bluuebunny/crossref_metadata_2025 huggingface dataset:
A bibliometric review on vitamins and Alzheimer’s disease between 1996 and 2023
Authors: Sun Xiaoyu , Xu Haichun , Qu Huiling , Dong Wenwu
Published: May 2023

Objective

Alzheimer’s disease (AD) is a major disease that affects the elderly worldwide. Several studies have revealed that vitamins may influence the risk of developing AD. However, information in this field remains ambiguous. Therefore, this study aimed to examine the relationship between AD and vitamins, identify journal publications and collaborators, and analyze keywords and research trends using a bibliometric method.

Methods

We systematically searched the Web of Science (WOS) Core Collection for papers published on AD and vitamins. Retrieved data regarding institutions, journals, countries, authors, journal distribution, keywords, and so on. SPSS 25 software was used for the statistical analysis, and CiteSpace V.6.1.R6 was used to visualize the information through collaborative networks.

Results

A total of 2,838 publications were ultimately included in accordance with the specified inclusion criteria. The number of publications gradually increased from 1996 to 2023, with papers published in 87 countries/regions and 329 institutions. China (centrality: 0.02) and the University of Kentucky (centrality: 0.09) were the major research countries and institutions, respectively. NEUROLOGY was cited most frequently, reaching 1,573, and had the greatest impact. The cited keywords show that “Alzheimer’s disease,” “oxidative stress,” “vitamin E,” and “dementia” have been research hotspots in recent years. Beta-carotene emerged in 2023 and was identified as a developmental trend in this field.

Conclusion

This is the first bibliometric analysis of vitamins associated with AD. We identified 2,838 articles in the field of vitamins and AD, analyzed the information of major countries/regions, institutions, and core journals in this field, and summarized the research hotspots and frontiers. These findings provide useful information for researchers to explore the role of vitamins in AD further.
Empirically validated theoretical analysis of visual-spatial perception under change of nervous system arousal
Authors: Purohit Pratik , Dutta Prasun , Roy Prasun K.
Published: May 2023

Introduction

Visual-spatial perception is a process for extracting the spatial relationship between objects in the environment. The changes in visual-spatial perception due to factors such as the activity of the sympathetic nervous system (hyperactivation) or parasympathetic nervous system (hypoactivation) can affect the internal representation of the external visual-spatial world. We formulated a quantitative model of the modulation of visual-perceptual space under action by hyperactivation or hypoactivation-inducing neuromodulating agents. We showed a Hill equation based relationship between neuromodulator agent concentration and alteration of visual-spatial perception utilizing the metric tensor to quantify the visual space.

Methods

We computed the dynamics of the psilocybin (hyperactivation-inducing agent) and chlorpromazine (hypoactivation-inducing agent) in brain tissue. Then, we validated our quantitative model by analyzing the findings of different independent behavioral studies where subjects were assessed for alterations in visual-spatial perception under the action of psilocybin and under chlorpromazine. To validate the neuronal correlates, we simulated the effect of the neuromodulating agent on the computational model of the grid-cell network, and also performed diffusion MRI-based tractography to find the neural tracts between the cortical areas involved: V2 and the entorhinal cortex.

Results

We applied our computational model to an experiment (where perceptual alterations were measured under psilocybin) and found that for n (Hill-coefficient) = 14.8 and k = 1.39, the theoretical prediction followed experimental observations very well (χ2 test robustly satisfied, p > 0.99). We predicted the outcome of another psilocybin-based experiment using these values (n = 14.8 and k = 1.39), whereby our prediction and experimental outcomes were well corroborated. Furthermore, we found that also under hypoactivation (chlorpromazine), the modulation of the visual-spatial perception follows our model. Moreover, we found neural tracts between the area V2 and entorhinal cortex, thus providing a possible brain network responsible for encoding visual-spatial perception. Thence, we simulated the altered grid-cell network activity, which was also found to follow the Hill equation.

Conclusion

We developed a computational model of visuospatial perceptual alterations under altered neural sympathetic/parasympathetic tone. We validated our model using analysis of behavioral studies, neuroimaging assessment, and neurocomputational evaluation. Our quantitative approach may be probed as a potential behavioral screening and monitoring methodology in neuropsychology to analyze perceptual misjudgment and mishaps by highly stressed workers.
CT-based thrombus radiomics nomogram for predicting secondary embolization during mechanical thrombectomy for large vessel occlusion
Authors: Yusuying Shadamu , Lu Yao , Zhang Shun , Wang Junjie , Chen Juan , Wang Daming , Lu Jun , Qi Peng
Published: May 2023

Background and aims

Secondary embolization (SE) during mechanical thrombectomy (MT) for cerebral large vessel occlusion (LVO) could reduce the anterior blood flow and worsen clinical outcomes. The current SE prediction tools have limited accuracy. In this study, we aimed to develop a nomogram to predict SE following MT for LVO based on clinical features and radiomics extracted from computed tomography (CT) images.

