bluuebunny/crossref_metadata_2025 huggingface dataset:
Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome
Authors: Zemitis Arturs , Vanags Juris , Schiemer Theresa , Klavins Kristaps , Laganovska Guna
Published: January 2025

Purpose

PEXS was first described in 1917, yet its etiology still needs clarification. An imbalance between oxidants and antioxidants plays a significant role. PEXS leads to various ocular complications, including increased risk during cataract surgery due to weak zonules, lens dislocation, and reduced visual outcomes. Our study investigates whether metabolomics can provide insights into this ocular pathology.

Methods

The study included 183 patients undergoing cataract surgery at Pauls Stradins Clinical University Hospital. 104 patients did not have PEXS, while 79 were diagnosed with the condition. Intraocular fluid samples from these patients were analyzed using targeted metabolite analysis, performed through HILIC liquid chromatography coupled with mass spectrometry detection.

Results

The aqueous humor of PEXS patients contains statistically significant higher levels of cystine (p < 0.001), citrulline (p < 0.001), phenylalanine (p = 0.041), tyrosine (p = 0.025), serine (p = 0.030), arginine (p = 0.017), lactic acid (p = 0.055), tryptophan (p = 0.055), and creatinine (p = 0.022). These results suggest a potential link to ferroptosis.

Conclusion

Ferroptosis is a form of programmed cell death characterized by iron-dependent LPO. The inhibition of the antiporter system Xc− leads to increased oxidative stress, suggesting that the changes seen in PEXS could be linked to ferroptosis. Our findings indicate that cysteine synthesis occurs via the transsulfation pathway, attributable to inhibiting the antiporter system Xc−. Treatment of pseudoexfoliation should lower the oxidative stress inside the anterior chamber by reducing the uptake of PUFAs, lower iron levels, and cysteine supplementation.
Aging restricts the initial neural patterning potential of developing neural stem and progenitor cells in the adult brain
Authors: Aran Saeideh , Golmohammadi Mohammad Ghasem , Sagha Mohsen , Ghaedi Kamran
Published: January 2025

Introduction

Neurosphere culture is widely used to expand neural stem and progenitor cells (NSPCs) of the nervous system. Understanding the identity of NSPCs, such as the principals involved in spatiotemporal patterning, will improve our chances of using NSPCs for neurodevelopmental and brain repair studies with the ability to direct NSPCs toward distinct fates. Some reports indicate that aging can affect the nature of NSPCs over time. Therefore, in this study, we aimed to investigate how the initial neural patterning of developing NSPCs changes over time.

Methods

In this research, evidence of changing neural patterning potential in the nervous system over time was presented. Thus, the embryonic and adult-derived NSPCs for cardinal characteristics were analyzed, and then, the expression of candidate genes related to neural patterning using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was evaluated at various stages of embryonic (E14 and E18), neonatal, and adult brains. Finally, it was assessed the effect of cell attachment and passage on the initial neural patterning of NSPCs.

Results

The analysis of gene expression revealed that although temporal patterning is maintained in vitro, it shows a decrease over time. Embryonic NSPCs exhibited the highest potential for retaining regional identity than neonatal and adult NSPCs. Additionally, it was found that culture conditions, such as cell passaging and attachment status, could affect the initial neural patterning potential, resulting in a decrease over time.

Conclusion

Our study demonstrates that patterning potential decreases over time and aging imposes restrictions on preliminary neural patterning. These results emphasize the significance of patterning in the nervous system and the close relationship between patterning and fate determination, raising questions about the application of aged NSPCs in the treatment of neurodegenerative diseases.
Identifying P100 and N170 as electrophysiological markers for conscious and unconscious processing of emotional facial expressions
Authors: Herzberg Lennard , Schräder Julia , Jo Han-Gue , Habel Ute , Wagels Lisa
Published: January 2025

Introduction

Everyday life requires correct processing of emotions constantly, partly occurring unconsciously. This study aims to clarify the effect of emotion perception on different event-related potentials (ERP; P100, N170). The P100 and N170 are tested for their suitability as electrophysiological markers in unconscious processing.

Methods

Using a modified backward masking paradigm, 52 healthy participants evaluated emotional facial expressions (happy, sad, or neutral) during EEG recording. While varying primer presentation time (16.7 ms for unconscious; 150 ms for conscious perception), either congruent or incongruent primer / target emotions were displayed.

Results

The N170 was significantly larger in trials with conscious compared to unconscious primer presentation, while the P100 showed opposite results displaying higher amplitudes in unconscious versus conscious trials. The N170 amplitude was modulated by emotion.

Discussion

Both P100 and N170 were modulated by stimulus presentation time, demonstrating the suitability as potential biomarkers and for systematic research on conscious and unconscious face processing.
Fractional amplitude of low-frequency fluctuations during music-evoked autobiographical memories in neurotypical older adults
Authors: Lesiuk Teresa , Dillon Kaitlyn , Ripani Giulia , Iliadis Ioannis , Perez Gabriel , Levin Bonnie , Sun Xiaoyan , McIntosh Roger
Published: January 2025

Introduction

Researchers have shown that music-evoked autobiographical memories (MEAMs) can stimulate long-term memory mechanisms while requiring little retrieval effort and may therefore be used in promising non-pharmacological interventions to mitigate memory deficits. Despite an increasing number of studies on MEAMs, few researchers have explored how MEAMs are bound in the brain.

