bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive analysis of the diagnostic and therapeutic value, immune infiltration, and drug treatment mechanisms of GTSE1 in lung adenocarcinoma
Authors: Yan Guanqiang , Li Jingxiao , Gao Xiang , Liu Jun , Feng Guiyu , Li Yue , Zhou Huafu
Published: November 2024

Objective

The aim of this investigation was to assess the diagnostic and therapeutic efficacy of G2 and S-phase expressed 1 (GTSE1) in lung adenocarcinoma (LUAD), while examining its impact on immune infiltration and drug treatment mechanisms.

Methods

This research involved examining the expression patterns and diagnostic accuracy of GTSE1 in LUAD using various databases and clinical samples. The databases utilized included Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and The Cancer Genome Atlas (TCGA). Both gene expression and protein levels were analyzed. Subsequently, the prognostic ability of GTSE1 was evaluated based on clinical follow-up data using methods such as using univariate, multivariate, and prognostic meta-analysis. Additionally, potential mechanisms of action of GTSE1 were explored through enrichment analysis. Furthermore, the correlation between GTSE1 expression and the tumor microenvironment, immune cell infiltration, and immune checkpoints was assessed using ESTIMATE and CIBERSORT algorithms. The effectiveness of chemotherapy and targeted therapy was predicted using the “pRophetic” R package, which analyzed gene expression data.

Results

Analysis of GEO data, CPTAC data, TCGA data, and clinical samples revealed increased levels of GTSE1 in LUAD tissues. Enhanced GTSE1 expression demonstrated excellent diagnostic accuracy and served as a significant prognostic indicator for LUAD patients. GTSE1 expression emerged as an independent predictive factor in both univariate and multivariate Cox regression analyses. Furthermore, functional enrichment analysis suggested a potential association between GTSE1 and the cell cycle, p53 signaling pathway, as well as ubiquitin-mediated protein degradation. High expression of GTSE1 was associated with increased immune cell infiltration and heightened sensitivity to a specific type of chemotherapy and targeted drugs.

Conclusion

Increased expression of GTSE1 in patients with LUAD showed significant diagnostic and prognostic significance. It was also associated with increased immune infiltration and an unfavorable response to targeted medication.
Effect of omalizumab on inflammatory markers in COVID-19: an exploratory analysis of the COVID-19 immunologic antiviral therapy with omalizumab (CIAO) trial
Authors: Prosty Connor , Le Michelle , Lu Yang , Khoury Lauren , Cormier Maxime , Cheng Mathew P. , Fowler Robert , Murthy Srinivas , Tsang Jennifer LY , Lejtenyi Duncan , Ben-Shoshan Moshe , Rahme Elham , Golchi Shirin , Dendukuri Nandini , Lee Todd C. , Netchiporouk Elena
Published: November 2024

Background

The CIAO trial recently demonstrated a probable clinical benefit of omalizumab in the treatment of severe COVID-19; however, the mechanism underlying this benefit remains unclear. Therefore, we sought to longitudinally assess the impact of omalizumab on serum cytokines in CIAO trial patients to determine its mechanism of action.

Methods

Blood samples were collected on days 0, 2, 7, and 14 from patients recruited into the CIAO trial and who consented to this substudy. Blood samples were tested by a panel of 25 inflammatory cytokines, as well as for markers of mast cell activation. Levels of inflammatory biomarkers were compared over time between omalizumab- and placebo-treated patients by generalized linear mixed-effects model. Associations between biomarkers and clinical outcomes were investigated by mixed-effects logistic regression.

Results

Nineteen patients were recruited into this substudy; 10 were assigned to placebo and 9 to omalizumab. Monokine induced by gamma interferon was significantly positively associated with severe COVID-19 (Odds Ratio [OR] = 1.06, 95%CI = 1.00–1.11, p = 0.043). Further, omalizumab significantly reduced interleukin-15 (Coefficient = −0.95, p = 0.048) and macrophage inflammatory protein-1 (Coefficient = −1.31, p = 0.010) levels. However, neither was significant in analyses adjusting for multiple hypothesis testing.

Conclusion

Although limited by a small sample size, these results suggest that omalizumab’s potential benefit in COVID-19 may be mediated independently of modulation of the measured serum biomarkers. Further studies are needed to investigate omalizumab’s mechanism of action in COVID-19.
Plasma neutrophil extracellular traps in patients with sepsis-induced acute kidney injury serve as a new biomarker to predict 28-day survival outcomes of disease
Authors: He Jian , Zheng Feng , Qiu Lihua , Wang Yilan , Zhang Jing , Ye Hongwei , Zhang Qian
Published: November 2024

Background

There is currently no accurate, readily available, or validated biomarker for assessing disease severity and survival outcomes in sepsis-induced acute kidney injury (SAKI), which limits the ability to conduct effective therapeutic interventions. The neutrophil extracellular traps (NETs) may be involved in the pathophysiology of SAKI. The present study investigated the predictive value of plasma NETs for the survival outcome of patients with SAKI.

Methods

This observational study included 136 SAKI patients, all of whom underwent a 28-day follow-up. According to the follow-up records, SAKI patients were divided into two groups: the non-survivor group (60 subjects) and the survivor group (76 subjects). Blood samples were collected after the diagnosis of AKI to measure three NET markers and 12 inflammatory indices. Correlation analysis, logistic regression analysis, receiver operating characteristic curve analysis, and survival analysis were performed.

