bluuebunny/crossref_metadata_2025 huggingface dataset:
L-shaped association between triglyceride-glucose body mass index and short-term mortality in ICU patients with sepsis-associated acute kidney injury
Authors: Xu Heping , Mo Ruiyong , Liu Yiqiao , Niu Huan , Cai Xiongwei , He Ping
Published: December 2024

Background

Sepsis is a systemic inflammatory response syndrome, with sepsis-associated acute kidney injury (SA-AKI) being a common complication. Insulin resistance (IR) is closely related to the stress response, inflammatory response, and severity of critical illness. The triglyceride-glucose body mass index (TyG-BMI) is a valuable tool for assessing IR. However, the relationships between TyG-BMI and clinical outcomes in patients with SA-AKI remain unclear.

Methods

We conducted a retrospective analysis of ICU patients with SA-AKI using data from the MIMIC-IV database. The Boruta algorithm was employed to select significant features for predicting short-term mortality in SA-AKI patients. Multivariate Cox proportional hazards regression, sensitivity analysis, restricted cubic spline (RCS) models, and Kaplan–Meier (K–M) survival analysis were used to assess the relationship between TyG-BMI and short-term mortality in SA-AKI patients. Subgroup analyses considered the effects of age, sex, ethnicity, comorbidities and septic shock.

Results

This study included 3,349 patients, with males accounting for 60.5% of the patients. The Boruta analysis identified the TyG-BMI as an important clinical feature. Higher TyG-BMI values were significantly associated with reduced short-term mortality rates (28, 90, and 180 days) in patients with SA-AKI; for each standard deviation increase in TyG-BMI, the risk of all-cause death decreased by 0.2% (p < 0.0001). Kaplan–Meier analysis demonstrated that patients with high TyG-BMIs had significantly lower mortality rates than did those with low TyG-BMIs. The RCS model revealed an L-shaped nonlinear relationship between the TyG-BMI and mortality. Sensitivity analyses indicated that the association remained significant even after excluding patients with myocardial infarction, congestive heart failure, or those who were hospitalized in the ICU for less than 2 days. Subgroup analyses revealed a significant interaction effect on short-term mortality in CRRT patients (p < 0.05).

Conclusion

The relationship between the TyG-BMI and short-term mortality in ICU patients with SA-AKI is significant, indicating its potential value for early risk assessment and clinical intervention.
Case report: A rare but fatal complication of hysteroscopy—air embolism during treatment for missed abortion
Authors: Ou Yang , Li Jun-Qiang , Tang Rong , Ma Duo-Na , Liu Yang
Published: December 2024

Hysteroscopic procedures complicated by air embolism (AE) are exceptionally rare occurrences in clinical practice, and there have been no previously reported cases of AE associated with hysteroscopic dilation and curettage. While the overall incidence of this complication is low, the consequences can be devastating. During early pregnancy, the unique physiological changes, such as elevated hormonal levels and increased uterine blood supply, significantly heighten the risk of AE development. Therefore, the prompt recognition of early signs and symptoms, coupled with the implementation of timely and effective interventions, are crucial to improve patient survival rates and minimize the risk of long-term sequelae. This case report presents the characteristic clinical manifestations and imaging findings associated with AE, providing a valuable clinical reference for obstetricians and gynecologists to recognize this rare yet potentially life-threatening complication of hysteroscopic procedures. Early detection and appropriate management are essential to optimize patient outcomes and prevent catastrophic consequences.
Mycobiome analysis of leaf, root, and soil of symptomatic oil palm trees (Elaeis guineensis Jacq.) affected by leaf spot disease
Authors: Azeez Abiodun Abeeb , Esiegbuya Daniel Ofeoritse , Lateef Adebola Azeez , Asiegbu Fred O.
Published: December 2024

Recently, attention has been shifting toward the perspective of the existence of plants and microbes as a functioning ecological unit. However, studies highlighting the impacts of the microbial community on plant health are still limited. In this study, fungal community (mycobiome) of leaf, root, and soil of symptomatic leaf-spot diseased (SS) oil palm were compared against asymptomatic (AS) trees using ITS2 rRNA gene metabarcoding. A total of 3,435,417 high-quality sequences were obtained from 29 samples investigated. Out of the 14 phyla identified, Ascomycota and Basidiomycota were the most dominant accounting for 94.2 and 4.7% of the total counts in AS, and 75 and 21.2% in SS, respectively. Neopestalotiopsis is the most abundant genus for AS representing 8.0% of the identified amplicons compared to 2.0% in SS while Peniophora is the most abundant with 8.6% of the identified amplicons for SS compared to 0.1% in AS. The biomarker discovery algorithm LEfSe revealed different taxa signatures for the sample categories, particularly soil samples from asymptomatic trees, which were the most enriched. Network analysis revealed high modularity across all groups, except in root samples. Additionally, a large proportion of the identified keystone species consisted of rare taxa, suggesting potential role in ecosystem functions. Surprisingly both AS and SS leaf samples shared taxa previously associated with oil palm leaf spot disease. The significant abundance of Trichoderma asperellum in the asymptomatic root samples could be further explored as a potential biocontrol agent against oil palm disease.
One-pot MCDA-CRISPR-Cas-based detection platform for point-of-care testing of severe acute respiratory syndrome coronavirus 2
Authors: Wang Xiaoxia , Yang Rui , Tang Tian , Zhou Yuzhen , Chen Heng , Jiang Yihao , Zhang Shirong , Qin Sihan , Wang Meijuan , Wang Chuan
Published: December 2024

