size and positive correlations with TOC, specific surface area, and total pore volume. A high D1 value indicates well-preserved nanoscale pore surface structures with low complexity, suggesting minimal alteration by external fluids and better shale gas preservation. D1 serves as an indicator for shale gas content and preservation conditions. D2 shows better correlations with various pore structure parameters, making it suitable for characterizing pore structures.
Analysis of combined series of hydrological angular momentum developed based on climate models
Authors: Nastula Jolanta , Śliwińska-Bronowicz Justyna , Wińska Małgorzata , Kur Tomasz
Published: April 2024

Mass changes in the hydrosphere represent an important contributor to polar motion (PM) variations, especially at seasonal time scales (i.e., annual and semiannual). Although well studied, hydrological angular momentum (HAM) remains a major source of uncertainty in estimating PM excitation. In this work, we use a large number of climate models from the sixth phase of the Coupled Model Intercomparison Project (CMIP6) to determine HAM series both from individual models and their combination, formed with a multi-model mean, a weighted mean, and a three-cornered hat (TCH) method. The CMIP6-based HAM series are analysed in several spectral bands and evaluated with a reference hydrological signal in geodetically observed PM excitation (GAO). HAM determined from CMIP6 were also compared to HAM calculated from Gravity Recovery and Climate Experiment (GRACE) measurements. We find that while climate models do not allow for reliable estimation of non-seasonal changes in HAM, they can help interpret seasonal variability. For annual prograde and semiannual retrograde oscillations, several combined CMIP6-based series exhibit higher amplitude and phase consistency with GAO than the corresponding series computed from GRACE data. Whether one uses a simple average of the models, a weighted average, or a combination of models from the TCH method has little impact on the resulting HAM series and their level of agreement with GAO. Our study advances the understanding of hydrological signal in Earth’s rotation at seasonal time scales.
Numerical study of the impact of stress concentration on shale gas production
Authors: Peng Yan , Wang Xiaohan , Sheng Liji
Published: April 2024

Predicting the production amounts has great significance for exploitation of oil and gas resources. The flow–geomechanical coupling effect plays an important role in predicting production. Shale rocks and the stress-dependent permeability model are critical for representing this coupling effect. The pore network of shale rock is not abundant like that of coal rock, and the matrix blocks of shale rock are not completely separated by the pore network. There is stress concentration around the pores when shale rock is deformed. Based on previous studies, the stress-dependent permeability model considering the impact of stress concentration is used in this study to build a numerical simulation model for flow–geomechanical coupling in a shale gas reservoir and validation using field data. Sensitivity studies are conducted to discuss the difference in production prediction between the new and common models. The main conclusions of this study are as follows: 1) The new model can fit both the field and experimental data well; the average error in daily production rate between the numerical solution and field data is 8%, which indicates that the new model can be used to predict shale gas production. 2) Under the geomechanical condition of a real reservoir, the difference in predicted production between models with and without stress concentration can be large and increase with the ratio of a to b. If this ratio is less than 50, the impact of stress concentration is not significant. Otherwise, the impact of stress concentration on production increases sharply and can exceed 20%. 3) The adsorption-induced strain enhances the impact of stress concentration on production. When the Langmuir pressure exceeds 1 MPa and Langmuir strain exceeds 0.01, the impact magnitude of stress concentration can exceed 10%.
The academic task performance scale: psychometric properties, and measurement invariance across ages, genders and nations
Authors: van Zyl Llewellyn Ellardus , Klibert Jeff , Shankland Rebecca , Stavros Jacqueline , Cole Matthew , Verger Nicolas B. , Rothmann Sebastiaan , Cho Vincent , Feng Katherine , See-To Eric W. K. , Roll Lara C. , Ghosh Anindita , Arijs Diane , Glinska-Neweś Aldona
Published: April 2024

