bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the effectiveness and safety of Dinoprostone vaginal insert and double-balloon catheter as cervical ripening treatments in Chinese patients
Authors: Yan Jinjing , Yin Baomin , Lv Hanghang
Published: September 2022

Background

This retrospective study was to compare the effectiveness and safety of Dinoprostone vaginal insert vs. double-balloon catheter as cervical ripening agents for labor induction.

Methods

Pregnant women with Bishop score <7, who received either Dinoprostone vaginal insert 10 mg or Cook's double-balloon catheter for labor induction, were studied. The primary outcome was the rate of vaginal delivery within 48 h; the secondary outcomes were the proportion of women undergoing cesarean section, labor duration, oxytocin administration, changes in Bishop score, complications during labor, and maternal/neonatal outcomes.

Results

One hundred and eighty-two women were included in Dinoprostone group, and 199 women were in double-balloon catheter group. The rate of vaginal delivery within 48 h was significantly higher in Dinoprostone group than that in double-balloon catheter group (90.11% vs. 75.38%, P = 0.0002). There were 18 cesarean section deliveries (9.89%) in Dinoprostone group and 49 cesarean section deliveries (24.62%) in double-balloon catheter group, with significant differences between two groups (P = 0.0002). The duration of labor was higher in Dinoprostone group, while the augmentation with oxytocin was significantly lower in Dinoprostone group than in double-balloon catheter group (all P < 0.0001). The incidence of chorioamnionitis was significantly higher in double-balloon catheter group as compared with Dinoprostone group (0 vs. 12, P = 0.0005), while neonatal outcomes were similar in two groups.

Conclusion

Dinoprostone vaginal insert as cervical ripening agent is more effective for labor induction and with lower risks of chorioamnionitis as compared with double balloon catheter in Chinese populations.
Point-of-care ultrasound of peripheral nerves in the diagnosis of Hansen's disease neuropathy
Authors: Voltan Glauber , Filho Fred Bernards , Leite Marcel Nani , De Paula Natália Aparecida , Santana Jaci Maria , Silva Claudia Maria Lincoln , Barreto Josafá Gonçalves , Da Silva Moises Batista , Conde Guilherme , Salgado Claudio Guedes , Frade Marco Andrey Cipriani
Published: September 2022

Introduction

Hansen's disease (HD) is the most common cause of treatable peripheral neuropathy in the world that may or may not involve skin manifestations, and physical examination based on simplified neurologic evaluation is a subjective and inaccurate procedure. High-resolution ultrasound (HRUS) can be used to evaluate peripheral nerves and is a validated technique of good reproducibility, permitting a detailed and precise examination.

Objectives

We proposed to establish objective criteria for absolute values of the measurement of the CSA of peripheral nerves and their indices of the ΔCSA and ΔTpT in the diagnosis of Hansen's disease neuropathy as compared with healthy voluntaries.

Materials and methods

In municipalities from different regions of Brazil, we randomly selected 234 volunteer Brazilian patients diagnosed with leprosy to be submitted to peripheral nerve echography and compared with 49 healthy Brazilian volunteers.

Results

Hansen Disease assessed by high resolution ultrasound is a primarily neural disease that leads to multiple hypertrophic mononeuropathy characterized by CSA values exceeding normal limits (Med CT = 10.2 mm2; UT = 9.8 mm2; UPT = 9.3 mm2; CFFH = 18.3 mm2; T = 9.6 mm2), and the pattern of asymmetry (ΔCSA>2.5 mm2with RR 13) and focality (ΔTPT > 2.5 mm2with RR 6.4) of this thickening has higher sensitivity (76,1%) and specificity (87,8 %) for its early diagnosis that laboratory tests. Analyzing each subject, the percentage of thickened nerves detected among the total number of nerves assessed was higher among patients with HD than among healthy individuals (p< 0.0001). Individuals with two or more thickened nerves were at 24.1 times higher relative risk (95% CI: 6.74–88.98) of HD.
Clinical utility of target amplicon sequencing test for rapid diagnosis of drug-resistant Mycobacterium tuberculosis from respiratory specimens
Authors: Leung Kenneth Siu-Sing , Tam Kingsley King-Gee , Ng Timothy Ting-Leung , Lao Hiu-Yin , Shek Raymond Chiu-Man , Ma Oliver Chiu Kit , Yu Shi-Hui , Chen Jing-Xian , Han Qi , Siu Gilman Kit-Hang , Yam Wing-Cheong
Published: September 2022

