bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing spatial navigation skills in mild cognitive impairment patients: a usability study of a new version of ANTaging software
Authors: Stramba-Badiale Chiara , Tuena Cosimo , Goulene Karine Marie , Cipresso Pietro , Morelli Sandra , Rossi Mirko , D’Avenio Giuseppe , Stramba-Badiale Marco , Riva Giuseppe
Published: January 2024

Introduction

Mild Cognitive Impairment (MCI) often presents challenges related to spatial navigation and retention of spatial information. Navigating space involves intricate integration of bodily and environmental cues. Spatial memory is dependent on two distinct frame of reference systems for organizing this information: egocentric and allocentric frames of reference. Virtual Reality (VR) has emerged as a promising technology for enhancing spatial navigation skills and spatial memory by facilitating the manipulation of bodily, environmental, and cognitive cues.

Methods

This usability study was based on a fully within-subjects design in which seven MCI patients underwent two kinds of VR conditions: participants were required to complete the ANTaging demo both in Oculus Rift S (immersive condition) and in Samsung UHD 4K monitor (semi-immersive condition). Participants were seated and they had to use a foot-motion pad to navigate and explore the environment to collect and relocate some objects in the virtual environment. Post-interaction, users provided feedback on their experiences. Additionally, usability, potential side effects, data analysis feasibility, and user preferences with immersive and semi-immersive technologies were assessed through questionnaires.

Results

Results indicated higher usability ratings for the semi-immersive setup, with fewer negative effects reported compared to the immersive counterpart. According to qualitative analyses of the interviews, patients do seem to like both VR apparatuses even though the semi-immersive condition was perceived as the most suitable choice because of the size of the screen. Patients generally found it difficult to remember object locations. Participants expressed the need for more practice with the foot-motion pad, despite an overall positive experience. They generally would like to use this system to improve their memory.

Discussion

Identifying these key aspects was crucial for refining the system before the upcoming clinical trial. This study sheds light on the potential of semi-immersive VR in aiding individuals with MCI, paving the way for enhanced spatial navigation interventions.
Insights into early pathogenesis of sporadic Alzheimer’s disease: role of oxidative stress and loss of synaptic proteins
Authors: Ansari Mubeen A. , Rao Muddanna Sakkattu , Al-Jarallah Aishah
Published: January 2024

Oxidative stress, induced by impaired insulin signaling in the brain contributes to cognitive loss in sporadic Alzheimer’s disease (sAD). This study evaluated early hippocampal oxidative stress, pre- and post-synaptic proteins in intraperitoneal (IP) and intracerebroventricular (ICV) streptozotocin (STZ) models of impaired insulin signaling. Adult male Wistar rats were injected with STZ, IP, or ICV, and sacrificed 1-, 3-, or 6-weeks post injection. Rat’s cognitive behavior was assessed using Morris water maze (MWM) tests at weeks 3 and 6. Hippocampal synaptosomal fractions were examined for oxidative stress markers and presynaptic [synapsin I, synaptophysin, growth-associated protein-43 (GAP-43), synaptosomal-associated protein-25 (SNAP-25)] and postsynaptic [drebrin, synapse-associated protein-97 (SAP-97), postsynaptic density protein-95 (PSD-95)] proteins. IP-STZ and ICV-STZ treatment impaired rat’s cognition, decreased the levels of reduced glutathione (GSH) and increased the levels of thiobarbituric acid reactive species (TBARS) in a time dependent manner. In addition, it reduced the expression of pre- and post-synaptic proteins in the hippocampus. The decline in cognition is significantly correlated with the reduction in synaptic proteins in the hippocampus. In conclusion, impaired insulin signaling in the brain is deleterious in causing early synaptosomal oxidative damage and synaptic loss that exacerbates with time and correlates with cognitive impairments. Our data implicates oxidative stress and synaptic protein loss as an early feature of sAD and provides insights into early biochemical and behavioral changes during disease progression.
Multi-label classification of retinal disease via a novel vision transformer model
Authors: Wang Dong , Lian Jian , Jiao Wanzhen
Published: January 2024

Introduction

The precise identification of retinal disorders is of utmost importance in the prevention of both temporary and permanent visual impairment. Prior research has yielded encouraging results in the classification of retinal images pertaining to a specific retinal condition. In clinical practice, it is not uncommon for a single patient to present with multiple retinal disorders concurrently. Hence, the task of classifying retinal images into multiple labels remains a significant obstacle for existing methodologies, but its successful accomplishment would yield valuable insights into a diverse array of situations simultaneously.

Methods

This study presents a novel vision transformer architecture called retinal ViT, which incorporates the self-attention mechanism into the field of medical image analysis. To note that this study supposed to prove that the transformer-based models can achieve competitive performance comparing with the CNN-based models, hence the convolutional modules have been eliminated from the proposed model. The suggested model concludes with a multi-label classifier that utilizes a feed-forward network architecture. This classifier consists of two layers and employs a sigmoid activation function.

