bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoplasmic reticulum stress in breast cancer: a predictive model for prognosis and therapy selection
Authors: Yang Bin , Wang Shu , Yang Yanfang , Li Xukui , Yu Fuxun , Wang Tao
Published: February 2024

Background

Breast cancer (BC) is a leading cause of mortality among women, underscoring the urgent need for improved therapeutic predictio. Developing a precise prognostic model is crucial. The role of Endoplasmic Reticulum Stress (ERS) in cancer suggests its potential as a critical factor in BC development and progression, highlighting the importance of precise prognostic models for tailored treatment strategies.

Methods

Through comprehensive analysis of ERS-related gene expression in BC, utilizing both single-cell and bulk sequencing data from varied BC subtypes, we identified eight key ERS-related genes. LASSO regression and machine learning techniques were employed to construct a prognostic model, validated across multiple datasets and compared with existing models for its predictive accuracy.

Results

The developed ERS-model categorizes BC patients into distinct risk groups with significant differences in clinical prognosis, confirmed by robust ROC, DCA, and KM analyses. The model forecasts survival rates with high precision, revealing distinct immune infiltration patterns and treatment responsiveness between risk groups. Notably, we discovered six druggable targets and validated Methotrexate and Gemcitabine as effective agents for high-risk BC treatment, based on their sensitivity profiles and potential for addressing the lack of active targets in BC.

Conclusion

Our study advances BC research by establishing a significant link between ERS and BC prognosis at both the molecular and cellular levels. By stratifying patients into risk-defined groups, we unveil disparities in immune cell infiltration and drug response, guiding personalized treatment. The identification of potential drug targets and therapeutic agents opens new avenues for targeted interventions, promising to enhance outcomes for high-risk BC patients and paving the way for personalized cancer therapy.
Functions of mucosal associated invariant T cells in eye diseases
Authors: Fukui Chihiro , Yamana Satoshi , Xue Yanqi , Shirane Mariko , Tsutsui Hiroki , Asahara Kenichiro , Yoshitomi Keiko , Ito Takako , Lestari Tantri , Hasegawa Eiichi , Yawata Nobuyo , Takeda Atsunobu , Sonoda Koh-Hei , Shibata Kensuke
Published: February 2024

Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye. The protective functions of MAIT cells are induced by T-cell receptor (TCR)-mediated activation. However, the underlying mechanisms remain unclear. Thus, this mini-review aims to discuss our findings and the complexity of MAIT cell-mediated immune regulation in the eye.
Insights into the heterogeneity of iNKT cells: tissue-resident and circulating subsets shaped by local microenvironmental cues
Authors: Cui Guangwei , Abe Shinya , Kato Ryoma , Ikuta Koichi
Published: February 2024

Invariant natural killer T (iNKT) cells are a distinct subpopulation of innate-like T lymphocytes. They are characterized by semi-invariant T cell receptors (TCRs) that recognize both self and foreign lipid antigens presented by CD1d, a non-polymorphic MHC class I-like molecule. iNKT cells play a critical role in stimulating innate and adaptive immune responses, providing an effective defense against infections and cancers, while also contributing to chronic inflammation. The functions of iNKT cells are specific to their location, ranging from lymphoid to non-lymphoid tissues, such as the thymus, lung, liver, intestine, and adipose tissue. This review aims to provide insights into the heterogeneity of development and function in iNKT cells. First, we will review the expression of master transcription factors that define subsets of iNKT cells and their production of effector molecules such as cytokines and granzymes. In this article, we describe the gene expression profiles contributing to the kinetics, distribution, and cytotoxicity of iNKT cells across different tissue types. We also review the impact of cytokine production in distinct immune microenvironments on iNKT cell heterogeneity, highlighting a recently identified circulating iNKT cell subset. Additionally, we explore the potential of exploiting iNKT cell heterogeneity to create potent immunotherapies for human cancers in the future.
Comprehensive bioinformatics analysis reveals the role of cuproptosis-related gene Ube2d3 in myocardial infarction
Authors: Yang Ming , Wang Yucheng , He Liming , Shi Xinxin , Huang Shuwei
Published: February 2024

Background

Myocardial infarction (MI) caused by severe coronary artery disease has high incidence and mortality rates, making its prevention and treatment a central and challenging aspect of clinical work for cardiovascular practitioners. Recently, researchers have turned their attention to a novel mechanism of cell death caused by Cu2+, cuproptosis.

Methods

This study integrated data from three MI-related bulk datasets downloaded from the Gene Expression Omnibus (GEO) database, and identified 16 differentially expressed genes (DEGs) related to cuproptosis by taking intersection of the 6378 DEGs obtained by differential analysis with 49 cuproptosis-related genes. Four hub genes, Dbt, Dlat, Ube2d1 and Ube2d3, were screened out through random forest analysis and Lasso analysis. In the disease group, Dbt, Dlat, and Ube2d1 showed low expression, while Ube2d3 exhibited high expression.