Methods

In the current study activation indexed by fractional amplitude of low frequency fluctuations (fALFF) during familiar and unfamiliar MEAM retrieval was compared in a sample of 24 healthy older adults. Additionally, we aimed to investigate the impact of age-related gray matter volume (GMV) reduction in key regions associated with MEAM-related activation. In addition to a T1 structural scan, neuroimaging data were collected while participants listened to familiar music (MEAM retrieval) versus unfamiliar music.

Results

When listening to familiar compared to unfamiliar music, greater fALFF activation patterns were observed in the right parahippocampal gyrus, controlling for age and GMV. The current findings for the familiar (MEAM) condition have implications for cognitive aging as persons experiencing age-related memory decline are particularly susceptible to volumetric reduction in the parahippocampal cortex. Post-hoc analyses to explore correlations between brain activity and the content of MEAMs were performed using the text analysis program Linguistic Inquiry and Word Count.

Discussion

Our findings suggest that MEAM-related activation of the parahippocampal cortex is evident in normative older adults. However, it is yet to be determined whether such brain states are attainable in older adult populations diagnosed with mild cognitive impairment and/or prodromal Alzheimer’s disease.
Energy intake insufficiency due to underestimated energy requirement by common predictive formulas can be identified by urinary amino acid levels in advanced heart failure
Authors: Sakamoto Yoko , Ohtani Tomohito , Nakamoto Kei , Sera Fusako , Hikoso Shungo , Sakata Yasushi
Published: January 2025

Background

Elevated resting energy expenditure (REE) promotes cachexia, worsening prognosis in patients with advanced heart failure (HF). However, adequate assessment of energy balance is challenging because of unvalidated common prediction methods and unestablished determinants of REE, resulting in a lack of biomarkers for predicting insufficient energy intake.

Objective

This cross-sectional study aimed to evaluate REE in patients with advanced HF and explore biomarkers for insufficient energy intake.

Methods

We measured REE by indirect calorimetry and calculated the total energy expenditure (TEE) of 72 hospitalized patients with advanced-stage HF. We compared these values with commonly-used formulas and analyzed the associations between REE per body weight (REEBW) and parameters related to hemodynamics and HF severity. In 17 of 72 patients, plasma amino acid (AA) and 24-h urinary AA concentrations were measured to analyze their correlations with energy balance, the ratio of caloric intake to REE.

Results

Resting energy expenditure and TEE values were significantly higher than the predicted values. The mean REEBW was 25 kcal/kg/day, while that for the underweight (<18.5 kg/m2) was 28 kcal/kg/day. We found a significant negative correlation between REEBW and body mass index (BMI), but no significant correlation between REEBW and HF-related parameters. The difference between TEE and predicted TEE using the European Society for Clinical Nutrition and Metabolism formula was most significant in the underweight patients because of underestimation, whereas TEE and pTEE using our modified formula with coefficients by BMI categories did not differ. There was a significant correlation between energy balance and urinary histidine and its metabolite 3-methylhistidine excretion, but no significant correlation with serum albumin and other AA concentrations.

Conclusion

Underweight patients with advanced HF require more energy per weight than the predicted value. Our proposed formula for pTEE in each BMI category may be useful in clinical practice to avoid underestimation of daily energy requirements. Inadequate energy intake, even with such an approach, may be identified by decreased urinary essential AA levels.
Exploring genetic structures and shared sites between alcohol, cheese intake, and inflammatory bowel disease
Authors: Huang Zhifang , Yuan Weichao
Published: January 2025

Background

An association has been observed between alcohol and cheese intake and the onset of inflammatory bowel disease (IBD), necessitating further exploration from a genetic structural perspective.

Methods

The present analysis was focused on the intake of alcohol and cheese in conjunction with IBD genome-wide association study (GWAS) data, with the objective of exploring genetic correlations and identifying common loci. Initially, overall genetic correlations were assessed employing two methodologies: linkage disequilibrium score regression (LDSC) and genetic covariance analyzer (GNOVA). Subsequently, local correlations were examined through the SUPERGNOVA method. A genetic overlap analysis between various traits was then conducted based on the statistical theory of conditional/conjunctional false discovery rate (cond/conjFDR). Ultimately, shared loci between the two traits were identified via conjFDR analysis and multi-trait analysis of GWAS (MTAG).

Results

Substantial overall correlations were noted at the genome-wide level between alcohol and cheese intake and both IBD and Crohn’s disease (CD), whereas the association with ulcerative colitis (UC) was of lesser significance. In the local genetic analysis, chromosome 16 emerged as a key region implicated in the relationship between alcohol and cheese intake and IBD (including both CD and UC). The conjFDR analysis confirmed the genetic overlap between the two diseases. Furthermore, both conjFDR and MTAG analyses identified multiple shared genetic loci, with nine genes (Y_RNA, DENND1B, GCKR, KPNA7, CLN3, SLC39A8, FUT2, ERAP2, and SMAD3) being.