Results and discussion

The experimental findings provide evidence of the improved performance exhibited by the suggested model when compared to state-of-the-art approaches such as ResNet, VGG, DenseNet, and MobileNet, on the publicly available dataset ODIR-2019, and the proposed approach has outperformed the state-of-the-art algorithms in terms of Kappa, F1 score, AUC, and AVG.
PARALLELPROJ—an open-source framework for fast calculation of projections in tomography
Authors: Schramm Georg , Thielemans Kris
Published: January 2024

In this article, we introduce parallelproj, a novel open-source framework designed for efficient parallel computation of projections in tomography leveraging either multiple CPU cores or GPUs. This framework efficiently implements forward and back projection functions for both sinogram and listmode data, utilizing Joseph’s method, which is further extended to encompass time-of-flight (TOF) PET projections. Our evaluation involves a series of tests focusing on PET image reconstruction using data sourced from a state-of-the-art clinical PET/CT system. We thoroughly benchmark the performance of the projectors in non-TOF and TOF, sinogram, and listmode employing multi CPU-cores, hybrid CPU/GPU, and exclusive GPU mode. Moreover, we also investigate the timing of non-TOF sinogram projections calculated in STIR (Software for Tomographic Image Reconstruction) which recently integrated parallelproj as one of its projection backends. Our results indicate that the exclusive GPU mode provides acceleration factors between 25 and 68 relative to the multi-CPU-core mode. Furthermore, we demonstrate that OSEM listmode reconstruction of state-of-the-art real-world PET data sets is achievable within a few seconds using a single consumer GPU.
Shedding light on the next pandemic path, from outpatient to ICU, the effect of vitamin D deficiency in the SARS-CoV-2 pandemic
Authors: Celikmen F. , Tunaligil V. , Keles E. C. , Celikmen D. S. M. , Sarikaya S.
Published: January 2024

Background

Vitamin D insufficiency is named “the pandemic of our era” by some experts. World Health Organization warns against a “deadlier outbreak” than the COVID-19 pandemic. Critical evidence is hereby for future pandemic prevention, with special emphasis on Vitamin D.

Methods

A cross-sectional study was conducted with 172 unvaccinated adult participants, who presented to the emergency department. Blood measurements, radiological findings, and demographic features were evaluated in the four categories of “healthy adults, COVID-19 outpatients, hospitalized inpatients on the wards, and in the ICU.”

Results

Results were statistically significant in association with age, gender, weight, Vitamin D, glucose, urea, creatinine, leucocyte, aspartate transaminase, hemoglobin, C-reactive protein, troponin, platelet/thrombocyte, ferritin, D-dimer, triglycerate, glycated haemoglobin, lactate dehydrogenase measurements, and chest computed tomography features (each p < 0.050).

Conclusion

This article presents evidence to support the importance of Vitamin D for global public health. Patients with adequate levels of Vitamin D, glucose, urea, creatinine, leucocyte, aspartate transaminase, hemoglobin, C-reactive protein, troponin, platelet/thrombocyte, ferritin, D-dimer, triglycerate, glycated haemoglobin, lactate dehydrogenase are less likely to be admitted to ICU versus being outpatients. Factors include gender, age, weight, comorbidities, and computed tomography findings. The ultimate goal is to globally minimize preventable burdens of disease and death.
Ready-to-eat cereal consumption is associated with improved nutrient intakes and diet quality in Canadian adults and children across income levels
Authors: Sanders Lisa M. , Zhu Yong , Jain Neha , Normington James , Holschuh Norton , Nechanicky Megan , Tucker Michelle , Garcia-Bailo Bibiana
Published: January 2024

Background

Results from observational studies suggest ready-to-eat cereal (RTEC) consumption is associated with higher diet quality. In the United States, studies have shown that RTEC is an important contributor to nutrient intakes across income levels. However, it is unknown if this association varies by income level in the Canadian population. Given its affordability, RTEC may represent an important source of nutrients for lower-income individuals.

Objective

This study evaluated the association of RTEC consumption with nutrient intakes and diet quality across household income levels in Canadian adults and children.

Methods

Income and dietary data from 24 h dietary recalls were obtained from the 2015 Canadian Community Health Survey (CCHS)—Nutrition in 6,181 children (2–18 years) and 13,908 adults (19+ years). Diet quality was assessed with a modified Nutrient Rich Food Index (NRF) 9.3. Income levels were stratified into low, middle, and high based on family size, and data were analyzed by RTEC consumption and income level using multivariate linear regression adjusted for energy, age, and sex.

Results

Diet quality was greater in adult and child RTEC consumers across all household income levels. Children and adults consuming RTEC also had higher nutrient intakes, including shortfall nutrients such as calcium, dietary fiber, iron, magnesium, and vitamin D. RTEC provided <10% of energy intake, <4% of saturated fat intake, and <9% of total sugar intake across all ages and income levels, while also providing one-third of daily iron intake and at least 10% of daily intake of dietary fiber, thiamin, folate, and vitamin B6.

Conclusion

RTEC consumption was associated with improved nutrient intakes and diet quality in adults and children across household income levels. Nutrient dense and affordable food choices, such as RTEC, may be a helpful strategy to improve the diet quality of Canadians, particularly those with a lower household income.
Isolated but not combined ergogenic effects of caffeine and L-arginine during an isokinetic knee extension
Authors: Zart Sebastian , Brachtendorf Maximilian , Becker Stephan , Fröhlich Michael
Published: January 2024

Introduction

The use of single supplements as ergogenic aids to enhance performance in strength-oriented sports is widespread among athletes (74%). The aim of this study was to increase knowledge about the combined effects of caffeine and L-arginine dietary supplements on performance.