Academic task performance (TP) refers to the proficiency with which students perform in academic tasks through making the right choices and completing core tasks central to their academic studies, on time and to specification. We adapted Koopmans et al.’s task performance scale (TPS) for use within tertiary education and investigated its psychometric properties, internal consistency and measurement invariance across age, gender and national groups in university students (n = 3,265). The results showed that a hierarchical ESEM model with one higher-order task performance factor consisting of time management and task efficiency fitted the data best. The TPS exhibited full measurement invariance across gender and age groups, implying that the latent mean scores can be used to determine differences. However, invariance could only partially be established for national cohorts, implying that cross-national comparisons may not be possible. These findings offer preliminary support for the TPS as a valid instrument for gauging students’ academic task performance.
Flexible assessments as a tool to improve student motivation: an explorative study on student motivation for flexible assessments
Authors: Kessels Giel , Xu Kate , Dirkx Kim , Martens Rob
Published: April 2024

Introduction

This study focuses on what choices in assessments students want to make in order to enhance their motivation. A flexible assessment can enhance students’ perceived autonomy and thereby contribute to more intrinsic motivation for working on these assessment tasks. Autonomy is more than offering choices, rather it is about the autonomy that students actually experience. An increase of autonomy and motivation leads to more fun in learning and deeper learning. Providing choices during assessment -also referred to as flexible assessments- in order to enhance students’ motivation for working on assessment tasks has not been researched extensively. Research on the topic of flexible assessments in order to enhance student motivation is valuable because motivation is the start for learning and assessments can serve as a starting point for learning.

Methods

The study took place in the context of Vocational Education and Training (VET) and consists of two approaches. A cross-sectional survey study to find out on what assessment characteristics students prefer to have choice on. Focus group interviews are used to gain more understanding on how such assessment choices should be designed according to the interviewed students.

Results and discussion

The participated students preferred to make choices in the moment of assessment, in the number of attempts and in the assessment form. The interviewed students suggested an increase in number of choice options and ownership in choice making decisions during their study. They would like to be coached by their teachers in the decision-making process and, as their study progresses, the guidance of their teacher should decrease. Giving students choice in assessment in order to support their perceived autonomy and thereby contribute to their intrinsic motivation is quite unanimously perceived as positive.
Optimal scheduling of integrated energy systems with a ladder-type carbon trading mechanism and demand response
Authors: Shi Linjun , Liang Changyu , Zhou Jianhua , Li Yang , Liu Jian , Wu Feng
Published: April 2024

Introduction: To achieve the “dual carbon” goal, the integrated energy system (IES) needs to take into account both economic and low-carbon requirements while meeting the growing energy demand.

Methods: Therefore, an optimal scheduling model for low-carbon economic operation is proposed. Firstly, a more accurate carbon emission model is used to consider the actual carbon emission of gas load, to improve the original carbon emission model. A ladder-type carbon trading mechanism is introduced to further constrain the carbon emission of IES. Then, the demand-side response model is proposed, which uses the time-of-use price and mutual substitution of electricity, heat, and gas loads to curtail, time-shift, and substitute the load. Finally, an optimal scheduling model with minimum energy purchase cost, wind and photovoltaic curtailment cost, demand response cost, and carbon emission cost is constructed, which is solved by the GUROBI solver.

Results: Through comparative simulation analysis of 6 cases, the results show that the objective function considers the traditional carbon trading cost to reduce carbon emission by about 19.3% compared with the case without considering. After adopting the ladder-type carbon trading mechanism, the carbon emission of IES can be further limited by about 0.35%, and the appropriate carbon trading base price is explored. In addition, after the demand response, the energy purchase cost, carbon trading cost, and carbon emission of IES are reduced by about 3.4%, 18.5%, and 36.2%, respectively, compared with those before the demand response. The simulation results verify the effectiveness of the proposed model.
Effects of aquifer size and formation fracture pressure on CO2 geological storage capacity
Authors: Jung Seungpil , Lee Kyungbook
Published: April 2024

Introduction: Carbon capture and storage (CCS) is important for achieving net-zero carbon emissions. However, although the current geological storage capacity stands at approximately 3,000 Gt-CO2, the formation pressure increases with CO2 injection, imposing severe constraints on capacity from a geomechanical perspective. This study numerically examined nine cases (combinations of three fracture pressures and three aquifer radius factors) through sensitivity analysis to quantify the effects of these parameters on CO2 injection mass and storage capacity.

