bluuebunny/crossref_metadata_2025 huggingface dataset:
Unfolding a sequence of sensory influences and interactions in the development of functional brain laterality
Authors: Rogers Lesley J.
Published: January 2023

Evidence of sensory experience influencing the development of lateralized brain and behavior is reviewed. The epigenetic role of light exposure during two specific stages of embryonic development of precocial avian species is a particular focus of the research discussed. Two specific periods of light sensitivity (in early versus late incubation), each depending on different subcellular and cellular processes, affect lateralized behavior after hatching. Auditory and olfactory stimulation during embryonic development is also discussed with consideration of interactions with light-generated visual lateralization.
The landscape of disparities in obstetric neurocritical care and a path forward
Authors: Mittal Shilipi , Alsbrook Diana , Okwechime Remi T. , Iqbal Farhana , Nobleza Christa O'Hana S.
Published: January 2023

Health disparities in the obstetric population affect maternal morbidity and mortality. In the past years, there has been no significant improvement in disparities in care in the obstetric population. Patients who are pregnant are known to have a higher risk of pregnancy-associated neurologic conditions such as stroke and intracerebral hemorrhage. They can also experience concomitant neurocritical care disease states such as status epilepticus and traumatic brain injury. Studies exploring the disparities of care among pregnant patients who are neurotically ill are lacking. We aim to provide the landscape of disparities of care among the obstetric neurocritically-ill population and provide potential actionable opportunities to address these disparities in care.
Autonomic dysfunction in epilepsy mouse models with implications for SUDEP research
Authors: Bauer Jennifer , Devinsky Orrin , Rothermel Markus , Koch Henner
Published: January 2023

Epilepsy has a high prevalence and can severely impair quality of life and increase the risk of premature death. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in drug-resistant epilepsy and most often results from respiratory and cardiac impairments due to brainstem dysfunction. Epileptic activity can spread widely, influencing neuronal activity in regions outside the epileptic network. The brainstem controls cardiorespiratory activity and arousal and reciprocally connects to cortical, diencephalic, and spinal cord areas. Epileptic activity can propagate trans-synaptically or via spreading depression (SD) to alter brainstem functions and cause cardiorespiratory dysfunction. The mechanisms by which seizures propagate to or otherwise impair brainstem function and trigger the cascading effects that cause SUDEP are poorly understood. We review insights from mouse models combined with new techniques to understand the pathophysiology of epilepsy and SUDEP. These techniques include in vivo, ex vivo, invasive and non-invasive methods in anesthetized and awake mice. Optogenetics combined with electrophysiological and optical manipulation and recording methods offer unique opportunities to study neuronal mechanisms under normal conditions, during and after non-fatal seizures, and in SUDEP. These combined approaches can advance our understanding of brainstem pathophysiology associated with seizures and SUDEP and may suggest strategies to prevent SUDEP.
Diagnostic performance of preoperative ultrasound for traumatic brachial plexus root injury: A comparison study with an electrophysiology study
Authors: Liu Ailin , Jia Xiaotian , Zhang Li , Huang Xiaoyun , Chen Weimin , Chen Lin
Published: January 2023

Purpose

Accurate preoperative assessment for traumatic brachial plexus injury (BPI) is critical for clinicians to establish a treatment plan. The objective of this study was to investigate the diagnostic performance of preoperative ultrasound (US) through comparison with an electrophysiology study (EPS) in the assessment of traumatic brachial plexus (BP) root injury.

Materials and methods

We performed a retrospective study in patients with traumatic BPI who had preoperative US and EPS, excluding obstetric palsy and other nontraumatic neuropathies. US examination was performed on an EPIQ 5 color Doppler equipment. EPS was performed on a Keypoint 9033A07 Electromyograph/Evoked Potentials Equipment, testing electromyography (EMG), nerve conduction studies (NCS), and somatosensory evoked potentials (SEP). Each BP root of all patients was assessed by US and EPS as completely injured or incompletely injured, respectively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated based on the correlation with intraoperative findings. The accuracy of US and EPS were compared using the McNemar test. The added benefit of US was evaluated by comparing the sensitivity and specificity between the combined tests with EPS using the McNemar test.

Results

This study included 49 patients with traumatic BPI who underwent BP surgeries from October 2018 to September 2022. Surgical exploration confirmed 89 completely injured BP roots in 28 patients. US correctly detected 80 completely injured BP roots (sensitivity, 0.899; specificity, 0.981; PPV, 0.964; NPV, 0.944; accuracy, 0.951). EPS correctly detected 75 completely injured BP roots (sensitivity, 0.843; specificity, 0.929; PPV, 0.872; NPV, 0.912; accuracy, 0.898). US showed significantly higher accuracy than EPS (p = 0.03). When combining US and EPS for completely injured BP root detection, the sensitivity of the inclusive combination (0.966) was significantly higher than EPS alone (p = 0.000977), and the specificity of the exclusive combination (1.000) was significantly higher than EPS alone (p = 0.000977).

