bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and pan-genome analysis of Enterobacter hormaechei Z129, a ureolytic bacterium, from the rumen of dairy cow
Authors: Zhong Huiyue , Zheng Nan , Wang Jiaqi , Zhao Shengguo
Published: April 2023

Introduction

Urea is an important non-protein nitrogen source for ruminants. In the rumen, ureolytic bacteria play critical roles in urea-nitrogen metabolism, however, a few ureolytic strains have been isolated and genomically sequenced. The purpose of this study was to isolate a novel ureolytic bacterial strain from cattle rumen and characterize its genome and function.

Methods

The ureolytic bacterium was isolated using an anaerobic medium with urea and phenol red as a screening indicator from the rumen fluid of dairy cattle. The genome of isolates was sequenced, assembled, annotated, and comparatively analyzed. The pan-genome analysis was performed using IPGA and the biochemical activity was also analyzed by test kits.

Results

A gram-positive ureolytic strain was isolated. Its genome had a length of 4.52 Mbp and predicted genes of 4223. The 16S rRNA gene and genome GTDB-Tk taxonomic annotation showed that it was a novel strain of Enterobacter hormaechei, and it was named E. hormaechei Z129. The pan-genome analysis showed that Z129 had the highest identity to E. hormaechei ATCC 49162 with a genome average nucleotide identity of 98.69% and possessed 238 unique genes. Strain Z129 was the first E. hormaechei strain isolated from the rumen as we know. The functional annotation of the Z129 genome showed genes related to urea metabolism, including urea transport (urtA-urtE), nickel ion transport (ureJ, tonB, nixA, exbB, exbD, and rcnA), urease activation (ureA-ureG) and ammonia assimilation (gdhA, glnA, glnB, glnE, glnL, glsA, gltB, and gltD) were present. Genes involved in carbohydrate metabolism were also present, including starch hydrolysis (amyE), cellulose hydrolysis (celB and bglX), xylose transport (xylF-xylH) and glycolysis (pgi, pgk, fbaA, eno, pfkA, gap, pyk, gpmL). Biochemical activity analysis showed that Z129 was positive for alkaline phosphatase, leucine arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase, α-glucosidase, β-glucosidase, and pyrrolidone arylaminase, and had the ability to use D-ribose, L-arabinose, and D-lactose. Urea-nitrogen hydrolysis rate of Z129 reached 55.37% at 48 h of incubation.

Discussion

Therefore, the isolated novel ureolytic strain E. hormaechei Z129 had diverse nitrogen and carbon metabolisms, and is a preferred model to study the urea hydrolysis mechanism in the rumen.
V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid
Authors: Wang Qili , Wolf Alexander , Ozkan Sebahat , Richert Ludovic , Mely Yves , Chasserot-Golaz Sylvette , Ory Stéphane , Gasman Stéphane , Vitale Nicolas
Published: April 2023

Although there is mounting evidence indicating that lipids serve crucial functions in cells and are implicated in a growing number of human diseases, their precise roles remain largely unknown. This is particularly true in the case of neurosecretion, where fusion with the plasma membrane of specific membrane organelles is essential. Yet, little attention has been given to the role of lipids. Recent groundbreaking research has emphasized the critical role of lipid localization at exocytotic sites and validated the essentiality of fusogenic lipids, such as phospholipase D (PLD)-generated phosphatidic acid (PA), during membrane fusion. Nevertheless, the regulatory mechanisms synchronizing the synthesis of these key lipids and neurosecretion remain poorly understood. The vacuolar ATPase (V-ATPase) has been involved both in vesicle neurotransmitter loading and in vesicle fusion. Thus, it represents an ideal candidate to regulate the fusogenic status of secretory vesicles according to their replenishment state. Indeed, the cytosolic V1 and vesicular membrane-associated V0 subdomains of V-ATPase were shown to dissociate during the stimulation of neurosecretory cells. This allows the subunits of the vesicular V0 to interact with different proteins of the secretory machinery. Here, we show that V0a1 interacts with the Arf nucleotide-binding site opener (ARNO) and promotes the activation of the Arf6 GTPase during the exocytosis in neuroendocrine cells. When the interaction between V0a1 and ARNO was disrupted, it resulted in the inhibition of PLD activation, synthesis of phosphatidic acid during exocytosis, and changes in the timing of fusion events. These findings indicate that the separation of V1 from V0 could function as a signal to initiate the ARNO-Arf6-PLD1 pathway and facilitate the production of phosphatidic acid, which is essential for effective exocytosis in neuroendocrine cells.
The contribution of the smartphone use to reducing depressive symptoms of Chinese older adults: The mediating effect of social participation
Authors: Ji Rong , Chen Wei-chao , Ding Meng-jun
Published: April 2023

Background

Depression is a prevalent mental health disorder. Although Internet use has been associated with depression, there is limited data on the association between smartphone use and depressive symptoms. The present study aimed to investigate the relationship between smartphone use and depressive symptoms among older individuals in China.