Conclusion

The present study provides genetic evidence supporting the comorbidity of alcohol and cheese intake with IBD, offering novel insights into potential strategies for the prevention and treatment of IBD through the modulation of alcohol and cheese consumption.
Association between the composite dietary antioxidant index and non-alcoholic fatty liver disease: evidence from National Health and Nutrition Examination Survey 2005–2016
Authors: Fu Yidian , Jiang Chao , Li Zonglin , Shi Xiangyun , Lv Peiyuan , Zhang Jingbo
Published: January 2025

Importance

Oxidative stress contributes to the progression of non-alcoholic fatty liver disease (NAFLD). Antioxidants from food can reduce NAFLD incidence, and the Composite Dietary Antioxidant Index (CDAI) measures total antioxidant capacity (TAC). However, the relationship between CDAI and NAFLD in the US adult population remains unclear.

Objective

To assess whether CDAI is associated with NAFLD in US adults.

Design, setting, and participants

This population-based cross-sectional study used data on US adults from the National Health and Nutrition Examination Survey (NHANES) 2005–2016 cycles. Data were analyzed from January to February 2024.

Exposures

CDAI obtained from the dietary intake questionnaire.

Main outcomes and measures

The main outcome was NAFLD which defined by the US fatty liver score (USFLI) ≥30. Sampling weights were calculated according to NHANES guidelines.

Results

Among 9,746 adults included in this study [mean age, 48.3 years; 4,662 (47.6%) males], 3,324 (33.0%) were classified as having NAFLD using USFLI. In the fully adjusted of multivariable logistic regression, CDAI was negatively associated with NAFLD (odds ratio [OR], 0.95; 95% CI, 0.93–0.98). Furthermore, individuals in the highest quartile of CDAI were 34% less likely to have NAFLD compared to those in the lowest quartile (OR, 0.66; 95% CI, 0.52–0.85). In subgroup analyses, CDAI was inversely associated with NAFLD among participants with a BMI <25 (OR, 0.89; 95% CI, 0.83–0.95) and without metabolic syndrome (OR, 0.93; 95% CI, 0.91–0.96). The interaction tests revealed significant differences in these subgroups (P for interaction = 0.04 for BMI and 0.003 for metabolic syndrome). Sensitivity analyses confirmed this association using the hepatic steatosis index (HSI) to define NAFLD, applying unweighted logistic regression, adjusting for physical activity or after excluding non-Hispanic Black participants, and after excluding medications known for their potential hepatotoxic effects.

Conclusions and relevance

In this cross-sectional study based on six cycles (2005–2016) of the NHANES, CDAI was negatively associated with NAFLD in US adult population. This association highlights the potential for dietary interventions to reduce NAFLD incidence and underscores the need for future research, including clinical trials and mechanistic studies, to further explore the role of dietary antioxidants in NAFLD prevention and management.
Effect of long-term exercise on circulating ghrelin in overweight and obese individuals: a systematic review and meta-analysis
Authors: Xin Xianyang , Wang Hai , Guo Yongqing , Xie Jun
Published: January 2025

Objective

Ghrelin, also known as the “hunger hormone,” is a pivotal hormone in controlling appetite, and it is the only known gastrointestinal hormone that promotes food intake, contributing to the regulation of energy balance and body weight. However, studies on the long-term effects of exercise on ghrelin levels in obese populations have shown conflicting results. This study aims to summarize RCT experiments exploring changes in ghrelin levels following long-term exercise in obese or overweight individuals through meta-analysis.

Methods

This study employed meta-analytical techniques, searching databases such as PubMed, Web of Science, and EMBASE, to gather research on exercise and ghrelin. The quality of the studies was assessed according to the Cochrane Handbook standards, and data analysis for ghrelin, BMI, and weight was performed using RevMan 5.4 and Stata 16.0 software. A total of 13 interventions involving 944 participants were included to systematically investigate the regulatory effects of exercise on ghrelin levels in obese and overweight individuals. Meta-analytical results were calculated using standardized mean differences (SMDs).

Results

Exercise interventions significantly increased ghrelin levels (SMD =1.16, 95% CI = 0.52 to 1.80, p < 0.0001), with high inter-study heterogeneity (I2 = 90%). Subgroup analysis suggested that RT and AE + RT were more effective than AE. For BMI, exercise led to a significant reduction (SMD = −0.43, 95% CI = −0.69 to −0.16, p = 0.002), with low heterogeneity (I2 = 21%). Similarly, exercise significantly reduced weight (SMD = −0.54, 95% CI = −0.98 to −0.11, p = 0.01), though with high heterogeneity (I2 = 75%). These results suggest exercise effectively improves ghrelin levels, BMI, and weight.

Conclusion

Prolonged exercise interventions demonstrated a statistically significant effect on ghrelin levels. This indicates that exercise interventions can elevate ghrelin levels, which may be associated with reductions in BMI and weight.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, CRD42024588259.
A dosimetric comparison of non-coplanar volumetric modulated arc therapy and non-coplanar fixed field intensity modulated radiation therapy in hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for brain metastases
Authors: Zeng Huaqu , Zhong MinZhi , Chen Zongyou , Tang Shukui , Wen Zunbei
Published: January 2025

Objective

The aim of this study was to investigate the dosimetric differences between non-coplanar volumetric modulated arc therapy (VMAT) and non-coplanar fixed-field intensity-modulated radiotherapy (IMRT) in hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for brain metastases using the Monaco treatment planning system (TPS).

