bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe acute respiratory syndrome coronavirus 2 detection by real time polymerase chain reaction using pooling strategy of nasal samples
Authors: Pratelli Annamaria , Pellegrini Francesco , Ceci Luigi , Tatò Daniela , Lucente Maria Stella , Capozzi Loredana , Camero Michele , Buonavoglia Alessio
Published: July 2022

COVID-19 is a life-threatening multisistemic infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection control relies on timely identification and isolation of infected people who can alberg the virus for up to 14 days, providing important opportunities for undetected transmission. This note describes the application of rRT-PCR test for simpler, faster and less invasive monitoring of SARS-CoV-2 infection using pooling strategy of samples. Seventeen positive patients were provided with sterile dry swabs and asked to self-collected 2 nasal specimens (#NS1 and #NS2). The #NS1 was individually placed in a single tube and the #NS2 was placed in another tube together with 19 NSs collected from 19 negative patients. Both tubes were then tested with conventional molecular rRT-PCR and the strength of pooling nasal testing was compared with the molecular test performed on the single NS of each positive patient. The pooling strategy detected SARS-CoV-2 RNA to a similar extent to the single test, even when Ct value is on average high (Ct 37–38), confirming that test sensibility is not substantially affected even if the pool contains only one low viral load positive sample. Furthermore, the pooling strategy have benefits for SARS-CoV-2 routinary monitoring of groups in regions with a low SARS-CoV-2 prevalence.
Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease
Authors: Guo Mengyuan , Ji Xunming , Liu Jia
Published: July 2022

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, with typical motor symptoms as the main clinical manifestations. At present, there are about 10 million patients with PD in the world, and its comorbidities and complications are numerous and incurable. Therefore, it is particularly important to explore the pathogenesis of PD and find possible therapeutic targets. Because the etiology of PD is complex, involving genes, environment, and aging, finding common factors is the key to identifying intervention targets. Hypoxia is ubiquitous in the natural environment and disease states, and it is considered to be closely related to the etiology of PD. Despite research showing that hypoxia increases the expression and aggregation of alpha-synuclein (α-syn), the most important pathogenic protein, there is still a lack of systematic studies on the role of hypoxia in α-syn pathology and PD pathogenesis. Considering that hypoxia is inextricably linked with various causes of PD, hypoxia may be a co-participant in many aspects of the PD pathologic process. In this review, we describe the risk factors for PD, and we discuss the possible role of hypoxia in inducing PD pathology by these risk factors. Furthermore, we attribute the pathological changes caused by PD etiology to oxygen uptake disorder and oxygen utilization disorder, thus emphasizing the possibility of hypoxia as a critical link in initiating or promoting α-syn pathology and PD pathogenesis. Our study provides novel insight for exploring the pathogenesis and therapeutic targets of PD.
The relationship between Comprehensive Geriatric Assessment parameters and depression in elderly patients
Authors: Ju Yanmin , Liu Ting , Zhang Kexin , Lin Xiaoye , Zheng Enlai , Leng Jiyan
Published: July 2022

Background

Depression is common and serious among elderly patients. The treatment of elderly depression is often delayed owing to insufficient diagnosis, which eventually leads to adverse consequences.

Aims

To explore the association between the parameters of the Comprehensive Geriatric Assessment and depression in elderly patients.

Methods

A cross-sectional study of 211 outpatients and inpatients aged ≥ 65 years from the Comprehensive Geriatric Assessment database was conducted. A Comprehensive Geriatric Assessment inventory was prepared by compiling and screening general characteristics, chronic diseases (cardiovascular disease, diabetes, and peptic ulcer disease), nutritional status, daily living ability, anthropometric measurements (body mass index (BMI), upper arm circumference, and calf circumference), and blood biochemical indicators (hemoglobin, albumin, prealbumin, triglycerides, and low-density lipoprotein cholesterol). The Geriatric Depression Scale was also conducted for each elderly patient to screen for depression. A multivariable logistic regression analysis was used to determine the association between the parameters of the Comprehensive Geriatric Assessment and geriatric depression.

Results

There were 63 patients in the depression group with a median age of 84.00 years, and 148 patients in the non-depression group with a median age of 78.50 years. After controlling for confounders, the risk of depression in elderly patients with cardiovascular diseases was 6.011 times higher than that in those without cardiovascular diseases (p < 0.001); and the risk of depression in elderly patients with peptic ulcer diseases was 4.352 times higher than that in those without peptic ulcer diseases (p < 0.001); the risk of depression in elderly patients decreased by 22.6% for each 1-point increase in the Mini Nutritional Assessment (p < 0.001). The risk of depression in elderly patients decreased by 19.9% for each 1-point increase in calf circumference (p = 0.002), and by 13.0% for each 1-point increase in albumin (p = 0.014).

Conclusion

Our findings suggest that Comprehensive Geriatric Assessment parameters, such as cardiovascular disease, peptic ulcer disease, Mini Nutritional Assessment score, calf circumference, and albumin, were associated with depression. The Comprehensive Geriatric Assessment can assist in the early identification of depression in the elderly population.
Alteration of plasma metabolic profile and physical performance combined with metabolites is more sensitive to early screening for mild cognitive impairment
Authors: Zhao Yinjiao , Song Peiyu , Zhang Hui , Chen Xiaoyu , Han Peipei , Yu Xing , Fang Chenghu , Xie Fandi , Guo Qi
Published: July 2022

Objective

Unbiased metabolic profiling has been initiated to identify novel metabolites. However, it remains a challenge to define reliable biomarkers for rapid and accurate diagnosis of mild cognitive impairment (MCI). Our study aimed to evaluate the association of serum metabolites with MCI, attempting to find new biomarkers and combination models that are distinct for MCI.