Methods

5,244 Chinese older individuals over the age of 60 were selected as the sample from the China Longitudinal Aging Social Survey (CLASS) 2018 dataset. The dependent variable “depression symptoms” was measured using the 9-item Center for Epidemiologic Studies-Depression (CES-D) scale. The study employed multiple linear regression to investigate the relationship between smartphone use (independent variable) and depressive symptoms in older people. Thorough analyses of robustness, sensitivity, and heterogeneity were conducted to ensure the robustness and sensitivity of the findings. Additionally, mediating effect analysis was performed to elucidate the mechanism through which the dependent and independent variables were related.

Results

Empirical study indicated that smartphone use had a negative impact on depressive symptoms among older adults, specifically leading to a reduction in such symptoms. The above-mentioned result was verified through endogenous and robustness tests. The heterogeneity analysis revealed that older individuals aged 70 years and above, male, and residing in urban areas exhibited a stronger association between smartphone use and depressive symptoms. Furthermore, the mediating effect model indicated that political participation, voluntary participation, and active leisure participation mediated the relationship between smartphone use and lower levels of depression symptoms among the older adults. However, passive leisure participation had a suppressing effect on the relationship between smartphone use and reduced depressive symptoms among the older adults.

Limitations

The causal relationship between variables required further investigation with a longitudinal design.

Conclusion

These findings suggested that smartphone use may be considered an intervention to reduce depression symptoms among older people by increasing levels of political participation, voluntary participation, and active leisure participation.
Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study
Authors: Baricich Alessio , Battaglia Marco , Cuneo Daria , Cosenza Lucia , Millevolte Marzia , Cosma Michela , Filippetti Mirko , Dalise Stefania , Azzollini Valentina , Chisari Carmelo , Spina Stefania , Cinone Nicoletta , Scotti Lorenza , Invernizzi Marco , Paolucci Stefano , Picelli Alessandro , Santamato Andrea
Published: April 2023

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs.

Clinical trial identifier

NCT04673240.
Efficacy of intratympanic or postauricular subperiosteal corticosteroid injection combined with systemic corticosteroid in the treatment of sudden sensorineural hearing loss: A prospective randomized study
Authors: Xie Wen , Karpeta Niki , Liu Jiali , Peng Haisen , Li Chunhua , Zhang Zhiling , Liu Yuehui , Duan Maoli
Published: April 2023

Objectives

This study aimed to investigate the efficacy and safety of intratympanic or postauricular subperiosteal glucocorticoid injection combined with systemic glucocorticoid in the treatment of sudden sensorineural hearing loss (SSNHL).

Methods

This study is a prospective randomized controlled study. This study included unilateral SSNHL patients who were hospitalized in our department between January 2020 and June 2021. Patients were randomly divided into three groups (groups A, B, and C). Patients in group A were treated with an intratympanic corticosteroid injection combined with systemic corticosteroid treatment, and patients in group B received a postauricular corticosteroid injection combined with systemic corticosteroid treatment. Patients in group C (control group) were treated with systemic corticosteroid alone. The case number of groups A, B, and C was 311, 375, and 369, respectively.

Results

There was no significant difference in gender distribution, the proportion of left and right affected ears, and the average interval from onset to treatment among the three groups (P > 0.05). However, there were significant differences in their average age, distribution of audiogram type, and hearing loss levels among them (P < 0.01). Our study shows that there was no significant difference in average hearing threshold improvement before and after treatment in the three groups (P > 0.05). Regarding the complications, in group A, 33 patients (10.6%) had a transient vertigo attack during tympanic injection, which lasted for ~1–3 min. In group B, 20 patients (6.43%) complained of pain at the injection site, which disappeared after 1–3 days. No other complications occurred in all the other patients.

Conclusion

The addition of intratympanic or postauricular corticosteroid to systemic steroids did not result in a significant effect on hearing recovery in SSNHL. No obvious complications occur in SSNHL patients treated with intratympanic injection or postauricular injection of corticosteroid.

Clinical trial registration

[chictr.org.cn], registration number: ChiCTR2100048762.
Should we treat pediatric radiologically isolated syndrome? An 18-year follow-up case report
Authors: Barbuti Elena , Nistri Riccardo , Ianniello Antonio , Pozzilli Carlo , Ruggieri Serena
Published: April 2023

Background

Radiologically isolated syndrome (RIS) describes asymptomatic individuals with incidental radiologic abnormalities suggestive of multiple sclerosis (MS). Much of RIS literature is about adult-onset cases. Treatment of RIS is controversial, especially in pediatric age, but early treatment in selected patients might improve long-term outcomes.