An in-house-developed target amplicon sequencing by next-generation sequencing technology (TB-NGS) enables simultaneous detection of resistance-related mutations in Mycobacterium tuberculosis (MTB) against 8 anti-tuberculosis drug classes. In this multi-center study, we investigated the clinical utility of incorporating TB-NGS for rapid drug-resistant MTB detection in high endemic regions in southeast China. From January 2018 to November 2019, 4,047 respiratory specimens were available from patients suffering lower respiratory tract infections in Hong Kong and Guangzhou, among which 501 were TB-positive as detected by in-house IS6110-qPCR assay with diagnostic sensitivity and specificity of 97.9 and 99.2%, respectively. Preliminary resistance screening by GenoType MTBDRplus and MTBDRsl identified 25 drug-resistant specimens including 10 multidrug-resistant TB. TB-NGS was performed using MiSeq on all drug-resistant specimens alongside 67 pan-susceptible specimens, and demonstrated 100% concordance to phenotypic drug susceptibility test. All phenotypically resistant specimens with dominating resistance-related mutations exhibited a mutation frequency of over 60%. Three quasispecies were identified with mutation frequency of less than 35% among phenotypically susceptible specimens. They were well distinguished from phenotypically resistant cases and thus would not complicate TB-NGS results interpretations. This is the first large-scale study that explored the use of laboratory-developed NGS platforms for rapid TB diagnosis. By incorporating TB-NGS with our proposed diagnostic algorithm, the workflow would provide a user-friendly, cost-effective routine diagnostic solution for complicated TB cases with an average turnaround time of 6 working days. This is critical for timely management of drug resistant TB patients and expediting public health control on the emergence of drug-resistant TB.
Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B
Authors: Yang Jiajia , Gu Juan , Wang Hongmei , Shi Jiayin , Lu Lingyun , She Wanxian , Wang Ying
Published: September 2022

Objective: To investigate the associations of Fc receptor-like 5 (FCRL5) gene polymorphisms and mRNA expression with liver fibrosis in chronic hepatitis B (CHB).

Methods: A total of 114 CHB patients with liver fibrosis and 120 CHB patients without liver fibrosis were selected for this study. The gender, age, body mass index (BMI), alanine transaminase (ALT) value, aspartate aminotransferase (AST) value, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) were recorded. Two polymorphisms of the FCRL5 gene (rs6427384 and rs6692977) were genotyped. The mRNA expression level of FCRL5 in peripheral blood monocytes was determined.

Results: ALT, AST, APRI, and FIB-4 in patients with fibrosis were significantly higher than those in non-fibrosis patients. There was statistically significant difference between fibrosis and non-fibrosis groups in the genotype distribution (χ2 = 7.805, p = 0.020) and allele frequencies (χ2 = 13.252, p < 0.001) at FCRL5 rs6692977. When compared with CC genotype, the genotype CT or TT at rs6692977 was significantly associated with a increased risk of liver fibrosis in CHB patients (CT vs. CC: OR = 1.921, 95% CI = 1.093–3.375, p = 0.023; TT vs. CC: OR = 2.598, 95% CI = 1.067–6.324, p = 0.031). The mRNA relative expression levels of FCRL5 in patients with liver fibrosis were significantly higher than those in the non-fibrosis group (t = 13.456, p < 0.001). The fibrosis patients carried TT or CT genotype of rs6692977 had significantly higher FCRL5 mRNA expression levels than those carried CC genotype (t = 2.859, p = 0.005). The mRNA expression levels of FCRL5, APRI, and FIB-4 index showed predictive efficacy in liver fibrosis with cut-off values of 0.75 (AUC = 0.896, 95% CI = 0.856–0.935), 0.45 (AUC = 0.852, 95% CI = 0.802–0.902) and 1.84 (AUC = 0.765, 95% CI = 0.703–0.826), respectively.

Conclusion: FCRL5 gene rs6692977 polymorphisms and mRNA expression levels are associated with liver fibrosis in CHB patients.
Risk of dementia or cognitive impairment in COPD patients: A meta-analysis of cohort studies
Authors: Wang Jun , Li Xuanlin , Lei Siyuan , Zhang Dong , Zhang Shujuan , Zhang Hailong , Li Jiansheng
Published: September 2022

Purpose

A meta-analysis of cohort studies was performed to evaluate the association between COPD and the risk of dementia or cognitive impairment.

Methods

Cohort studies that evaluated the association between COPD and the risk of dementia or cognitive impairment were identified by a systematic search of PubMed, Embase, Web of Science, and Cochrane Library databases. The search time frame was from database establishment to April 12, 2022, with two reviewers independently screening the literature and extracting data. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to conduct the quality evaluation. Then, a meta-analysis was performed using Stata 15.1 software.

Results

Six cohort studies including 428,030 participants were included. The overall quality of the included studies was high, with an average NOS score of over 7. Meta-analysis showed that compared to those without COPD at baseline, patients with COPD were associated with a significant increased risk of dementia (RR = 1.24, 95% CI = 1.03 ~ 1.50, I2 = 96.6%, z = 2.25, p = 0.024) and cognitive impairment (RR = 1.30, 95% CI = 1.13 ~ 1.49, I2 = 50.1%, z = 3.72, p < 0.001). Subgroup analysis suggested no significant difference in the risk of dementia among COPD patients of different genders. Nevertheless, in terms of age, the risk of dementia varied among COPD patients of different ages, which was most distinguished in patients younger than 65 years.