Conclusion

Preoperative US is an effective diagnostic tool in the assessment of traumatic BP root injury. US had higher accuracy than EPS in this study. Sensitivity and specificity were significantly higher than EPS when US was combined with EPS.
Altered spontaneous brain activity during dobutamine challenge in healthy young adults: A resting-state functional magnetic resonance imaging study
Authors: Liu Yawen , Niu Haijun , Zhang Tingting , Cai Linkun , Liu Dong , Zhao Erwei , Zhu Liang , Qiao PengGang , Zheng Wei , Ren Pengling , Wang Zhenchang
Published: January 2023

Introduction

There is a growing interest in exploring brain-heart interactions. However, few studies have investigated the brain-heart interactions in healthy populations, especially in healthy young adults. The aim of this study was to explore the association between cardiovascular and spontaneous brain activities during dobutamine infusion in healthy young adults.

Methods

Forty-eight right-handed healthy participants (43 males and 5 females, range: 22–34 years) underwent vital signs monitoring, cognitive function assessment and brain MRI scans. Cardiovascular function was evaluated using blood pressure and heart rate, while two resting-state functional magnetic resonance imaging (rs-fMRI) methods—regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF)—were used together to reflect the local neural activity of the brain. Logistic regression was used to model the association between brain and heart.

Results

Results showed that blood pressure and heart rate significantly increased after dobutamine infusion, and the performance in brain functional activity was the decrease in ReHo in the left gyrus rectus and in ALFF in the left frontal superior orbital. The results of logistic regression showed that the difference of diastolic blood pressure (DBP) had significant positive relationship with the degree of change of ReHo, while the difference of systolic blood pressure (SBP) had significant negative impact on the degree of change in ALFF.

Discussion

These findings suggest that the brain-heart interactions exist in healthy young adults under acute cardiovascular alterations, and more attention should be paid to blood pressure changes in young adults and assessment of frontal lobe function to provide them with more effective health protection management.
Effects of electrostatic therapy on nighttime sleep and daytime symptoms in patients with chronic insomnia: Evidences from an open label study
Authors: Dai Yanyuan , Qin Qingsong , Chen Baixin , Chen Le , Sun Qimeng , Vgontzas Alexandros N. , Basta Maria , Li Yun
Published: January 2023

Introduction

Transcranial electric stimulation (TES) is a neuromodulation approach that applies low-intensity electrical current to the brain and has been proposed as a treatment for insomnia. Electrostatic therapy is a kind of TES and people do not have a feeling of electrical stimuli when the voltage of static electricity is lower than 2,000 volts. However, no studies have examined the effects of electrostatic therapy on objective sleep and daytime symptoms in patients with insomnia.

Materials and methods

Thirty chronic insomnia patients were included. All patients received a 6 week electrostatic therapy and three comprehensive assessments including two consecutive polysomnography (PSG) and daytime symptoms assessments, at pre-treatment, 3 week and 6 week of treatment. Insomnia Severity Index (ISI) was used to assess the severity of insomnia. Multiple sleep latency test (MSLT), Epworth Sleepiness Scale (ESS), and Flinders Fatigue Scale (FFS) were used to assess objective and self-reported daytime sleepiness and fatigue, respectively. Attention network test (ANT) was used to assess attention levels.

Results

Total ISI scores decreased significantly at 3 weeks (p < 0.001) and 6 weeks (p < 0.001) after initiation of treatment. Furthermore, objective total sleep time (TST, p = 0.020) and sleep efficiency (SE, p = 0.009) increased and wake time after sleep onset (p = 0.012) decreased significantly after 6 weeks electrostatic therapy. Regarding daytime symptoms, ESS and FFS scores decreased significantly at 3 weeks (ESS, p = 0.047; FFS, p = 0.017) and 6 weeks (ESS, p = 0.008; FFS, p = 0.003) after initiation of treatment. Moreover, executive control improved significantly from pre-treatment to 3 weeks (p = 0.006) and 6 weeks (p = 0.013) and altering network improved significantly at 6 weeks (p = 0.003) after initiation of treatment. Secondary analyses showed that TST and SE improved significantly after electrostatic therapy in insomnia patients who slept < 390 min (all p-value < 0.05). However, no significant changes regarding TST and SE were observed in insomnia patients who slept ≥ 390 min.

Conclusion

Electrostatic therapy improves both nighttime sleep and daytime symptoms in patients with chronic insomnia. The effect on objective sleep appears to be stronger in patient with objective short sleep duration. Electrostatic therapy might be a therapeutic choice for insomnia patients with difficulty maintaining sleep and not responding to behavioral treatments.

Clinical trial registration

[www.clinicaltrials.gov], identifier [ChiCTR2100051590].
Effects of interoceptive accuracy on timing control in the synchronization tapping task
Authors: Tomyta Kenta , Katahira Kentaro , Ohira Hideki
Published: January 2023