Methods

A total of 380 participants were recruited (mean age: 72.5 ± 5.19 years). We performed an untargeted metabolomics analysis on older adults who underwent the Mini-Mental State Examination (MMSE), the Instrumental Activities of Daily Living (IADL), and physical performance tests such as hand grip, Timed Up and Go Test (TUGT), and walking speed. Orthogonal partial least squares discriminant analysis (OPLS-DA) and heat map were utilized to distinguish the metabolites that differ between groups.

Results

Among all the subjects, 47 subjects were diagnosed with MCI, and methods based on the propensity score are used to match the MCI group with the normal control (NC) group (n = 47). The final analytic sample comprised 94 participants (mean age: 75.2 years). The data process from the metabolic profiles identified 1,008 metabolites. A cluster and pathway enrichment analysis showed that sphingolipid metabolism is involved in the development of MCI. Combination of metabolite panel and physical performance were significantly increased discriminating abilities on MCI than a single physical performance test [model 1: the area under the curve (AUC) = 0.863; model 2: AUC = 0.886; and model 3: AUC = 0.870, P < 0.001].

Conclusion

In our study, untargeted metabolomics was used to detect the disturbance of metabolism that occurs in MCI. Physical performance tests combined with phosphatidylcholines (PCs) showed good utility in discriminating between NC and MCI, which is meaningful for the early diagnosis of MCI.
DMRT Transcription Factors in the Control of Nervous System Sexual Differentiation
Authors: Casado-Navarro Rafael , Serrano-Saiz Esther
Published: July 2022

Sexual phenotypic differences in the nervous system are one of the most prevalent features across the animal kingdom. The molecular mechanisms responsible for sexual dimorphism throughout metazoan nervous systems are extremely diverse, ranging from intrinsic cell autonomous mechanisms to gonad-dependent endocrine control of sexual traits, or even extrinsic environmental cues. In recent years, the DMRT ancient family of transcription factors has emerged as being central in the development of sex-specific differentiation in all animals in which they have been studied. In this review, we provide an overview of the function of Dmrt genes in nervous system sexual regulation from an evolutionary perspective.
Hypo-high density lipoproteinemia is a predictor for recurrent stroke during the long-term follow-up after revascularization in adult moyamoya disease
Authors: Yu Xiaofan , Ge Peicong , Zhai Yuanren , Wang Rong , Zhang Yan , Zhang Dong
Published: July 2022

Objective

Previous studies have reported that hypo-high-density lipoproteinemia (HHDL) was an independent risk factor for the cerebrovascular event. However, the risk of HHDL for stroke recurrence in moyamoya disease (MMD) during long-term follow-up after revascularization remains poorly understood. We aim to investigate the association between HHDL and stroke recurrence in adult patients with MMD.

Methods

A total of 138 adult patients with MMD were prospectively recruited from 1 July to 31 December 2019. After excluding 15 patients who did not meet the inclusion criteria, all the 123 patients were enrolled. Participants were grouped according to the stroke recurrence and HHDL presentation, respectively. Clinical data and laboratory examinations were compared by the statistical analysis. The Kaplan–Meier survival analysis was conducted to compare the stroke-free survival rates between participants with HHDL and those without. Univariate and multivariate logistic regression analyses were performed to identify independent factors of the neurological status. Univariate and multivariate Cox regression analyses were conducted to identify the predictors for the recurrent stroke.

Results

Participants with recurrent stroke group showed a lower level of high-density lipoprotein (HDL) (p = 0.030). More participants in the recurrent stroke group had HHDL (p = 0.045). What is more, there was statistical significance in the Kaplan–Meier curve of stroke incidence between the normal HDL group and the HHDL group (log-rank test, p = 0.034). Univariate logistic analysis results showed that HHDL (OR 0.916, 95% CI 0.237–3.543; p = 0.899) and HDL (OR 0.729, 95% CI 0.094–5.648; p = 0.763) were not predictive factors for the neurological status. In the multivariate Cox regression analysis, diabetes (HR 4.195, 95% CI 1.041–16.899; p = 0.044), HDL (HR 0.061, 95% CI 0.006–0.626; p = 0.019), and HHDL (HR 3.341, 95% CI 1.110–10.051; p = 0.032) were independent risk factors for the recurrent stroke.

Conclusions

Hypo-high-density lipoproteinemia might be a predictor or the potential therapeutic target for recurrent stroke during the long-term follow-up after revascularization in adult patients with MMD.
The Relationship Between Sleep, Cognition and Behavior in Children With Newly-Diagnosed Epilepsy Over 36 Months
Authors: Oyegbile-Chidi Temitayo , Harvey Danielle , Eisner Jordan , Dunn David , Jones Jana , Byars Anna , Hermann Bruce , Austin Joan
Published: July 2022

Introduction

There is substantial evidence that children with epilepsy experience more sleep, behavior and cognitive challenges than children without epilepsy. However, the literature is limited in describing the relationship between sleep, epilepsy, cognition and behavioral challenges and the interactions amongst these factors over time. This study aims to understand the nature and strength of the relationship between sleep, cognition, mood and behavior in children with new-onset epilepsy as assessed by multiple informants at multiple time periods using multiple different dependent measures.