Case presentation

We report a single RIS patient who followed up for 18 years in our MS center. At first, she was only monitored with follow-up MRIs. Then, as the lesion load increased, she was treated with a first-line disease-modifying treatment (DMT) reaching MRI stability.

Conclusion

This report highlights how treatment can be an appropriate choice in pediatric forms of RIS.
Application of quantitative electroencephalography in predicting early cerebral ischemia in patients undergoing carotid endarterectomy
Authors: Zhao Guanxu , Feng Guang , Zhao Lei , Feng Shuai , An Yi , Kong Cuicui , Wang Tianlong
Published: April 2023

Background

Quantitative electroencephalography (QEEG) has emerged as a promising monitoring method in cerebral ischemia, but the feasibility of QEEG in intraoperative cerebral perfusion-related ischemia monitoring is still uncertain. The purpose of this study was to investigate the value of QEEG monitoring in Carotid Endarterectomy (CEA) and the thresholds for intraoperative cerebral perfusion-related ischemia monitoring.

Methods

Sixty-three patients who underwent carotid endarterectomy with continuous Transcranial Doppler ultrasound (TCD) monitoring and QEEG monitoring at Xuanwu Hospital Capital Medical University from January 2021 to August 2021 were enrolled in this study. Each patient received total intravenous anesthesia. Middle cerebral artery blood flow velocity (V-MCA) was obtained by TCD. Relative alpha percentage (RA) and alpha-delta ratio (ADR) were obtained by QEEG monitoring. Patients were divided into ischemic and non-ischemic groups using a decline of more than 50% in the V-MCA monitored by TCD as the gold standard.

Results

Of the 63 patients, twenty patients were divided into the ischemic group, and forty-three patients into the non-ischemic group. Ipsilateral post-clamp RA and ADR values of QEEG were decreased for all patients in the ischemic group. The optimal threshold for RA and ADR to predict cerebral ischemia was a 14% decrease from baseline (sensitivity 90.0%, specificity 90.7%, Kappa value 0.786), a 21% decrease from baseline (sensitivity 85.0%, specificity 81.4%, Kappa value 0.622), respectively, indicated by TCD monitoring.

Conclusions

Our study demonstrated that QEEG is a promising monitoring method undergoing CEA under general anesthesia and has good consistency with TCD.
Efficient training of spiking neural networks with temporally-truncated local backpropagation through time
Authors: Guo Wenzhe , Fouda Mohammed E. , Eltawil Ahmed M. , Salama Khaled Nabil
Published: April 2023

Directly training spiking neural networks (SNNs) has remained challenging due to complex neural dynamics and intrinsic non-differentiability in firing functions. The well-known backpropagation through time (BPTT) algorithm proposed to train SNNs suffers from large memory footprint and prohibits backward and update unlocking, making it impossible to exploit the potential of locally-supervised training methods. This work proposes an efficient and direct training algorithm for SNNs that integrates a locally-supervised training method with a temporally-truncated BPTT algorithm. The proposed algorithm explores both temporal and spatial locality in BPTT and contributes to significant reduction in computational cost including GPU memory utilization, main memory access and arithmetic operations. We thoroughly explore the design space concerning temporal truncation length and local training block size and benchmark their impact on classification accuracy of different networks running different types of tasks. The results reveal that temporal truncation has a negative effect on the accuracy of classifying frame-based datasets, but leads to improvement in accuracy on event-based datasets. In spite of resulting information loss, local training is capable of alleviating overfitting. The combined effect of temporal truncation and local training can lead to the slowdown of accuracy drop and even improvement in accuracy. In addition, training deep SNNs' models such as AlexNet classifying CIFAR10-DVS dataset leads to 7.26% increase in accuracy, 89.94% reduction in GPU memory, 10.79% reduction in memory access, and 99.64% reduction in MAC operations compared to the standard end-to-end BPTT. Thus, the proposed method has shown high potential to enable fast and energy-efficient on-chip training for real-time learning at the edge.
Neurophysiological mechanisms of transcranial alternating current stimulation
Authors: He Yuchen , Liu Shuang , Chen Long , Ke Yufeng , Ming Dong
Published: April 2023

