bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive testing in metabolic dysfunction-associated steatotic liver disease
Authors: Dawod Sanad , Brown Kimberly
Published: November 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease, affecting up to 30% of the global population. MASLD is strongly associated with metabolic risk factors such as obesity and type 2 diabetes, and can progress to advanced stages including cirrhosis and hepatocellular carcinoma. Early diagnosis and accurate staging of fibrosis are critical in managing the disease and preventing complications. While liver biopsy has long been considered the gold standard for assessing fibrosis, it is invasive and carries associated risks. In response, non-invasive tests (NITs) have emerged as essential alternatives for the diagnosis and monitoring of MASLD. Key methods include blood-based biomarkers such as the Fibrosis-4 (FIB-4) score, NAFLD Fibrosis Score (NFS), and Enhanced Liver Fibrosis (ELF) test, as well as imaging modalities like vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). These tests provide safer, more accessible methods for identifying liver fibrosis and guiding clinical management. They are integral in assessing disease severity, guiding treatment decisions, and monitoring disease progression, particularly in light of emerging therapies. NITs have become increasingly recommended by clinical guidelines as they reduce the need for invasive procedures like liver biopsy, improving patient care and outcomes. In conclusion, non-invasive testing plays a crucial role in the effective management of MASLD, offering reliable alternatives for diagnosis and monitoring while minimizing risks associated with traditional invasive methods.
The influence of host genotype and gut microbial interactions on feed efficiency traits in pigs
Authors: Lu Zhuoda , Zhang Tao , Zhao Yunxiang , Pang Yanqin , Guo Meng , Zhu Xiaoping , Li Ying , Li Zhili
Published: November 2024

Feed efficiency and growth performance are economically important traits in pigs. Precious studies have been revealed that both genetics and gut microbes could influence host phenotypes, however, the mechanisms by which they affect pig growth and feed efficiency remain poorly understood. In this study, 361 crossbred Duroc × (Landrace × Yorkshire) commercial pigs were genotyped using GeneSeek Porcine SNP50K BeadChip, and the microbiotas from fecal samples were acquired using microbial 16S rRNA gene sequencing technology to investigate the impact of host genetics and gut microorganisms on growth and feed efficiency. The results showed that the heritability and enterobacterial force ranged from 0.27 to 0.46 and 0 to 0.03, respectively. Genome-wide association studies (GWAS) identified seven significant SNPs to be associated with growth and feed efficiency, and several genes, including AIF1L, ASS1, and QRFP were highlighted as candidates for the analyzed traits. Additionally, microbiome-genome-wide association studies GWAS revealed potential links between CCAR2, EGR3, GSTM3, and GPR61 genes and the abundance of microorganisms, such as Trueperella, Victivallis, and Erysipelatoclostridium. In addition, six microbial genera linked to growth and feed efficiency were identified as follows Lachnospiraceae_UCG-005, Prevotellaceae_UCG-003, Prevotellaceae_NK3B31_group, Prevotella_1, Prevotella_9, and Veillonella. Our findings provide novel insights into the factors influencing host phenotypic complexity and identify potential microbial targets for enhancing pig feed efficiency through selective breeding. This could aid in the development of strategies to manipulate the gut microbiota to optimize growth rates and feed efficiency in pig breeding.
Mechanism of a novel Bacillus subtilis JNF2 in suppressing Fusarium oxysporum f. sp. cucumerium and enhancing cucumber growth
Authors: Yang Fan , Wang Xin , Jiang Huayan , Yao Qiuju , Liang Shen , Chen Weiwei , Shi Gongyao , Tian Baoming , Hegazy Abeer , Ding Shengli
Published: November 2024

Cucumber Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerium (FOC), is a prevalent soil-borne disease. In this study, Bacillus subtilis JNF2, isolated from the high incidence area of cucumber Fusarium wilt in Luoyang, demonstrated significant inhibitory effects on FOC and promoted cucumber seedling growth. The biocontrol mechanism of strain JNF2 were elucidated through morphological observation, physiological and biochemical experiments, and whole genome sequence analysis. Pot experiments revealed an 81.33 ± 0.21% control efficacy against Fusarium wilt, surpassing the 64.10 ± 0.06% efficacy of hymexazol. Seedlings inoculated with JNF2 exhibited enhanced stem thickness and leaf area compared to control and hymexazol-treated plants. Physiological tests confirmed JNF2’s production of indole-3-acetic acid (IAA), siderophores, and hydrolytic enzymes, such as β-1,3-glucanase, amylase, and protease, which inhibited FOC growth and promoted plant development. Genome analysis identified genes encoding antimicrobial peptides and hydrolases, as well as a novel glycocin synthetic gene cluster. These findings underscore B. subtilis JNF2’s potential as a biocontrol agent for sustainable cucumber cultivation.
Construction, molecular characterization, and safety assessment of purB mutant of Salmonella Gallinarum
Authors: Mukhtar Masham , Ghafoor Aamir , McClelland Michael , Akhtar Fareeha , Rasheed Muhammad Adil
Published: November 2024