Methods

In this double-blind, randomized and counterbalanced crossover study, 29 participants (age: 23.2 ± 3.6 yr.; height: 181.0 ± 7.6 cm; weight: 77.0 ± 8.8 kg) each underwent six trials. In each trial performance tests were conducted to examine the effects of the supplement combinations on maximum (NmMax) and averaged torque (NmM), maximum (JMax) and averaged work (JM), the blockwise mean values of torque and work, and rate of perceived exertion (RPE) during an isokinetic leg extension task (90°·s−1) with the right leg for two sets of 40 repetitions and a set rest of 3 min on a dynamometer. The first and second trials were used to familiarize the participants with the movements in the dynamometer and no supplements were taken. After this 2-week pre-test trial, the supplement combinations of placebo/placebo, caffeine/placebo (5 mg·kg−1), L-arginine/placebo (0.15 g·kg−1), and caffeine/L-arginine (5 mg·kg−1 + 0.15 g·kg−1) were ingested.

Results

The main finding of this study is the absence of an ergogenic effect of the combined supplements caffeine and L-arginine during voluntary maximal isokinetic leg extensions, although an increase of 3.5% was noted for Nmmax compared to the placebo trial. However, the administration of caffeine was able to increase the NmMax of the quadriceps femoris muscle about 5.1% (p = 0.043). In addition, caffeine (4.2%, p = 0.026) and also L-arginine (4.2%, p = 0.040) significantly increased NmM over a complete set. No single or combined supplement had an effect on muscle fatigue looking at the blockwise mean values of torque and work or RPE (all p > 0.05).

Conclusion

The combination of caffeine and L-arginine was not superior to the isolated intake of both supplements in a strength-based exercise and a synergistic effect was absent.
Integrated 16s RNA sequencing and network pharmacology to explore the effects of polyphenol-rich raspberry leaf extract on weight control
Authors: Wang Tao , Yang Jing , Huang Ziang , Wang Fei , Liu Ruzi , Liu Yongping , Li Xiaojun
Published: January 2024

Introduction

Obesity is recognized as a chronic low-grade inflammation associated with intestinal flora imbalance, leading to dyslipidemia and inflammation. Modern research has found that polyphenols have anti-obesity effects. However, the mechanism of action of raspberry leaf extract (RLE) with high polyphenols in regulating obesity is still unknown. This study investigated the improvement effect of supplementing RLE on high-fat diet (HFD) induced obesity in mice.

Methods

RLE was used to intervene in HFD induced C57BL/6J male mice during prevention stage (1-16 weeks) and treatment stage (17-20 weeks). Their weight changes and obesity-related biochemical indicators were measured. The changes in intestinal flora were analyzed using 16S rRNA sequencing, and finally the targets and pathways of the 7 typical polyphenols (quercetin-3-O-glucuronide, ellagic acid, kaempferol-3-O-rutinoside, chlorogenic acid, brevifolin carboxylic acid, quercetin-3-O-rutinoside, and quercetin) of RLE in the regulation of obesity were predicted by network pharmacology approach.

Results and discussion

The results showed that RLE effectively prevented and treated weight gain in obese mice induced by HFD, alleviated adipocyte hypertrophy, reduced Interleukin-6 and Tumor Necrosis Factor Alpha levels, and improved intestinal flora, especially Muriaculaceae, Alistipes and Alloprevotella, and decreased the Firmicutes/Bacteroidota ratio. Network pharmacology analysis selected 60 common targets for 7 RLE polyphenols and obesity. Combined with protein-protein interaction network, enrichment analysis and experimental results, TNF, IL-6, AKT1, and PPAR were predicted as potential key targets for RLE polyphenols.

Conclusion

The potential mechanism by which polyphenol-rich RLE regulates obesity may be attributed to the specific polyphenols of RLE and their synergistic effects, therefore RLE has a great anti-obesity potential and may be used as a means to alleviate obesity and related diseases.
Comparison of reduced field-of-view DWI and conventional DWI techniques for the assessment of lumbar bone marrow infiltration in patients with acute leukemia
Authors: Bian Wenjin , Wang Luyao , Li Jianting , Cui Sha , Wu Wenqi , Fan Rong , Niu Jinliang
Published: January 2024

Objectives

To compare the imaging quality, apparent diffusion coefficient (ADC), and the value of assessing bone marrow infiltration between reduced field-of-view diffusion-weighted imaging (r-FOV DWI) and conventional DWI in the lumbar spine of acute leukemia (AL).

Methods

Patients with newly diagnosed AL were recruited and underwent both r-FOV DWI and conventional DWI in the lumbar spine. Two radiologists evaluated image quality scores using 5-Likert-type scales qualitatively and measured signal-to-noise ratio (SNR), contrast-to-noise (CNR), signal intensity ratio (SIR), and ADC quantitatively. Patients were divided into hypo- and normocellular group, moderately hypercellular group, and severely hypercellular group according to bone marrow cellularity (BMC) obtained from bone marrow biopsies. The image quality parameters and ADC value between the two sequences were compared. One-way analysis of variance followed by LSD post hoc test was used for the comparisons of the ADC values among the three groups. The performance of ADC obtained with r-FOV DWI (ADCr) and conventional DWI(ADCc) in evaluating BMC and their correlations with BMC and white blood cells (WBC) were analyzed and compared.