Humans often perform rhythmic synchronized movements. Professional musicians and dancers particularly perform such movement tasks well and have a higher interoceptive accuracy (IAcc) than non-musicians and non-dancers. We thus hypothesized that rhythmic synchronized movements might be enhanced by a higher IAcc. To investigate this hypothesis, this study conducted a heartbeat counting task and a rhythmic synchronization tapping task with normal (easier) and slow (harder) tempi metronomes. Inconsistent with our hypothesis, however, a higher IAcc was negatively correlated with timing control, but only in the slow tempo condition [r (30) = 0.46, p < 0.05]. This suggests that a higher IAcc did not enhance timing control in rhythmic synchronized movements but rather weakened it, resting heart rate variability was not correlated with timing control.
Poly(I:C)-exposed zebrafish shows autism-like behaviors which are ameliorated by fabp2 gene knockout
Authors: Wu Jing , Lin Xueting , Wu Dian , Yan Binhong , Bao Mengyi , Zheng Peilei , Wang Jiangping , Yang Cuiwei , Li Zhongxia , Jin Xiaoming , Jiang Kewen
Published: January 2023

Introduction

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly representing impaired social communication. The etiology of ASD includes genetic and environmental risk factors. Rodent models containing ASD risk gene mutations or environmental risk factors, such as exposure to maternal inflammation, show abnormal behavior. Although zebrafish conserves many important brain structures of humans and has sophisticated and fine behaviors in social interaction, it is unknown whether the social behaviors of their offspring would be impaired due to exposure to maternal inflammation.

Methods

We exposed zebrafish to maternal immune activation (MIA) by injection with polyinosinic:polycytidylic acid [poly(I:C)], and screened their behaviors through social behavioral tests such as social preference and shoaling behavior tests. We compared phenotypes resulted from different ways of poly(I:C) exposure. RNA sequencing was performed to explore the differential expression genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) network analysis was performed with the detected DEGs to find the concentrated pathways. Finally, we knocked out the fatty acid-binding protein 2 (fabp2), a key node of the concentrated PPI network, to find its rescues on the altered social behavior.

Results

We reported here that MIA offspring born to mothers injected with poly(I:C) exhibited impaired social approach and social cohesion that mimicked human ASD phenotypes. Both maternal exposure and direct embryo exposure to poly(I:C) resulted in activations of the innate immune system through toll-like receptors 3 and 4. RNA-sequencing results from MIA brain tissues illustrated that the numbers of overexpressed genes were significantly more than that of underexpressed genes. GO and KEGG analyses found that MIA-induced DEGs were mainly concentrated in complement and coagulation cascade pathways. PPI network analyses suggested that villin-1 (vil1) pathway might play a key role in MIA-induced ASD. Knockout of fabp2 in F0 zebrafish rescued the social behavior deficits in MIA offspring.

Conclusions

Overall, our work established an ASD model with assessable behavior phenotype in zebrafish and provided key insights into environmental risk factor in ASD etiology and the influence of fabp2 gene on ASD-like behavior.
Metaplasticity framework for cross-modal synaptic plasticity in adults
Authors: Lee Hey-Kyoung
Published: January 2023

Sensory loss leads to widespread adaptation of neural circuits to mediate cross-modal plasticity, which allows the organism to better utilize the remaining senses to guide behavior. While cross-modal interactions are often thought to engage multisensory areas, cross-modal plasticity is often prominently observed at the level of the primary sensory cortices. One dramatic example is from functional imaging studies in humans where cross-modal recruitment of the deprived primary sensory cortex has been observed during the processing of the spared senses. In addition, loss of a sensory modality can lead to enhancement and refinement of the spared senses, some of which have been attributed to compensatory plasticity of the spared sensory cortices. Cross-modal plasticity is not restricted to early sensory loss but is also observed in adults, which suggests that it engages or enables plasticity mechanisms available in the adult cortical circuit. Because adult cross-modal plasticity is observed without gross anatomical connectivity changes, it is thought to occur mainly through functional plasticity of pre-existing circuits. The underlying cellular and molecular mechanisms involve activity-dependent homeostatic and Hebbian mechanisms. A particularly attractive mechanism is the sliding threshold metaplasticity model because it innately allows neurons to dynamically optimize their feature selectivity. In this mini review, I will summarize the cellular and molecular mechanisms that mediate cross-modal plasticity in the adult primary sensory cortices and evaluate the metaplasticity model as an effective framework to understand the underlying mechanisms.
Sorption of lead on cementitious materials in presence of organics
Authors: Drtinová Barbora , Kittnerová Jana , Bergelová Karolína , Burešová Marta , Baborová Lucie
Published: January 2023

Commercial cementitious material, hydrated cement pastes of type CEM I and CEM III, and a synthetic cementitious phase CSH (calcium-silicate-hydrates) with a Ca/Si ratio equal to 1.0, 1.2, and 1.4 were used in the study of lead sorption. Kinetic and equilibrium experiments were performed under different conditions, namely liquid to solid phase ratio and the presence of organic compounds (EDTA, phthalate). The duration of equilibrium experiments was determined based on kinetic experiments, 1 week for calcium-silicate-hydrates and 3 weeks for hydrated cement paste. Equilibrium experiments were evaluated using the distribution ratio Rd and sorption isotherms. For both hydrated cement pastes, Rd’s in the range 102–103 L kg−1 were found while for calcium-silicate-hydrates the distribution ratio values were an order of magnitude higher under comparable conditions. The difference in the studied cementitious materials was also manifested in the shape of the sorption isotherm, while the behavior of calcium-silicate-hydrates can be fitted linearly and therefore by the Kd-model, for hydrated cement paste as more complex cement material it is necessary to use a non-linear isotherm description. The effect of organic matter, represented here by EDTA and phthalate, described by the sorption reduction factor SRF was more apparent for calcium-silicate-hydrates, where its value was always higher than one and reached up to 500. On the contrary, for hydrated cement paste CEM I and CEM III, all determined SRFs were less than 1.
Polystyrene microplastics induced nephrotoxicity associated with oxidative stress, inflammation, and endoplasmic reticulum stress in juvenile rats
Authors: Wang Wanzhen , Guan Jiafu , Feng Yueying , Nie Liju , Xu Yuanyuan , Xu Hengyi , Fu Fen
Published: January 2023