This study involves the development and molecular characterization of the isogenic markerless knockout mutant SG ΔpurB, a genetically engineered live attenuated strain aimed at controlling Salmonella Gallinarum (SG) infection in poultry. The mutant was generated by deleting the purB gene using λ-Red recombination technology, impairing adenylosuccinate lyase, necessary for purine biosynthesis. An 1,180 bp deletion was engineered within the purB gene, leaving a residual 298 bp genomic scar resulting in a purine auxotrophic mutant. Phenotypically, SG ΔpurB showed a 66.5% reduction in growth in LB broth compared to the wild-type strain and failed to grow in minimal media without adenosine. Growth was restored to near wild-type levels with 0.3 mM adenosine supplementation, demonstrating the strain’s conditional attenuation. In vivo pathogenicity assessments revealed that oral inoculation of SG ΔpurB into 3-day-old chickens at a dose of 2 × 108 CFU resulted in zero mortality, compared to an 80% mortality rate in chickens challenged with the wild-type strain. The SG ΔpurB strain exhibited significantly reduced clinical signs and lesion scores, with clinical sign scores dropping from 2.5/3 with the wild-type to 0.4/3 with the ΔpurB mutant, and lesion scores decreasing from 2.9/3 to 0.3/3. Additionally, the mutant was efficiently cleared from liver and spleen tissues by 14 days post-inoculation, unlike the wild-type strain, which persisted until the experiment’s end on day 21. The SG ΔpurB mutant shows potential as a safe alternative for preventing fowl typhoid, highlighting the promise of targeted genetic attenuation in developing effective vaccines for poultry diseases.
Effects of sex and estrous cycle on extended-access oxycodone self-administration and cue-induced drug seeking behavior
Authors: Patel Bhumiben P. , Loweth Jessica A.
Published: November 2024

Introduction

Increasing evidence indicates that sex is a factor that impacts the abuse liability and relapse vulnerability of prescription opioids like oxycodone. However, while women are more likely than men to be prescribed and to use these drugs, the impact of sex and ovarian hormones on prescription opioid use and relapse vulnerability remains unclear. Accurately assessing these measures is complicated by the fact that chronic opioid exposure can lower ovarian hormone levels and cause cycle irregularities.

Methods

Adult male and female Sprague–Dawley rats self-administered oxycodone (0.1 mg/kg/infusion) under extended-access conditions (6 h/day, 10 days) followed by forced abstinence. Separate groups of animals received cue-induced seeking tests in a drug-free state during early (1–2 days) or later periods of abstinence (43–45 days). To track estrous cycle stage, animals were regularly vaginally swabbed throughout the study.

Results

We observed oxycodone-induced estrous cycle dysregulation in the majority (~60%) of the animals during both self-administration and the first month of abstinence. In animals whose cycles were not dysregulated, we found a reduction in oxycodone intake during estrus compared to all other cycle stages (non-estrus). We also found that males but not females showed a time-dependent intensification or incubation of cue-induced oxycodone craving over the first 6 weeks of abstinence. This sex difference was estrous cycle-dependent, driven by a selective reduction in drug seeking during estrus.

Discussion

These findings highlight the importance of tracking drug-induced estrous cyclicity and identify a clear impact of ovarian hormones on oxycodone taking and seeking behavior.
Neural speech tracking and auditory attention decoding in everyday life
Authors: Straetmans Lisa , Adiloglu Kamil , Debener Stefan
Published: November 2024

Introduction

In our complex world, the auditory system plays a crucial role in perceiving and processing our environment. Humans are able to segment and stream concurrent auditory objects, allowing them to focus on specific sounds, such as speech, and suppress irrelevant auditory objects. The attentional enhancement or suppression of sound processing is evident in neural data through a phenomenon called neural speech tracking. Previous studies have identified correlates of neural speech tracking in electroencephalography (EEG) data, but EEG measures are susceptible to motion artefacts, and the association between neural data and auditory objects is vulnerable to distraction.

Methods

The current study investigated EEG-based auditory attention decoding in realistic everyday scenarios. N=20 participants were exposed to the sound of a busy cafeteria or walked along busy and quiet streets while listening to one or two simultaneous speech streams. We also investigated the robustness of neural speech tracking estimates within subjects. Linear decoding models were used to determine the magnitude of neural speech tracking.

Results

The results confirmed that neural speech tracking was strongest in single speaker scenarios. In dual speaker conditions, there was significantly stronger neural speech tracking for the attended speaker compared to the ignored speaker, even in complex environments such as a busy cafeteria or outdoor settings.

Discussion

In conclusion, EEG-based attention decoding is feasible in highly complex and realistic everyday conditions while humans behave naturally.
Mutations in mitochondrial ATAD3 gene and disease, lessons from in vivo models
Authors: Brügel Marcel , Kiesel Ann-Sophie , Haack Tobias B. , Peralta Susana
Published: November 2024

Pathogenic variants in the ATAD3 gene cluster have been associated with different neurodevelopmental disorders showing clinical symptoms like global developmental delay, muscular hypotonia, cardiomyopathy, congenital cataracts, and cerebellar atrophy. ATAD3A encodes for a mitochondrial ATPase whose function is unclear and has been considered one of the five most common nuclear genes associated with mitochondrial diseases in childhood. However, the mechanism causing ATAD3-associated disorders is still unknown. In vivo models have been used to identify ATAD3 function. Here we summarize the features of mouse models with ATAD3 loss of function and Drosophila models overexpressing pathogenic ATAD3 variants. We discuss how these models have contributed to our understanding of ATAD3 function and the pathomechanism of the ATAD3-associated disease.
(+)-Borneol inhibits neuroinflammation and M1 phenotype polarization of microglia in epileptogenesis through the TLR4-NFκB signaling pathway
Authors: Li Shuo , Adamu Alhamdu , Ye Yucai , Gao Fankai , Mi Rulin , Xue Guofang , Wang Zhaojun
Published: November 2024

Objective

To investigate the effect of (+)-borneol on neuroinflammation and microglia phenotype polarization in epileptogenesis and its possible mechanism.