Methods: The CO2 injection mass was determined as the cumulative CO2 injected until the formation pressure reached a specified fracture pressure. Storage capacity was defined as the amount of CO2 enclosed within the reservoir based on a fill-and-spill analysis encompassing 200 years after the start of injection (2230).

Results: Based on the sensitivity analysis, the aquifer radius had a greater impact on the CO2 injection mass and storage capacity than the fracture pressure. A sufficiently high aquifer radius factor can compensate for the capacity limitations imposed by a low fracture pressure. For the lowest fracture pressure (20.95 MPa), considering a safety factor of 0.8, the CO2 injection mass increased approximately 5.5 times, from 3.2 to 17.6 Mt-CO2, depending on the aquifer radius factor ranging from 2 to 7.

Discussion: Therefore, geological sites with high aquifer radius factors and low fracture pressures were preferred over those with low aquifer radius factors and high fracture pressures. Nevertheless, when considering space-limited capacity, storage efficiency, defined as the ratio of injected to stored CO2, tends to be higher (approximately 80%) when both parameters are low. The scenario featuring the highest aquifer radius factor and fracture pressure reached an injection mass of 68.9 Mt-CO2. However, the storage efficiency was only 23% due to space constraints. This study provides key insights into two pivotal parameters from pressure- and space-limited perspectives, which must be collectively considered to reliably evaluate CCS projects.
Hydroxychloroquine-induced hyperpigmentation of the skin and bull’s-eye maculopathy in rheumatic patients: a case report and literature review
Authors: Peng Ji-peng , Yang Xiao-yu , Luo Feng , Yuan Xue-mei , Xiong Hong , Ma Wu-kai , Yao Xue-ming
Published: April 2024

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull’s-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull’s-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient ‘s skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull’s-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull’s-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.
Targeting PD-1/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges
Authors: Javed Sadique A. , Najmi Asim , Ahsan Waquar , Zoghebi Khalid
Published: April 2024

The programmed death-1 receptor (PD-1) acts as a T-cell brake, and its interaction with ligand-1 (PD-L-1) interferes with signal transduction of the T-cell receptor. This leads to suppression of T-cell survival, proliferation, and activity in the tumor microenvironment resulting in compromised anticancer immunity. PD-1/PD-L-1 interaction blockade shown remarkable clinical success in various cancer immunotherapies. To date, most PD-1/PD-L-1 blockers approved for clinical use are monoclonal antibodies (mAbs); however, their therapeutic use are limited owing to poor clinical responses in a proportion of patients. mAbs also displayed low tumor penetration, steep production costs, and incidences of immune-related side effects. This strongly indicates the importance of developing novel inhibitors as cancer immunotherapeutic agents. Recently, advancements in the small molecule-based inhibitors (SMIs) that directly block the PD-1/PD-L-1 axis gained attention from the scientific community involved in cancer research. SMIs demonstrated certain advantages over mAbs, including longer half-lives, low cost, greater cell penetration, and possibility of oral administration. Currently, several SMIs are in development pipeline as potential therapeutics for cancer immunotherapy. To develop new SMIs, a wide range of structural scaffolds have been explored with excellent outcomes; biphenyl-based scaffolds are most studied. In this review, we analyzed the development of mAbs and SMIs targeting PD-1/PD-L-1 axis for cancer treatment. Altogether, the present review delves into the problems related to mAbs use and a detailed discussion on the development and current status of SMIs. This article may provide a comprehensive guide to medicinal chemists regarding the potential structural scaffolds required for PD-1/PD-L-1 interaction inhibition.
Distribution of polysaccharidic and proteinaceous gel−like particles in three cyclonic eddies in the Eastern Tropical North Atlantic
Authors: Devresse Quentin , Becker Kevin W. , Engel Anja
Published: April 2024