Compared to quantitative real-time PCR (q-PCR), CRISPR-Cas-mediated technology is more suitable for point-of-care testing (POCT) and has potential for wider application in the future. Generally, the operational procedure of CRISPR-Cas-mediated diagnostic method consists of two independent steps, the reaction of signal amplification and the CRISPR-Cas-mediated signal detection. Complex multi-step procedures can easily lead to cross-contamination. To develop a convenient and rapid method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection, we propose a MCTOP method (Multiple cross displacement amplification-CRISPR-Cas12b-based testing in one-pot), which targets the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) gene of SARS-CoV-2. This method combines MCDA isothermal amplification and CRISPR-Cas-mediated sequence-specific detection into a one-pot reaction. The optimal reaction was achieved with isothermal amplification of 40 min and CRISPR-Cas-based detection of 15 min, both at 64°C. Then, the results can be visualized by the real-time fluorescence instrument and also lateral flow biosensor. The lowest detection limit of the proposed method is 10 copies of each of target sequences, and it has no cross-reactivity with non-SARS-CoV-2 templates. In a clinical test of 70 pharyngeal swab samples, MCTOP assay showed a specificity of 100% and sensitivities of 98 and 96% for the real-time fluorescence instrument and lateral flow biosensor, respectively. The MCTOP developed in this study is a rapid, convenient, highly sensitive, and specific method for SARS-CoV-2 nucleic acid detection. It can be used as an effective point-of-care testing (POCT) tool for clinical diagnosis and epidemiologic surveillance of SARS-CoV-2 infections, especially suitable for the basic, field and clinical laboratory.
Dynamic microbial changes in exacerbation of chronic obstructive pulmonary disease
Authors: Choi Yong Jun , Park Hye Jung , Kim Chi Young , Choi Aeri , Cho Jae Hwa , Byun Min Kwang
Published: December 2024

Background

Microbial profiles in patients with chronic obstructive pulmonary disease (COPD) provide insights for predicting, preventing, and treating exacerbations. This study aimed to analyze the impact of microbial diversity and spectrum on COPD exacerbation.

Methods

From November 1, 2018, to May 31, 2023, we prospectively enrolled patients with stable disease (SD) and exacerbation of COPD (ECOPD). Sputum samples were collected for microbiome DNA sequencing, and amplicon sequence variants were analyzed.

Results

We collected sputum samples from 38 patients: 17 samples from patients with SD and samples from patients with ECOPD at two time points—during exacerbation (AE-1: 21 samples) and again during stabilization after 2 weeks of treatment (AE-2: 17 samples). Alpha diversity indices, specifically observed feature count and Fisher’s alpha index, were significantly higher in SD (133.0 [98.0–145.0]; 17.1 [12.7–19.6]) compared to AE-1 (88.0 [72.0–125.0], p = 0.025; 10.9 [8.5–16.1], p = 0.031). The SD showed significantly higher abundances of Neisseria (linear discriminant analysis [LDA] 4.996, adj.p = 0.021), Fusobacterium (LDA 3.688, adj.p = 0.047), and Peptostreptococcus (LDA 3.379, adj.p = 0.039) at the genus level compared to AE-1. At the species level, N. perflava (LDA 5.074, adj.p = 0.010) and H. parainfluenzae (LDA 4.467, adj. p = 0.011) were more abundant in SD. Hub genera in the microbial network included Haemophilus, Granulicatella, Neisseria, Lactobacillus, and Butyrivibrio in SD and Streptococcus, Gemella, Actinomyces, Klebsiella, and Staphylococcus in AE-1.

Conclusion

COPD exacerbations are linked to changes in specific strains of normal flora. Maintaining microbial diversity and balance within the microbial network is critical for preventing and managing COPD exacerbations.
Identification of genetic associations between acute myocardial infarction and non-small cell lung cancer
Authors: Zheng Hao , Wang Jie , Zheng Yijia , Hong Xiaofan , Wang Luxi
Published: December 2024

Introduction

A growing body of evidence suggests a potential connection between myocardial infarction (MI) and lung cancer (LC). However, the underlying pathogenesis and molecular mechanisms remain unclear. This research aims to identify common genes and pathways between MI and LC through bioinformatics analysis.

Methods

Two public datasets (GSE166780 and GSE8569) were analyzed to identify differentially expressed genes (DEGs). Common DEGs were enriched using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were identified and their diagnostic performance was evaluated. Gene co-expression networks, as well as regulatory networks involving miRNA-hub genes and TF-hub genes, were also constructed. Finally, candidate drugs were predicted.

Results

Among the datasets, 34 common trend DEGs were identified. Enrichment analysis linked these DEGs to key biological processes, cellular components, and molecular functions. Eight hub genes (CEBPA, TGFBR2, EZH2, JUNB, JUN, FOS, PLAU, COL1A1) were identified, demonstrating promising diagnostic accuracy. Key transcription factors associated with these hub genes include SP1, ESR1, CREB1, ETS1, NFKB1, and RELA, while key miRNAs include hsa-mir-101-3p, hsa-mir-124-3p, hsa-mir-29c-3p, hsa-mir-93-5p, and hsa-mir-155-5p. Additionally, potential therapeutic drugs were identified, with zoledronic acid anhydrous showing potential value in reducing the co-occurrence of the two diseases.