Methods

Based on mouse models of status epilepticus (SE) induced by pilocarpine, and treated with 15 mg/kg (+)-borneol, western-blot was used to detect the expressions of NeuN, Iba-1, TLR4, p65 and p-p65 in the hippocampus. Immunofluorescence was used to detect the expression of apoptosis-related proteins Bax and Bcl-2. To explore the effect of (+)-borneol on microglia in vitro, we used the kainic acid-induced microglia model and the concentration of (+)-borneol was 25 μM according to CCK-8 results. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in the supernatant of each group was detected by ELISA. The nitric oxide (NO) content in the supernatant was detected by Griess method. The expressions of Iba-1 and TLR4-NFκB signaling pathway-related proteins (TLR4, p65, p-p65) were detected by Western-Blot. Immunofluorescence was used to detect microglia’s M1 and M2 phenotype polarization and the expression of Iba-1 and TLR4.

Results

(+)-borneol reduced hippocampal neuronal injury, apoptosis, and microglia activation by inhibiting the TLR-NFκB signaling pathway in SE mice. TLR4 agonist LPS partially reversed the neuroprotective effect of (+)-borneol. In the KA-induced microglia model, (+)-borneol inhibited microglia activation, M1 phenotype polarization, and secretion of pro-inflammatory cytokines through the TLR4-NFκB signaling pathway. LPS treatment inhibited the therapeutic effects of (+)-borneol.

Conclusion

(+)-borneol inhibits microglial neuroinflammation and M1 phenotype polarization through TLR4-NFκB signaling pathway and reduces neuronal damage and apoptosis in SE mice. Therefore, (+)-borneol may be a potential drug for epilepsy modification therapy.
Epileptiform activity in brain organoids derived from patient with Glucose Transporter 1 Deficiency Syndrome
Authors: Müller Y. , Lengacher L. , Friscourt F. , Quairiaux C. , Stoppini L. , Magistretti P. J. , Lengacher S. , Finsterwald C.
Published: November 2024

Introduction

Glucose Transporter 1-Deficiency Syndrome (GLUT1-DS) is a rare genetic disorder caused by mutations in the gene encoding for GLUT1 and characterized by impaired glucose uptake in the brain. This leads to brain hypometabolism and the development of symptoms that include epilepsy, motor dysfunctions and cognitive impairment. The development of patient-specific in vitro models is a valuable tool for understanding the pathophysiology of rare genetic disorders and testing new therapeutic interventions.

Methods

In this study, we generated brain organoids from induced pluripotent stem cells (iPSCs) derived either from a GLUT1-DS patient or a healthy individual. The functional organoids were analyzed for cellular composition, maturity, and electrophysiological activity using a custom-made microelectrode array (MEA) platform, which allowed for the detection of spikes, burst patterns, and epileptiform discharges.

Results

Immunostaining revealed a similar distribution of neurons and astrocytes in both healthy and GLUT1-DS brain organoids, though GLUT1-DS brain organoids exhibited reduced cellular density and smaller overall size. Electrophysiological recordings demonstrated functional spike profiles in both organoid types. Notably, our study demonstrates that brain organoids derived from a GLUT1-DS patient exhibit distinct epileptiform activity and heightened sensitivity to glucose deprivation, reflecting key features of the disorder.

Discussion

These findings validate the use of brain organoids as a model for studying GLUT1-DS and highlight their potential for testing novel therapeutic strategies aimed at improving glucose metabolism and managing epilepsy in patients.
The role of low-carbohydrate, high-fat diet in modulating autophagy and endoplasmic reticulum stress in aortic endothelial dysfunction of metabolic syndrome animal model
Authors: Eldakhakhny Basmah , Bima Abdulhadi , Alamoudi Aliaa A. , Alnami Abrar , Abo-Elkhair Salwa Mohamed , Sakr Hussein , Almoghrabi Yousef , Ghoneim Fatma Mohamed , Nagib Reham Mohamed , Elsamanoudy Ayman
Published: November 2024

Background

Endothelial dysfunction (ED) is induced by insulin resistance, mediated by endoplasmic reticulum (ER) stress and disturbed autophagy. This study investigates the protective role of a low-carbohydrate, high-fat (LCHF) diet on ED, ER stress, and autophagy dysregulation in an experimental animal model of metabolic syndrome.

Methods

Forty male Sprague–Dawley rats were divided into four groups: a Control group (standard diet) and three Dexamethasone (DEX) treated groups. Group II continued the standard diet, Group III received an LCHF diet, and Group IV received a high-carbohydrate, low-fat (HCLF) diet. At the end of the experiment, aortic tissue samples were obtained and used for histological, immunohistochemical (Endothelin and PCNA, biochemical MDA, TCA, NO, 8-OH-dG, and Nrf2/ARE protein) and molecular (Endothelin, eNOS, Nrf-2 α, p62, LC3, BECN-1, PINK1, CHOP, BNIP3, PCNA) analysis.