Materials and methods

A total of 61 patients with LVO stroke treated by MT at Beijing Hospital were included in this retrospective study, of whom 27 developed SE during the MT procedure. The patients were randomly divided (7:3) into training (n = 42) and testing (n = 19) cohorts. The thrombus radiomics features were extracted from the pre-interventional thin-slice CT images, and the conventional clinical and radiological indicators associated with SE were recorded. A support vector machine (SVM) learning model with 5-fold cross-verification was used to obtain the radiomics and clinical signatures. For both signatures, a prediction nomogram for SE was constructed. The signatures were then combined using the logistic regression analysis to construct a combined clinical radiomics nomogram.

Results

In the training cohort, the area under the receiver operating characteristic curve (AUC) of the nomograms was 0.963 for the combined model, 0.911 for the radiomics, and 0.891 for the clinical model. Following validation, the AUCs were 0.762 for the combined model, 0.714 for the radiomics model, and 0.637 for the clinical model. The combined clinical and radiomics nomogram had the best prediction accuracy in both the training and test cohort.

Conclusion

This nomogram could be used to optimize the surgical MT procedure for LVO based on the risk of developing SE.
Therapeutic effects of repetitive transcranial magnetic stimulation on cognitive impairment in stroke patients: a systematic review and meta-analysis
Authors: Gong Cheng , Hu Hao , Peng Xu-Miao , Li Hai , Xiao Li , Liu Zhen , Zhong Yan-Biao , Wang Mao-Yuan , Luo Yun
Published: May 2023

Background

In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as a noninvasive and painless treatment for post-stroke cognitive impairment (PSCI). However, few studies have analyzed the intervention parameters of cognitive function and the effectiveness and safety of rTMS for treating patients with PSCI. Thus, this meta-analysis aimed to analyze the interventional parameters of rTMS and evaluate the safety and effectiveness of rTMS for treating patients with PSCI.

Methods

According to the PRISMA guidelines, we searched the Web of Science, PubMed, EBSCO, Cochrane Library, PEDro, and Embase to retrieve randomized controlled trials (RCTs) of rTMS for the treatment of patients with PSCI. Studies were screened according to the inclusion and exclusion criteria, and two reviewers independently performed literature screening, data extraction, and quality assessment. RevMan 5.40 software was used for data analysis.

Results

12 RCTs involving 497 patients with PSCI met the inclusion criteria. In our analysis, rTMS had a positive therapeutic effect on cognitive rehabilitation in patients with PSCI (P < 0.05). Both high-frequency rTMS and low-frequency rTMS were effective in improving the cognitive function of patients with PSCI by stimulating the dorsolateral prefrontal cortex (DLPFC), but their efficacy was not statistically different (P > 0.05).

Conclusions

rTMS treatment on the DLPFC can improve cognitive function in patients with PSCI. There is no significant difference in the treatment effect of high-frequency rTMS and low-frequency rTMS in patients with PSCI between high-frequency and low-frequency rTMS.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323720, identifier CRD 42022323720.
Intranasal 15d-PGJ2 inhibits the growth of rat lactotroph pituitary neuroendocrine tumors by inducing PPARγ-dependent apoptotic and autophagic cell death
Authors: Li Zongyang , Chen Lei , Zhang Di , Huang Xianjian , Yang Jihu , Li Weiping , Wang Chuanfang , Meng Xiangbao , Huang Guodong
Published: May 2023

PPARγ agonists have been reported to induce cell death in pituitary neuroendocrine tumor (PitNET) cell cultures. However, the therapeutic effects of PPARγ agonists in vivo remain unclear. In the present study, we found that intranasal 15d-PGJ2, an endogenous PPARγ agonist, resulted in growth suppression of Fischer 344 rat lactotroph PitNETs induced by subcutaneous implantation with a mini-osmotic pump containing estradiol. Intranasal 15d-PGJ2 reduced the volume and weight of the pituitary gland and the level of serum prolactin (PRL) in rat lactotroph PitNETs. 15d-PGJ2 treatment attenuated pathological changes and significantly decreased the ratio of PRL/pituitary-specific transcription factor 1 (Pit-1) and estrogen receptor α (ERα)/Pit-1 double-positive cells. Moreover, 15d-PGJ2 treatment induced apoptosis in the pituitary gland characterized by an increased ratio of TUNEL-positive cells, cleavage of caspase-3, and elevated activity of caspase-3. 15d-PGJ2 treatment decreased the levels of cytokines, including TNF-α, IL-1β, and IL-6. Furthermore, 15d-PGJ2 treatment markedly increased the protein expression of PPARγ and blocked autophagic flux, as evidenced by the accumulation of LC3-II and SQSTM1/p62 and the decrease in LAMP-1 expression. Importantly, all these effects mediated by 15d-PGJ2 were abolished by cotreatment with the PPARγ antagonist GW9662. In conclusion, intranasal 15d-PGJ2 suppressed the growth of rat lactotroph PitNETs by inducing PPARγ-dependent apoptotic and autophagic cell death. Therefore, 15d-PGJ2 may be a potential new drug for lactotroph PitNETs.
Allocation of cognitive resources in cognitive processing of rhythmic visual stimuli before gait-related motor initiation
Authors: Zhou Huilin , Yan Wenfeng , Xu Jialin , Ma Yehao , Zuo Guokun , Shi Changcheng
Published: May 2023