Introduction

Unintended intake of microplastic particles has been demonstrated to exert adverse health effects, however, studies on relevant nephrotoxicity in juvenile mammals are lacking.

Methods

Therefore, we investigated the potential nephrotoxicity of oral-exposed polystyrene microplastics (PSMPs) (1,000 nm, 2.0 mg/kg/d) for 28 days in juvenile rats. Levels of oxidative stress, inflammation, and endoplasmic reticulum (ER) stress in kidneys were analyzed.

Results and discussion

Results revealed that PSMPs noticeably decreased the growth rate of bodyweight, and organ index of the kidney, cardiac, and ovary. The intestinal injury caused by PSMPs exposure was also observed, which was distinctly alleviated with N-acetyl-cysteine (NAC) and Salubrinal (Sal) treatment compared with the single PSMPs group. PSMPs caused histological lesions of the kidney via disrupting the serum blood urea nitrogen (BUN), creatinine (CRE), and pro-inflammatory mediators IL-1β, IL-6, and TNF-α. Furthermore, PSMPs exposure induced ER stress and inflammation presumably potentially mediated by oxidative stress in kidneys of rats. Eventually, PSMPs also promoted renal cells apoptosis, manifested as an obvious increase in the number of positive cells for the dUTP nick end labeling of Terminal deoxynucleotidyl transferase, which also can be confirmed by the elevated expression of genes associated with apoptosis Bcl-2, Bax, Caspase-12, Caspase-9, Caspase-3, and IHC score of Caspase-12 in the PSMPs group. Supplementation of NAC and Sal not only ameliorated the PSMPs-induced oxidative stress and ER stress but also the inflammation and apoptosis in the kidney. Collectively, this study suggested that PSMPs caused nephrotoxicity in juvenile rats potentially through oxidative damage and ER stress, which call for greater efforts to be taken on regulating the PSMPs ingestion in children.
Ramadan fasting reduces high-sensitivity C-reactive protein among HIV-infected patients receiving antiretroviral therapy
Authors: Widhani Alvina , Yunihastuti Evy , Setiati Siti , Witjaksono Fiastuti , Karjadi Teguh H.
Published: January 2023

Background

Inflammatory conditions and oxidative stress increase in HIV infection, and inflammation increases the risk of cardiovascular disease. Ramadan fasting is known to reduce inflammation and oxidative stress in diabetic patients. This study examined the effects of Ramadan fasting on high-sensitivity C-reactive protein (hs-CRP) levels and total antioxidant status (TAOS) in HIV patients on antiretroviral therapy (ART).

Methods

This was a prospective cohort study comparing HIV-infected patients on stable ART who fasted throughout Ramadan to HIV-infected patients who did not fast during Ramadan. Inclusion criteria were men aged 20–40 years, taking first-line ART for at least 6 months, Muslims intent to fast for Ramadan, no current hospitalization because of acute conditions and not being treated for opportunistic infections.

Results

After 2 weeks, hs-CRP had decreased significantly in the fasting group (−0.41 mg/L [IQR = −1; 0.10]) compared to the non-fasting group (0.20 mg/L [IQR = −0.30; 1.50]) (p = 0.004). The linear regression analysis has shown that Ramadan fasting contributed to 10.10% of the variance in hs-CRP value (R2 = 0.101) and decreased its value by 0.317 points (B = −0.317). Changes in TAOS did not significantly different (p = 0.405) between the fasting group (0.05 mmol/L [IQR = −0.03; 0.12]) and the non-fasting group (0.04 mmol/L [IQR = −0.13; 0.36]). In the fasting group, there were significant changes in polyunsaturated fatty acid consumption (p = 0.029), body weight (p = 0.001), cigarette smoking (p = 0.001), and sleeping duration (p = 0.001).

Conclusion

Ramadan fasting reduces hs-CRP concentrations among HIV patients on ART.
Nutrient combinations exhibit universal antianxiety, antioxidant, neuro-protecting, and memory-improving activities
Authors: Zhao Bangcheng , Jia Xiuzhen , Feng Haotian , Tang Cheng , Huang Yixin , Zhao Zifu , Hao Jingyu , Li Haoqiu , Du Jinrui , Liu Yan , Bao Xingyu , Zhong Zhihui , Zhang Yingqian , Zhong Qixing
Published: January 2023