Results

Compared to survivors, non-survivors among SAKI patients exhibited significantly higher levels of three plasma NET markers (all p < 0.001). Meanwhile, in SAKI patients, plasma levels of NET markers were significantly associated with serum levels of inflammatory indices. Additionally, serum interleukin (IL)-2, IL-8, IL-10, and tumor necrosis factor-alpha showed an interactive effect with plasma NET markers on the survival of SAKI patients. Furthermore, the combination of three plasma NET markers could identify SAKI patients with a poor 28-day survival with better accuracy (area under the curve = 0.857). Finally, plasma NET markers may independently predict the 28-day survival in SAKI patients.

Conclusion

Plasma NET markers were elevated in SAKI patients with poor outcomes and served as biomarkers for predicting 28-day survival in SAKI patients.
Factors associated with unfavorable outcomes in older patients with traumatic brain injury: analysis from the “All of Us” research program
Authors: Chen Zhangying , Wang Zihao , Mentis Alexios-Fotios A. , Stey Anne M. , Schwulst Steven J.
Published: November 2024

Traumatic brain injury (TBI) afflicts approximately 70 million people worldwide annually, with patients aged 65 years and older accounting for an increasing proportion of TBI patients. Older patients also experience increased morbidity and mortality post-TBI compared to their younger counterparts. Nevertheless, clinical trials often exclude older TBI patients, and age-specific TBI treatment is lacking. We hypothesized that the APOE genotype and age-associated comorbidities, such as heart disease, are associated with unfavorable outcomes following TBI in older patients. We utilized a dataset from the “All of Us research” (AoU) to study this vulnerable population post-TBI. Launched by the National Institutes of Health (NIH), AoU is a nationwide prospective cohort study aiming to enroll 1 million or more individuals by emphasizing traditionally underrepresented populations in the United States. We defined patients diagnosed with post-concussion syndromes (PCS) as those with unfavorable TBI outcomes, and we also assessed the associations between PCS observed in older patients and different comorbidities variables/APOE genotypes via multiple logistic regression models. Consequently, APOE ε4 allele was strongly associated with PCS in patients aged 65 and older. Our findings provide direct evidence for developing better predictive tools and potentially improving the clinical guidance and management of older adults with TBI.
Assessing stroke recurrence in sICAS: a study on mCSVD score and culprit plaque magnetic resonance characteristics
Authors: Ren Kaixuan , He Juan , Zhu Li , Gu Yue , Qu Hang , Zhao Yi , Wang Wei
Published: November 2024

Background

Recurrent ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) can be attributed to two main causes: intracranial atherosclerotic stenosis (ICAS) and cerebral small vessel disease (CSVD). This study investigates the potential associations between stroke recurrence and the modified cerebral small vessel disease (mCSVD) burden score, as well as the characteristics of culprit plaques related to intracranial artery high-resolution vessel wall imaging (HR-VWI).

Methods

A total of 145 patients presenting sICAS underwent intracranial artery HR-VWI and routine cranial MRI at two large Chinese hospitals from December 2019–2022 were participants of this retrospective analysis. Standard MRI scans were used to calculate the mCSVD score. Following a 12-month observation period, the patients were categorized into two distinct groups depending on whether or not they experienced a subsequent stroke.

Results

Within 12 months, 32 patients experienced stroke recurrence. The recurrence group’s mCSVD score was higher compared to the non-recurrence group (p < 0.001). Their luminal stenosis and culprit plaque thickness and burden were also higher (p < 0.05). Additionally, higher rates of diabetes, T1WI hyperintensity of culprit plaques, and significant plaque enhancement were observed in the recurrence group (p < 0.05). The adjusted Cox regression model indicated that the mCSVD score (HR = 1.730, 95% CI 1.021–2.933, p = 0.042) and T1WI hyperintensity of the culprit plaque (HR = 6.568, 95% CI 1.104–39.059, p = 0.039) remained significantly independent risk variables. The combination of the mCSVD score and T1WI hyperintensity of the culprit plaque demonstrated the highest efficacy in predicting stroke recurrence (z = 2.678, p < 0.05).

Conclusion

The mCSVD score, associated with T1WI hyperintensity of culprit plaque, effectively predicts stroke recurrence and can be easily obtained, offering high clinical value.
Elevated plasma total homocysteine levels are associated with behavioral and psychological symptoms in dementia with Lewy bodies
Authors: Zhang Guili , Liu Shuai , Xu Ying , Ma Ling-Yun , Zhang Wei , Ji Yong
Published: November 2024

Objective

To investigate the association between plasma total homocysteine (tHcy) levels and behavioral and psychological symptoms of dementia (BPSD) in dementia with Lewy bodies (DLB) patients.

Methods

A total of 82 DLB patients and 134 age-matched healthy controls were included in this study. DLB patients were assessed using the Mini-Mental Status Examination (MMSE), the Clinical Dementia Rating Scale (CDR), and the Neuropsychiatric Inventory (NPI). Plasma tHcy, serum vitamin B12, and folate levels were measured in all study participants. We used Spearman’s rank correlation test to analyze the association between tHcy concentrations and NPI scores, MMSE, CDR, and the duration of dementia in DLB patients.

Results

Clinically significant BPSD was present in 92.7% of DLB patients. The most frequent BPSD were hallucinations (30.4%), apathy (30.4%), and delusions (26.8%). Elevated plasma tHcy levels were significantly associated with total NPI scores in DLB patients, particularly in 10 NPI sub-domains, except for agitation/aggression and disinhibition. No statistically significant association was found between plasma tHcy levels and MMSE, CDR, or dementia duration.