Results

71 AL patients (hypo- and normocellular: n=20; moderately hypercellular: n=19; severely hypercellular: n=32) were evaluated. The image quality scores, CNR, SIR, and ADC value of r-FOV DWI were significantly higher than those of conventional DWI (all p<0.05), and the SNR of r-FOV DWI was significantly lower (p<0.001). ADCr showed statistical differences in all pairwise comparisons among the three groups (all p<0.05), while ADCc showed significant difference only between hypo- and normocellular group and severely hypercellular group (p=0.014). The performance of ADCr in evaluating BMC (Z=2.380, p=0.017) and its correlations with BMC (Z=-2.008, p = 0.045) and WBC (Z=-2.022, p = 0.043) were significantly higher than those of ADCc.

Conclusion

Compared with conventional DWI, r-FOV DWI provides superior image quality of the lumbar spine in AL patients, thus yielding better performance in assessing bone marrow infiltration.
Case Report: An extremely rare penile shrapnel injury
Authors: Pan Renbing , Liu Jingwen , Wan Lijun , Zhu Jianyong
Published: January 2024

Penile shrapnel injuries are an exceedingly rare occurrence and a medical emergency. Herein, we present a case of penile shrapnel wounds in an adolescent male and discuss the management and complications associated with penetrating injuries to penile. We reported that an 18-year-old Chinese armed police soldier underwent debridement, shrapnel removal and suturing under spinal anesthesia. Six days postoperatively, he was discharged from the hospital smoothly. The patient reported normal erectile function and urination following discharge. With a follow-up of three months, the patient exhibited no symptoms of dysuria or erectile dysfunction. It is explicitly stated that prompt surgery intervention described in this report resulted in optimal prognosis. Penile shrapnel injury is a rare phenomenon typically associated with emergency drill and military training involving explosive shells. With regard to penetrating penile injury, timely surgical exploration is essential because it avoids penile plaque formation, penile fibrosis and angulation, and accelerates the return to erectile and urination function.
Antibiotic use at planned central line removal in reducing neonatal post-catheter removal sepsis: a systematic review and meta-analysis
Authors: Ji Ruoyu , He Zhangyuting , Zhou Jiawei , Fang Shiyuan , Ge Lili
Published: January 2024

Background

Post-catheter removal sepsis (PCRS) is a notable complication of indwelling central venous catheters (CVCs) in neonates, which is postulated to be secondary to the disruption of biofilms formed along catheter tips up on CVCs removal. It remains controversial whether this could be prevented by antibiotic use upon CVCs removal. We aimed to evaluate the protective effect of antibiotic administration at the time of CVCs removal.

Methods

We searched through PubMed, EMBASE, Cochrane databases and reference lists of review articles for studies comparing the use of antibiotics versus no use within 12 h of CVCs removal. Risk of bias was assessed using the modified Newcastle-Ottawa Scale and Cochrane risk-of-bias tool accordingly. Results of quantitative analyses were presented as mean differences (MD) or odds ratio (OR). Subgroup and univariate meta-regression analyses were performed to identify heterogeneity.

Results

The review included 470 CVCs in the antibiotic group and 658 in the control group. Antibiotic use within 12 h of CVCs removal did not significantly reduce the incidence of PCRS (OR = 0.35, 95% CI: 0.08–1.53), but was associated with a lower incidence of post-catheter removal blood stream infection (OR = 0.31, 95% CI: 0.11–0.86). Dosage of vancomycin and world region were major sources of heterogeneity.

Conclusion

Antibiotic administration upon CVCs removal does not significantly reduce the incidence of PCRS but offers less post-catheter removal blood stream infection. Whether this will be converted to better clinical outcomes lacks evidential support. Further randomized controlled studies with longer follow-up are needed.

Results of our meta-analysis suggest that antibiotic use at planned central line removal removal does not significantly reduce the incidence of PCRS but offers less blood stream infection, which might contribute to future management of central lines in neonates.

Systematic Review Registration

https://www.crd.york.ac.uk/, PROSPERO (CRD42022359677).
Antidepressant sertraline increases thioflavin-S and Congo red deposition in APPswe/PSEN1dE9 transgenic mice
Authors: Liao Ming-Hsuan , Lin Yen-Kuang , Gau Fong-Ying , Tseng Chun-Che , Wu Da-Chih , Hsu Chu-Yuan , Chung Kuo-Hsuan , Li Rung-Chi , Hu Chaur-Jong , Then Chee Kin , Shen Shing-Chuan
Published: January 2024

Introduction: Depression is strongly associated with Alzheimer’s disease (AD). Antidepressants are commonly used in patients before and after their diagnosis of AD. To date, the relationship between antidepressants and AD remains unclear.

Methods: In our study, we administered sertraline or paroxetine to wild type (WT) and APPswe/PSEN1dE9 (APP/PSEN1) transgenic mouse models for up to 12 months. We quantified the drug concentrations using LC-MS/MS analysis and measured serum serotonin level using an ELISA assay. Additionally, we evaluated the amyloid burdens through thioflavin-S and Congo red stainings, and recognition memory using the novel object recognition test.