Conclusion

COPD patients have a higher risk of developing dementia or cognitive impairment compared to those without COPD, and this risk is not affected by gender but seems to be associated with age.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022325832.
Hypothalamic orexinergic neuron changes during the hibernation of the Syrian hamster
Authors: López Jesús M. , Carballeira Paula , Pozo Javier , León-Espinosa Gonzalo , Muñoz Alberto
Published: September 2022

Hibernation in small mammals is a highly regulated process with periods of torpor involving drops in body temperature and metabolic rate, as well as a general decrease in neural activity, all of which proceed alongside complex brain adaptive changes that appear to protect the brain from extreme hypoxia and low temperatures. All these changes are rapidly reversed, with no apparent brain damage occurring, during the short periods of arousal, interspersed during torpor—characterized by transitory and partial rewarming and activity, including sleep activation, and feeding in some species. The orexins are neuropeptides synthesized in hypothalamic neurons that project to multiple brain regions and are known to participate in the regulation of a variety of processes including feeding behavior, the sleep-wake cycle, and autonomic functions such as brown adipose tissue thermogenesis. Using multiple immunohistochemical techniques and quantitative analysis, we have characterized the orexinergic system in the brain of the Syrian hamster—a facultative hibernator. Our results revealed that orexinergic neurons in this species consisted of a neuronal population restricted to the lateral hypothalamic area, whereas orexinergic fibers distribute throughout the rostrocaudal extent of the brain, particularly innervating catecholaminergic and serotonergic neuronal populations. We characterized the changes of orexinergic cells in the different phases of hibernation based on the intensity of immunostaining for the neuronal activity marker C-Fos and orexin A (OXA). During torpor, we found an increase in C-Fos immunostaining intensity in orexinergic neurons, accompanied by a decrease in OXA immunostaining. These changes were accompanied by a volume reduction and a fragmentation of the Golgi apparatus (GA) as well as a decrease in the colocalization of OXA and the GA marker GM-130. Importantly, during arousal, C-Fos and OXA expression in orexinergic neurons was highest and the structural appearance and the volume of the GA along with the colocalization of OXA/GM-130 reverted to euthermic levels. We discuss the involvement of orexinergic cells in the regulation of mammalian hibernation and, in particular, the possibility that the high activation of orexinergic cells during the arousal stage guides the rewarming as well as the feeding and sleep behaviors characteristic of this phase.
Brain-wide neuronal activation and functional connectivity are modulated by prior exposure to repetitive learning episodes
Authors: Terstege Dylan J. , Durante Isabella M. , Epp Jonathan R.
Published: September 2022

Memory storage and retrieval are shaped by past experiences. Prior learning and memory episodes have numerous impacts on brain structure from micro to macroscale. Previous experience with specific forms of learning increases the efficiency of future learning. It is less clear whether such practice effects on one type of memory might also have transferable effects to other forms of memory. Different forms of learning and memory rely on different brain-wide networks but there are many points of overlap in these networks. Enhanced structural or functional connectivity caused by one type of learning may be transferable to another type of learning due to overlap in underlying memory networks. Here, we investigated the impact of prior chronic spatial training on the task-specific functional connectivity related to subsequent contextual fear memory recall in mice. Our results show that mice exposed to prior spatial training exhibited decreased brain-wide activation compared to control mice during the retrieval of a context fear memory. With respect to functional connectivity, we observed changes in several network measures, notably an increase in global efficiency. Interestingly, we also observed an increase in network resilience based on simulated targeted node deletion. Overall, this study suggests that chronic learning has transferable effects on the functional connectivity networks of other types of learning and memory. The generalized enhancements in network efficiency and resilience suggest that learning itself may protect brain networks against deterioration.
Safety and effects of transcranial direct current stimulation on hand function in preschool children with hemiplegic cerebral palsy: A pilot study
Authors: He Wenjie , Huang Yuan , He Lu , Liu Liru , Zeng Peishan , Qiu Huiying , Wang Xiaoyue , Zhou Hongyu , Chen Zhaofang , Xu Yi , Zhao Jingyi , Wang Wenda , Tang Hongmei , Xu Kaishou
Published: September 2022

Transcranial direct current stimulation (tDCS) has shown a promising prospect in improving function and spasticity in school-aged children with cerebral palsy, but little is known in preschool children. The aim of this study was to explore the safety and effects of tDCS on hand function in preschool children (aged 3–6 years) with hemiplegic cerebral palsy (HCP). We designed a crossover, single-blind, sham-controlled study in 30 preschool children with HCP, who were recruited to receive one session of sham and one session of active anodal tDCS (1.5 mA, 20 min) on the primary motor cortex of the affected hemisphere, with a 24-h interval between the two sessions. Questionnaire was completed by each participant and their attendants immediately, 90 min, and 24 h after each session to monitor common adverse events of tDCS, such as skin irritation, skin erythema, burning sensation, headache, dizziness, etc. Box and Block Test, Selective Control of the Upper Extremity Scale, Modified Ashworth Scale, and Melbourne Assessment 2 were conducted at baseline, immediately, and 90 min after each session. No severe adverse event occurred during the study and only a few of them felt transient and slight discomfort. Results also showed that all participants performed better at Box and Block Test of the hemiplegic hand immediately after a single anodal tDCS (P < 0.05) and this improvement lasted at least 90 min and more than 24 h. However, there was no significant improvement in Selective Control of the Upper Extremity Scale of both hands, Box and Block Test of the non-hemiplegic hand, Modified Ashworth Scale, and Melbourne Assessment 2 of the hemiplegic upper limb (P > 0.05). Shortly, this study supported the safety and effects of a single anodal tDCS on improving the manual dexterity of the hemiplegic hand for preschool children with HCP. Further researches with larger samples about the optimal dose and treatment cycle of tDCS for preschool children with HCP are warranted. This study gained the approval of ethics committee of the organization and was registered at chictr.org (ChiCTR2000031141).
Voluntary wheel-running activities ameliorate depressive-like behaviors in mouse dry eye models
Authors: Nakano Katsuya , Nakazawa Hitomi , He Qiang , Uwada Junsuke , Kiyoi Takeshi , Ishibashi Takaharu , Masuoka Takayoshi
Published: September 2022