Rhythmic visual cues can affect the allocation of cognitive resources during gait initiation (GI) and motor preparation. However, it is unclear how the input of rhythmic visual information modulates the allocation of cognitive resources and affects GI. The purpose of this study was to explore the effect of rhythmic visual cues on the dynamic allocation of cognitive resources by recording electroencephalographic (EEG) activity during exposure to visual stimuli. This study assessed event-related potentials (ERPs), event-related synchronization/desynchronization (ERS/ERD), and EEG microstates at 32 electrodes during presentation of non-rhythmic and rhythmic visual stimuli in 20 healthy participants. The ERP results showed that the amplitude of the C1 component was positive under exposure to rhythmic visual stimuli, while the amplitude of the N1 component was higher under exposure to rhythmic visual stimuli compared to their non-rhythmic counterparts. Within the first 200 ms of the onset of rhythmic visual stimuli, ERS in the theta band was highly pronounced in all brain regions analyzed. The results of microstate analysis showed that rhythmic visual stimuli were associated with an increase in cognitive processing over time, while non-rhythmic visual stimuli were associated with a decrease. Overall, these findings indicated that, under exposure to rhythmic visual stimuli, consumption of cognitive resources is lower during the first 200 ms of visual cognitive processing, but the consumption of cognitive resources gradually increases over time. After approximately 300 ms, cognitive processing of rhythmic visual stimuli consumes more cognitive resources than processing of stimuli in the non-rhythmic condition. This indicates that the former is more conducive to the completion of gait-related motor preparation activities, based on processing of rhythmic visual information during the later stages. This finding indicates that the dynamic allocation of cognitive resources is the key to improving gait-related movement based on rhythmic visual cues.
High fidelity sensory-evoked responses in neocortex after intravenous injection of genetically encoded calcium sensors
Authors: Leikvoll Austin , Kara Prakash
Published: May 2023

Two-photon imaging of genetically-encoded calcium indicators (GECIs) has traditionally relied on intracranial injections of adeno-associated virus (AAV) or transgenic animals to achieve expression. Intracranial injections require an invasive surgery and result in a relatively small volume of tissue labeling. Transgenic animals, although they can have brain-wide GECI expression, often express GECIs in only a small subset of neurons, may have abnormal behavioral phenotypes, and are currently limited to older generations of GECIs. Inspired by recent developments in the synthesis of AAVs that readily cross the blood brain barrier, we tested whether an alternative strategy of intravenously injecting AAV-PHP.eB is suitable for two-photon calcium imaging of neurons over many months after injection. We injected C57BL/6 J mice with AAV-PHP.eB-Synapsin-jGCaMP7s via the retro-orbital sinus. After allowing 5 to 34 weeks for expression, we performed conventional and widefield two-photon imaging of layers 2/3, 4 and 5 of the primary visual cortex. We found reproducible trial-by-trial neural responses and tuning properties consistent with known feature selectivity in the visual cortex. Thus, intravenous injection of AAV-PHP.eB does not interfere with the normal processing in neural circuits. In vivo and histological images show no nuclear expression of jGCaMP7s for at least 34 weeks post-injection.
Mitochondria-associated endoplasmic reticulum membranes (MAMs) and their role in glaucomatous retinal ganglion cell degeneration—a mini review
Authors: Pham Jennifer H. , Stankowska Dorota L.
Published: May 2023

Glaucoma is a leading cause of blindness worldwide, commonly associated with elevated intraocular pressure (IOP), leading to degeneration of the optic nerve and death of retinal ganglion cells, the output neurons in the eye. In recent years, many studies have implicated mitochondrial dysfunction as a crucial player in glaucomatous neurodegeneration. Mitochondrial function has been an increasingly researched topic in glaucoma, given its vital role in bioenergetics and propagation of action potentials. One of the most metabolically active tissues in the body characterized by high oxygen consumption is the retina, particularly the retinal ganglion cells (RGCs). RGCs, which have long axons that extend from the eyes to the brain, rely heavily on the energy generated by oxidative phosphorylation for signal transduction, rendering them more vulnerable to oxidative damage. In various glaucoma models, mitochondrial dysfunction and stress from protein aggregates in the endoplasmic reticulum (ER) have been observed in the RGCs. However, it has been shown that the two organelles are connected through a network called mitochondria-associated ER membranes (MAMs); hence this crosstalk in a pathophysiological condition such as glaucoma should be evaluated. Here, we review the current literature suggestive of mitochondrial and ER stress related to glaucoma, indicating potential cross-signaling and the potential roles of MAMs.
Factors influencing the relationship between cochlear health measures and speech recognition in cochlear implant users
Authors: Zamaninezhad Ladan , Mert Berkutay , Benav Heval , Tillein Jochen , Garnham Carolyn , Baumann Uwe
Published: May 2023

Background

One factor which influences the speech intelligibility of cochlear implant (CI) users is the number and the extent of the functionality of spiral ganglion neurons (SGNs), referred to as “cochlear health.” To explain the interindividual variability in speech perception of CI users, a clinically applicable estimate of cochlear health could be insightful. The change in the slope of the electrically evoked compound action potentials (eCAP), amplitude growth function (AGF) as a response to increased interphase gap (IPG) (IPGEslope) has been introduced as a potential measure of cochlear health. Although this measure has been widely used in research, its relationship to other parameters requires further investigation.