Methods

332 participants (6–16years) were recruited within 6 weeks of their first recognized seizure. The comparison group was comprised of 266 healthy siblings. Participants underwent sleep evaluation by a parent using the Sleep Behavioral Questionnaire (SBQ), cognitive evaluation using a comprehensive neuropsychological test battery, a behavioral evaluation using the Child Behavior Checklist (CBCL from parents and TRF from teachers) and the Children's Depression Inventory (CDI). These evaluations were completed at baseline (B), at 18 months, and at 36 months.

Results

Compared to siblings, children with new-onset epilepsy had more sleep disturbance (SBQ), higher rates of behavioral problems (CBCL and TRF), lower cognitive testing scores, and higher rates of depression; which persisted over the 36-month study. Sleep significantly correlated with behavioral problems, cognitive scores and depression. When divided into categories based of sleep disturbance scores, 39.7% of children with epilepsy experienced “Persistently Abnormal Sleep”, while 14.8% experienced “Persistently Normal Sleep”. Children with persistently abnormal sleep experienced the highest rates of behavioral problems, depression and cognitive impairment compared to those with persistently normal sleep, regardless of epilepsy syndrome. Younger age of seizure onset, younger age at testing, and lower grade level at baseline were associated with persistently abnormal sleep.

Conclusions

To our knowledge, this is the first demonstration of the nature, strength, reliability, stability and persistence of the relationship between sleep, cognition, and behavioral problems over time in a large cohort of children with newly diagnosed epilepsy, as assessed by multiple informants at different timepoints. The results of this study indicate that children with epilepsy are at a high risk of significant persisting neurobehavioral multimorbidity. Therefore, early screening for these challenges may be essential for optimizing quality of life long-term.
Porphyromonas gingivalis: A key role in Parkinson's disease with cognitive impairment?
Authors: Li Dongcheng , Ren Tengzhu , Li Hao , Liao Geng , Zhang Xiong
Published: July 2022

Cognitive impairment (CI) is a common complication of Parkinson's disease (PD). The major features of Parkinson's disease with cognitive impairment (PD-CI) include convergence of α-Synuclein (α-Syn) and Alzheimer's disease (AD)-like pathologies, neuroinflammation, and dysbiosis of gut microbiota. Porphyromonas gingivalis (P. gingivalis) is an important pathogen in periodontitis. Recent research has suggested a role of P. gingivalis and its virulence factor in the pathogenesis of PD and AD, in particular concerning neuroinflammation and deposition of α-Synuclein (α-Syn) and amyloid-β (Aβ). Furthermore, in animal models, oral P. gingivalis could cause neurodegeneration through regulating the gut-brain axis, suggesting an oral-gut-brain axis might exist. In this article, we discussed the pathological characteristics of PD-CI and the role of P. gingivalis in them.
Case report and literature analysis: Autoimmune cerebellar ataxia associated with homer-3 antibodies
Authors: Wu Qisi , Gong Beibei , Jiang Anan , Qin Xinyue
Published: July 2022

Objective

We present a case of autoimmune cerebellar ataxia (ACA) associated with Homer protein homolog 3 (Homer-3) antibodies. Then, a review of the literature was conducted to summarize its clinical spectrum to improve clinicians' understanding of this rare entity.

Case presentation

A 25-year-old man suffered from the subacute onset of cerebellar ataxia and psychiatric symptoms with abnormalities in the cerebellum on initial brain MRI and Homer-3 antibodies titers of 1:100 in the serum. His neurological symptoms did not improve after intravenous methylprednisolone but significantly improved following plasma exchange with a modified Rankin Scale (mRS) score of 1. However, 5 months later, he experienced relapse during oral prednisone tapering with enhanced cerebellar lesions and obvious cerebellar atrophy on repeated MRI. Various immunomodulatory approaches, including corticosteroids and plasma exchange, were utilized with no improvement. Then rituximab was given for the first time to treat Homer-3 autoimmunity with partial improvement of symptoms. However, the patient remained profoundly disabled with an mRS score of 4.

Conclusion

ACA associated with Homer-3 antibodies may have a suboptimal response to corticosteroid therapy. More intense immunotherapy such as rituximab may contribute to the improvement of cerebellar syndrome. Relapsing courses and presentation of cerebellar atrophy may suggest a poor prognosis in this entity.
Decreased soluble Nogo-B in serum as a promising biomarker for Parkinson's disease
Authors: Liang Hongming , Guo Wenyuan , He Honghu , Zhang Hui , Ye Qiongyu , Zhang Qingxin , Liao Jiajia , Shen Yuefei , Wang Jin , Xiao Yousheng , Qin Chao
Published: July 2022

Background

Recently, the neurite outgrowth inhibitor-B (Nogo-B) receptor has been reported as a novel candidate gene for Parkinson's disease (PD). Nogo-B receptors need to combine with soluble Nogo-B to exert their physiological function. However, little is known about the relationship between serum soluble Nogo-B and PD.

Methods

Serum levels of sNogo-B and α-Synuclein (α-Syn) were measured in a cohort of 53 patients with PD and 49 healthy controls with the ELISA kit method.