Results

Focusing on Ube2d3 for subsequent functional studies, we confirmed its high expression in the MI group through qRT-PCR and Western Blot detection after successful construction of a MI mouse model by left anterior descending (LAD) coronary artery ligation, and further clarified the correlation of cuproptosis with MI development by detecting the levels of cuproptosis-related proteins. Moreover, through in vitro experiments, Ube2d3 was confirmed to be highly expressed in oxygen-glucose deprivation (OGD)-treated cardiomyocytes AC16. In order to further clarify the role of Ube2d3, we knocked down Ube2d3 expression in OGD-treated AC16 cells, and confirmed Ube2d3’s promoting role in the hypoxia damage of AC16 cells by inducing cuproptosis, as evidenced by the detection of MTT, TUNEL, LDH release and cuproptosis-related proteins.

Conclusion

In summary, our findings indicate that Ube2d3 regulates cuproptosis to affect the progression of MI.
Prevalence and co-incidence of geriatric syndromes according to the ECOG performance status in older cancer patients
Authors: Topcu Atakan , Yasin Ayse Irem , Besiroglu Mehmet , Sucuoglu Isleyen Zehra , Alaca Topcu Zeynep , Simsek Melih , Turk Haci Mehmet , Seker Mesut , Soysal Pinar
Published: February 2024

Background

Geriatric syndromes may be more common in older cancer patients than in those without cancer. Geriatric syndromes can cause poor clinical outcomes. The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is often used as a clinically reported functional status score in oncology practice.

Methods

Our study was designed as a cross-sectional study and included 218 older cancer patients. This study aimed to determine the prevalence and relationship of geriatric syndromes according to the ECOG-PS in older cancer patients.

Results

The mean age of 218 participants was 73.0 ± 5.6 years, with 47.7% being women and 52.3% men in our study. ECOG-PS 0, 1, and 2 groups contained 51, 39, and 10% of the patients, respectively. The mean number of geriatric syndromes in the ECOG 0, 1, and 2 groups was 2.3 ± 2.2, 4.3 ± 2.4, and 5.7 ± 2.1, respectively (p < 0.001). After adjusting for age and sex, it was determined that dynapenia was 2.9 times, probable sarcopenia was 3.5 times, frailty was 4.2 times, depression was 2.6 times, malnutrition was 3.3 times, insomnia 2 was.2 times, falls was 2.5 times, and the risk of falling (TUG) was 2.4 times more likely in those with ECOG-PS 1 compared to those with ECOG-PS 0. In addition, it was found that dynapenia was 6 times, probable sarcopenia was 6.8 times, frailty was 10.8 times, depression was 3.3 times, malnutrition was 6.3 times, the risk of falling (Tinnetti Balance) was 28 times, and the risk of falling (TUG) was 13.6 times more likely in those with ECOG-PS 2 compared to those with ECOG-PS 0.

Conclusion

Our study found that the prevalence of geriatric syndromes increased as the ECOG-PS increased. Geriatric syndromes and their co-incidence were common in older cancer patients, even in normal performance status. Oncologists should incorporate geriatric syndromes into the decision-making process of cancer treatment to maximize the impact on clinical outcomes in older patients with cancer.
Decoding seasonal changes: soil parameters and microbial communities in tropical dry deciduous forests
Authors: Solanki Anjali Chandrol , Gurjar Narendra Singh , Sharma Satish , Wang Zhen , Kumar Ajay , Solanki Manoj Kumar , Kumar Divvela Praveen , Yadav Kajal , Kashyap Brijendra Kumar
Published: February 2024

In dry deciduous tropical forests, both seasons (winter and summer) offer habitats that are essential ecologically. How these seasonal changes affect soil properties and microbial communities is not yet fully understood. This study aimed to investigate the influence of seasonal fluctuations on soil characteristics and microbial populations. The soil moisture content dramatically increases in the summer. However, the soil pH only gradually shifts from acidic to slightly neutral. During the summer, electrical conductivity (EC) values range from 0.62 to 1.03 ds m-1, in contrast to their decline in the winter. The levels of soil macronutrients and micronutrients increase during the summer, as does the quantity of soil organic carbon (SOC). A two-way ANOVA analysis reveals limited impacts of seasonal fluctuations and specific geographic locations on the amounts of accessible nitrogen (N) and phosphorus (P). Moreover, dehydrogenase, nitrate reductase, and urease activities rise in the summer, while chitinase, protease, and acid phosphatase activities are more pronounced in the winter. The soil microbes were identified in both seasons through 16S rRNA and ITS (Internal Transcribed Spacer) gene sequencing. Results revealed Proteobacteria and Ascomycota as predominant bacterial and fungal phyla. However, Bacillus, Pseudomonas, and Burkholderia are dominant bacterial genera, and Aspergillus, Alternaria, and Trichoderma are dominant fungal genera in the forest soil samples. Dominant bacterial and fungal genera may play a role in essential ecosystem services such as soil health management and nutrient cycling. In both seasons, clear relationships exist between soil properties, including pH, moisture, iron (Fe), zinc (Zn), and microbial diversity. Enzymatic activities and microbial shift relate positively with soil parameters. This study highlights robust soil-microbial interactions that persist mainly in the top layers of tropical dry deciduous forests in the summer and winter seasons. It provides insights into the responses of soil-microbial communities to seasonal changes, advancing our understanding of ecosystem dynamics and biodiversity preservation.
Association between MTHFR C677T polymorphism and cognitive impairment in patients with cerebral small vessel disease: a cross-sectional study
Authors: Wang Qijin , Yuan Cuihua , Zheng Zhixiong , Chen Caihua , Zhan Xiao , Lin Xiaodan
Published: February 2024