Method

A total of 22 patients with brain metastases were retrospectively enrolled. Two radiotherapy treatment plans were designed for each patient: non-coplanar VMAT and non-coplanar fixed field IMRT. The dose distribution of targets and organs at risk (OAR), the number of monitor units (MUs), and pre-treatment plan verification were compared between the two plans while meeting the prescribed dose requirements of the target volume.

Results

There were no significant differences in V50, V55, Dmax, heterogeneity index (HI) and conformity index (CI) of target PGTV between the two plans (p>0.05). For PTV-brain-SIB, there was no significant difference in D98% between IMRT and VMAT (p=0.103). VMAT significantly improved the V30 of PTV-brain-SIB (p<0.001), decreased HI (p=0.003), and increased CI (p<0.001). There were no significant differences in the Dmax to the brain stem, left and right lens, optic chiasm, pituitary gland, and left and right hippocampus between the two plans (p>0.05). Compared with IMRT, VMAT significantly reduced the Dmax to the left and right eyes (p<0.001) and significantly increased the Dmax to the right inner ear (p=0.010). There was no significant difference in the Dmax to the left inner ear between VMAT and IMRT (p=0.458). Compared with IMRT, VMAT significantly reduced the Dmax to the left optic nerve (p=0.006), but significantly increased the Dmax to the right optic nerve (p=0.001). There was no significant difference in the Dmax to the left and right hippocampus between VMAT and IMRT (p>0.05), but VMAT significantly increased the D100% (p<0.05) compared with IMRT. Compared with VMAT, IMRT significantly reduced the MU (p<0.001) but VMAT has a higher treatment efficiency than IMRT, with an average reduction of 41 seconds (294.1 ± 16.4 s for VMAT, 335.8 ± 34.9 s for IMRT, p<0.001). Under the conditions of 3%/2 mm, and 2%/2 mm, the gamma passing rate of the IMRT QA was improved compared to VMAT, with an average increase of 0.6%, p=0.013, and 1.7%, p<0.001, respectively.

Conclusion

Both non-coplanar VMAT and non-coplanar fixed field IMRT based on the Monaco TPS produce clinically acceptable results for HA-WBRT+SIB in patients with brain metastases. Compared with IMRT, VMAT has better dose distribution in the target volume and treatment efficiency, but IMRT can better protect the hippocampus and reduce the number of MUs.
Development and approval of a Lasso score based on nutritional and inflammatory parameters to predict prognosis in patients with glioma
Authors: Li Huixian , Hong Hui , Zhang Jinling
Published: January 2025

Objectives

Preoperative peripheral hematological indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and prognostic nutritional index (PNI), exhibit promise as prognostic markers for glioma. This study evaluated the prognostic value of a combined scoring system incorporating NLR, PLR, MLR, and PNI, and developed a nomogram to predict glioma prognosis.

Methods

Data on preoperative NLR, PLR, MLR, and PNI were collected from 380 patients with pathologically diagnosed glioma (266 in the training cohort, 114 in the validation cohort). The Least Absolute Shrinkage and Selection Operator (Lasso) was employed to select relevant hematological indicators and generate a Lasso score. A nomogram was constructed utilizing Cox regression and Lasso variable selection. This nomogram incorporated the Lasso score, age, pathological type, chemotherapy status, and Ki67 expression to predict overall survival (OS). Model performance was evaluated utilizing Harrell’s c-index, calibration curves, DCA, and clinical utility (stratification into low-risk and high-risk groups), and verified utilizing the independent validation cohort.

Results

A total of 380 glioma patients were enrolled and separated into training (n = 266) and validation (n = 114) cohorts. The two cohorts demonstrated no significant differences in baseline characteristics. NLR, PLR, MLR, and PNI from the training dataset were utilized for Lasso calculation. Multivariable analysis indicated that age, pathological grade, chemotherapy status, Ki-67 expression, and the Lasso score were independent predictors of OS and were then included in the nomogram. The nomogram model based on the training cohort had a C index of 0.742 (95% CI: 0.700-0.783) and AUC values of 0.802, 0.775, and 0.815 for ROC curves at 1, 3, and 5 years after surgery. The validation cohort derived a similar C-index of 0.734 (95% CI: 0.671–0.798) and AUC values of 0.785, 0.778, and 0.767 at 1, 3, and 5 years, respectively. The nomogram demonstrated good calibration in both cohorts, indicating strong agreement between predicted and observed outcomes. The threshold probabilities for DCA at 1-, 3-, and 5-years post-surgery in the training and validation cohorts were 0.08~k0.74, 0.25~0.80, and 0.08~0.89, and 0.13~0.60, 0.28~0.81, and 0.25~0.88, respectively.