Results: Our findings revealed that mice treated with paroxetine exhibited a significantly higher level of weight gain compared to the control group and increased mortality in APP/PSEN1 mice. After 12 months of antidepressant treatment, the sertraline level was measured at 289.8 ng/g for cerebellum, while the paroxetine level was 792.9 ng/g for cerebellum. Sertraline significantly increased thioflavin-S and Congo red depositions, along with gliosis, in both isocortex and hippocampus of APP/PSEN1 mice compared to the control group. Both antidepressants also led to a decreased recognition index in APP/PSEN1 mice.

Conclusion: These findings suggest a potential role of sertraline in AD pathogenesis, emphasizing the need to reassess the use of these antidepressants in patients with AD.
Drug compatibility with various closed intravenous infusion containers
Authors: Zhu Chang-yu , Zuo Hui-ying , Li Hong-lin , Tong Rong-sheng
Published: January 2024

Objective: The aim was to systematically compare the drug compatibility with various closed intravenous (i.v.) infusion containers, to provide a reference for selecting a relatively superior infusion container and improve the medication safety for patients in clinical practice.

Methods: The compatibility of four commonly used clinical injections (ceftazidime, pantoprazole sodium, ambroxol hydrochloride, edaravone) with three representative closed i. v. infusion containers (non-PVC infusion bags, upright polypropylene infusion bags, inner sealed polypropylene infusion bags) prefilled with infusion fluids (0.9% sodium chloride or 5% dextrose) in the Chinese market were investigated in this study. The particle counts of both infusion fluids and diluted chemical injections by infusion fluids in various infusion containers were determined by the light obscuration method. At 0, 2 and 6 h after four injections following dilution with infusion fluids in each container, the pH of the solutions was detected, and the physical properties were examined by visual inspection. Meanwhile, the drug concentrations were assessed by high performance liquid chromatography (HPLC).

Results: As for either infusion fluids or diluted injections by infusion fluids, the particle counts in non-PVC infusion bags were significantly greater than those in the other two bags under some circumstances. The particle counts in diluted injections by infusion fluids increased dramatically compared with those in infusion fluids in all infusion containers, especially for the small-size particles. But pH, physical properties and drug concentrations of diluted infusion solutions in all infusion containers remained nearly unchanged over the test period.

Conclusion: Closed i. v. infusion containers included in this study are all well-compatible with four injections. Moreover, the closed infusion containers produced by Chinese manufacturers have met the international quality standard. Particularly, the intravenous admixture preparation process needs to be optimized to reduce the overall particulate contaminants.
Enhancing antidepressant safety surveillance: comparative analysis of adverse drug reaction signals in spontaneous reporting and healthcare claims databases
Authors: Kim Taehyung , Jiang Xinying , Noh Youran , Kim Maryanne , Hong Song Hee
Published: January 2024

Background/Objective: Spontaneous reporting systems (SRS) such as the Korea Adverse Event Reporting System (KAERS) are limited in their ability to detect adverse drug reaction (ADR) signals due to their limited data on drug use. Conversely, the national health insurance claim (NHIC) data include drug use information for all qualifying residents. This study aimed to compare ADR signal profiles for antidepressants between KAERS and NHIC, evaluating the extent to which detected signals belong to common ADRs and labeling information.

Materials and Methods: ADR signal detection in KAERS and NHIC databases, spanning January to December 2017, employed disproportionality analysis. Signal classes were determined based on System Organ Class (SOC) of the Medical Dictionary for Regulatory Activities (MedDRA). Also, Common ADR Coverage (CAC), the proportion of detected signals deemed common ADRs, and labeling information coverage (LIC) represented by mean average precision (mAP) were calculated. Additionally, protopathic bias and relative risk (RR) evaluation were performed to check for signal robustness.

Results: Signal detection revealed 51 and 62 signals in KAERS and NHIC databases, respectively. Both systems predominantly captured signals related to nervous system disorders, comprising 33.3% (N = 17) in KAERS and 50.8% (N = 31) in NHIC. Regarding the type of antidepressants, KAERS predominantly reported signals associated with tricyclic antidepressants (TCAs) (N = 21, 41.2%), while NHIC produced most signals linked to selective serotonin reuptake inhibitors (SSRIs) (N = 22, 35.5%). KAERS exhibited higher CAC (68.63% vs. 29.03%) than NHIC. LIC was also higher in KAERS than in NHIC (mAP for EB05: 1.00 vs. 0.983); i.e., NHIC identified 5 signals not documented in drug labeling information, while KAERS found none. Among the unlabeled signals, one (Duloxetine-Myelopathy) was from protopathic bias, and two (duloxetine-myelopathy and tianeptine-osteomalacia) were statistically significant in RR.