Anxiety disorders are the most common mental disorders and, without proper treatment, may lead to severe conditions: e.g., somatic disorders or permanent damage to central nervous system. Although there are drugs in clinical trials, this study focuses on exploring the efficacy of nutrients in treating these diseases. We built different zebrafish models and screened several nutrient combinations for their antianxiety, antioxidant, neuro-protecting, and memory-improving activities. Our results showed that the combinations of nutrients (e.g., Walnut Peptides + Theanine at 14.2 + 33.3 μg/ml) have similar or better activities than the positive control drugs. In addition, we discovered that the effects of the nutrients in the above four aspects were universal and highly related. This study is noteworthy as it suggested that nutrients could be healthier and greener drug alternatives and provide similar or better universal treatments for anxiety and related conditions.
Survival outcomes of autologous breast reconstruction after mastectomy: A matched case-control study
Authors: Wu Shang , Ma Xindi , Zhang Xiangmei , Yang Chao , Wang Yubin , Liu Yunjiang
Published: January 2023

Background

Due to the lack of strong evidence-based medical evidence, the relationship between autologous breast reconstruction (ABR) after mastectomy and long-term prognosis is unclear. This study aims to explore if ABR after mastectomy is associated with the prognosis of breast cancer (BC) patients based on the data from the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

We collected data for all cases diagnosed with BC who underwent or did not undergo ABR after mastectomy from 2010-2015 in the SEER database. The primary outcome of our study was overall survival (OS) and cancer specific survival (CSS). The Propensity Score-Matched (PSM) analysis was used to eliminate the effects of non-random statistics, setting the caliper as 0.0001 to balance the baseline variables within the groups. Chi-square test, Kaplan-Meier method, univariate and multivariate cox regression analysis were used to analyze the data and subgroup analysis was performed to find the subgroups of people who might benefit from ABR.

Result

Of 27893 eligible patients, 11038 patients were matched. The cohort consisted of 5519 (50%) ABR patients and 5519 (50%) non-ABR patients after PSM. After PSM, on multivariate cox regression analysis, ABR still exerted a significant influence on the OS (hazard ratio (HR), 0.83, P< 0.05). However, no statistical difference was shown on CSS (HR, 0.93, P = 0.31). Kaplan-Meier survival analysis showed ABR group had better OS (P = 0.001), but similar CSS (P = 0.174) between ARB and mastectomy groups. Subgroup analysis showed that after matching, those with 50-59 years old, earlier stages of disease, without a marital partner and living in urban areas had better OS after ABR.

Conclusions

ABR after mastectomy was associated with better OS, but not affect CSS.
Investigation of the prevalence and clinical implications of ERBB2 exon 16 skipping mutations in Chinese pan-cancer patients
Authors: Shang Yanhong , Mo Jianming , Huo Ran , Li Xiaofang , Fang Guotao , Wei Zichun , Gu Guomin , Zhu Xiaodan , Zhang Chan , Liu Chunling , Yan Dong
Published: January 2023

Background

Although rare, ERBB2 exon 16 skipping mutations (ERBB2ΔEx16) have been implicated in resistance to anti-HER2 and anti-EGFR targeted agents. Our study investigated the prevalence and clinical significance of ERBB2ΔEx16 in Chinese pan-cancer patients.

Methods

We retrospectively screened 40996 patients, spanning 19 cancer types, who had available genomic profiles acquired with DNA-based next-generation sequencing (NGS). We characterized the clinical and molecular features of the ERBB2ΔEx16-positive patients. Furthermore, we also analyzed a pan-cancer dataset from the Cancer Genome Atlas (TCGA; n=8705).

Results

A total of 22 patients were detected with ERBB2ΔEx16, resulting in an overall prevalence rate of 0.054% (22/40996). Of them, 16 patients had lung cancer (LC; 0.05%, 16/30890), five patients had gastric cancer (GC; 0.35%, 5/1448), and one patient had ovarian cancer (0.12%, 1/826). Among the 16 LC patients, ERBB2ΔEx16 was detected in four treatment-naïve EGFR/ALK-negative patients and 12 EGFR-positive patients after the onset of resistance to EGFR tyrosine kinase inhibitors (TKIs). The treatment-naïve patients harbored no LC-associated oncogenic drivers except ERBB2 amplification, suggesting a potential oncogenic role for ERBB2ΔEx16. Consistently, ERBB2ΔEx16+ patients from TCGA data also carried no known drivers despite various concurrent alterations. In the 12 EGFR TKI-resistant LC patients, relative variant frequencies for ERBB2ΔEx16 were lower than in untreated patients, suggesting ERBB2ΔEx16 as secondary alterations following TKI treatment and thereby implicating ERBB2ΔEx16 in mediating therapeutic resistance.

Conclusions

Our study identified an overall ERBB2ΔEx16 prevalence rate of 0.054% and provided insights into the clinical implications of ERBB2ΔEx16 in Chinese pan-cancer patients.
Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology
Authors: Valentini Virginia , Silvestri Valentina , Bucalo Agostino , Conti Giulia , Karimi Mina , Di Francesco Linda , Pomati Giulia , Mezi Silvia , Cerbelli Bruna , Pignataro Maria Gemma , Nicolussi Arianna , Coppa Anna , D’Amati Giulia , Giannini Giuseppe , Ottini Laura
Published: January 2023

Introduction

Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI).

Methods

In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples.