Transparent exopolymer particles (TEP) and Coomassie stainable particles (CSP), two prominent classes of gel−like particles in the ocean primarily produced by phytoplankton, play crucial roles in ecological and biogeochemical processes, influencing microbial nutrition, growth, and particle aggregation. The distribution of these particles is intricately linked to the spatiotemporal dynamics of phytoplankton. Mesoscale cyclonic eddies (CEs) are known to stimulate phytoplankton growth and influence particle transport, but their effects on TEP and CSP remain to be determined. In the Eastern Tropical North Atlantic (ETNA), we examined three CEs: one off the Mauritanian coast during summer (Mau), one offshore during winter (Sal), and another near Brava island during winter. Mau and Brava CEs were in their intensification/maturity phase, while the Sal CE was in its decay phase. Both TEP and CSP concentrations correlated with primary productivity, but TEP increased with chlorophyll−a concentration, whereas elevated CSP coincided also with the highest abundance of pico−nanophytoplankton (<20 µm), mainly Synechococcus. Both gels exhibited a positive correlation with bacterial biomass production, indicating their consumption by heterotrophic bacteria. TEP total area in the epipelagic waters of all CEs (Mau, Brava, and Sal) was elevated compared to surrounding waters, with on average 4, 2.5, and 1.6−fold higher values, respectively. However, no significant difference in TEP size distribution was observed within any CEs and their surroundings. Similarly, CSP total area increased in the epipelagic waters of Mau and Brava CEs, with on average 5 and 2.4−fold higher values, respectively, compared to surrounding waters. CSP particles were notably larger in these two eddies, while the Sal CE showed no significant difference from surrounding waters in CSP abundance and size. Overall, TEP and CSP exhibited distinct responses to CEs, with increased concentrations during their intensification/maturation stage and remineralization dominating during their decaying stage.
Precision isolation and cultivation of single cells by vortex and flat-top laser ejection
Authors: Chen Fuyuan , Liu Kunxiang , Shang Lindong , Wang Yuntong , Tang Xusheng , Liang Peng , Li Bei
Published: April 2024

Single-cell isolation stands as a critical step in single-cell studies, and single-cell ejection technology based on laser induced forward transfer technology (LIFT) is considered one of the most promising methods in this regard for its ability of visible isolating single cell from complex samples. In this study, we improve the LIFT technology and introduce optical vortex laser-induced forward transfer (OV-LIFT) and flat-top laser-induced forward transfer (FT-LIFT) by utilizing spatial light modulator (SLM), aiming to enhance the precision of single-cell sorting and the cell’s viability after ejection. Experimental results demonstrate that applying vortex and flat-top beams during the sorting and collection process enables precise retrieval of single cells within diameter ranges of 50 μm and 100 μm, respectively. The recovery rates of Saccharomyces cerevisiae and Escherichia coli DH5α single cell ejected by vortex beam are 89 and 78%, by flat-top beam are 85 and 57%. When employing Gaussian beam sorting, the receiving range extends to 400 μm, with cultivation success rates of S. cerevisiae and E. coli DH5α single cell are 48 and 19%, respectively. This marks the first application of different mode beams in the ejection and cultivation of single cells, providing a novel and effective approach for the precise isolation and improving the viability of single cells.
Interplay of soil characteristics and arbuscular mycorrhizal fungi diversity in alpine wetland restoration and carbon stabilization
Authors: Tang Hao , Li Qian , Bao Qian , Tang Biao , Li Kun , Ding Yang , Luo Xiaojuan , Zeng Qiushu , Liu Size , Shu Xiangyang , Liu Weijia , Du Lei
Published: April 2024

Alpine wetlands are critical ecosystems for global carbon (C) cycling and climate change mitigation. Ecological restoration projects for alpine grazing wetlands are urgently needed, especially due to their critical role as carbon (C) sinks. However, the fate of the C pool in alpine wetlands after restoration from grazing remains unclear. In this study, soil samples from both grazed and restored wetlands in Zoige (near Hongyuan County, Sichuan Province, China) were collected to analyze soil organic carbon (SOC) fractions, arbuscular mycorrhizal fungi (AMF), soil properties, and plant biomass. Moreover, the Tea Bag Index (TBI) was applied to assess the initial decomposition rate (k) and stabilization factor (S), providing a novel perspective on SOC dynamics. The results of this research revealed that the mineral-associated organic carbon (MAOC) was 1.40 times higher in restored sites compared to grazed sites, although no significant difference in particulate organic carbon (POC) was detected between the two site types. Furthermore, the increased MAOC after restoration exhibited a significant positive correlation with various parameters including S, C and N content, aboveground biomass, WSOC, AMF diversity, and NH4+. This indicates that restoration significantly increases plant primary production, litter turnover, soil characteristics, and AMF diversity, thereby enhancing the C stabilization capacity of alpine wetland soils.
Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories
Authors: Frigon Eve-Marie , Gérin-Lajoie Amy , Dadar Mahsa , Boire Denis , Maranzano Josefina
Published: April 2024