Recent clinical studies indicate that dry eye is closely associated with psychiatric disorders such as depression and anxiety. Here, we investigated whether two types of mouse dry eye models showed depressive-like behavior in forced swim and sucrose preference tests, and whether voluntary wheel-running helped ameliorate depressive states. To reproduce the dry eye models, the exorbital lacrimal glands (ELG) or exorbital and intraorbital lacrimal glands (ELG+ILG) were bilaterally excised from male C57BL/6J mice. Tear volume was persistently reduced in both models, but the ELG+ILG excision mice exhibited more severe corneal damage than the ELG excision mice. In the forced swim and sucrose preference tests, the gland excision mice showed longer immobility and shorter climbing times, and lower sucrose preference than sham-operated mice, respectively, which appeared earlier in the ELG+ILG excision mice. Wheel-running activities were significantly lower in the ELG+ILG excision mice, but not in the ELG excision mice. After short-period wheel-running, the longer immobility times and the shorter climbing times in the forced swim completely disappeared in both models. Our results suggest that dry eyes might directly cause a depressive disorder that depends on the severity and duration of the ocular surface damage, and that voluntary motor activity could help recovery from a depressive state induced by dry eye.
Projective quasi-synchronization of coupled memristive neural networks with uncertainties and impulsive effect
Authors: Yuan Manman , Luo Xiong , Hu Jun , Wang Songxin
Published: September 2022

The dynamic behavior of memristive neural networks (MNNs), including synchronization, effectively keeps the robotic stability against numerous uncertainties from the mimic of the human brain. However, it is challenging to perform projective quasi-synchronization of coupled MNNs with low-consumer control devices. This is partly because complete synchronization is difficult to realize under various projective factors and parameter mismatch. This article aims to investigate projective quasi-synchronization from the perspective of the controller. Here, two approaches are considered to find the event-triggered scheme for lag synchronization of coupled MNNs. In the first approach, the projective quasi-synchronization issue is formulated for coupled MNNs for the first time, where the networks are combined with time-varying delays and uncertainties under the constraints imposed by the frequency of controller updates within limited system communication resources. It is shown that our methods can avoid the Zeno-behavior under the newly determined triggered functions. In the second approach, following classical methods, a novel projective quasi-synchronization criterion that combines the nonlinear property of the memristor and the framework of Lyapunov-Krasovskii functional (LKF) is proposed. Simulation results indicate that the proposed two approaches are useful for coupled MNNs, and they have less control cost for different types of quasi-synchronization.
Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy
Authors: Qi Zhongbing , Long Xiangyu , Liu Jiyan , Cheng Ping
Published: September 2022

Glioblastoma (GBM), a highly aggressive form of brain tumor, responds poorly to current conventional therapies, including surgery, radiation therapy, and systemic chemotherapy. The reason is that the delicate location of the primary tumor and the existence of the blood-brain barrier limit the effectiveness of traditional local and systemic therapies. The immunosuppressive status and multiple carcinogenic pathways in the complex GBM microenvironment also pose challenges for immunotherapy and single-targeted therapy. With an improving understanding of the GBM microenvironment, it has become possible to consider the immunosuppressive and highly angiogenic GBM microenvironment as an excellent opportunity to improve the existing therapeutic efficacy. Oncolytic virus therapy can exert antitumor effects on various components of the GBM microenvironment. In this review, we have focused on the current status of oncolytic virus therapy for GBM and the related literature on antitumor mechanisms. Moreover, the limitations of oncolytic virus therapy as a monotherapy and future directions that may enhance the field have also been discussed.
A multi-head self-attention deep learning approach for detection and recommendation of neuromagnetic high frequency oscillations in epilepsy
Authors: Zhao Xiangyu , Peng Xueping , Niu Ke , Li Hailong , He Lili , Yang Feng , Wu Ting , Chen Duo , Zhang Qiusi , Ouyang Menglin , Guo Jiayang , Pan Yijie
Published: September 2022

Magnetoencephalography is a noninvasive neuromagnetic technology to record epileptic activities for the pre-operative localization of epileptogenic zones, which has received increasing attention in the diagnosis and surgery of epilepsy. As reported by recent studies, pathological high frequency oscillations (HFOs), when utilized as a biomarker to localize the epileptogenic zones, result in a significant reduction in seizure frequency, even seizure elimination in around 80% of cases. Thus, objective, rapid, and automatic detection and recommendation of HFOs are highly desirable for clinicians to alleviate the burden of reviewing a large amount of MEG data from a given patient. Despite the advantage, the performance of existing HFOs rarely satisfies the clinical requirement. Consequently, no HFOs have been successfully applied to real clinical applications so far. In this work, we propose a multi-head self-attention-based detector for recommendation, termed MSADR, to detect and recommend HFO signals. Taking advantage of the state-of-the-art multi-head self-attention mechanism in deep learning, the proposed MSADR achieves a more superior accuracy of 88.6% than peer machine learning models in both detection and recommendation tasks. In addition, the robustness of MSADR is also extensively assessed with various ablation tests, results of which further demonstrate the effectiveness and generalizability of the proposed approach.
Brain functional connectivity analysis in patients with relapsing-remitting multiple sclerosis: A graph theory approach of EEG resting state
Authors: Shirani Sepehr , Mohebbi Maryam
Published: September 2022