Methods

This study investigated the relationship between IPGEslope, demographics and speech intelligibility by (1) considering the relative importance of each frequency band to speech perception, and (2) investigating the effect of the stimulus polarity of the stimulating pulse. The eCAPs were measured in three different conditions: (1) Forward masking with anodic-leading (FMA) pulse, (2) Forward masking with cathodic-leading (FMC) pulse, and (3) with alternating polarity (AP). This allowed the investigation of the effect of polarity on the diagnosis of cochlear health. For an accurate investigation of the correlation between IPGEslope and speech intelligibility, a weighting function was applied to the measured IPGEslopes on each electrode in the array to consider the relative importance of each frequency band for speech perception. A weighted Pearson correlation analysis was also applied to compensate for the effect of missing data by giving higher weights to the ears with more successful IPGEslope measurements.

Results

A significant correlation was observed between IPGEslope and speech perception in both quiet and noise for between-subject data especially when the relative importance of frequency bands was considered. A strong and significant correlation was also observed between IPGEslope and age when stimulation was performed with cathodic-leading pulses but not for the anodic-leading pulse condition.

Conclusion

Based on the outcome of this study it can be concluded that IPGEslope has potential as a relevant clinical measure indicative of cochlear health and its relationship to speech intelligibility. The polarity of the stimulating pulse could influence the diagnostic potential of IPGEslope.
Derivation and validation of a nutrition-covered prognostic scoring system for extranodal NK/T-cell lymphoma
Authors: Lu Tiange , Shi Xue , Ge Xueling , Li Ying , Cai Yiqing , Chen Xiaomin , Hu Shunfeng , Ding Mei , Fang Xiaosheng , Liu Fang , Zhou Xiangxiang , Wang Xin
Published: May 2023

Introduction

Patients with aggressive lymphomas are at high risk of losing body resources, resulting in malnutrition, immunodeficiency and inferior outcomes. Nutritional status is closely associated with survival, but often neglected in the prognostic assessment. This study aimed to explore the significance of nutritional status in extranodal NK/T-cell lymphoma (ENKTL).

Methods

Univariate and multivariate Cox regression analyses were conducted to examine the significance of nutritional index on overall survival (OS) and progression-free survival (PFS). A nutrition-incorporated score system was constructed based on the multivariate results, and its calibration, discrimination and clinical utility were tested in the training and validation cohort.

Results

Multivariate analysis revealed controlling nutritional status (CONUT) score could independently predict OS (HR 10.247, P=0.001) and PFS (HR 5.587, P=0.001) in addition to prognostic index of natural killer lymphoma plus EBV (PINK-E). Herein, a reformative model, CONUT-PINK-E, was developed and further verified in external validation cohort. CONUT-PINK-E classified patients into three risk grades with significant survival differences (P < 0.001). Compared with the current models, CONUT-PINK-E presented superior discrimination, calibration and clinical benefit.

Discussion

In this study, we firstly verified that CONUT score was efficient to screen prognosis-related malnutrition in ENKTL. Moreover, we developed the first nutritional assessment-covered scoring system, CONUT-PINK-E, which might be a promising tool to provide references for clinical decision-making of ENKTL patients.
Serum vitamin C levels and risk of non-alcoholic fatty liver disease: results from a cross-sectional study and Mendelian randomization analysis
Authors: Wu Hui , Guo Jiang-Long , Yao Jing-Jiong , Yu Jia-Jun , Xia Run-Yu , Huang Wei-Qing , Tang Xuan , He Guang-Ming
Published: May 2023

Background and aims

Vitamin C, as an antioxidant, may play a role in the treatment of NAFLD. This research aimed to investigate the association of serum vitamin C levels with the risk of NAFLD and to further examine the causal relationship by Mendelian randomization (MR) method.

Methods

The cross-sectional study selected 5,578 participants of the National Health and Nutrition Examination Survey (NHANES), 2005–2006 and 2017–2018. The association of serum vitamin C levels with NAFLD risk was evaluated under a multivariable logistic regression model. A two-sample MR study, using genetic data from large-scale genome-wide association studies (GWAS) of serum vitamin C levels (52,014 individuals) and NAFLD (primary analysis: 1,483 cases /17,781 controls; secondary analysis: 1,908 cases/340,591 controls), was conducted to infer causality between them. The inverse-variance-weighted (IVW) was applied as the main method of MR analysis. A series of sensitivity analyzes were used to evaluate the pleiotropy.

Results

In the cross-sectional study, results showed that Tertile 3 group (Tertile 3: ≥1.06 mg/dl) had a significantly lower risk (OR = 0.59, 95% CI: 0.48 ~ 0.74, p < 0.001) of NAFLD than Tertile 1 group (Tertile 1: ≤0.69 mg/dl) after full adjustments. In regard to gender, serum vitamin C was protective against NAFLD in both women (OR = 0.63, 95% CI: 0.49 ~ 0.80, p < 0.001) and men (OR = 0.73, 95% CI: 0.55 ~ 0.97, p = 0.029) but was stronger among women. However, in the IVW of MR analyzes, no causal relationship between serum vitamin C levels and NAFLD risk was observed in the primary analysis (OR = 0.82, 95% CI: 0.47 ~ 1.45, p = 0.502) and secondary analysis (OR = 0.80, 95% CI: 0.53 ~ 1.22, p = 0.308). MR sensitivity analyzes yielded consistent results.