Discussion

This study identified eight common signature genes shared between NSCLC and AMI. Validation datasets confirmed the diagnostic value of key hub genes COL1A1 and PLAU. These findings suggest that shared hub genes may serve as novel therapeutic targets for patients with both diseases. Ten candidate drugs were predicted, with zoledronic acid showing potential for targeting dual hub genes, offering a promising therapeutic approach for the comorbidity of lung cancer and myocardial infarction.
Anemia-associated smaller brain volume and sex differences: a cross-sectional study of magnetic resonance imaging in brain health checkups
Authors: Omori Naoki , Ishida Manabu , Takamura Masahiro , Abe Satoshi , Nagai Atsushi
Published: December 2024

Introduction

Anemia is a risk factor for dementia development. However, few studies have examined the relationship between brain volume and anemia. This study aimed to analyze the association between anemia and brain volume using magnetic resonance imaging data from brain health checkups.

Method

Participants underwent brain health checkups between January 2015 and March 2022. Blood samples were collected to measure hemoglobin concentrations and mean corpuscular volumes. The modified Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. Magnetic resonance images were analyzed using voxel-based Morphometry to evaluate the overall patterns of brain volume. After extracting the principal components (PCs) from PC analysis, we investigated their association with MMSE scores and anemia.

Results

This study included 1,029 participants and identified principal components, representing smaller volume in the frontal lobe (PC1), and smaller volume in the limbic system to the temporal lobe (PC2). A higher PC2 score was significantly associated with a lower MMSE score. Male participants with anemia had smaller bilateral PC1 volumes and left hippocampal volumes, and female participants with anemia had smaller bilateral PC2 volumes and hippocampus volumes.

Discussion

PC2 may represent the extent of disease affecting limbic system volume, such as Alzheimer’s disease. Our results suggest that anemia may be associated with smaller volumes in the limbic system, especially in women. Further studies are required to determine which type of anemia is more strongly correlated with smaller brain volumes.
Serum glial fibrillary acidic protein in acute stroke: feasibility to determine stroke-type, timeline and tissue-impact
Authors: Paul Julien F. , Ducroux Célina , Correia Pamela , Daigneault Audrey , Larochelle Catherine , Stapf Christian , Gioia Laura C.
Published: December 2024

Background

Interest is emerging regarding the role of blood biomarkers in acute stroke. The aim of this pilot study was to determine the feasibility of biomarker acquisition in suspected acute stroke, using modern ultrasensitive immunoassay techniques, and explore their potential usefulness for stroke diagnosis and management.

Methods

In 62 patients with suspected acute stroke, blood samples were prospectively obtained upon arrival and prior to neuroimaging. Serum levels of glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) were analyzed using a single molecule array (SIMOA®) method, according to time of symptom onset, neuroimaging, and final diagnosis.

Results

Acute ischemic stroke (AIS) was diagnosed in 35 patients, 10 with large-vessel occlusion (LVO). The remaining were diagnosed with intracerebral hemorrhage (ICH) (n = 12), transient ischemic attack (n = 4), and stroke mimics (n = 11). Median (IQR) sGFAP levels were significantly higher in ICH (2,877.8 [1,002.1–10,402.5] pg./mL) compared to others diagnoses. In AIS, GFAP levels appear to increase with longer delays since symptom onset and were higher in patients with more extensive ischemic changes on baseline CT (ASPECTS ≤7) than those without, particularly in LVO stroke. NfL values were similar across groups.

Conclusion

In acute stroke, serum GFAP levels show potential as an adjunct tool for the distinction between ICH and AIS. Specific to AIS, GFAP may also offer insight into time from onset, and extent of ischemic tissue injury on neuroimaging, particularly in LVO stroke. These preliminary findings merit further study.
Comparative efficacy and tolerability of ublituximab vs. other monoclonal antibodies in the treatment of relapsing multiple sclerosis: a systematic review and network meta-analysis of randomized trials
Authors: Moloney Eoin , Mashayekhi Atefeh , Sharma Sakshi , Kontogiannis Vasileios , Ansaripour Amir , Brownlee Wallace , Paling David , Javanbakht Mehdi
Published: December 2024

Background

Relapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).

Methods

The SLR involved a comprehensive search across various medical databases to identify relevant studies. Included studies were randomized controlled trials (RCTs) of an adult RMS population, focusing on treatment with at least one of ublituximab, alemtuzumab, natalizumab, ocrelizumab, or ofatumumab. For outcomes included in the NMA (annualized relapse rate (ARR), confirmed disability progression (CDP), and treatment discontinuation rate), rate ratios (RR) or hazard ratios (HR), along with their 95% confidence intervals (CIs), were calculated. We performed NMA using a contrast-based random-effects model within a frequentist framework for all outcomes. Ranking probabilities among comparators, and intervention rankings for the NMA, were estimated using surface under the cumulative ranking curve (SUCRA).

Results

We included 15 RCTs in the review. For the ARR outcome, there was no statistically significant difference between ublituximab and the other included mAbs [ofatumumab (RR 1.02 (95% CI 0.64–1.62)), natalizumab (RR 0.99 (0.59–1.65)), alemtuzumab (RR 0.86 (0.51–1.46)), and ocrelizumab (RR 0.75 (0.44–1.28))]. For CDP at 6 months, our results showed no statistically significant difference between ublituximab and the comparator mAbs [ofatumumab (HR 0.97 (0.49–1.92)), natalizumab (HR 1.13 (0.53–2.40)), alemtuzumab (HR 1.25 (0.56–2.81)), and ocrelizumab (HR 1.29 (0.57–2.90))]. For CDP at 3 and 6 months, there was no statistically significant difference between ublituximab and placebo. The all-cause treatment discontinuation rate analysis showed no significant difference between ublituximab and other mAbs, except for alemtuzumab.