Conclusion: NHIC exhibited greater capability in detecting ADR signals associated with antidepressant use, encompassing unlabeled ADR signals, compared to KAERS. NHIC also demonstrated greater potential for identifying less common ADRs. Further investigation is needed for signals detected exclusively in NHIC but not covered by labeling information. This study underscores the value of integrating different sources of data, offering substantial regulatory insights and enriching the scope of pharmacovigilance.
Ethnomedicinal uses, phytochemistry, and pharmacology of the genus Sarcophyte: a review
Authors: Jared Misonge Onyancha , Gervason Apiri Moriasi , James Onsinyo Meroka , Samuel Murigi Wainaina , Geoffrey Ogeto Sengera , Vincent Obaga Nyandoro
Published: January 2024

Although medicinal plants have been used by ethnic communities since ancient times to prevent and treat various diseases, only a few have been scientifically documented. Therefore, due to their rare availability and lack of comprehensive scientific information, we reviewed the ethnomedicinal uses, phytochemistry, and pharmacological activities of plants within the genus Sarcophyte. To do this, we used specific search terms and phrases to retrieve relevant information from online sources published in English from 2000 to July 2023. The results showed that there are only two plants in the genus Sarcophyte (Sarcophyte sanguinea Sparrm. and Sarcophyte piriei Hutch.), which are traditionally used to treat a wide range of diseases, especially cancer, and skin, gastrointestinal, and urinogenital tract ailments in humans, and to cure animals in ethnoveterinary practices. It was noted that 13 secondary metabolites have been isolated from the two plants, the most prominent of which are flavonoids (diinsininol, diinsinin, and naringenin). The antioxidant activity of S. piriei is reported based on the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50: 4.26 ± 0.22 μg/mL) and 2 -2′-Azino-di-[3-ethylbenzthiazoline sulfonate (ABTS) radicals (IC50: 4.62 ± 0.14 μg/mL), chelating iron (IC50: 1.82 ± 0.01 μg/mL, 3.50 ± 0.09 μg/mL), and nitric oxide (IC50: 9.97 ± 0.88 μg/mL, 9.09 ± 0.11 μg/mL). The methanolic stem extracts of S. piriei possess antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Vibrio fluvialis, and Enterococcus avium, with minimum inhibitory concentration (MIC) values ranging from 0.16 to 0.625 mg/mL, and a minimum bactericidal concentration (MBC) of 1.25 to 5 mg/mL. Cytotoxic effects of the extracts from the two plant species were also demonstrated. Sarcophyte piriei possesses therapeutic potential as evidenced by the inhibitory effects of the aqueous rhizome extract on edema (1,000 mg/kg) and prostaglandin synthesis (IC50 = 0.2 mg/mL). In addition, diinsininol and diinsinin were isolated from S. sanguinea inhibited prostaglandin synthesis (IC50: 9.20 µM, 13.14 µM) and platelet-activating factor-induced exocytosis. Therefore, based on this review, further scientific research is needed to demystify the links between traditional medicinal uses, various secondary metabolites, and the pharmacology of the two plants.
Network pharmacology and experiment validation investigate the potential mechanism of triptolide in oral squamous cell carcinoma
Authors: Hao Puyu , Zhang Pengcheng , Liu Ying , Cao Yang , Du Lianqun , Gao Li , Dong Qingyang
Published: January 2024

Objective: This study aimed to investigate the molecular mechanism of triptolide in the treatment of oral squamous cell carcinoma (OSCC) via network pharmacology and experimental validation.

Methods: The network pharmacological method was used to predict the key targets, detect the signal pathways for the treatment of OSCC, and screen the critical components and targets for molecular docking. Predicted targets were validated in cellular and xenograft mouse model.

Results: In this study, we predicted action on 17 relevant targets of OSCC by network pharmacology. PPI network demonstrated that Jun, MAPK8, TP53, STAT3, VEGFA, IL2, CXCR4, PTGS2, IL4 might be the critical targets of triptolide in the treatment of OSCC. These potential targets are mainly closely related to JAK-STAT and MAPK signaling pathways. The analysis of molecular docking showed that triptolide has high affinity with Jun, MAPK8 and TP53. Triptolide can suppress the growth of OSCC cells and xenograft mice tumor, and downregulate the expression of Jun, MAPK8, TP53, STAT3, VEGFA, IL2, CXCR4, PTGS2 to achieve the therapeutic effect of OSCC.

Conclusion: Through network pharmacological methods and experimental studies, we predicted and validated the potential targets and related pathways of triptolide for OSCC treatment. The results suggest that triptolide can inhibit the growth of OSCC via several key targets.
An updated review of experimental rodent models of pulmonary hypertension and left heart disease
Authors: Jasińska-Stroschein Magdalena
Published: January 2024