Limitations

Longitudinal studies with larger sample sizes are required to further explore the relationship between tHcy levels and BPSD in DLB patients as the disease progresses.

Conclusion

Our study highlighted the high incidence of BPSD and was the first to show that BPSD is associated with elevated plasma tHcy levels in DLB patients in China. These results support the hypothesis that controlling homocysteine levels could offer a new direction for managing BPSD.
Multi-perspective characterization of seizure prediction based on microstate analysis
Authors: Shi Wei , Cao Yina , Chen Fangni , Tong Wei , Zhang Lei , Wan Jian
Published: November 2024

Epilepsy is an irregular and recurrent cerebral dysfunction that significantly impacts the affected individual's social functionality and quality of life. This study aims to integrate cognitive dynamic attributes of the brain into seizure prediction, evaluating the effectiveness of various characterization perspectives for seizure prediction, while delving into the impact of varying fragment lengths on the performance of each characterization. We adopted microstate analysis to extract the dynamic properties of cognitive states, calculated the EEG-based and microstate-based features to characterize nonlinear attributes, and assessed the power values across different frequency bands to represent the spectral information of the EEG. Based on the aforementioned characteristics, the predictor achieved a sensitivity of 93.82% on the private FH-ZJU seizure dataset and 93.22% on the Siena Scalp EEG dataset. The study outperforms state-of-the-art works in terms of sensitivity metrics in seizure prediction, indicating that it is crucial to incorporate cognitive dynamic attributes of the brain in seizure prediction.
Branched-chain amino acid supplementation and voluntary running have distinct effects on the serum metabolome of rats with high or low intrinsic aerobic capacity
Authors: Karvinen Sira , Korhonen Tia-Marje K. , Kiviö Ronja , Lensu Sanna , Gajera Bharat , Britton Steven L. , Koch Lauren G. , Nieminen Anni I. , Kainulainen Heikki
Published: November 2024

Introduction

A growing body of literature associates branched-chain amino acid (BCAA) catabolism to increased fatty acid oxidation and better metabolic health. Hence, BCAA-rich diets may improve body composition and muscle protein synthesis. However, the role of individual characteristics such as a low aerobic fitness, a well-established risk factor for cardio-metabolic diseases, has not been studied.

Methods

This study examined 64 female rats from the high-capacity runner (HCR) and low-capacity runner (LCR) rat model. Rats from each line (HCR or LCR) were divided into four groups; differing from diet (CTRL or BCAA) and from the opportunity to voluntarily run on a running wheel (NONRUNNER or RUNNER). Groups were matched for body mass and maximal running capacity within each line. We measured maximal running capacity and metabolism before and after the intervention of diet and voluntary running activity. After the end of the experiment, serum samples were collected for metabolome analysis.

Results

We are the first to show that BCAA supplementation has a more pronounced impact on LCRs compared to HCRs. Specifically, in LCR rats, BCAA supplementation led to reduced daily voluntary running distance and an enrichment of serine metabolism in the serum metabolome. While voluntary running increased food intake and energy expenditure, its effects on the serum metabolome were minimal in HCRs.

Conclusion

The present research highlights the benefit achieved by combining BCAA supplementation with running activity, especially in the LCR line. Importantly, our results underscore the interconnected role of BCAAs and fatty acid metabolism in promoting overall metabolic health.
A global analysis of portion size recommendations in food-based dietary guidelines
Authors: Salesse Fanny , Eldridge Alison L. , Mak Tsz Ning , Gibney Eileen R.
Published: November 2024

Objective

Since large food portion sizes (PS) lead to overconsumption, our objective was to review PS recommendations for commonly consumed food groups reported in Food-Based Dietary Guidelines (FBDGs) globally and to assess variation in PS across countries and regions.

Methods

Consumer-oriented FBDGs from the Food and Agriculture Organization (FAO) online repository were used to evaluate dietary recommendations, PS and number of portions for common food groups. Guidelines were classified for each group as qualitative, quantitative, or missing. A standardized approach was applied to convert PS recommendations given as household measures, cup equivalents, pieces and other measures into grams for cross comparison. Variation of recommended PS of common food groups within and across regions was examined.

Results

Among 96 FBDGs, variations were found both across and within regions. At a regional level, the highest median PS recommendations were seen in Europe for Meat, Fish and Pulses, in the Near East for Dairy products, and in Africa for most grain-based foods. Recommendations for Fruits and Vegetables showed the highest consistency across FBDGs worldwide, whereas guidance on Meat, fish & eggs and Cooked cereals/grains showed discrepancies in the classification of foods into categories, as well as in the number of portions per day.

Discussion

While some variation in PS recommendations across countries can be expected due to cultural and regional dietary practices, inconsistent definitions to refer to a portion and varied derivation methods may further produce discrepancies. Harmonizing development methods for FBDG could help establish more consistent reference portion sizes and therefore provide clearer guidance to consumers.
African walnut (Plukenetia conophora) oil promotes glucose uptake while improving energy metabolism and steroidogenesis and maintaining surface architecture in rat testes
Authors: Erukainure Ochuko L. , Chukwuma Chika I.
Published: November 2024

Background

African walnut (Plukenetia conophora) oil (AWO) has been reported for its nutritional and medicinal properties and has been employed for the management of metabolic diseases including hyperglycemia-mediated ailments.