Conclusions

Results of this SLR-informed NMA showed that there is no statistically significant difference between ublituximab and the other mAbs in terms of clinical efficacy. Additionally, the findings show that there is no statistically significant difference in discontinuation rates with the exception of the comparison with alemtuzumab, which may be attributed to its unique dosing schedule.
Development and validation of a two-dimensional pseudorandom balance perturbation test
Authors: Wagner Andrew R. , Chirumbole Sophia G. , Caccese Jaclyn B. , Chaudhari Ajit M. W. , Merfeld Daniel M.
Published: December 2024

Introduction

Pseudorandom balance perturbations use unpredictable disturbances of the support surface to quantify reactive postural control. The ability to quantify postural responses to a continuous multidirectional perturbation in two orthogonal dimensions of sway (e.g., AP and ML) has yet to be investigated.

Methods

We developed a balance perturbation paradigm that used two spectrally independent sum of sinusoids signals (SoS1, SoS2), one for each orthogonal dimension of tilt (roll and pitch), to deliver a two-dimensional (2D) balance perturbation. In a group of 10 healthy adults we measured postural sway during 2D perturbations, as well as for each of the two individual 1D perturbation components.

Results

We found that during 2D perturbations, spectral peaks in the sway response were larger at the perturbed frequencies when compared to (1) the adjacent non-perturbed frequencies and (2) the frequencies contained within the orthogonal, spectrally independent perturbation signal. We also found that for each of the two spectra (SoS1, SoS2), the magnitude and timing of the sway response relative to the platform disturbance was similar when measured during 1D and 2D conditions.

Discussion

These data support that our novel 2D SoS perturbation test was able to evoke ML and AP postural responses that were (1) specific to the roll and pitch perturbations, respectively, and (2) similar to the responses provoked by individual 1D perturbations.
Mediterranean diet and brain functional connectivity in a population without dementia
Authors: Karavasilis Efstratios , Balomenos Vasileios , Christidi Foteini , Velonakis Georgios , Angelopoulou Georgia , Yannakoulia Mary , Mamalaki Eirini , Drouka Archontoula , Brikou Dora , Tsapanou Angeliki , Gu Yian , Scarmeas Nikolaos
Published: December 2024

Introduction

Adjustable lifestyle factors, such as diet, are associated with cognitive functions, structural and functional brain measures, but the association between the functional connectivity (FC) and the Mediterranean Diet (Medicine) in population without dementia is yet to be explored.

Methods

The association between MeDi and brain FC in 105 individuals without dementia aged 63 (SD ± 8.72) years old who underwent brain MRI including resting-state (rs) functional MRI (fMRI) was examined. Dietary intake was evaluated through four 24-h recalls using the multiple-pass method and adherence to the MeDi was estimated using the MedDietScore, with higher values indicating greater adherence to MeDi. Multivariable linear regression models were used to investigate the associations between FC (both positive and negative associations) and MedDietScore.

Results

Rs-fMRI analysis revealed significant associations between FC and MedDietScore. The FC between the medial prefrontal cortex and a cluster located in left postcentral gyrus and in the left supramarginal gyrus was positively associated with MedDietScore. On the other hand, the FC between medial visual and right posterior division of both middle and superior temporal gyrus was negatively associated with MedDietScore. Of note, a temporal negative correlation was detected between above-mentioned FC networks. The FC between superior temporal gyrus and occipital regions was associated with participants' attention, executive functions, and memory scores. Furthermore, the associations for attention and executive functions were pronounced in participants with high adherence to MeDi compared to those with low adherence to MeDi.

Discussion

In conclusion, our study documented an association between higher adherence to MeDi and rs-FC in fronto-parietal and temporo-occipital regions, particularly in areas that are involved in cognitive processes altered across normal and pathological aging. From a clinical point of view, our findings support a favorable role of MeDi on FC which may have significant clinical implications in the rapidly aging population. Rs-fMRI is also proposed as a useful tool in the emerging field of nutritional neuroscience and a candidate non-invasive biomarker of brain aging.
The cerebellum is involved in implicit motor sequence learning
Authors: Firouzi Mahyar , Baetens Kris , Duta Catalina , Baeken Chris , Van Overwalle Frank , Swinnen Eva , Deroost Natacha
Published: December 2024

Background

Implicit motor sequence learning (IMSL) is a cognitive function that allows us to execute multiple movements in a specific sequential order and plays a crucial role in our daily functional activities. Although the role of the basal ganglia network in IMSL is well-established, the exact involvement of the cerebellar network is less clear.

Aim

Here, we aimed to address this issue by investigating the effects of cerebellar transcranial direct-current stimulation (tDCS) on IMSL.

Methods

In this sham-controlled, crossover study in 45 healthy young adults, we used mixed-effects models to analyze sequence-specific (primary outcome) and general learning effects (secondary outcome) in the acquisition (during tDCS), short- (five minutes post-tDCS) and long-term consolidation (one week post-tDCS) phases of IMSL, as measured by the serial reaction time (SRT) task.