Results

Oxidative stress, autophagy markers, and ED markers are increased in the metabolic syndrome group. LCHF diet mitigates the adverse effects of DEX on endothelial dysfunction and oxidative stress, as evidenced by reduced BMI, HOMA-IR, and improved histological and molecular parameters.

Conclusion

Oxidative stress, autophagy dysregulation, and ER stress play crucial roles in the pathogenesis of insulin resistance-induced endothelial dysfunction. An LCHF diet offers protective benefits against insulin resistance and related comorbidities, including endothelial dysfunction.
Association between advanced lung cancer inflammation index and unstable asthma: a population-based study from the NHANES 2007–2018
Authors: Jin Zhou , Sun Wen , Huang Junjun , Wang Guangfa
Published: November 2024

Background

Asthma exacerbation is associated with obesity and systemic inflammatory diseases, and advanced lung cancer inflammation index (ALI) is a novel biomarker of nutritional inflammation. The purpose of this study was to investigate the potential relationship between ALI and unstable asthma.

Methods

This cross-sectional study utilized data from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Asthma was assessed through self-reported questionnaires. Multifactorial logistic regression, subgroup analyses, interaction assessments, smoothed curve fitting, and threshold effect analysis models were conducted to investigate the association between ALI and unstable asthma.

Results

The study included 1,822 subjects with current asthma, and we found a linear positive association between ALI and unstable asthma, with higher levels of ALI significantly associated with an increased risk of asthma exacerbations in fully corrected models. However, the associations were not entirely consistent across subgroups. In subgroup analyses by body mass index (BMI) and race, unstable asthma and ALI were independently significant in the BMI (25–29.9) range and the Non-Hispanic White group. Interaction analysis suggested that BMI moderated the relationship between ALI and unstable asthma. Furthermore, smoothed curve fitting showed an inverted U-shaped relationship between log ALI and unstable asthma in subjects with a BMI <25 and male individuals, with inflection points observed at 1.53 and 2.13, respectively.

Conclusion

We found a linear positive association between ALI and unstable asthma, which remained constant in the fully adjusted model. These findings suggest that higher levels of ALI were significantly associated with an increased risk of asthma exacerbation, particularly in asthmatic populations with BMI in the 25–29.9 range. However, more prospective studies are required to confirm our findings.
Molecular mechanism of bone metastasis in breast cancer
Authors: Sui Laijian , Wang Jing , Jiang Wen G. , Song Xicheng , Ye Lin
Published: November 2024

Bone metastasis is a debilitating complication that frequently occurs in the advanced stages of breast cancer. However, the underlying molecular and cellular mechanisms of the bone metastasis remain unclear. Here, we elucidate how bone metastasis arises from tumor cells that detach from the primary lesions and infiltrate into the surrounding tissue, as well as how these cells disseminate to distant sites. Specifically, we elaborate how tumor cells preferentially grow within the bone micro-environment and interact with bone cells to facilitate bone destruction, characterized as osteoclastic bone metastasis, as well as new bone matrix deposition, characterized as osteoblastic bone metastasis. We also updated the current understanding of the molecular mechanisms underlying bone metastasis and reasons for relapse in breast cancer, and also opportunities of developing novel diagnostic approaches and treatment.
Comparison of multiple machine learning models for predicting prognosis of pancreatic ductal adenocarcinoma based on contrast-enhanced CT radiomics and clinical features
Authors: Huang Yue , Zhang Han , Ding Qingzhu , Chen Dehua , Zhang Xiang , Weng Shangeng , Liu Guozhong
Published: November 2024

Objective

The aim of this study was to evaluate the prognostic potential of combining clinical features and radiomics with multiple machine learning (ML) algorithms in pancreatic ductal adenocarcinoma (PDAC).

Methods

A total of 116 patients with PDAC who met the eligibility criteria were randomly assigned to a training or validation cohort. Seven ML algorithms, including Supervised Principal Components, stepwise Cox, Random Survival Forest, CoxBoost, Least absolute shrinkage and selection operation (Lasso), Ridge, and Elastic network, were integrated into 43 algorithm combinations. Forty-three radiomics models were constructed separately using radiomics features extracted from arterial phase (AP), venous phase (VP), and combined arterial and venous phase (AP+VP) images. The concordance index (C-index) of each model was calculated. The model with the highest mean C-index was identified as the best model for calculating the radiomics score (Radscore). Univariate and multivariate Cox analyses were used to identify independent prognostic indicators and create a clinical model for prognosis prediction. The multivariable Cox regression was used to combine Radscore with clinical features to create a combined model. The efficacy of the model was evaluated using the C-index, calibration curves, and decision curve analysis (DCA).

Results

The model based on the Lasso+StepCox[both] algorithm constructed using AP+VP radiomics features showed the best predictive ability among the 114 radiomics models. The C-indices of the model in the training and validation cohorts were 0.742 and 0.722, respectively. Based on the results of the univariate and multivariate Cox regression analyses, sex, Tumor-Node-Metastasis (TNM) stage, and systemic inflammation response index were included to build the clinical model. The combined model, incorporating three clinical factors and AP+VP-Radscore, achieved the highest C-indices of 0.764 and 0.746 in the training and validation cohorts, respectively. In terms of preoperative prognosis prediction for PDAC, the calibration curve and DCA showed that the combined model had a good consistency and greatest net benefit.