Objective

In the present study, AWO was investigated for its ability to stimulate glucose uptake and its effect on energy metabolism, steroidogenesis, and tissue morphology in isolated testes of Wistar rats.

Methods

Isolated testes were incubated with AWO (30–240 μg/mL) in the presence of 11.1 mMol glucose at 37°C for 2 h. Control consisted of testes incubated with glucose only, while normal control consisted of testes not incubated with AWO and/or glucose. The standard antidiabetic drug was metformin.

Results and conclusion

Incubation with AWO led to significant increase in glucose uptake, hexokinase, glyoxalase 1, glutathione reductase, glutathione peroxidase, 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase activities, GLUT4, glutathione, and ATP levels while concomitantly suppressing glucose-6-phosphatase, fructose-1,6-biphosphatase, glycogen phosphorylase, aldose reductase, polyol dehydrogenase, E-NTPDase, and ATPase activities. Furthermore, incubation with AWO led to improved testicular morphology while elevating testicular levels of magnesium, sulfur, potassium, calcium, and iron. Fatty acid profiling with GC-MS revealed linoleic acid and linolenic acid as the predominant essential fatty acids in AWO. Molecular docking analysis revealed potent molecular interactions of linoleic acid and linolenic acid with GLUT4. These results suggest the ability of AWO to improve testicular glucose metabolism and steroidogenesis and can be explored in the management of male infertility.
Invasive aspergillosis complicated in a patient with non-small cell lung cancer harboring RET fusion during treatment with RET-TKIs: a case report and literature review
Authors: Setiwalidi Kaidiriye , Li Yimeng , Ma Yuyan , Hao Zhanpeng , Zhao Yujia , Zhang Yuxin , Liang Xuan , Tian Tao , Ruan Zhiping , Yao Yu , Fu Xiao
Published: November 2024

Pralsetinib and selpercatinib have been approved as specific tyrosine kinase inhibitors (TKIs) for the treatment of patients with non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) fusion and mutation. However, adverse events associated with pralsetinib and selpercatinib are not fully understood, especially in the real world. In this case, invasive aspergillosis that appeared concurrent with RET-TKI targeted therapy is proposed to be an additional adverse drug reaction (ADR) that was not mentioned in previous reports. Here, we describe the process of clinical diagnosis and treatment of invasive aspergillosis and attempt to explore its possible pathogenesis in association with RET-TKI targeted therapy, with the aim of providing clinicians a more in-depth understanding of the ADR associated with RET-TKIs, as well as to prevent serious outcomes caused by reduction or discontinuation of antitumor therapy.
Progress on angiogenic and antiangiogenic agents in the tumor microenvironment
Authors: Xu Jian , Tang Zhihua
Published: November 2024

The development of tumors and their metastasis relies heavily on the process of angiogenesis. When the volume of a tumor expands, the resulting internal hypoxic conditions trigger the body to enhance the production of various angiogenic factors. These include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor-α (TGF-α), all of which work together to stimulate the activation of endothelial cells and catalyze angiogenesis. Antiangiogenic therapy (AAT) aims to normalize tumor blood vessels by inhibiting these angiogenic signals. In this review, we will explore the molecular mechanisms of angiogenesis within the tumor microenvironment, discuss traditional antiangiogenic drugs along with their limitations, examine new antiangiogenic drugs and the advantages of combination therapy, and consider future research directions in the field of antiangiogenic drugs. This comprehensive overview aims to provide insights that may aid in the development of more effective anti-tumor treatments.
Efficacy and safety of lebrikizumab for the treatment of moderate-to-severe atopic dermatitis: a systematic review and meta-analysis
Authors: Lin Jinger , Luo Min , Zhuo Qianwei , Chen Nuo , Zhang Haosong , Han Yue
Published: November 2024

Background

Lebrikizumab, an IL-13 immunomodulator, has shown recommendable effectiveness and safety in clinical studies for the treatment of moderate-to-severe atopic dermatitis (AD) in adolescents and adults.

Objective

To evaluate the efficacy and safety of lebrikizumab in the treatment of moderate-to-severe AD through a meta-analysis.

Methods

PubMed, Embase, Web of Science, Medline, and ClinicalTrials.gov databases were searched up to 8 August 2023. Randomized clinical trials of lebrikizumab treatment for moderate-to-severe AD were included by screening titles, abstracts, and papers.

Results

Five studies involving 1,551 patients with AD were identified. Pooled analysis revealed significant improvements in the Eczema Area and Severity Index (EASI) score (SMD = −0.527; 95% CI = [−0.617, −0.436]), Investigator’s Global Assessment (IGA) score (RR = 2.122; 95% CI = [1.803, 2.496]), Body Surface Area (BSA) score (SMD = −0.608; 95% CI = [−1.099, −0.118]), SCORing Atopic Dermatitis (SCORAD) score (SMD = −0.441; 95% CI = [−0.633, −0.250]). Moreover, Pruritus Numeric Rating Scale (P-NRS) score, Patient-oriented Eczema Measure (POEM) scores, Sleep-loss score and Dermatology Life Quality Index (DLQI) scores showed similar results. Adverse events (AEs) (RR = 0.984; 95% CI = [0.907, 1.068]) for lebrikizumab showed no statistically significant difference compared to placebo, with similar results for serious adverse events (SAEs) (RR = 0.748; 95% CI = [0.410, 1.364]).