Multiple sclerosis (MS) is an autoimmune disease related to the central nervous system (CNS). This study aims to investigate the effects of MS on the brain's functional connectivity network using the electroencephalogram (EEG) resting-state signals and graph theory approach. Resting-state eyes-closed EEG signals were recorded from 20 patients with relapsing-remitting MS (RRMS) and 18 healthy cases. In this study, the prime objective is to calculate the connectivity between EEG channels to assess the differences in brain functional network global features. The results demonstrated lower cortical activity in the alpha frequency bands and higher activity for the gamma frequency bands in patients with RRMS compared to the healthy group. In this study, graph metric calculations revealed a significant difference in the diameter of the functional brain network based on the directed transfer function (DTF) measure between the two groups, indicating a higher diameter in RRMS cases for the alpha frequency band. A higher diameter for the functional brain network in MS cases can result from anatomical damage. In addition, considerable differences between the networks' global efficiency and transitivity based on the imaginary part of the coherence (iCoh) measure were observed, indicating higher global efficiency and transitivity in the delta, theta, and beta frequency bands for RRMS cases, which can be related to the compensatory functional reaction from the brain. This study indicated that in RRMS cases, some of the global characteristics of the brain's functional network, such as diameter and global efficiency, change and can be illustrated even in the resting-state condition when the brain is not under cognitive load.
Case report: A variant of wall-eyed bilateral internuclear ophthalmoplegia from unilateral pons infarction
Authors: Wang Tingting , Cao Duanhua , Han Jingzhe
Published: September 2022

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is an uncommon ocular motility disorder that encompasses the following clinical signs: bilateral adduction deficits, bilateral abducting nystagmus, convergence lost, and a large angle exotropia in primary gaze. Here we report a case of a 55-year-old man presenting with atypical WEBINO syndrome with unilateral exotropia. The coverage test was used to record the patient's alternating exotropia. The patient experienced diplopia and ophthalmoplegia and was admitted to our hospital 3 days after the onset of the double vision. Neurologic examination showed left eye exotropia and bilateral internuclear ophthalmoplegia with impaired convergence. Vertical saccades of the left eye were also limited. Consequently, an MRI scan suggested an acute infarction in the left of the pontine tegmentum. The patient was finally diagnosed with pons infarction and was treated with anticoagulation and anti-platelet aggregation therapy.
White matter alterations in pediatric brainstem glioma: An national brain tumor registry of China study
Authors: Zhang Peng , Gu Guocan , Duan Yunyun , Zhuo Zhizheng , Pan Changcun , Zuo Pengcheng , Wang Yi , Li Xiaoou , Jiang Zhuang , Qu Liying , Liu Yaou , Zhang Liwei
Published: September 2022

Background

Previous studies have identified alterations in structural connectivity of patients with glioma. However, white matter (WM) integrity measured by diffusion kurtosis imaging (DKI) in pediatric patients with brainstem glioma (BSG) was lack of study. Here, the alterations in WM of patients with BSG were assessed through DKI analyses.

Materials and methods

This study involved 100 patients with BSG from the National Brain Tumor Registry of China (NBTRC) and 50 age- and sex-matched healthy controls from social recruitment. WM tracts were segmented and reconstructed using U-Net and probabilistic bundle-specific tracking. Next, automatic fiber quantitative (AFQ) analyses of WM tracts were performed using tractometry module embedded in TractSeg.

Results

WM quantitative analysis identified alterations in DKI-derived values in patients with BSG compared with healthy controls. WM abnormalities were detected in the projection fibers involved in the brainstem, including corticospinal tract (CST), superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP) and inferior cerebellar peduncle (ICP). Significant WM alterations were also identified in commissural fibers and association fibers, which were away from tumor location. Statistical analyses indicated the severity of WM abnormality was statistically correlated with the preoperative Karnofsky Performance Scale (KPS) and symptom duration of patients respectively.

Conclusion

The results of this study indicated the widely distributed WM alterations in patients with BSG. DKI-derived quantitative assessment may provide additional information and insight into comprehensively understanding the neuropathological mechanisms of brainstem glioma.
WIPI proteins: Biological functions and related syndromes
Authors: Almannai Mohammed , Marafi Dana , El-Hattab Ayman W.
Published: September 2022