Objective

Cerebral small vessel disease (CSVD) is the most common vascular cause of cognitive impairment. This study aimed to explore the association between MTHFR C677T polymorphism and cognitive impairment in CSVD patients.

Methods

Demographic, medical, laboratory, cognitive evaluation, and MTHFR C677T polymorphism data were collected from CSVD patients admitted to our hospital between January 2019 and July 2023. Inclusion criteria for CSVD were based on the Standards for Reporting Vascular changes on Neuroimaging (STRIVE) criteria, with age ≥ 45 years. Binary logistic regression models were used to analyze risk factors associated with WMH and cognitive impairment.

Results

A total of 330 CSVD participants were recruited in this study, including 179 male and 151 female, with a median age of 64 years (interquartile range: 58–73 years). There were 185 patients (56.1%) with cognitive impairment, 236 patients (71.5%) with WMH, 89 patients (27.0%) with CMB, 87 patients (26.4%) with lacunes. All participants completed MTHFR polymorphism analysis, 149 cases (45.2%) of the CC genotype, 112 cases (33.9%) of the CT genotype and 69 cases (20.9%) of the TT genotype. Patients with TT genotype exhibited higher plasma homocysteine levels and more severe WMH and cognitive impairment (p < 0.001). Multivariable binary logistic regression model showed that WMH was significantly associated with age (p = 0.019), history of hypertension (p = 0.011), HHcy (p = 0.019) and MTHFR genotype (p = 0.041); while cognitive impairment was significantly associated with age (p = 0.033), history of hypertension (p = 0.019), HHcy (p = 0.040), MTHFR genotype (p = 0.039), WMH (p = 0.041), and lacunes (p = 0.001).

Conclusion

In this cross-sectional study, we investigated the association between MTHFR C677T polymorphism and cognitive function in CSVD patients. We found that MTHFR 677 TT genotype was an independent risk factor for the progression of WMH and cognitive impairment in CSVD patients.
Recent advances in heavy metal/metalloid ion treatment from wastewater using nanocomposites and bionanocomposites
Authors: Singh Namita , Yadav Annu , Das Sumistha , Debnath Nitai
Published: February 2024

Wastewater remediation is of paramount importance for the water-stressed modern civilization from the perspective of sustainable development and the management of limited freshwater resources. Contaminants such as heavy metal and metalloid ions, toxic dyes, and pathogenic microbes present in the aquatic ecosystem have adverse effects not only on the environment but also on human health. Traditional wastewater remediation processes are costly, energy-consuming, and have less efficiency in removing pollutants from wastewater. Multi-phasic nanomaterials or nanocomposites have enormous potential for removing contaminants from water bodies. These materials have an enormous tunable surface area for interacting with the target toxicants and are extremely stable in the aquatic system, but they readily agglomerate. Many research groups have exploited biosorption, bioleaching, and bioprecipitation capacities of fungal hyphae for wastewater remediation. Recently, researchers have attempted to explore the synergistic effect of the bionanocomposite of fungal hyphae and nanomaterials for removing pollutants from wastewater. This bionanocomposite has already shown promise as a superior material for wastewater treatment and can easily be separated from the polluted water for reuse over several cycles. The bionanocomposite-mediated decontamination of water can lead to a total paradigm shift in wastewater management strategies.
Priority setting: women’s health topics in multiple sclerosis
Authors: Ross Lindsay , Finlayson Marcia , Amato Maria Pia , Cohen Jeffrey Alan , Hellwig Kerstin , Tintore Mar , Vukusic Sandra , Salter Amber , Marrie Ruth Ann
Published: February 2024

Background

A scoping review found that most studies on women’s health in multiple sclerosis (MS) focused on pregnancy, fetal/neonatal outcomes and sexual dysfunction. Few studies addressed menopause, contraception, gynecologic cancers/cancer screening. However, the perceived relative importance of these knowledge gaps to people living with MS and other partners is unknown. We engaged a range of partners, including people living with MS, health care providers, researchers, and patient advocacy groups, to set priorities for future research in women’s health in MS.

Methods

We employed a three-step global engagement process. First, we identified which broad research topics relevant to women’s health in MS were of highest priority using two surveys. Second, we developed specific research questions within these topics using focus groups. Finally, we prioritized the research questions with a third survey.