Results

Serum sNogo-B level is significantly lower in the PD group than that in healthy controls and is negatively correlated with UPDRS-III score (p = 0.049), H&Y stage (p = 0.0108) as well as serum α-Syn level (p = 0.0001). The area under the curve (AUC) of serum sNogo-B in differentiating patients with PD from controls was 0.801 while the AUC of serum α-Syn was 0.93. Combining serum sNogo-B and α-Syn in differentiating patients with PD from HC presented higher discriminatory potential (AUC = 0.9534).

Conclusion

Decreased serum sNogo-B may be a potential biomarker for PD. Lower Nogo-B level reflects worse motor function and disease progression of PD. Serum sNogo-B is of added value to serum α-Syn panel in distinguishing PD from controls. Future studies are needed to confirm in larger samples and different populations.
Neurogenic Hypotension and Bradycardia Modulated by Electroacupuncture in Hypothalamic Paraventricular Nucleus
Authors: Tjen-A-Looi Stephanie C. , Fu Liang-Wu , Guo Zhi-Ling , Gong Yiwei D. , Nguyen Anh Thi Ngoc , Nguyen Ai-Thuan P. , Malik Shaista
Published: July 2022

Electroacupuncture (EA) stimulates somatic median afferents underlying P5-6 acupoints and modulates parasympathoexcitatory reflex responses through central processing in the brainstem. Although decreases in blood pressure and heart rate by the neural-mediated Bezold-Jarisch reflex responses are modulated by EA through opioid actions in the nucleus tractus solitarius and nucleus ambiguus, the role of the hypothalamus is unclear. The hypothalamic paraventricular nucleus (PVN) is activated by sympathetic afferents and regulates sympathetic outflow and sympathoexcitatory cardiovascular responses. In addition, the PVN is activated by vagal afferents, but little is known about its regulation of cardiopulmonary inhibitory hemodynamic responses. We hypothesized that the PVN participates in the Bezold-Jarisch reflex responses and EA inhibits these cardiopulmonary responses through the PVN opioid system. Rats were anesthetized and ventilated, and their heart rate and blood pressures were monitored. Application of phenylbiguanide every 10 min close to the right atrium induced consistent depressor and bradycardia reflex responses. Unilateral microinjection of the depolarization blockade agent kainic acid or glutamate receptor antagonist kynurenic acid in the PVN reduced these reflex responses. In at least 70% of the rats, 30 min of bilateral EA at P5-6 acupoints reduced the depressor and bradycardia responses for at least 60 min. Blockade of the CCK-1 receptors converted the non-responders into EA-responders. Unilateral PVN-microinjection with naloxone reversed the EA inhibition. Vagal-evoked activity of the PVN cardiovascular neurons was reduced by 30 min EA (P5-6) through opioid receptor activation. These data indicate that PVN processes inhibitory cardiopulmonary reflexes and participates in EA-modulation of the neural-mediated vasodepression and bradycardia.
Characteristics of prefrontal activity during emotional and cognitive processing in patients with bipolar disorder: A multi-channel functional near-infrared spectroscopy study
Authors: Mao Mengchai , Chen Guifang , Feng Kun , Xu Dongsheng , Hua Xuyun , Shan Chunlei , Liu Pozi
Published: July 2022

Bipolar disorder (BD) is a recurrent chronic mental disorder with a broad profile of functional deficits including disturbed emotional processing and cognitive impairments. The goal of the current study was to further explore the underlying neural mechanism of dysfunction in patients with BD from a comprehensive perspective of both cognition and emotion. Forty-six clinical patients with BD and forty-five healthy controls performed emotion induction task and verbal fluency task (VFT), with frontal activity measured by functional near-infrared spectroscopy (fNIRS). Our results show distinct hemodynamic activity in the prefrontal region during emotional and cognitive processing between patients with BD and healthy controls. Patients with BD exhibit valence-dependent prefrontal cortex (PFC) hemodynamic response to emotional stimuli, with bilateral frontal hypoactivity indicating decreased positive reactivity and left frontal hyperactivity indicating increased negative reactivity. On the other hand, patients with BD showed impaired performance with bilateral frontal hypoactivity during VFT. Taken together, frontal dysfunction of cognition and emotionality in patients with BD probed by fNIRS would be a potential biomarker in clinical assessment.
Advances in otolith-related protein research
Authors: Huang Shouju , Qian Shuxia
Published: July 2022

Otoliths are biological crystals formed by a layer of calcium carbonate crystal that adhere to the ciliary surface of the utricular and saccular receptors in the vestibule of all vertebrates inner ear, enabling the utricle and saccule to better perceive the changes in linear and gravitational acceleration. However, the molecular etiology of otolith related diseases is still unclear. In this review, we have summarized the recent findings and provided an overview of the proteins that play important roles in otolith formation and maintenance (Otoconin-90, Otolin-1, Otolith Matrix Protein-1, Cochlin, Otogelin, α-Tectorin, β-Tectorin, Otopetrin-1, and Otopetrin-2, PMCA2, etc.), providing new insight for the prevention and management of benign paroxysmal positional vertigo (BPPV) with basis for otolith-related proteins as potential biomarkers of vestibular disease.
Multi-person feature fusion transfer learning-based convolutional neural network for SSVEP-based collaborative BCI
Authors: Li Penghai , Su Jianxian , Belkacem Abdelkader Nasreddine , Cheng Longlong , Chen Chao
Published: July 2022

Objective

The conventional single-person brain–computer interface (BCI) systems have some intrinsic deficiencies such as low signal-to-noise ratio, distinct individual differences, and volatile experimental effect. To solve these problems, a centralized steady-state visually evoked potential collaborative BCI system (SSVEP-cBCI), which characterizes multi-person electroencephalography (EEG) feature fusion was constructed in this paper. Furthermore, three different feature fusion methods compatible with this new system were developed and applied to EEG classification, and a comparative analysis of their classification accuracy was performed with transfer learning-based convolutional neural network (TL-CNN) approach.