Conclusion

This meta-analysis reveals that lebrikizumab has higher efficacy and safety in the treatment of moderate-to-severe AD, with the 250 mg Q2W dosage regimen appearing to be more advantageous.
Comparison of the effects of deferasirox film-coated tablets (Jadenu®) and deferasirox dispersible tablets (Exjade®) in patients with beta thalassemia major: a preliminary report of the effects on the satisfaction, convenience, cardiac/liver MRI T2*, serum ferritin level, and biochemical profiles
Authors: Mobinikhaledi Mahya , Falahati Vahid , Tajerian Amin , Hashiani Amir Almasi , Ghaffari Kazem , Ghasemi Ali
Published: November 2024

Background

Deferasirox (DFX) is a once-daily oral iron chelator with proven dose-dependent efficacy in patients with thalassemia major (TM). The reason for switching from DFX dispersible tablets (Exjade®) to DFX film-coated tablets (Jadenu®) was intolerance. Many patients also reported that deferasirox® did not taste good. In this study, we compared the effect of Jadenu® and Exjade® on satisfaction, convenience, cardiac/liver MRI T2*, serum ferritin levels, and biochemical profiles in patients with thalassemia major.

Method

Sixty-two patients with thalassemia over 2 years of age, who had iron overload indicated by chelation therapy, were randomly divided into two groups. The first group (n = 32) is treated with Exjade®, and the second group (n = 30) is treated with Jadenu®. Laboratory investigations included alkaline phosphatase (ALK), alanine transferase (ALT), aspartate transferase (AST), and serum ferritin levels. Cardiac/liver MRI T2* levels and patient satisfaction and convenience, were assessed before and 1 year after starting therapy.

Results

The study found that 53.3% of Jadenu® patients were satisfied with the taste of the medication compared to only 12.5% of Exjade® patients, which was statistically significant (p = 0.001). Additionally, 40% of Jadenu® patients were satisfied with the ease of taking the medication compared to 28.1% of Exjade® patients, and again, the difference was statistically significant (p = 0.047). A comparison of the cardiac MRI T2* levels between the two studied groups showed no significant difference (p = 0.851).

Conclusion

Jadenu® offers patients an improved formulation that can be taken on an empty stomach, has a better taste, and presents fewer gastrointestinal tolerability concerns. Overall, patient satisfaction is higher with Jadenu®, which may improve adherence and reduce the frequency and severity of complications associated with iron overload. This, in turn, may help mitigate cardiovascular and hepatic complications from iron overload in the long term.

Clinical Trial Registration

https://irct.behdasht.gov.ir/search/result?query=IRCT20210830052346N1
Dipeptide alanine-glutamine ameliorates retinal neurodegeneration in an STZ-induced rat model
Authors: Zhang Yuhan , Wei Mingyan , Wang Xin , Xu Yuan , Zong Rongrong , Lin Xiang , Li Shiying , Chen Wensheng , Liu Zuguo , Chen Qian
Published: November 2024

Introduction

Diabetic retinopathy (DR) is a common complication of diabetes. Retinal neuronal degeneration is an early event in DR, indicated by the declined electroretinogram (ERG). Dipeptide alanine-glutamine (Ala-Gln) is widely used as a nutritional supplement in the clinic and has anti-inflammatory effects on the gastrointestinal system. Studies also reported that glutamine has beneficial effects on diabetes. This study aimed to investigate the possible therapeutic effects of Ala-Gln in diabetic retinal neurodegeneration and to delineate its mechanism of action.

Methods

The Streptozotocin (STZ)-induced rat model was used as a DR model. ERG was used to measure the neuronal function of the retina. Western blot analysis was performed to test the expression of proteins. Immunofluorescence staining was used for the detection and localization of proteins.

Results

In diabetic rats, the amplitudes of ERG were declined, while Ala-Gln restored the declined ERG. Retinal levels of inflammatory factors were significantly decreased in Ala-Gln-treated diabetic rats. Ala-Gln mitigated the declined levels of glutamine synthetase and ameliorated the upregulated levels of glial fibrillary acidic protein (GFAP) in diabetic retinas. Moreover, Ala-Gln upregulated the glycolytic enzymes pyruvate kinase isozymes 2 (PKM2), lactate dehydrogenase A (LDHA) and LDHB and stimulated the mTOR signaling pathway in diabetic retinas. The mitochondrial function was improved after the treatment of Ala-Gln in diabetic retinas.

Discussion

Ala-Gln ameliorates retinal neurodegeneration by reducing inflammation and enhancing glucose metabolism and mitochondrial function in DR. Therefore, manipulation of metabolism by Ala-Gln may be a novel therapeutic avenue for retinal neurodegeneration in DR.
Single to multiple digital holograms for phase compensation and defect detection
Authors: Chen Zhenkai , Zhou Wenjing , Ge Zhou , Yu Yingjie , Zhang Hongbo , Poon Ting-Chung
Published: November 2024

Digital holography enables quantitative phase imaging based on interference. A digital hologram often encodes the phase information along with aberrations or deformations. This article reviews phase analysis and its diverse application solutions and challenges in digital holography including aberrations removal in a single hologram, defect and deformation detection using dual-holograms, and defect location in multi-holograms. The state-of-the-art of the techniques are presented and discussed in detail for phase analysis, separation, and quantification. Phase analysis in digital holography can provide high precision, high resolution, rapid quantitative and intelligent imaging abilities.
Divertor Tokamak Test: Impact of NBI shine-through and beam-plasma interaction on Divertor Tokamak Test facility
Authors: De Piccoli C. , Vincenzi P. , Veronese F. , Agostinetti P. , Casiraghi I. , Castaldo A. , Mantica P. , Murari A. , Bolzonella T.
Published: November 2024

Introduction

In this work, we aim to explore numerically the behavior of beam energetic particles in the Divertor Tokamak Test (DTT), a superconductive device equipped with a Neutral Beam Injection (NBI) system capable of injecting neutrals up to 510 keV.