Conclusion

A combined model of clinical features and AP+VP-Radscore screened using multiple ML algorithms has an excellent ability to predict the prognosis of PDAC and may provide a noninvasive and effective method for clinical decision-making.
Case report: Mullerian cyst of mediastinum: report of two cases
Authors: Abulizi Aliye , Yang Yuan , An Peng , Gao Ping
Published: November 2024

Posterior mediastinal Mullerian cyst is rare. Due to its special location, it is easy to be misdiagnosed clinically, imaging and pathologically. Imaging is often misdiagnosed as a bronchial cyst or neurogenic tumor. The postoperative misdiagnosis rate is high and it is easy to be misdiagnosed as a bronchogenic cyst. Careful histopathological observation and necessary immunohistochemical marker staining of the resected specimens, such as PAX 8, WT1, ER and PR positivity, can confirm the diagnosis and avoid misdiagnosis of other lesions. This article introduces the clinical, imaging characteristics, histopathological morphology, and immunohistochemical characteristics of 2 cases of posterior mediastinal Mullerian duct cysts. To explore the clinicopathological characteristics, diagnosis and differential diagnosis of posterior mediastinal Mullerian duct cysts.
Case report: Cochlear implantation for deafness caused by endolymphatic sac tumors in patients with von Hippel–Lindau syndrome
Authors: Rosiak Oskar , Pietrzak Nikodem , Jankowska Katarzyna , Kucharski Andrzej , Konopka Wiesław , Szymański Marcin
Published: November 2024

Introduction

Endolymphatic sac tumors (ELSTs) are rare neuroectodermal neoplasms that originate in the endolymphatic sac and duct. They exhibit no specific age or gender predilection, although they are more prevalent in patients with von Hippel–Lindau syndrome.

Material and methods

The manuscript preparation adhered to the CARE guidelines for standardizing clinical cases and the PRISMA guidelines for scientific reviews. Three studies that met the inclusion criteria were selected from an analysis of 15 articles, supplemented by two additional studies identified through citation review.

Results

The presented case describes a 16-year-old boy diagnosed with unilateral sensorineural hearing loss secondary to bilateral ELST. Surgical excision of the right ear tumor with simultaneous cochlear implantation was performed, followed by left ear surgery. Hearing restoration was achieved in the implanted right ear, with normal hearing in the left ear, and no postoperative vestibular symptoms were observed.

Conclusion

Prompt surgical intervention remains the cornerstone of ELST treatment. While cochlear implantation is sporadically reported in scientific literature, it offers a potential option for hearing improvement in patients suffering from deafness caused by the disease.
Dysregulation of deubiquitinases in gastric cancer progression
Authors: Xu Zifan , Lei Zi , Peng Shilan , Fu Xiaonan , Xu Yuanyuan , Pan Guoqing
Published: November 2024

Gastric cancer (GC), characterized by a high incidence rate, poses significant clinical challenges owing to its poor prognosis despite advancements in diagnostic and therapeutic approaches. Therefore, a comprehensive understanding of the molecular mechanisms driving GC progression is crucial for identifying predictive markers and defining treatment targets. Deubiquitinating enzymes (DUBs), also called deubiquitinases, function as reverse transcriptases within the ubiquitin-proteasome system to counteract protein degradation. Recent findings suggest that DUB dysregulation could be a crucial factor in GC pathogenesis. In this review, we examined recent research findings on DUBs in the context of GC, elucidating their molecular characteristics, categorizations, and roles while also exploring the potential mechanisms underlying their dysregulation in GC. Furthermore, we assessed the therapeutic efficacy of DUB inhibitors in treating malignancies and evaluated the prevalence of aberrant DUB expression in GC.
An event-related potential study of P300 in preschool children with attention deficit hyperactivity disorder
Authors: Tao Mengjiao , Sun Jing , Liu Siqi , Zhu Yike , Ren Yongying , Liu Ziqi , Wang Xiaoyue , Yang Wenmin , Li Guannan , Wang Xin , Zheng Wei , Zhang Jianzhao , Yang Jian
Published: November 2024

Objective

To study the characteristics of event related potential P300 in preschool children with attention deficit hyperactivity disorder (ADHD) aged 4–6 years (4≤ age <6), and to explore the differences in cognitive function compared with healthy children. To explore a new method for the study of cognitive function in preschool children with ADHD.

Methods

A total of 73 preschool children aged 4–6 years were selected from the outpatient clinic of Neurology Department, the ADHD-specialized Clinic and Health Care Department of the Children's Hospital Affiliated to the Capital Institute of Pediatrics from March 2021 to May 2024. They were divided into the ADHD group (45 cases) and healthy children group (28 cases). Event related potential P300 was measured in all children and the amplitude and latency of the wave were compared between the two groups separately.

Results

The latency of P300 at all the recording electrodes (Fz, Cz, Pz, Oz, C3, C4) in the ADHD group was significantly longer than controls (p < 0.05). The wave amplitudes of children with ADHD were significantly higher than controls at Pz and Oz points.