Approach

An EEG-based SSVEP-cBCI system was set up to merge different individuals’ EEG features stimulated by the instructions for the same task, and three feature fusion methods were adopted, namely parallel connection, serial connection, and multi-person averaging. The fused features were then input into CNN for classification. Additionally, transfer learning (TL) was applied first to a Tsinghua University (THU) benchmark dataset, and then to a collected dataset, so as to meet the CNN training requirement with a much smaller size of collected dataset and increase the classification accuracy. Ten subjects were recruited for data collection, and both datasets were used to gauge the three fusion algorithms’ performance.

Main results

The results predicted by TL-CNN approach in single-person mode and in multi-person mode with the three feature fusion methods were compared. The experimental results show that each multi-person mode is superior to single-person mode. Within the 3 s time window, the classification accuracy of the single-person CNN is only 90.6%, while the same measure of the two-person parallel connection fusion method can reach 96.6%, achieving better classification effect.

Significance

The results show that the three multi-person feature fusion methods and the deep learning classification algorithm based on TL-CNN can effectively improve the SSVEP-cBCI classification performance. The feature fusion method of multi -person parallel feature connection achieves better classification results. Different feature fusion methods can be selected in different application scenarios to further optimize cBCI.
RISC-y Business: Limitations of Short Hairpin RNA-Mediated Gene Silencing in the Brain and a Discussion of CRISPR/Cas-Based Alternatives
Authors: Goel Kanishk , Ploski Jonathan E.
Published: July 2022

Manipulating gene expression within and outside the nervous system is useful for interrogating gene function and developing therapeutic interventions for a variety of diseases. Several approaches exist which enable gene manipulation in preclinical models, and some of these have been approved to treat human diseases. For the last couple of decades, RNA interference (RNAi) has been a leading technique to knockdown (i.e., suppress) specific RNA expression. This has been partly due to the technology’s simplicity, which has promoted its adoption throughout biomedical science. However, accumulating evidence indicates that this technology can possess significant shortcomings. This review highlights the overwhelming evidence that RNAi can be prone to off-target effects and is capable of inducing cytotoxicity in some cases. With this in mind, we consider alternative CRISPR/Cas-based approaches, which may be safer and more reliable for gene knockdown. We also discuss the pros and cons of each approach.
Compound dietary fiber and high-grade protein diet improves glycemic control and ameliorates diabetes and its comorbidities through remodeling the gut microbiota in mice
Authors: Ni Yinhua , Zheng Aqian , Hu Yating , Rong Nianke , Zhang Qianpeng , Long Wenmin , Yang Song , Nan Sujie , Zhang Liqian , Zhou Kexin , Wu Tianxing , Fu Zhengwei
Published: July 2022

Dietary intervention with a low glycemic index and full nutritional support is emerging as an effective strategy for diabetes management. Here, we found that the treatment of a novel compound dietary fiber and high-grade protein diet (CFP) improved glycemic control and insulin resistance in streptozotocin-induced diabetic mice, with a similar effect to liraglutide. In addition, CFP treatment ameliorated diabetes-related metabolic syndromes, such as hyperlipidemia, hepatic lipid accumulation and adipogenesis, systemic inflammation, and diabetes-related kidney damage. These results were greatly associated with enhanced gut barrier function and altered gut microbiota composition and function, especially those bacteria, microbial functions, and metabolites related to amino acid metabolism. Importantly, no adverse effect of CFP was found in our study, and CFP exerted a wider arrange of protection against diabetes than liraglutide. Thereby, fortification with balanced dietary fiber and high-grade protein, like CFP, might be an effective strategy for the management and treatment of diabetes.
Double-dose icotinib may induce the emergence of the EGFR exon 20 T790M mutation in non-small cell lung cancer patients harboring EGFR-sensitive mutation
Authors: Chen Jianxin , Wu Xilin , Wang Junhui
Published: July 2022

Background

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) inevitably occurs in non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations. There are approximately half of the patients who developed resistance to EGFR-TKIs treatment, the mechanism of which remains undiscovered. We occasionally found that double-dose icotinib as further-line salvage treatment may induce the emerging mutation of EGFR exon 20 T790M in NSCLC patients. The present study, therefore, was conducted to explore the probability of the emerging T790M mutation after exposure to double-dose icotinib in metastatic NSCLC patients.

Patients and Methods

Metastatic NSCLC patients who received double-dose icotinib as salvage treatment after progression on first-generation TKIs and systematic chemotherapy were screened. Thereafter, patients who received a repeated next-generation sequencing (NGS) test with tumor sample were further enrolled. The procedure of NGS was performed with the standard criteria. Finally, the clinical characteristics, treatment procedures, and outcomes of eligible patients were reviewed and presented.