Method

We explore beam ionization and beam slowing down for different DTT plasma scenarios. Numerical simulations are performed using the ASCOT suite of codes, including a wide-range scan of plasma density and beam injection energy. For different plasma conditions, we estimate shine-through losses, including the heat fluxes on the first wall thanks to dedicated particle tracing simulations. Orbits of newly-born fast ions are characterized by means of the constant of motion phase space, showing how trapped energetic particles’ population and prompt losses change with plasma density and NBI energy.

Results and discussion

Slowing down simulations show that NBI injection at 510 keV is well coupled to DTT plasmas. DTT NBI will be one of the sources of auxiliary ion heating, with an absorbed power ratio of up to ∼50% depending on plasma and beam parameters. At low plasma densities, energetic particle confinement is less efficient, and NBI power and/or energy reduction is expected.
Characterisation of 3D trench silicon pixel sensors irradiated at 1⋅1017 1 MeV neqcm-2
Authors: Addison M. , Bellora A. , Borgato F. , Brundu D. , Cardini A. , Cossu G. M. , Dalla Betta G. F. , La Delfa L. , Lai A. , Lampis A. , Loi A. , Obertino M. M. , Vecchi S. , Verdoglia M.
Published: November 2024

The 3D trench silicon pixel sensors developed by the TimeSPOT collaboration have demonstrated exceptional performance, even after exposure to extreme radiation fluences up to 1⋅1017 1 MeV neq/cm2. This study assesses the radiation tolerance of these sensors using minimum ionizing particles during a beam test campaign. The results indicate that while radiation damage reduces charge collection efficiency and overall detection efficiency, these losses can be mitigated to levels comparable to non-irradiated sensors by increasing the reverse bias voltage. Charge multiplication was observed and characterised for the first time in 3D trench sensors, revealing a distinct operating regime post-irradiation achievable at bias voltages close to 300 V. Additionally, the timing performance of irradiated sensors remains comparable to their non-irradiated counterparts, underscoring their resilience to radiation damage. Currently, 3D trench silicon detectors are among the fastest and most radiation-hard pixel sensors available for vertex detectors in high-energy physics colliders. These findings highlight the potential of these sensors for new 4D tracking systems of future experiments at the Future Circular Hadron Collider (FCC-hh), advancing the capabilities of radiation-hard sensor technology.
Multiorgan ultrastructural changes in rats induced in synthetic torpor
Authors: Salucci Sara , Hitrec Timna , Piscitiello Emiliana , Occhinegro Alessandra , Alberti Luca , Taddei Ludovico , Burattini Sabrina , Luppi Marco , Tupone Domenico , Amici Roberto , Faenza Irene , Cerri Matteo
Published: November 2024

Torpor is a state used by several mammals to survive harsh winters and avoid predation, characterized by a drastic reduction in metabolic rate followed by a decrease in body temperature, heart rate, and many physiological variables. During torpor, all organs and systems must adapt to the new low-energy expenditure conditions to preserve physiological homeostasis. These adaptations may be exploited in a translational perspective in several fields. Recently, many features of torpor were shown to be mimicked in non-hibernators by the inhibition of neurons within the brainstem region of the Raphe Pallidus. The physiological resemblance of this artificial state, called synthetic torpor, with natural torpor has so far been described only in physiological terms, but no data have been shown regarding the induced morphological changes. Here, we show the first description of the ultrastructural changes in the liver, kidney, lung, skeletal muscle, and testis induced by a 6-hours inhibition of Raphe Pallidus neurons in a non-hibernating species, the rat.
Early detection of pine wilt disease based on UAV reconstructed hyperspectral image
Authors: Liu Wentao , Xie Ziran , Du Jun , Li Yuanhang , Long Yongbing , Lan Yubin , Liu Tianyi , Sun Si , Zhao Jing
Published: November 2024

Pine wilt disease (PWD) is a highly destructive infectious disease that affects pine forests. Therefore, an accurate and effective method to monitor PWD infection is crucial. However, the majority of existing technologies can detect PWD only in the later stages. To curb the spread of PWD, it is imperative to develop an efficient method for early detection. We presented an early stage detection method for PWD utilizing UAV remote sensing, hyperspectral image reconstruction, and SVM classification. Initially, employ UAV to capture RGB remote sensing images of pine forests, followed by labeling infected plants using these images. Hyperspectral reconstruction networks, including HSCNN+, HRNet, MST++, and a self-built DW3D network, were employed to reconstruct the RGB images obtained from remote sensing. This resulted in hyperspectral images in the 400-700nm range, which were used as the dataset of early PWD detection in pine forests. Spectral reflectance curves of infected and uninfected plants were extracted. SVM algorithms with various kernel functions were then employed to detect early pine wilt disease. The results showed that using SVM for early detection of PWD infection based on reconstructed hyperspectral images achieved the highest accuracy, enabling the detection of PWD in its early stage. Among the experiments, MST++, DW3D, HRNet, and HSCNN+ were combined with Poly kernel SVM performed the best in terms of cross-validation accuracy, achieving 0.77, 0.74, 0.71, and 0.70, respectively. Regarding the reconstruction network parameters, the DW3D network had only 0.61M parameters, significantly lower than the MST++ network, which had the highest reconstruction accuracy with 1.6M parameters. The accuracy was improved by 27% compared to the detection results obtained using RGB images. This paper demonstrated that the hyperspectral reconstruction-poly SVM model could effectively detect the Early stage of PWD. In comparison to UAV hyperspectral remote sensing methods, the proposed method in this article offers a same precision, but a higher operational efficiency and cost-effectiveness. It also enables the detection of PWD at an earlier stage compared to RGB remote sensing, yielding more accurate and reliable results.
Functional nutritional rice: current progresses and future prospects
Authors: Duan Sumei , Ai Hao , Liu Shengqin , Zhou Aifeng , Cao Yuhong , Huang Xianzhong
Published: November 2024