Background

Brain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous work in mice showed that two gross-anatomy laboratory solutions, a saturated-salt-solution (SSS) and an alcohol-formaldehyde-solution (AFS), preserve antigenicity of the main cellular markers (neurons, astrocytes, microglia, and myelin). Our goal is now to compare the quality of histology and antigenicity preservation of human brains fixed with NBF by immersion (practice of brain banks) vs. those fixed with a SSS and an AFS by whole body perfusion, practice of gross-anatomy laboratories.

Methods

We used a convenience sample of 42 brains (31 males, 11 females; 25–90 years old) fixed with NBF (N = 12), SSS (N = 13), and AFS (N = 17). One cm3 tissue blocks were cut, cryoprotected, frozen and sliced into 40 μm sections. The four cell populations were labeled using immunohistochemistry (Neurons = neuronal-nuclei = NeuN, astrocytes = glial-fibrillary-acidic-protein = GFAP, microglia = ionized-calcium-binding-adaptor-molecule1 = Iba1 and oligodendrocytes = myelin-proteolipid-protein = PLP). We qualitatively assessed antigenicity and cell distribution, and compared the ease of manipulation of the sections, the microscopic tissue quality, and the quality of common histochemical stains (e.g., Cresyl violet, Luxol fast blue, etc.) across solutions.

Results

Sections of SSS-fixed brains were more difficult to manipulate and showed poorer tissue quality than those from brains fixed with the other solutions. The four antigens were preserved, and cell labeling was more often homogeneous in AFS-fixed specimens. NeuN and GFAP were not always present in NBF and SSS samples. Some antigens were heterogeneously distributed in some specimens, independently of the fixative, but an antigen retrieval protocol successfully recovered them. Finally, the histochemical stains were of sufficient quality regardless of the fixative, although neurons were more often paler in SSS-fixed specimens.

Conclusion

Antigenicity was preserved in human brains fixed with solutions used in human gross-anatomy (albeit the poorer quality of SSS-fixed specimens). For some specific variables, histology quality was superior in AFS-fixed brains. Furthermore, we show the feasibility of frequently used histochemical stains. These results are promising for neuroscientists interested in using brain specimens from anatomy laboratories.
Neuronal, affective, and sensory correlates of targeted helping behavior in male and female Sprague Dawley rats
Authors: Cox Stewart S. , Brown Brogan J. , Wood Samuel K. , Brown Samantha J. , Kearns Angela M. , Reichel Carmela M.
Published: April 2024

Introduction

Empathic behaviors are driven by the ability to understand the emotional states of others along with the motivation to improve it. Evidence points towards forms of empathy, like targeted helping, in many species including rats. There are several variables that may modulate targeted helping, including sex, sensory modalities, and activity of multiple neural substrates.

Methods

Using a model of social contact-independent targeted helping, we first tested whether sex differences exist in helping behavior. Next, we explored sex differences in sensory and affective signaling, including direct visualization and an analysis of ultrasonic vocalizations made between animal pairs. Finally, we examined the neural activity in males and females of multiple regions of interest across time. Here, we aim to examine any behavioral differences in our lab’s social contact independent targeted helping task between males and females.

Results and Discussion

These findings are the first to intimate that, like other prosocial behaviors, males and females may exhibit similar social-independent targeted helping behavior, but the underlying sensory communication in males and females may differ. In addition, this is the first set of experiments that explore the neural correlates of social-independent targeted helping in both males and females. These results lay the groundwork for future studies to explore the similarities and differences that drive targeted helping in both sexes.
People with newly diagnosed multiple sclerosis benefit from a complex preventative intervention—a single group prospective study with follow up
Authors: Hrušková Natália , Berchová Bímová Kateřina , Davies Smith Angela , Škodová Tereza , Bičíková Marie , Kolátorová Lucie , Štětkářová Ivana , Brožek Ľuba , Javůrková Alena , Angelová Gabriela , Řasová Kamila
Published: April 2024

Background

Newly diagnosed people with multiple sclerosis frequently report fatigue, pain, depression and anxiety. Preventative programmes may be beneficial, but there is limited evidence of their effectiveness, especially long-term follow-up.