Neuronal oscillations are the primary basis for precise temporal coordination of neuronal processing and are linked to different brain functions. Transcranial alternating current stimulation (tACS) has demonstrated promising potential in improving cognition by entraining neural oscillations. Despite positive findings in recent decades, the results obtained are sometimes rife with variance and replicability problems, and the findings translation to humans is quite challenging. A thorough understanding of the mechanisms underlying tACS is necessitated for accurate interpretation of experimental results. Animal models are useful for understanding tACS mechanisms, optimizing parameter administration, and improving rational design for broad horizons of tACS. Here, we review recent electrophysiological advances in tACS from animal models, as well as discuss some critical issues for results coordination and translation. We hope to provide an overview of neurophysiological mechanisms and recommendations for future consideration to improve its validity, specificity, and reproducibility.
Effect of epidural spinal cord stimulation on female sexual function after spinal cord injury
Authors: Shackleton Claire , Samejima Soshi , Miller Tiev , Sachdeva Rahul , Parr Ann , Samadani Uzma , Netoff Theoden , Hocaloski Shea , Elliott Stacy , Walter Matthias , Darrow David , Krassioukov Andrei
Published: April 2023

Sexual dysfunction is a common consequence for women with spinal cord injury (SCI); however, current treatments are ineffective, especially in the under-prioritized population of women with SCI. This case-series, a secondary analysis of the Epidural Stimulation After Neurologic Damage (E-STAND) clinical trial aimed to investigate the effect of epidural spinal cord stimulation (ESCS) on sexual function and distress in women with SCI. Three females, with chronic, thoracic, sensorimotor complete SCI received daily (24 h/day) tonic ESCS for 13 months. Questionnaires, including the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) were collected monthly. There was a 3.2-point (13.2%) mean increase in total FSFI from baseline (24.5 ± 4.1) to post-intervention (27.8 ± 6.6), with a 4.8–50% improvement in the sub-domains of desire, arousal, orgasm and satisfaction. Sexual distress was reduced by 55%, with a mean decrease of 12 points (55.4%) from baseline (21.7 ± 17.2) to post-intervention (9.7 ± 10.8). There was a clinically meaningful change of 14 points in the International Standards for Neurological Classification of Spinal Cord Injury total sensory score from baseline (102 ± 10.5) to post-intervention (116 ± 17.4), without aggravating dyspareunia. ESCS is a promising treatment for sexual dysfunction and distress in women with severe SCI. Developing therapeutic interventions for sexual function is one of the most meaningful recovery targets for people with SCI. Additional large-scale investigations are needed to understand the long-term safety and feasibility of ESCS as a viable therapy for sexual dysfunction.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03026816, NCT03026816.
A fluidic platform for mobility evaluation of zebrafish with gene deficiency
Authors: Jia Xiaoyu , Feng Yibo , Ma Wenju , Zhao Wei , Liu Yanan , Jing Guangyin , Tian Jing , Yang Tao , Zhang Ce
Published: April 2023

Introduction

Zebrafish is a suitable animal model for molecular genetic tests and drug discovery due to its characteristics including optical transparency, genetic manipulability, genetic similarity to humans, and cost-effectiveness. Mobility of the zebrafish reflects pathological conditions leading to brain disorders, disrupted motor functions, and sensitivity to environmental challenges. However, it remains technologically challenging to quantitively assess zebrafish's mobility in a flowing environment and simultaneously monitor cellular behavior in vivo.

Methods

We herein developed a facile fluidic device using mechanical vibration to controllably generate various flow patterns in a droplet housing single zebrafish, which mimics its dynamically flowing habitats.

Results

We observe that in the four recirculating flow patterns, there are two equilibrium stagnation positions for zebrafish constrained in the droplet, i.e., the “source” with the outward flow and the “sink” with the inward flow. Wild-type zebrafish, whose mobility remains intact, tend to swim against the flow and fight to stay at the source point. A slight deviation from streamline leads to an increased torque pushing the zebrafish further away, whereas zebrafish with motor neuron dysfunction caused by lipin-1 deficiency are forced to stay in the “sink,” where both their head and tail align with the flow direction. Deviation angle from the source point can, therefore, be used to quantify the mobility of zebrafish under flowing environmental conditions. Moreover, in a droplet of comparable size, single zebrafish can be effectively restrained for high-resolution imaging.

Conclusion

Using the proposed methodology, zebrafish mobility reflecting pathological symptoms can be quantitively investigated and directly linked to cellular behavior in vivo.
Early life adversity impaired dorsal striatal synaptic transmission and behavioral adaptability to appropriate action selection in a sex-dependent manner
Authors: de Carvalho Gregory , Khoja Sheraz , Haile Mulatwa T. , Chen Lulu Y.
Published: April 2023