Results

Overall, 5,266 individuals responded to the initial surveys [n = 1,430 global survey, mean (SD) age 50.0 (12.6), all continents; n = 3,836 North American Research Committee on Multiple Sclerosis survey, mean (SD) age 64.8 (9.6), United States]. Menopause, sexual dysfunction, pregnancy, gynecologic cancer/cancer screening, hormones and parenthood were identified as the most important topics. Focus groups generated 80 potential research questions related to these topics. In the final survey 712 individuals prioritized these questions. The highest priority questions in each research topic were: (i) How do perimenopause and menopause affect disease activity, course, response to disease-modifying treatment and quality of life in MS; (ii) What are the most effective strategies for managing issues around sexual intimacy, including related to low sexual desire, changes in physical function, and MS symptoms; (iii) Are there long-term effects of disease-modifying therapies on the children of persons with MS; (iv) What are the short and long-term effects of disease-modifying drugs on gynecologic cancer risk, particularly for high efficacy disease-modifying drugs and hematopoietic stem cell transplantation; (v) Are there hormone related treatments that can stabilize fluctuations in MS symptoms; and (vi) How does MS fatigue impact parenting strategies.

Conclusion

Priorities for research relating to women’s health issues for persons with MS have been delineated using a collaborative process with key partners. Alignment of future research with these priorities should be monitored.
PFO-spectrum disorder: two different cerebrovascular diseases in patients with PFO as detected by AI brain imaging software
Authors: Badea Raluca Ștefania , Mihăilă-Bâldea Sorina , Ribigan Athena , Negrilă Anca , Grecu Nicolae , Marinescu Andreea Nicoleta , Antochi Florina , Tiu Cristina , Vinereanu Dragos , Popescu Bogdan Ovidiu
Published: February 2024

Background

Patent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions.

Patients and methods

Retrospective, case–control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume.

Results

Of the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03–0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02–0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes.

Discussion

We suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and “silent” WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the “at-risk” PFOs and gain deeper insights into their clinical implications.
Efficacy and safety of Argatroban in patients with acute ischemic stroke: a systematic review and meta-analysis
Authors: Cheng YiRan , Liu ChangNing , Li ShanShan , Meng Miao Miao , Li He
Published: February 2024

Objective

Argatroban is a highly promising drug for the treatment of acute ischemic stroke (AIS), but there is currently insufficient strong evidence regarding the efficacy and safety of using Argatroban in the treatment of AIS. Therefore, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of Argatroban in the treatment of AIS.

Methods

Articles on PubMed, Embase and the Cochrane Library databases were searched from these websites’ inceptions to 2th February 2023. Randomized controlled trials and observational studies on Argatroban therapy for acute ischemic stroke were included. Meta-analyses were conducted using a random-effects model.

Results

Fourteen studies involving 10,315 patients were included in the meta-analysis. The results showed a significant reduction in the rate of early neurological deterioration (END) in the Argatroban group compared with the control group (OR = 0.47, 95% CI: 0.31–0.73, I2 = 15.17%). The rates of adverse events were no significant difference between the two groups (ICH: OR = 1.02, 95% CI: 0.68–1.51, I2 = 0.00%; major extracranial bleeding: OR = 1.22, 95% CI: 1.01–1.48, I2 = 0.00%; mortality: OR = 1.16, 95% CI: 0.84–1.59, I2 = 0.00%). However, the rates of mRS score of 0–1 (OR = 1.38, 95% CI: 0.71–2.67, I2 = 77.56%) and mRS score of 0–2 (OR = 1.18, 95% CI: 0.98–1.42, I2 = 0.00%) during the 90 days did not significantly improved in the Argatroban group. Subgroup analyses showed that the rate of END (OR = 0.41, 95% CI: 0.26–0.65, I2 = 2.77%) and mRS score of 0–2 (OR = 1.38, 95% CI: 1.06–1.81, I2 = 0.00%) had significantly improved when the intervention group adopted Argatroban plus Antiplatelet.

Conclusion

Argatroban can improve neurological deterioration, with a low incidence of adverse events such as bleeding and death, and general analysis showed no improvement in mRS. However, subgroup analysis suggests that compared to mono-antiplatelet therapy, combination therapy of Argatroban combined with antiplatelet therapy significantly reduced the incidence of END and improved mRS scores. After using Argatroban, there was no increase in the risk and mortality of intracranial hemorrhage and other bleeding sites.
No effects of the theta-frequency transcranial electrical stimulation for recall, attention control, and relation integration in working memory
Authors: Ociepka Michał , Chinta Suvarna Rekha , Basoń Paweł , Chuderski Adam
Published: February 2024

Introduction

Recent studies have suggested that transcranial alternating current stimulation (tACS), and especially the theta-frequency tACS, can improve human performance on working memory tasks. However, evidence to date is mixed. Moreover, the two WM tasks applied most frequently, namely the n-back and change-detection tasks, might not constitute canonical measures of WM capacity.