More than half of the world’s population relies on rice as their staple food for three meals a day. From a dietary perspective, rice can be considered the most important grain in the world. With the continuous improvement of people’s living standards, the demand for food has gradually shifted from being full and eating well to being nutritious and healthy. Developing functional nutritional rice has become an important research direction and strategic initiative for developing a major food concept. In this paper, we review the current progress in the breeding of functional nutritional rice and mineral-biofortified rice. This review focuses on the following aspects: (i) the concept, rice basic structure, nutritional components, and categorization of functional nutritional rice; (ii) genes that have been applied and identified so far, including nutritional functional rice genes, mineral bioenhancement-related genes, and their regulatory mechanisms; (iii) based on the history and technical mainline of rice breeding, research progress in nutritional functional rice using conventional breeding, a combination of conventional breeding and marker-assisted breeding, mutagenesis breeding, genetic engineering technology, and gene editing technology. Based on the current research and industrialization issues, we highlight an outlook of the problems and future developmental directions in nutritional functional rice research.
Short Italian Wilkins Rate of Reading Test for repeated-measures designs in optometry and neuropsychology
Authors: De Luca Maria , Nardo Davide , Rizzo Giulia Carlotta , Daini Roberta , Tavazzi Silvia , Zeri Fabrizio
Published: November 2024

Background

The recently published New Italian version of the Wilkins Rate of Reading Test (standard Italian WRRT) was designed to measure reading speed in repeated-measures designs in research and/or clinical examinations. The test features 15 equivalent 10-line passages made up of unrelated words, adhering to the principles established by the Wilkins Rate of Reading Test in English (original WRRT).

Aim

To develop a short Italian version of the WRRT (SI-WRRT), and to determine the equivalence across the new, shorter passages of text. The introduction of 5-line passages, instead of the original 10-line ones, aims to enhance the tool's suitability for the elderly or neuropsychological patients by reducing administration time.

Method

The same 15 high-frequency Italian words from the standard Italian WRRT were used to generate 15 5-line passages for the SI-WRRT. Comprehensive eye examination and vision assessment, including the Radner Reading Charts, were performed before the administration of the SI-WRRT. Forty healthy Italian-speaking higher education students read the SI-WRRT passages aloud in random order. Reading speed and accuracy were measured offline from digital recordings of the readings. Equivalence across passages and the effects of practice and fatigue were assessed for reading speed and accuracy, along with test-retest reliability.

Results

No significant difference in reading speed was found across 14 out of the 15 passages. In addition, no differences were observed in accuracy, and the error rate was very low. Practice and fatigue effects were minimal for reading speed, whereas they were absent for accuracy. Reading speed, the reference metric for the WRRT, showed moderate-to-good test-retest reliability.

Conclusions

Equivalence was confirmed across 14 passages of the SI-WRRT. Therefore, the test may be suitable for examining the elderly or neuropsychological patients, as reading time of the 5-line passages is halved with respect to the standard Italian WRRT. However, the 5-line passages still allow the assessment of prolonged reading. Since one passage was not equivalent, we recommend avoiding the use of random rearrangements of words without formally checking their validity.
Single prolonged stress induces behavior and transcriptomic changes in the medial prefrontal cortex to increase susceptibility to anxiety-like behavior in rats
Authors: Iqbal Javed , Huang Geng-Di , Shen Dan , Xue Yan-Xue , Yang Mei , Jia Xiao-Jian
Published: November 2024

Introduction

Transcriptomic studies offer valuable insights into the pathophysiology of traumatic stress-induced neuropsychiatric disorders, including generalized anxiety disorder and post-traumatic stress disorder (PTSD). The medial prefrontal cortex (mPFC) has been implicated in emotion, cognitive function, and psychiatric disorders. Alterations in the function of mPFC have been observed in PTSD patients. However, the specific transcriptomic mechanisms governed by genes within the mPFC under traumatic stress remain elusive.

Methods

In this study, we conducted transcriptome-wide RNA-seq analysis in the prelimbic (PL) and infralimbic (IL) cortices. We employed the single prolonged stress (SPS) animal model to simulate anxiety-like behavior, which was assessed using the open field and elevated plus maze tests.