Early life adversity (ELA) is a major health burden in the United States, with 62% of adults reporting at least one adverse childhood experience. These experiences during critical stages of brain development can perturb the development of neural circuits that mediate sensory cue processing and behavioral regulation. Recent studies have reported that ELA impaired the maturation of dendritic spines on neurons in the dorsolateral striatum (DLS) but not in the dorsomedial striatum (DMS). The DMS and DLS are part of two distinct corticostriatal circuits that have been extensively implicated in behavioral flexibility by regulating and integrating action selection with the reward value of those actions. To date, no studies have investigated the multifaceted effects of ELA on aspects of behavioral flexibility that require alternating between different action selection strategies or higher-order cognitive processes, and the underlying synaptic transmission in corticostriatal circuitries. To address this, we employed whole-cell patch-clamp electrophysiology to assess the effects of ELA on synaptic transmission in the DMS and DLS. We also investigated the effects of ELA on the ability to update action control in response to outcome devaluation in an instrumental learning paradigm and reversal of action-outcome contingency in a water T-maze paradigm. At the circuit level, ELA decreased corticostriatal glutamate transmission in male but not in female mice. Interestingly, in DMS, glutamate transmission is decreased in male ELA mice, but increased in female ELA mice. ELA impaired the ability to update action control in response to reward devaluation in a context that promotes goal-directedness in male mice and induced deficits in reversal learning. Overall, our findings demonstrate the sex- and region-dependent effects of ELA on behavioral flexibility and underlying corticostriatal glutamate transmission. By establishing a link between ELA and circuit mechanisms underlying behavioral flexibility, our findings will begin to identify novel molecular mechanisms that can represent strategies for treating behavioral inflexibility in individuals who experienced early life traumatic incidents.
System analysis based on the migration- and invasion-related gene sets identifies the infiltration-related genes of glioma
Authors: Shi Shuang , Zhong Jiacheng , Peng Wen , Yin Haoyang , Zhong Dong , Cui Hongjuan , Sun Xiaochuan
Published: April 2023

The current database has no information on the infiltration of glioma samples. Here, we assessed the glioma samples’ infiltration in The Cancer Gene Atlas (TCGA) through the single-sample Gene Set Enrichment Analysis (ssGSEA) with migration and invasion gene sets. The Weighted Gene Co-expression Network Analysis (WGCNA) and the differentially expressed genes (DEGs) were used to identify the genes most associated with infiltration. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the major biological processes and pathways. Protein–protein interaction (PPI) network analysis and the least absolute shrinkage and selection operator (LASSO) were used to screen the key genes. Furthermore, the nomograms and receiver operating characteristic (ROC) curve were used to evaluate the prognostic and predictive accuracy of this clinical model in patients in TCGA and the Chinese Glioma Genome Atlas (CGGA). The results showed that turquoise was selected as the hub module, and with the intersection of DEGs, we screened 104 common genes. Through LASSO regression, TIMP1, EMP3, IGFBP2, and the other nine genes were screened mostly in correlation with infiltration and prognosis. EMP3 was selected to be verified in vitro. These findings could help researchers better understand the infiltration of gliomas and provide novel therapeutic targets for the treatment of gliomas.
Clinical efficacy of customized modular prosthesis in the treatment of femoral shaft metastases
Authors: Pu Feifei , Yu Yihan , Shao Zengwu , Wu Wei , Feng Jing , Chen Fengxia , Zhang Zhicai
Published: April 2023

Purpose

To examine clinical outcomes of a specialized modular prosthesis used to fill a bone deficiency following removal of femoral shaft metastases.

Methods

Eighteen patients with femoral shaft metastases who underwent en bloc resection and implantation of a personalized modular prosthesis between December 2014 and December 2019 were retrospectively analyzed. Pain, limb function, and quality of life were evaluated using the visual analog scale (VAS), Musculoskeletal Tumor Society (MSTS) scale, International Society of Limb Salvage (ISOLS) scoring system, Karnofsky Performance Status (KPS) scale, and Nottingham Health Profile (NHP) scale. The Kaplan–Meier technique was used to analyze patient survival.

Results

The operation duration was 90–150 min (mean, 115 min), and the osteotomy length was 9–16 cm (mean, 11.72 cm). The patients were followed for 12–62 months (mean, 25.28 months). The VAS and NHP ratings were lower at 3, 6, and 12 months after surgery than before surgery, while the MSTS, ISOLS, and KPS scores were higher after surgery than they had been before. These differences were statistically significant (P<0.05). The survival period was between 7 and 62 months (mean, 20.89 months), and the rates of survival at 1-year and 2-year were 72.22% and 27.78%, respectively. Except for two patients with aseptic prosthesis loosening during the follow-up period, there were no problems.