Results and discussion

A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.
Macrophage scavenger receptors: Tumor support and tumor inhibition
Authors: Kazakova Elena , Iamshchikov Pavel , Larionova Irina , Kzhyshkowska Julia
Published: January 2023

Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells that constitute up to 50% of the cell mass of human tumors. TAMs interact with the components of the tumor microenvironment (TME) by using scavenger receptors (SRs), a large superfamily of multifunctional receptors that recognize, internalize and transport to the endosomal/lysosomal pathway apoptotic cells, cytokines, matrix molecules, lipid modified lipoproteins and other unwanted-self ligands. In our review, we summarized state-of-the art for the role of macrophage scavenger receptors in tumor development and their significance as cancer biomarkers. In this review we focused on functional activity of TAM-expressing SRs in animal models and in patients, and summarized the data for different human cancer types about the prognostic significance of TAM-expressed SRs. We discussed the role of SRs in the regulation of cancer cell biology, cell-cell and cell-matrix interaction in TME, immune status in TME, angiogenesis, and intratumoral metabolism. Targeting of tumor-promoting SRs can be a promising therapeutic approach in anti-cancer therapy. In our review we provide evidence for both tumor supporting and tumor inhibiting functions of scavenger receptors expressed on TAMs. We focused on the key differences in the prognostic and functional roles of SRs that are specific for cancer types. We highlighted perspectives for inhibition of tumor-promoting SRs in anti-cancer therapy.
The effects of the SARS-CoV-2 pandemic on children and youth with special health care needs
Authors: Michaud Mel , Dietz Irene Cihon
Published: January 2023

This article seeks to review the current knowledge of the SARS-CoV-2 virus and the health effects for children and youth with special health care needs (CYSHCN). COVID-19, an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a major pandemic in 2020. Recognition of the disease could be difficult, as symptoms in children are at times different than adults and can mimic other common childhood viral infections. Children with underlying medical conditions did make up a higher proportion of those hospitalized, but also were affected in other ways including loss of nursing support, missed education and rehabilitative services, and increased stress for themselves and their families, affecting mental health in this vulnerable population.

This review seeks to address what is currently known about the overall effects on CYSHCN and their families, and identify gaps in research, including the implementation of health care systems, and possible suggestions for change in the educational and community supports for this group of individuals. Ongoing analysis of large national and international data sets, as well as smaller reports based on specific congenital anomaly, genetics disease, and acquired childhood illness, and then attention to local resources and family resilience is still necessary.
Posterior urethral valves: Role of prenatal diagnosis and long-term management of bladder function; a single center point of view and review of literature
Authors: Pellegrino Chiara , Capitanucci Maria Luisa , Forlini Valentina , Zaccara Antonio , Lena Federica , Sollini Maria Laura , Castelli Enrico , Mosiello Giovanni
Published: January 2023

Posterior Urethral Valves (PUV) are the most common cause of lower urinary tract obstruction. More severe forms are detected early in pregnancy (mainly type I), while other forms are usually discovered later in childhood when investigating lower urinary tract symptoms. Bladder dysfunction is common and is associated with urinary incontinence in about 55% (0%–72%). Despite the removal of the obstruction by urethral valve ablation, pathological changes of the urinary tract can occur with progressive bladder dysfunction, which can cause deterioration of the upper urinary tract as well. For this reason, all children with PUV require long-term follow-up, always until puberty, and in many cases life-long. Therefore, management of PUV is not only limited to obstruction relief, but prevention and treatment of bladder dysfunction, based on urodynamic observations, is paramount. During time, urodynamic patterns may change from detrusor overactivity to decreased compliance/small capacity bladder, to myogenic failure (valve bladder). In the past, an aggressive surgical approach was performed in all patients, and valve resection was considered an emergency procedure. With the development of fetal surgery, vesico-amniotic shunting has been performed as well. Due to improvements of prenatal ultrasound, the presence of PUV is usually already suspected during pregnancy, and subsequent treatment should be performed in high-volume centers, with a multidisciplinary, more conservative approach. This is considered to be more effective and safer. Primary valve ablation is performed after clinical stability and is no longer considered an emergency procedure after birth. During childhood, a multidisciplinary approach (pediatric urologist, nephrologist, urotherapist) is recommended as well in all patients, to improve toilet training, using an advanced urotherapy program with medical treatments and urodynamic evaluations. The aim of this paper is to present our single center experience over 30 years.
Machine learning for predicting the treatment effect of orthokeratology in children
Authors: Fang Jianxia , Zheng Yuxi , Mou Haochen , Shi Meipan , Yu Wangshu , Du Chixin
Published: January 2023

Purpose

Myopia treatment using orthokeratology (ortho-k) slows myopia progression. However, it is not equally effective in all patients. We aimed to predict the treatment effect of ortho-k using a machine-learning-assisted (ML) prediction model.

Methods

Of the 119 patients who started ortho-k treatment between January 1, 2019, and January 1, 2022, 91 met the inclusion criteria and were included in the model. Ocular parameters and clinical characteristics were collected. A logistic regression model with least absolute shrinkage and selection operator regression was used to select factors associated with the treatment effect.