Methods

The programme consisted of 6-month face to face intervention (an introductory workshop, psychology-led group sessions and individual physical therapy) followed by 6-month self-guided therapy. Outcome measures were taken at baseline, 6 and 12 months. Primary outcomes measures were self-report questionnaires for fatigue, satisfaction with life and disease acceptance. Secondary outcomes were spirometry, spiroergometric parameters and neuroactive steroid levels.

Results

From 22 participants enrolled, 17 completed the first 6 months and 13 the follow-up. Fatigue measured on the Fatigue scale for motor and cognitive functions decreased significantly at 6 months (p = 0.035) and at follow-up (p = 0.007). The Modified Fatigue Impact Scale (p = 0.035) and Satisfaction With Life Scale (p = 0.007) significantly increased at follow-up. Spirometry, spiroergometric parameters, steroid hormones and neuroactive steroids levels did not change significantly.

Conclusion

This programme reduces fatigue and improves satisfaction with life in this patient group with improvements sustained at 12 months. People who participated more frequently showed greater benefit.

Clinical rehabilitation impact

The paper describes the effects of a complex preventative intervention for people with newly diagnosed Multiple Sclerosis. The study found that this programme reduces fatigue and improves satisfaction with life with long-term benefit (at 12-month follow up). The individuals who participated less frequently experienced fewer benefits.
Modeling the volume of tissue activated in deep brain stimulation and its clinical influence: a review
Authors: Patrick Erin E. , Fleeting Chance R. , Patel Drashti R. , Casauay Jed T. , Patel Aashay , Shepherd Hunter , Wong Joshua K.
Published: April 2024

Deep brain stimulation (DBS) is a neuromodulatory therapy that has been FDA approved for the treatment of various disorders, including but not limited to, movement disorders (e.g., Parkinson’s disease and essential tremor), epilepsy, and obsessive-compulsive disorder. Computational methods for estimating the volume of tissue activated (VTA), coupled with brain imaging techniques, form the basis of models that are being generated from retrospective clinical studies for predicting DBS patient outcomes. For instance, VTA models are used to generate target-and network-based probabilistic stimulation maps that play a crucial role in predicting DBS treatment outcomes. This review defines the methods for calculation of tissue activation (or modulation) including ones that use heuristic and clinically derived estimates and more computationally involved ones that rely on finite-element methods and biophysical axon models. We define model parameters and provide a comparison of commercial, open-source, and academic simulation platforms available for integrated neuroimaging and neural activation prediction. In addition, we review clinical studies that use these modeling methods as a function of disease. By describing the tissue-activation modeling methods and highlighting their application in clinical studies, we provide the neural engineering and clinical neuromodulation communities with perspectives that may influence the adoption of modeling methods for future DBS studies.
Gabor filter-based statistical features for ADHD detection
Authors: Sathiya E. , Rao T. D. , Kumar T. Sunil
Published: April 2024

Attention deficit/hyperactivity disorder (ADHD) is a neuropsychological disorder that occurs in children and is characterized by inattention, impulsivity, and hyperactivity. Early and accurate diagnosis of ADHD is very important for effective intervention. The aim of this study is to develop a computer-aided approach to detecting ADHD using electroencephalogram (EEG) signals. Specifically, we explore a Gabor filter-based statistical features approach for the classification of EEG signals into ADHD and healthy control (HC). The EEG signal is processed by a bank of Gabor filters to obtain narrow-band signals. Subsequently, a set of statistical features is extracted. The computed features are then subjected to feature selection. Finally, the obtained feature vector is given to a classifier to detect ADHD and HC. Our approach achieves the highest classification accuracy of 96.4% on a publicly available dataset. Furthermore, our approach demonstrates better classification accuracy than the existing methods.
PLC-γ-Ca2+ pathway regulates axonal TrkB endocytosis and is required for long-distance propagation of BDNF signaling
Authors: Moya-Alvarado Guillermo , Valero-Peña Xavier , Aguirre-Soto Alejandro , Bustos Fernando J. , Lazo Oscar M. , Bronfman Francisca C.
Published: April 2024