Conclusion

En bloc excision and implantation of a personalized modular prosthesis can reduce pain and improve the ability of patients with femoral shaft metastases to perform daily activities, thereby improving their quality of life.
Dictionary learning LASSO for feature selection with application to hepatocellular carcinoma grading using contrast enhanced magnetic resonance imaging
Authors: Lei Lei , Du Li-Xin , He Ying-Long , Yuan Jian-Peng , Wang Pan , Ye Bao-Lin , Wang Cong , Hou ZuJun
Published: April 2023

Introduction

The successful use of machine learning (ML) for medical diagnostic purposes has prompted myriad applications in cancer image analysis. Particularly for hepatocellular carcinoma (HCC) grading, there has been a surge of interest in ML-based selection of the discriminative features from high-dimensional magnetic resonance imaging (MRI) radiomics data. As one of the most commonly used ML-based selection methods, the least absolute shrinkage and selection operator (LASSO) has high discriminative power of the essential feature based on linear representation between input features and output labels. However, most LASSO methods directly explore the original training data rather than effectively exploiting the most informative features of radiomics data for HCC grading. To overcome this limitation, this study marks the first attempt to propose a feature selection method based on LASSO with dictionary learning, where a dictionary is learned from the training features, using the Fisher ratio to maximize the discriminative information in the feature.

Methods

This study proposes a LASSO method with dictionary learning to ensure the accuracy and discrimination of feature selection. Specifically, based on the Fisher ratio score, each radiomic feature is classified into two groups: the high-information and the low-information group. Then, a dictionary is learned through an optimal mapping matrix to enhance the high-information part and suppress the low discriminative information for the task of HCC grading. Finally, we select the most discrimination features according to the LASSO coefficients based on the learned dictionary.

Results and discussion

The experimental results based on two classifiers (KNN and SVM) showed that the proposed method yielded accuracy gains, compared favorably with another 5 state-of-the-practice feature selection methods.
Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer
Authors: Fang Wei Bin , Medrano Marcela , Cote Paige , Portsche Mike , Rao Vinamratha , Hong Yan , Behbod Fariba , Knapp Jennifer R. , Bloomer Clark , Noel-Macdonnell Janelle , Cheng Nikki
Published: April 2023

Background/Introduction

As the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25% of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression.

Goals

We sought to determine 1) whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, and 2) the contributions of DCIS fibroblasts to breast cancer progression.

Methods

Fibroblasts underwent transcriptome profiling and pathway analysis. Significant DCIS fibroblast-associated genes were further analyzed in existing breast cancer mRNA databases and through tissue array immunostaining. Using the sub-renal capsule graft model, fibroblasts from normal breast, DCIS and IDC tissues were co-transplanted with DCIS.com breast cancer cells.

Results

Through transcriptome profiling, we found that DCIS fibroblasts were characterized by unique alterations in cell cycle and motility related genes such as PKMYT1, TGF-α, SFRP1 and SFRP2, which predicted increased cell growth and invasion by Ingenuity Pathway Analysis. Immunostaining analysis revealed corresponding increases in expression of stromal derived PKMYT1, TGF-α and corresponding decreases in expression of SFRP1 and SFRP2 in DCIS and IDC tissues. Grafting studies in mice revealed that DCIS fibroblasts enhanced breast cancer growth and invasion associated with arginase-1+ cell recruitment.

Conclusion

DCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications.
MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
Authors: Rico-Jimenez Jose J. , Jovanovic Joel , Nolen Stephanie L. , Malone Joseph D. , Rao Gopikrishna M. , Levine Edward M. , Tao Yuankai K.
Published: April 2023

Introduction

Laser-induced photodamage is a robust method for investigating retinal pathologies in small animals. However, aiming of the photocoagulation laser is often limited by manual alignment and lacks real-time feedback on lesion location and severity. Here, we demonstrate MURIN: MUltimodal Retinal Imaging and Navigated-laser-delivery, a multimodality OCT and SLO ophthalmic imaging system with an image-guided scanning laser lesioning module optimized for the murine retina. The proposed system enables targeting of focal and extended area lesions under OCT guidance to benefit visualization of photodamage response and the precision and repeatability of laser lesion models of retinal injury.

Methods

MURIN optics were optimized for simultaneous near-infrared and visible wavelength imaging/laser lesioning. Custom LabView control software was developed to steer the photocoagulation laser and automatically deliver laser pulses to targets-of-interest. In vivo retinal imaging was performed in transgenic Müller glia-tdTomato reporter mice (Rlbp1:CreER; Rosaai14, 5 animals, 10 eyes) and microglia-GFP/Müller glia-tdTomato reporter mice (Cx3cr1GFP; Rlbp1:CreER; Rosaai14, 9 animals, 15 eyes) to visualize cellular changes in the retina after laser lesion delivery.

Results

Real-time MURIN imaging concurrent with laser lesioning allowed us to visualize lesion formation dynamics and any corresponding changes in retinal morphology. We observe increasing fluorescence photoconversion on SLO and scattering contrast on OCT. Significant morphological changes are visible on MURIN after high-severity photodamage. OCT cross-sections show the spatial extent of the lesions contract over time from diffusion areas of increased scattering to granular scatterers and corresponding SLO images show a radial pattern surrounding severe focal lesions, which may be a result of a change in Müller cell shape or orientation in response to injury. The inner plexiform layer is distorted and increased RPE thickness and scattering are observed, all of which are confirmed on corresponding hematoxylin and eosin (H&E) histology and differential interference contrast (DIC) microscopy.