Conclusion

Our MR study did not support a causal association between serum vitamin C levels and NAFLD risk. Further studies with greater cases are warranted to confirm our findings.
Serum-free alginate-C2C12 cells microcapsule as a model of alternative animal protein source
Authors: Scheffold Jana , Bruheim Per , Kjesbu Joachim Sebastian , Jang Mi
Published: May 2023

Due to the climate change crisis, and environmental impacts of the traditional meat sector, the production of artificial animal protein based on in vitro cell culture technology is proposed as an alternative. Furthermore, since traditional animal serum-supplemented cultures pose scientific challenges such as batch variation and contamination risks, artificial animal protein cultures are currently in urgent need of not only serum-free cultures, but also microcarrier culture systems for scalability. However, serum-free microcarrier-based culture system for the differentiation of muscle cells is not available to date. Therefore, we established an edible alginate microcapsules culture system for the differentiation of C2C12 cells in serum-free conditions. Furthermore, metabolites related to central carbon metabolism were profiled based on targeted metabolomics using mass spectrometry. The C2C12 cells cultured in alginate microcapsules displayed high viability throughout 7 days and successfully differentiated within 4 days in serum and serum-free cultures except for AIM-V cultures, which was confirmed by CK activity and MHC immunostaining. Lastly, to the best of our knowledge, this is the first report to compare metabolite profiles between monolayer and alginate microcapsule culture systems. Alginate microcapsule culture showed higher levels of intracellular glycolysis and TCA cycle intermediates, lactate, and the contribution of essential amino acids compared to the monolayer culture. We believe our serum-free alginate microcapsule culture system is adaptable to different species of muscle cells and contributes to future food technology as a proof of concept for the scalability of alternative animal protein source production.
Babao Dan decreases hepatocarcinogenesis by inhibiting hepatic progenitor cells malignant transformation via down-regulating toll-like receptor 4
Authors: Liang Lei , Zhang Lu-Yao , Liu Wen-Ting , Zong Chen , Gao Lu , Li Rong , Zhao Qiu-Dong , Zhao Na-Ping , Wei Li-Xin , Zhang Li , Han Zhi-Peng
Published: May 2023

Background

Babao Dan (BBD) is a traditional Chinese medicine that has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the effect of BBD on the incidence of diethylnitrosamine (DEN)-initiated hepatocellular carcinoma formation in rats and explored its possible mechanism.

Methods

To verify this hypothesis, BBD was administrated to rats at a dose of 0.5g/kg body weight per two days from the 9th to 12th week in HCC-induced by DEN. Liver injury biomarkers and hepatic inflammatory parameters were evaluated by histopathology as well as serum and hepatic content analysis. We applied immunohistochemical analysis to investigate the expression of CK-19 and SOX-9 in liver tissues. The expression of TLR4 was determined by immunohistochemical, RT-PCR, and western blot analysis. Furthermore, we also detected the efficacy of BBD against primary HPCs neoplastic transformation induced by LPS.

Results

We observed that DEN could induce hepatocarcinogenesis, and BBD could obviously decrease the incidence. The biochemical and histopathological examination results confirmed that BBD could protect against liver injury and decrease inflammatory infiltration. Immunohistochemistry staining results showed that BBD could effectively inhibit the ductal reaction and the expression of TLR4. The results showed that BBD-serumcould obviously inhibit primary HPCs neoplastic transformation induced by regulating the TLR4/Ras/ERK signaling pathway.

Conclusion

In summary, our results indicate that BBD has potential applications in the prevention and treatment of HCC, which may be related to its effect on hepatic progenitor cells malignant transformation via inhibiting the TLR4/Ras/ERK signaling pathway.
Metabolic syndrome is independently associated with improved overall survival to first-line therapy with immune checkpoint inhibitors in non-small cell lung cancer
Authors: Bou Zerdan Maroun , Ashok Kumar Prashanth , Barrios Dulce M. , Glidden Alanna , Nasr Dayana , Niforatos Stephanie , Ghelani Ghanshyam , Leibovitch Jennifer , Nasr Sandy , KC Binod , Ombada Mulham , Khokhar Farzam , Poudyal Bhavya , Bhandari Jenish , Shahnawaz Myera , Graziano Stephen , Lim Seah H.
Published: May 2023

Background

Many co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC).

Methods

We carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC.

Results

One hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival.

Conclusions

Our results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.
Xerna™ TME Panel is a machine learning-based transcriptomic biomarker designed to predict therapeutic response in multiple cancers
Authors: Uhlik Mark , Pointing Daniel , Iyer Seema , Ausec Luka , Štajdohar Miha , Cvitkovič Robert , Žganec Matjaž , Culm Kerry , Santos Valerie Chamberlain , Pytowski Bronislaw , Malafa Mokenge , Liu Hong , Krieg Arthur M. , Lee Jeeyun , Rosengarten Rafael , Benjamin Laura
Published: May 2023

Introduction

Most predictive biomarkers approved for clinical use measure single analytes such as genetic alteration or protein overexpression. We developed and validated a novel biomarker with the aim of achieving broad clinical utility. The Xerna™ TME Panel is a pan-tumor, RNA expression-based classifier, designed to predict response to multiple tumor microenvironment (TME)-targeted therapies, including immunotherapies and anti-angiogenic agents.