Results

Analyses based on response times (RTs) revealed that anodal tDCS over the cerebellum significantly increased sequence-specific learning during acquisition, compared to sham (anodal: M = 38.24 ms, sham: M = 26.78 ms, p = 0.032); did not affect general learning; and significantly slowed overall RTs (anodal: M = 362.03 ms, sham: M = 356.37 ms, p = 0.049). Accuracy-based analyses revealed that anodal tDCS reduced the probability of correct responses occurring in random trials versus sequential trials by 1.17%, p = 0.009, whereas sham tDCS had no effect, p = 0.999.

Conclusion

Our finding of enhanced sequence-specific learning, but not general learning, suggests that the cerebellar network not only plays a role in error correction processes, but also serves a sequence-specific function within the integrated motor learning network that connects the basal ganglia and cerebellum.
Determination of weight loss methods and effects among wrestlers before an official championship
Authors: Seker Ramazan , Isik Ozkan , Durukan Erdil , Eraslan Meric , Talaghir Laurentiu-Gabriel , Dorgan Viorel
Published: December 2024

Introduction

It is known that combat athletes frequently lose weight before a competition. This study aimed to determine the weight loss methods before an official championship and the effects of these weight loss methods on the performance of wrestlers.

Method

The sample of the study consisted of 350 competitive wrestlers. The “Athlete Weight Loss Methodology and Effects Scale” and personal information form were used as data collection tools in the study. In the data analysis, independent samples T-test, One-way ANOVA, and Pearson correlation analysis were used in addition to descriptive statistics.

Results

Wrestlers generally reported dieting by restricting fatty (89.1%) and carbohydrate (83.4%) foods. It was observed that they preferred jogging with a raincoat (89.1%) and/or using the sauna (79.7%) as a weight loss method. Wrestlers also reported that they performed weight loss, although at a low level, by using ergogenic aids such as laxatives (31.7%) and/or diuretic pills (28.0%). They were observed to experience physiological effects such as muscle cramps (72.9%), injury (71.1%), and/or difficulty breathing (60.9%), as well as psychological effects such as feeling extremely tired (81.7%), stress (79.7%), decreased performance (78.6%) and/or extremely irritability (71.4%). It was determined that there was no difference between the weight loss methods and effects of the wrestlers according to their gender and wrestling style (p > 0.05). On the other hand, it was determined that the diet level of U20 wrestlers was higher than U17 (p < 0.05) and Senior wrestlers and that U17 and U20 wrestlers were exposed to higher levels of physiological and psychological effects than Senior wrestlers (p < 0.05).

Conclusion

It was determined that wrestlers preferred methods such as restricting food and fluids, using a sauna, and jogging with a raincoat to lose weight. It is necessary to prevent young wrestlers from losing weight before the competition. Thus, it is possible to prevent wrestlers in their development period (U17 and U20) from being exposed to physiological and psychological effects caused by losing weight.
Direct comparison of an ultrasensitive real-time PCR assay with droplet digital PCR for the detection of PIK3CA hotspot mutations in primary tumors, plasma cell-free DNA and paired CTC-derived gDNAs
Authors: Smilkou Stavroula , Kaklamanis Loukas , Balgouranidou Ioanna , Linardou Helena , Papatheodoridi Alkistis Maria , Zagouri Flora , Razis Evangelia , Kakolyris Stylianos , Psyrri Amanda , Papadimitriou Christos , Markou Athina , Lianidou Evi
Published: December 2024

Introduction

Detection of PIK3CA mutations in primary tumors and liquid biopsy samples is of increasing importance for treatment decisions and therapy resistance in many types of cancer. The aim of the present study was to directly compare the efficacy of a relatively inexpensive ultrasensitive real-time PCR with the well-established and highly sensitive technology of ddPCR for the detection of the three most common hotspot mutations of PIK3CA, in exons 9 and 20, that are all of clinical importance in various types of cancer.

Patients and methods

We analyzed 42 gDNAs from primary tumors (FFPEs), 29 plasma-cfDNA samples, and 29 paired CTC-derived gDNAs, all from patients with ER+ metastatic breast cancer, and plasma from 10 healthy donors. The same blood draws were used for CTC isolation using EpCAM beads for positive immunomagnetic enrichment. All FFPEs and plasma-cfDNA samples were analyzed in parallel for PIK3CA mutations by ultrasensitive real-time PCR assay and droplet digital PCR.

Results

In gDNAs from FFPEs, using ultrasensitive real-time PCR, the p.E545K mutation was detected in 22/42(52.4%), and the p.E542K and p.H1047R mutations were detected in 14/42(33.3%) and 16/42(38.1%), respectively. Using ddPCR, the p.E545K mutation was detected in 22/42(52.4%), p.E542K in 17/42(40.5%), and p.H1047R in 19/42(45.2%) samples, revealing a concordance between the two methodologies of 81%, 78.6% and 78.6% for each mutation respectively. In plasma-cfDNA, using ultrasensitive real-time PCR, the p.E545K mutation was detected in 11/29(38%) and both p.E542K and p.H1047R mutations in 2/29(6.9%).In the same plasma-cfDNA samples using ddPCR, p.E545K was detected in 1/29(3.5%), p.E542K in 2/29(6.9%), and p.H1047R in 3/29(10.5%) samples, revealing a concordance of 65.5%,100% and 93.1% for each mutation respectively. In paired CTC-derived gDNAs p.E545K was detected in 11/29(38%), p.E542K in 3/29(10.3%), and p.H1047R in 7/29(24.1%) samples.