Discussion

MURIN as a unique imaging platform that enables combined SLO and OCT imaging with an integrated image-guided laser lesioning module. This technology has clear benefits over existing multimodal imaging and laser lesioning systems by enabling simultaneous multimodal imaging, independent and precise control of Iridex laser pulse parameters and patterns, and real-time OCT and SLO visualization of lesion formation.
Chinese Herbal Medicine Combined With Antiepileptic Drugs for Intractable Epilepsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhao Ying , Zhou Hufang , Liu Qingxuan , Liu Jialin , Wu Mengwei , Yuan Siyuan , Xu Weiwei , Wang Ying , Wang Kaiyue , Li Lili , Liu Jinmin
Published: April 2023

Background: Intractable epilepsy (IE) is still a major concern in neurology, and existing therapies do not adequately control symptoms. Chinese Herbal Medicine (CHM) has been widely used as an adjunct to antiepileptic drugs (AEDs) for IE. However, because of the contradictory findings reported in previous studies, it is uncertain if the present evidence is robust enough to warrant its usage. The purpose of this meta-analysis was to systematically evaluate the efficacy of the combination of CHM and AEDs for IE.

Methods: From inception to September 2021, Medline, Ovid, Embase, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, and Wanfang Database were searched. Only randomized controlled trials (RCTs) that assessed the efficacy of the combination of CHM and AEDs for IE were included. We defined monthly seizure frequency as the primary outcome. The secondary outcomes included the abnormal rate of electroencephalogram (EEG), seizure duration, quality of life (QoL), and adverse events (AEs).

Results: Twenty studies with 1,830 patients were enrolled. Most trials had poor methodological quality. The meta-analysis showed that the combination of CHM and AEDs was more efficient than AEDs alone in reducing monthly seizure frequency [MD = −1.26%, 95% CI (−1.62, −0.91); p < 0.00001], the abnormal rate of EEG [RR = 0.66%, 95% CI (0.53, 0.82); p = 0.0002], and improving the QoL [MD = 6.96%, 95% CI (3.44, 10.49); p = 0.0001]. There was no significant difference in seizure duration between groups. Moreover, the combination of CHM and AEDs significantly reduced the AEs [RR = 0.45%, 95% CI (0.32, 0.64); p < 0.00001].

Conclusion: The combination of CHM and AEDs could improve seizure control by reducing monthly seizure frequency and abnormal rate of EEG with a decreased risk of adverse events in patients with IE. However, these findings must be interpreted carefully due to the high or uncertain risk of bias in the included trials. To provide stronger evidence for the use of CHM combined with AEDs in IE, high-quality RCTs will be urgently warranted in the future.
Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
Authors: Rivara-Espasandín Martin , Palumbo Miranda Clara , Sosa Ezequiel J. , Radío Santiago , Turjanski Adrián G. , Sotelo-Silveira José , Fernandez Do Porto Dario , Smircich Pablo
Published: April 2023

Introduction:Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches.

Methods: In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development.

Results and Discussion: Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery.
The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus
Authors: Xie Long , Zhao Yu-Xin , Zheng Yu , Li Xiao-Fang
Published: April 2023

Chinese doctors widely prescribed Platycodon grandiflorus A. DC. (PG) to treat lung carbuncles in ancient China. Modern clinical experiences have demonstrated that PG plays a crucial role in treating chronic pharyngitis, plum pneumonia, pneumoconiosis, acute and chronic laryngitis, and so forth. Additionally, PG is a food with a long history in China, Japan, and Korea. Furthermore, Platycodin D (PLD), an oleanane-type triterpenoid saponin, is one of the active substances in PG. PLD has been revealed to have anti-inflammatory, anti-viral, anti-oxidation, anti-obesity, anticoagulant, spermicidal, anti-tumor etc., activities. And the mechanism of the effects draws lots of attention, with various signaling pathways involved in these processes. Additionally, research on PLD’s pharmacokinetics and extraction processes is under study. The bioavailability of PLD could be improved by being prescribed with Glycyrrhiza uralensis Fisch. or by creating a new dosage form. PLD has been recently considered to have the potential to be a solubilizer or an immunologic adjuvant. Meanwhile, PLD was discovered to have hemolytic activity correlated. PLD has broad application prospects and reveals practical pharmacological activities in pre-clinical research. The authors believe that these activities of PLD contribute to the efficacy of PG. What is apparent is that the clinical translation of PLD still has a long way to go. With the help of modern technology, the scope of clinical applications of PLD is probable to be expanded from traditional applications to new fields.
Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells
Authors: Mazurakova Alena , Koklesova Lenka , Vybohova Desanka , Samec Marek , Kudela Erik , Biringer Kamil , Šudomová Miroslava , Hassan Sherif T. S. , Kello Martin , Büsselberg Dietrich , Golubnitschaja Olga , Kubatka Peter
Published: April 2023