Methods

The Panel algorithm is an artificial neural network (ANN) trained with an input signature of 124 genes that was optimized across various solid tumors. From the 298-patient training data, the model learned to discriminate four TME subtypes: Angiogenic (A), Immune Active (IA), Immune Desert (ID), and Immune Suppressed (IS). The final classifier was evaluated in four independent clinical cohorts to test whether TME subtype could predict response to anti-angiogenic agents and immunotherapies across gastric, ovarian, and melanoma datasets.

Results

The TME subtypes represent stromal phenotypes defined by angiogenesis and immune biological axes. The model yields clear boundaries between biomarker-positive and -negative and showed 1.6-to-7-fold enrichment of clinical benefit for multiple therapeutic hypotheses. The Panel performed better across all criteria compared to a null model for gastric and ovarian anti-angiogenic datasets. It also outperformed PD-L1 combined positive score (>1) in accuracy, specificity, and positive predictive value (PPV), and microsatellite-instability high (MSI-H) in sensitivity and negative predictive value (NPV) for the gastric immunotherapy cohort.

Discussion

The TME Panel’s strong performance on diverse datasets suggests it may be amenable for use as a clinical diagnostic for varied cancer types and therapeutic modalities.
EGFR p.V774M/p.L833V compound mutations in lung adenocarcinoma responded well to almonertinib: a case report
Authors: Pan Hai , Zhang Linlin , Meng Fanlu , Guan Shasha , Zhong Diansheng
Published: May 2023

Background

There are about 10-15% of uncommon EGFR mutations found in NSCLC patients, and their sensitivity to EGFR TKIs still lack sufficient clinical evidence, especially for rare compound mutations. Almonertinib is the third generation of EGFR-TKI that has demonstrated excellent efficacy in classical mutations, however, effects in rare mutations have also been rarely reported.

Case presentation

In this case report, we present a patient with advanced lung adenocarcinoma with a rare EGFR p.V774M/p.L833V compound mutations, who achieved long-lasting and stable disease control after first-line Almonertinib targeted therapy. This case report could provide more information for therapeutic strategy selecting of NSCLC patients harboring rare EGFR mutations.

Conclusion

We report for the first time the long-lasting and stable disease control with Almonertinib for EGFR p.V774M/p.L833V compound mutations treatment, hoping to provide more clinical case references for the treatment of rare compound mutations.
Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer
Authors: Shi Demin , Li Yan , Liang Xueyan , Chen Lingyuan
Published: May 2023

Background

The efficiency and safety of sacituzumab govitecan (SG) for the therapy of hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) metastatic breast cancer (BC) has been demonstrated. The aim of this study is to evaluate its cost-effectiveness on HR+/HER2- metastatic BC from the third-party payer perspective in the United States.

Methods

We performed the cost-effectiveness of SG and chemotherapy using a partitioned survival model. TROPiCS-02 provided clinical patients for this study. We evaluated the robustness of this study by one-way and probabilistic sensitivity analyses. Subgroup analyses were also conducted. The outcomes were costs, life-years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB).

Results

SG treatment was related to an increase of 0.284 life years and 0.217 QALYs over chemotherapy, as well as a cost increase of $132,689, reaching an ICER of $612,772/QALY. The INHB was -0.668 QALYs, and the INMB was -$100,208. SG was not cost-effective at the willingness to pay (WTP) threshold of $150,000/QALY. The outcomes were sensitive to patient body weight and cost of SG. SG may be cost-effective at the WTP threshold of $150,000/QALY if the price is less than $3.997/mg or the weight of patients is under 19.88 kg. Based on the subgroup analysis, SG did not prove cost-effective in all subgroups at the WTP threshold of $150,000/QALY.

Conclusion

From a third-party payer standpoint in the United States, SG was not cost-effective, even though it had a clinically significant advantage over chemotherapy for the treatment of HR+/HER2- metastatic BC. The cost-effectiveness of SG can be improved if the price is substantially reduced.
Intragenic β-synuclein rearrangements in malignancy
Authors: Xiao Peifang , Chen Nan , Shao Tingting , Bian Xinni , Miao Jie , Zheng Jiajia , Lang Xingping , Wang Yiting , Chen Xiaojun , Jin Liqin , Hu Shaoyan , Xiao Sheng
Published: May 2023

The synuclein family, consisting of α-, β-, and γ-synuclein, is primarily expressed in neurons. Mutations of α- and β-synuclein have been linked to Parkinson’s disease and dementia with Lewy bodies, respectively. Recent studies have shown that synucleins are upregulated in various tumors, including breast, ovarian, meningioma, and melanoma, and high synuclein expression is associated with poor prognosis and drug resistance. We report a novel rearrangement of β-synuclein in a pediatric T-cell acute lymphoblastic leukemia (T-ALL) case, where β-synuclein (SNCB) is fused in-frame with ETS variant transcription factor 6 (ETV6), a gene frequently rearranged in acute leukemia including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and T-ALL. An additional case of β-synuclein rearrangement was identified in a squamous cell carcinoma of the lung through analysis of the public TCGA database. Both rearrangements involve the C-terminal of β-synuclein. Since β-synuclein shares extensive amino acid similarities with α-synuclein and α-synuclein binds to 14-3-3, an important regulator of apoptosis, the rearranged β-synuclein may contribute to tumorigenesis by deregulating apoptosis. In addition, overexpression of synucleins has been shown to increase cell proliferation, suggesting that the rearranged β-synuclein may also deregulate the cell cycle.
Comprehensive analysis and molecular map of Hippo signaling pathway in lower grade glioma: the perspective toward immune microenvironment and prognosis
Authors: Guo Yu-Duo , Sun Jie , Zhao Chao , Han Le , Yu Chun-Jiang , Zhang Hong-Wei
Published: May 2023