Method

In a relatively large sample of young healthy participants (N = 62), we administered a more canonical WM task that required stimuli recall, as well as we applied two WM tasks tapping into other key WM functions: attention control (the antisaccade task) and relational integration (the graph mapping task). The participants performed these three tasks three times: during the left frontal 5.5-Hz and the left parietal 5.5-Hz tACS session as well as during the sham session, with a random order of sessions. Attentional vigilance and subjective experience were monitored.

Results

For each task administered, we observed significant gains in accuracy neither for the frontal tACS session nor for the parietal tACS session, as compared to the sham session. By contrast, the scores on each task positively inter-correlated across the three sessions.

Discussion

The results suggest that canonical measures of WM capacity are strongly stable in time and hardly affected by theta-frequency tACS. Either the tACS effects observed in the n-back and change detection tasks do not generalize onto other WM tasks, or the tACS method has limited effectiveness with regard to WM, and might require further methodological advancements.
A robust approach for multi-type classification of brain tumor using deep feature fusion
Authors: Chen Wenna , Tan Xinghua , Zhang Jincan , Du Ganqin , Fu Qizhi , Jiang Hongwei
Published: February 2024

Brain tumors can be classified into many different types based on their shape, texture, and location. Accurate diagnosis of brain tumor types can help doctors to develop appropriate treatment plans to save patients’ lives. Therefore, it is very crucial to improve the accuracy of this classification system for brain tumors to assist doctors in their treatment. We propose a deep feature fusion method based on convolutional neural networks to enhance the accuracy and robustness of brain tumor classification while mitigating the risk of over-fitting. Firstly, the extracted features of three pre-trained models including ResNet101, DenseNet121, and EfficientNetB0 are adjusted to ensure that the shape of extracted features for the three models is the same. Secondly, the three models are fine-tuned to extract features from brain tumor images. Thirdly, pairwise summation of the extracted features is carried out to achieve feature fusion. Finally, classification of brain tumors based on fused features is performed. The public datasets including Figshare (Dataset 1) and Kaggle (Dataset 2) are used to verify the reliability of the proposed method. Experimental results demonstrate that the fusion method of ResNet101 and DenseNet121 features achieves the best performance, which achieves classification accuracy of 99.18 and 97.24% in Figshare dataset and Kaggle dataset, respectively.
Object recognition via echoes: quantifying the crossmodal transfer of three-dimensional shape information between echolocation, vision, and haptics
Authors: Teng Santani , Danforth Caroline , Paternoster Nickolas , Ezeana Michael , Puri Amrita
Published: February 2024

Active echolocation allows blind individuals to explore their surroundings via self-generated sounds, similarly to dolphins and other echolocating animals. Echolocators emit sounds, such as finger snaps or mouth clicks, and parse the returning echoes for information about their surroundings, including the location, size, and material composition of objects. Because a crucial function of perceiving objects is to enable effective interaction with them, it is important to understand the degree to which three-dimensional shape information extracted from object echoes is useful in the context of other modalities such as haptics or vision. Here, we investigated the resolution of crossmodal transfer of object-level information between acoustic echoes and other senses. First, in a delayed match-to-sample task, blind expert echolocators and sighted control participants inspected common (everyday) and novel target objects using echolocation, then distinguished the target object from a distractor using only haptic information. For blind participants, discrimination accuracy was overall above chance and similar for both common and novel objects, whereas as a group, sighted participants performed above chance for the common, but not novel objects, suggesting that some coarse object information (a) is available to both expert blind and novice sighted echolocators, (b) transfers from auditory to haptic modalities, and (c) may be facilitated by prior object familiarity and/or material differences, particularly for novice echolocators. Next, to estimate an equivalent resolution in visual terms, we briefly presented blurred images of the novel stimuli to sighted participants (N = 22), who then performed the same haptic discrimination task. We found that visuo-haptic discrimination performance approximately matched echo-haptic discrimination for a Gaussian blur kernel σ of ~2.5°. In this way, by matching visual and echo-based contributions to object discrimination, we can estimate the quality of echoacoustic information that transfers to other sensory modalities, predict theoretical bounds on perception, and inform the design of assistive techniques and technology available for blind individuals.
Brain structural correlates of subjective sleepiness and insomnia symptoms in shift workers
Authors: Jeong Hyunwoo , Yeo Hyewon , Lee Kyung Hwa , Kim Nambeom , Shin Jiyoon , Seo Min Cheol , Jeon Sehyun , Lee Yu Jin , Kim Seog Ju
Published: February 2024

Background

Studies on the brain structures of shift workers are limited; thus, this cross-sectional study aimed to compare the brain structures and the brain structural correlates of subjective sleepiness and insomnia symptoms between shift workers and non-shift workers.

Methods

Shift workers (n = 63) and non-shift workers (n = 58) completed questionnaires assessing subjective sleepiness and insomnia symptoms. Cortical thickness, cortical surface area, and subcortical volumes were measured by magnetic resonance imaging. The brain morphometric measures were compared between the groups, and interaction analyses using the brain morphometric measures as the dependent variable were performed to test the interactions between the study group and measures of sleep disturbance (i.e., subjective sleepiness and insomnia symptoms).