Brain-derived neurotrophic factor (BDNF) and its tropomyosin receptor kinase B (TrkB) are important signaling proteins that regulate dendritic growth and maintenance in the central nervous system (CNS). After binding of BDNF, TrkB is endocytosed into endosomes and continues signaling within the cell soma, dendrites, and axon. In previous studies, we showed that BDNF signaling initiated in axons triggers long-distance signaling, inducing dendritic arborization in a CREB-dependent manner in cell bodies, processes that depend on axonal dynein and TrkB activities. The binding of BDNF to TrkB triggers the activation of different signaling pathways, including the ERK, PLC-γ and PI3K-mTOR pathways, to induce dendritic growth and synaptic plasticity. How TrkB downstream pathways regulate long-distance signaling is unclear. Here, we studied the role of PLC-γ-Ca2+ in BDNF-induced long-distance signaling using compartmentalized microfluidic cultures. We found that dendritic branching and CREB phosphorylation induced by axonal BDNF stimulation require the activation of PLC-γ in the axons of cortical neurons. Locally, in axons, BDNF increases PLC-γ phosphorylation and induces intracellular Ca2+ waves in a PLC-γ-dependent manner. In parallel, we observed that BDNF-containing signaling endosomes transport to the cell body was dependent on PLC-γ activity and intracellular Ca2+ stores. Furthermore, the activity of PLC-γ is required for BDNF-dependent TrkB endocytosis, suggesting a role for the TrkB/PLC-γ signaling pathway in axonal signaling endosome formation.
The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma
Authors: Lu Yan , Lin Bo , Li Mengsen
Published: April 2024

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.
A hepatic sparganosis misdiagnosed as intrahepatic mass-forming cholangiocarcinoma: a case report and literature review
Authors: Wang Yinjiao , Lou Yu , Chen Lang , Yang Xin , Cao Aihong , Du Peng
Published: April 2024

Hepatic sparganosis (HS) is extremely rare and has not been previously reported in Eastern China. We report the diagnosis and treatment of a patient with HS from Xuzhou City, Jiangsu Province, China. The patient was admitted due to an acute biliary tract infection, and the symptoms improved after treatment at the Gastroenterology Department. During an ultrasound examination on admission, an abnormal echo was incidentally discovered at the junction of the left and right lobes of the liver. Thereafter, upper abdominal computed tomography (CT) and magnetic resonance imaging (MRI) non-contrast and contrast-enhanced examinations, and serum tumor biomarker examination were completed. After a multidisciplinary treatment (MDT) discussion at the Department of Hepatobiliary Surgery, the patient was diagnosed with intrahepatic mass-type cholangiocarcinoma (IMCC) and surgery was recommended. The patient underwent surgical treatment, and postoperative pathology revealed HS. No signs of intrahepatic recurrence were observed during the 1-year follow-up period.
Case report: Robust response to sintilimab in advanced distal cholangiocarcinoma with PD-L1 expression and DNA damage repair
Authors: He Wenguang , Song Congcong , Ren Jiwei , Ji Xiao , Wang Xiuyan , Liu Lixia
Published: April 2024