Results

Age, baseline axial length, pupil diameter, lens wearing time, time spent outdoors, time spent on near work, white-to-white distance, anterior corneal flat keratometry, and posterior corneal astigmatism were selected in the model (aera under curve: 0.949). The decision curve analysis showed beneficial effects. The C-statistic of the predictive model was 0.821 (95% CI: 0.815, 0.827).

Conclusion

Ocular parameters and clinical characteristics were used to predict the treatment effect of ortho-k. This ML-assisted model may assist ophthalmologists in making clinical decisions for patients, improving myopia control, and predicting the clinical effect of ortho-k treatment via a retrospective non-intervention trial.
Analysis of association between eating behaviours and childhood obesity among pre-school children: A cross-sectional study
Authors: Wu Yi-Xin , Fan Hai-Ling , Dai Jin , Wu Hui-Lan , Yang Jing-Yun , Wang Yun , Tung Tao-Hsin , Wang Li-Zhen , Zhang Mei-Xian
Published: January 2023

Background

Childhood obesity is a worldwide critical health concern. We aimed to clarify whether eating behaviours increased the risk of childhood obesity.

Methods

We recruited 2,049 pre-school children aged 3–6 years between 1 December 2021 and 31 January 2022 in Taizhou, China. Children's weight status was classified according to the International Obesity Task Force criteria, and their eating behaviours were evaluated using the Children's Eating Behaviour Questionnaire. Correlation analyses, linear regressions, and one-way ANCOVA. were performed to analyse the association between children's eating behaviours and weight status.

Results

In ‘Food Avoidant' subscales, the scores of satiety responsiveness (P < 0.001) and slowness in eating (P = 0.001) were negatively associated with body mass index z score among pre-school children of both sexes. In ‘Food Approach’ subscales, the score of enjoyment of food was positively associated with body mass index z score in both boys (P = 0.007) and girls (P = 0.035), but the association of scores of food responsiveness with body mass index z score was found only in girls (P = 0.001).

Conclusion

Our results supported that pre-school children with low scores in ‘Food Avoidant’ subscales and high scores in ‘Food Approach’ scales were more likely to become obese.
Functional evaluation of cyclosporine metabolism by CYP3A4 variants and potential drug interactions
Authors: Kong Qihui , Gao Nanyong , Wang Yahui , Hu Guoxin , Qian Jianchang , Chen Bingbing
Published: January 2023

The aim of this study is to investigate the effects of CYP3A4 genetic polymorphisms on the metabolism of cyclosporine (CsA) in vitro and identify drugs that interact with CsA. An enzymatic incubation system was developed to evaluate the kinetic parameters of CYP3A4 on CsA catalysis. A total of 132 drugs were screened to identify potential drug–drug interactions. Sprague–Dawley rats were used to determine the interaction between CsA and nimodipine and nisoldipine. The metabolite AM1 was measured by ultra-performance liquid chromatography–tandem mass spectrometry. The results demonstrate that 16 CYP3A4 variants (CYP3A4.7, 8, 9, 12, 13, 14, 16, 18, 19, 23, 24, 28, 31, 32, 33, and 34) have a lower metabolic capacity for CsA, ranging from 7.19% to 72.10%, than CYP3A4.1. In contrast, the relative clearance rate of CYP3A4.5 is significantly higher than that of CYP3A4.1. Moreover, CYP3A4.20 loses its catalytic ability, and five other variants have no significant difference. A total of 12 drugs, especially calcium channel blockers, were found to remarkably inhibit the metabolism of CsA with an inhibitory rate of over 80%. Nimodipine inhibits the activity of CsA in rat liver microsomes with an IC50 of 20.54 ± 0.93 μM, while nisoldipine has an IC50 of 16.16 ± 0.78 μM. In in vivo, three groups of Sprague–Dawley rats were administered CsA with or without nimodipine or nisoldipine; the AUC(0-t) and AUC(0-∞) of CsA were significantly increased in the nimodipine group but not obviously in the nisoldipine group. Mechanistically, the inhibition mode of nimodipine on cyclosporine metabolism is a mixed inhibition. Our data show that gene polymorphisms of CYP3A4 and nimodipine remarkably affect the metabolism of CsA, thus providing a reference for the precise administration of CsA.
Extracellular vesicles derived from host and gut microbiota as promising nanocarriers for targeted therapy in osteoporosis and osteoarthritis
Authors: Cheung Kenneth Chat Pan , Jiao Ma , Xingxuan Chen , Wei Jia
Published: January 2023

Osteoporosis (OP), a systemic bone disease that causes structural bone loss and bone mass loss, is often associated with fragility fractures. Extracellular vesicles (EVs) generated by mammalian and gut bacteria have recently been identified as important mediators in the intercellular signaling pathway that may play a crucial role in microbiota-host communication. EVs are tiny membrane-bound vesicles, which range in size from 20 to 400 nm. They carry a variety of biologically active substances across intra- and intercellular space. These EVs have developed as a promising research area for the treatment of OP because of their nanosized architecture, enhanced biocompatibility, reduced toxicity, drug loading capacity, ease of customization, and industrialization. This review describes the latest development of EVs derived from mammals and bacteria, including their internalization, isolation, biogenesis, classifications, topologies, and compositions. Additionally, breakthroughs in chemical sciences and the distinctive biological features of bacterial extracellular vesicles (BEVs) allow for the customization of modified BEVs for the therapy of OP. In conclusion, we give a thorough and in-depth summary of the main difficulties and potential future of EVs in the treatment of OP, as well as highlight innovative uses and choices for the treatment of osteoarthritis (OA).
Identification of therapeutic targets for osteosarcoma by integrating single-cell RNA sequencing and network pharmacology
Authors: Wang Yan , Qin Di , Gao Yiyao , Zhang Yunxin , Liu Yao , Huang Lihong
Published: January 2023