Results

Three patients have been detected with the emerging T790M mutation after double-dose icotinib exposure, with a mutation frequency of 19.6%, 8.2%, and 87.5%. During the treatment of targetable TKIs including almonertinib or osimertinib, partial response was observed in two patients, and stable disease was observed in the other. The progression-free survival by targetable TKIs for the patients was 3.7+ months (still in extension), 4.9+ months (still in extension), and 6.3 months. Manageable adverse events were observed during the treatment of TKIs.

Conclusion

The results of the present study revealed that the emerging EGFR exon 20 T790M mutation might be induced by double-dose icotinib exposure in further-line treatment. Patients with the emerging T790M mutation responded well to the treatment of targetable TKIs including almonertinib or osimertinib.
NUT Carcinoma—An Underdiagnosed Malignancy
Authors: Lauer Ulrich M. , Hinterleitner Martina , Horger Marius , Ohnesorge Paul V. , Zender Lars
Published: July 2022

NUT carcinoma (NC) is a rare and highly aggressive malignancy with a dismal prognosis and a median survival of 6–9 months only. Although very few cases of NC are reported each year, the true prevalence is estimated to be much higher, with NC potentially widely underdiagnosed due to the lack of awareness. NC primarily occurs in midline structures including thorax, head, and neck; however, other sites such as pancreas and kidney are also affected, albeit at lower frequencies. NC is characterized by a single translocation involving the NUTM1 (NUT midline carcinoma family member 1) gene and different partner genes. The resulting fusion proteins initiate tumorigenesis through a mechanism involving BET (bromo-domain and extra-terminal motif) proteins such as Bromodomain-containing protein 4 (BRD4) and inordinate acetylation of chromatin, leading to the dysregulation of growth and differentiation genes. While no clinical characteristics are specific for NC, some histologic features can be indicative; therefore, patients with these tumor characteristics should be routinely tested for NUTM1. The diagnosis of NC using immunohistochemistry with a highly specific antibody is straightforward. There are currently no standard-of-care treatment options for patients with NC. However, novel therapies specifically addressing the unique tumorigenic mechanism are under investigation, including BET inhibitors. This review aims to raise awareness of this underdiagnosed cancer entity and provide all patients the opportunity to be properly diagnosed and referred to a clinical study.
Partial Nephrectomy Versus Radical Nephrectomy for Endophytic Renal Tumors: Comparison of Operative, Functional, and Oncological Outcomes by Propensity Score Matching Analysis
Authors: Xiong Situ , Jiang Ming , Jiang Yi , Hu Bing , Chen Ru , Yao Zhijun , Deng Wen , Wan Xianwen , Liu Xiaoqiang , Chen Luyao , Fu Bin
Published: July 2022

Purpose

The study aimed to compare operative, functional, and oncological outcomes between partial nephrectomy (PN) and radical nephrectomy (RN) for entophytic renal tumors (ERTs) by propensity score matching (PSM) analysis.

Methods

A total of 228 patients with ERTs who underwent PN or RN between August 2014 and December 2021 were assessed. A PSM in a 1:1 ratio was conducted to balance the differences between groups. Perioperative characteristics, renal functional, and oncological outcomes were compared between groups. Univariate and multivariate logistic and Cox proportional hazard regression analyses were used to determine the predictors of functional and survival outcomes.

Results

After PSM, 136 cases were matched to the PN group (n = 68) and the RN group (n = 68). Patients who underwent RN had shorter OT, less EBL, and lower high-grade complications (all p <0.05) relative to those who underwent PN. However, better perseveration of renal function was observed in the PN group, which was reflected in 48-h postoperative AKI (44.1% vs. 70.6%, p = 0.002), 1-year postoperative 90% eGFR preservation (45.6% vs. 22.1%, p = 0.004), and new-onset CKD Stage ≥III at last follow-up (2.9% vs. 29.4%, p <0.001). RN was the independent factor of short-term (OR, 2.812; 95% CI, 1.369–5.778; p = 0.005) and long-term renal function decline (OR, 10.242; 95% CI, 2.175–48.240; p = 0.003). Furthermore, PN resulted in a better OS and similar PFS and CSS as compared to RN (p = 0.042, 0.15, and 0.21, respectively). RN (OR, 7.361; 95% CI, 1.143–47.423; p = 0.036) and pT3 stage (OR, 4.241; 95% CI, 1.079–16.664; p = 0.039) were independent predictors of overall mortality.

Conclusion

Among patients with ERTs, although the PN group showed a higher incidence of high-grade complications than RN, when technically feasible and with experienced surgeons, PN is recommended for better preservation of renal function, longer OS, and similar oncological outcomes.
CEMIP Promotes Osteosarcoma Progression and Metastasis Through Activating Notch Signaling Pathway
Authors: Cheng Jun , Zhang Yan , Wan Rongjun , Zhou Jun , Wu Xin , Fan Qizhi , He Jingpeng , Tan Wei , Deng Youwen
Published: July 2022