Left heart disease (LHD) is the leading cause of pulmonary hypertension (PH). Its recent growth has not been matched by the design of therapeutic agents directly targeting the disease. Effective therapies approved for pulmonary arterial hypertension (PAH) have been shown to be inefficient in patients with PH-LHD. Hence, there is a need for an animal model that would closely mimic PH-LHD in preclinical experiments. The current study describes and compares a number of rodent models of left ventricular failure and their potential to induce PH. It also evaluates whether, and to what extent, common PH models could develop LV failure. Articles were identified in the Pubmed/Medline and Web of Science online electronic databases following the PRISMA Protocol between 1992 and 2022. Quality assessment was carried out using the SYRCLE risk-of-bias tool for animal studies. Publication bias across studies using Egger’s regression test statistic, was performed together with sensitivity analysis. A wide spectrum of protocols–135 studies and 207 interventions, was examined, including systemic hypertensive models, pressure-overload-induced HF, model of ischemic heart failure, and metabolic approaches based on high fat diet or metabolic syndrome. The most pronounced alterations in PH-related parameters were demonstrated for the common PH models, but were also seen in animals with LV failure induced by ischemic conditions, pressure overload or metabolic conditions. Models based on aortic banding, transverse aortic constriction (TAC), or with myocardial infarction (MI) caused by coronary artery ligation, demonstrated more pronounced worsening in PH due to LV failure; however, they also demonstrated poor survival, especially the ischemic-HF model. Common PH models, excluding prolonged exposure to monocrotaline, do not promote LV hypertrophy. Prolonged exposure to a high-fat diet, or a two-hit model of an obese ZSF1 rat combined with SU5416-induced pulmonary endothelial impairment (a VEGF receptor antagonist) worsened PH and impaired diastolic dysfunction. Due to the limited number of protocols, further trials are needed to confirm the utility of such approaches for modeling PH in subjects with metabolic syndrome. This would provide a clearer insight into the complexity of LHD, PH and metabolic disorders in PH-LHD, and thus accelerate the development of new therapies in clinical trials.
Pharmacological functions of salidroside in renal diseases: facts and perspectives
Authors: Liu Qiong , Chen Jianzhu , Zeng Anqi , Song Linjiang
Published: January 2024

Rhodiola rosea is a valuable functional medicinal plant widely utilized in China and other Asian countries for its anti-fatigue, anti-aging, and altitude sickness prevention properties. Salidroside, a most active constituent derived from Rhodiola rosea, exhibits potent antioxidative, hypoxia-resistant, anti-inflammatory, anticancer, and anti-aging effects that have garnered significant attention. The appreciation of the pharmacological role of salidroside has burgeoned over the last decade, making it a beneficial option for the prevention and treatment of multiple diseases, including atherosclerosis, Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, and more. With its anti-aging and renoprotective effects, in parallel with the inhibition of oxidative stress and inflammation, salidroside holds promise as a potential therapeutic agent for kidney damage. This article provides an overview of the microinflammatory state in kidney disease and discuss the current therapeutic strategies, with a particular focus on highlighting the recent advancements in utilizing salidroside for renal disease. The potential mechanisms of action of salidroside are primarily associated with the regulation of gene and protein expression in glomerular endothelial cells, podocytes, renal tubule cells, renal mesangial cells and renal cell carcinoma cell, including TNF-α, TGF-β, IL-1β, IL-17A, IL-6, MCP-1, Bcl-2, VEGF, ECM protein, caspase-3, HIF-1α, BIM, as well as the modulation of AMPK/SIRT1, Nrf2/HO-1, Sirt1/PGC-1α, ROS/Src/Cav-1, Akt/GSK-3β, TXNIP-NLRP3, ERK1/2, TGF-β1/Smad2/3, PI3K/Akt, Wnt1/Wnt3a β-catenin, TLR4/NF-κB, MAPK, JAK2/STAT3, SIRT1/Nrf2 pathways. To the best of our knowledge, this review is the first to comprehensively cover the protective effects of salidroside on diverse renal diseases, and suggests that salidroside has great potential to be developed as a drug for the prevention and treatment of metabolic syndrome, cardiovascular and cerebrovascular diseases and renal complications.
Comparative pharmacoeconomic analysis of rituximab and traditional tacrolimus regimens in membranous nephropathy in China
Authors: Zeng Li , Chen Huihui , Xiang Heng , Zeng Mengru , Zhou Mi , Tan Chongqing , Liu Hong , Chen Guochun
Published: January 2024

Background: Rituximab (RTX) is a monoclonal antibody that selectively targets CD20 and is frequently used in the treatment of membranous nephropathy (MN). Analysis of the therapeutic efficacy and safety of RTX in treating MN in practice and a comparative pharmacoeconomic analysis of the RTX and traditional tacrolimus (TAC) regimens can provide valuable insights to aid decision-making by the government and relevant medical insurance departments.

Methods: We conducted a statistical analysis of medical records from patients diagnosed with MN who underwent RTX treatment between 1 January 2019 and 1 January 2023. The TAC data were obtained from the clinical literature. The efficacy rates and incidence of adverse effects (AEs) were calculated to compare the efficacy and safety of RTX and TAC. Based on the patient’s disease status, we developed a Markov model to compare the total cost, remission rate, and incremental cost-effectiveness ratio (ICER) of the two regimens. Both univariate and probability sensitivity analyses were performed to validate the stability of the developed model.

Results: The RTX group enrolled 53 patients with MN, and the 12-month overall efficacy rate was not significantly different from that of the TAC group with 35 patients (86.79% vs. 71.4%, p = 0.0131); however, the relapse rate was significantly lower in the RTX group (3.77% vs. 22.8%, p = 0.016). The RTX group demonstrated no severe AEs (SAEs), while the TAC group demonstrated six cases of SAEs, including 4 cases of severe pneumonia, 1 case of lung abscess and 1 case of interstitial lung disease, accounting for 7.89% of traditional tacrolimus-treated patients. The baseline analysis results revealed that over a 5-year post-treatment period, RTX increased quality-adjusted life years (QALYs) by 0.058 and costs by ¥7,341. Assuming three times the 2022 domestic gross domestic product as the willingness-to-pay (WTP) threshold per QALY, the ICER of RTX compared to TAC was ¥124,631.14/QALY, which is less than the WTP threshold of ¥257,094/QALY, indicating that RTX treatment is approximately two times more cost-effective compared to TAC.