Conclusion

The differences between two groups in P300 test show that preschool children with ADHD present longer latency at central line of the brain and bilateral central lobes compared with healthy children, and higher amplitude at the central parietal lobe and central occipital lobe. It may suggest that attention cognition has already impaired in preschool children with ADHD.
Integrated analysis of single-cell and bulk transcriptome reveals hypoxia-induced immunosuppressive microenvironment to predict immunotherapy response in high-grade serous ovarian cancer
Authors: Chen Qingshan , Zhang Yue , Wang Chao , Ding Hui , Chi Liqun
Published: November 2024

Background

Hypoxia is significantly associated with cancer progression and treatment outcomes. Nevertheless, the precise molecular mechanisms underlying the hypoxia-induced immunosuppressive microenvironment in high-grade serous ovarian cancer (HGSOC) are still not fully understood.

Methods

By analyzing five independent transcriptomic datasets, we investigated the effect of hypoxia on prognosis and tumor microenvironment (TME) in HGSOC. The hypoxia levels and the intercellular communication signaling pathways were studied by using single-cell analysis. Furthermore, the Hypoxia-TME classifier was developed and then validated in the multiple HGSOC datasets. In addition, we also investigated the prognostic significance, genetic variations, signaling pathways, and the potential for immunotherapy benefits in different Hypoxia-TME subgroups.

Results

Hypoxia was identified as a crucial risk factor in HGSOC, and strongly correlated with an immunosuppressive microenvironment characterized by alterations in the composition and distribution of immune cells. Single-cell analysis elucidated the heterogeneity inherent within the TME in HGSOC, and demonstrated an association between the hypoxic TME and fibroblasts as well as macrophages. CellChat analysis identified SPP1-CD44 and CXCL12-CXCR4 as the principal signaling axes through which macrophages and fibroblasts interact with T cells, respectively. Moreover, a personalized Hypoxia-TME classifier was constructed and validated through the integration of the hypoxia (18 genes) and TME (7 immune cells) scores. It was observed that patients in the Hypoxialow/TMEhigh subgroup displayed a significantly better prognosis than other subgroups. Different subgroups exhibited unique genomic alterations and variations in signaling pathway differences, including TGF-β and Wnt/β-catenin pathways, which are closely associated with various biological functions. Finally, our results indicated that patients in the Hypoxialow/TMEhigh subgroup exhibit a better response to immunotherapy, suggesting the potential utility of the Hypoxia-TME classifier as a new biomarker in HGSOC.

Conclusion

Our study revealed hypoxia-induced immunosuppressive microenvironment, and developed Hypoxia-TME classifier to distinguish the prognosis, immune characteristics, and potential benefits of immunotherapy in HGSOC.
Inhibition of CISD2 enhances sensitivity to doxorubicin in diffuse large B-cell lymphoma by regulating ferroptosis and ferritinophagy
Authors: Zhang Chaofeng , Zhan Siting , He Yanjun , Pan Zhiqun , You Zhongyi , Zhu Xiongpeng , Lin Qi
Published: November 2024

Background

CDGSH iron-sulfur domain 2 (CISD2), an iron-sulfur protein with a [2Fe-2S] cluster, plays a pivotal role in the progression of various cancers, including Diffuse Large B-cell Lymphoma (DLBCL). However, the mechanisms by which CISD2 regulates the occurrence and development of DLBCL remain to be fully elucidated.

Methods

The potential role of CISD2 as a predictive marker in DLBCL patients treated with the R-CHOP regimen was investigated through bioinformatics analysis and clinical cohort studies. DLBCL cell lines (SUDHL-4 and HBL-1) were employed in this research. Adenoviral (AV) plasmids were used to either silence or overexpress CISD2 in these DLBCL cell lines. Additionally, the induction of ferroptosis in DLBCL cell lines was assessed. Various parameters, including cell proliferation, intracellular free iron levels, lipid peroxides, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), were measured. Furthermore, the expression of proteins associated with ferroptosis and ferritinophagy was analyzed. Drug-resistant DLBCL cell lines were developed by gradually increasing doxorubicin (DOX) concentration over 6 months. The biological role of CISD2 in these drug-resistant DLBCL cell lines was subsequently assessed.

Results

Elevated CISD2 levels were found to be associated with decreased sensitivity of DLBCL patients to the R-CHOP regimen, as indicated by bioinformatics and clinical cohort analysis. Silencing CISD2 significantly reduced cell proliferation, increased iron accumulation, depleted glutathione (GSH), and elevated malondialdehyde (MDA) levels, alongside the accumulation of ROS and increased MMP. Additionally, BECN1 and NCOA4 expressions were upregulated, while p62, FTH1, and GPX4 expressions were downregulated. Conversely, overexpression of CISD2 reversed these effects. Treatment of DLBCL cell lines with Erastin led to decreased CISD2 levels. Notably, in drug-resistant DLBCL cell lines, CISD2 knockdown promoted ferroptosis and ferritinophagy, restoring sensitivity to DOX and enhancing the efficacy of Erastin treatment.