WIPI (WD-repeat protein Interacting with PhosphoInositides) are important effectors in autophagy. These proteins bind phosphoinositides and recruit autophagy proteins. In mammals, there are four WIPI proteins: WIPI1, WIPI2, WIPI3 (WDR45B), and WIPI4 (WDR45). These proteins consist of a seven-bladed β-propeller structure. Recently, pathogenic variants in genes encoding these proteins have been recognized to cause human diseases with a predominant neurological phenotype. Defects in WIPI2 cause a disease characterized mainly by intellectual disability and variable other features while pathogenic variants in WDR45B and WDR45 have been recently reported to cause El-Hattab-Alkuraya syndrome and beta-propeller protein-associated neurodegeneration (BPAN), respectively. Whereas, there is no disease linked to WIPI1 yet, one study linked it neural tube defects (NTD). In this review, the role of WIPI proteins in autophagy is discussed first, then syndromes related to these proteins are summarized.
Precision machine learning to understand micro-RNA regulation in neurodegenerative diseases
Authors: Mégret Lucile , Mendoza Cloé , Arrieta Lobo Maialen , Brouillet Emmanuel , Nguyen Thi-Thanh-Yen , Bouaziz Olivier , Chambaz Antoine , Néri Christian
Published: September 2022

Micro-RNAs (miRNAs) are short (∼21 nt) non-coding RNAs that regulate gene expression through the degradation or translational repression of mRNAs. Accumulating evidence points to a role of miRNA regulation in the pathogenesis of a wide range of neurodegenerative (ND) diseases such as, for example, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and Huntington disease (HD). Several systems level studies aimed to explore the role of miRNA regulation in NDs, but these studies remain challenging. Part of the problem may be related to the lack of sufficiently rich or homogeneous data, such as time series or cell-type-specific data obtained in model systems or human biosamples, to account for context dependency. Part of the problem may also be related to the methodological challenges associated with the accurate system-level modeling of miRNA and mRNA data. Here, we critically review the main families of machine learning methods used to analyze expression data, highlighting the added value of using shape-analysis concepts as a solution for precisely modeling highly dimensional miRNA and mRNA data such as the ones obtained in the study of the HD process, and elaborating on the potential of these concepts and methods for modeling complex omics data.
Extraction, purification, structure, modification, and biological activity of traditional Chinese medicine polysaccharides: A review
Authors: Xue Hongkun , Li Pengcheng , Bian Jiayue , Gao Yuchao , Sang Yumei , Tan Jiaqi
Published: September 2022

Traditional Chinese medicines (TCM), as the unique natural resource, are rich in polysaccharides, polyphenols, proteins, amino acid, fats, vitamins, and other components. Hence, TCM have high medical and nutritional values. Polysaccharides are one of the most important active components in TCM. Growing reports have indicated that TCM polysaccharides (TCMPs) have various biological activities, such as antioxidant, anti-aging, immunomodulatory, hypoglycemic, hypolipidemic, anti-tumor, anti-inflammatory, and other activities. Hence, the research progresses and future prospects of TCMPs must be systematically reviewed to promote their better understanding. The aim of this review is to provide comprehensive and systematic recombinant information on the extraction, purification, structure, chemical modification, biological activities, and potential mechanism of TCMPs to support their therapeutic effects and health functions. The findings provide new valuable insights and theoretical basis for future research and development of TCMPs.
Neutrophilia and post-radiation thrombocytopenia predict for poor prognosis in radiation-treated glioma patients
Authors: Hsu Eric J. , Thomas Jamie , Maher Elizabeth A. , Youssef Michael , Timmerman Robert D. , Wardak Zabi , Lee Minjae , Dan Tu D. , Patel Toral R. , Vo Dat T.
Published: September 2022

Introduction

Poor outcomes in glioma patients indicate a need to determine prognostic indicators of survival to better guide patient specific treatment options. While preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been suggested as prognostic systemic inflammation markers, the impact of post-radiation changes in these cell types is unclear. We sought to identify which hematologic cell measurements before, during, or after radiation predicted for patient survival.

Methods

A cohort of 182 patients with pathologically confirmed gliomas treated at our institution was retrospectively reviewed. Patient blood samples were collected within one month before, during, or within 3 months after radiation for quantification of hematologic cell counts, for which failure patterns were evaluated. Multivariable cox proportional hazards analysis for overall survival (OS) and progression-free survival (PFS) was performed to control for patient variables.

Results

Multivariable analysis identified pre-radiation NLR > 4.0 (Hazard ratio = 1.847, p = 0.0039) and neutrophilia prior to (Hazard ratio = 1.706, p = 0.0185), during (Hazard ratio = 1.641, p = 0.0277), or after (Hazard ratio = 1.517, p = 0.0879) radiation as significant predictors of worse OS, with similar results for PFS. Post-radiation PLR > 200 (Hazard ratio = 0.587, p = 0.0062) and a percent increase in platelets after radiation (Hazard ratio = 0.387, p = 0.0077) were also associated with improved OS. Patients receiving more than 15 fractions of radiation exhibited greater post-radiation decreases in neutrophil and platelet counts than those receiving fewer. Patients receiving dexamethasone during radiation exhibited greater increases in neutrophil counts than those not receiving steroids. Lymphopenia, changes in lymphocyte counts, monocytosis, MLR, and changes in monocyte counts did not impact patient survival.