Conclusions

This low-cost, high-throughput and ultrasensitive real-time PCR assay provides accurate and specific detection of PIK3CA hotspot mutations in liquid biopsy samples and gives similar results to ddPCR. This assay can be performed in labs where digital PCR instrumentation is not available. In CTC-derived gDNA and paired plasma-cfDNA, PIK3CA mutations detected were not identical, revealing that CTC and plasma-cfDNA give complementary information.
Cost-effectiveness of camrelizumab plus rivoceranib for advanced hepatocellular carcinoma in the context of regional disparities in China
Authors: Zhao Zhonghua , Jiang Xiongying , Wen Shiping , Hao Yanzhang
Published: December 2024

Objective

To assess the cost-effectiveness of combining camrelizumab with rivoceranib versus sorafenib as initial treatment options for advanced hepatocellular carcinoma (HCC) across different developmental regions in China.

Methods

Utilizing TreeAge Pro and data from the phase III randomized CARES-310 clinical trial, a model based on Markov state transitions was developed. Health state utility values were derived from the CARES-310 trial, and direct medical costs were obtained from relevant literature and local pricing data. The primary outcome measured was the incremental cost-effectiveness ratio (ICER), defined as the cost per additional quality-adjusted life year (QALY) gained per person. The ICERs were compared against the willingness-to-pay (WTP) thresholds of different regions in China, including low-income ($16,426.80), medium-income ($34,319.01), and high-income regions ($81,036.63). Sensitivity analyses were also conducted to assess the robustness and reliability of the model under various assumptions. A tornado diagram was used to illustrate the impact of parameter variations on the model’s cost-effectiveness.

Results

For base case analysis, QALYs per person for the cohort receiving sorafenib were 0.91, with a corresponding cost of $8,860.97. For the cohort receiving camrelizumab plus rivoceranib, the QALYs per person were 1.71, with a corresponding cost of $16,190.72. The camrelizumab plus rivoceranib treatment group exhibited an increase of 0.80 QALYs and an additional expenditure of $7,329.75. The calculated ICER was $9,150.75 per QALY, which is below the WTP thresholds for all regions in China. The camrelizumab plus rivoceranib regimen is regarded as highly cost-effective in medium-income areas of China, with a probability of 99.9%. In high-income regions, the probability reaches 100.0%. Even in low-income regions, this regimen is considered 95.6% cost-effective. Sensitivity analysis further verified that these findings were robust across various assumptions.

Conclusion

The combination of camrelizumab and rivoceranib as a treatment strategy not only improves health outcomes but also represents a cost-effective option across different developmental regions in China.
Conversion surgery for stage IV gastric cancer after third-line immunotherapy: a case report
Authors: Evdokimova Sevindzh F. , Kornietskaya Anna L. , Bolotina Larisa V. , Kolobayev Iliya V. , Fedenko Alexander A. , Kaprin Andrey D.
Published: December 2024

The 5-year overall survival rate for stage IV gastric cancer is lower than 10%, despite the development of systemic therapy. Conversion surgery has shown to improve survival outcomes in patients with durable clinical response on chemotherapy. We report a clinical case of a patient, who underwent conversion surgery after pembrolizumab in the third-line setting for stage IV gastric cancer. The patient did not have recurrence for 22 months after conversion surgery.
Case report: Giant meningioma of the left hemisphere
Authors: Cui Junxiang , Sun Hu , Sun Shuo , Zhao Hao , Gu Yinghao
Published: December 2024

Meningiomas are some of the most prevalent primary brain tumors in adults, and are typically non-neuroglial in nature. A variety of symptoms may be observed, including headaches, fluctuations in mental status, ataxia, muscle weakness, nausea and vomiting, seizures, visual changes, speech disorders, and sensory abnormalities. The World Health Organization (WHO) has a grading system for meningiomas based on histological criteria, which is as follows: Grade 1 meningiomas are considered benign; Grade 2 meningiomas have a moderately aggressive nature and usually present with histological atypia; and Grade 3 meningiomas exhibit aggressive malignant behavior. Grade 3 meningiomas are distinguished by aberrant and accelerated cellular proliferation, which increases the probability of invasion and recurrence within the central nervous system relative to the other grades. Malignant meningiomas are further classified by tumor size. For example, WHO grade 3 meningiomas with diameter >5 cm are designated giant meningiomas. Giant meningiomas are complicated by their potential for compression of the brain tissue, which can lead to increased intracranial pressure and hemodynamic changes. In many cases, these changes induce vasogenic edema in the adjacent brain tissue. This article details a rare case of rapidly growing atypical giant meningioma that progressed to an anterior-posterior diameter of 13 cm within 3 years, occupying the majority of the left hemisphere of the brain and encroaching upon the right intracranial structures. Through recent advances in medical diagnostics and heightened public awareness of health issues, cases with such large meningiomas have become exceedingly rare. Fortunately, the tumor in the present case was successfully resected using advanced surgical techniques that employed microscopy in conjunction with sodium fluorescein, resulting in complete removal of the tumor and restoration of the patient’s muscle strength postoperatively. The value of fluorescence-guided surgery in this type of procedure is support in the present case report.
Pharmacological inhibition of receptor protein tyrosine phosphatase β/ζ decreases Aβ plaques and neuroinflammation in the hippocampus of APP/PS1 mice
Authors: Fontán-Baselga Teresa , Cañeque-Rufo Héctor , Rivera-Illades Elisa , Gramage Esther , Zapico José María , de Pascual-Teresa Beatriz , Ramos-Álvarez María Del Pilar , Herradón Gonzalo , Vicente-Rodríguez Marta
Published: December 2024