Cell migration inducing protein (CEMIP) has been linked to carcinogenesis in several types of cancers. However, the role and mechanism of CEMIP in osteosarcoma remain unclear. This study investigated the role of CEMIP in the progression and metastasis of osteosarcoma, CEMIP was found to be overexpressed in osteosarcoma tissues when compared to adjacent non-tumor tissues, and its expression was positively associated with a poor prognosis in osteosarcoma patients. Silencing CEMIP decreased osteosarcoma cells proliferation, migration, and invasion, but enhanced apoptosis in vitro, and suppressed tumor growth and metastasis in vivo. Mechanistically, CEMIP promoted osteosarcoma cells growth and metastasis through activating Notch signaling pathway, silencing CEMIP would reduce the protein expression and activation of Notch/Jagged1/Hes1 signaling pathway in vitro and in vivo, activation of Notch signaling pathway could partially reversed cell proliferation and migration in shCEMIP osteosarcoma cells. In conclusion, our study demonstrated that CEMIP plays a substantial role in the progression of osteosarcoma via Notch signaling pathway, providing a promising therapeutic target in osteosarcoma.
Patient-derived rectal cancer organoids—applications in basic and translational cancer research
Authors: Yan Yumeng , Cheong Io Hong , Chen Peizhan , Li Xiaoguang , Wang Xianli , Wang Hui
Published: July 2022

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and among the leading causes of death in both men and women. Rectal cancer (RC) is particularly challenging compared with colon cancer as the treatment after diagnosis of RC is more complex on account of its narrow anatomical location in the pelvis adjacent to the urogenital organs. More and more existing studies have begun to refine the research on RC and colon cancer separately. Early diagnosis and multiple treatment strategies optimize outcomes for individual patients. However, the need for more accurate and precise models to facilitate RC research is underscored due to the heterogeneity of clinical response and morbidity interrelated with radical surgery. Organoids generated from biopsies of patients have developed as powerful models to recapitulate many aspects of their primary tissue, consisting of 3-D self-organizing structures, which shed great light on the applications in both biomedical and clinical research. As the preclinical research models for RC are usually confused with colon cancer, research on patient-derived RC organoid models enable personalized analysis of cancer pathobiology, organizational function, and tumor initiation and progression. In this review, we discuss the various applications of patient-derived RC organoids over the past two years in basic cancer biology and clinical translation, including sequencing analysis, drug screening, precision therapy practice, tumor microenvironment studies, and genetic engineering opportunities.
Phyllanthus emblica aqueous extract retards hepatic steatosis and fibrosis in NAFLD mice in association with the reshaping of intestinal microecology
Authors: Luo Xiaomin , Zhang Boyu , Pan Yehua , Gu Jian , Tan Rui , Gong Puyang
Published: July 2022

Accumulating evidence suggests that dysregulation of the intestinal flora potentially contributes to the occurrence and development of nonalcoholic fatty liver disease (NAFLD). Phyllanthus emblica (PE), an edible and medicinal natural resource, exerts excellent effects on ameliorating NAFLD, but the potential mechanism remains unclear. In the present study, a mouse NAFLD model was established by administering a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). The protective effects of the aqueous extract of PE (AEPE) on the gut microbiota and fecal metabolites in NAFLD mice were detected by performing 16S rRNA gene sequencing and untargeted metabolomics. The administration of middle- and high-dose AEPE decreased the levels of ALT, AST, LDL-C, TG, and Hyp and increased HDL-C levels in CDAHFD-fed mice. Hematoxylin–eosin (H&E), Oil Red O, and Masson’s trichrome staining indicated that AEPE treatment attenuated hepatic steatosis and fibrotic lesions. Moreover, the disordered intestinal microflora was remodeled by AEPE, including decreases in the abundance of Peptostreptococcaceae, Faecalibaculum, and Romboutsia. The untargeted metabolomics analysis showed that AEPE restored the disturbed glutathione metabolism, tryptophan metabolism, taurine and hypotaurine metabolism, and primary bile acid biosynthesis of the gut bacterial community in NAFLD mice, which strongly correlated with hepatic steatosis and fibrosis. Collectively, AEPE potentially ameliorates NAFLD induced by a CDAHFD through a mechanism associated with its modulatory effects on the gut microbiota and microbial metabolism.
GABA Receptor Agonists Protect From Excitotoxic Damage Induced by AMPA in Oligodendrocytes
Authors: Bayón-Cordero Laura , Ochoa-Bueno Blanca Isabel , Ruiz Asier , Ozalla Marina , Matute Carlos , Sánchez-Gómez María Victoria
Published: July 2022

Oligodendrocytes are the myelin forming cells of the central nervous system, and their vulnerability to excitotoxicity induced by glutamate contributes to the pathogenesis of neurological disorders including brain ischemia and neurodegenerative diseases, such as multiple sclerosis. In addition to glutamate receptors, oligodendrocytes express GABA receptors (GABAR) that are involved in their survival and differentiation. The interactions between glutamate and GABAergic systems are well documented in neurons, under both physiological and pathological conditions, but this potential crosstalk in oligodendrocytes has not been studied in depth. Here, we evaluated the protective effect of GABAR agonists, baclofen (GABAB) and muscimol (GABAA), against AMPA-induced excitotoxicity in cultured rat oligodendrocytes. First, we observed that both baclofen and muscimol reduced cell death and caspase-3 activation after AMPA insult, proving their oligoprotective potential. Interestingly, analysis of the cell-surface expression of calcium-impermeable GluR2 subunits in oligodendrocytes revealed that GABAergic agonists significantly reverted GluR2 internalization induced by AMPA. We determined that baclofen and muscimol also impaired AMPA-induced intracellular calcium increase and subsequent mitochondrial membrane potential alteration, ROS generation, and calpain activation. However, AMPA-triggered activation of Src, Akt, JNK and CREB was not affected by baclofen or muscimol. Overall, our results suggest that GABAR activation initiates alternative molecular mechanisms that attenuate AMPA-mediated apoptotic excitotoxicity in oligodendrocytes by interfering with expression of GluR subunits in membranes and with calcium-dependent intracellular signaling pathways. Together, these findings provide evidence of GABAR agonists as potential oligodendroglial protectants in central nervous system disorders.
Simulating Microswimmers Under Confinement With Dissipative Particle (Hydro) Dynamics
Authors: Barriuso Gutiérrez C. Miguel , Martín-Roca José , Bianco Valentino , Pagonabarraga Ignacio , Valeriani Chantal
Published: July 2022