Conclusion

Neutrophilia at any time interval surrounding radiotherapy, pre-radiation NLR, and post-radiation thrombocytopenia, but not lymphocytes or monocytes, are predictors of poor patient survival in glioma patients.
Controversial topics in metastatic HR+/HER2- breast cancer: Guiding treatment by a modified Delphi approach
Authors: Fabi Alessandra , Buono Giuseppe , Bria Emilio , Bianchini Giampaolo , Curigliano Giuseppe , De Laurentiis Michelino , De Placido Sabino , Del Mastro Lucia , Guarneri Valentina , Generali Daniele , Livi Lorenzo , Lorusso Vito , Montemurro Filippo , Puglisi Fabio , Vigneri Paolo , Zambelli Alberto , Arpino Grazia
Published: September 2022

The treatment of HR+/HER2- metastatic breast cancer with cyclin-dependent kinases 4 and 6 inhibitors combined with endocrine therapy has recently emerged as the most relevant therapeutic strategy. However, in routine clinical practice, the best therapeutic approach in patients with comorbidities at early relapsing or ab initio metastatic disease, PI3KCA mutation, is still debated among oncologists. Given these areas of uncertainty, we conducted a Delphi survey to describe and confront the level of agreement or disagreement between clinicians working in referral vs local spoke oncological hospitals and summarize a consensus on these debated topics. In total, 56 items were drafted using the Nominal Group Technique and used for the Delphi Survey. A total of 46 clinicians participated in the survey. Overall, the consensus threshold among all participants was reached in 46/56 items (82%), and Delphi Survey results showed a high level of consensus. For the 10 items (18%) that did not reach the consensus threshold, possible explanations considering differences in clinical practice and recent findings from literature are provided in the Discussion. Outcomes from the present survey may help guide treatment in multiple comorbidities, early recurring and ab initio metastatic disease, and PI3KCA mutation, where evidence from randomized trials and level 1 evidence is currently missing.
Broad genomic workup including optical genome mapping uncovers a DDX3X: MLLT10 gene fusion in acute myeloid leukemia
Authors: Nilius-Eliliwi Verena , Tembrink Marco , Gerding Wanda Maria , Lubieniecki Krzystof P. , Lubieniecka Joanna M. , Kankel Stefanie , Liehr Thomas , Mika Thomas , Dimopoulos Fotios , Döhner Konstanze , Schroers Roland , Nguyen Hoa Huu Phuc , Vangala Deepak Ben
Published: September 2022

In acute myeloid leukemia (AML), treatment decisions are currently made according to the risk classification of the European LeukemiaNet (ELN), which is based on genetic alterations. Recently, optical genome mapping (OGM) as a novel method proved to yield a genome-wide and detailed cytogenetic characterization at the time of diagnosis. A young female patient suffered from a rather unexpected aggressive disease course under FLT3 targeted therapy in combination with induction chemotherapy. By applying a “next-generation diagnostic workup“ strategy with OGM and whole-exome sequencing (WES), a DDX3X: MLLT10 gene fusion could be detected, otherwise missed by routine diagnostics. Furthermore, several aspects of lineage ambiguity not shown by standard diagnostics were unraveled such as deletions of SUZ12 and ARPP21, as well as T-cell receptor recombination. In summary, the detection of this particular gene fusion DDX3X: MLLT10 in a female AML patient and the findings of lineage ambiguity are potential explanations for the aggressive course of disease. Our study demonstrates that OGM can yield novel clinically significant results, including additional information helpful in disease monitoring and disease biology.
Pathogenesis of central nervous system germ cell tumors
Authors: Liu Siyuan , Ren Linan , Gao Xue , Hao Mengjin , Wang Guixia
Published: September 2022

Intracranial germ cell tumors (IGCTs) are clinically rare. They are more common in children and adolescents and the incidence in Asia is higher than in Western countries. Histologically, IGCTs are divided into germinoma and non-germinomatous germ cell tumor (NGGCT). Germinoma is sensitive to radiotherapy and chemotherapy and therefore, patients with germinoma have a good prognosis. However, NGGCTs, especially those with malignant components, are not sensitive to radiotherapy and chemoradiotherapy, leading to a poor prognosis. The pathogenesis of IGCTs is not fully understood. By summarizing previous literature, we found that the occurrence of IGCTs may be related to the following factors: chromosomal instability, MAPK and/or PI3K pathway changes, and DNA hypomethylation in pure germ cell tumors.
Normal ranges of non-invasive left ventricular myocardial work indices in healthy young people
Authors: Luo Xiuxia , Ge Quanrong , Su Jin , Zhou Ning , Li Ping , Xiao Xu , Chen Yan , Wang Dong , Ma Yujing , Ma Li , Zhu Yongsheng
Published: September 2022

Objectives

Echocardiographic global myocardial work (GMW) indices recently emerged to non-invasively evaluate left ventricular (LV) myocardial performance with less load-dependence than LV ejection fraction (LVEF) or global longitudinal strain (GLS). Yet, few data exist on the descriptions of LV GMW indices in young people. We therefore aimed to provide normal reference values of LV GMW in a healthy young cohort, and simultaneously to investigate factors associated with non-invasive GMW indices.

Materials and methods

A total of 155 healthy young people (age 10–24 years, 59% male) underwent transthoracic echocardiography were recruited and further stratified for age groups and divided by gender. Two-dimensional speckle-tracking echocardiography (2D-STE) were performed to determine LV GLS, peak strain dispersion (PSD) and GMW indices, which include global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). LV peak systolic pressure was assumed to be equal to the systolic brachial artery cuff blood pressure.