Alzheimer’s disease (AD) is a major neurodegenerative disorder that courses with chronic neuroinflammation. Pleiotrophin (PTN) is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ which is upregulated in different neuroinflammatory disorders of diverse origin, including AD. To investigate the role of RPTPβ/ζ in neuroinflammation and neurodegeneration, we used eight-to ten-month-old APP/PS1 AD mouse model. They were administered intragastrically with MY10, an inhibitor of RPTPβ/ζ, at different doses (60 and 90 mg/kg) every day for 14 days. Treatment with 90 mg/kg MY10 significantly reduced the number and size of amyloid beta (Aβ) plaques in the dorsal subiculum of the hippocampus of APP/PS1 mice. In addition, we observed a significant decrease in the number and size of astrocytes in both sexes and in the number of microglial cells in a sex-dependent manner. This suggests that RPTPβ/ζ plays an important role in modulating Aβ plaque formation and influences glial responses, which may contribute to improved Aβ clearance. In addition, MY10 treatment decreased the interaction of glial cells with Aβ plaques in the hippocampus of APP/PS1 mice. Furthermore, the analysis of proinflammatory markers in the hippocampus revealed that MY10 treatment decreased the mRNA levels of Tnfa and Hmgb1. Notably, treatment with MY10 increased Bace1 mRNA expression, which could be involved in enhancing Aβ degradation, and it decreased Mmp9 levels, which might reflect changes in the neuroinflammatory environment and impact Aβ plaque dynamics. These results support the therapeutic potential of inhibition of RPTPβ/ζ in modulating Aβ pathology and neuroinflammation in AD.
Mixing of isoscalar and isovector characteristics in the low-energy dipole mode
Authors: Inakura Tsunenori , Ebata Shuichiro
Published: December 2024

We investigated isospin splitting in low-energy dipole (LED) states of spherical nuclei such as 40Ca, 90Zr, 132Sn, 208Pb, and several N=50 isotones using self-consistent Hartree–Fock plus random phase approximation calculations. Our analysis of isovector dipole (IVD) and isoscalar dipole (ISD) strengths, along with transition densities, reveals a clear energy-dependent relationship between IS and IV modes in 40Ca and 90Zr. For 208Pb and 132Sn, LED states show mixed IS + IV characteristics due to different neutron and proton shell structures. In N=50 isotones, E1 modes exhibit varying IS and IV properties with smooth transitions as neutron excess increases. Our results suggest that compressional ISD strengths could provide valuable insights into the slope parameter of the nuclear equation of state. The observed dependence on nuclear shell structures and neutron–proton correlations highlights the need for precise measurements and further research in nuclear physics.
Two detoxification enzyme genes, CYP6DA2 and CarFE4, mediate the susceptibility to afidopyropen in Semiaphis heraclei
Authors: Fu Xiaochen , Xue Chao , Wang Xin , Wang Aiyu , Zhu Yanwei , Yang Yuanxue , Zhang Yun , Zhou Yun , Zhao Ming , Shan Chenggang , Zhang Jianhua
Published: December 2024

Introduction

Semiaphis heraclei is an important economic pest affecting Caprifoliaceae and Apiaceae plants, and chemical control is still the main effective control method in the field. Afidopyropen is a new type of pyridine cyclopropyl insecticide, which can effectively control piercing-sucking mouthparts pests and is suitable for pest resistance management. However, the detoxification mechanism of S. heraclei to afidopyropen is still poorly cleared.

Methods

The insecticidal activity of afidopyropen against S. heraclei and the enzyme activity assay and synergism bioassay were evaluated. The detoxification enzyme genes were obtained by transcriptome and validated by quantitative real-time PCR (RT-qPCR). Furthermore, RNA interference was used to study the functions of detoxification enzyme genes.

Results

The activities of cytochrome P450 monooxygenases (P450s) and carboxylesterases (CarEs) were significantly increased under afidopyropen treatment. The toxicity of afidopyropen against S. heraclei was significantly increased after application the inhibitors of piperonyl butoxide and triphenyl phosphate. Sixteen P450 genes and three CarE genes were identified in the transcriptome of S. heraclei. The RT-qPCR results showed that eleven P450 genes and two CarE genes were significantly upregulated under afidopyropen treatment, and the expression of CYP6DA2 and CarFE4 was upregulated by more than 2.5 times. The expression pattern of CYP6DA2 and CarFE4 was further analyzed in different developmental stages of S. heraclei and knockdown of CYP6DA2 and CarFE4 significantly increased the susceptibility of S. heraclei to afidopyropen.

Conclusion

The results of this study uncover the key functions of CYP6DA2 and CarFE4 in the detoxification mechanism of S. heraclei to afidopyropen, and provide a theoretical basis for the scientific use of afidopyropen in the field.
Predicting the potential distribution of Astragali Radix in China under climate change adopting the MaxEnt model
Authors: Wen Zixuan , Yan Ke , Zhang Man , Ma Ruiqing , Zhu Xiaoyan , Duan Qing , Jiang Xiaolin
Published: December 2024

Introduction

Astragali Radix is the dried root of Astragalus mongoliae or Astragalus membranaceus, a leguminous plant. Since ancient times, Astragali Radix has been widely used in Chinese traditional Chinese medicine. As people become more health-conscious, the market demand for Astragali Radix grows and its popularity is increasing in the international market. As an important medicinal plant, the growth of Astragali Radix is strongly influenced by environmental conditions. In order to meet the market demand for high quality Astragali Radix herbs, it is necessary to search and find areas suitable for the growth of Astragali Radix.