Results

We identified sixty-two differentially expressed genes (DEGs) (FDR adjusted p < 0.05) with significant expression changes in the PL and IL mPFC. In the PL cortex, DEGs in the susceptible group exhibited reduced enrichment for cellular, biological, and molecular functions such as postsynaptic density proteins, glutamatergic synapses, synapse formation, transmembrane transport proteins, and actin cytoskeleton reorganization. In contrast, the IL-susceptible group displayed diminished enrichment for synapse formation, neuronal activity, dendrite development, axon regeneration, learning processes, and glucocorticoid receptor binding compared to control and insusceptible groups. DEGs in the PL-susceptible group were enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to Parkinson’s disease, Huntington's disease, Alzheimer's disease, and neurodegeneration processes. In the IL cortex, the susceptible group demonstrated enrichment for KEGG pathways involved in regulating stress signaling pathways and addiction-like behaviors, compared to control and insusceptible groups.

Conclusion

Our findings suggest that SPS activates distinct transcriptional and molecular pathways in PL and IL cortices of mPFC, enabling differential coping mechanisms in response to the effects of traumatic stress. The enhanced enrichment of identified KEGG pathways in the PL and IL mPFC may underlie the anxiety-like behavior observed in susceptible rats.
Exercise habits in adolescence and old age are positively associated with geriatric depressive symptoms: the Bunkyo Health Study
Authors: Shi Huicong , Tabata Hiroki , Otsuka Hikaru , Kaga Hideyoshi , Someya Yuki , Abudurezake Abulaiti , Kakehi Saori , Naito Hitoshi , Ito Naoaki , Tajima Tsubasa , Yoshizawa Yasuyo , Kawamori Ryuzo , Watada Hirotaka , Tamura Yoshifumi
Published: November 2024

Introduction

Exercise is a crucial method for preventing geriatric depression. In this cross-sectional study, we investigated the associations between exercise habits in adolescence and old age and geriatric depressive symptoms.

Methods

This study used baseline data from the Bunkyo Health Study, a prospective observational cohort study investigating the preventive effects of physical activity on causative diseases requiring long-term care. This analysis included 1,629 older adults (687 men and 942 women) aged 65–84 years who participated in the Bunkyo Health Study. Participants were divided into four groups according to their exercise habits in adolescence and old age: never exercised (none-none; NN), exercised only in old age (none-active; NA), exercised only in adolescence (active-none; AN), and exercised in adolescence and old age (active-active; AA). Geriatric depressive symptoms were defined as the short version of the Geriatric Depression Scale score ≥ 5, including depression tendency. Multivariate-adjusted logistic regression models were used to estimate the odds ratios (ORs) and associated 95% confidence intervals in each group for the prevalence of geriatric depressive symptoms compared with the NN group.

Results

The ORs for geriatric depressive symptoms were notably lower in the AN, NA, and AA groups than in the NN group in both older men and older women.

Conclusion

These results indicate that older adults with exercise habits in adolescence and/or in old age exhibit a lower prevalence of geriatric depressive symptoms.
Characteristics and quality of life of people living with comorbid disorders in substance use recovery residences
Authors: Obekpa Elizabeth O. , McCurdy Sheryl A. , Gallardo Kathryn R. , Rodriguez Serena A. , Cazaban Cecilia Ganduglia , Brown H. Shelton , Yang James J. , Wilkerson J. Michael
Published: November 2024

Background

Opioid use disorder (OUD) is associated with significant morbidity and mortality; however, research on physical and mental health comorbidities and health-related quality of life (HRQoL) among people taking medication for OUD (MOUD) and living in recovery residences is sparse. We investigated the prevalence of comorbidities and examined which EQ-5D-5L HRQoL dimensions are most affected by these comorbidities.

Methods

Data were collected from 358 residents living in 14 Texas-based recovery residences from April 2021 to June 2023. The EQ-5D-5L descriptive system comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has five levels of perceived problems, dichotomized into “No problems” (level 1) and “Any problems” (levels 2–5) for analyses. Cross-sectional analyses of residents' characteristics, comorbidities (categorized as mental health disorders or association with major body systems), and EQ-5D-5L dimensions were conducted using Chi-squared or Student t-tests. Multivariable logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The mean [SD] age of residents was 36.0 [8.9]. Most residents were non-Hispanic White (68.7%), male (59.7%), unemployed (66.3%), and engaged in polysubstance use (75.4%). The most frequently reported comorbidities were mental health (26.5%), respiratory (26.3%), neurological (19.3%), cardiovascular (18.2%), and musculoskeletal (17.0%) disorders. The most reported HRQoL problems were anxiety/depression (75.8%) and pain/discomfort (53.2%). In the unadjusted regression models, all comorbidities, except mental health (negative association) and digestive (no association) disorders, were positively associated with HRQoL problems. The usual activities dimension was the most affected by comorbidities, followed by mobility and pain/discomfort. Increasing age was positively associated with cardiovascular disorders (aOR = 1.06; 95% CI = 1.03–1.10), musculoskeletal disorders (aOR = 1.03; 95% CI = 1.00–1.06), mobility problems (aOR = 1.05; 95% CI = 1.01–1.09), and pain/discomfort problems (aOR = 1.02; 95% CI = 1.00–1.05). Illicit drug use was positively associated with mobility problems (aOR = 3.36; 95% CI = 1.20–9.45). Neurological (aOR = 2.71; 95% CI = 1.38–5.33) and musculoskeletal (aOR = 2.57; 95% CI = 1.25–5.29) disorders were positively associated with pain/discomfort problems. MOUD duration was negatively associated with mental health disorders (aOR = 0.14; 95% CI = 0.08–0.22) but not HRQoL.

Conclusions

Comorbidities significantly predict HRQoL among individuals with OUD. Our findings highlight the need for an integrated care model to treat OUD and comorbidities to sustain recovery and improve health and HRQoL.