Conclusions

A nomogram incorporating a Lasso score effectively predicted prognosis in glioma patients. However, its performance did not significantly exceed that of standard clinical nomograms.
Hepatic epithelioid hemangioendothelioma with TFE3 rearrangement: a case report and literature review
Authors: Meng Ke , Yang Xingrong , Guo Sitong , Tao Juan
Published: January 2025

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant tumor of vascular origin. It may be confusing as its manifestations of multifocal lesions on imaging and epithelial histomorphology in pathology. EHE is easy to be mistaken for a metastatic tumor by radiologists and clinicians. Correct diagnosis and therapy are important owing to the variable clinical course and special treatment. EHEs harbor major CAMTA1 rearrangement and <5% TFE3 rearrangement. Meanwhile, EHE with TFE3 rearrangement has distinctive morphology features. Currently, there are only two cases of hepatic EHE with TFE3 rearrangement reported, we present another case here that occurred in a 34-year-old female. Both the clinician and radiologist provisionally considered it as a metastatic tumor. The tumor cells have mild atypia but infiltrative growth patterns like benign vascular tumors. Our case is unique mainly in that the absence of its characteristic well-defined vessels, and the presence of unreported morphology of intraluminal papillary proliferation of tombstone or hobnail endothelial cells. The final diagnosis of EHE with TFE3 rearrangement was made by combining morphological, immunohistochemical, and molecular test results. The patient did not receive any treatment according to her condition and no change was detected in the mass’s size and number on CT images during 3.5 years of follow-up.
Rare skin adverse reactions induced by osimertinib: a case report and literature review
Authors: Zhang Ye , Ling Mingzhu , Wang Min , Chen Ye , Zhang Liting
Published: January 2025

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in the treatment of EGFR mutation-positive advanced non-small cell lung cancer. Osimertinib-induced cutaneous vasculitis is a rare skin adverse reaction. We present a case study of a 49-year-old female who developed palpable purpura on her lower extremities on the 11th day of osimertinib treatment. Systemic involvement was not observed in the test results. The multidisciplinary team considered the clinical presentation of purpura as a potential case of cutaneous vasculitis. Osimertinib was immediately discontinued, and intravenous methylprednisolone along with oral cetirizine treatment was initiated. After 8 days since discontinuation of osimertinib, the patient’s skin purpura completely subsided. Subsequently, she was switched to almonertinib for treatment. We also conducted a literature review cutaneous vasculitis induced by osimertinib and other EGFR-TKIs. We hope to provide some safety alert information for clinical practice and recommend enhanced monitoring during the medication process.
Atypical hemolytic uremic syndrome with a C3 variant following COVID-19: a case report
Authors: Ando Masato , Kubota Kazuo , Kadowaki Saori , Kawamoto Minako , Kawamoto Norio , Okamoto Haruka , Nagaya Soichiro , Miwa Yuki , Ohnishi Hidenori
Published: January 2025

Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, and is caused by overactivation of the alternative complement pathway. A 13-year-old Japanese boy with an unremarkable medical history developed symptoms of TMA following coronavirus disease 2019 (COVID-19) infection with mild respiratory symptoms. He was eventually diagnosed with aHUS with a gain-of-function C3 variant. He improved with supportive therapy and plasma exchange, and did not require anti-C5 antibody therapy. In the literature, more than 20 cases of de novo or relapsed aHUS have been described following COVID-19. It has been shown that the complement lectin pathway can be activated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike and N proteins, and the alternative pathway can be activated by the SARS-CoV-2 spike protein. The current case highlights the possibility that COVID-19, even when respiratory symptoms are not severe, can trigger aHUS.
Comparative efficacy and safety of 20 intravenous pharmaceutical intervention for prevention of etomidate-induced myoclonus: a systematic review and Bayesian network meta-analysis
Authors: Chen Lu , Zhou Pengxiang , Li Zhengqian , Wu Ziyang , Zhai Suodi
Published: January 2025

Objective

To compare the efficacy and safety of pharmaceutical interventions to prevent etomidate-induced myoclonus (EIM), providing the optimal intervention for clinical practice.

Methods

PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to sixth May 2024. We included randomized controlled trials (RCTs) comparing intravenous pharmaceutical interventions to prevent EIM with placebo, no intervention, or another pharmaceutical intervention.

Results

Forty-eight RCTs involving 4,768 participants randomly assigned to 20 intravenous pharmaceutical interventions and normal saline were included. Granisetron (odds ratio [OR]: 0.01, 95% confidence interval [CI]: 0.00 to 0.06; one study, moderate certainty) and oxycodone (OR: 0.01, 95% CI: 0.00 to 0.05; three studies, low certainty) was found to be the most effective intervention in reducing the risk of EIM and ranked highest in terms of surface under the cumulative ranking values (94.4% and 89.7% probability), followed by sufentanil (76.5% probability) and remifentanil (74.8% probability). Further subgroup analysis of EIM at mild, moderate-to-severe levels highlighted granisetron and oxycodone as the favorable interventions for reducing EIM. For safety outcomes, the synthesized results indicated that opioids were associated with a higher risk of adverse events (AEs), while no severe AEs were observed.

Conclusion

Moderate-to-low certainty evidence indicated that granisetron and oxycodone may represent the optimal intervention for reducing the risk of overall and moderate-to-severe EIM with a reasonable safety profile, providing the potential interventions for clinical practice.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=291275.
Real-world pharmacovigilance of ofatumumab in multiple sclerosis: a comprehensive FAERS data analysis
Authors: Chen Hui
Published: January 2025

Background

Ofatumumab, a fully human monoclonal antibody targeting CD20, is approved for the treatment of relapsing multiple sclerosis. Comprehensive real-world safety data are crucial for informing clinical practice.