Background

The activation of YAP/TAZ transcriptional co-activators, downstream effectors of the Hippo/YAP pathway, is commonly observed in human cancers, promoting tumor growth and invasion. The aim of this study was to use machine learning models and molecular map based on the Hippo/YAP pathway to explore the prognosis, immune microenvironment and therapeutic regimen of patients with lower grade glioma (LGG).

Methods

SW1783 and SW1088 cell lines were used as in vitro models for LGG, and the cell viability of the XMU-MP-1 (a small molecule inhibitor of the Hippo signaling pathway) treated group was evaluated using a Cell Counting Kit-8 (CCK-8). Univariate Cox analysis on 19 Hippo/YAP pathway related genes (HPRGs) was performed to identify 16 HPRGs that exhibited significant prognostic value in meta cohort. Consensus clustering algorithm was used to classify the meta cohort into three molecular subtypes associated with Hippo/YAP Pathway activation profiles. The Hippo/YAP pathway’s potential for guiding therapeutic interventions was also investigated by evaluating the efficacy of small molecule inhibitors. Finally, a composite machine learning models was used to predict individual patients’ survival risk profiles and the Hippo/YAP pathway status.

Results

The findings showed that XMU-MP-1 significantly enhanced the proliferation of LGG cells. Different Hippo/YAP Pathway activation profiles were associated with different prognostic and clinical features. The immune scores of subtype B were dominated by MDSC and Treg cells, which are known to have immunosuppressive effects. Gene Set Variation Analysis (GSVA) indicated that subtypes B with a poor prognosis exhibited decreased propanoate metabolic activity and suppressed Hippo pathway signaling. Subtype B had the lowest IC50 value, indicating sensitivity to drugs that target the Hippo/YAP pathway. Finally, the random forest tree model predicted the Hippo/YAP pathway status in patients with different survival risk profiles.

Conclusions

This study demonstrates the significance of the Hippo/YAP pathway in predicting the prognosis of patients with LGG. The different Hippo/YAP Pathway activation profiles associated with different prognostic and clinical features suggest the potential for personalized treatments.
Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review
Authors: Johnson Ken B. , Sharma Anukriti , Henry N. Lynn , Wei Mei , Bie Bihua , Hershberger Courtney E. , Rhoades Emily E. , Sen Alper , Johnson Ryan E. , Steenblik Jacob , Hockings Jennifer , Budd G. Thomas , Eng Charis , Foss Joseph , Rotroff Daniel M.
Published: May 2023

Taxanes, particularly paclitaxel and docetaxel, are chemotherapeutic agents commonly used to treat breast cancers. A frequent side effect is chemotherapy-induced peripheral neuropathy (CIPN) that occurs in up to 70% of all treated patients and impacts the quality of life during and after treatment. CIPN presents as glove and stocking sensory deficits and diminished motor and autonomic function. Nerves with longer axons are at higher risk of developing CIPN. The causes of CIPN are multifactorial and poorly understood, limiting treatment options. Pathophysiologic mechanisms can include: (i) disruptions of mitochondrial and intracellular microtubule functions, (ii) disruption of axon morphology, and (iii) activation of microglial and other immune cell responses, among others. Recent work has explored the contribution of genetic variation and selected epigenetic changes in response to taxanes for any insights into their relation to pathophysiologic mechanisms of CIPN20, with the hope of identifying predictive and targetable biomarkers. Although promising, many genetic studies of CIPN are inconsistent making it difficult to develop reliable biomarkers of CIPN. The aims of this narrative review are to benchmark available evidence and identify gaps in the understanding of the role genetic variation has in influencing paclitaxel's pharmacokinetics and cellular membrane transport potentially related to the development of CIPN.
A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
Authors: Huang Renhong , Wang Han , Hong Jin , Wang Zheng , Wu Jiayi , Huang Ou , He Jianrong , Chen Weiguo , Li Yafen , Chen Xiaosong , Shen Kunwei
Published: May 2023

Background: Recent studies have found that senescence-associated genes play a significant role in cancer biological processes. We aimed to analyze the characteristics and role of senescence-associated genes in triple-negative breast cancer (TNBC).

Methods: We systematically screened senescence-associated secretory phenotype (SASP) genes based on the gene expression information in the TCGA database. According to the expression levels of senescence-associated genes, TNBC was classified into two subtypes, namely, TNBCSASP1 and TNBCSASP2, using an unsupervised cluster algorithm. We then performed gene expression, enrichment pathway, immune infiltration, mutational profile characterization, drug sensitivity and prognostic value analyses for the two subtypes. The reliability and prognostic predictive utility of this classification model were validated. The most prognostically relevant gene, FAM3B, was comprehensively identified and validated by tissue microarray in TNBC.