Conclusion: The current analysis indicates that despite the expensive unit price of RTX, it remains a cost-effective treatment option for MN compared to TAC.
Analysis of risk factors for acute pancreatitis complicated with pancreatic sinistral portal hypertension and construction of predictive model
Authors: Zhao Xin , Mao Tian-Yang , Jiang Kang-Yi , Xie Qing-Yun , Yang Jie , Du Bo , Wang Zhi-Xu , Fu Jin-Qiang , Gao Feng-Wei , Lei Ze-Hua
Published: January 2024

Objective: Pancreatic sinistral portal hypertension (PSPH) is a common complication of acute pancreatitis (AP) and can cause massive gastrointestinal bleeding, which is one of the causes of AP-related mortality. However, there is currently no predictive model for AP concurrent with PSPH. This study aimed to identify the risk factors for AP concurrent with PSPH and use these factors to build a related predictive model.

Materials and methods: We collected clinical data from 282 patients with AP. 192 patients were used as a training group and 90 patients as a validation group. Univariate and multivariate analyses were used to identify independent risk factors for AP complicated with PSPH, and then a nomogram was established. The models are cross verification and Internal verification. The predictive ability and accuracy of the model were evaluated based on the working curve of the subjects and the calibration curve, respectively. The clinical value of the model was evaluated using decision curve analysis (DCA).

Results: The univariate analysis revealed significant differences in the occurrence of PSPH with respect to sex, recurrent AP, history of hypertension, smoking history, patency of the splenic vein, pancreatic necrosis or pancreatic pseudocyst formation, the most significant site of pancreatic swelling, presence of a Dmure D polymer, MCTSI, and involvement of lipase and amylase. The logistic multivariate regression analysis showed that male sex, splenic-vein stenosis or occlusion and swelling were located in the body-tail, and MCTSI was an independent risk factor for PSPH. The nomogram and ROC curve were constructed. The area under the working curve of the subjects was 0.91, and the sensitivity and specificity were 82.5% and 89.1%, respectively. In the validation group, the C-index is 0.826. The nomogram was internally validated using 1,000 bootstrap samples, and the c-index was 0.898. The calibration curve demonstrated that the predicted probability was concordant with the observed probability, and the DCA confirmed that the model had robust clinical utility.

Conclusion: Male sex, splenic-vein stenosis or occlusion, recurrent AP, and swelling are located in the body-tail, and MCTSI is an independent risk factor for the occurrence of PSPH. The predictive model developed for AP complicated with PSPH may serve toward developing preventive and therapeutic approaches for PSPH.
Unraveling the “golden ratio”: a pilot study investigating acute-to-chronic workload ratio in breast cancer patients undergoing active treatment
Authors: Skouras Apostolos Z. , Antonakis-Karamintzas Dimitrios , Tsolakis Charilaos , Koulouvaris Panagiotis
Published: January 2024

Training load monitoring is a common practice in sports medicine for supporting athletes’ health and performance. Despite progress in exercise oncology research for breast cancer patients, training load monitoring is underutilized. This study retrospectively investigated the relationship between maintained training load within a defined range and physical and health outcomes of ten breast cancer patients during active anticancer treatment who underwent a 12-week exercise program. Intervention consisted of endurance and resistance training, three times a week, with each session lasting 30–45 min. Assessments were conducted at baseline, 6 and 12 weeks after enrollment, evaluating physical function (6-min walk test–6MWT, and sit-to-stand), muscle strength, body composition, sleep quality (Pittsburgh Sleep Quality Index–Pittsburgh Sleep Quality Index), quality of life (EORTC-QLQ-C30), heart rate variability and physical activity levels (International Physical Activity Questionnaire–International Physical Activity Questionnaire). The Physiological Cost Index/Energy Expenditure Index (PCI/EEI) was estimated using the 6MWT and Heart rate. Training load monitoring was performed by session rating of perceived exertion (sRPE, relative intensity multiplying with session duration). Acute-to-Chronic Workload Ratio (ACWR) (7:28, rolling average) was calculated accordingly. Analyses were performed within-subjects across time points and between-subjects, comparing those who maintained from weeks 6–12 an ACWR of 0.8–1.3 with those who did not. Adherence rates were similar between groups. Physical function improved in the total sample with large effect sizes (Δ6MWT = 56.5 m [95%CI: 6–100 m], effect size [w] = 0.52, p = 0.006; ΔSit-to-Stand = 1.5 [95%CI: 1–5], effect size [w] = 0.681, p < 0.001), demonstrating greater changes in patients with higher ACWR. Sleep quality improvements were higher in the appropriate ACWR group (p = 0.016). A positive correlation was demonstrated between global health status and 6MWT change from baseline to 12 weeks (ρ = 0.689, p = 0.04). Despite a small sample size, patients maintaining sufficient relative training load presented greater physical fitness and sleep quality improvements. Thus, training load monitoring may enhance exercise program benefits in breast cancer patients under active treatment.