Methods

The FDA Adverse Event Reporting System database was utilized to perform a disproportionality analysis, covering reports from Q3 2020 to Q2 2024, in which ofatumumab was identified as the primary suspected drug. Statistical approaches used included the Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. The timing of adverse events was assessed using the Weibull distribution model to highlight temporal risk patterns.

Results

Known adverse reactions, such as injection site reactions and upper respiratory tract infections, displayed positive signals. Additionally, novel off-label adverse events, including brain fog, muscle spasms, and mood alterations, were identified, marking the first real-world evidence of these potential risks. Temporal analysis revealed that most adverse events occurred within the first month of treatment, indicating an early risk phase. Subgroup analysis demonstrated notable differences in adverse event profiles by gender and age, with males more prone to hyperhidrosis and older patients more susceptible to neurological symptoms.

Conclusion

This real-world analysis of ofatumumab provides important safety insights, confirming known adverse reactions and identifying additional potential risks. Early and tailored monitoring protocols during the initial treatment phase, including regular neurological and psychiatric assessments, are recommended to optimize patient safety and outcomes. Prospective studies are recommended to validate these results and explore the underlying mechanisms.
A ketogenic diet regulates microglial activation to treat drug addiction
Authors: Ji Jie , Tang Yi
Published: January 2025

Drug addiction is a chronic and potentially deadly disease that is considered a global health problem and describes the alteration of brain function by psychostimulant drugs through changes in the reward system. However, there is still no ideal strategy for the management of drug addiction. Previous studies have suggested that microglia are involved in events associated with neuroplasticity and memory, which are also related to drug addiction. Many studies have shown that psychoactive substances may act directly on immune cells, altering their function and inducing the production of various inflammatory mediators. In recent years, a ketogenic diet (KD) was shown to have therapeutic benefits as a dietary therapy for a variety of neurological disorders. With respect to drug addiction, studies have shown that a KD can alleviate glucose metabolism disorders caused by alcohol use disorders by increasing ketone metabolism, thereby reducing withdrawal symptoms. This finding indicates the potential of a KD as a treatment for drug addiction, since a KD may promote the transition of microglia to a predominantly anti-inflammatory state through several mechanisms. Here, we discuss recent research showing that a KD plays a variety of roles in controlling microglia-mediated inflammation, opening new treatment avenues to treat drug addiction. This succinct analysis offers evidence of the enormous potential of a KD to treat drug addiction through the inhibition of microglial activation.
Regulation of Hippo-YAP1/TAZ pathway in metabolic dysfunction-associated steatotic liver disease
Authors: Xuan Wei , Song Dandan , Hou Jianghua , Meng Xiuping
Published: January 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, but effective treatments are still lacking. Metabolic disorders such as iron overload, glycolysis, insulin resistance, lipid dysregulation, and glutaminolysis are found to induce liver senescence and ferroptosis, which are hot topics in the research of MASLD. Recent studies have shown that Hippo–YAP1/TAZ pathway is involved in the regulations of metabolism disorders, senescence, ferroptosis, inflammation, and fibrosis in MASLD, but their complex connections and contrast roles are also reported. In addition, therapeutics based on the Hippo–YAP1/TAZ pathway hold promising for MASLD treatment. In this review, we highlight the regulation and molecular mechanism of the Hippo–YAP1/TAZ pathway in MASLD and summarize potential therapeutic strategies for MASLD by regulating Hippo–YAP1/TAZ pathway.
A review on eye diseases induced by blue light: pathology, model, active ingredients and mechanisms
Authors: Yan Yuan , Wu Yiyao , Zhao Yu , Yang Yaguang , An Guangtao , Liu Zhidong , Qi Dongli
Published: January 2025

Blue light induced eye damage (BLED) belongs to modern diseases. It is an ophthalmic disease caused by prolonged exposure to electronic devices or screens containing a large amount of high-energy short waves (blue light). Specific symptoms include dryness and discomfort in the eyes, blurred vision, headache, insomnia, and in severe cases, it may also cause various eye diseases such as cataracts and glaucoma. At present, the development of health products and drugs for eye blue light injury faces many difficulties. Therefore, further exploration and research are needed on the pathogenesis, pathophysiology, and pharmacological mechanisms of blue light injury. Natural medicine ingredients and preparations have unique advantages in targeting eye blue light injury fatigue products due to their multi-component synergistic effects, overall regulation, and mild and safe characteristics. Starting from the disease-related mechanisms and pathophysiological characteristics of eye blue light injury, this article elucidates the pharmacological mechanisms of various drugs for treating eye blue light injury. At the same time, it reviews the research on in vitro cultured cell and animal model conditions for blue light injury eyes, in order to provide reference for subsequent blue light injury modeling experiments. And explore future research directions to provide new ideas and methods for the prevention and treatment of BLED.
Modified citrus pectin ameliorates methotrexate-induced hepatic and pulmonary toxicity: role of Nrf2, galectin-3/TLR-4/NF-κB/TNF-α and TGF-β signaling pathways
Authors: Ismail Randa , Habib Heba A. , Anter Aliaa F. , Amin Amr , Heeba Gehan H.
Published: January 2025

Introduction

Methotrexate (MTX) is a frequently utilized anti-inflammatory and anticancer agent. Its potential liver and lung toxicity often limits its clinical effectiveness. We conducted this study to demonstrate the possible protective impacts of a natural galectin-3 (Gal-3) inhibitor, modified citrus pectin (MCP), against MTX-induced liver and lung toxicity and verify the potential signaling pathways of these suggested effects. In vitro, the cytotoxicity of MCP and its modulatory effect on MTX cytotoxic efficacy were assessed.