Results

No differences in cortical thickness, cortical surface area, or subcortical volumes were detected between shift workers and non-shift workers. A single cluster in the left motor cortex showed a significant interaction between the study group and subjective sleepiness in the cortical surface area. The correlation between the left motor cortex surface area and the subjective sleepiness level was negative in shift workers and positive in non-shift workers. Significant interaction between the study group and insomnia symptoms was present for the left/right putamen volumes. The correlation between the left/right putamen volumes and insomnia symptom levels was positive in shift workers and negative in non-shift workers.

Conclusion

Left motor cortex surface area and bilateral putamen volumes were unique structural correlates of subjective sleepiness and insomnia symptoms in shift workers, respectively.
Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies
Authors: González-González María Alejandra , Conde Silvia V. , Latorre Ramon , Thébault Stéphanie C. , Pratelli Marta , Spitzer Nicholas C. , Verkhratsky Alexei , Tremblay Marie-Ève , Akcora Cuneyt G. , Hernández-Reynoso Ana G. , Ecker Melanie , Coates Jayme , Vincent Kathleen L. , Ma Brandy
Published: February 2024

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural interfaces, along with the integration of biocompatible and reliable materials and compliance with biomedical regulations for translational applications. Preclinical validation is foundational to the translational process, and we will discuss the critical aspects of such animal studies. Finally, we will focus on the patient point-of-care and challenges in neuromodulation as the ultimate goal of bioelectronic medicine. This review is a call to scientists from different fields to work together with a common endeavor: accelerate the decoding and modulation of the nervous system in a new era of therapeutic possibilities.
Effects of wolfberry (Lycium barbarum) consumption on the human plasma lipidome and its association with cardiovascular disease risk factors: a randomized controlled trial of middle-aged and older adults
Authors: Toh Darel Wee Kiat , Zhou Hanzhang , Cazenave-Gassiot Amaury , Choi Hyungwon , Burla Bo , Bendt Anne Katherin , Wenk Markus R. , Ling Lieng Hsi , Kim Jung Eun
Published: February 2024

Background

Long-term wolfberry intake as part of a healthy dietary pattern was recognized to have beneficial vascular outcomes. Characterization of the plasma lipidome may further provide comprehensive insights into pathways underlying these cardiovascular protective effects.

Objective

We analyzed the plasma lipidome of subjects who adhered to a healthy dietary pattern either with or without wolfberry and investigated the associations between the plasma lipidomic profile and cardiovascular health-related indicators.

Methods

In this 16-week, parallel design, randomized controlled trial, middle-aged and older adults (n = 41) were provided dietary counseling and assigned to either consume or not consume 15 g of wolfberry daily. At baseline and post-intervention, plasma lipidomics was assayed, and its relationships with classical CVD risk factors, vascular health, oxidant burden, carotenoids status, body composition, and anthropometry were examined.

Results

From the plasma lipidome, 427 lipid species from 26 sub-classes were quantified. In the wolfberry and control groups, significant changes were prominent for 27 and 42 lipid species, respectively (P < 0.05 with > 0.2-fold change). Fold changes for seven lipid species were also markedly different between the two groups. Examining the relationships between the plasma lipidome and CVD-related risk factors, total cholesterol revealed a marked positive correlation with 13 ceramide species, while HDL-cholesterol which was notably increased with wolfberry consumption showed a positive correlation with 10 phosphatidylcholine species. Oxidant burden, as represented by plasma 8-isoprostanes, was also inversely associated with lipidomic triglycerides and ether-triglycerides (41 species) and directly associated with hexosylceramides (eight species) and sphingomyelins (six species). There were no differential associations with CVD risk detected between groups.

Conclusion

Characteristic alterations to the plasma lipidome were observed with healthy dietary pattern adherence and wolfberry consumption. An examination of these fluctuations suggests potential biochemical mechanisms that may mediate the antioxidant and cardiovascular protective effects of healthy dietary pattern adherence and wolfberry intake. This study was registered at clinicaltrials.gov as NCT0353584.
Natural feed additives and bioactive supplements versus chemical additives as a safe and practical approach to combat foodborne mycotoxicoses
Authors: Stoev Stoycho D.
Published: February 2024