Results: TNBC was classified into two senescence-associated subtypes, TNBCSASP1 and TNBCSASP2, based on the set of senescence-associated secretory phenotype genes, among which the TNBCSASP1 subtype had a poor prognosis. The TNBCSASP1 subtype was immunosuppressed, with suppressed immune-related signaling pathways and low immune cell infiltration. The effect of the mutation on the TP53 and TGF-β pathways could be related to the poor prognosis of the TNBCSASP1 subtype. Drug sensitivity analysis showed that AMG.706, CCT007093, and CHIR.99021 were potential targeted drugs for the TNBCSASP1 subtype. Finally, FAM3B was a key biomarker affecting the prognosis of patients with triple-negative breast cancer. Compared to normal breast tissue, the expression of FAM3B was reduced in triple-negative breast cancer. Survival analysis showed that overall survival was significantly shorter in triple-negative breast cancer patients with high FAM3B expression.

Conclusion: A senescence-associated signature with different modification patterns has critical potential for providing a better understanding of TNBC biological processes, and FAM3B might serve as an applicable target for TNBC therapy.
The manufacture and reliability analysis of the all-rigid Fabry–Perot resonator for fiber-optic acoustic sensors
Authors: Zheng Yongqiu , Chen Jiamin , Bai Jiandong , Li Zonghao , Zhao Xinyu , Xue Chenyang
Published: May 2023

By the continuous development of aerospace, petroleum exploration, and other industrial fields, the fiber-optic acoustic sensor (FOAS) with high reliability is a desideration sensor, which can be used for noise monitoring in the extremely harsh environment. The FOAS based on the all-rigid Fabry–Perot resonator (FPR) relies on the new acoustic sensitive principle, where the change in the air refractive index is induced by sound waves and gets rid of the distortion caused by the mechanical characteristics of the acoustic sensor based on the movable parts. So, the FPR-based FOAS is very suitable for acoustic sensing in the harsh environment. In this paper, the reliability of this kind of FOASs is simulated and analyzed. The modal and anti-vibration simulation results of FPR with different sizes show that the FPR has a high natural frequency, and the external vibration environment does not affect the acoustic sensitivity of the FPR. The micro and small-batch all-rigid FPR can be manufactured by the optical contact. Moreover, the FPR can withstand the high temperature of 500°C that is verified by rapid heat treatment equipment. In order to improve the reliability of the FOAS, the metal packing shell is designed and fabricated. Moreover, the vibration and high-temperature tests of the packaged sensor are carried out. The two groups of tests show that the sensor can work normally under 10 g of acceleration vibration and 200°C high temperature, respectively. Therefore, the FOAS based on the FPR has high reliability and is very suitable for noise monitoring in the extreme harsh environment of various industrial fields. Furthermore, the research results of this paper will enhance the competitiveness and influence of the commercialized FOAS.
Drying temperatures affect the qualitative–quantitative variation of aromatic profiling in Anethum graveolens L. ecotypes as an industrial–medicinal–vegetable plant
Authors: Farmanpour Kalalagh Karim , Mohebodini Mehdi , Fattahi Reza , Beyraghdar Kashkooli Arman , Davarpanah Dizaj Sanaz , Salehifar Fatemeh , Mokhtari Amir Mohammad
Published: May 2023

Introduction

There are several factors that affect the quality and quantity of active ingredients and essential oil (EO) content, including pre and postharvest practices such as drying conditions. One of the most important factors in drying is temperature and then selective drying temperature (DT). In general, DT has a direct effect on the aromatic properties of Anethum graveolens.

Methods

On this basis, the present study was conducted to evaluate the effects of different DTs on the aroma profile of A. graveolens ecotypes.

Results and discussion

The results showed that different DTs, ecotypes, and their interaction significantly affect EO content and composition. The highest EO yield was obtained from the Parsabad ecotype (1.86%) followed by the Ardabil ecotype (1.4%), both at 40° C. More than 60 EO compounds were identified, mainly monoterpenes and sesquiterpenes, highlighting α-Phellandrene, Germacrene D, and Dill apiole as major components in all treatments. Besides α-Phellandrene, the major EO compounds at shad drying (ShD) were β-Phellandrene and p-Cymene, while plant parts dried at 40° C showed l-Limonene and Limonene as the main constituents, and Dill apiole was detected in greater amounts in the samples dried at 60 °C. To determine the appropriate DT, simple and factorial based-ANOVA together multivariate analysis demonstrated significant differences in the compounds produced under different DTs. The results indicated that more EO compounds, mainly monoterpenes, were extracted at ShD than other DTs. On the other hand, the content and composition of sesquiterpenes increased significantly when DT was increased to 60 °C. From the genetic backgrounds point of view, the Parsabad ecotype (with 12 similar compounds) and Esfahan ecotype (with 10 similar compounds) were the most suitable ecotypes under all DTs in terms of EO compounds. Accordingly, the present study would help various industries to optimize specific DT(s) to obtain special EO compound(s) from different A. graveolens ecotypes based on commercial requirements.