Methods

Four groups of rats were used: control, MTX (40 mg/kg, single intraperitoneal injection on day 9), MTX + MCP (200 mg/kg/day, orally, for 2 weeks), and MCP alone. MCF7, Nalm6, and JEG3 cell lines were used for the in vitro cytotoxicity assay.

Results

MCP counteracted liver and lung toxicity evidenced by ameliorating the markers of liver and lung functions. Moreover, MCP minimized oxidative stress elicited by MTX in lung and liver tissues, as indicated by reduced malondialdehyde levels, elevated levels of reduced glutathione, increased superoxide dismutase activity, and upregulated Nrf2 protein expression. In hepatic and pulmonary tissues, MCP downregulated the inflammatory signaling pathway, Gal-3/TLR-4/NF-κB/TNF-α. MCP pretreatment decreased TGF-β, collagen content, and cleaved caspase-3 levels. MCP enhanced the cytotoxicity of MTX in Nalm6 and JEG3 and did not interfere with its cytotoxicity in the MCF7 cell lines.

Discussion

MCP attenuated MTX-induced liver and lung toxicity through antioxidant, anti-fibrotic, anti-inflammatory, and anti-apoptotic influences, as demonstrated by the improved histopathological changes induced by MTX in pulmonary and hepatic tissues. Moreover, it increased MTX cytotoxicity in different human cell lines.
Itraconazole promotes melanoma cells apoptosis via inhibiting hedgehog signaling pathway-mediated autophagy
Authors: Jin Shunqiao , Liu Xiaojiao , Cai Lingqin , Yan Jiayu , Li Ling , Dong Hongjun , Gao Yuxue , Zhu Xicong , Zhang Cong , Xu Xuezhu
Published: January 2025

Background

Itraconazole, a widely used antifungal medication, has shown potential in inhibiting tumor growth and reducing angiogenesis. However, its role in melanoma tumor growth remains insufficiently explored. This study investigates the inductive effect of itraconazole on autophagy-mediated apoptosis in melanoma cells.

Method

Potential drug targets were identified using the PMF machine learning algorithm. Apoptosis and cell cycle in melanoma cell lines A375 and A2058 were assessed via flow cytometry. Western blot analysis was performed to examine autophagy and associated signaling proteins, while autophagy flux and autophagosome formation were visualized using fluorescence microscopy. A melanoma cell xenograft mouse model was established to evaluate the inhibitory mechanisms of itraconazole on tumor cell proliferation.

Result

Using the PMF machine learning algorithm, SQSTM1 was identified as the primary target of itraconazole. Itraconazole inhibited melanoma cell proliferation by inducing G1 phase arrest and autophagy-mediated apoptosis in A375 and A2058 cells. Furthermore, itraconazole suppressed Hedgehog signaling and counteracted the activation of the Hedgehog agonist recombinant human Sonic Hedgehog (rhShh). In vivo, itraconazole significantly reduced tumor growth in A375 and A2058 xenograft models.

Conclusion

Itraconazole induces autophagy-mediated apoptosis in melanoma cells by inhibiting Hedgehog signaling, underscoring its potential as a therapeutic option for melanoma treatment.
Comparison and verification of detection accuracy for late deceleration with and without uterine contractions signals using convolutional neural networks
Authors: Sato Ikumi , Hirono Yuta , Shima Eiri , Yamamoto Hiroto , Yoshihara Kousuke , Kai Chiharu , Yoshida Akifumi , Uchida Fumikage , Kodama Naoki , Kasai Satoshi
Published: January 2025

Introduction

Cardiotocography (CTG) is used to monitor and evaluate fetal health by recording the fetal heart rate (FHR) and uterine contractions (UC) over time. Among these, the detection of late deceleration (LD), the early marker of fetal mild hypoxemia, is important, and the temporal relationship between FHR and UC is an essential factor in deciphering it. However, there is a problem with UC signals generally tending to have poor signal quality due to defects in installation or obesity in pregnant women. Since obstetricians evaluate potential LD signals only from the FHR signal when the UC signal quality is poor, we hypothesized that LD could be detected by capturing the morphological features of the FHR signal using Artificial Intelligence (AI). Therefore, this study compares models using FHR only (FHR-only model) and FHR with UC (FHR + UC model) constructed using a Convolutional Neural Network (CNN) to examine whether LD could be detected using only the FHR signal.

Methods

The data used to construct the CNN model were obtained from the publicly available CTU-UHB database. We used 86 cases with LDs and 440 cases without LDs from the database, confirmed by expert obstetricians.

Results

The results showed high accuracy with an area under the curve (AUC) of 0.896 for the FHR-only model and 0.928 for the FHR + UC model. Furthermore, in a validation using 23 cases in which obstetricians judged that the UC signals were poor and the FHR signal had an LD-like morphology, the FHR-only model achieved an AUC of 0.867.