This review highlights the possible hazard of mycotoxins occurrence in foods and feeds in regards to foodborne diseases. The possible management of the risk of contamination of foods and feeds with mycotoxins by using natural feed additives, protecting against deleterious effects of mycotoxins or inhibiting the growth of fungi and mycotoxin production, is deeply investigated in the available literature and some effective measures for safe utilization of mycotoxin contaminated feed/food are proposed. The biological methods of decontamination, degradation or biotransformation of mycotoxins are deeply analyzed and discussed. Some natural antagonists against target fungi are also reviewed and a comparison is made with conventional fungicides for ensuring a safe prevention of mycotoxin contamination. The most common and useful chemical methods of mycotoxins decontamination of agricultural commodities or raw materials are also investigated, e.g., chemical additives inactivating or destroying and/or adsorbing mycotoxins as well as chemical additives inhibiting the growth of fungi and mycotoxin production. The practical use and safety of various kind of feed/food additives or herbal/biological supplements as possible approach for ameliorating the adverse effects of some dangerous mycotoxins is deeply investigated and some suggestions are given. Various possibilities for decreasing mycotoxins toxicity, e.g., by clarifying the mechanisms of their toxicity and using some target antidotes and vitamins as supplements to the diet, are also studied in the literature and appropriate discussions or suggestions are made in this regard. Some studies on animal diets such as low carbohydrate intake, increased protein content, calorie restriction or the importance of dietary fats are also investigated in the available literature for possible amelioration of the ailments associated with mycotoxins exposure. It could be concluded that natural feed additives and bioactive supplements would be more safe and practical approach to combat foodborne mycotoxicoses as compared to chemical additives.
The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies
Authors: Filipek-Gorzała Jadwiga , Kwiecińska Patrycja , Szade Agata , Szade Krzysztof
Published: February 2024

Hematopoietic stem cells (HSCs) produce all blood cells throughout the life of the organism. However, the high self-renewal and longevity of HSCs predispose them to accumulate mutations. The acquired mutations drive preleukemic clonal hematopoiesis, which is frequent among elderly people. The preleukemic state, although often asymptomatic, increases the risk of blood cancers. Nevertheless, the direct role of preleukemic HSCs is well-evidenced in adult myeloid leukemia (AML), while their contribution to other hematopoietic malignancies remains less understood. Here, we review the evidence supporting the role of preleukemic HSCs in different types of blood cancers, as well as present the alternative models of malignant evolution. Finally, we discuss the clinical importance of preleukemic HSCs in choosing the therapeutic strategies and provide the perspective on further studies on biology of preleukemic HSCs.
Multi-segment osteotomy with interlocking intramedullary nail fixation in the treatment of lower limb deformity in older children with hypophosphatemic rickets
Authors: Lu Ming , You Haifeng , Wang Yukun
Published: February 2024

Objective

Malformations of the lower limbs caused by hypophosphatemic rickets in older children are mostly complex, occurring on multiple planes without a single apex and showing arcuate bending of the diaphysis combined with torsion deformity, and are difficult to correct. This study retrospectively investigated the effect of and indicators for multi-segment osteotomy with interlocking intramedullary nail fixation in the treatment of bony deformity caused by hypophosphatemic rickets.

Methods

The clinical data of 21 hypophosphatemic rickets patients seen between August 2007 and March 2022 were collected. The age range of the patients at the first surgery was 11 years and 1 month old to 15 years and 3 months old, with an average age of 12 years and 8 months. There were 6 males and 15 females. All patients had abnormal alignment of their lower limbs, with 32 limbs having varus deformity and 10 limbs having valgus deformity.

Results

A total of 67 surgeries were performed across the 21 patients, including 24 cases of femoral osteotomy with antegrade intramedullary nail fixation, 6 cases of femoral osteotomy with retrograde intramedullary nail fixation, and 20 cases of tibial osteotomy with interlocking intramedullary nail fixation. A total of 34 limbs eventually underwent interlocking intramedullary nail fixation, 9 with genu valgum and 25 with genu varus. All 21 patients were followed up for a period of 14∼96 months, with an average of 42.6 months. The ends of the osteotomies achieved bony union in 4–9 months (average 6.8 months), after which normal weight-bearing walking could be resumed. No infection, vascular or neurological complications, or nonunion occurred. During postoperative follow-up, the alignment the lower limbs passed through zone 1 in 13 limbs, zone 2 in 12 limbs, and zone 3 in 5 limbs. The overall rate of an excellent effect was 83.3%.

Conclusion

For lower limb deformity caused by hypophosphatemic rickets in older children, multi-segment osteotomy and strong fixation with interlocking intramedullary nails can achieve good correction outcomes.
Comparing ATPase activity of ATP-binding cassette subfamily C member 4, lamprey CFTR, and human CFTR using an antimony-phosphomolybdate assay
Authors: Cui Guiying , Strickland Kerry M. , Vazquez Cegla Analia J. , McCarty Nael A.
Published: February 2024

Introduction: ATP-binding cassette (ABC) transporters use the hydrolysis of ATP to power the active transport of molecules, but paradoxically the cystic fibrosis transmembrane regulator (CFTR, ABCC7) forms an ion channel. We previously showed that ATP-binding cassette subfamily C member 4 (ABCC4) is the closest mammalian paralog to CFTR, compared to other ABC transporters. In addition, Lamprey CFTR (Lp-CFTR) is the oldest known CFTR ortholog and has unique structural and functional features compared to human CFTR (hCFTR). The availability of these evolutionarily distant orthologs gives us the opportunity to study the changes in ATPase activity that may be related to their disparate functions.