Cholangiocarcinoma (CCA) is a highly heterogeneous tumor that occurs in the bile duct epithelium; adenosquamous carcinoma is a rare pathological subtype of CCA. The clinical treatment of patients with metastatic distal CCA poses significant challenges. We report a 53-year-old female diagnosed with a stage III adenosquamous carcinomas of distal CCA. Metastasis occurred 4 months postoperatively and she was diagnosed with stage IV disease. The patient was treated with Gemcitabine + Oxaliplatin (GEMOX) and Capecitabine + Oxaliplatin (CAPEOX), followed by sintilimab monotherapy. After two cycles of treatment, the patient achieved partial response (PR) and the lesion continued to shrink. After 37 months of follow-up, the patient’s liver metastasis had almost completely disappeared, and complete response (CR) was achieved. Moreover, she had more than 46 months of disease progression-free survival (PFS). Immunohistochemical testing showed high expression of PD-L1, and next-generation sequencing revealed the presence of mutations in DNA damage repair (DDR) pathway genes. To the best of our knowledge, this is the first reported case of the successful treatment of metastatic distal adenosquamous CCA with sintilimab alone. Remarkably, patients of CCA with high PD-L1 expression and DDR pathway gene mutations may benefit from sintilimab treatment.
Machine learning-based identification of a consensus immune-derived gene signature to improve head and neck squamous cell carcinoma therapy and outcome
Authors: Hu Xueying , Dong Haiqun , Qin Wen , Bin Ying , Huang Wenhua , Kang Min , Wang Rensheng
Published: April 2024

Background

Head and neck squamous cell carcinoma (HNSCC), an extremely aggressive tumor, is often associated with poor outcomes. The standard anatomy-based tumor–node–metastasis staging system does not satisfy the requirements for screening treatment-sensitive patients. Thus, an ideal biomarker leading to precise screening and treatment of HNSCC is urgently needed.

Methods

Ten machine learning algorithms—Lasso, Ridge, stepwise Cox, CoxBoost, elastic network (Enet), partial least squares regression for Cox (plsRcox), random survival forest (RSF), generalized boosted regression modelling (GBM), supervised principal components (SuperPC), and survival support vector machine (survival-SVM)—as well as 85 algorithm combinations were applied to construct and identify a consensus immune-derived gene signature (CIDGS).

Results

Based on the expression profiles of three cohorts comprising 719 patients with HNSCC, we identified 236 consensus prognostic genes, which were then filtered into a CIDGS, using the 10 machine learning algorithms and 85 algorithm combinations. The results of a study involving a training cohort, two testing cohorts, and a meta-cohort consistently demonstrated that CIDGS was capable of accurately predicting prognoses for HNSCC. Incorporation of several core clinical features and 51 previously reported signatures, enhanced the predictive capacity of the CIDGS to a level which was markedly superior to that of other signatures. Notably, patients with low CIDGS displayed fewer genomic alterations and higher immune cell infiltrate levels, as well as increased sensitivity to immunotherapy and other therapeutic agents, in addition to receiving better prognoses. The survival times of HNSCC patients with high CIDGS, in particular, were shorter. Moreover, CIDGS enabled accurate stratification of the response to immunotherapy and prognoses for bladder cancer. Niclosamide and ruxolitinib showed potential as therapeutic agents in HNSCC patients with high CIDGS.

Conclusion

CIDGS may be used for stratifying risks as well as for predicting the outcome of patients with HNSCC in a clinical setting.
Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy
Authors: Liu Fengzhao , Zhao Lijuan , Wu Tao , Yu Wenfei , Li Jixin , Wang Wenru , Huang Chengcheng , Diao Zhihao , Xu Yunsheng
Published: April 2024

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people’s health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic β-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.
Nanometer refractive index sensor based on water droplet cavity structure with rectangular short rod
Authors: Wang Jin , Yan Shubin , Liu Feng , Chang Shuwen , Cao Yuhao , Cui Yang , Liu Jilai , Zhang Yi , Ren Yifeng
Published: April 2024

In this paper, a novel nano sensor structure is proposed, which consists of a metal-insulator-metal waveguide (MIM) with rectangular baffles and a water droplet cavity with rectangular stubs (WDCRS). The WDCRS structure optimizes the sensitivity of a single water droplet cavity and makes the transmission curve clearer and smoother. The transmission characteristics of WDCRS structure were simulated using finite element method (FEM). The transmission characteristics of the exported structure were analyzed in detail. In addition, the influence of structural geometric parameters on sensing performance was also studied, and it was found that the size of the water droplet cavity is a key factor in improving sensitivity. When applied to a refractive index sensor, the structure achieves a sensitivity of up to 2,300 nm/RIU with a corresponding figure of merit (FOM) of 60.5. These works provide some ideas for the design of high-performance nanostructures and multiple Fano resonance excitation structures.