Conclusion

This indicates that using only the FHR signal as input to the CNN could detect LDs and potential LDs with high accuracy. These results are expected to improve fetal outcomes by promptly alerting obstetric healthcare providers to signs of nonreassuring fetal status, even when the UC signal quality is poor, and encouraging them to monitor closely and prepare for emergency delivery.
Combining genotyping approaches improves resolution for association mapping: a case study in tropical maize under water stress conditions
Authors: de Pontes Fernanda Carla Ferreira , Machado Ingrid Pinheiro , Silveira Maria Valnice de Souza , Lobo Antônio Lucas Aguiar , Sabadin Felipe , Fritsche-Neto Roberto , DoVale Júlio César
Published: January 2025

Genome-wide Association Studies (GWAS) identify genome variations related to specific phenotypes using Single Nucleotide Polymorphism (SNP) markers. Genotyping platforms like SNP-Array or sequencing-based techniques (GBS) can genotype samples with many SNPs. These approaches may bias tropical maize analyses due to reliance on the temperate line B73 as the reference genome. An alternative is a simulated genome called “Mock,” adapted to the population using bioinformatics. Recent studies show SNP-Array, GBS, and Mock yield similar results for population structure, heterotic groups definition, tester selection, and genomic hybrid prediction. However, no studies have examined the results generated by these different genotyping approaches for GWAS. This study aims to test the equivalence among the three genotyping scenarios in identifying significant effect genes in GWAS. To achieve this, maize was used as the model species, where SNP-Array genotyped 360 inbred lines from a public panel via the Affymetrix platform and GBS. The GBS data were used to perform SNP calling using the temperate inbred line B73 as the reference genome (GBS-B73) and a simulated genome “Mock” obtained in-silico (GBS-Mock). The study encompassed four above-ground traits with plants grown under two levels of water supply: well-watered (WW) and water-stressed (WS). In total, 46, 34, and 31 SNP were identified in the SNP-Array, GBS-B73, and GBS-Mock scenarios, respectively, across the two water levels, associated with the evaluated traits following the comparative analysis of each genotyping method individually. Overall, the identified candidate genes varied along the various scenarios but had the same functionality. Regarding SNP-Array and GBS-B73, genes with functional similarity were identified even without coincidence in the physical position of the SNPs. These genes and regions are involved in various processes and responses with applications in plant breeding. In terms of accuracy, the combination of genotyping scenarios compared to those isolated is feasible and recommended, as it increased all traits under both water conditions. In this sense, it is worth highlighting the combination of GBS-B73 and GBS-Mock scenarios, not only due to the increase in the resolution of GWAS results but also the reduction of costs associated with genotyping and the possibility of conducting genomic breeding methods.
Transcriptomic and metabolomic analyses reveal the mechanism of color difference between two kinds of Cistanche deserticola before and after drying
Authors: Zhu Tiantian , Zhang Jing , Liu Tianle , Zhang Shuai , Yang Baimei , Xu Li , Zhao Lei , Li Mengfei , Jin Ling
Published: January 2025

Introduction

Cistanche deserticola is an important traditional Chinese herbal medicine. The fresh cistanche squamous stem is typically yellow-white and brown after drying. Oil cistanche is a cistanche variant with a purple squamous stem that turns black after drying. The color difference between oil cistanche and cistanche is obvious, and the former has a higher market price. However, the mechanism underlying the color difference of oil cistanche and cistanche remains unclear.

Methods

This study evaluated the total flavone contents in oil cistanche and cistanche and compared the differential metabolites and differentially expressed genes (DEGs) and the contents of iridoid of dried oil cistanche and cistanche samples were determined by high-performance liquid chromatography, and finally the polysaccharides contents of them were determined to comprehensively analyze the formation mechanism of color difference between oil cistanche and cistanche.

Results

The results showed that the total flavonoid content in oil cistanche was significantly higher than that in cistanche. Metabolomic analysis identified 50 differentially accumulated metabolites (DAMs) (34 up-regulated and 16 down-regulated), including carbohydrates, terpenoids, and flavonoids. Moreover, 3,376 DEGs were selected, among which significant up-regulated of IGS1 and CYP84A1 and down-regulated of 4CLL1, F6H2-2-1 and 5MAT1 genes jointly regulated flavonoid biosynthesis and affected the accumulation of differentially accumulated metabolites. Significant up-regulated of the CCD7 gene affected carotenoid component production, and significant up-regulated of the UGT85A24 gene promoted the accumulation of geniposidic acid. In addition, the contents of iridoid and polysaccharide in oil cistanche were significantly higher than those in cistanche.

Discussion

The differential expression of flavonoids and terpenoid differential metabolites and CYP84A1, 5MAT1, FLS, UGT85A24 and CCD7 mainly caused the purple color of fresh oil cistanche. Dried samples of oil cistanche were darker in color than those of cistanche, due to the higher content of iridoids and polysaccharides in the former. This study preliminarily revealed the causes of the color differences between oil cistanche and cistanche, and provided references for the systematic study of cistanche and its germplasm resources, as well as for the breeding of C. deserticola.