Conclusion

Our findings suggest that CISD2 may play a role in the drug resistance observed in DLBCL patients. Inhibition of CISD2 could enhance ferroptosis and ferritinophagy, potentially improving the sensitivity of DLBCL cells to DOX treatment.
Anti-breast cancer effects of dairy protein active peptides, dairy products, and dairy protein-based nanoparticles
Authors: Zhang Deju , Yuan Ying , Xiong Juan , Zeng Qingdong , Gan Yiming , Jiang Kai , Xie Ni
Published: November 2024

Breast cancer is the most frequently diagnosed and fatal cancer among women worldwide. Dairy protein-derived peptides and dairy products are important parts of the daily human diet and have shown promising activities in suppressing the proliferation, migration, and invasion of breast cancer cells, both in vitro and in vivo. Most of the review literature employs meta-analysis methods to explore the association between dairy intake and breast cancer risk. However, there is a lack of comprehensive summary regarding the anti-breast cancer properties of dairy protein-derived peptides, dairy products, and dairy protein-based nanoparticles as well as their underlying mechanisms of action. Therefore, the present study discussed the breast cancer inhibitory effects and mechanisms of active peptides derived from various dairy protein sources. Additionally, the characteristics, anti-breast cancer activities and active components of several types of dairy products, including fermented milk, yogurt and cheeses, were summarized. Furthermore, the preparation methods and therapeutic effects of various dairy protein-containing nanoparticle delivery systems for breast cancer therapy were briefly described. Lastly, this work also provided an overview of what is currently known about the anti-breast cancer effects of dairy products in clinical studies. Our review will be of interest to the development of natural anticancer drugs.
Mechanism of Apigenin against breast cancer stem cells: network pharmacology and experimental validation
Authors: Ou Mengdie , Deng Zhicheng , Shi Yonghui , He Jianxiong , Ye Zicong , Guo Ming , Cheng Guohua , Wu Junyan , Lv Li
Published: November 2024

Apigenin (API), a traditionally sourced flavonoid, is recognized for its anti-neoplastic properties. Despite well-documented effects on tumorigenesis, the detailed therapeutic impact on breast cancer stem cells (BCSCs) and the associated molecular mechanisms are yet to be clarified. The objective of this study is to elucidate the therapeutic effects of API on BCSCs and to uncover its molecular mechanisms through network pharmacology and experimental validation. Interactions of API with candidate targets were examined through target screening, enrichment analysis, construction of protein-protein interaction networks, and molecular docking. MCF-7-derived BCSCs were utilized as a model system to investigate and substantiate the anti-BCSC effects of API and the underlying mechanism. Molecular docking studies have shown that API and TP53 exhibit favorable binding affinity. Compared with the negative control group, API effectively suppressed the expression of BCSC-related proteins such as ALDH1A1, NANOG, EpCAM, and MYC, downregulated p-PI3K and p-AKT, and upregulated p53. This study demonstrates that API can play an anti-BCSC role by regulating the PI3K/AKT/p53 pathway in BCSCs of MCF-7 cells, highlighting its potential as a therapeutic agent for targeting BCSCs.
Predicting adverse drug event using machine learning based on electronic health records: a systematic review and meta-analysis
Authors: Hu Qiaozhi , Chen Yuxian , Zou Dan , He Zhiyao , Xu Ting
Published: November 2024

Introduction

Adverse drug events (ADEs) pose a significant challenge in current clinical practice. Machine learning (ML) has been increasingly used to predict specific ADEs using electronic health record (EHR) data. This systematic review provides a comprehensive overview of the application of ML in predicting specific ADEs based on EHR data.

Methods

A systematic search of PubMed, Web of Science, Embase, and IEEE Xplore was conducted to identify relevant articles published from the inception to 20 May 2024. Studies that developed ML models for predicting specific ADEs or ADEs associated with particular drugs were included using EHR data.

Results

A total of 59 studies met the inclusion criteria, covering 15 drugs and 15 ADEs. In total, 38 machine learning algorithms were reported, with random forest (RF) being the most frequently used, followed by support vector machine (SVM), eXtreme gradient boosting (XGBoost), decision tree (DT), and light gradient boosting machine (LightGBM). The performance of the ML models was generally strong, with an average area under the curve (AUC) of 76.68% ± 10.73, accuracy of 76.00% ± 11.26, precision of 60.13% ± 24.81, sensitivity of 62.35% ± 20.19, specificity of 75.13% ± 16.60, and an F1 score of 52.60% ± 21.10. The combined sensitivity, specificity, diagnostic odds ratio (DOR), and AUC from the summary receiver operating characteristic (SROC) curve using a random effects model were 0.65 (95% CI: 0.65–0.66), 0.89 (95% CI: 0.89–0.90), 12.11 (95% CI: 8.17–17.95), and 0.8069, respectively. The risk factors associated with different drugs and ADEs varied.

Discussion

Future research should focus on improving standardization, conducting multicenter studies that incorporate diverse data types, and evaluating the impact of artificial intelligence predictive models in real-world clinical settings.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565842, identifier CRD42024565842.
A diffusion tensor imaging-based multidimensional study of brain structural changes after long-term high-altitude exposure and their relationships with cognitive function
Authors: Liu Ning , Feng Li , Chai Shuangwei , Li Hailong , He Yuanyuan , Guo Yongyue , Hu Xin , Li Hengyan , Li Xiangwei , Zhou Zan , Li Xiaomei , Huang Yonghong , He Wanlin , Huang Xiaoqi , Wu Yunhong , Meng Jinli
Published: November 2024

Background

Brain structure changes after long-term adaptation to the high-altitude environment; however, related studies are few, results are in consistent, and long-term effects on cognitive function and pathophysiological mechanisms are unclear. Therefore, diffusion tensor imaging (DTI) was used to investigate the damage to white matter fiber tracts and correlations between brain structural abnormalities and cognitive function.