In this work we study microwimmers, whether colloids or polymers, embedded in bulk or in confinement. We explicitly consider hydrodynamic interactions and simulate the swimmers via an implementation inspired by the squirmer model. Concerning the surrounding fluid, we employ a Dissipative Particle Dynamics scheme. Differently from the Lattice-Boltzmann technique, on the one side this approach allows us to properly deal not only with hydrodynamics but also with thermal fluctuations. On the other side, this approach enables us to study microwimmers with complex shapes, ranging from spherical colloids to polymers. To start with, we study a simple spherical colloid. We analyze the features of the velocity fields of the surrounding solvent, when the colloid is a pusher, a puller or a neutral swimmer either in bulk or confined in a cylindrical channel. Next, we characterise its dynamical behaviour by computing the mean square displacement and the long time diffusion when the active colloid is in bulk or in a channel (varying its radius) and analyze the orientation autocorrelation function in the latter case. While the three studied squirmer types are characterised by the same bulk diffusion, the cylindrical confinement considerably modulates the diffusion and the orientation autocorrelation function. Finally, we focus our attention on a more complex shape: an active polymer. We first characterise the structural features computing its radius of gyration when in bulk or in cylindrical confinement, and compare to known results obtained without hydrodynamics. Next, we characterise the dynamical behaviour of the active polymer by computing its mean square displacement and the long time diffusion. On the one hand, both diffusion and radius of gyration decrease due to the hydrodynamic interaction when the system is in bulk. On the other hand, the effect of confinement is to decrease the radius of gyration, disturbing the motion of the polymer and thus reducing its diffusion.
Boundaries control active channel flows
Authors: Gulati Paarth , Shankar Suraj , Marchetti M. Cristina
Published: July 2022

Boundary conditions dictate how fluids, including liquid crystals, flow when pumped through a channel. Can boundary conditions also be used to control internally driven active fluids that generate flows spontaneously? By using numerical simulations and stability analysis we explore how parallel surface anchoring of active agents at the boundaries and substrate drag can be used to rectify coherent flow of an active polar fluid in a 2D channel. Upon increasing activity, a succession of dynamical states is obtained, from laminar flow to vortex arrays to eventual turbulence, that are controlled by the interplay between the hydrodynamic screening length and the extrapolation length quantifying the anchoring strength of the orientational order parameter. We highlight the key role of symmetry in both flow and order and show that coherent laminar flow with net throughput is only possible for weak anchoring and intermediate activity. Our work demonstrates the possibility of controlling the nature and properties of active flows in a channel simply by patterning the confining boundaries.
Exogenous Gamma-Aminobutyric Acid Application Induced Modulations in the Performance of Aromatic Rice Under Lead Toxicity
Authors: Ashraf Umair , Mahmood Sammina , Anjum Shakeel Ahmad , Abbas Rana Nadeem , Rasul Fahd , Iqbal Javed , Mo Zhaowen , Tang Xiangru
Published: July 2022

Gamma-aminobutyric acid (GABA) is a non-protein amino acid and has a multi-functional role in abiotic stress tolerance. A pot experiment was conducted to assess the role of exogenous gamma-aminobutyric acid (GABA) application to modulate the growth, yield, and related physio-biochemical mechanisms in two aromatic rice cultivars, that is, Guixiangzhan (GXZ) and Nongxiang 18 (NX-18), under Pb toxic and normal conditions. The experimental treatments were comprised of Ck: without Pb and GABA (control), GABA: 1 mM GABA is applied under normal conditions (without Pb), Pb + GABA: 1 mM GABA is applied under Pb toxicity (800 mg kg−1 of soil), and Pb= only Pb (800 mg kg−1 of soil) is applied (no GABA). The required concentrations of GABA were applied as a foliar spray. Results revealed that Pb stress induced oxidative damage in terms of enhanced malondialdehyde (MDA), electrolyte leakage (EL), and H2O2 contents, while exogenous GABA application improved leaf chlorophyll, proline, protein and GABA contents, photosynthesis and gas exchange, and antioxidant defense under Pb toxicity in both rice cultivars. Moreover, glutamine synthetase (GS) and nitrate reductase (NR) activities were variably affected due to GABA application under Pb stress. The yield and related traits, that is, productive tillers/pot, grains/panicle, filled grain %, 1,000-grain weight, and grain yield were 13.64 and 10.29, 0.37% and 2.26%, 3.89 and 19.06%, 7.35 and 12.84%, and 17.92 and 40.56 lower under Pb treatment than Pb + GABA for GXZ and NX-18, respectively. Furthermore, exogenous GABA application in rice reduced Pb contents in shoot, leaves, panicle, and grains compared with Pb-exposed plants without GABA. Overall, GXZ performed better than NX-18 under Pb toxic conditions.