Results

Age and gender specific normal ranges for LV GMW indices were presented. On multivariable analysis, GWI and GCW correlated more closely with systolic blood pressure (SBP) than LV GLS, while both GWW and GWE independently correlated with PSD (P < 0.05 for all). There were no associations between any of the GMW indices with age, sex, body mass index, heart rate, left ventricular mass index as well as LV sizes or LVEF. Of noted, LV GMW indices had good intra-observer and inter-observer reproducibility.

Conclusion

We reported echocardiographic reference ranges for non-invasive LV GMW indices in a large group of healthy young subjects, which are reproducible and reliable, and thus can be further used when assessing subclinical dysfunction in young people with myocardial diseases.
Building research capacity for sickle cell disease in Africa: Lessons and challenges from establishing a birth cohort in Tanzania
Authors: Nkya Siana , Njiro Belinda J. , Ngowi Doreen , Solomon David , Kaywanger Frida , Nyangasa Salama , Ndoje Godfrey , Marco Emmanuela , Moses Mazoea , Makani Julie
Published: September 2022

Sickle Cell Disease (SCD) is a known public health burden in sub-Saharan Africa (SSA). The manifestation of SCD starts in early childhood and if not well-managed may lead to early death (before the age of 5 years). Understanding the underlying mechanisms that influence early SCD manifestation is of great importance for early disease and intervention management which will in turn, reduce both morbidity and mortality rates in children. One approach of achieving this is by establishing SCD birth cohorts that can be followed for a period of time (3–5 years) whilst documenting necessary information related to early childhood illnesses. To date, there are few SCD birth cohorts in Africa. To address this gap, we have established a birth cohort of babies with and without SCD (with sickle cell trait and healthy babies). These babies are followed up for 3 years with their study visits synchronized to the immunization schedule. During enrollment and follow-up visits, information on demographic, clinical, and laboratory parameters are collected. To date, we have enrolled a total of 341 babies with and without SCD. Out of these, a total of 311, 186, 133, 81, 44, and 16 babies have returned for their 1st, 2nd, 3rd, 4th, 5th, and 6th visits, respectively. We have collected both demographic and clinical information for these babies at enrollment and during follow-up. We have also utilized this platform to learn on the best approaches of establishing and maintaining a research birth cohort in an African context. We have analyzed the practical issues pertaining to the integration of the birth cohort with the immunization platform which seems to be the most effective and sustainable strategy for maintaining a birth cohort in our context.
Macrophage-targeted nanomedicine for the diagnosis and management of atherosclerosis
Authors: Hu Ping Ping , Luo Shuang Xue , Fan Xiao Qing , Li Di , Tong Xiao Yong
Published: September 2022

Atherosclerosis is the primary cause of cardiovascular diseases, such as myocardial infarction and stroke, which account for the highest death toll worldwide. Macrophage is the major contributor to atherosclerosis progression, and therefore, macrophage-associated pathological process is considered an extremely important target for the diagnosis and treatment of atherosclerosis. However, the existing clinical strategies still have many bottlenecks and challenges in atherosclerosis’s early detection and management. Nanomedicine, using various nanoparticles/nanocarriers for medical purposes, can effectively load therapeutic agents, significantly improve their stability and accurately deliver them to the atherosclerotic plaques. In this review, we summarized the latest progress of the macrophage-targeted nanomedicine in the diagnosis and treatment of atherosclerosis, and their potential applications and clinical benefits are also discussed.
The cardioprotective effects and mechanisms of naringenin in myocardial ischemia based on network pharmacology and experiment verification
Authors: Yang Yakun , Qi Jiaying , Zhang Muqing , Chen Pingping , Liu Yanshuang , Sun Xiaorun , Chu Li
Published: September 2022

Naringenin (Nar) is a natural flavonoid extracted from citrus fruits with abundant pharmacological properties against cardiac diseases, but existing studies are unsystematic and scattered. The present research systematically investigates the mechanism of action of Nar in the treatment of myocardial ischemia (MI). Network pharmacology was used to analyze the relevant targets of Nar against MI as well as the biological mechanisms. The protective effect of Nar was initially assessed in H9c2 cells induced by CoCl2. In acutely isolated rat cardiomyocytes, Nar was further explored for effects on L-type Ca2+ currents, cell contractility and Ca2+ transients by using patch-clamp technique and Ion Optix system. Network pharmacology analysis indicated that Nar improved apoptosis, mitochondrial energy metabolism, inflammation and oxidative stress. Experimental validation demonstrated that Nar decreased ROS and MDA levels and increased antioxidant activity (e.g., GSH-PX, SOD, and CAT), mitochondrial membrane potential, ATP and Ca2+-ATPase contents. Nar also markedly reduced inflammatory factor levels, apoptosis, and intracellular Ca2+ concentrations in H9c2 cells. Based on the experimental results, it is speculated that Ca2+ signals play an essential role in the process of Nar against MI. Thus, we further confirmed that Nar significantly inhibited the L-type Ca2+ currents, contractility and Ca2+ transients in acutely isolated cardiomyocytes. The inhibition of Ca2+ overload by Nar may be a novel cardioprotective mechanism. The present study may serve as a basis for future clinical research, and Nar as a Ca2+ channel inhibitor may provide new perspectives for the treatment of myocardial ischemic diseases.