Methods: We utilized the baculovirus expression system with Sf9 insect cells and made use of the highly sensitive antimony-phosphomolybdate assay for testing the ATPase activity of human ABCC4 (hABCC4), Lp-CFTR, and hCFTR under similar experimental conditions. This assay measures the production of inorganic phosphate (Pi) in the nanomolar range.

Results: Crude plasma membranes were purified, and protein concentration, determined semi-quantitatively, of hABCC4, Lp-CFTR, and hCFTR ranged from 0.01 to 0.36 μg/μL. No significant difference in expression level was found although hABCC4 trended toward the highest level. hABCC4 was activated by ATP with the equilibrium constant (Kd) 0.55 ± 0.28 mM (n = 8). Estimated maximum ATPase rate (Vmax) for hABCC4 was about 0.2 nmol/μg/min when the protein was activated with 1 mM ATP at 37°C (n = 7). Estimated maximum ATPase rate for PKA-phosphorylated Lp-CFTR reached about half of hCFTR levels in the same conditions. Vmax for both Lp-CFTR and hCFTR were significantly increased in high PKA conditions compared to low PKA conditions. Maximum intrinsic ATPase rate of hABCC4 in the absence of substrate was twice that of hCFTR when activated in 1 mM ATP.

Conclusion: The findings here suggest that while both ABCC4 and hCFTR bear one consensus and one degenerate ATPase site, the hCFTR exhibited a reduced intrinsic ATPase activity. In addition, ATPase activity in the CFTR lineage increased from Lp-CFTR to hCFTR. Finally, the studies pave the way to purify hABCC4, Lp-CFTR, and hCFTR from Sf9 cells for their structural investigation, including by cryo-EM, and for studies of evolution in the ABC transporter superfamily.
Automatic identification and analysis of cells using digital holographic microscopy and Sobel segmentation
Authors: Xiong Zihan , Yu Lan , An Sha , Zheng Juanjuan , Ma Ying , Micó Vicente , Gao Peng
Published: February 2024

Counting and analyzing of blood cells, as well as their subcellular structures, are indispensable for understanding biological processes, studying cell functions, and diagnosing diseases. In this paper, we combine digital holographic microscopy with cell segmentation guided by the Sobel operator using Dice coefficients for automatic threshold selection and aimed to automatic counting and analysis of blood cells in flow and different kinds of cells in the static state. We demonstrate the proposed method with automatic counting and analyzing rat red blood cells (RBCS) flowing in a microfluidic device, extracting quickly and accurately the size, concentration, and dry mass of the sample in a label-free manner. The proposed technique was also demonstrated for automatic segmentation of different cell types, such as COS7 and Siha. This method can help us in blood inspection, providing pathological information in disease diagnosis and treatment.
Bioenergetic signatures of neurodevelopmental regression
Authors: Frye Richard E. , McCarty Patrick J. , Werner Brianna A. , Rose Shannon , Scheck Adrienne C.
Published: February 2024

Background: Studies have linked autism spectrum disorder (ASD) to physiological abnormalities including mitochondrial dysfunction. Mitochondrial dysfunction may be linked to a subset of children with ASD who have neurodevelopmental regression (NDR). We have developed a cell model of ASD which demonstrates a unique mitochondrial profile with mitochondrial respiration higher than normal and sensitive to physiological stress. We have previously shown similar mitochondrial profiles in individuals with ASD and NDR.

Methods: Twenty-six ASD individuals without a history of NDR (ASD-NoNDR) and 15 ASD individuals with a history of NDR (ASD-NDR) were recruited from 34 families. From these families, 30 mothers, 17 fathers and 5 typically developing (TD) siblings participated. Mitochondrial respiration was measured in peripheral blood mononuclear cells (PBMCs) with the Seahorse 96 XF Analyzer. PBMCs were exposed to various levels of physiological stress for 1 h prior to the assay using 2,3-dimethoxy-1,4-napthoquinone.

Results: ASD-NDR children were found to have higher respiratory rates with mitochondria that were more sensitive to physiological stress as compared to ASD-NoNDR children, similar to our cellular model of NDR. Differences in mitochondrial respiration between ASD-NDR and TD siblings were similar to the differences between ASD-NDR and ASD-NoNDR children. Interesting, parents of children with ASD and NDR demonstrated patterns of mitochondrial respiration similar to their children such that parents of children with ASD and NDR demonstrated elevated respiratory rates with mitochondria that were more sensitive to physiological stress. In addition, sex differences were seen in ASD children and parents. Age effects in parents suggested that mitochondria of older parents were more sensitive to physiological stress.

Conclusion: This study provides further evidence that children with ASD and NDR may have a unique type of mitochondrial physiology that may make them susceptible to physiological stressors. Identifying these children early in life before NDR occurs and providing treatment to protect mitochondrial physiology may protect children from experiencing NDR. The fact that parents also demonstrate mitochondrial respiration patterns similar to their children implies that this unique change in mitochondrial physiology may be a heritable factor (genetic or epigenetic), a result of shared environment, or both.