Significant limitations of the reactive medical approach in breast cancer management are clearly reflected by alarming statistics recorded worldwide. According to the WHO updates, breast malignancies become the leading cancer type. Further, the portion of premenopausal breast cancer cases is permanently increasing and demonstrates particularly aggressive patterns and poor outcomes exemplified by young patients with triple-negative breast cancer that lacks targeted therapy. Accumulating studies suggest the crucial role of stem cells in tumour biology, high metastatic activity, and therapy resistance of aggressive breast cancer. Therefore, targeting breast cancer stem cells is a promising treatment approach in secondary and tertiary breast cancer care. To this end, naturally occurring substances demonstrate high potential to target cancer stem cells which, however, require in-depth analysis to identify effective anti-cancer agents for cost-effective breast cancer management. The current article highlights the properties of flavonoids particularly relevant for targeting breast cancer stem cells to mitigate therapy resistance. The proposed approach is conformed with the principles of 3P medicine by applying predictive diagnostics, patient stratification and treatments tailored to the individualised patient profile. Expected impacts are very high, namely, to overcome limitations of reactive medical services improving individual outcomes and the healthcare economy in breast cancer management. Relevant clinical applications are exemplified in the paper.
2D, 3D-QSAR study and docking of vascular endothelial growth factor receptor 3 (VEGFR3) inhibitors for potential treatment of retinoblastoma
Authors: Ren Rui , Gao Liyu , Li Guoqi , Wang Shuqiang , Zhao Yangzhong , Wang Haitong , Liu Jianwei
Published: April 2023

Background: Retinoblastoma is currently the most common malignant tumor seen in newborns and children’s eyes worldwide, posing a life-threatening hazard. Chemotherapy is an integral part of retinoblastoma treatment. However, the chemotherapeutic agents used in clinics often lead to drug resistance. Thus there is a need to investigate new chemotherapy-targeted agents. VEGFR3 inhibitors are anti-tumour-growth and could be used to develop novel retinoblastoma-targeted agents.

Objective: To predict drug activity, discover influencing factors and design new drugs by building 2D, 3D-QSAR models.

Method: First, linear and non-linear QSAR models were built using heuristic methods and gene expression programming (GEP). The comparative molecular similarity indices analysis (COMISA) was then used to construct 3D-QSAR models through the SYBYL software. New drugs were designed by changing drug activity factors in both models, and molecular docking experiments were performed.

Result: The best linear model created using HM had an R2, S2, and R2cv of 0.82, 0.02, and 0.77, respectively. For the training and test sets, the best non-linear model created using GEP had correlation coefficients of 0.83 and 0.72 with mean errors of 0.02 and 0.04. The 3D model designed using SYBYL passed external validation due to its high Q2 (0.503), R2 (0.805), and F-value (76.52), as well as its low standard error of SEE value (0.172). This demonstrates the model’s reliability and excellent predictive ability. Based on the molecular descriptors of the 2D model and the contour plots of the 3D model, we designed 100 new compounds using the best active compound 14 as a template. We performed activity prediction and molecular docking experiments on them, in which compound 14.d performed best regarding combined drug activity and docking ability.

Conclusion: The non-linear model created using GEP was more stable and had a more substantial predictive power than the linear model built using the heuristic technique (HM). The compound 14.d designed in this experiment has the potential for anti-retinoblastoma treatment, which provides new design ideas and directions for retinoblastoma-targeted drugs.
Neurotrophic basis to the pathogenesis of depression and phytotherapy
Authors: Wang Huiqin , Yang Yantao , Pei Gang , Wang Zhenzhen , Chen Naihong
Published: April 2023

Depression is a major neuropsychiatric disease that considerably impacts individuals’ psychosocial function and life quality. Neurotrophic factors are now connected to the pathogenesis of depression, while the definitive neurotrophic basis remains elusive. Besides, phytotherapy is alternative to conventional antidepressants that may minimize undesirable adverse reactions. Thus, further research into the interaction between neurotrophic factors and depression and phytochemicals that repair neurotrophic factors deficit is highly required. This review highlighted the implication of neurotrophic factors in depression, with a focus on the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), and detailed the antidepressant activities of various phytochemicals targeting neurotrophic factors. Additionally, we presented future opportunities for novel diagnostic and therapeutic strategies for depression and provided solutions to challenges in this area to accelerate the clinical translation of neurotrophic factors for the treatment of depression.