Background: Osteosarcoma (OS) is a common primary tumor with extensive heterogeneity. In this study, we used single-cell RNA sequencing (scRNA-seq) and network pharmacology to analyze effective targets for Osteosarcoma treatment.

Methods: The cell heterogeneity of the Osteosarcoma single-cell dataset GSE162454 was analyzed using the Seurat package. The bulk-RNA transcriptome dataset GSE36001 was downloaded and analyzed using the CIBERSORT algorithm. The key targets for OS therapy were determined using Pearson’s correlation analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on key targets. The DeepDR algorithm was used to predict potential drugs for Osteosarcoma treatment. Molecular docking analysis was performed to verify the binding abilities of the predicted drugs and key targets. qRT-PCR assay was used to detect the expression of key targets in osteoblasts and OS cells.

Results: A total of 21 cell clusters were obtained based on the GSE162454 dataset, which were labeled as eight cell types by marker gene tagging. Four cell types (B cells, cancer-associated fibroblasts (CAFs), endothelial cells, and plasmocytes) were identified in Osteosarcoma and normal tissues, based on differences in cell abundance. In total, 17 key targets were identified by Pearson’s correlation analysis. GO and KEGG analysis showed that these 17 genes were associated with immune regulation pathways. Molecular docking analysis showed that RUNX2, OMD, and CD4 all bound well to vincristine, dexamethasone, and vinblastine. The expression of CD4, OMD, and JUN was decreased in Osteosarcoma cells compared with osteoblasts, whereas RUNX2 and COL9A3 expression was increased.

Conclusion: We identified five key targets (CD4, RUNX2, OMD, COL9A3, and JUN) that are associated with Osteosarcoma progression. Vincristine, dexamethasone, and vinblastine may form a promising drug–target pair with RUNX2, OMD, and CD4 for Osteosarcoma treatment.
A comparison of linear and non-linear strategies for energy harvesting from mechanical vibrations
Authors: Andò Bruno , Baglio Salvatore , Marletta Vincenzo , Bulsara Adi R.
Published: January 2023

Energy Harvesting strategies coupled with the improvement of electronics and the progressive reduction of power requirements have been widely recognized as fundamental to enable self-powered (or autonomous) devices. Among all the potential energy sources, kinetic energy stemming from mechanical vibrations has been particularly extensively investigated for EH purposes due to its characteristics of heterogeneity and ubiquity. To exploit such energy sources, a suitable coupling mechanism to convert vibrations into electric charge is required; it must take into account the wide frequency bandwidth of mechanical vibrations as encountered in everyday scenarios. This review offers an overview of linear vs. non-linear strategies for EH, with a specific focus on different approaches to implement efficient coupling mechanisms; the performances of the specific solutions covered in this work are discussed.
Measuring the impact of Wuhan’s COVID-19 lockdown on the growth enterprise market in China
Authors: Wang Li , Huang Zeyu , Wang Yanan
Published: January 2023

The outbreak of COVID-19 had a huge impact on the financial market. As a new growth point in China, it’s necessary to study how SMEs (small and medium-sized enterprises) represented by listed companies on the GEM (growth enterprise market) can withstand sudden shocks. This paper examines the impact of Wuhan’s COVID-19 lockdown on the financial markets based on the data of GEM listed companies and the method of event analysis. The results show that investors had a great response to epidemic related news. Compared with the interest rate cut policy, the targeted RRR reduction policy had a more significant positive influence on the financial markets. Furthermore, in the early stages of COVID-19, there was not a significant effect of distance on the firms’ CARs (cumulative abnormal returns). In an improving epidemic environment, the farther the firms were from Wuhan City, the more positive the impact on their CARs would be. This paper provides new evidence and important enlightenment for preventing the impact of public health emergencies on the GEM market and highlights the significance of developing digital inclusive finance, which can mitigate regional risk and financing issues.
Plant salt response: Perception, signaling, and tolerance
Authors: Xiao Fei , Zhou Huapeng
Published: January 2023

Salt stress is one of the significant environmental stressors that severely affects plant growth and development. Plant responses to salt stress involve a series of biological mechanisms, including osmoregulation, redox and ionic homeostasis regulation, as well as hormone or light signaling-mediated growth adjustment, which are regulated by different functional components. Unraveling these adaptive mechanisms and identifying the critical genes involved in salt response and adaption are crucial for developing salt-tolerant cultivars. This review summarizes the current research progress in the regulatory networks for plant salt tolerance, highlighting the mechanisms of salt stress perception, signaling, and tolerance response. Finally, we also discuss the possible contribution of microbiota and nanobiotechnology to plant salt tolerance.