Methods

In this study, we assessed the potential impacts of climate change on the distribution of the Chinese medicinal plant Astragali Radix using the maximum entropy (MaxEnt) model in combination with a geographic information system(GIS). Distribution data and environmental variables were analyzed to predict suitable areas for Astragali Radix under the SSP126, SSP245 and SSP585 scenario for current and future (2041-2060, 2061-2080, 2081-2100). Jackknife is used to assess the importance of environmental variables, and environmental variables with a model contribution greater than 5% were considered to be the main drivers.

Results

The results showed that the current area of suitable area for Astragali Radix is 188.41 km2, and the three climate scenarios show an increasing trend in the future, with a maximum of 212.70 km2. North China has always been the main suitable area, while the area of suitable area in Southwest China is decreasing, and Xinjiang will be developed as a new suitable area in the future. Annual precipitation (41.6%), elevation (15.9%), topsoil calcium carbonate (14.8%), annual mean temperature (8.3%), precipitation seasonality (8%) and topsoil pH (6%) contributed more to the model and were the main environmental influences on the distribution of Astragali Radix. In addition, the centroids of the suitable areas shifted northward under all three climate scenarios, indicating a migratory response to global warming.

Discussion

Our study found that suitable area of Astragali Radix has been expanding for most of the time in each period of the three climate scenarios compared with the current situation. In the future, humans can focus on enhancing the cultivation techniques of Astragali Radix in these suitable areas. This study provide a scientific basis for the development of planting strategies and spatial distribution management of Astragali Radix. It helps to optimize the selection of planting areas and resource conservation of Chinese herbs.
How watching sports events empowers people’s sense of wellbeing? The role of chain mediation in social interaction and emotional experience
Authors: Guo Jiru , Yang Hong , Zhang Xiaoli
Published: December 2024

Background

While engaging in sports is widely recognized for enhancing wellbeing, limited research has examined the effects of watching sports events on individuals’ subjective wellbeing. The mechanisms and pathways underlying this relationship remain unclear.

Objectives

This study explores the correlation between watching sports events and the wellbeing of Chinese individuals, based on the theoretical framework of “spectator behavior → social interaction → emotional experience → happiness.” The aim is to investigate the mediating effects of social interaction and emotional experience, providing insights for promoting greater participation in sports events and supporting the healthy development of the sports industry.

Methods

The study involved 885 participants from five representative provinces and cities in China. Assessment tools included the Physical Activity Rating Scale, Social Interaction Questionnaire, Emotional Experience Questionnaire, and Subjective Wellbeing Scale. Data were analyzed using Stata and the PROCESS plug-in of SPSS for comprehensive multivariate statistical analysis.

Results

Watching sports events significantly and positively affects subjective wellbeing, social interaction, and emotional experience (p < 0.001). Three mediating pathways were identified: (1) watching sports events → social interaction → subjective wellbeing (effect size: 0.024), (2) watching sports events → emotional experience → subjective wellbeing (effect size: 0.011), and (3) watching sports events → social interaction → emotional experience → subjective wellbeing (effect size: 0.003).

Conclusion

The direct impact of watching sports events on subjective wellbeing was positive. Indirect effects were facilitated by the mediating roles of social interaction and emotional experience, with the effect of social interaction being more substantial than that of emotional experience.

Implications

These findings suggest that watching sports events can serve as a catalyst for enhancing wellbeing, primarily through fostering social connections and enriching emotional experiences. Practically, this indicates the potential value of encouraging viewership of sports events as a means of promoting community engagement and mental health, thus contributing to the holistic growth of the sports sector and public health initiatives.
Psilocybin-assisted psychotherapy for methamphetamine dependence: a case report involving daily methamphetamine use
Authors: Brett Jonathan , Knock Elizabeth , Watson Kathy , Albert Steven , Siefried Krista J. , Guss Jeffrey
Published: December 2024

Methamphetamine (MA) dependence leads to severe physical and psychological issues. Current treatments, including psychosocial therapies and residential rehabilitation, face limitations such as high relapse rates, cost, and accessibility issues. As a result, there is an urgent need for novel approaches to treat MA dependence that are effective, affordable, and accessible to patients. Psilocybin, the active component in numerous mushrooms of the Psilocybe genus, has shown potential for enhancing psychotherapy for various addiction and mental health issues due to its effects on perception, cognition, and affect. Psilocybin-assisted psychotherapy (PAT) has demonstrated initial safety and efficacy in treating alcohol, cocaine, and nicotine dependence. The case presented here describes a 36-year-old transwoman and daily MA user, who participated in a single-arm open-label clinical trial assessing feasibility and safety of PAT for MA dependence at St. Vincent’s Hospital, Sydney. Following inpatient withdrawal management and one session of psilocybin-assisted therapy, she experienced significant cognitive and emotional shifts and sustained MA abstinence. She reported improved mental health over 3 months following treatment completion. She also noted increased self-esteem, mindfulness, and distress tolerance. This study suggests that PAT (following inpatient MA withdrawal management) may offer a scalable, safe, and effective approach for treating MA dependence. However, further research is required to confirm the generalisability and efficacy of PAT for broader populations of people using MA. It is encouraging that this participant, a daily MA user, showed improvements in mood and cognition, in addition to abstinence from MA.