Methods

Forty healthy Han people living on the high-altitude and 40 healthy Han people living on the plains were enrolled in this study and underwent magnetic resonance imaging, emotional state assessment, and cognitive function tests. The sex, age, education level, and social status of the two groups were not different. The tract-based spatial statistics (TBSS) method was used to analyze the DTI parameters of the white matter fiber tracts of the two groups. Moreover, the partial correlation method (age and sex as covariates) was used to analyze the correlations between the intergroup differences in the DTI parameters and a series of clinical indicators of emotional state and cognitive function. Two-sample t tests, Mann-Whitney U test, generalized linear model, or chi-square tests were used for statistical analysis.

Results

Compared with those individuals in the plain group, the scores on the PSQI, SDS, SAS, PHQ-9, and GAD-7 of individuals in the high-altitude group were higher, while the scores on the DST-Backwards, MoCA, and MMSE in the high-altitude group were lower. The fractional anisotropy (FA) value of the body of the corpus callosum in the high-altitude group was lower than that in the plain group. The FA value of the body of the corpus callosum in the plain group was negatively correlated with the Logical Memory, while no significant correlation was found in the high-altitude group.

Conclusion

This study revealed that long-term exposure to a high-altitude environment could lead to a series of changes in sleep, emotion, and cognitive function and irreversible damage to the white matter microstructure of the body of the corpus callosum, which is the related brain region responsible for logical memory. The absence of logical memory impairment in the healthy Han Chinese population living on the high-altitude in this study may be due to the existence of adaptive compensation after long-term high-altitude exposure.
Psychosocial predictors of attitude toward premarital sexual practice among university students, Ethiopia
Authors: Yedemie Yordanos Yibeltal
Published: November 2024

Objectives

Premarital sexual practice during adolescence may lead to different sexual and reproductive health problems, including HIV/AIDS. The objective of this study was to assess psychosocial predictors of attitudes toward premarital sex among Bahir Dar University students.

Methods

A correlational design was used. A multi-stage sampling technique was used to select 375 respondents for the study, although the analysis was based on the 361 questionnaires that were returned from the field and found useful for analysis. Data was collected using a self-developed and modified instrument on standardized scales. The internal consistency of the Perception of Peer Pressure Scale was 0.83, while the self-esteem measuring scale had a reliability of 0.77. The internal consistency of the sexual attitude inventory scale was 0.97. The data were quantitatively analyzed using (inferential statistics) logistic regression, one sample t test, and an independent sample t test.

Results

The findings of the study showed that all the psychological variables investigated were found to significantly predict premarital sexual relationships among the respondents. Male students with the experience of premarital sex have a higher level of self-esteem and exposure to peer pressure than their female counterparts. A study suggests that male students with the experience of premarital sex have a higher level of self-esteem and exposure to peer pressure than their female counterparts. Self-esteem negatively predicted attitudes toward premarital sex.

Conclusion

Scaling up the level of school counseling, especially in the area of sexual adjustment and modification of the psychological variables investigated, was recommended.
Encouraging water-saving behavior during a “Moment of Change”: the efficacy of implementation intentions on water conservation during the transition to university
Authors: Mitev Kaloyan , Rennison Freya , Haggar Paul , Hafner Rebecca , Lowe Alice , Whitmarsh Lorraine
Published: November 2024

Water saving behavior is of substantial importance in climate change mitigation and resilience, including reducing time spent in the shower. However, water use is, for many, a strong habit, and, as such, incorporating new water saving behaviors into one's domestic routines may be unsuccessful. In this study, we consider the extent to which a composite behavior change intervention (of water-saving information, implementation intention formation, and monitoring using a shower timer) is effective in reducing the domestic water consumption of new university students who have recently moved into university accommodation. We focus on aspects of the habit discontinuity hypothesis, namely that a natural moment of change facilitates behavior change by weaking existing habits. The intervention was found to be effective, increasing the frequency of self-reported water-saving behavior over behavior measured in a control group. However, shower times, and water usage (measured at the residential level), were not affected by the intervention, and strength of existing habits, readiness to change water behavior, and recency of starting university were each not significantly associated with the effectiveness of the intervention. However, all participants (irrespective of intervention) increased water-saving behavior and reduced shower time during the study, with residential water usage being less for residences with more participating students. Contrary to expectations, the timing of the intervention did not show a clear effect upon the efficacy of the intervention. We discuss these findings with respect to moments of change and habit discontinuity theory as well as implications for practical behavior change interventions.
The role of attitude toward nature in learning about environmental issues
Authors: Baierl Tessa-Marie , Kaiser Florian G. , Bogner Franz X.
Published: November 2024

Attitude toward nature and environmental attitude are two distinct propensities that both further learning about the environment. The present study builds upon prior research by investigating the role of attitude toward nature in learning about environmental issues. In a sample of 1,486 university, middle and high school students (Mage = 15.25, SD = 3.2), we first calibrated a pool of items expressing attitude toward nature. We found differences in how adolescents expressed their appreciation for nature at different ages. It is essential to consider these differences to accurately ascertain adolescents’ attitudes toward nature. We then conducted a mediation test. Whereas attitude toward nature determined the levels of knowledge students gained and retained, environmental attitude fully mediated the environmental knowledge subsequently demonstrated by the students. Our research suggests that researchers and educators may benefit from taking an experiential approach to learning about sustainable development by promoting appreciation for nature.